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an invention directed to a soccer training device , method of use and training system . the device is a deflection wall that may be portable . the wall having a larger and smaller embodiment , mimicking the silhouette of a soccer goal or an average player of a given age range from a far distance at simulated closer range . the inventive features of the wall intended to enhance quantity , quality , speed , and accuracy of interaction and perception between the user , the ball and the wall according to professional quality and professional level training techniques . multiple wall units may be combined to create individualized training modules wherein one person may train in a simulated multi - player environment of varying levels of complexity . two or more module units may be combined to create a soccer training system . the modules and systems may be staged in limited ground surface area both indoor and outdoor .

reference will now be made in detail to exemplary aspects of the present invention which are illustrated in the accompanying drawings . wherever possible , the same reference numbers will be used throughout the drawings to refer to the same or like parts . fig1 a and 1b provide a general embodiment of the device , a deflection wall . the device in fig1 a and 1b is not drawn to scale and represents a generic illustrated description of the claimed features . fig1 a is a front view of the device , a deflection wall 100 comprising one panel 101 and having a preferred rectangular shape . fig1 a illustrates an exposed front surface 102 of the panel . the front surface 102 being flat and smooth , containing no attachments or cavities that would interfere with the interaction with the ball . fig1 b illustrates a side view of the panel , having an exposed front surface 102 with greater surface area than the exposed side surface of the surrounding edge 103 a , b . the corners 104 of the panel would preferably be soft and curved such that deflection of a ball from said corner would closely simulate a ball being kicked from the curve of a person &# 39 ; s padded shoe as opposed to a hard jagged surface . the curved or rounded corners 104 further minimize wear and tear on a ball typically experienced with sharp or jagged edges . as stated above , the device may be embodied in two preferred sizes . a larger size according to fig2 b defined as a shooting wall 200 , and a smaller size according to fig2 a defined as a passing wall 201 . the shooting wall having a dimension proportional in perspective to a standard soccer goal post frame from a far distance ; preferably between three to four feet high 202 and approximately six to eight feet wide 203 . the passing wall would preferably be approximately two to three feet high 204 and three and a half feet to four and a half feet wide 205 , simulating the silhouette of an average adult soccer player standing in ready position with legs spread apart . the two sizes may be scaled down to the proportional dimensions of average users of a particular age range such as shorter youth players or smaller infant - children players . the panel is placed on its widest side surface 103 a directly on and perpendicular to the ground during use . the panel surface is comprised of a thick , semi - flexible and semi - viscous material similar to rubber or neoprene . the panel surface may be textured to enhance grip over the ball but should not have substantial grooves , cavities or raised features otherwise interfering with simulated ball interaction . the interior of the panel , substantially comprised of any solid material such as but not limited to wood , plastic , glass , metal , foam , carbon fiber or any combination each . the interior composition of the preferred embodiment would be comprised of wood or wood composite material . fig2 illustrates an alternative embodiment of the deflection wall 200 having two panels 201 . each panel according to this side view illustration having one exposed front or main surface 202 , a substantially exposed side edge surface 203 ( all but the bottom which is in contact with the ground ) and an obstructed back surface 204 ( facing a central stabilizing unit and the second panel ). this alternative embodiment is fully usable from both sides 202 of the device . as stated above , the device may have one or more panels 201 , each panel having one or more exposed surface 202 . therefore , the device may have a multiplicity of panels 201 or exposed surfaces 202 . fig2 illustrates the device relying on an anchor support assembly 205 ( generally illustrated in the drawings ). fig3 illustrates an alternative embodiment of the device 300 having one panel 301 attached to an anchor 302 support assembly ( generally illustrated in the drawings ). fig3 illustrates a side view of this embodiment of the device demonstrating the support 302 connected to the back surface 303 of the panel 301 , the support detachably connected to an anchor portion below the ground surface ( not shown ) such that the panel 301 is stabilized in an erect position above ground and ready for use . one or more support or support components 302 may be connected to a particular panel 301 . the need for more would depend on the size and composition of the panel design or the ground surface composition . the embodiment of fig3 illustrates one of many potential manner of construction known in the art and should not be read in a limiting fashion . fig4 , 5 a and 5 b illustrates another embodiment of the device 400 having one panel 401 attached to a support assembly 402 . fig4 illustrates a side view of this embodiment of the device in which the support comprises two angled brackets 403 each bracket connected to a fixturing means 404 . the angled bracket 403 may comprise any hard weather resistant material such as but not limited to stainless or galvanized steel , durable plastic , carbon fiber or any combination of such material . the bracket may be adjustable folding towards the panel &# 39 ; s back surface in the collapsed position for ease of transport or be detachable from the panel piece as a separate component for transport . the support assembly 402 is not limited to an angled bracket means 403 but may include any similar manner of structural and stabilizing support of the panel 401 in a vertical upright position over a soccer field or arena . preferably the supporting assembly 402 would be attached to the panel 401 without holes or protrusion through any exposed surfaces of said panel 401 , such as but not limited to nails and screws . further , the connection between parts of the device 400 in whole and upon fixture to the ground surface for intended use should be substantially sturdy and having minimal movement or noise , particular upon forceful impact . unwanted sounds or deflection interaction arising from the wall upon impact may negatively affect psychological aspects of training , resulting in secondary unwanted habits or else simply interfering with the overall focus of training . the choice of material , composition and design of attachment features , many of which are already known in the art , can be chosen to minimize this unwanted effect . fig4 illustrates the back side 405 view of an embodiment having two triangular brackets 403 attached to the back surface 405 of a panel 401 . each angled bracket 403 recessed approximately seven to ten inches inward from the edges 406 a of the panel sides so as to minimize obstruction to a soccer ball trajectory path . the angled bracket 403 having a horizontal piece 407 resting above the ground surface and extends perpendicularly from the bottom edge 406 b of the back surface 405 in a vertical direction . the horizontal piece 407 and a vertical piece 408 are connected by a tangential piece 409 . the connection between the back wall surface 405 , the horizontal piece 407 and the tangential piece 409 creating a triangular shape as illustrated in the drawings . the horizontal 407 and tangential 409 pieces preferably comprised of weather resistant metal . fig6 c further illustrates a portable detachable version of the angled support brackets 651 wherein the brackets 651 may be attachable and detachable by a spring lock or clip mechanism 652 . a fixturing means 500 according to fig5 a , 5 b and 5 c is connected to the joint end 501 where the horizontal piece 502 and tangential piece 503 meets . an exploded view of the fixturing means 500 as illustrated in fig5 a , 5 b and 5 c comprising a flat triangular wedge 504 whose wider end 505 contains a hollowed sleeve or tubular portion 506 ( shown in part ) within whereby a link or thin axle rod ( or any equivalent thereof ) ( not shown ) is slid through said sleeve such that the wider side of the wedge swivels around the link or rod 507 . the fixturing means 500 is connected to the horizontal piece 502 at the joint end 501 such that it may swivel around the axis of the horizontal piece . when in use according to fig6 a and 6b , the pointed end 601 of the flat wedge 602 is positioned downward perpendicular to the ground surface and perpendicular to the cross section of the horizontal piece 603 at the joint end 604 . the wedge is then driven into the ground with the flat side buttressing or abutting a blunt end ( see fig5 a , 509 ) of the horizontal piece 603 . the abutment of the flat wedge 504 against the blunt end 509 of the horizontal piece 502 , as illustrated in fig5 a , prevents the wedge from rotating further along the axle rod thus stabilizing the device against forceful impact . fig7 a , 7 b and 7 c illustrating the exposed front or main surface 703 of a preferred embodiment of the device 700 , 701 , 702 . fig7 b and 7c illustrating a larger 702 and smaller 701 sized version of the panel device 700 . the devices are not drawn to exact scale but are drawn to relative scale as intended for an adult user and a standard goal post . the exposed front panel 703 having soft rounded or curved corners 704 , a white colored border 705 comprising less than fifty percent of the surface area of the exposed main surface 703 , the central area or portion 706 of the exposed main surface within the perimeter of the white border 705 having a color mimicking a real soccer field or arena such as tan , beige , brown or green . fig8 a illustrates a soccer training module 800 comprising two smaller passing walls 801 wherein each respective exposed main or front surface 802 is positioned directly opposite from each other . fig8 b illustrates an alternative embodiment of a two passing wall 801 module 805 that is spaced further apart . variations in the distance between passing walls will vary but should be ten yards distance or less as a rule for purposes of mimicking actual distance between players within close practical passing range according to standard practice in the game of soccer . this range of distance further facilitating and encourage rapid , high repetition passing interaction between the player and the passing walls . fig8 a and 8b are not drawn to scale or perspective . fig9 illustrates a more complex soccer training module 900 having three passing walls 901 and one shooting wall 902 , whose exposed main surfaces 903 are centrally facing wherein the combination of panels are oriented to create a rectangular or square pattern . this configuration and other module configurations may be embodied in permanent attachments to the ground surface by way of an anchor support assembly or system . fig9 is not drawn to scale or perspective either . fig1 illustrates an even more complex embodiment of a soccer training module 150 having eight permanently positioned devices 151 a , b , c with two additional portable devices 152 in angled positions . this embodiment of the module having three pairs of passing walls 151 b , c and one pair of shooting walls 151 a , simulating a complete multiplayer game environment . the three pairs of passing walls 151 b , c are positioned opposite to each other in parallel form , with two rows of three passing walls 151 b , c . the pair of shooting walls 151 a is positioned opposite each other between the two rows of passing walls 151 b , c and at each ends of the two rows . the eight walls 151 a , b , c forming a rectangular shaped module 150 . the distance between the exposed main surfaces of the two rows of passing walls 151 a , b , c ( along the length of the rectangle between exterior surfaces of the two opposing walls ) is approximately eight yards . the distance between the exposed main surface 154 of the opposing shooting walls 151 a is approximately 32 yards . the distance between adjacent passing walls within a given row ( from side edge 155 to side edge 155 ) is approximately two yards or greater . fig1 illustrates an alternative embodiment of a complete field module 250 with six permanently fixed devices 251 a , b , c and two portable devices 252 in an angled position . the distance between side edges 253 of the passing walls within the same row 250 a , c remains at least two yards of separation at a minimum , mimicking the natural minimum spread between players in actual play according to standard practice and training of the game . fig1 illustrates three circular modules 350 , each module containing eight passing walls 351 , the exposed front surface of each passing wall 352 centrally facing the same central radial point to form a substantially circular or oval pattern . the distance between side edges 353 of the passing walls remains at least two yards of separation at a minimum , mimicking the minimum natural spread between players in actual play according to standard practice and training of the game . fig1 illustrating one embodiment of a complete soccer training system 450 having nine sets of modules ( 451 , 452 , 453 , 454 , 455 , 456 , 457 , 458 , 459 of progressive levels of complexity . the first six sets of modules ( 451 , 452 , 453 , 454 , 455 , 456 ) representing the least complex types , each containing two passing walls . the distance between the exposed front surface of the opposing passing walls within each of the first six modules are as follows : module 1 ( 451 )= 10 yard ; module 2 ( 452 )= 9 ; module 3 ( 453 )= 8 ; module 4 ( 454 )= 7 ; module 5 ( 455 )= 6 ; module 6 ( 456 )= 5 . these distances reflect the closest range of separation between players in passing position in actual play according to standard practice and training within the game of soccer . any distance further than 10 yard would require shooting of the ball and detract from training passing techniques . modules 6 ( 457 ) and 8 ( 458 ) of fig1 represents the next progressing levels of modular complexity . these two sets each contain four permanent devices with three passing walls and one shooting wall . both module units contain three passing walls and one shooting wall . the dimensional requirements of module 7 & amp ; 8 are as follows : two passing walls in opposing position with the respective exposed surfaces separated by approximately seven yards distance ; one passing wall perpendicularly positioned 460 between the two passing walls at approximately two yards distance between side edges 461 ; a shooting wall perpendicularly positioned relative to the two opposing shooting walls on the opposite end from the perpendicular passing wall 460 ; the shooting wall separated from the perpendicularly positioned passing wall 461 at approximately 14 . 13 yards distance . portable devices or walls may be added to existing permanent modules to increase complexity of training . the last module 9 ( 459 ) of this system 450 , is substantially similar to the complete field module described in fig1 or 11 . alternative modular embodiments , such as the type described in fig1 , may be added or substituted for any of the modules described within fig1 . the described training system and modules described above may be reconfigured to add extra levels of complexity by adding more devices at desired position on an existing modular environment . alternative embodiments of the system may comprise less numbers of module units or fewer training levels . the described training system and module units may be permanently affixed onto a dedicated field or may be transported and movable anywhere along a field . the claimed device may be manufactured with either manner of construction in mind . having fully described at least one embodiment of the present invention , other equivalent or alternative methods according to the present invention will be apparent to those skilled in the art . the invention has been described by way of summary , detailed description and illustration . the specific embodiments disclosed in the above drawings are not intended to be limiting . implementations of the present invention with various different configurations are contemplated as within the scope of the present invention . the invention is thus to cover all modifications , equivalents , and alternatives falling within the spirit and scope of the following claims .

US-201213587715-A

an external fixation system and method for realigning , compressing or distracting broken bones has a planar ring element with an adjustable device having a body releasably mounted on the ring element . the adjustable device includes a first member for movement in a direction generally perpendicular to the ring element . a second member is mounted on the first member for movement in a direction parallel to the first member and with respect to a circumference of the planar ring element . the method includes inserting a k - wire through a first piece of bone and affixing the k - wire to the ring element . then inserting a second k - wire through a second piece of bone and affixing the k - wire to the adjustable device second member . the pieces of bone are realigned , compressed or distracted by adjusting at least one of a first and second adjustable members forming the device .

referring to fig1 a - 1b , in accordance with a preferred embodiment of the present invention , an isometric view of a dynamic external fixator generally denoted as 100 is shown mounted on a foot 101 by pins . dynamic external fixator 100 includes a u - shaped ring element 102 having a plurality of mounting holes 103 with at least one adjustable device 104 , and preferably two , releasably attached to a pair of mounting holes 103 . adjustable device 104 includes a body 106 releasably attached to arms 108 , 108 ′ of ring element 102 . the adjustable device further includes a first member 110 slidably mounted on body 106 capable of providing movement in a direction perpendicular to a proximal surface 109 of arm 108 , 108 ′ of ring element 102 . further , a second member 112 pivotally mounts on first member 110 for providing angular movement ( i . e ., rotation ) with respect to first member 110 . further still , a third member 114 mounts on second member 112 providing linear movement along arms 108 , 108 ′. preferably one or more wire engagement elements 116 ′ attach first or second k - wires 118 that pass through a fractured bone respectively . the wire engagement elements are mounted to third member 114 and / or to ring 102 directly . for example , as shown , first k - wire 118 attaches to a standard bone engagement element 116 . further , a second k - wire 120 can attach directly to ring element 102 . for example , as shown , second k - wire 120 attaches to ring element 102 by being clamped in a standard ring engagement element 122 mounted in a hole 103 . preferably first and second k - wires 118 , 120 are substantially smooth pins with a drill tip . in some instances , however , first and second k - wires 118 , 120 may not include a drill tip . further , first and second k - wires 118 , 120 can be made of any suitable material , such as , but not limited to , stainless steel , titanium , and titanium alloy . further , first and second k - wires 118 , 120 can connect to bone engagement element 116 and ring engagement element 122 by being inserted through a hole ( not shown ) in bone engagement element 116 or ring engagement element 122 and applying a force on first or second k - wires 118 , 120 by , for example , a set screw ( not shown ). alternatively , bone engagement element 116 or ring engagement element 122 can be a wire / rod nut . any reasonable method for attaching first and second k - wires 118 , 120 to bone engagement element 116 or ring engagement element 122 can be used . ring element 102 can be a substantially monolithic material designed to releasably attach to at least one adjustable device 104 . ring element 102 can be made of metal ( e . g ., stainless steel , titanium , etc . ), composites ( e . g ., carbon peek , etc . ), or any other material deemed suitable . further , although described as a u - shaped ring , ring element 102 can include any shape that allows at least one adjustable device to be releasably connected to it . for example , ring element 102 can be a circle shape , horseshoe shape , square shape , rectangle shape , or any other shape deemed suitable . ring element 102 preferably is planer creating a relatively flat surface on ring element 102 . this flat surface is used to provide a flat surface to releasably attach ring element 102 with adjustable device 104 . such a ring can have four levels as shown in u . s . patent application ser . no . 12 / 157 , 612 filed jun . 11 , 2008 , the disclosure of which is incorporated herein by reference . referring to fig2 a , adjustable device 104 is shown in greater detail . adjustable device 104 has a body 106 with a pair of expandable connectors 202 a that releasably connect adjustable device 104 to holes 103 of ring element 102 . attached to body 106 is first member 110 which slidably mounts on body 106 . while mounted on body 106 , when fixed on ring 102 , first member 110 can move up and down with respect to top planar surface 206 of body 106 . that is , first member 110 can move in a direction perpendicular to upper surface 206 of body 106 and the plane of the ring 102 . this is accomplished by the rotating threaded pin 308 as will be described below . further , because , in the preferred embodiment , surface 206 of body 106 is parallel to the plane of ring element 102 ( see , fig1 a - 1b ) first member 110 moves in a direction perpendicular to the plane of ring element 102 . referring to fig2 b an exemplary ring element connector is displayed . as shown , preferred connector 202 a includes a lower outer portion 215 located under body 106 split into two sections 214 , 216 and an inner portion 217 with a pair of drive heads 208 , 209 located above body 106 for engaging a drive tool . further , inner portion 217 has a threaded shaft 212 coupled to drive heads 208 , 209 and extends between the two halves 214 , 216 . threaded shaft 212 includes tapered nut 218 which when moved toward body 106 caused sections 214 and 216 to expand . after connector 202 a is placed through body 106 and into hole 103 in the ring element 102 , nut 218 is threaded on the bottom of threaded shaft 212 . as drives 208 , 209 are rotated nut 218 causes the two halves 214 , 216 to expand thereby securing the adjustable device to the ring element . although described as two halves the split portion can include any number of sections ( e . g ., three or four sections ). referring to fig2 c there is shown an alternative ring element connector 202 b . as shown , ring connector 202 b can include a shaft 219 with a screw thread portion 222 and a drive head 221 . the threaded shaft portion 222 is inserted through the bore in body 106 until drive head 221 comes into contact with upper surface body 106 . threaded shaft portion 222 is further inserted through an opening 103 in ring element 102 and threaded into a nut 224 . as threaded shaft portion 222 is threaded into nut 224 adjustable device 104 is secured onto ring element 102 . further , any method of releasably securing adjustable device 104 to the ring element can be used . for example , the adjustable device can be releasably attached to the ring element by a screw and nut , a bolt assembly , or any other securing method deemed suitable . referring to fig3 a , a rear view of two parts of the preferred adjusting device 104 is shown . the two parts are members 110 and 106 . first member 110 has a first portion 113 and a central portion 306 which can move in a direction perpendicular to the plane of ring element 102 by rotating a screw shaft 302 via drive head 308 . screw shaft 302 is placed through a hole 115 in body 106 and is threaded into a second threaded hole 117 located in central flange 306 extending rearwardly from first portion 113 of first member 110 . shaft 302 has an end 338 with a pin 340 to ensure the assembly does not come apart during use . in use , a user rotates a drive head 308 causing screw 302 to thread into the second hole thereby moving first member 110 up and down with respect to body 106 ( i . e ., perpendicular to planar surface 206 of body 106 and perpendicular to the plane of ring element 102 ). alternatively , although screw shaft 302 is described as threaded into a second hole in member 110 , screw 302 may thread into a threaded hole in body 106 and fixed in part 306 . it will be understood that any method of making first member 110 move up and down with respect to body 106 can be used . further , increasing the number of threads on screw shaft 302 increases the number of rotations needed to move first member 110 up and down . thus , increasing the number of threads increases the precision of up and down movement . in some embodiments , flange 306 extending from first member 110 is designed to ride along a protruding track 310 extending from body 106 . riding on track 310 reduces the amount of movement in an undesired direction . further , any method of mating first member 110 with body 106 designed to decrease movement in an undesired direction can be used . for example , first member 110 and body 106 can include any male - female mating features ( e . g ., tongue and groove or dovetail ) for providing guided movement up and down . referring to fig2 a , 4 and 6a , second member 112 is rotably mounted on first member 110 . while mounted on first member 110 , second member 112 can rotate through a range of angles with respect to first member 110 . that is , second member 112 is pivotally mounted by guide tracks 612 on first member 110 and can rotate with respect to first member 110 . for example , in the preferred embodiment , second member 112 can pivot up to 120 degrees around its center on guide 614 mounted on first member 110 as shown in fig6 a . that is , second member 112 can , for example , rotate 60 degrees from parallel in an upward direction and 60 degrees in a downward direction with respect to surface 306 . referring to fig3 b in the preferred embodiment , second member 112 rotates through a range of angles by the interaction of a worm 312 ( i . e ., a gear in the form of a screw ) with an arcuate worm gear 314 mounted on second member 112 on the outer surface of the portion thereof forming track 612 ( i . e ., a worm wheel ). for example , worm 312 can thread into worm gear 314 causing second member 112 to rotate relative to first member 110 . in use , a user rotates drive head 316 of worm 312 causing worm 312 to rotate while engaged with worm gear 314 . because first member 110 is attached to body 106 that is fixed to ring element 102 , rotating worm 312 while engaged with worm gear 314 causes second member 112 to rotate upwardly or downwardly with respect to the plane of ring 102 . although described as a worm gear and worm any reasonable method can be used to change the angle of second member 112 with respect to first member 110 . for example , the angle can be changed by spur gears , helical gears , double helical gears , bevel gears , crown gears , or any other gearing deemed suitable . further increasing the number of threads ( i . e ., increasing the number of threads on the worm gear and worm ) increases the number of rotations of user interface 316 required to move through a given angle . thus , increasing the number of threads provides a greater level of precision during rotation . referring to fig2 a and 6a , as shown , third member 114 is mounted on second member 112 . while mounted on second member 112 , third member 114 can move linearly with respect to second member 112 . that is , third member 114 can linearly move along arms 108 , 108 ′ of the ring element in a direction parallel to the plane of ring 102 in an anterior - posterior direction . referring to fig3 c in the preferred embodiments , third member 114 includes a dovetail protrusion 322 ( i . e ., guide element ) that mates with a groove 324 extending along second member 112 . protrusions 322 mates with groove 322 thereby providing a guide for the linear motion . for example , in the preferred embodiment , a male dovetail protrusion 322 extending from third member 114 can mate with a female dovetail 324 located on second member 112 thereby providing a linear guide between second member 112 and third member 114 . any form of male and female guide elements can be used to provide a linear guide between third member 114 and second member 112 . referring to fig3 c and 3d , in the preferred embodiment , second member 112 includes a bore 326 for receiving an end 327 of a threaded rod 328 . further , third member 114 can translate on threaded rod 328 as it is rotated via drive head 331 or 332 . translation is possible because third member 114 includes a threaded bore 330 for receiving threaded rod 328 . thus , rotating threaded rod 328 translates third member 114 along the axis of threaded rod 328 . in use , a user rotates drive head 331 or 332 causing threaded rod 328 to rotate in bore 330 of third member 114 thereby causing third member 114 to move linearly along arm 108 , 108 ′ of ring element 102 . alternately , any reasonable method for moving third member 114 linearly can be used . further , increasing the number of threads / grooves on third member 114 and the number of threads / grooves on rod 328 increases the amount of precision in linearly moving third member 114 . in the preferred embodiment , one rotation moves member 114 about one millimeter . referring to fig4 , the adjustable device having the first , second , and third member in a first position is illustratively depicted . as shown , first member 110 has not moved perpendicular to planar surface 206 of body 106 . further , second member 112 has not been rotated with respect to first member 110 . lastly , third member 114 is depicted in a first position . referring to fig5 , the relative displacement of each of the first , second , and third members is illustratively depicted as compared to fig4 . as shown , first member 110 has been displaced perpendicularly to planar surface 206 of body 106 . further , second member 112 , has rotated with respect to first member 110 . lastly , third member 114 is depicted in a second position where it has moved linearly with respect to second member 112 . referring to fig6 a and 6b , there is shown an exploded view of adjustable device 104 of the preferred embodiment illustratively depicts the internal contact surfaces for each of body 106 , first member 110 , and second member 112 . as shown , body 108 includes internal planar surface 602 which contacts internal planar surface 604 of first member 110 . these planar surfaces provide a guide surface as first member 110 is displaced in a direction perpendicular to the plane of ring 102 . preferably , internal planar surfaces 602 , 604 are substantially smooth surfaces permitting low friction sliding movement . alternatively , in other instances , internal planar surfaces 602 , 604 can include male and female protrusions ( not shown ) for allowing movement only perpendicular to planar surface 206 of body 106 . further , as shown , internal planar surface 606 of first member 110 contacts an internal planar surface 608 of second member 112 . thus , during rotation these guide surfaces minimize motion in an undesired direction . further , the angular motion of second member 112 is guided by track 612 which is in the form of an arcuate guide surface that rides on an arcuate guide element 614 which is attached to a planar surface 616 located on first member 110 . further , track 612 provides a center of rotation centrally located on first member 110 . disc 614 attaches to planar surface 616 by , for example , screws 618 threaded into holes 620 located in first member 110 . because track 612 rides on disc 614 motion in any direction other than the desired angular rotation direction is minimized gear teeth 315 are provided on the outer surfaces of track 612 which are driven by worm 312 . a lock element 350 may be provided to lock second member 112 in the desired angular position . further , third member 114 includes a male dovetail protrusion 610 that mates with a female guide surface 609 acting as a guiding surface when third member 114 moves linearly . each of the above described surfaces increase the control of the adjustable device by minimizing motion other than in the desired directions . referring to fig7 a - 7b , in some embodiments , adjustable device 104 can move only in the anterior - posterior and inferior - posterior directions . as shown , an alternate adjustable device 700 can include a body 702 attached to a ring element 704 . further mounted on body 702 is a first member 706 providing movement perpendicular to body 702 by rotation of screw 714 and a second member 708 mounted on first member 706 providing linear movement along arms 710 of ring element 704 by rotation of screw 712 . in this embodiment there is no rotational movement between member 706 and 702 . as shown , unlike the preferred adjustable device capable of motion in three directions , the adjustable device of fig7 a and 7b is only capable of movement in two directions . as depicted , first member 706 mounted on body 702 provides movement perpendicular to body 702 . further , second member 708 mounted on first member 706 provides motion parallel to the plane of the ring . further , in some embodiments , a scale can be located on at least one of first member 110 and second member 112 . this scale can be used to determine the length of angular or linear displacement by the member . further , a scale can be located on any of the body , first member , second member , or third member for respectively determining the amount of linear , angular , or circumferential movement of each of the members . referring to fig8 a - 9 , there is shown an alternate adjustable device as shown in fig8 a and 8b . the device generally denoted as 700 includes a body 702 , first member 706 and second member 708 but does not provide rotational movement between member 706 and 702 as in adjustable device 104 ( fig5 ). movement parallel to the ring is accomplished by turning screw shaft 712 to move element 708 and movement perpendicular to the ring is accomplished by turning screw shaft 714 and moving element 706 in relation to body 702 . pin holder can be located in one or both of holes 718 . fig9 shows an exploded view of the alternate adjustable device 700 including body 702 and element 708 slidably mounted in a groove 716 in member 706 via a dovetail extension 728 and sliding element 708 . again , screw 712 is rotated in a threaded bore 720 of element 708 to cause the movement of element 708 parallel to the ring arm 710 . element 706 and body 702 includes contacting surfaces 722 and 724 respectively . these surfaces contact when the element 706 is moved in a direction perpendicular to the plane of the ring by turning screw 714 in threaded bore 725 . this movement may be guide by tongue and groove interconnection as in device 104 . referring to fig1 and 11 , there is shown a top view of an alternate system in which the adjustable device 700 is mounted on the inner surface 730 of ring 704 . again , kirschner wires 118 and 120 may be engaged with a foot 101 . referring to fig1 though 13 , there is shown as an alternate adjustable device 700 ′ which is similar to adjustable device 700 with the exception that a second pin holder 740 is attached to a block 742 which is slidably mounted within the groove 716 of element 706 . block 742 has a threaded bore which is mounted on screw shaft 712 and is moveable with respect to element 706 . first block 708 a is also provided with a pin holder and is operated as block 708 . this allows the mounting of two kirschner wires on element 706 with both kirschner wires being adjustable along the length of the arm 710 . again , screw shaft 714 allows the block 706 to move in the direction perpendicular to the plane of arm 710 . as shown in fig1 , indicators scales 746 and 748 may be provided to indicate the amount of movement of the kirschner wires in millimeters . although the invention herein has been described with reference to particular embodiments , it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention . it is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims .

US-201615138722-A

the present invention enhances the player &# 39 ; s gameplay visual , feedback and other experiences by taking advantage of optical adapters , feedback mechanics , advancements in theatrical audio , frame rate throttle , meta - file object framework for storage and retrieval , calibration advancements , vocal command enhancements , voice object lookups , facial / body scan , color / clothing coordination , party or celebration capabilities , noise cancellation , interactive object placement , heart rate monitor , pan - tilt - zoom camera advances , cooperative gameplay advances and programming advancements .

referring to fig1 , a projector 101 ( used in a conventional system 100 , not fully shown ) sends a projected image having an upper bound 102 and a lower bound 104 described by a vertical angle of view 103 to a receiving screen 105 . the arc of the angle of view 103 varies with the settings within the projector limited by the candle output and lens construction . this is an example of the limited height of the field of view presented using a projector in a modern system . overhead - mounted projection allows the player to position themselves under the projection path without producing a shadow on the projection screen . referring now to fig2 , the projector 201 ( used in a conventional system 200 , not fully shown ) sends a projected image having an left bound 202 and a right bound 204 described by a horizontal angle of view 203 to a receiving screen 205 . the arc of the angle of view 203 varies with the settings within the project limited by the candle output and lens construction . this is an example of the limited width of the field of view presented using a projector in a modern system . overhead - mounted projection allows the player to position themselves under the projection path without producing a shadow on the projection screen . referring now to fig3 , a player has the ability to view a much wider and higher angle of view than most projection systems output . a player 301 has the ability to view an upward vertical area 302 , for example , without moving the head 301 , seeing well beyond the border 303 of a regular display screen ( used in a system 300 of the instant invention , not fully shown ). referring now to fig4 , a player 402 has the ability to view an upward vertical area 401 and a corresponding lower area described by an angle 403 which is much greater than the height of a given screen 404 ( used in a system 400 of the instant invention , not fully shown ). referring now to fig5 , a player 501 has the ability to view an left horizontal area 502 and a right horizontal area 503 described by an angle 504 which is much greater than the width of the screen 505 . this gives the player 501 the ability to have sight of , for example , opponents overhead , to the front and / or to the sides 506 , for example , which cannot be displayed on screen 505 ( used in a system 500 of the instant invention , not fully shown ). referring now to fig6 , the sending component of the current invention where light and image data for the purpose of projection are transmitted through a lens adapter 601 ( which may be an optical adapter ) and multiple facets 602 . these facets 602 , which can be constructed of glass , mirrors , plastic , metal , and the like , are responsible for projecting the video images onto a receiving screen at angles well beyond the modern projection capabilities ( used in a system 600 of the instant invention , not fully shown ). referring now to fig7 , the outer body of the projector video adapter 700 is shown . the adapter 700 is composed on a lens connector and lens filter 701 as well as an upper facet set 702 and a lower facet set 703 of the lens adapter 601 . the upper facet 702 and lower facet 703 as well as right and left side facets emit a video signal using enhanced power adapters and increased lighting capability . referring now to fig8 , an alternate embodiment of the current invention shows a half - circular screen 801 with a player 804 standing inside of the screen 801 . the walls of the screen 801 are around the player 804 so that the game surrounds the player 804 from all sides . details of the pixels 802 which make up the screen 801 are shown as 803 . the electrical and video connections between the screen 801 and an instant system ( not fully shown ) are shown in 805 . in this embodiment , the lens adapter and projector may not be used ( used in a system 800 of the instant invention , not fully shown ). fig9 shows another embodiment of the current invention where a screen 902 has a top screen 901 which covers the player 903 overhead and provides additional game interactivity . the screen 902 is connected to the instant system ( not fully shown ) and electricity represented by 904 ( used in a system 900 of the instant invention , not fully shown ). referring to fig1 , the unit 1000 rests on a moving platter 1001 which is positioned by a vertical servo 1004 providing vertical motion 1007 and a horizontal servo 1003 providing horizontal motion 1008 used to track the movements of one or more players using a motion detector 1022 and camera 1010 tethered by a control wire 1011 . the motion detector 1022 is held in a casing 1013 which is connected to a motor 1014 , providing feedback to the servo motor 1005 through a control wire 1015 . the servo motor 1005 sends and receives position signals to and from the vertical servo 1004 and horizontal servo 1003 . a replaceable scent cartridge , also 1014 , is connected to a scent emitter 1012 which can spray a various number of scents into the room . for example , if the player is experiencing a wooded area , an evergreen scent can be delivered based on program settings within the game . the air cannon 1012 can also be programmed to release varying levels of compressed air based on a game experience . the air cannon 1012 is connected to the air chamber 1002 which is controlled by a computer chip inside of 1005 . the units described are supported by a mounting bracket 1011 which also supports the microphone 1021 and speaker 1017 and speaker wire 1018 . the unit rests on a mounting platform 1006 which can be connected to a wall , a table , the floor or a speaker in the room . based on the power levels set within the system , it is best to have the unit mounted to a table or on a wall . the unit is further connected to a computer for receiving program settings by a wire ( s ) 1020 that are attached to the instant system ( not fully shown ). the current invention makes use of input devices such as one or more cameras and motion detection apparatuses to detect player movements which symbolize the addition or use of one or more devices within the context of a game . referring to fig1 , the player 1101 within a play area 1100 hoists and rests a pretend bazooka on his arm while holding the trigger 1102 and aiming the gun in a particular direction 1103 . the bazooka has a handle at the base with a trigger and a handle at the nose used for aiming the unit at the given target . referring now to fig1 , the game 1200 shows the player &# 39 ; s avatar 1201 holding a realistic bazooka by the trigger 1202 and pointing the gun in the same direction 1203 which is determined by the player . the bazooka shows the two handles which are imitating the player &# 39 ; s use of the unit . combining fig1 and fig1 in a gameplay environment shows the relationship of how the players &# 39 ; motions are interpreted on the screen as motion instructions for an avatar within the context of the given game in accordance with an embodiment of the instant application . referring now to fig1 , the example 1300 shows the operation of storing the gameplay file , transmitting the gameplay file , and representing it on the screen . the gameplay file encoder 1310 collects the interactive objects 1301 , the binary codes 1302 , the media objects 1303 , the author objects 1304 , the user objects 1305 , timing objects 1306 , licensing and security objects 1307 , error concealment objects 1308 and prioritization and scalability objects 1309 into one file object 1311 . this format provides the ability to store and retrieve the complex interactive media objects used for the game , game attributes , as well as other components used by the one or more players as well as the objects and actions used by the player and their effects within the game in accordance with an embodiment of the instant application . the sending service 1312 sends the deliverable container 1311 to the one or more storage objects 1315 while the one or more receiving services 1313 receive a retrieved deliverable content 1311 from the one or more storage objects 1315 to one or more receiving player or interactive object / console 1314 . in this manner , the content is shown to the user or player . referring now to fig1 , 1400 represents the components of the current invention and their relationship to each other . under the display section 1401 of the current invention , the perceptual angle of view model 1402 , calibration advancements 1403 , optical advancements 1404 , projection advancements 1405 , and other functionality 1401 related to the display ( such as touch - screen elements or borderless screen elements , and the like 1406 ) are noted and collected together in the display category 1401 . several other topics are shown under the system 1407 , user controls 1414 , feedback 1420 and programming 1425 component headings . related to the display category , is the system section 1407 . the multi - player system aspects 1408 , frame rate throttle 1409 , body / facial scanning 1410 , color coordination 1411 and heart rate monitoring 1412 elements of the system fall into this section . the system 1407 is a portion of the architecture of the game system and is located in the game console as both software and hardware . as another embodiment of the instant invention , even though the system 1407 may reside in the system console , the system may also reside as one or more components distributed across a network and may be accessed across that network by the system console . other functionality 1413 related to the system 1407 ( such as upgrade service handlers , hardware connection modules , and the like 1413 ) are noted . related to the system section 1407 , is the user control advancements 1414 of the instant invention . the voice recognition aspects 1415 , object addition 1416 , team coordination 1417 , and action addition capabilities 1418 and other elements 1419 , such as object and action editors , fall into this section . related to the user control category 1414 , is the feedback section 1420 . the noise cancellation 1421 , system attachments 1422 which include the air cannon , microphone , etc ., and the camera and motion control items 1423 , as well as other elements such as global positioning systems , maps and alarm components 1424 of the feedback system fall into this section . finally , the programming aspects 1425 of the system architecture include the perceptual angle of view software logic 1426 , the multi - player program elements 1427 as well as other elements 1428 related to each of the previous sections such as guidance systems , network modules and the like . referring now to fig1 , 1500 represents the processing steps taken for the game program based on the screen type in which the game is projected or displayed . the game software used to process the logic needed to display one or more visual objects on the one or more screens resides in the game console and could produce the one or more images to display on one or more screens by determining the physical arrangement of the attached one or more screens or optical adapters described in the one or more alternate embodiments of the instant invention . in addition to the embodiment of the multi - screen logic game software residing within the local game console , this software could be located on a network node connected to the game system either through a wired or wireless connection . a particular embodiment of the current invention could receive an indicator from the one or more display units , screens or projector and / or optical adapters to determine the number , dimensions and arrangement of the screens or one or more walls which could be available to present the one or more images to the one or more players . for example , if the screen is a multi - screen or multi - faceted screen , different logic paths are taken than for a simple flat screen . in addition to this , logic is required to scale the capabilities of the system back for a single screen so that the multi - screen capabilities are not used when the one or more receiving display units may not be capable of receiving the data . images and game logic within the software of the game console could receive one or more video settings 1502 which dictate how the game software manages the output to the one or more facets and how the hardware receives the one or more facets and produces the output to the one or more displays . the one or more video settings 1502 are received by the model generation component 1503 which produce the image frames and sprite animations necessary for the given output channel . if the output type is a projection 1504 where the image is transformed in a projection attachment , the image from the projection 1504 is passed to one of either the single facet game process option 1510 or the multi - facet game process option 1506 . if the output type is not a projection 1504 , the image data is passed to one of either the multi - screen process option 1516 or the single screen processing option 1511 . if the image data is displayed using a projected image against a multi - facet receiver 1501 , the output is generated for each facet and repeated while the game play indicator 1508 shows that the game is not done . as each facet is received , the process is repeated from 1506 to 1508 until the game finished indicator 1508 is done . at the point when the game done indicator 1508 is set , the process is stopped 1509 . if the output type is a projection 1504 but is not a multi - facet receiver or the output type is not a projection 1504 but a single screen output 1514 , both output types are handled using the single screen processing receiver 1511 . the output is generated using the single screen processing receiver 1511 and repeated while the game play indicator 1512 shows that the game is not done . as each image is received , the process is repeated from 1510 to 1512 until the game finished indicator 1512 is set . at the point when the game done indicator 1512 is set , the process is stopped 1513 . if the output type is an array of screens 1514 where the images are delivered as multiple facets 1516 , each facet is delivered to an individual screen processor 1517 for that given facet . this is repeated for each facet 1516 where the game done setting 1518 is false . once all of the facets for a single iteration have completed processing , the step is repeated from 1515 and then each facet in the iteration is processed from the facet counter 1516 , using the single screen process receiver 1517 until the game play done indicator 1518 is set to true . once the game play done indicator is set to true , the process is stopped 1519 . referring now to fig1 , an over - head representation of the advanced field of view projection system 1600 with cameras , speakers , feedback units and effective waveforms used to enhance the gameplay experience is depicted . the player 1601 is shown in the center , but the player can be located any where in the room and the system 1600 can support as many players as desired . the example embodiment of the current invention makes use of several advancements in technology in the system . as described previously , the projector 1602 transmits one or more images to the screen or walls as shown in fig8 by the curved wall 801 or fig9 by the overhead 901 and curved wall 902 , which surrounds the one or more players 1601 . speakers and feedback systems 1607 - 1614 are noted in multiple positions surrounding the one or more players 1601 and distributed in this example as a surround sound system where 1613 , by example only , denotes the sub - woofer and corresponding feedback unit . recall the feedback system is shown in fig1 of the present invention . the waveform signals 1615 surrounding the one or more players denote the responding air blasts from the air cannons , shown in fig1 as reference number 1009 , or sounds from the speaker system 1607 - 1614 . waveform signals may also be emitted from the one or more players 1601 and picked up by the one or more microphones as part of the feedback systems 1607 - 1614 . cameras 1603 - 1606 are used to track the one or more player motions , receive motion commands , detect target ranges , help in calculating trajectory pressure , and scan player information into the system . the camera 1604 , by example only , is located above and just behind the player 1601 looking down . all devices , wired or wireless , are connected to a game console . fig1 represents the high - level process logic made in utilizing many of the aspects of the current invention in a one or more player embodiment 1700 . gameplay begins 1701 where the option is made by the one or more players to either turn on the game learning mode or not 1702 by one or more motion instructions , or turned on automatically one the game starts . in the diagram , the one or more players are shown in the center of the play area , but one or more players can be any where in the room and can have as many players in the room as desired and can , again , be expanded by network connections to one or more other one or more player gameplay sessions . the game software used to process the ability to add , remove and change certain aspects of the one or more motion or audio instructions as a portion of the learning mode of the game system may reside within the game console and could store and / or retrieve the one or more motion or audio instructions within the game console , but also could reside on a network node connected to the game system either through a wired or wireless connection . if the game learning mode 1702 is turned on 1703 , the game software detects the player &# 39 ; s motion or audio messages 1704 by use of the motion detection , camera and audio recording equipment described in fig1 as a microphone 1021 referred to 1012 , 1010 and 1021 and defines the specified motions as game commands by converting the one or more motions made by one or more players and comparing the one or more motions with existing motion instructions in the system storage unit which is connected to the game console or attached to the system over a network connection later described in fig1 referring to number 1804 , 1808 and 1807 , as example only . in the manner described , a motion instruction is added to the game system &# 39 ; s storage unit by first having the game learning mode turned on . this is performed by either a predetermined , pre - stored motion instruction made by the player or an audio command . for example , by the player waving their hand in front of the screen , the motion detection unit senses the motion , the camera captures the motion , the game system receives the motion images and compares them to images stored in the system storage unit , performs a match on the data analyzed from the images and searches for a match . in this example , the match is made to turning the learning mode on in the system . once the match is made , the game learning mode is switched on and the player can begin adding , editing or removing audio and motion instructions . alternatively , an audio command can also be issued by the player . this audio command is received by the game system microphone , matched against a storage unit of pre - recorded audio commands , and , if a match is found , performs the command . in this case , the command is to start the system &# 39 ; s learning mode . once the match is found , the learning mode begins and the player can begin to add , remove or edit motion instructions or audio commands . once the learning mode is on , the system repeatedly learns the physical movements of a player or group of players and provides on - screen lists , for example , of items , tasks , or other actions the player may wish the game system to produce or perform . in the example described in fig1 and fig1 , the player makes a motion to hoist a bazooka and , even though the player may not physically have a bazooka in their possession , the bazooka appears and is hoisted by the avatar on the player &# 39 ; s screen . in this example , the player makes a motion to hoist a gun . the player may stagger , as an example , due to the weight of the imaginary gun . once the game system captures the motion , compares the information it receives from the motion , and either finds one or more matches , or none at all , it presents either the player &# 39 ; s avatar performing the intended one or more commands or , for example , a list of possible one or more commands the player may be interested in having the avatar or system perform . in addition to a single avatar performing one or more commands , the motion or audio commands could set off a series of one or more commands or reactions within one or more avatars , other players , objects as well as object , players , avatars , etc . which are not even appearing on the screen yet . at the point where the player is presented with a list , for example , of choices for the related motion or audio instruction , the player can choose the resulting action , item , etc . from the list presented to them , or they can choose additional levels of detail which could provide them with many more choices , if desired . in this manner , a motion or audio instruction produces a motion result , where the motion result can be any of one or more actions , items or another motion / position change . for example , a single command or motion could be issued by one or more players to contact all teammates for a game session . the system , for example , could attempt to contact each teammate , by text , email , phone call , system notification , etc . to organize the gameplay and could satisfy the requirements for the game by substituting in virtual players until the real players joined . once the player makes a selection from the list , for example , the motion instruction may be reviewed so that the player can confirm the motion instruction and the motion instruction with the resulting motion result is stored in the system storage unit . this motion instruction can be made private , public or it can be stored in a collection or it can be sent to a server which can allow other players to purchase and / or download the associated motion instruction for their own game . the player also has the ability to make a motion instruction editable by another player or fixed so that players using the motion instruction could use the instruction for its original intent . motion instructions also have the ability to be modified by the one or more players and re - associated with other one or more motion results if the one or more players desire . to do this , the player could use a universal motion or audible instruction to open the motion instruction editor . they could then form the motion or audible command so that the system could retrieve the motion instruction and associated motion result from the storage unit , for example . at this point , the player could have the opportunity to either change the motion instruction and overwrite the existing one , delete it or copy it to another motion instruction . the player could also have the ability to modify , remove or change the motion result . once the player has finished making their changes to the motion instruction , the motion instruction is stored in the game console storage unit . in order to modify , add to or remove one or more existing motion or audible instructions , either in full or partial , the instruction must be either selected by the player from a list , for example . to do this , the player could review a list of instruction text or images on the screen and select one or more of them by using , for example , a series of one or more motions to select the one or more instructions . this could be done by hand motion , audible command , finger motion , touch screen , using a pen , or any other method . once the one or more instructions have been selected , the player may choose one or more actions that can be taken upon the one or more instructions . in this case , these could include the modification or removal or one or more full or partial portions of one or more instructions . for example , in the case of the bazooka scenario , the player may want to add to the motion when they act like they are lifting a bazooka , they could immediately fire it at an opponent once it has been aimed and then the bazooka is put away because the player does not want to carry it around with them . in this case , the player would add the motion of aiming , firing and putting the bazooka away to the already existing instruction which shows the avatar lifting the bazooka when instructed to do so . in this manner , the player would have the ability to save over the existing instruction , create a new copy of one , as well as transmit it , for example , over the network , for other players to use it . the game system of the current invention also provides range flexibility which allows the user to produce a motion instruction within a range of motions , motion speeds and direction and generalizes the motions it detects and associates with the storage unit the related motion result . in this manner , the player is not required to produce the motion instruction in the same position or orientation as the motion instruction was originally created ; so there is not reason to memorize the exact position , orientation , speed and range of motion of the original motion instruction . this range flexibility covers the player being , in the case of the football scenario , a left - handed or right - handed thrower , their head being back or cocked in a certain direction , as well as many other positions and motions so that there are a large number of potential motions which fall into the range flexibility window however , these are not infinite . this being said , there are specific motions which could be as subtle as a glance or a turn , for example , by the player to “ fake ” a pass or a pass &# 39 ; direction , etc . and the player and system could be aware of these nuances so that the system can compensate for the differences required to retrieve the associated motion result from the game system &# 39 ; s storage unit . restrictions , based on the game system , may also be in place where the player may not have what they want until a certain level has been achieved or a certain amount of virtual money is available to spend . this restriction is dictated by the game author and it tied to the array of potential items , actions , or motions available for the player to choose from . for example , a player may have just started a game and they want a super - cannon they could use to overwhelm their opponents . however , the game author has locked this item until a particular level by the player has been achieved . the player has the opportunity to add , modify and remove these motion instructions stored or to be stored in the game console or remote server by associating the physical movements with the commands or actions in the game . these commands and motion sequences or audio messages 1704 are stored in the advanced meta - file object format 1705 in the system storage unit , shown in fig1 as 1315 , fig1 as either 1807 or 1809 , or fig1 within the console 1907 , the one or more servers 1907 or the console 1908 . further player motion sequences or audio messages 1704 are interpreted as the associated commands or actions by performing storage unit searches using signatures from the audio or command instructions and searching for comparative data which could result in a match against the given audio or command instruction in the game console or network storage unit . when the player turns off the game learning mode 1706 , either by an audio or motion command or when it automatically turns off , normal gameplay begins 1707 . if the game learning mode 1702 is not turned on 1708 by the one or more players , either by an audio or motion command , normal gameplay begins 1707 . if audio or motion instructions are performed during gameplay and a match is not found in the system for the audio or motion command , then the motion or audio command is ignored by the system . if the one or more audio or motion instructions are intended to have one or more responses by the system console , the game learning mode can be switched on by a given command and can be added to the game system storage unit at any time . as gameplay progresses , the game software in the game console or received across the network to the game console , as an example only , either presents the one or more players with targets 1709 which can be fired upon or receives commands from the one or more players 1713 . these targets are produced by the game software running on the game console . the one or more players can fire at the one or more targets by , as an example , moving their hands back and forth in a shooting motion . this shooting motion is interpreted by the game system as a motion instruction and , taking in consideration the angle and timings of the one or more motions , can hit or miss the targets and show the one or more results to the one or more players on the screen as they “ fire ” upon the one or more targets . during the time that the game software presents the one or more targets to the one or more players 1709 , the game software tracks the one or more players &# 39 ; positions 1710 . if the one or more targets in this example have the ability to fire at the one or more players , the game software reads and analyzes the target type , its capabilities , and “ fires ” 1711 upon the one or more players using the one or more air cannons , for example , as depicted in fig1 referring to number 1009 and / or other devices shown in fig1 to simulate a gun or cannon , etc . firing on the one or more players in battle . the player , in turn , responds to the one or more target attacks 1712 by moving their hands at the targets in a shooting motion . in the described example , the game software , stored in either a local or remote game console , either by disk , chip , drive , memory , etc ., would be accessed to react to motion commands in a method similar to the following description . as a hypothetical , simplified example , five aircraft could be flying over the one or more player &# 39 ; s heads . the aircraft may , for example , appear on the ceiling portion of the screen , as shown in fig5 as 506 or fig9 as 901 . the aircraft could be shooting at the one or more players on the “ ground ” at , for example , 45 degree angles . since the aircraft are moving at a certain velocity relative to the one or more players &# 39 ; velocities , the angles of each of the one or more players &# 39 ; devices , such as bazookas , aircraft , etc ., must be considered in the mathematical calculation necessary to simulate a “ hit ” either by the approaching aircraft or the one or more players . in addition to the vertical and horizontal angles , multiple velocities of the one or more players , the velocities and capabilities of the one or more “ guns ”, including their corresponding firepower and damage capabilities , the damage to and around units in the area must be considered , for example . in this way , a “ hit ” made by the one or more players on the approaching aircraft would be achieved if the angle of the aircraft , the aircraft speed , the player speed , angle of the projectile , and the speed of the one or more projectiles “ meet ”, for example , at a particular point . regardless of how the game software receives the commands from the player 1713 , the game software receives the commands either by a wired or wireless controller 1714 , touch screen commands 1715 , audio messages 1716 or motion sequences 1717 and attempts to interpret the command ( s ) as stored or not 1718 . if the command is not stored , it is considered a player move or other response 1720 and the game software displays the results of the actions 1721 . for example , if a player is walking and they turn a corner , the avatar on the screen can perform the same motion , but this is simply done by the gameplay system monitoring and mimicking the player on the screen . this is not handled in the same way in the system as a player drawing back to throw a virtual football to an open wide receiver . even though the avatar could walk through a city , for example , and certain three - dimensional graphical models of the city could be generated by the gameplay system , as well as the avatar looking like they are moving , it does not require a lookup in the gameplay storage unit to determine the motion result of a motion which instigates a new gameplay result , for example , the first time the player , as a quarterback in a game , receives and throws the football . subsequent plays made by the player in the context of the game are expected to be playing as a quarterback until a new motion instruction is received by the system . other motions are ignored altogether . as an example , if the player has instructed the avatar to make a particular move which takes , for example , a few minutes , the player has the opportunity to get a drink of water . the motions made by the player to get a drink of water or to rest are not recorded in the system as a gameplay motion and these are , in essence , ignored by the system . in a scenario where a player is playing a football game , for example , the player could snap the ball and throw it to a receiver . once the ball has been thrown by the quarterback , the players &# 39 ; motions could be ignored by the system as control is now given to the other players which include a potential receiver and potential tacklers . if the receiver catches the ball and gets tackled and the gameplay ends for the given down , the motion of the other players can be ignored . in addition , in this scenario , the receiving player , if real , can be virtually tackled by a player remotely located and connected to the game through a network connection . in the case when this takes place , the player playing as the receiver may still be standing in their room , but their avatar on the screen is lying on the ground with several tacklers on top of him . this picture is shown on the screens of all players ( and / or observers of the gameplay ). there is also a point where the game software derives a random outcome and advances play in the direction of that outcome . at this point , all motion made by other real players is ignored by the system and picked up again when a motion instruction or other interactive play segment begins . there could also be times during gameplay where a slight variation of a “ known ” move is made by one or more players . in this case , the system may ask the one or more players what they are intending to do and may present the ability for the one or more players to attach a motion result to the suspected motion instruction or to ignore the instruction . if they wish to add the move to the system as a new or appended motion instruction , they may have the ability to do this and it may be stored in the game system storage unit . if the one or more players notify the game system that the move was really an already existing motion instruction , for example , the one or more players may have the opportunity to connect the move to an already existing one or more motion instructions so that the game system may interpret both of the moves as a single motion instruction . in this manner , the system may have the ability to characterize particular motions and when a motion lies outside of the range of these characteristics , the player may have the opportunity to notify the game system of their intent . for example , a player playing as a quarterback in a football game could be trying to fake a thrown to a receiver by dropping the ball behind them before throwing it and then catching it with their other hand and tossing it to another player . since the real player does not necessarily have a ball , the system could determine that their left hand , for example , is being placed behind their back in a very unusual position . at this point , the game system could determine that the motion is new by receiving the motion data from the camera and motion detector , comparing the motion data with the system &# 39 ; s storage unit , checking if the motion data already exists in the system . if the system does not find this set of moves within the storage unit , it could prompt the one or more players on the screen if this is a special move . if it is , the player could perform many tasks or simply ignore the prompt . for example , the player could agree that this is a new motion instruction . in this case , the player would see the prompt on the screen , for example , and react to it by performing an audio of motion instruction . in this way , the system could , for example , receive the instruction and show a series on one or more menu items on the screen . the one or more menu items could be answered by the one or more players on the screen . in this case , this new move could be given a name , posted to the one or more players &# 39 ; storage units as well as shared over the network and stored in a storage unit which could be accessed by other players or another one or more players storage units , such as a team . again , in the described example , the motion instruction could be stored and shared by the one or more players publicly or privately among themselves for their team to utilize . beyond this , the subsequent motions , such as tossing the ball to the left or the right to another player could be captured and handled accordingly instead of throwing the ball as normal . if the command is stored 1722 and found by the console software comparing the one or more player audio or motion command signatures to the one or more motion instruction records stored in the system storage unit , the game software retrieves the one or more items or enables the actions &# 39 ; capabilities associated with the stored command 1723 signature which is found in the database ( storage unit ). the result is presented to the player on the display unit 1721 by either presenting the item associated with the audio or motion instruction or by showing the avatar on the screen producing the movement associated with the audio or motion instruction found in the database record . if the gameplay is finished 1724 , the gameplay ends 1725 , otherwise , it continues 1707 . the processes used to relate the motion instructions to the resulting items or commands in the game system are described in fig1 where a motion instruction is captured by the camera system 1801 , transforming the motion into a motion sequence , sending the motion sequence to the motion detection unit 1802 . the motion detection unit 1802 converts the motion sequence into one or more motion packets , transforming the motion packets into edge points , sending the edge points to the motion logic component 1803 . the motion logic component 1803 receiving the edge points , forming a database query made up of the edge points , sending the database query to the database logic component 1804 where the database query is run against the database 1807 , the database logic component 1804 receiving the query results from the database 1807 , sending the results to the response handler 1805 . the response handler 1805 , receiving the results of the database query from the database logic component 1804 , either prompts the player for more information , receiving the one or more responses from the player and / or sending the results of the motion instruction and / or the results of the player prompts to the significance learning module 1806 . the significance learning module , receiving the information from the response handler 1805 , stores the motion instruction and result in the database 1807 . in addition , each of the nodes described in fig1 could be located in a single or multiple nodes , each of these being located either locally within the game system or outside of the game system on a network device , disk , chip , etc . over a wired or wireless connection . at any time , the player may ask the system to store or retrieve additional motion instructions and / or updates from a network 1808 which is connected to a remote database 1809 which may include connections from many other players having the same ability to store and retrieve motion instructions and / or updates . the system can include a set of motion or audio instructions and can be updated from a server based on the universal instruction lists as well as motion instructions for a particular game the player has purchased . these updates can be made by system developers and may also be made by other players . in this manner , motion or audible instructions are not limited to players or system developers . the associated audio or motion instructions could be provided , for example , by professional quarterbacks . these could be uploaded , as an example , to a remote server and made available to players . motion instructions which may appear to override custom motion instructions that the player has already produced on their system may result in a prompt which the player can answer . these updates can happen when the player first starts the system or in the background so that gameplay is not interrupted . players can also choose to have the system overwrite any potential conflicting motion instructions with the updates if they wish . likewise , in the same way that motion instructions are continually updated , the models for allowable ranges of motion is continually updated . so as range models improve over use and time , the details to these models are also updated in the player systems to improve the player &# 39 ; s experiences . for example , if an improvement is made in a lateral snap where the quarterback can hide the ball for a second and toss it to a receiver , the original models for this may be crude or missing from the system so that the motion result is not available to the player for them to choose , then an update to the system could provide the system with the motion result the player wished to associate with the motion instruction in the first place . referring now to fig1 , gaming system 1900 includes multiple players , represented as the players 1901 and 1902 receiving and sending information to and from the input / output device 1903 connected to the console 1904 connected to a screen 1905 and a network 1906 where information can be shared , retrieved or stored at the server 1907 . in addition to the above , multiple players represented as player 1911 and player 1912 send and receive input from the input / output device 1910 connected to a console 1908 and a screen 1909 and a network 1906 where information can be shared , retrieved or stored at the server 1907 as well as interact with multiple players 1901 and 1902 across the network . likewise , players 1901 and 1902 can interact through the input / output device 1903 with players 1911 and 1912 using their input / output device 1910 . in this scenario , if the players 1901 , 1902 , 1911 and 1912 are playing together in the same game , the screen interactions , avatars of the associated players , including the motion instructions for multiple players 1901 and 1902 could appear on the screen 1909 across the network for the multiple players 1911 and 1912 to view and interact with , and the avatars of the other players 1911 and 1912 , as well as the motion instructions , could appear on the screen 1905 which is viewed by players 1901 and 1902 . furthermore , in addition to the described scenarios resulting in a collection of one or more motion or audible instruction sets , the player could designate the collection as a playbook . the playbook could belong to a team , real or virtual , for example , and could have private or public characteristics associated with it . the playbook could be made up of motion instructions and audible instructions . the audible instructions could be configured by the player to be heard , for example , by teammates , but not by opponents . for example , if the team is in a huddle and the quarterback is speaking to the players , the players on the side of the avatar speaking the commands could hear the information , while the opponents might not . the audio level of the quarterback also varies by their loudness level and the direction in which they are speaking . for example , the audio information from the quarterback in the huddle could not be heard by the opposing team members but the commands screamed by the quarterback on the line of scrimmage could be heard by both player team members but it might by muffled by the crowd or because the quarterback is shouting in the opposite direction . the parameters required for the audible commands to be public or private , for example , could be stored with the audible commands so that , when the commands are retrieved , the system would know that only certain speakers for certain players , for example , would play the corresponding sound are that the volume levels would be different on the corresponding speakers so that they would mimic the player &# 39 ; s position , audio level , intent , etc . likewise , the same could be stated pertaining to the coaches and their signals to their players , other coaches , etc . quarterbacks , for example , could hear their coaches , but not the opposing coaches as well as determining their hand signals , etc . the present invention also lends itself to advertising around this technology as well as selling virtual seating , using virtual currency or otherwise , where fans could purchase a seat to get a particular angle on the game . the better price paid for the seat , the better the angle and audio quality is presented to them by the system . player &# 39 ; s could also open up private data such as playbooks and audio commands to particular observers if they desire . furthermore , the present invention incentives to become early adopters to the technology is large due to the ability to promote the particular motion information creator &# 39 ; s name or brand so that later adopters have the luxury of making use of the existing motion information that the early adopters created . referring now to fig2 and fig2 , gaming system 2000 and 2100 show an example of the multiple physical connections of the present invention including the base unit 2001 which includes at least one processor 2002 and at least one memory 2003 having at least one learning module 2004 and at least one storage unit 2005 connected to at least one feedback system 2007 , having at least one camera 2008 , microphone 2009 , and optionally one or more motion detectors 2010 , speakers 2011 and location units 2012 , and at least one display 2006 , alternatively , a projector 2013 optionally having a lens adapter 2014 or multiple projectors 2013 without a lens adapter 2014 . the gaming system 2000 optionally connected by a connection 2015 to a wired or wireless network 2016 via connector a , connected to fig2 using connector a ′ connected using a connection 2101 to at least one base system 2102 which includes at least one processor 2103 and at least one memory 2104 having at least one learning module 2105 and at least one storage unit 2106 connected to at least one feedback system 2110 , having at least one camera 2111 , microphone 2112 , and optionally one or more motion detectors 2113 , speakers 2114 and location units 2115 , and at least one display 2107 , alternatively , a projector 2108 optionally having a lens adapter 2109 or multiple projectors 2108 without a lens adapter 2109 . in one embodiment , a controller - less gaming system comprises a base system including at least one processor and memory , and a learning module , a feedback system including at least one : camera , microphone , and motion detector , wherein the feedback system is communicatively coupled to the base system , a display communicatively coupled to the base system , and a storage unit communicatively coupled to the base system , wherein the feedback system receives input from at least one of the camera , the microphone , and the motion detector , and sends the input to the base system , wherein the base system compares the input to other input in the storage unit and if the comparison produces a non - satisfactory result : the base system chooses a closest result to the input if the closest result is above or equal to a threshold and displays the closest result or the base system chooses a default result to the input if the closest result is below the threshold and displays the default result , and if the closest result or the default result is not an intended result , the base system receives an adjusted input from the feedback system and displays a result of the adjusted input on the display . the input and the other input include at least one of : angles of a body and body part , movement of the body and the body part , direction of the body and the body part , speed of the body and the body part , audio from the body or the body part , biometric information the body or the body part , items attached to the body or the body part , or items supporting the body or the body part . the base system stores the adjusted input result as another one of the closest result in the storage unit , displays the closest result when it receives another adjusted input result without an adjusted input from the feedback system , displays the closest result and the adjusted input result and provides an intended action associated with the closest result and an intended action associated with the adjusted input result . the base system is communicatively coupled to at least one of : a plurality of network connections , a remote storage unit , a projection system , a projection system using a lens adapter , a feedback system , a feedback system using one or a plurality of speakers , a feedback system having a location unit , a base system , a display , a curved display , a curved display with an overhead component , a wired display , a wireless display , a local display , a remote display , a wired connection , a wireless connection , an air cannon or a storage unit . at least one person ( which may be a player or a spectator or both at varying times during the game ) is present locally with the base system or present remotely from the base system . the current invention provides a number of solutions including : a controller - less gaming system , comprising : a base system including at least one processor and memory , and a learning module ; a feedback system including at least one : camera , microphone , and motion detector , wherein the feedback system is communicatively coupled to the base system ; a display communicatively coupled to the base system ; and a storage unit communicatively coupled to the base system ; wherein the feedback system receives input from at least one of the camera , the microphone , and the motion detector , and sends the input to the base system ; wherein the base system compares the input to other input in the storage unit and if the comparison produces a non - satisfactory result : the base system chooses a closest result to the input if the closest result is above or equal to a threshold and displays the closest result ; or the base system chooses a default result to the input if the closest result is below the threshold and displays the default result ; and if the closest result or the default result is not an intended result , the base system receives an adjusted input from the feedback system and displays a result of the adjusted input on the display . the base system stores the adjusted input result as another one of the closest result in the storage unit , the base system displays the closest result when it receives another adjusted input result without an adjusted input from the feedback system , the base system displays the closest result and the adjusted input result and provides an intended action associated with the closest result and an intended action associated with the adjusted input result , the base system is communicatively coupled to at least one of : a plurality of network connections ; a remote storage unit ; a projection system ; a projection system using a lens adapter ; a feedback system ; a feedback system using one or a plurality of speakers ; a feedback system having a location unit ; a base system ; a display ; a curved display ; a curved display with an overhead component ; a wired display ; a wireless display ; a local display ; a remote display ; a wired connection ; a wireless connection ; an air cannon ; or a storage unit . at least one person is : present locally with the base system ; or present remotely from the base system . the input and the other input include at least one of : angles of a body or a body part ; movement of the body or the body part ; direction of the body or the body part ; speed of the body or the body part ; audio from the body or the body part ; biometric information the body or the body part ; items attached to the body or the body part ; or items supporting the body or the body part .

US-201113159514-A

disclosed is an articulated headrest for use with dental chairs and the like which can be quickly and easily converted from left hand to right hand operation . a simple clutch mechanism locks the headrest at any adjusted position . the mechanism for unlocking the clutch is a push button located at the side of the headrest . this mechanism is contained in a housing which can be easily removed and its components rearranged to move the push button from one side of the headrest to the other .

referring to the drawings , fig1 shows a headrest generally indicated at 10 . it should be appreciated that the upholstery material covering the front of the headrest has been removed so as to expose the internal components . the headrest includes a frame 12 which is journaled at its lower end to a tang , a portion of which is shown at 14 . the tang is attached to the backrest of the dental chair ( not shown ) in a conventional manner and forms no part of the present invention . the means for locking the headrest in an adjusted position is also conventional . briefly , the lock means includes a first clutch member 16 which is fixed to the tang , a second clutch member 18 which is axially movable with respect to the first member , a lever arm 20 pivoted to the headrest at 22 for moving the second clutch member out of engagement with the first member and a spring 24 for urging the second clutch member 18 into engagement with the first . the end of lever 20 on the other side of pivot 22 from clutch member 18 is bifurcate . one branch 26 of this bifurcate end carries a pin 28 . the other branch 30 of the bifurcate end has two tapped holes 32 , for purposes set out hereinbelow . the headrest frame 12 has a rectangular opening 34 ( fig1 and 2 ) for receiving a square housing 36 , the housing being attached to flanges 38 within the headrest frame by any suitable means such as screws 40 . the square configuration and the location of the screws permit the housing to be attached to the headrest frame either in a first position as shown in fig1 or in a second position wherein the housing is rotated 180 ° from the first position . the housing has a base 42 . upstanding from the base according to the orientation as shown in fig1 is a front wall 44 and a rear wall 46 and a side wall 48 . completing the construction of housing 36 is an opening 50 which extends through side wall 48 and a pivot post 52 which is formed integral with the front wall 44 of the housing . opening 50 is adapted to receive a push button member 54 which extends into the housing . the portion of the push button within housing 36 is pivotally attached to one end of a link 56 . the other end of link 56 is provided with three openings ; two openings 58 , are clearance holes matching the tap holes 32 on the lever arm second branch 30 and the third opening , 60 is elongated and is elongated and is adapted to receive pin 28 . link 56 has yet another opening 62 intermediate its ends for receiving the pivot post 52 . with respect to the arrangement of the various components as shown in fig1 the operation of the mechanism is as follows . spring 24 , as set out hereinabove , is biased to urge clutch member 16 and 18 into engagement . in order to disengage the clutch , clutch member 18 must be moved to the right as viewed in fig1 . this is accomplished in the present invention simply by operating push button 54 . since the operator would normally be standing behind the head of the patient ( at the top as viewed in fig1 ) operation of the button 54 would be accomplished with the right hand of the dentist or his assistant . accordingly , operating push button 54 moves it to the right as shown in fig1 causing link 56 to rotate clockwise about pivot post 52 . because link 56 is pivotally connected to lever arm 20 by means of pin 28 , this movement of the link causes the lever arm to rotate counterclockwise about its pivot 22 . counterclockwise movement of lever 20 in turn carries clutch member 18 away from fixed clutch member 16 so as to unlock the headrest . thus , with the configuration as shown in fig1 link 56 and lever 20 together form a compound lever system wherein movement of push button 54 at one end of the lever system to the right as shown in fig1 causes clutch member 18 on the other end of the lever system to move in the same direction . in order to permit operation from the left hand side of the headrest , housing 36 is attached to the headrest frame in a second position which is rotated 180 ° from the first position as shown in fig1 . the second position and the configuration of the various components at the second position is illustrated in fig4 . as shown in fig4 link 56 is rigidly attached to the second branch 30 of the lever arm . this is accomplished by any suitable means such as with screws 64 that pass through clearance openings 58 and are threaded to tap holes 32 in the second branch . with this arrangement , link 56 merely forms an extension of the second branch 30 so that when push button 54 is operated , link 56 is moved to the left as shown in fig4 which rotates the lever arm counterclockwise about its pivot 22 . as set forth hereinabove , counterclockwise rotation of lever arm 20 moves clutch member 18 to the right and away from the fixed clutch member 16 to unlock the headrest . with link 56 merely forming an extension of lever arm branch 30 , the link and lever arm together form a simple lever system for disengaging the clutch members wherein movement of push button 54 on one end of the lever system causes clutch member 18 on the other end to move in the opposite direction . thus , it should be appreciated that the present invention accomplishes its intended objects by providing a simple , easily assembled mechanism for unlocking an articulated headrest of a dental chair or the like . the invention allows the identical components to be quickly and easily rearranged so as to permit either a left hand or a right hand operation of the mechanism .

US-86135177-A

methods for diagnosing and treating neuropsychiatric disorders , especially bipolar disorder , and to methods for identifying compounds for use in the diagnosis and treatment of neuropsychiatric disorders are disclosed . also disclosed are novel compounds and pharmaceutical compositions for use in the diagnosis and treatment of neuropsychiatric disorders such as bipolar disorder .

the development and maintenance of the vertebrate nervous system depends , in part , on the physiological availability of neuronal survival proteins known as neurotrophic factors . neurotrophic factors play a role in maintaining neurons and their differentiated phenotypes in the adult nervous system . nerve growth factor ( ngf ) remains the best characterized neurotrophic factor . however , brain - derived neurotrophic factor ( bdnf ) has been cloned and shown to be homologous to ngf ( leibrock et al ., nature 341 : 149 - 152 ( 1989 ); hofer et al ., embo j . 9 : 2459 - 2464 ( 1990 ); maisonpierre et al ., genomics 10 : 558 - 568 ( 1991 )). bdnf is initially synthesized as a 251 amino acid protein precursor that is subsequently cleaved to yield the mature protein . the mature form of bdnf essentially corresponds to the c - terminal half of its precursor and comprises 119 amino acids . in the developing rat , bdnf expression undergoes an increase from initially low levels , and in the adult rat central nervous system , bdnf is expressed at its highest level in the hippocampus . expression of bdnf is detectable in adult tissues outside of the central nervous system only in heart , lung and skeletal muscle ( maisonpierre et al ., science 247 : 1446 - 1451 ( 1990 ); hofer et al ., embo j . 9 : 2459 - 2464 ( 1990 )). as shown in fig1 a and 1b , the human genomic sequence of bdnf is seq id no : 1 , the human cdna sequence is seq id no : 2 , the rat genomic sequence is seq id no : 3 , the rat cdna sequence is seq id no : 4 , the mouse cdna sequence is seq id no : 5 , and the pig cdna sequence is seq id no : 6 . the human amino acid sequence is seq id no : 7 , the rat amino acid sequence is seq id no : 8 , the mouse amino acid sequence is seq id no : 9 , and the pig amino acid sequence is seq id no : 10 . sequences are designated with a lowercase letter signifying species , an uppercase “ b ” for bdnf , and a g or a c in parentheses distinguishing between either a genomic or cdna source for the sequence . dna sequence identities to the top human sequence are indicated by a dot , and gaps are indicated by a dash . in - frame stop codons in the upstream regions are underlined . amino acid translation is indicated above the human nucleotide sequence ; only amino acid differences with the human sequence are indicated for the other sequences . amino acids are numbered with position + 1 assigned to the first residue in the mature protein sequence . rna splice sites ( splice1 and splice2 ), the b start site , the consensus protein glycosylation signal , and the consensus protein cleavage signal involved in release of the mature bdnf are indicated . only sequence flanking splice site 1 is shown for the human and rat genomic clones , since this is the only region in which they differ from their respective cdna sequences . an exception to this is the presence of a single mismatch ( a for g ) between the human bdnf genomic and cdna sequence at nucleotide position 424 , resulting in the substitution of a methionine residue for a valine residue at amino acid position − 63 in the genomic - derived protein sequence . as used herein , polymorphism refers to the occurrence of two or more genetically determined alternative sequences or alleles in a population . a polymorphic marker or site is the locus at which divergence occurs . preferred markers have at least two alleles , each occurring at frequency of greater than 1 %, and more preferably greater than 10 % or 20 % of a selected population . a polymorphic locus may be as small as one base pair , in which case it is referred to as a single nucleotide polymorphism . as described herein , it has been discovered that a polymorphism in the gene for bdnf is negatively correlated with incidence of neuropsychiatric disorders ( e . g ., bipolar disorder ). in particular , it has been discovered that one or more single nucleotide polymorphisms within the nucleotide sequence encoding the 132 amino acid prepro portion of the bdnf gene product are correlated with a reduced incidence of bipolar disorder in the sample population assessed as described herein . in one embodiment , a single polymorphism from g to a at nucleotide position 424 in fig1 or at a nucleotide position corresponding thereto , resulting in an amino acid change from valine to methionine at amino acid position − 63 ( relative to the start of the mature protein ; see fig1 ), or at an amino acid position corresponding thereto , is correlated with a reduced incidence of bipolar disorder in the sample population assessed as described herein . this polymorphism resides within the 132 amino acid precursor portion ( the prepro portion ) which is cleaved from the mature protein . data from the work described herein has shown that there is a variation from random ( i . e ., that which would be expected by chance ) in the transmission of the reference ( g ) and variant ( a ) alleles from a parent who is heterozygous for the bdnf alleles to an offspring diagnosed with bipolar disorder . the variant allele ( a ) is transmitted less frequently ( 34 of 98 times ) to the bipolar offspring than would be expected by chance , while the reference allele ( g ) is transmitted more frequently ( 64 of 98 times ) than would be expected by chance ( p = 0 . 004 ). thus , it appears that the variant allele may contribute to protection or reduction in symptomology with respect to bipolar disorder . alternatively , this particular polymorphism may be one of a group of two or more polymorphisms in the bdnf gene which contributes to the presence , absence or severity of the neuropsychiatric disorder , e . g ., bipolar disorder . thus , the invention relates to a method for predicting the likelihood that an individual will have a neuropsychiatric disorder , or for aiding in the diagnosis of a neuropsychiatric disorder , e . g ., bipolar disorder , or a greater likelihood of having reduced symptomology associated with a neuropsychiatric disorder , e . g ., bipolar disorder , comprising the steps of obtaining a dna sample from an individual to be assessed and determining the nucleotide present at nucleotide position 424 of the brain - derived neurotrophic factor ( bdnf ) gene . the presence of an “ a ” ( the variant nucleotide ) at position 424 indicates that the individual has a lower likelihood of having a neuropsychiatric disorder , or a greater likelihood of having reduced symptomology associated with a neuropsychiatric disorder , than if that individual had the reference nucleotide at that position . conversely , the presence of a “ g ” ( the reference nucleotide ) at position 424 indicates that the individual has a greater likelihood of having a neuropsychiatric disorder , or a likelihood of having increased symptomology associated with a neuropsychiatric disorder , than if that individual had the variant nucleotide at that position . in a preferred embodiment , the neuropsychiatric disorder is bipolar disorder . in a particular embodiment , the individual is an individual at risk for development of bipolar disorder . in another embodiment the individual exhibits clinical symptomology associated with bipolar disorder . in one embodiment , the individual has been clinically diagnosed as having bipolar disorder . the genetic material to be assessed can be obtained from any nucleated cell from the individual . for assay of genomic dna , virtually any biological sample ( other than pure red blood cells ) is suitable . for example , convenient tissue samples include whole blood , semen , saliva , tears , urine , fecal material , sweat , skin and hair . for assay of cdna or mrna , the tissue sample must be obtained from an organ in which the target nucleic acid is expressed . for example , cells from the central nervous system ( such as cells of the hippocampus ), neural crest - derived cells , skin , heart , lung and skeletal muscle are suitable sources for obtaining cdna for the bdnf gene . neural crest derived cells include , for example , melanocytes and keratinocytes . many of the methods described herein require amplification of dna from target samples . this can be accomplished by e . g ., pcr . see generally pcr technology : principles and applications for dna amplification ( ed . h . a . erlich , freeman press , new york , n . y ., 1992 ); pcr protocols : a guide to methods and applications ( eds . innis , et al ., academic press , san diego , calif ., 1990 ); mattila et al ., nucleic acids res . 19 , 4967 ( 1991 ); eckert et al ., pcr methods and applications 1 , 17 ( 1991 ); pcr ( eds . mcpherson et al ., irl press , oxford ); and u . s . pat . no . 4 , 683 , 202 . other suitable amplification methods include the ligase chain reaction ( lcr ) ( see wu and wallace , genomics 4 , 560 ( 1989 ), landegren et al ., science 241 , 1077 ( 1988 ), transcription amplification ( kwoh et al ., proc . natl . acad . sci . usa 86 , 1173 ( 1989 )), and self - sustained sequence replication ( guatelli et al ., proc . nat . acad . sci . usa , 87 , 1874 ( 1990 )) and nucleic acid based sequence amplification ( nasba ). the latter two amplification methods involve isothermal reactions based on isothermal transcription , which produce both single stranded rna ( ssrna ) and double stranded dna ( dsdna ) as the amplification products in a ratio of about 30 or 100 to 1 , respectively . the nucleotide which occupies the polymorphic site of interest ( e . g ., nucleotide position 424 in bdnf ) can be identified by a variety methods , such as southern analysis of genomic dna ; direct mutation analysis by restriction enzyme digestion ; northern analysis of rna ; denaturing high pressure liquid chromatography ( dhplc ); gene isolation and sequencing ; hybridization of an allele - specific oligonucleotide with amplified gene products ; single base extension ( sbe ); or analysis of the bdnf protein . in a preferred embodiment , determination of the allelic form of bdnf is carried out using sbe - fret methods as described in the examples , or using chip - based oligonucleotide arrays . a sampling of suitable procedures are discussed below in turn . the design and use of allele - specific probes for analyzing polymorphisms is described by e . g ., saiki et al ., nature 324 , 163 - 166 ( 1986 ); dattagupta , ep 235 , 726 , saiki , wo 89 / 11548 . allele - specific probes can be designed that hybridize to a segment of target dna from one individual but do not hybridize to the corresponding segment from another individual due to the presence of different polymorphic forms in the respective segments from the two individuals . hybridization conditions should be sufficiently stringent that there is a significant difference in hybridization intensity between alleles , and preferably an essentially binary response , whereby a probe hybridizes to only one of the alleles . hybridizations are usually performed under stringent conditions , for example , at a salt concentration of no more than 1 m and a temperature of at least 25 ° c . for example , conditions of 5 × sspe ( 750 mm nacl , 50 mm naphosphate , 5 mm edta , ph 7 . 4 ) and a temperature of 25 - 30 ° c ., or equivalent conditions , are suitable for allele - specific probe hybridizations . equivalent conditions can be determined by varying one or more of the parameters given as an example , as known in the art , while maintaining a similar degree of identity or similarity between the target nucleotide sequence and the primer or probe used . some probes are designed to hybridize to a segment of target dna such that the polymorphic site aligns with a central position ( e . g ., in a 15 - mer at the 7 position ; in a 16 - mer , at either the 8 or 9 position ) of the probe . this design of probe achieves good discrimination in hybridization between different allelic forms . allele - specific probes are often used in pairs , one member of a pair showing a perfect match to a reference form of a target sequence and the other member showing a perfect match to a variant form . several pairs of probes can then be immobilized on the same support for simultaneous analysis of multiple polymorphisms within the same target sequence . the polymorphisms can also be identified by hybridization to nucleic acid arrays , some examples of which are described in wo 95 / 11995 . wo 95 / 11995 also describes subarrays that are optimized for detection of a variant form of a precharacterized polymorphism . such a subarray contains probes designed to be complementary to a second reference sequence , which is an allelic variant of the first reference sequence . the second . group of probes is designed by the same principles , except that the probes exhibit complementarity to the second reference sequence . the inclusion of a second group ( or further groups ) can be particularly useful for analyzing short subsequences of the primary reference sequence in which multiple mutations are expected to occur within a short distance commensurate with the length of the probes ( e . g ., two or more mutations within 9 to 21 bases ). an allele - specific primer hybridizes to a site on target dna overlapping a polymorphism and only primes amplification of an allelic form to which the primer exhibits perfect complementarity . see gibbs , nucleic acid res . 17 , 2427 - 2448 ( 1989 ). this primer is used in conjunction with a second primer which hybridizes at a distal site . amplification proceeds from the two primers , resulting in a detectable product which indicates the particular allelic form is present . a control is usually performed with a second pair of primers , one of which shows a single base mismatch at the polymorphic site and the other of which exhibits perfect complementarity to a distal site . the single - base mismatch prevents amplification and no detectable product is formed . the method works best when the mismatch is included in the 3 ′- most position of the oligonucleotide aligned with the polymorphism because this position is most destabilizing to elongation from the primer ( see , e . g ., wo 93 / 22456 ). the direct analysis of the sequence of polymorphisms of the present invention can be accomplished using either the dideoxy chain termination method or the maxam - gilbert method ( see sambrook et al ., molecular cloning , a laboratory manual ( 2nd ed ., cshp , new york 1989 ); zyskind et al ., recombinant dna laboratory manual , ( acad . press , 1988 )). amplification products generated using the polymerase chain reaction can be analyzed by the use of denaturing gradient gel electrophoresis . different alleles can be identified based on the different sequence - dependent melting properties and electrophoretic migration of dna in solution . erlich , ed ., pcr technology , principles and applications for dna amplification , ( w . h . freeman and co , new york , 1992 ), chapter 7 . alleles of target sequences can be differentiated using single - strand conformation polymorphism analysis , which identifies base differences by alteration in electrophoretic migration of single stranded pcr products , as described in orita et al ., proc . nat . acad . sci . 86 , 2766 - 2770 ( 1989 ). amplified pcr products can be generated as described above , and heated or otherwise denatured , to form single stranded amplification products . single - stranded nucleic acids may refold or form secondary structures which are partially dependent on the base sequence . the different electrophoretic mobilities of single - stranded amplification products can be related to base - sequence differences between alleles of target sequences . the polymorphism of the invention may contribute to the protection of an individual against bipolar disorder in different ways . the polymorphism may contribute to phenotype by affecting protein structure . by altering amino acid sequence , the polymorphism may alter the function of the encoded protein . the polymorphism may exert phenotypic effects indirectly via influence on replication , transcription , and translation . for example , the substitution of a methionine for a valine in the prepro portion of the bdnf gene product may create an alternative translation start site which alters the length of the gene product and the prepro portion itself . alteration of the length of the gene product may affect cleavage of the mature protein either positively or negatively . alternatively , the presence of the variant amino acid may alter the properties of the gene product so as to alter cleavage of the gene product . more than one phenotypic trait may be affected . for example , other neuropsychiatric disorders which are believed to be alternate expressions of a bipolar genotype , including variants of schizoaffective disorder , recurrent unipolar depression and hypomania ( bipolar ii disorder ), may also be affected by the bdnf polymorphism described herein . additionally , the described polymorphism may predispose an individual to a distinct mutation that is causally related to a certain phenotype , such as susceptibility or resistance to bipolar disorder . the discovery of the polymorphism and its correlation with bipolar disorder facilitates biochemical analysis of the variant and the development of assays to characterize the variant and to screen for pharmaceuticals that interact directly with one or another form of the protein . alternatively , this particular polymorphism may be one of a group of two or more polymorphisms in the bdnf gene which contributes to the presence , absence or severity of the neuropsychiatric disorder , e . g ., bipolar disorder . an assessment of other polymorphisms within the bdnf gene can be undertaken , and the separate and combined effects of these polymorphisms on the neuropsychiatric disorder phenotype can be assessed . correlation between a particular phenotype , e . g ., the bipolar phenotype , and the presence or absence of a particular allele is performed for a population of individuals who have been tested for the presence or absence of the phenotype . correlation can be performed by standard statistical methods such as a chi - squared test and statistically significant correlations between polymorphic form ( s ) and phenotypic characteristics are noted . for example , as described herein , it has been found that the presence of the bdnf variant allele , having an a at polymorphic site 424 , correlates negatively with bipolar disorder with a p value of p = 0 . 004 by chi - squared test . this correlation can be exploited in several ways . in the case of a strong correlation between a particular polymorphic form , e . g ., the reference allele for bdnf , and a disease for which treatment is available , e . g ., bipolar disorder , detection of the polymorphic form in an individual may justify immediate administration of treatment , or at least the institution of regular monitoring of the individual . detection of a polymorphic form correlated with a disorder in a couple contemplating a family may also be valuable to the couple in their reproductive decisions . for example , the female partner might elect to undergo in vitro fertilization to avoid the possibility of transmitting such a polymorphism from her husband to her offspring . in the case of a weaker , but still statistically significant correlation between a polymorphic form and a particular disorder , immediate therapeutic intervention or monitoring may not be justified . nevertheless , the individual can be motivated to begin simple life - style changes ( e . g ., therapy or counseling ) that can be accomplished at little cost to the individual but confer potential benefits in reducing the risk of conditions to which the individual may have increased susceptibility by virtue of the particular allele . furthermore , identification of a polymorphic form correlated with enhanced receptiveness to one of several treatment regimes for a disorder indicates that this treatment regime should be followed for the individual in question . furthermore , it may be possible to identify a physical linkage between a genetic locus associated with a trait of interest ( e . g ., bipolar disorder ) and polymorphic markers that are not associated with the trait , but are in physical proximity with the genetic locus responsible for the trait and co - segregate with it . such analysis is useful for mapping a genetic locus associated with a phenotypic trait to a chromosomal position , and thereby cloning gene ( s ) responsible for the trait . see lander et al ., proc . natl . acad . sci . ( usa ) 83 , 7353 - 7357 ( 1986 ); lander et al ., proc . natl . acad . sci . ( usa ) 84 , 2363 - 2367 ( 1987 ); donis - keller et al ., cell 51 , 319 - 337 ( 1987 ); lander et al ., genetics 121 , 185 - 199 ( 1989 )). genes localized by linkage can be cloned by a process known as directional cloning . see wainwright , med . j . australia 159 , 170 - 174 ( 1993 ); collins , nature genetics 1 , 3 - 6 ( 1992 ). linkage studies are typically performed on members of a family . available members of the family are characterized for the presence or absence of a phenotypic trait and for a set of polymorphic markers . the distribution of polymorphic markers in an informative meiosis is then analyzed to determine which polymorphic markers co - segregate with a phenotypic trait . see , e . g ., kerem et al ., science 245 , 1073 - 1080 ( 1989 ); monaco et al ., nature 316 , 842 ( 1985 ); yamoka et al ., neurology 40 , 222 - 226 ( 1990 ); rossiter et al ., faseb journal 5 , 21 - 27 ( 1991 ). linkage is analyzed by calculation of lod ( log of the odds ) values . a lod value is the relative likelihood of obtaining observed segregation data for a marker and a genetic locus when the two are located at a recombination fraction θ , versus the situation in which the two are not linked , and thus segregating independently ( thompson & amp ; thompson , genetics in medicine ( 5th ed , w . b . saunders company , philadelphia , 1991 ); strachan , “ mapping the human genome ” in the human genome ( bios scientific publishers ltd , oxford ), chapter 4 ). a series of likelihood ratios are calculated at various recombination fractions ( θ ), ranging from θ = 0 . 0 ( coincident loci ) to θ = 0 . 50 ( unlinked ). thus , the likelihood at a given value of θ is : probability of data if loci linked at θ to probability of data if loci unlinked . the computed likelihoods are usually expressed as the logso of this ratio ( i . e ., a lod score ). for example , a lod score of 3 indicates 1000 : 1 odds against an apparent observed linkage being a coincidence . the use of logarithms allows data collected from different families to be combined by simple addition . computer programs are available for the calculation of lod scores for differing values of θ ( e . g ., liped , mlink ( lathrop , proc . nat . acad . sci . ( usa ) 81 , 3443 - 3446 ( 1984 )). for any particular lod score , a recombination fraction may be determined from mathematical tables . see smith et al ., mathematical tables for research workers in human genetics ( churchill , london , 1961 ); smith , ann . hum . genet . 32 , 127 - 150 ( 1968 ). the value of θ at which the lod score is the highest is considered to be the best estimate of the recombination fraction . positive lod score values suggest that the two loci are linked , whereas negative values suggest that linkage is less likely ( at that value of θ ) than the possibility that the two loci are unlinked . by convention , a combined lod score of + 3 or greater ( equivalent to greater than 1000 : 1 odds in favor of linkage ) is considered definitive evidence that two loci are linked . similarly , by convention , a negative lod score of − 2 or less is taken as definitive evidence against linkage of the two loci being compared . negative linkage data are useful in excluding a chromosome or a segment thereof from consideration . the search focuses on the remaining non - excluded chromosomal locations . in another embodiment , the invention relates to pharmaceutical compositions comprising a variant bdnf gene product . as used herein , a variant bdnf gene product is intended to mean gene products which are encoded by the variant allele of the bdnf gene and includes , but is not limited to , the complete ( uncleaved ) variant bdnf gene product , the cleaved bdnf protein and the cleaved prepro portion of the gene product . in one embodiment , the gene product is a peptide comprising amino acids − 1 through − 132 of a variant bdnf gene product , or a functional portion thereof , for use in the treatment of neuropsychiatric disorders . the invention further relates to the use of compositions ( i . e ., agonists ) which enhance or increase the activity of a peptide comprising amino acids − 1 through − 132 of the variant bdnf gene product , or a functional portion thereof , for use in the treatment of neuropsychiatric disorders . the invention also relates to the use of compositions ( i . e ., antagonists ) which reduce or decrease the activity of a peptide comprising amino acids − 1 through − 132 of the variant bdnf gene product , or a functional portion thereof , for use in the treatment of neuropsychiatric disorders . in a particular embodiment the neuropsychiatric disorder is bipolar disorder . in addition to substantially full - length polypeptides expressed by variant genes , the present invention includes biologically active fragments of the polypeptides , or analogs thereof , including organic molecules which simulate the interactions of the peptides . biologically active fragments include any portion of the full - length polypeptide which confers a biological function on the variant gene product , including ligand binding , and antibody binding . ligand binding includes binding by nucleic acids , proteins or polypeptides , small biologically active molecules , or large cellular structures . for instance , the variant polypeptide or protein , or fragment thereof , of the present invention can be formulated with a physiologically acceptable medium to prepare a pharmaceutical composition . the particular physiological medium may include , but is not limited to , water , buffered saline , polyols ( e . g ., glycerol , propylene glycol , liquid polyethylene glycol ) and dextrose solutions . the optimum concentration of the active ingredient ( s ) in the chosen medium can be determined empirically , according to procedures well known to medicinal chemists , and will depend on the ultimate pharmaceutical formulation desired . methods of introduction of exogenous peptides at the site of treatment include , but are not limited to , intradermal , intramuscular , intraperitoneal , intravenous , subcutaneous , oral and intranasal . other suitable methods of introduction can also include rechargeable or biodegradable devices and slow release polymeric devices . the pharmaceutical compositions of this invention can also be administered as part of a combinatorial therapy with other agents and treatment regimens . polyclonal and / or monoclonal antibodies that specifically bind one form of the gene product but not to the other form of the gene product are also provided . antibodies are also provided that bind a portion of either the variant or the reference gene product that contains the polymorphic site . antibodies can be made by injecting mice or other animals with , for example , the variant gene product or peptide fragments thereof comprising the variant portion . the peptide framents can be synthetically produced or produced in a suitable host cell expressing a nucleic acid encoding said peptide . in another embodiment , the animal is injected with the reference gene product or fragments thereof containing amino acid position − 63 . monoclonal antibodies are screened as are described , for example , in harlow & amp ; lane , antibodies , a laboratory manual , cold spring harbor press , new york ( 1988 ); goding , monoclonal antibodies , principles and practice ( 2d ed .) academic press , new york ( 1986 ). monoclonal antibodies are tested for specific immunoreactivity with , for example , a variant gene product and lack of immunoreactivity to the corresponding prototypical gene product . in another embodiment , antibodies are produced and tested for specific immunoreactivity to the reference gene product and lack of immunoreactivity to the variant gene product . these antibodies are useful in diagnostic assays for detection of the variant form , or as an active ingredient in a pharmaceutical composition . the invention further relates to a method of diagnosing or aiding in the diagnosis of a disorder associated with the presence of all or a portion of the prepro bdnf protein in an individual . the method comprises obtaining a biological sample containing the prepro bdnf protein or relevant portion thereof from the individual and determining the amino acid present at amino acid position − 63 relative to the first amino acid of the mature protein . wherein the presence of the reference amino acid , valine at this position is indicative of increased likelihood of the disorder in the individual as compared with an appropriate control , e . g ., an individual having the variant amino acid at position − 63 . in one embodiment , the prepro portion of bdnf from an individual is analyzed . in one embodiment , the method comprises obtaining a biological sample containing the prepro bdnf protein or relevant portion thereof from the individual and determining the amino acid present at position − 63 relative to the first amino acid of the mature protein , wherein presence of a variant amino acid , e . g ., methionine , at said position is indicative of decreased likelihood of the disorder in the individual as compared with an appropriate control , e . g ., an individual having the reference ( valine ) amino acid said position . in one embodiment , the prepro portion of bdnf is analyzed . in one embodiment , the invention relates to a method for predicting the likelihood that an individual will have a bipolar disorder ( or aiding in the diagnosis of a bipolar disorder ), comprising the steps of obtaining a biological sample comprising the prepro bdnf protein or fragment thereof containing amino acid position − 63 from an individual to be assessed and determining the amino acid present at amino acid position − 63 . the presence of the variant amino acid at this position indicates that the individual has a lower likelihood of having a bipolar disorder than an individual having the reference amino acid at this position , or a lower likelihood of having severe symptomology . in a particular embodiment , the individual is an individual at risk for development of bipolar disorder . the invention also relates to a method for predicting the likelihood that an individual will have a bipolar disorder , or for aiding in the diagnosis of a bipolar disorder , or predicting the likelihood of having altered symptomology associated with a bipolar disorder , comprising the steps of obtaining a biological sample comprising prepro bdnf protein or fragment thereof containing amino acid position − 63 from an individual to be assessed and determining the amino acid present at amino acid positions − 63 of the prepro bdnf gene product . for example , the prepro region of the bdnf can be cleaned from or linked to the mature bdnf protein . as used herein , the term “ fragment thereof ” of the prepro bdnf protein is intended to encompass any portion of the protein which comprises the polymorphic amino acid position . the presence of valine at position − 63 indicates that the individual has a greater likelihood of having bipolar disorder , or a greater likelihood of having severe symptomology associated with a bipolar disorder , than if that individual had a variant amino acid at this position . conversely , the presence of methionine indicates that the individual has a reduced likelihood of having a bipolar disorder or a likelihood of having reduced symptomology associated with a bipolar disorder , than if that individual had the reference amino acid at this position . in a particular embodiment , the individual is an individual at risk for development of a bipolar disorder . in another embodiment the individual exhibits clinical symptomology associated with a bipolar disorder . in one embodiment , the individual has been clinically diagnosed as having a bipolar disorder . in this embodiment of the invention , the biological sample contains protein molecules from the test subject . as described above for bdnf cdna or mrna , suitable sources for the biological sample are any tissue or bodily fluid that is expected to express or contain prepro bdnf protein or the prepro portion of bdnf can be used . in vitro techniques for detection of protein of interest include enzyme linked immunosorbent assays ( elisas ), western blots , immunoprecipitations and immunofluorescence . furthermore , in vivo techniques for detection of protein include introducing into a subject a labeled anti - protein antibody . for example , the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques . polyclonal and / or monoclonal antibodies that specifically bind to variant gene products but not to corresponding reference gene products , and vice versa , are also provided . antibodies can be made as described above . these antibodies are useful in diagnostic assays for detection of the variant form , or as an active ingredient in a pharmaceutical composition . the invention also encompasses kits for detecting the presence of proteins or nucleic acid molecules of the invention in a biological sample . for example , the kit can comprise a labeled compound or agent ( e . g ., nucleic acid probe such as seq id no : 11 ,) capable of detecting protein or mrna ( or cdna produced from the mrna ) in a biological sample ; means for determining the identity of nucleotide 424 of the bdnf gene in the mrna corresponding mrna in the sample or the amino acid identity at position − 63 of the prepro portion of bdnf in the sample ; and means for comparing said identities of mrna in the sample with a suitable standard . the kit can also comprise control samples for use as standards , representing individuals homozygous for the reference or variant nucleotide in the case of analyzing nucleic acid , or the reference or variant amino acid in the case of analyzing proteins , or representing a heterozygous individual . for the detection of the reference or the variant prepro portion of bdnf , the kit can contain antibodies specific for either the reference or the variant prepro portion of bdnf together with suitable regents to detect antibody binding to its target antigen . the compound or agent can be packaged in a suitable container . the kit can further comprise instructions for using the kit to detect protein or nucleic acid . the invention further pertains to compositions , e . g ., vectors , comprising a nucleotide sequence encoding variant bdnf gene product . in one embodiment , the gene product is a peptide comprising amino acids − 1 through − 132 of the variant bdnf gene product , or a functional portion thereof , for use in the treatment of neuropsychiatric disorders . for example , variant genes can be expressed in an expression vector in which a variant gene is operably linked to a native or other promoter . usually , the promoter is a eukaryotic promoter for expression in a mammalian cell . the transcription regulation sequences typically include a heterologous promoter and optionally an enhancer which is recognized by the host . the selection of an appropriate promoter , for example trp , lac , phage promoters , glycolytic enzyme promoters and trna promoters , depends on the host selected . commercially available expression vectors can be used . vectors can include host - recognized replication systems , amplifiable genes , selectable markers , host sequences useful for insertion into the host genome , and the like . the means of introducing the expression construct into a host cell varies depending upon the particular construction and the target host . suitable means include fusion , conjugation , transfection , transduction , electroporation or injection , as described in sambrook , supra . a wide variety of host cells can be employed for expression of the variant gene , both prokaryotic and eukaryotic . suitable host cells include bacteria such as e . coli , yeast , filamentous fungi , insect cells , mammalian cells , typically immortalized , e . g ., mouse , cho , human and monkey cell lines and derivatives thereof . preferred host cells are able to process the variant gene product to produce an appropriate mature polypeptide . processing includes glycosylation , ubiquitination , disulfide bond formation , general post - translational modification , and the like . it is also contemplated that cells can be engineered to express the variant bdnf allele of the invention by gene therapy methods . for example , dna encoding the variant bdnf gene product , or an active fragment or derivative thereof , can be introduced into an expression vector , such as a viral vector , and the vector can be introduced into appropriate cells in an animal . in such a method , the cell population can be engineered to inducibly or constitutively express active variant bdnf gene product . in a preferred embodiment , the vector is delivered to the bone marrow , for example as described in corey et al . ( science 244 : 1275 - 1281 ( 1989 )). the invention further provides transgenic nonhuman animals capable of expressing an exogenous variant bdnf gene and / or having one or both alleles of an endogenous variant bdnf gene inactivated . expression of an exogenous variant gene is usually achieved by operably linking the gene to a promoter and optionally an enhancer , and microinjecting the construct into a zygote . see hogan et al ., “ manipulating the mouse embryo , a laboratory manual ,” cold spring harbor laboratory . inactivation of endogenous variant genes can be achieved by forming a transgene in which a cloned variant gene is inactivated by insertion of a positive selection marker . see capecchi , science 244 , 1288 - 1292 ( 1989 ). the transgene is then introduced into an embryonic stem cell , where it undergoes homologous recombination with an endogenous variant gene . mice and other rodents are preferred animals . such animals provide useful drug screening systems . the invention will be further illustrated by the following non - limiting examples . the teachings of the references cited herein are incorporated herein by reference in their entirety . a sample population of 150 trios was initially assessed by genotyping methods for heterozygousity with respect to the bdnf reference and variant alleles as described herein . a trio included two parents and an offspring diagnosed as having bipolar disorder according to the american psychiatric association &# 39 ; s diagnostic and statistical manual of mental disorders . of the 150 trios assessed , 98 of these trios had at least one parent who was heterozygous for the bdnf reference and variant alleles ; these 98 trios were selected for further study , as the heterozygousity of the parent allowed a determination of which allele the parent transmitted to the bipolar offspring . the bipolar offspring in the trios were assessed by genotyping methods to determine which bdnf allele had been transmitted to them by the heterozygous parent . in instances where two parents had two offspring diagnosed with bipolar disorder , each trio ( i . e ., two parents and one offspring ) was considered individually . the genotyping method used for these studies was based on single - base extension ( sbe ) and fluorescence resonance energy transfer ( fret ). a locus - specific primer ( fret primer ; 5 ′- ggctgacactttcgaacac ( seq id no : 11 ) was ordered 5 ′ labeled with fam . the primer was designed so that the 3 ′ end was one base 5 ′ to the polymorphic site of interest ( e . g ., nucleotide 424 ). the locus of interest was amplified and single base extension of the fret primer was performed with fluorescently labeled ddntps in dye - terminator sequencing fashion , except that no deoxyribonucleotides are present . pcr primers were : the ddntp corresponding to the variant base ( a ) was labeled with tamra , and the reference base ( g ) was labeled with rox . depending on the genotype of the individual , the fret primer was extended with a rox - labeled or tamra - labeled ddntp . upon incorporation of either rox - or tamra - labeled ddntps , energy transfer occurs between the donor dye ( fam on fret primer ) and the acceptor dye ( the rox - or tamra - labeled ddntp ). an increase in the fluorescence intensity of one ( for a homozygote ) or both ( for a heterozygote ) of the acceptor dyes was used to infer the genotype of an individual . ii clean - up of pcr products with shrimp alkaline phosphate ( sap ) and exonuclease i ( exo ) fifteen microliters of the pcr mix were added to a 96 - well mj plate . five microliters of genomic dna ( 5 ng / μl ) were added to the aliquoted pcr mix . ( 5 μl of 1 ng / μl is often adequate ). the plate was sealed with mj plate - seal ‘ a ’. pcr was conducted using the following program : five microliters of sap / exo mix were added to a clean mj plate . five microliters of the pcr product were added directly to the aliquoted sap / exp mix . the pcr plates were spun down and sealed with microseal a film . the mixture was incubated at 37 ° c . for 45 minutes and then at 96 ° c . for 15 minutes . ( the reactions were carried out in the same mj plate used for sap / exo step , capped with 8 - strip microamp optical caps ) the ddntps that should be incorporated in the genotyping reaction were selected . in this experiment , tamra was used to identify the variant base and rox for the reference base , although other possibilities exist . ten microliters of sbe - fret mix were added to the mj plates containing 10 μl sap / exo treated pcr products . the plates were tapped on bench to mix , they can also be spun briefly if necessary . the wells were capped with optical caps . the capped wells can be rolled with roller if necessary . the plates were incubated for 6 cycles of ( for a 20 μl reaction ) as follows : data were collected in the 60 ° c . stage using detection settings suitable for measuring tamra and rox fluorescence . at the end of the run , the plate was saved as “ projectname . sbexxx . pyyy ”, where project name is the project ( e . g . cancer ), xxx is the number of the polymorphism being genotyped ( e . g . 48 ), and yyy is the plate number ( e . g . 04 ). to analyze the data , “ analyze ” was selected under the analysis menu ( command - l ). the 7700 apparatus provides a screen to adjust the threshold levels . “ 0 ” was input in the “ use threshold ” box and “ 2 ” for cycle number in both the baseline start and stop boxes . “ update calculations ” was selected . the resulting error message box was closed . data were analyzed by plotting rox fluorescence versus tamra fluorescence and comparing the values between samples , control samples containing no template and samples of known geneotype . typically , homozygous reference controls have little or no tamra fluorescence , homozygous variant controls have little or no rox fluorescence and heterozygous controls have similar tamra and rox fluorescence . genotypes determined included ref , het , var , fail ( signal too low ) or a - fail ( ambiguous — signal not within one of the values set above ). data from the work described herein has shown that there is a variation from random ( i . e ., that which would be expected by chance ) in the transmission of the reference ( g ) and variant ( a ) alleles from an individual parent who is heterozygous for the bdnf alleles to an offspring diagnosed with bipolar disorder . fig2 a - 2j show data resulting from a genotyping assessment of the reference and variant alleles of bdnf in a group of trios having one or more bipolar offspring . column 1 shows the family reference number for the trio . column 2 shows the reference number for the individual being assessed . columns 3 and 4 show the reference number for the father and the mother , respectively , in the trio . column 5 shows the gender of the individual being assessed . column 6 shows the genotype of the individual being assessed with respect to bdnf ; ref indicates that the individual was homozygous for the reference ( g ) allele , var indicates that the individual was homozygous for the variant allele , het indicates that the individual was heterozygous , and fail indicates that no data was collected for that individual . columns 7 and 8 show the number of times that the reference and variant allele , respectively , were transmitted to offspring by the heterozygous parent . fig3 a - 3c show data resulting from a genotyping assessment of the reference and variant alleles of bdnf in an additional group of trios having one or more bipolar offspring . column i shows the family reference number for the trio . column 2 shows the individual reference number for the individual being assessed . column 3 shows whether the individual being assessed was the offspring ( patient ) or parent . column 4 shows the genotype of the individual being assessed with respect to bdnf ; ref indicates that the individual was homozygous for the reference ( g ) allele , var indicates that the individual was homozygous for the variant allele , het indicates that the individual was heterozygous , and fail indicates that no data was collected for that individual . columns 5 and 6 show the number of times that the reference and variant allele , respectively , were transmitted to offspring by the heterozygous parent . the data demonstrate that the variant allele ( a ) is transmitted less frequently ( 34 of 98 times ) to the bipolar offspring than would be expected by chance , while the reference allele ( g ) is transmitted more frequently ( 64 of 98 times ) than would be expected by chance ( p = 0 . 004 ). in the general population ( in which about 0 . 8 percent of the individuals are diagnosed with bipolar disorder ), the variant ( a ) allele occurs with a frequency of 15 percent , while the reference allele occurs with a frequency of 85 percent . in the sample population assessed as described herein , in which all of the individuals are diagnosed with bipolar disorder , the variant allele occurs with a frequency of 7 percent . thus , it appears that the variant allele may contribute to protection or reduction in symptomology with respect to bipolar disorder . fig4 and table v show data obtained from additional human samples . “ hopkins ” refers to a to a group of patients with bipolar disorder obtained in collaboration with johns hopkins . “ u01 and nimh ” refer to a group of 155 trios some of which are from johns hopkins and some are from the genetics initiative at the nimh . “ british ” refers to 145 trios from 5 collaborators in england . in table v , “ trans ” is the number of times the allele in question ( in this case the reference allele ) was transmitted from a heterozygous parents to a bipolar child . “ untrans ” is the number of times the other ( variant ) allele was passed from the heterozygous parent to the bipolar child . the number of trios used is show in the column labeled “# trios ” and is the number of trios for which genotypes were available . not all of the parents were considered to be “ informative ”. to be included in the analysis , the parent in question had to be a heterozygote . the relative risk ( estimated relative risk on fig4 ) is defined as the transmission ratio in trios ( i . e # transmitted alleles /# untransmitted alleles ). under a multiplicative disease model , this is an estimator of genotypic relative risk . the confidence interval was calculated using a binomial distribution . while this invention has been particularly shown and described with references to preferred embodiments thereof , it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims . ser tyr phe gly cys met lys ala ala pro met lys glu ala asn ile leu glu ser val asn gly pro lys ala gly ser arg gly leu thr ser leu ser val cys asp ser ile ser glu trp val thr ala ala asp lys val pro val ser lys gly gln leu lys gln tyr phe tyr glu thr lys cys asn pro met gly tyr thr lys glu gly cys arg gly ile asp lys arg his trp asn ser gln cys arg thr thr gln ser tyr val arg ala leu thr met asp ser lys lys arg ile gly trp arg phe ile arg ile ile ser tyr phe gly cys met lys ala ala pro met lys glu ala asn val his gly gln gly asn leu ala tyr pro ala val arg thr his gly ala asp leu tyr thr ser arg val met leu ser ser gln val pro leu arg gly glu leu ser val cys asp ser ile ser glu trp val thr ala ile asp lys arg his trp asn ser gln cys arg thr thr gln ser tyr val arg ala leu thr met asp ser lys lys arg ile gly trp arg phe ser tyr phe gly cys met lys ala ala pro met lys glu val asn val his gly gln gly asn leu ala tyr pro gly val arg thr his gly thr asp leu tyr thr ser arg val met leu ser ser gln val pro leu glu gly glu leu ser val cys asp ser ile ser glu trp val thr ala ala thr lys cys asn pro met gly tyr thr lys glu gly cys arg gly ile asp lys arg his trp asn ser gln cys arg thr thr gln ser tyr val ala arg gly ala leu thr met asp ser lys lys arg ile gly trp arg gly cys met lys ala ala pro met lys glu ala asn val arg gly gln gly ser leu ala tyr pro gly val arg thr his gly thr leu glu ser lys val pro val ser lys gly gln leu lys gln tyr phe tyr glu thr lys cys asn pro met gly tyr thr lys glu gly cys arg gly ile asp lys arg his trp asn ser gln cys arg thr thr gln ser tyr val arg ala leu thr met asp ser lys lys arg ile gly trp arg phe ile arg

US-63636800-A

a multipurpose machine for close - row production of tree or shrub plantations , such as vineyards or orchards includes a working head including a rotor powered by a motor and designed for receiving at least two interchangeable tools . the invention also includes a meshing guide peripherally configured to mesh with the foot of trees or shrubs and arranged above the tools , the meshing guide being capable of rotating at a speed different from that of the rotor and having , viewed from the direction of said axis , the general shape of a notched disc having at its periphery alternating notches and projecting parts , the length of the operating radius of the rotary tools being not more than that of the radius of a circle tangent to the base of the notches of the guide , which can thereby , in operation , successively mesh with the base of the trees or shrubs , when coming in contact with the latter .

reference is made to the drawings in order to describe examples that are of interest but in no way restrictive , of the embodiment of the multifunctional cultivating machine according to the invention . according to the example shown in fig1 to 13 , the machine consists of a towing attachment frame allowing it to be affixed to one of the sides of the chassis of a farm tractor , but it is specified that this frame can be adapted in shape in order to allow its installation on any other position of the frame of a tractor or a vehicle of another type specially designed for hoeing work or other work . it is also possible to mount two machines according to the invention on a same farm tractor , one on each side of it , which signifies that according to the placement of its mounting , the machine can be adapted in order to work to the right or to the left of the tractor or another carrying vehicle . according to the very advantageous example shown in the drawings , the machine consists of a working head 1 , attached to a heavy runner 2 itself affixed to an adjustable arm 3 of the towing attachment frame 4 . the working head 1 ( fig4 and 5 ) consists of a geared motor preferably comprised of a hydraulic motor 5 and of a reduction gear 6 driving a rotor 7 by means of a shaft 8 mounted to turn in a housing 9 . in an advantageous manner , the reduction gear 6 is a reduction gear in mesh making it possible to shift , the hydraulic motor 5 towards the inside relative to the center of the working head 1 , in thus moving it away from the vinestocks it would run the risk of hitting during work . over a peripheral zone of the rotor 7 , at least two tools are affixed , in a detachable manner , and by means of a cylindrical joint . when the machine is used as a hoeing machine or a similar machine ( fig4 ) designed to pull out harmful grasses or plants and / or break up the surface of the ground , the tools are comprised of flyweights containing a leading edge that is somewhat sharp . in a very advantageous manner , these hoeing tools 10 a are of a particular type described in another patent application by the applicant . on the other hand , when the machine is used as a mowing or shearing machine , the tools are comprised of cutting blades 10 b ( fig5 ). the rotor 7 , the tools 10 a or 10 b and the detachable fixation system of these tools are shaped and constructed in order to make possible the mounting on the rotor , with a freedom of turning having a limited amplitude , of at least two tools 10 a or 10 b . in an advantageous manner , the tools 10 a or 10 b are mounted in conditions such that when they are installed on the rotor , their axes of turning b - b converge to the bottom in the direction of the axis of rotation a - a of it , in forming an angle with the axis of rotation a - a , for example , at an angle on the order of 9 °. the detachable system for attaching the tools 10 a or 10 b , consists of , for each of them , a hinge pin 11 around which is mounted , with a turning amplitude , the collar joint 10 a of the tool . one of the ends of this hinge pin is housed in a bore hole arranged in the vicinity of the periphery of the rotor 7 , while its opposite end is engaged in an opening in a clamp 12 . a pressure disk 15 can be arranged around the lower end of the hinge pin 11 , between a circular collar 11 a of it , and the clamp 12 , in a manner so as to allow the turning of the tool . the holes arranged in the rotor 7 for the mounting of the interchangeable tools 10 a or 10 b have an axis b - b inclined relative to the axis of rotation a - a of the rotor , in a manner so that the hinge pin 11 and the axes of the collar mounting joints 10 a are also inclined along the axis b - b . the clamp 12 is affixed axially to the base of the rotor 7 by means of a single screw 13 going through a central opening of the clamp and screwing into a threading arranged in the lower portion of the shaft 8 . on this manner , in order to replace the tools 10 a or 10 b , for example in case they become worn , it is sufficient to unscrew the bolt 13 , to take off the clamp 12 and the washers 15 , to detach the tool to be replaced with its hinge pin 11 . in order to affix the new tools , the procedure is done in the reverse order . the working head of the machine for cultivating the ground according to the invention can be equipped with at least two tools 10 a or 10 b , but its rotor 7 can be shaped in order to accommodate three or more tools , angularly and regularly spaced . when the working head is equipped with two tools 10 a or 10 b , these tools are affixed in the diametrally opposed sites of the rotor 7 ( fig4 and 5 ). in this case , and as shown in fig4 and 5 , the support surfaces of the clamp 12 comprised of the lower sides of the washers 15 and the central portion of the rotor 7 , are placed in a circular arc , thus the clamp is roughly planar and equipped with a capacity for elastic deformation . when the bolt 13 is screwed at the bottom , a concave deformation of the clamp 12 is caused , the ends of which are then greatly applied , by a spring effect , onto the support washers 15 of the hinge pins 11 . when the rotor turns at speeds between 200 and 3000 rpm , the tools 10 a or 10 b have a tendency to move apart from their axis of rotation a - a , under the action of centrifugal force , and their working part occupies their lowest position . when a knife encounters an obstacle ( large rock ), it turns and moves aside in climbing back up to the rear , because of the slope of its turning axis b - b . this arrangement makes it possible to reduce the violence of possible shocks and to prevent the blades from becoming prematurely unusable . the rotor 7 comprises a lower cylindrical part 7 a having a more reduced diameter than that of its upper part 7 b under which the tools 10 a or 10 b are affixed . this lower cylindrical part 7 a functions as a stop limiting the retraction movement of the tools towards the rear when they encounter a hard obstacle . according to another important characteristic arrangement of the invention , a turning guide 14 is arranged above the tools 10 a or 10 b , preferably coaxially to the axis of rotation a - a of them . this guide is , for example , mounted around the lower cylindrical portion 9 a of the casing 9 , by means of a rolling bearing 37 , in a manner such that it can turn around the axis of rotation a - a of the rotor 7 . this turning guide has , seen in the direction of the axis a - a , the general shape of a notched disc consisting of , alternately , on its periphery , notches 16 and projecting parts 17 . when the meshing guide 14 is , according to a preferred embodiment mode , mounted coaxially to the axis of rotation a - a of the tools 10 a or 10 b , this guide is dimensioned in such a manner that the length of the maximum operating radius r 1 of these rotary tools 10 a or 10 b , is either less than or equal to the length of the radius r 2 of a circle tangent to the base of the notches 16 of the guide ( fig2 ). the notched guide 14 can be mounted in free rotation . however , according to an advantageous embodiment mode described in the following present explanation , the notched guide 14 is coupled to a motorization that ensures it is driven in rotation at a speed approximately equal to the linear speed of advancement of the tractor or other vehicle equipped with the cultivating machine , this ratio of speeds can be obtained by using a hydraulic converter that is known itself , or , preferably , by the hydraulic circuit described in the following . fig1 to 13 show the operating mode of the notched turning guide 14 according to the invention . during the encounter with a vinestock or trunk of a vine c ( or other vertical obstacle such as a trunk of a fruit tree , fence pole ), the notched guide 14 comes to grasp the vinestock , by means of one of its notches 16 ( fig1 ). the machine continues its progression parallel to the alignment of the vinestocks , the guide 14 rolls around the vinestock with which it is in contact , in moving away from its normal path ( fig1 ). it thus follows a path around the vinestock c corresponding to approximately the half circumference of it , during which the vinestock remains constantly in the bottom of the notch 16 , in a manner such that the hoeing tools 10 a or the mowing blades 10 b operate continually very close to the vinestock , but without being able to touch and injure it . it is understood that the fixed vinestock and the notched turning guide act like components of a gear in which the vinestock would be a fixed tooth and the guide a rotary toothed wheel ; for this reason , the guide will be described as “ meshing ” in the description that follows and in the claims . at the end of its rotation around the vinestock c ( fig1 ), the meshing guide separates from it , and returns to its normal initial position . according to another important characteristic arrangement of the invention , the meshing guide 14 has , in its central part 14 a approximately delimited by the base of the notches 16 , the general shape of a bell . the base of this bell is comprised in a first plane p - p delimiting a closed space e in which the rotor 7 is housed entirely , having a base that is located above the plane p - p , in a manner so that its lower part does not drag on the ground when the machine is operating . when the machine is used as a mowing machine ( fig5 ), the blades or cutting edges 10 b are also housed in the space e delimited by the base of the bell 14 a and located above the plane p - p , in a manner such that they do not scrape the ground . when the machine is used as a hoeing machine ( fig4 ), the bottom of the bell is arranged above and at a distance from a second plane p - p below which the hoeing tools 10 a are located . in an advantageous manner , the teeth or peripheral projecting parts 17 of the meshing guide 14 are raised relative to the bottom of its central part , in such a manner that the guide has the shape of a bell equipped with a crenellated edge . the raised projecting parts have an outside curved surface 17 a in the vertical direction , this arrangement encouraging the slide of the guide - bell on the ground . the meshing guide shaped in this way can easily climb up banks , while its capacity to easily slide makes it possible to obtain its return into a normal position with weaker springs , as is explained in the following . preferably , the guide 14 consists of a peripheral raised edge 14 c oriented towards the top . the meshing guide in the shape of a bell 14 can be advantageously made of a material equipped with a large capacity for elastic deformation , such as , for example , anti - abrasion polyurethane . according to another very important characteristic arrangement of the invention , the working head 1 is coupled to a heavy runner 2 shaped in order to be able to slide easily on the ground s , by means of a coupling arrangement enabling turning movements of the working head around at least two perpendicular axes . this positioning runner is comprised of a heavy piece of metal having , seen from above , an approximately trapezoidal shape . it includes a planar soleplate and its front side has , in its lower part , a curved surface that encourages it to slide on the ground while preventing it from crossing a furrow in the ground . for example , this runner can have a weight on the order of 50 kg . on the other hand , its outside lateral face consists , in the front , of a part 2 c sloped relative to its longitudinal axis and connected to a rear part approximately planar 2 b and parallel to the axis . in its rear part , the runner consists of a large opening 18 that opens to the back . this opening prevents a jam from forming between the runner 2 and the surrounding guide 14 of the working head . the positioning runner 2 is connected to the working head by means of a coupling arm 19 . the rear end of this arm is affixed to the runner 2 by means of a connecting device of the cardan joint type . more specifically , the arm 19 is affixed by means of a cylindrical joint to the horizontal axis 20 in a cap piece 21 a that has an arm support 21 . this cap piece is mounted with a turning capability on a vertical axis 22 that is a rigid single piece with the runner 2 and rises up from its central zone . it is understood that the arm can thus turn around the two perpendicular axes , in a manner so that the working head affixed to the rear end of this arm can swing in the vertical direction around the horizontal axis 20 and turn laterally to the right or to the left around the vertical axis 22 . in the normal position corresponding to the working position of the machine between the vinestocks c , the meshing guide 14 is placed , at least partially and , preferably , at least for half of it , to the outside of a line l - l passing by the outside edge 2 b of the runner 2 ( fig1 ). as shown previously , when a vinestock c is encountered , the runner 2 , by means of its sloped side 2 c , pre - positions the working head 1 and the guide 14 comes to catch with this vinestock , around which it rolls in moving ( according to the arrow f 1 in fig1 ) to the inside , in the direction of the center of the area between the rows . mechanisms support the working head 1 in this position , and allow the lateral displacement of the head in the direction of the inter - row areas and ensure its return into the normal position , after passing the vinestock . these mechanisms are , for example , comprised of a helicoidal spring 23 arranged around a cylindrical sleeve 21 b for mounting of the support of the arm 21 and fixed by means of its ends , on the one hand , in a hole 24 that contains it , and , on the other hand , in a hole 25 that has an instrument that is unified as a single piece with the axis 22 or the runner 2 . the support of the arm 21 and / or the runner ( or the attachment instrument rigidly unified as a single piece with the runner ) can consist of several holes located in a circular arc ( fig2 ) in order to make it possible to modify the placement of the anchorage point of at least one of the ends of the spring 23 . it is thus possible to control the restoring moment or the stiffness of this spring . on the other hand , a damping device , preferably comprised of an adjustable hydraulic damping device 26 , connects the support of the arm 21 or casing of the cardan device and the coupling arm 19 . this damping device 26 makes it possible to stabilize the hoeing or mowing head during work , in preventing the head from progressing by successive bounces , notably on rocky ground ; it thus allows a better work in good conditions of safety . the working head 1 is mounted with a latitude for swinging around an axis parallel to the longitudinal axis of the runner 2 or the axis of progression of the equipment : runner 2 working head 1 . the rear end of the coupling arm 19 is connected to the working head 1 by means of a cylindrical joint 27 , in a manner such that the working head can swing around this end . a stopper system , preferably controllable , limits the amplitude of this swinging , in a manner so as to prevent the working head from be able to swing with too large an extent that would create a risk of turning around the head . this stopper system is , for example , comprised of a helicoidal spring 28 around the coupling arm 19 and fixed , on the one hand , to a sleeve 29 or other piece that is rigidly united with the casing 9 of the working head , and , on the other hand , to a collar 30 mounted around this arm and held solidly to this piece , for example , by means of a pressure screw 31 , or other mounting instrument that can be dismounted , making it possible to modify the angular position of the collar . the collar makes it possible to adjust the stiffness of the spring 28 . in addition to its anti - swing function , the arrangement mentioned above makes it possible to absorb the swinging movements of the hoeing or mowing head during work and to pin the base of the guide - bell against the ground , notably when it is in the contact zones with the vinestocks . the tractor runner 2 is connected to the distal end of the arm 3 of the adjustable towing attachment frame 4 by means of a coupling device that permits turning movements of the runner around two perpendicular horizontal or approximately horizontal axes . this device is of the cardan joint type and consists of : an axis 32 affixed rigidly to the runner 2 and oriented in parallel to the longitudinal axis of it ; a piece in the shape of a t comprised of a bushing 33 and an axis 34 oriented transversally and solidly connected as a single piece with it ; this bushing being mounted in free rotation around the axis 32 ; and a bushing 35 affixed to the distal end of the arm 3 and in which the axis 34 is mounted with a latitude of rotation . it is noted that because of its swinging radius around the two horizontal perpendicular axes , the runner moves while closely following the surface of the ground regardless of the unevenness encountered during its progression ( sloping or banking ). the transverse axis 34 makes it possible to follow the shape of the ground in the direction of progress , while the longitudinal axis 32 makes it possible to free itself of problems of banking . in this manner , the hoeing or mowing head 1 coupled to the runner acts in the same way and the surrounding guide 14 stays pinned against the ground regardless of the configuration of it . a balancing device , preferably adjustable , for example comprised of a helicoid spring 36 acting by tension , is affixed , by means of its opposite ends , on the one hand , to a point close to the distal end of the arm 3 and , on the other hand , to the front part of the runner ( fig8 ); this balancing spring makes it possible to prevent the runner from being planted in the ground , in limiting the amplitude of its swinging to the front . [ 0101 ] fig6 shows , as an example , a position of the swinging of the runner 2 around the axis 32 corresponding to the sliding of the runner on banked ground . [ 0102 ] fig7 shows the action of a hoeing head moving on banked ground ; you can see that by the guide in the shape of a bell , the tools are ideally positioned in the ground s , in order to effectively perform their function . as previously indicated , when a vinestock c or other vertical obstacle is encountered , the runner 2 can be caused to slide , by means of its sloped surface 2 c , on this obstacle , in a manner so that the runner is pushed back laterally in the direction of the center of the inter - row areas of the vineyard in which the working head is gliding . the distal end of the arm 3 is arranged in a manner so as to allow this movement and to ensure the return of the runner into its normal position . this situation is shown in fig9 and 10 . the bushing 35 in which the axis 34 is housed is rigidly united with the lower end of a swinging part 38 that has an upper part that is fixed , by means of a joint 39 onto the distal end of the arm 3 . on the end of this part , affixed by means of a joint 40 , is one of the ends of a shaft 41 around which a spring 42 is arranged acting in extension . this spring 42 is supported , by means of its opposed ends , on the one hand , against a washer 43 held by a nut 44 screwed down on the free end of the shaft 41 , and on the other hand , against a stopper 45 mounted so that it turns , by means of the axes 46 , in a sleeve 47 that is rigidly united with the base 3 . [ 0106 ] fig9 shows a withdrawal position of the runner 2 , in the direction of the center of the inter - rows , according to which the spring 42 of the device described above is compressed , while in the situation of return to normal position , shown in fig1 , the spring is relaxed . the adjustable towing attachment frame supporting the arm 3 is mounted , in a detachable manner , on an attachment fitting 48 affixed on the frame of the carrying vehicle , on the side , or in front , or in the rear , on the right , or on the left of this vehicle . when the meshing guide 14 is mounted free in rotation , the rotation of the hoeing tools 10 a at a speed on the order of 200 to 3000 revolutions / minute , causes a movement of the ground and the pulled - out roots , and this shuffled mass can play the role of engaging by friction causing the meshing guide then to turn the tools and turning guide in the same direction , as if it was a motor . this rotation can reach large speeds that are undesirable , notably in the applications to hoeing machines . according to a characteristic device of the invention , this problem is solved by a construction according to which the meshing guide 14 is coupled to a motorization that ensures it is driven at a speed that is approximately equal to , or preferably , slightly greater than the speed for the progression of the machine during work . according to the example shown in fig1 to 16 , a toothed crown 49 is affixed concentrically on the meshing guide 14 , by screwing down or otherwise . this toothed wheel 49 is in mesh with a pinion 50 set on the output shaft 51 a of a hydraulic motor 51 ; the choice of the hydraulic energy in order to ensure the driving in rotation of the meshing guide is a preferred option , this energy is in effect used in order to drive the tool - holder rotor 7 . shown in fig1 is the hydraulic control circuit of the motor 51 ensuring the driving in rotation of the meshing guide 14 . for the sake of simplicity , the drive motor 51 is mounted in parallel with the drive motor 5 of the tool - holder rotor ( a mounting called “ in series ” would also be possible ). the hydraulic supply circuit of the motor 51 consists of a distributor unit designated in its entirety by the reference 52 and including a properly calibrated first nozzle 53 connected to the input of the motor 51 , a second adequately calibrated nozzle 54 connected to the output of the motor , and a discharge valve 55 ( pressure limiter ). the distributor unit 52 draws off , by the action of the calibrated nozzle 53 arranged on the supply line al of the hydraulic circuit , an oil flow that is sufficient so that the motor 51 drives the meshing guide 14 at an optimal rotational speed without excessively penalizing the flow rate necessary for the drive of the motor 5 , in spite of the fact that the pressure of the circuit varies constantly because of the irregular couple induced by the rotation of the tools in the ground . a nozzle 54 connected to the output of the motor 51 allows the control of the rotation of the meshing guide 14 in the case where it would have the tendency to become “ carried ” ( effect of engaging created by the moved ground ) while controlling a low compression in the body of this motor , which prevents any possibility of cavitation ( necessary condition for an excellent lifetime of the motor ). the discharge valve 55 makes it possible to control the moment supplied by the motor 51 in thus making it possible , on the one hand , to adapt the speed of rotation of the meshing guide 14 to the speed of displacement of the machine and , on the other hand , the gentle engaging of the meshing guide 14 on the vinestocks or trunks of the shrubs , in a manner so as to not injure them . it is observed that if the movement of the machine is interrupted while maintaining the rotation of the motor 5 , the rotation of the meshing guide 14 stops , in a manner such that it can not damage the vinestock or trunk with which it could come into contact at the moment the machine stops . it is understood that the hydraulic circuit shown in fig1 comprises a device for the assistance and regulation of the rotational speed of the motor 51 for driving the meshing guide 14 , this speed being proportional to the speed of displacement of the machine . [ 0118 ] fig1 and 15 show another embodiment mode of the mechanisms limiting the amplitude of the swinging of the working head around the coupling arm 19 , in order to prevent it from be able to turn with too large an extent creating a risk of the return of the working head , or so that it does not progress with jolts harmful to the quality of the work and able to damage the vinestocks . in this case , these mechanisms comprise a damping device 56 connected , by means of its opposed ends and by means of joints 57 , 58 , respectively , on the one hand , to the casing or support 9 of the working head , and , on the other hand , to a swinging lever 59 set on the coupling arm 19 . on the other hand , a helicoid spring 60 , acting in compression , is arranged around the damping device 56 . this helicoid spring is set against the stopper washers 61 , 62 affixed , respectively to the mobile shaft 56 a and to the body 56 b of the damping device . the stopper 62 has a position that is adjustable on the damping device 56 , in a manner so as to allow a control of the stiffness of the spring 60 . according to the embodiment mode shown in fig1 and 17 , a peripheral anti - ejection curtain 63 , flexible and detachable , is affixed under the meshing guide 14 inside of a circle tangent to the base of the notches 16 of it . this curtain is , for example , made up of chains 64 having straight or twisted links , held by a retaining ring 65 housed in a groove 68 arranged in the soleplate of the meshing guide 14 , these chains being held in place by the small annular spacers 66 . the anti - ejection curtain 63 is affixed to the meshing guide 14 , by means of cotter pins 67 going through holes arranged in the meshing guide 14 , near the periphery of it , where these holes are spaced , for example , on the order of 36 °. it is understood that this peripheral flexible protection curtain effectively prevents any ejection of rocks , earth , dust , etc . during work , regardless of the position of the rotary tools relative to the level of the ground .

US-20398902-A

toothbrush holder 10 is formed from a single piece of sheet material and is easily folded along its fold lines 14 , 18 , 19 , 28 and 29 into an isosolese triangular shape , with toothbrush openings 23 and 24 formed across the apex fold line 14 . the toothbrushes 29 are inserted downwardly through the openings 23 and 24 and are supported in an upright attitude suitable for drying .

referring now in more detail to the drawings , in which like numerals indicate like parts throughout the several views , fig1 shows the toothbrush holder 10 which comprises upwardly sloped side walls 11 and 12 folded along a fold line 14 , and bottom panels 15 and 16 which are folded along lower fold lines 18 and 19 and which are split and interleaved together to retain the shape of the holder . as illustrated in fig5 the bottom panels 15 and 16 are partially split by cuts 20 and 21 . rectangular toothbrush openings 23 and 24 are formed at the upper fold line 14 , with the rectangular openings 23 and 24 being spaced apart from one another and extending on both sides of the fold line 14 into the side walls 11 and 12 . the rectangular openings 23 and 24 have long parallel edges 23a , 23b , 24a and 24b extending at right angles to the fold line 14 , and have short parallel edges 23c , 23d , 2c and 24d extending parallel to the fold line 14 . bottom panels 15 and 16 further include side tabs 25 and 26 , respectively , with one side tab 26 extending from one side of the holder and with the other side tab extending from the other side of the holder . the side tabs 25 and 26 are separated from bottom panels 15 and 16 by fold lines 27 and 28 . the toothbrush holders normally will be packaged and shipped in a flat configuration as illustrated in fig5 with many of the toothbrush holders packaged in a single package . when received at the location of use , a hotel , etc ., the room attendant will open a package of toothbrush holders and will assemble a holder from the flat configuration of fig5 into the formed configuration of fig1 . the attendant typically will fold the toothbrush holder along its fold lines 14 , 18 , 19 , 27 and 28 into the triangular configuration of fig1 and will interleave the bottom panels 15 and 16 , by placing bottom panel half 15a on top of bottom panel half 16a , and by placing bottom panel half 16b on top of bottom panel half 15b . this interleaving of the bottom panels together tends to frictionally maintain the toothbrush holder in its triangular configuration . in addition , the side tabs 25 and 26 are folded along their respective fold lines 27 and 28 to an upright attitute . when the occupant of the hotel room has brushed his or her teeth , the handle 30 of a toothbrush 29 can be inserted downwardly through one of the toothbrush openings 23 or 24 . typically , the toothbrush handle 30 will be long enough so that the distal end of the handle will engage a bottom panel 15 or 16 . the handle is prevented from moving laterally out of the confines of the toothbrush holder by the side tabs 25 and 26 so that the bristles will not come in contact with the holder . the open sides of the toothbrush holder allow for the hygienic drying of the handle , by allowing moisture to evaporate rapidly from the handle of the brush and from the bottom panels of the holder . since the effective cross - sectional dimension of the toothbrush openings 23 and 24 become smaller when the side walls 11 and 12 are folded along the fold line 14 , it may be necessary to slightly wedge the toothbrush handle 30 into an opening 23 or 24 . the side walls 11 and 12 will spread apart slightly to accomodate this wedging action , and the tendency of the side walls to resume their original folded shape tends to apply slight frictional force to the toothbrush handle so as to apply a slight gripping force to the handle . thus , is the user of the holder desires to leave the bristles 31 of the toothbrush slightly elevated above the toothbrush holder , this slight frictional engagement will permit this . the generally open shape of the toothbrush holder permits not only the bristles of the brush to be positioned above the holder and exposed for drying , but also permits the handle located within the sloped side walls 11 and 12 to be ventilated for drying . when the supply of toothbrush holders is ordered by the hotel , the name of the hotel can be printed on the outside surface of the sloped side walls 11 and 12 , together with other information such as telephone numbers , addresses , etc . further , the entire device is reversible so that certain advertisements can be placed on one side of each sloped side wall 11 and 12 , and different advertisements can be placed on the reverse sides of the side walls 11 and 12 , and the room attendants can be instructed as to which advertisements should confront the occupant of the room . for example , if the business activity at the hotel restaurant is low , the cards can be printed with an advertisement of the restaurant on one panel 11 or 12 and the room attendants instructed to fold the cards to expose that particular advertisement . it should be understood that the embodiments of the invention disclosed herein illustrate principles of the invention in a preferred form . other modifications , additions and deletions may be made thereto without departure from the spirit and scope of the invention as set forth in the following claims .

US-5711387-A

a disposable lunch container liner to protect the interior of a lunch container from food particles . the lunch container liner has adhesive pieces on its under side for removable attachment to the interior of a lunch container .

an embodiment of the invention will be described with reference to fig1 - 4 . with reference to fig1 - 4 , the invention includes a first side piece 1 , a second side piece 2 , a third side piece 3 , a fourth side piece 4 , and a base 5 . as shown in fig1 and 2 , the base 5 is attached to each side piece 1 , 2 , 3 , 4 . the base 5 and the four side pieces 1 , 2 , 3 , 4 are made of a single piece of continuous material . as shown in fig1 and 2 , the invention is in a flat , unfolded state . fig1 is a plan view of the top side of the invention in a flat , unfolded state . the top side is the side that is exposed to the lunch contents once the liner is inserted into the lunch container . fig2 is a plan view of the under side of the invention in a flat , unfolded state . an adhesive strip 6 is located on the under side of each side piece 1 , 2 , 3 , 4 of the liner to affix the liner to the interior of the lunch container . fig3 and 4 show the invention in a folded state , as it would be inserted in a lunch container . in fig3 and 4 , the adhesive strips 6 are affixed to the under side of the liner for contact with the interior of a lunch container . in one embodiment , the liner is made of a heavy duty material that is quilted and absorbent on one side and non - porous on the other side . the non - porous side is inserted into the lunch container so that it is adjacent the interior of the lunch container . the quilted side would be the top side of the liner , as shown in fig1 . the quilted , absorbent side is exposed to the lunch contents to absorb spills . the non - porous material can be selected from , for example , paper ( including cardboard or so - called wax - paper ) or plastic . in other embodiments of the invention , the liner may conform to lunch containers of various shapes and sizes . the liner is designed to cover all interior surfaces of a container except for the interior surface of the cover of the container . in the embodiment shown in fig1 - 4 , the liner is designed to conform to a container having a square base . in another embodiment , the liner may be designed to conform to a container having a rectangular base . in an embodiment shown in fig5 and 6 , the liner is designed to conform to a container having a circular base . in fig5 and 6 , the invention includes a first side piece 7 , a second side piece 8 , a third side piece 9 , a fourth side piece 10 , and a base 11 . as shown in fig5 and 6 , the base 11 is attached to each side piece 7 , 8 , 9 , 10 . the base 11 and the four side pieces 7 , 8 , 9 , 10 are made of a single piece of continuous material . in fig6 adhesive strips 12 are affixed to the side pieces 7 , 8 , 9 , 10 .

US-98491497-A

methods and apparatus for interpreting vaginal measurement data by electronic means without the need for the user to take part in the data interpretation process . more specifically , an intelligent probe monitors folliculogenesis and correlates the ovarian function data to probe profile characteristics of the female reproductive cycle . a fertile window is defined with reference to the correlation between folliculogenesis and probe cyclic profiles . data stored within the apparatus can be downloaded into an external display appliance or data analysis unit . another aspect of the invention allows for continuous layout of the memory of preceding cycles in the inventory of the apparatus , retaining the most recent while erasing the most distant stored data . these methods assure a reliable fit for the diagnosis of fertility , treatment of infertility as far as timing of treatment procedures , management of subfertility and other gynecological disorders such as luteal phase deficiency or short luteal phase , and the management of premenstrual mood disorders , and of premenopausal and menopausal patients .

the present invention is directed to electronic interpretation of data , monitored in relation to the day of cycle , on the physiological state of the cervix uteri and cervical mucus by means of the probe of my prior art patent application , and to automatically providing a display of the current fertility status . this is based on the measurement with the probe depicted in fig1 to 5 . the electronics of the probe contain a microchip , preferably an application - specific integrated circuit with a microprocessor , that performs the measurement as well as the data interpretation and data management according to the methods and programs of the present invention . fig1 to 4 are perspective , front , side , and rear views of the intelligent probe . fig1 to 4 resemble a fertility probe of my prior art , in particular they resemble the mammalian fertility probe of my design patent application filed under docket number 9064 / 102 to which i am now adding new features that provide for the intelligent characteristics of the apparatus of this invention . the probe comprises several cylindrical sections , preferably three as shown . the first section is a rigid or semirigid cylindrical body 11 approximately 10 centimeters long and 1 centimeter in diameter . the first section 11 has a rounded distal or insertion end insertable into the vagina , with the insertion end extending into the region of the posterior fornix with electrode 211 of fig2 contacting the cervix . two electrodes or elements 211 and 312 in fig3 are embedded into probe body 11 . the electrodes 211 and 312 can be of any shape and size within reason . the attachment of the electrodes to the body can be accomplished by any method known for attaching an electrode to a substrate , including , but not limited to gluing , bonding and embedding . the cylindrical body 11 of the first section may be modified in any of the ways anticipated by my patent application “ method and apparatus for monitoring fertility status in the mammalian vagina ” filed under docket number 9064 / 101 . the second section 12 may be of a larger diameter but smaller than the third section , as shown , but this mid - size diameter is a cosmetic rather than a functional feature . the second section contains three functional elements , one on the top or front side and two on the back . an infra red or other data transfer interface port 14 appears as a small opening on the front side defined as the side that carries the display - cum - controls well 15 and the electrode 211 . on the back side of this section are , as seen in fig3 and 4 , two wells 313 and 315 with two buttons 314 and 316 that are provided to control the less frequently used functions . the screw - like button 314 initiates , by being turned 90 degrees , data downloading once the port 14 is lined up with the corresponding port on a data receiving device . this function is independent of and separate from the daily - use program , in order to conserve energy and , equally significant , to keep the operation user - friendly ( undemanding ). the well - recessed small button 316 is used to register intercourse and save its timing ( day of cycle ) in the memory of the intelligent probe . either or both controls 314 and 316 may be behind a little door ( or two separate doors ) protecting them further from accidental actuation . other possible embodiments of the i - register input control include a sliding switch that slides from one groove into another and back , or two buttons that may be concentric and must be pressed together . the port may be located in the third section instead of in the indicated position , interchanging the location with the “ confirm ” button 19 , in another embodiment of the apparatus of this invention . it could also be located closer to the well 15 , either on the second section 12 or on the third section 13 . the third section 13 carries most of the microelectronics and is the handle of the hand - held probe device . the oblong narrow well 15 carries the on button 16 at the proximal end , followed by the lcd ( or led or other ) display 17 . this is then followed by the special control 18 which is a rocker switch that enables either positive (+) or negative (−) response to a displayed question , or adding 1 to (+) or subtracting 1 from (−) a displayed numerical value . the control switch 18 also makes it possible to perform its key role , which is the initialization of the day of cycle counter ( or relative time clock ), by being pressed straight down in its flat middle portion , where the numeral 1 is seen embossed or otherwise imprinted on its surface . other possible embodiments of the control element 18 include three separate buttons or other switches performing the same roles . they could be located outside of the well 15 such as on the opposite , back , side of the third section 13 . at the proximal or non - insertion end of the intelligent probe is the “ confirm ” button 19 located in a crater - like well 10 the purpose of which is to prevent accidental actuation of the control 19 . in another embodiment of the intelligent probe , the “ confirm ” button 19 and the well 110 are not present because the role of the “ confirm ” button is performed by the plus (+) segment of the controls 18 ( or by a separate button as noted above in discussing other possible embodiments of the control button 18 . the space in which the “ confirm ” button 19 is now shown in fig1 may be utilized for an external power supply connection useful for data downloading ( and / or offloading ) under the control of the intelligent probe . this preserves battery life for the daily use of the intelligent probe . fig5 is a block diagram of the electronic configuration of the probe of the invention which involves a microchip , preferably an application - specific integrated circuit . the electrodes 501 and 502 are actuated by means of the electrode interface conditioning electronics 503 by a waveform digitally generated by the microprocessor 507 . the waveform is applied after conversion into an analog signal in the a to d / d to a converter 505 which then also converts the electrode response to digital data for processing by the microprocessor 507 . unlike in the previous generation of the fertility probe , data processing now includes the data - interpretation treatment which is the subject of this application . the processed data is displayed on lcd ( or led or other ) display and stored in memory 506 for use as context for data interpretation on following days of the present menstrual cycle ; the stored data can also be optionally downloaded later ( for display and analysis ) via the input / output interface 508 into an external device 509 . the external device is typically a personal computer which may be dedicated to this purpose of analyzing patient data in a physician &# 39 ; s office . it may also be a decoder - interface unit custom - made for the purpose of receiving the data from the probe for display on an ordinary television set or on the new generation of computer - tv hybrids ( such as the web - tv , for example ). a web - tv may be equipped with an infrared port and may thus be able to receive the data directly , without the decoder - interface device . for such a case in particular , the intelligent probe includes an embedded program for elementary manipulation of the tv - downloaded multiple cyclic profiles , for the user &# 39 ; s convenience . in this way , the intelligent probe may provide access to the new generation of the so - called natural family planning to almost any woman in any household , regardless of whether they do or don &# 39 ; t own a home computer . this is useful since tv set ownership is generally more widely spread than personal or home computer ownership . fig6 is a flow diagram of the program associated with the use of the intercourse - register i - button 316 . this routine is independent of the data - interpretation program and of the daily - measurement procedure ; it is initiated by pressing the i - button 316 and terminated automatically by switching power off once the entry into the i - register is completed . the routine allows for a belated retrospective entry and for a possibly uncertain timing of such a retrospective entry . in the event the woman - user forgets to register the intercourse on the day , and then later wants to do this retrospectively but is not certain of the time elapsed , the routine downgrades reliability of the i - register . under the preferred normal circumstances , the user activates the i - registering routine on the day of the intercourse . the function of the i - button 316 commences with start i - register routine block 600 and proceeds to look up in today &# 39 ; s memory location the day of cycle xx ( and / or date ) in block 601 . this is then queried in block 602 . in response , the lcd 17 displays the entry “ i on day xx ?” as a question with a flashing question - mark , prompting the woman to confirm this in inquiry block 603 ( xx represents here today &# 39 ; s day of cycle , e . g ., 09 or 15 , as the case may be ) by pressing the “ confirm ” button 19 . upon this confirmation , the question - mark is extinguished as an acknowledgment of the confirmation and the entry is made in the i - register as in block 604 , and the power is turned off in block 605 . repeated entries on the same day simply write over without further changing the i - register status , i . e ., intercourse on a given day is registered whether it occurred and was entered once or more than once . if the woman is making the registration on a following day , today &# 39 ; s day of cycle xx is not confirmed in inquiry 602 by pressing the minus sign on button 18 , and consequently the inquiry know how many days ago ? is made in block 606 . in response she either steps the i - register down using button 18 by one day or by whatever number of days she remembers as the elapsed time with confidence , or she registers her uncertainty first by setting the flag in block 607 , before setting the i - register back in block 608 by the guessed number of days using again button 18 . the uncertainty will eventually be displayed on the downloaded cyclic pattern graph as “ i ?” instead of the definitive “ i ”. either the definitive “ i ” or the uncertain “ i ?” will appear on the time ( day of cycle ) axis of the graph and also by or in place of the respective data points in the line graph displayed on the external device 509 . the realtime , calendar date , will also be displayed . the calendar date information is useful for the purpose of calculating the estimated date of delivery , in case of conception resulting from the intercourse . the day of cycle information may be used for the purpose of fetal sex preselection . a similar design approach is adopted for the control of the optional data downloading into a display appliance ( external device 509 ), whether it be a personal computer or a web tv or the proprietary decoder - interface unit for interfacing with an ordinary tv set . the guiding principle is again to achieve user - friendly simplicity and power - supply energy conservation . fig7 is a flow diagram of the program associated with the use of the download control 314 . the program , which commences with start downloading block 700 , first enables to decide , through the inquiry of block 701 , whether to download data via blocks 702 ( have software ?) and 703 ( transfer control to pc ) into a personal computer which then can take control over the downloading process ; or whether the downloading will be into another display appliance that is devoid of the required software . in the latter case , a simple data manipulation is made possible by the intelligent probe using the few already described elements of the user interface , contained within the third section 13 of the apparatus . fig7 describes the process of downloading , i . e ., data - copying , under the control of the intelligent probe . any amount of data may be downloaded for display on the external device 509 , whether only the present cycle or all stored cycles or anything between these two extremes . however , only the total of the raw data can be offloaded so as to make the probe &# 39 ; s memory all available again for new data . the user is not allowed to edit the data for offloading while she can manipulate the data for viewing on the external display appliance 509 , the simple display manipulation sub - routine being described in fig9 ( shifting data along the day of cycle axis ). care is taken to allow offloading , for external archive storage , only of the complete set of raw data , unaffected by the manipulation available in the display sub - routine ( particularly the option to erase or display only some of the stored cyclic profiles ). once the decision has been made in block 701 to download under the control of the intelligent probe , the inquiry is made in block 704 whether only present cycle data is to be downloaded . if so , copying of data proceeds as per block 705 ( using the confirm button 19 ). with that cycle displayed on the display appliance , additional cyclic profiles may be added to the display via blocks 706 ( add another ? ), 707 ( key in number = c − i ) where c is the present cycle number and i is an integer for counting cycles backward , and finally block 708 ( copy data ). negative response to the inquiry in block 704 allows to download all stored cycles ( via block 709 ) or almost all after selective deletion in block 710 . either option goes to the sub - routine of fig8 . negative response to the inquiry in block 706 , namely no more stored cycles to be displayed , proceeds to exit in block 712 via the inquiry 711 which allows for a change of mind on the part of the user who may , upon viewing the present cycle data , decide to view all stored cycles rather than adding some of them piecemeal as already described . the remainder of the logical elements in fig7 describe the functions performed upon return from the two sub - routines shown in fig8 and 9 . the inquiry in block 713 allows the user to remove some cycles from the display on the external appliance upon return from the “ offload or merely view ” sub - routine of fig8 . this is achieved by means of blocks 714 ( identifying the cycles to remove , 715 erasing ) and 716 ( deciding to whether to exit or whether to remove some more data for a simplified viewing display prior to eventual exit via block 712 ). the inquiry of block 717 handles the return from the “ simple display manipulation ” sub - routine of fig9 . the feature to note in fig7 is that the woman can first examine the data selectively , before returning to offload the total memory contents in its raw state . fig8 is a flow chart of the sub - routine that offloads the entire memory contents of raw data . after block 800 has copied the data , the inquiry is made in block 801 whether to offload or not . the user responds via the plus or minus control 18 , possibly in combination with the confirm button 19 . if affirmative , the entire memory is transferred in block 802 into the external appliance capable of receiving the data ( e . g ., a personal computer ), the sub - routine is exited and the intelligent probe is powered off ( in block 803 ). if the user does not wish ( or cannot ) offload , the program goes into the sub - routine of fig9 via the connector c . also included in fig8 is a return from the sub - routine of fig9 via the connector d . this allows the user to change her mind , in block 804 , and offload the previously viewed and manipulated data but only after the data set has been returned to its raw state : to that end , the displayed data is erased in block 805 , then the entire memory is copied again in block 800 and offloaded via blocks 801 and 802 as already described . fig9 performs the rudimentary data manipulation that is of significance to any woman interested enough in the history of her menstrual cycle data to wish to review it on a display screen . the “ raw state ” of the consecutive cycles is a sequence showing the several months worth of menstrual cycles one after another so that the last day of cycle i is also the first day of cycle i + 1 as per the well known convention . the sub - routine first enables a decision in block 900 ( by means of the plus or minus functions of the control 18 , possibly in combination with the confirm button 19 ) whether to display the data on the same time scale , i . e ., in the manner of fig1 or fig1 . if so , all the data are shifted accordingly . after a time delay , the next inquiry is in block 902 , namely , does the user want to synchronize the displayed cyclic profiles on the day of the ovulation marker ( synchro on t = om ?). this inquiry would also be arrived at had the previous type of display not been desired by the user . the shift is performed by block 903 and , after a time delay , the sub - routine connects with the offloading sub - routine via connector d , as already discussed in fig8 above . a very important feature of the design is the option , open to the woman - user , to continue using the probe without offloading ( i . e . without clearing up ) a full memory . this is achieved by retaining the most recent preceding cycles in the inventory and erasing the most distant , the oldest stored data ; she therefore always has the most recent history ( whether it be six or twelve cycles or whatever the limit capacity built into the apparatus ) available for examination . this is made possible by the continuous layout of the memory discussed below in connection with the bookkeeping routine for stored prior cycles . the main control button 16 initiates , by switching on the power , the daily measurement and its diagnostic interpretation . the data - interpretation program interprets today &# 39 ; s probe measurement data : it develops the diagnostic meaning of the data in terms of fertility status ( either fertile or infertile ). it does that by cross - correlating the amplitude of the probe signal with at least one other running variable , day of cycle , as measured by the instrument &# 39 ; s clock which must be set to day 1 on first day of menstruation . ( other measurement variables may be introduced to potentially increase the quality of interpretation at the cost of increased complexity of the program and of increased production cost of the probe .) “ cross - correlation ” means to answer the question : what probe data interpretation is consistent with the other running variable , namely the day of cycle ? the method used in this application is based on fitting data points into a curve that has a multitude of reproducible features . other methods , known to those skilled in the art ( such as artificial intelligence methods ) are to be considered as falling within the scope of this invention . the data - interpretation program is based on the reproducibility of the features of the probe cyclic pattern ( or “ profiles ). the characteristic features of the profiles were described in section 2 . 3 with reference to fig1 and further experimental evidence is illustrated by three baseline and three non - baseline patterns in fig1 and 12 . the three baseline cyclic profiles in fig1 were obtained with three probe monitors pm 1 , pm 2 , and pm 3 by three clinical trial volunteers who satisfied the criteria for baseline characteristics . they were perfectly healthy young women below the age of 35 ( here 26 to 30 years of age ) who used no medication and no contraception . they had no prior pregnancies and they were non - smokers . the term “ baseline ” refers to the fact that these women were characterized by minimal , if any , potential complications of physiological or biochemical nature that could cause deviations from a norm or baseline ; they were as close to the idealized , stereotypical menstruating female as can be . the baseline cycles in fig1 exhibit at least two important characteristic features that were not known at the time of filing my u . s . &# 39 ; 247 patent and the subsequent patent applications . one , the data of the first minimum , fm , predicts the amplitude of the probe signal on the day of the beginning of the fertile window , bf , which is the end of the interval of dominance ( refer to fig1 ). and two , the end of the dominance interval is followed by a slowdown in the descent of the probe signal from the first peak , fp ( into the second minimum , sm ) which anticipates the ascent forming the second peak . i refer to this slowdown as a “ synchronization arrest ”. i consider both these characteristics a consequence of the ovarian mechanism that regulates the antral fluid steroid milieu , i . e ., an indicator of the intrafollicular hormonal profile of the dominant follicle [ e . y . adashi , j . a . rock , and z . rosenwaks , editors : reproductive endocrinology , surgery , and technology , lippincott - raven publishers , 19961 . those skilled in the art of reproductive physiology or endocrinology will appreciate the significance of these phenomena , tied to the previously mentioned ( section 2 . 2 ) prerogative of the dominant follicle to synchronize the entire reproductive system in order to make conception possible . the “ synchronization arrest ” is significant also with respect to the short luteal phase phenomenon as illustrated by two of the non - baseline cycles in fig1 ( cycles lk 4 and lk 5 ). i believe that the mechanism involved in some maimer the brain , probably the circhoral clock ( the hypothalamic gnrh pulse generator ) on which the circamensual ovarian clock is obligatorily dependent ; or this could be a case of failed gonadotropic ( lh ) support by the brain for the corpus luteum &# 39 ; s pre - programmed luteolytic self - destruct mechanism . it is significant that the details of the luteolytic control mechanism in primates are yet to be worked out [ ibid . idem .]. the complexity of the measurements of the differences between intrafollicular and circulating levels of hormones adds to the significance of the two probe profile characteristic which reflect what is going on in the ovary . the three non - baseline cyclic profiles in fig1 are three consecutive menstrual cycle probe records by a subject who did not satisfy the baseline criteria . mrs . lk was not “ chemically clean ” because she was a cigarette smoker ; she also routinely ingested various nutritional supplements that may have affected her reproductive biochemistry and physiology . she was over the age limit of 35 and had some history of amenorrhea , and of ovarian cysts diagnosed years earlier by palpation . she was also a mother , unlike the baseline subjects . in the years before her pregnancies , her cycles were consistently rather long , at 34 or 35 days ( as opposed to her cycle lengths here of 24 , 26 , and 28 days ). the non - baseline cyclic profiles in fig1 nevertheless exhibit the same features as those in fig1 that were obtained under more controlled laboratory conditions . the non - baseline profiles do present certain quantitative deviations from baseline : namely , in two cases ( cycles lk 5 and lk 6 ) their dynamic range is significantly lower compared to the baseline cycles in fig1 , and their post - ovulation ( luteal ) phase is not of the normal , inherent , length of 14 days ( 12 to 16 ). in such cycles with short luteal phases (& lt ; 11 days ), observed more often in older women , there is a lack of synchrony between the ovarian and the menstrual events due to a luteal - phase mismatch between the ovarian steroids and the pituitary peptides ( s . k . smith et al ., j . reprod . fert . 75 : 363 , 19851 . mrs . lk &# 39 ; s history of amenorrhea and ovarian cysts is pertinent to the case of short luteal phase . however , so is stress and its effect on the gnrh hormone generator in the hypothalamus of the brain , that affects the output of the pituitary peptides . for example , it is known in a general way that norepinephrine and possibly epinephrine in the hypothalamus increase the gnrh pulse frequency . conversely , the endogeneous opioid peptides , the enkephalins and beta - endorphin , reduce the frequency of the gnrh pulses . these interactions are particularly important at the time of the mid - cycle lh surge , affecting its timing and intensity [ w . f . ganong , review of medical physiology , 17th edition , appleton & amp ; lange , 1995 , chapter 23 ]. the slow rate of descent of the data from sp to om is a useful diagnostic variable that differentiates cycle lk 4 from cycle lk 5 . it is indicative of an extended period of time required in cycle lk 4 for the two “ clocks ” ( the circhoral and the circamensual ) to become synchronized as a precondition of ovulation . further , these “ real life ” ( non - laboratory ) records also contain gaps in data and possible effects of improper sensor positioning , in addition to the deviations from “ ideality ” ( or stereotype ). they therefore present a “ real life ” test for the data - interpretation program . the program does not analyze the data beyond the one day after the ovulation marker day because that is the postovulatory infertile phase of any menstrual cycle by definition . it is noticeable though that both the baseline and non - baseline profiles exhibit repeatable postovulatory features that are consistent with known biological facts and are likely associated with the pulsatile release of progesterone from the corpus luteum ( the postovulatory entity formed from the former dominant follicle ). these postovulatory features may be of use in a future extension of the program ; they may also be of use in a future extension of the applicability of the apparatus and method beyond that discussed here . the structure of the data - interpretation program , as shown in table 2 , consists of numerous layers of routines within two blocks , i . e ., block i = preparation for interpretation and block ii = interpretation of today &# 39 ; s probe data . the routines of the first block , preparation , establish the information required for data interpretation : today &# 39 ; s cycle day , today &# 39 ; s measurement data , and the “ inventory ” of prior data , if any , from previous measurements in the present cycle as may be stored in the probe &# 39 ; s memory . the routines of the second block perform the actual interpretation : the process consists of making five decisions on whether today &# 39 ; s probe measurement is consistent with infertile or with fertile interpretation and how reliable that diagnostic assessment is . the program looks for the much more frequent infertile diagnosis before looking to confirm fertile diagnosis , in the following systematic manner . first , it decides whether today is the first , so far the only , measurement in the present cycle which demands a “ single - shot ” diagnosis , or whether a contextual interpretation will be made possible by previously measured and stored data providing a context for today &# 39 ; s data point and thus increasing the reliability of the interpretation . if contextual interpretation is made possible by previously stored data in memory , the second decision is whether the today &# 39 ; s data point fits the characteristics of postovulatory data . if postovulatory , the interpretation is infertile unless the data fit the characteristics of ovulation marker + 1 day ( which requires the interpretation of fertile ). if the outcome of the second decision is not postovulatory data characteristics , the third decision is whether the data fits the characteristics of data before or after the first peak fp ( the long - term predictive peak ); if before , then the interpretation is infertile . if the outcome of the third decision is that the data point fits the characteristics of data after the first peak , the fourth decision is made on whether the data fits far enough before the second peak sp ( also known as the short - term predictive peak ) which means infertile or whether it fits at the second peak which means fertile . for the data point of today to fit at the second peak means that it corresponds to one of the characteristic features of the second peak as discussed below ( table 4 ): either to sm or to sp or to om , the three data points that define the peak . in either case , the fifth decision follows to assess the reliability of either of the diagnostic conclusions ( fertile or infertile ). the reliability descriptor is one of three degrees : 1 . high reliability , 2 . moderately high reliability , 3 . moderately low reliability . the reliability assessment is a function of several factors : a ) the number of data points from this cycle &# 39 ; s inventory that have been used for today &# 39 ; s data contextual interpretation , b ) the conception statistics for today &# 39 ; s day of cycle referenced to the characteristic feature of the cyclic profile including the ovulation marker and the long - term predictive peak , c ) the reproducibility of the measurement data if the user opts to repeat the measurement within the allowed two hours , d ) the amplitude of today &# 39 ; s probe data with respect to the fertility threshold and the ovulation threshold which in certain instances increases the reliability more than in others depending on day of cycle ( e . g ., data above 220 on day 9 ± 1 increases the reliability of infertile interpretation ), and e ) the uncertainty , if registered , about the correctness of the day of cycle which may have arisen upon the initialization of the day of cycle counter ( relative time clock ) if the user forgot to do this on day 1 of the cycle ( i . e ., on the day of her first menstrual bleeding ). each time the display of the intelligent probe is to indicate either “ fertile ” or “ infertile ” according to the flow diagrams in the figures below , the diagnostic interpretation is stored along with the raw data and a connection is made with the routine of the fifth decision ( reliability assessment ). a relatively high reliability of the diagnostic data interpretation is then indicated by a steady appearance of the fertility diagnosis on the lcd display , versus a relatively low reliability of the diagnostic data interpretation which is indicated by slow , letter by letter , emergence of the word “ fertile ” ( or “ infertile ” as the case may be ) on the display , in such a manner that the complete word never appears but rather the “ spelling ” is repeated at least twice . this focuses the user &# 39 ; s mind on the fact that the diagnostic statement is relatively unreliable , although it is always more reliable than merely guessing the fertility status based on the day of cycle alone ( as in the discredited so - called calendar or rhythm method of birth control ). the only truly indeterminate situations , no better than the day - of - cycle based guess , arise from the discouraged possible use of the intelligent probe in the inadequate - context diagnostic mode such as in the single - shot diagnosis discussed below . the lcd display then indicates “ unsure ” or similar indication of indeterminate diagnostic interpretation . in recommended use , a moderately high reliability of the diagnostic interpretation of data is indicated by fast emergence , i . e ., rapid spelling of the diagnostic outcome on the display , revealing the complete word (“ fertile ” or “ infertile ”) for a brief moment before repeating the fast “ spelling ” procedure at least four times . in summary , there is an unambiguous , easily intuitively understood distinction made between the different confidence levels of the diagnostic data - interpretation statements . either diagnostic statement is available on the display for a limited period of time ; if this turns out to be insufficient , the user can easily bring the result up again by simply pressing the “ on ” button 16 again . with reference to the reliability decision about the confidence level of the diagnostic interpretation , the quality requirements of the conception statistics , particularly in terms of homogeneity of the data , must be emphasized . in so far as the reliability descriptor of the fertility status diagnosis is one innovation of this application , and in so far as the conception statistics are factored into the descriptor , this point is of utmost importance . the clinical trial , that will generate the data on the conception statistics with reference to the long - term predictive peak , is yet to be performed . the basic requirement of the trial must be the single - attempt requirement : the women participating in the trial will be required to make a single attempt at conception in the cycles they contribute to the trial . at least four cycles each will be required . the women will be divided into several groups that make single attempts at conception on different days of cycle after their long - term predictive peaks . in this manner , the probabilities of conception will be established statistically for individual cycle days , allowing for the tonic growth phase of the antral follicle . it is planned to finalize the design of the reliability assessment routine at that time . the numerical values of the measurement data in tables 3 to 5 , just as those in the graph of fig1 to 12 , pertain to the particular calibration of the particular preferred embodiment of the method and apparatus of the invention discussed in this patent application . the qualitative aspects of the probe profile features listed in tables 3 to 5 similarly pertain to the particular embodiment of the apparatus and method utilized here for the purpose of teaching the invention . it is to be understood that the characteristic features of the cyclic profile depend on , and change with , the particular biological species to which the probe may be applied as well as with the waveform selected and , more generally , the characteristic features depend on and change with the mode of electrode excitation and the mode of monitoring . the data in fig1 to 12 and in tables 3 to 5 are provided by way of examples , without prejudice to the scope of the invention . table 2 summarizes the structure and basic elements of the data - interpretation program . in the tabulated systematic manner , most diagnostic interpretations are made with a high degree of confidence , due to the high information content of the probe cyclic pattern . the high information content is summarized in table 3 ( characteristic features of the probe cyclic pattern ). the wealth of characteristic features allows certain diagnostic interpretations to be made more readily , and / or with a higher reliability of the diagnosis , than others . for example , ovulation marker is readily and reliably determined if all the conditions are satisfied as follows : today &# 39 ; s reading is between 85 and 100 ua and two peaks have occurred beforehand with the features of the predictive peaks as listed in tables 3 , 4 , and 5 . in the case of the ovulation marker , the diagnosis is also quite reliable even if made in the absence of extended context information in the probe memory . table 4 lists the numerical details of the characteristic features of the second peak of the probe cyclic profile , also called the short - term predictive peak . * except for pm3 which is a short cycle with a short follicular phase and its bf therefore anomalously coincides with the apex of the first peak ( which otherwise precedes bf by several days in cycles with longer follicular phases ) table 4 is the list of the characteristics of the second peak that occurs within the window of fertility : a ) the start of the peak , i . e ., the second minimum sm is within the range of cycle day 10 to 14 and its amplitude ranges from 128 to 164 ua ; b ) the peak day coordinate of sp is within the range of cycle day 11 - 15 and the range of its amplitude coordinate is 158 - 220 ua ; c ) the ovulation marker om occurs within the day of cycle range 12 - 16 and its amplitude range is 88 - 108 ua ; d ) the timing of the second peak of the non - baseline cycles does not deviate from the baseline range of the respective cycle days ; e ) amplitude - wise , the deviation from baseline of the non - baseline range of probe measurement data is , as consistent with expectable estrogenic differences between baseline and non - baseline subjects , most pronounced at the peak &# 39 ; s apex ( downward ) and least pronounced at the ovulation marker minimum which is reproducible within the narrow range noted under c ) above ; f ) the gradient of the ascending ( gup ) and of the descending ( gdown ) branches of the second peak sp are high in comparison to the top sections of the first peak . where the non - baseline data are within the range of the first peak , they anticipate the short luteal phases of those cycles ; g ) the beginning of fertility ( bf ) data are within the range of cycle day 9 to 13 and their amplitude ranges from 129 to 183 microamperes . this range excludes cycle pm 3 which is a short cycle with a short follicular phase that causes a too high bf reading that lies , in fact , at the apex of the first peak . the anomalous first peak of cycle pm 3 is a consequence of the short follicular phase which has clearly recognizable high gradients comparable with the high gradients of the second ( fertile ) peak ; h ) the lowest second peak of the six ( 158 ua in cycle lk 4 ) is associated with an unusually slow descent into the ovulation marker minimum . a ) the start of the peak , i . e ., the first minimum fm , is within the range of cycle day 6 to 8 and its amplitude ranges from 128 to 164 ua . b ) cycles shorter than 28 days have the fm on day 8 and therefore record the prior descent to the minimum whereas longer cycles have the fm on day 6 ( meaning that the descent was completed during the menstrual bleeding period of days 1 through 5 ). c ) comparing the amplitude range of the first minimum with the amplitude range of the bf data listed here as well as in table 4 ( from fig1 and 12 ) reveals that the bf range of amplitudes ( beginning of fertility ) is approximated by the range of the first minimum . the amplitude of the fm therefore anticipates the amplitude of the bf data . provided that we exclude the short luteal phase cycles ( that are distinguished by the steep gradients of the first peak ), this finding can be used to identify the beginning of fertility bf on the day it occurs ( in extended context - data interpretation ), rather than identifying bf retrospectively from sm and sp data . d ) the peak day of fp is within the very narrow range of cycle days 9 or 10 and its amplitude is 200 ua and above . e ) the gradients g up and g down are low : excluding the short cycle pm 3 because of its short follicular phase ( associated with its anomalously narrow , low and sharp first peak ), the gradients are distinctly lower than those of the second peak . fig1 is a flow diagram for the daily initiation of the diagnostic measurement , the main purpose of which is to examine and , if appropriate , to set the relative time clock that counts the days of cycle starting on the first day of menstrual bleeding . the routine is user - friendly in several ways . it allows the user to set day 1 retrospectively , if she forgets to do so on her first day of menstrual bleeding , although this causes a downgrade in the reliability assessment of any subsequent diagnostic interpretation of the data . the downgrading of the confidence level is more serious if the user forgets to set day 1 on day 1 and then only guesses how long ago day 1 was . however , since the shape of the cyclic pattern is more significant than the day of cycle alone , even this downgrade is not too serious in extended - context diagnosis . the user is asked to confirm the correctness of the day counter ( relative time clock ) setting in the first eight days of cycle , i . e ., during the first three or so post - bleeding days , far from having to go through this interrogation every day . the initiation of the daily measurement and its interpretation commences with start block 1300 and proceeds to inquire in block 1301 whether the relative time t ( day of cycle ) is greater than 18 . this relative - time boundary condition of the fertile window is used here - by way of example within the frame of reference of the cyclic data in fig1 and 12 . the particular numerical value of t = 18 is used , rather than the general t = ef , with the proviso that its final numerical value , to be imbedded into the intelligent probe according to this invention , will depend on the outcome of the large - scale clinical trial invoked above in connection with the assessment of data - interpretation reliability in the discussion of table 2 . therefore , the value to be adopted as the result of the clinical trial may be larger than 18 . clearly , should the “ statistical extension ” of this limit be too high , the program would be extended to rely on analysis of the shape of the postovulatory part of the cyclic profile rather than on a particular numerical value as adopted here . if the day of cycle counter shows greater than 18 , then block 1302 makes the interpretation of infertile till next cycle and displays this indication on the lcd display 17 . block 1303 then inquires whether today is the first day of the next cycle which the user judges by the presence or absence of menstrual blood flow . the confirm button 19 or , in another preferred embodiment , the positive side of control 18 is used to confirm the first day if blood is found to be present and to confirm this in response to block 1304 ( sure ?). if not sure , the inquiry 1303 is repeated until a definitive answer is provided . if the response to 1303 is negative ( by means of the negative side of control 18 ), then block 1306 inquires again whether bleeding and receives negative response causing exit and power off in block 1307 . if bleeding is present even though today is not the first day , then block 1308 inquires into how many days ago . if known with certainty , then block 1309 allows the day number to be keyed in , using any or all three functions of control 18 ( 1 , +, −, in any combination but logically starting with 1 and adding to it if more than one day ). if not known for sure , block 1310 downgrades the reliability of the answer before proceeding to enter the less than certain number of days since bleeding started . block 1309 also caps the count of days in the completed cycle ( now “ previous cycle ”) so as to eliminate any overrun due to the fact that the first day was not registered when bleeding actually started . these decisions are queried for correctness in block 1311 which allows for rectification of any mistakes by going again through the loop of the inquiry of block 1308 , either with certainty ( simply correcting a possible miskeyed answer in block 1309 ) or further downgrading reliability in block 1310 . confirmatory response to the sure correct ? inquiry of block 1311 leads to another bleeding ? inquiry of block 1312 . this differentiates between the first five or so days when readings are obviated by menstrual bleeding ( block 1313 : wait till stop bleeding ) and the commencement of measurement in the new cycle for which the program goes into the routine of fig1 via connector 1 . returning to the first inquiry of this routine in block 1301 , if the answer were negative , the next inquiry in block 1314 is as to whether relative time ( cycle day register ) has been set . if not , the just described loop beginning with query 1303 ( today first day ?) is entered . this allows for belated start of monitoring in the present cycle . the last element in this routine is the inquiry in block 1315 ( t & lt ; 9 ?) which , for practical reasons based on experience , gives the user another chance to make a correction of the day of cycle setting every day during the first three or 50 days after the cessation of menstrual blood flow . since women know that these early days are infertile , some may be slack on the routine procedure and so this loop gives them a chance to rectify any mistakes due to belated start of the day of cycle counter . since this relative - time clock routine handles the initiation of new cycles , it must also handle the bookkeeping of previous cycles in relation to the memory space available for data storage . the flow diagram of this bookkeeping function is in fig1 and it uses a counter of stored cycles , c , which is stepped up upon completion of the present cycle ( i . e ., the start of the next cycle , indicated by the start of menstrual bleeding ). the design of the intelligent probe allows for a limited number , clim , of menstrual cycles to be stored , prompting the user to offload the stored data once the limit has been reached . one preferred limit is twelve menstrual cycles and this is based on the clinical definition of infertility which involves absence of conception after twelve months of unprotected intercourse ; another preferred limit is six months which tends to prompt an earlier consultation with a physician if reduced fertility is a problem . the bookkeeping aspect of this routine is based on continuous structure of the memory , such as a circular structure with a delineated point of first entry . the day of cycle , measurement and ancillary ( e . g ., cycle number intercourse registered , diagnosis and reliability ) data for every day are stored in a continuous manner , including gaps should the user skip the daily measurement . upon starting a new cycle by setting day 1 in the start - up routine depicted in fig1 which connects with this bookkeeping routine via connector 1 , the cycle counter c is stepped up in block 1401 and compared with the limit , clim , allowed for the number of stored cycles ( block 1402 ). when the limit is reached , the user is prompted to offload the data ( user instructions will recommend a physician &# 39 ; s office visit in case of difficulty to conceive ). the prompt to initiate the download is in block 1404 which is predicated by a positive response to the inquiry of block 1403 as to whether the woman has a capability to offload . even if she is not in a position to offload and thus renew the memory availability , the user is likely to have enough memory space left to continue , via connector 2 , since allowance is made for long cycles ( e . g ., forty days long ). availability of memory space is queried in block 1405 . in the absence of the offloading clearance , the memory will be filled up eventually and when the “ not enough memory left ” condition is detected in block 1405 , the software erases , in block 1406 , the oldest stored cycle data . this is where the continuance ( e . g ., circular or more likely rectangular layout ) of the memory comes into play , so as to facilitate the erasure of the oldest data before the more recently stored data may be treated in the same manner , should the user continue using the probe without offloading . this design secures the availability of the most recent inventory or history of the woman &# 39 ; s menstrual cycles even in the event of having exceeded the memory limit ( whether it be six or twelve or any other number of previously stored cyclic profiles ). the fact that the intelligent probe can never refuse to perform the daily measurements on account of an over - filled memory is an important and essential aspect of its user - friendly design . it is to be highlighted , however , that for the many near - stereotypical cycles of around 28 days in cycle length , there is an approximately 30 % spare memory space available because of the allowance for approximately 30 % longer cycles in the setting of the limit clim . the greater the number of cycles allowed to be stored ( gum ), the greater the favorable impact of this design feature . all the stored data , including the “ extra ” cycles are accessible for offloading and downloading . the remaining element in this routine is block 1407 which is a bookkeeping inquiry into whether the data is overflowing the memory limits ( handled as discussed above ) or whether it is still below the clim in which case the program goes to the next routine . fig1 is a flow diagram of the routine that performs the actual measurement once the time coordinate has been ascertained . this routine is again user - friendly in that it allows the user to repeat her daily measurement should she feel compelled to do so within two hours of first use . ( the time of daily measurements is a personal choice and the user instructions advocate to adhere to the selected time of day , give or take an hour .) any new measurement data for today is written over the data stored in today &# 39 ; s memory location within the allowed two hours . a comparison with the previous data of today , if any , is made because the reproducibility of the measurement data , in case of more than one measurement , becomes a factor for the reliability ( confidence level ) of diagnosis assessment in the fifth decision of the data - interpretation program ( not shown ). the routine charted in fig1 also performs the task of optionally repeating the display of today &# 39 ; s fertility diagnosis , whether the user wishes to merely check the status or whether she wishes to repeat the measurement within the allowed two hours of the first measurement of the day . the routine starts with an inquiry in block 1501 as to whether today &# 39 ; s memory location is still empty in which case block 1502 starts the ancillary hours counter just before block 1503 takes the actual measurement ( instructing the microprocessor 507 to actuate the electrodes 501 and 502 , and to record the response ; the instructions are not shown ). if the memory location is not found empty by block 1501 , block 1504 instructs the microprocessor to display the data from today &# 39 ; s memory location and then the diagnostic interpretation of that data . after a brief period of time , sufficient for user &# 39 ; s assessment of the displayed information , block 1505 tests the hours counter that had been started in block 1502 and , if the time elapsed is within the two hours allowance of the first measurement of today , block 1509 allows the user to repeat the measurement by means of block 1503 . if the elapsed time is beyond the two hour limit introduced at block 1505 or if the user does not wish to repeat the measurement in block 1509 , the previous data and diagnosis of today &# 39 ; s fertility status are displayed again in block 1506 after which , following again a suitable delay for user &# 39 ; s contemplation , the routine is exited and the intelligent probe is powered off in block 1507 . returning to the preferred extended - context mode of data interpretation , fig1 a is a flow diagram of the routine that makes the decision , whether the data taken today is postovulatory infertile ( i . e ., after the ef boundary of the window of fertility ), or not . the routine starts the examination of this cycle &# 39 ; s inventory of data on the earliest day available in c memory ( preferably day 6 or earlier ), having initialized the counters of peaks and minima by means of which it looks for the postovulatory condition . the postovulatory condition is defined by having found in the inventory of the present cycle , prior to today &# 39 ; s data , two peaks and three minima , all complying with the characteristics of the two predictive peaks and the associated minima , plus the day of cycle coordinate must correspond to two days after the third minimum which is the ovulation marker . the characteristics that this routine refers to are those listed in tables 4 and 5 ( numerical ranges of respective coordinates ). as pointed out in the discussion of tables 4 and 5 above , these characteristics pertain to the particular calibration and , more generally , to the particular mode of electrode excitation and the mode of monitoring in the particular embodiment of the apparatus and method of the invention . the decision routine is written out in two parts , fig1 a and 16b , because of its length and complexity . the chief reason for the complexity is the possibility of gaps in the flow of data , should the user skip some daily measurement ( s ) and the possible occurrence of noise in the data . both these complications are present in the examples of non - baseline cyclic profiles in fig1 . the second part of the routine in fig1 b re - defines as noise any lack of compliance of a detected peak or minimum with the characteristic features of the follicular phase of the profile . this is then recognized in the subsequent routines of the third and fourth decisions as a factor for downgrading the reliability of the diagnostic interpretation of the data . the first element of the routine , block 1901 , clears out the peaks and minima counters and the second , block 1902 , instructs the microprocessor to seek or look up next day data ( it has just found the earliest data of this cycle in the preceding routine ). the third block , 1903 , inquires as to whether the search has reached today &# 39 ; s date yet and if so , the peaks and minima counters are interrogated , in succession , in blocks 1905 and 1908 , respectively , as is the condition of today &# 39 ; s day of cycle t ( t = om + 2 ?) in block 1911 . the subsequent steps are identical for all the three inquiries of blocks 1905 , 1908 and 1911 if the answers are negative : blocks 1906 , 1909 and 1912 , respectively , inquire whether no gaps were found ; if so , the program goes into the routine of the third decision ( fig1 ) whereas if the answer is negative since gap ( s ) found , the program goes into the fourth decision routine ( fig1 ). fig1 is a flow diagram of the routine that makes the decision if the outcome of the previous , second decision in fig1 a was “ not postovulatory ”. the decision is whether the data fits before the first peak which means infertile diagnosis , or whether the data fits at or after the first peak . the condition of before the first peak is p = 0 and m = 1 ( registers p and m count the peaks and minima , respectively ) and it translates as infertile . if the condition is not satisfied ( i . e ., more than one minimum and at least one peak have been found ), the fourth decision is to be made next . fig1 is a flow diagram of the routine of the decision which must be made if the outcome of the previous decision was “ not before the first peak ”. the decision is whether the data fits well before the second peak or at any of the five points of the fertility window : the three points that define the second peak or one day before the “ foot ” of the peak which means one day before the second minimum , meaning the beginning of fertility bf , or one day after the ovulation marker ( i . e ., the third ) minimum , meaning the end of fertility ef . the conditions queried in the decision routine of fig1 have been dealt with earlier and the fertility window has also been defined . end of fertility ef − om + 1 ( end of fertility is defined as one day after ovulation marker om ). ovulation marker om = d & lt ; ot ( ovulation threshold ) & amp ; p = 2 ( ovulation marker is defined by measurement data below the ovulation threshold and the peak counter registering two peaks ). second peak sp is defined by p & gt ; 1 & amp ; m = 2 & amp ; 155 & lt ; d & lt ; 225 & amp ; 10 & lt ; t & lt ; 16 . second minimum sm is defined by m = 1 & amp ; p = 1 & amp ; 125 & lt ; d & lt ; 165 & amp ; 9 & lt ; t & lt ; 15 . beginning of fertility bf is defined by m = 1 & amp ; p = 0 & amp ; 125 & lt ; d & lt ; 240 & amp ; 8 & lt ; t & lt ; 14 or bf is defined by m = 1 & amp ; p = 1 & amp ; d . sub . bf = d . sub . fm +− 10 . this is where the characteristic features of the first and second peaks come into play and the program looks them up just like the human expert does : namely in a list such as those in tables 4 and 5 . the second part of the routine of the decision described in fig1 b above is also important for another reason in addition to that discussed above . the compliance queries therein are also the points where aberrant features of a qualitatively deviant cyclic profile are discerned and separated from the merely quantitative deviations such as those exemplified by the data in fig1 . this separation is achieved by providing to the program another set of characteristic features that belong to another type of cyclic profile . an example of an aberrant cyclic profile is shown in fig1 depicting a case of an aberrant luteal phase defect ( lpd ) which occurred m a perfectly healthy , 25 year old woman . this defect , a frequent cause of failure to conceive , is characterized by a complete absence of the first and second peaks . this means that the telltale signs of the reproductive system preparing for ovulation , by going through the stages of folliculogenesis as described above , are completely absent in this aberrant cyclic profile . as such , this qualitative deviation from the classical or baseline profile is readily characterized for recognition by the intelligent probe &# 39 ; s microprocessor . the diagnostic indication throughout the cycle is “ infertile - lpd ”. both the woman - user and her physician have the benefit of early recognition ( by day 10 ) of the defect , a significant benefit in the context of infertility management .

US-61017503-A

a need exists to improve the ice cream soda float and allow the consumer to selectively drink unmixed , carbonated soda , and also be able to mix an ice cream float to ones taste preference within the same cup holding apparatus . this invention describes a portable ice cream float cup that is joined together from two cups holding drink liquids and / or foods like ice cream . one straw can now be used to drink several different drinks by adjoining two or more cups together thus allow a consumer to have both an ice cream float and / or different drinks . the top cup holds either drink and / or ice cream and the first fluid chamber housing lower cup holds drink such as soda . the two cups snap together to form an air tight seal between the two cups . the first fluid chamber housing lower cup has a straw that allows the consumer to blow into the straw that builds up pressure into the first fluid chamber housing lower cup that houses liquid such as soda . when the first fluid chamber housing lower cup is pressurized , the fluid in the first fluid chamber housing lower cup is pushed up thru an interconnecting secondary tube , pipe pump straw allowing fluid to enter the secondary chamber upper cup that holds ice cream , making an ice cream float . the consumer can also sip and drink thru the same straw that was used to pressurize the first fluid chamber housing lower cup , and drink just the contents of the cup that houses the drink from either the first fluid chamber housing lower cup , or the top cup . the consumer can now have an ice cream float mixed to his / her preference , and also may drink unmixed , carbonated soda and have fun making the ice cream float by blowing fluid into the top cup .

although specific embodiments of the invention will now be described with reference to the drawings , it should be understood that such embodiments are by way of example only and merely illustrative of but a small number of the many possible specific embodiments which can represent applications of the principles of the invention . various changes and modifications obvious to one skilled in the art to which the invention pertains are deemed to be within the spirit , scope and contemplation of the invention as further defined in the appended claims . in the preferred embodiment , the cup as shown in fig1 is made of any moldable substance with memory such as rubber , urethane , nylon , plastic , polyvinyl . it is also within the spirit and scope of the present invention for the attachment to be made of flexible but strong plastic such as mylar , polypropylene or any other flexible material exhibiting the required characteristics . a first singular tube , pipe , pipe , straw , conveyor that is used to sip , drink , consume from and also be used to blow air pressure into thus creating positive pressure into the first fluid chamber housing that contains , stores , houses a consumable liquid product that is adjoined , linked attached to a secondary separate chamber housing by way of a tube , straw , conveyor that contains , houses , stores , holds the same and / or different type of consumable food product thus when the first fluid chamber is pressurized with a positive air source that was transferred from the first singular tube , pipe the fluid will transfer to the adjoined secondary chamber , by way of a secondary tube , pipe , straw , conveyor thus creating another type of mixed consumable food . referring to fig1 , there is shown in its entirety assembled cup assembly 777 the three sections adjoined together to form a two chamber cup with air tight sealed straws . referring to fig2 . there is illustrated in a perspective cross sectional view between the upper lid cap 411 , secondary chamber upper cup 511 , and first fluid chamber housing lower cup 711 . when upper lid cap 411 , secondary chamber upper cup 511 , and lower cup 711 are assembled together they combine to form the complete assembly as shown in fig1 . other than the first singular tube , pipe blow / sip 903 and secondary tube , pipe pump straw 902 the secondary chamber upper cup 511 and first fluid chamber housing lower cup 711 have an air tight seal between the two chambers via secondary chamber upper cup lip seal 802 and first fluid chamber housing lower cup lip 999 . when assembled an end user can blow into the first singular tube , pipe , blow / sip straw 903 causing pressure to build up into the first fluid chamber housing lower cup 711 first fluid chamber housing lower cup chamber 921 . the built up of pressure in the first fluid chamber housing lower cup chamber 921 causes fluid that resides and housed in the first fluid chamber housing lower cup chamber 921 to flow into the secondary tube , pipe pump straw 902 secondary tube , pipe pump straw outlet hole 977 and flow up and exit the fountain spray nozzle 904 that fills up the secondary chamber upper cup 511 secondary chamber upper cup holding chamber 807 thus creating either an ice cream float , if ice cream is housed in the secondary chamber upper cup holding chamber 807 , or a mixed drink if another type of drink is housed or placed into the secondary chamber upper cup holding chamber 807 . the same first singular tube , pipe blow / sip straw 903 can also be used to sip and drink , like a normal straw is used , drink / fluid that is housed in the first fluid chamber housing lower cup 711 first fluid chamber housing lower cup holding chamber 921 thru first singular tube , pipe blow / sip inlet / exit hole 873 at the end of first singular tube , pipe blow / sip straw . the same first singular tube , pipe blow / sip straw can have at the end of the first singular tube , pipe blow / sip inlet / exit hole 873 a spoon shaped straw 877 thus allowing the same straw to also be used to scoop out ice cream from secondary chamber upper cup holding chamber 511 when pulling out the first singular tube , pipe blow / sip straw from the secondary chamber upper cup 511 secondary chamber upper cup first singular tube , pipe blow / sip straw inlet 805 and inserting the spoon type straw into the opening of the upper lid cap access hole 987 to gain access to ice cream housed in secondary chamber upper cup holding chamber 807 . the upper lid cap 411 has a lower cap lip 914 that seals against secondary chamber upper cup 803 . upper lid cap hole 987 allows the consumer to drink and / or spoon the contents out of the secondary chamber upper cup 511 . the secondary chamber upper cup first singular tube , pipe blow / sip straw support channel 810 and secondary chamber upper cup pump support channel 910 are shown that houses the first singular tube , pipe blow / sip straw 903 and secondary tube , pipe pump straw 902 via an interference air tight fit between the outside diameter of the straws and the inside diameter of the support channels 810 and 910 . upper lid cap 411 has a lower cap lip 914 that has a water tight seal when adjoined to secondary chamber upper cup 511 secondary chamber upper cup lip seal 803 thus allowing sipping from the upper lid cap access hole 987 . first fluid chamber housing lower cup lip 802 is shown that adjoins to first fluid chamber housing lower cup upper lip 999 to ensure a pressurized air tight fit between secondary chamber upper cup 511 and first fluid chamber housing lower cup 711 . it should be noted that a third chamber and fourth chamber and other chambers could be utilized for consumable liquid therefore allowing the first singular tube , pipe blow / sip straw to gain access into these other chamber cups to access other types of drinks by pulling the first singular tube , pipe blow / sip straw 903 and placing them into the other chambers and / or could have more than one first singular tube , pipe blow / sip straw 903 thus allowing access into other drink chambers like secondary chamber upper cup 511 . the same can be said for the secondary tube , pipe pump straw 902 that could be adjoined to other chambers like secondary chamber upper cup 511 or could have more than one secondary tube , pipe pump straws that access to these chambers like secondary chamber upper cup 511 . it should be noted that this patent is not limited by the amount of straws and or chambers that can have access to several different drinks by way of either one or more first singular tube , pipe straws that could remain static , stationary or require pulling the tube , straw to gain access into one or more holding chambers like 511 that contains one or more types of consumable food items . again stated one or more first singular tube , pipe straws can have access to one or more chambers and / or pulling one or more first singular tube , pipe straws and placing them into one or more secondary chambers that holds one or more consumable foods or have more than one first singular tube , pipe type straws that remain static yet have also access to more or more chambers that the pipe can be sipped to gain access to more or more chambers . first singular tube , pipe blow / sip straw 903 can be seen inserted into the secondary chamber upper cup first singular tube , pipe blow / sip straw support channel 810 . it should be noted that also loose fitted straws can be used as a means to allow excess air to blow by the loose fitted first singular tube , pipe blow / sip 903 and / or secondary tube , pipe pump straw 902 thus eliminate excessive pressure causing the secondary chamber upper cup from blowing off the first fluid chamber housing lower cup . it should also be noted that first singular tube , pipe blow / sip straw is not limited by the type or shape of the straw and can either be an accordion type bendable straw and / or spoon straw for ease of removing ice cream from the secondary chamber upper cup 511 . also , a relief hole 307 could be incorporated to possibly eliminate either too much pressure that could build up in the first fluid chamber housing lower cup chamber 921 causing fluid to come back into the first singular tube , pipe blow / sip straw 903 or blow off the secondary chamber upper cup 511 from first fluid chamber housing lower cup 711 . referring to fig3 . illustrates a top down view of the assembled cup assembly 777 . secondary chamber upper cup first singular tube , pipe blow / sip straw inlet 805 and fountain spray nozzle 904 in fountain spray housing 804 are shown . upper lid cap access hole 987 can vary in shape from cylindrical , square , rectangular or any other shape thus allowing access to the secondary chamber upper cup chamber 807 . thus shown is an elliptical shape to eliminate any spillage from the fountain spray nozzle 904 and also allow access to secondary chamber upper cup first singular tube , pipe blow / sip straw inlet 805 . it should be noted that the blow sip straw could also be inserted in the wall of the secondary chamber upper cup lip as shown in fig5 . also , the upper lid cap 411 can be adjoined to the secondary chamber upper cup 511 thus making a one piece unitary part that is both a lid and secondary chamber upper cup . referring to fig4 . there is illustrated in a perspective view of the secondary chamber upper cup 511 without the first singular tube , pipe blow / sip and secondary tube , pipe pump straws . secondary chamber upper cup first singular tube , pipe blow / sip straw inlet 805 allows for the first singular tube , pipe blow / sip straw 903 to enter the secondary chamber upper cup first singular tube , pipe blow / sip straw support channel 810 . an air tight seal is created between the outside circumference and the inside circumference of items 805 and 810 . ice cream and / or fluids reside in secondary chamber upper cup chamber 807 . liquids could be poured into secondary chamber upper cup chamber 807 by either fluid coming from the fountain spray housing 804 fountain spray nozzle 904 or poured directly from above from the secondary chamber upper cup opening 933 from fig3 &# 39 ; s upper lid cap access hole 987 . secondary chamber upper cup pump support channel 910 forms an air tight seal for not shown secondary tube , pipe pump straw 902 . secondary chamber upper cup lip seal 803 and first fluid chamber housing lower cup lip 802 are shown and used to seal the secondary chamber upper cup to both the upper lid cap and first fluid chamber housing lower cup . referring to fig5 . there is illustrates all three components in a disassembled view . upper lid cap 411 is above secondary chamber upper cup 511 and above first fluid chamber housing lower cup 711 . referring to fig6 , there is shown in its entirety the three sections adjoined together to form a two chamber cup with air tight sealed straws . referring to fig7 . there is illustrated in a perspective cross sectional view of an alternate but similar system with the secondary chamber upper cup 200 residing on top of the first fluid chamber housing lower cup 300 . when upper lid cap 100 , ice cream cup 200 , and liquid container cup 300 are pressed together they combine to form the complete assembly as shown in fig6 . the upper lid cap 100 has a lower cap lip 101 that seals against secondary chamber upper cup lip 203 . upper lid cap hole 103 allows the consumer to drink or spoon the contents out of the secondary chamber upper cup 200 . secondary chamber upper cup pump support channel 205 is shown that houses the secondary tube , pipe pump straw 302 via an interference air tight fit between the straw and the spray hole housing 204 thus ensuring the fluid goes into the secondary chamber upper cup chamber 206 . secondary chamber upper cup lip 203 allows for a press fit between the upper lid cap lip 101 and secondary chamber upper cup upper lip 203 . secondary chamber upper cup lower lip 202 is shown that adjoins to first fluid chamber housing lower cup upper lip 301 to ensure a pressurized air tight fit between secondary chamber upper cup 200 and first fluid chamber housing lower cup 300 . first singular tube , pipe blow / sip straw 303 can be seen inserted into secondary chamber upper cup first singular tube , pipe blow / sip air tight seal 201 . it should be noted that a loose fitted straws can also be used as a means to allow excess air to blow by the loose fitted first singular tube , pipe blow / sip 303 and / or secondary tube , pipe pump straw 302 thus eliminate excessive pressure causing the secondary chamber upper cup from blowing off the first fluid chamber housing lower cup . also , a relief hole 307 could be incorporated to also eliminate either too much pressure built up in the first fluid chamber housing lower cup 300 that can also cause fluid to come back into the first singular tube , pipe blow / sip straw 303 . secondary tube , pipe pump straw inlet 305 allows fluid to travel secondary tube , pipe pump straw 302 thus allowing fluid to be pumped into secondary chamber upper cup holding chamber 206 when air pressure is blown into first singular tube , pipe blow / sip straw 303 therefore building pressure causing fluids to exit secondary tube , pipe pump straw inlet and coming out of fountain spray nozzle 207 . the bottom underside of the secondary chamber upper cup 757 can be various shapes e . g . convex , concave , cylindrical , flat etc . thus reduce any excessive pressure build up or cause fluid to spill out of first fluid chamber housing . referring to fig8 . illustrates a top down view of the assembled cup assembly 401 . fountain spray nozzle 204 and upper lid cap hole 103 and lower cap lip 101 and is cylindrical in shape . referring to fig9 . there is illustrated in a perspective view of an alternate system to move fluid from the liquid container cup 300 to the ice cream cup 200 thru t - chamber 402 . t - chamber 402 comprises of t - chamber first singular tube , pipe blow / sip straw inlet 405 that adjoins to t - chamber mid - section 404 that stores liquid and t - chamber liquid inlet 403 and t - chamber ice cream cup straw outlet 402 . when the consumer is sipping from first singular tube , pipe blow / sip straw 303 , fluid comes thru t - chamber inlet 303 . when blowing into first singular tube , pipe blow / sip straw 303 , the fluid stored in t - chamber mid - section 404 is moved out to ice cream cup straw 302 and into ice cream cup 200 . also the fluid passing in the t - chamber causes a venturri effect drawing fluid from t - chamber liquid inlet 403 . also shown is an alternate version of the upper lid cap 136 that has a upper lid inlet opening 122 that is approximately 2 . 5 inches in diameter . the upper lid flange boarder 135 has a concaved apex shaped raised flange thus allowing the fluid leaving the secondary tube , pipe pump straw 302 to bounce off the underside of the upper lid flange boarder allowing the fluid to deflect back into the secondary chamber upper cup 200 . the advantages to the upper lid flange boarder allows for the first singular tube , pipe blow / sip straw exit , exhaust opening 145 to not be constrained thus allowing larger amounts of fluid to be spilled into the secondary chamber upper cup 200 . the singular tube , pipe blow / sip straw exit , exhaust opening 145 can be accomplished several different ways and not limited in this invention and could include closing or sealing off the end of the singular tube , pipe blow / sip straw exit and having holes placed at the end of the singular tube , pipe blow / sip straw thus when fluid is being pumped out makes a fountain effect . referring to fig1 . there is illustrated an alternate embodiment to the t - chamber with check valves to improve the flow of fluid to and from the ice cream cup 200 and liquid container cup 300 . inlet check valve 502 will open and outlet check valve 501 will close when a consumer sips from first singular tube , pipe blow / sip straw 303 allowing a continuous flow of fluid . when the consumer blows inlet check valve 502 will close and outlet check valve 501 will open moving the fluid out of the t - chamber 402 . inlet check valve 502 is open in the static position . referring to fig1 . there is illustrated a cross sectional view of another alternate design of the secondary chamber upper cup whereas the secondary chamber upper cup 700 has a inward cone shaped funnel 703 and opening 707 allowing drink to be filled into the first fluid chamber housing lower cup 717 that secondary chamber upper cup 700 sits on top of . the advantage of this alternate design is that one can fill up the first fluid chamber housing lower cup chamber 721 via opening of funnel 707 and being forced past check valve 712 with drink without removing the secondary chamber upper cup 700 from the first fluid chamber housing lower cup 717 . in this alternate configuration ice cream or another type of drink is filled in chamber 704 that is separated from the funnel drink fill chamber 707 by separating wall 721 thus separating the drink inlet funnel 703 from the ice cream holding chamber 704 . it should be noted that this separating wall 721 could be a funnel shaped wall in the center of the secondary chamber upper cup 700 or splitting the secondary chamber upper cup into two chambers depending on the configuration selected . a center shaped funnel would assist the end user to fill up the first fluid chamber housing lower cup when using a soda fountain machine . sealing lip 710 creates an airtight seal between secondary chamber upper cup 700 and first fluid chamber housing lower cup 717 . secondary chamber upper cup 700 sits on top of the lower drink cup 717 . funnel 703 has a check valve 712 at the bottom of the funnel that is adjoined to a hinge 701 that attaches to the secondary chamber upper cup 700 and adjoined to the funnel shaped inlet 707 at the lower end of the funnel opening thus allowing drink to enter the first fluid chamber housing lower cup via a one way check valve 712 that is closed in the stowed position therefore stopping any air from escaping the first fluid chamber housing lower cup 717 when first singular tube , pipe blow / sip straw has positive pressure applied to it via end user blowing into straw , and the check valve can open or deploy when being pushed down from the secondary chamber upper cup when a force is applied like fluid drink is being filled into the first fluid chamber housing lower cup 717 thru inlet funnel 707 . check valve is adjoined to a preloaded hinge 701 that is adjoined to the bottom of secondary chamber upper cup 700 and sealed accordingly with an air tight seal around the check valve and surrounding hole that is located in the secondary chamber upper cup . when pressure is built up in the first fluid chamber housing lower cup 717 by the end user blowing into the first singular tube , pipe blow / sip straw 709 the check valve 712 is in the stowed closed position , pressure will build up in the first fluid chamber housing lower cup 717 causing fluid to exit the secondary tube , pipe pump straw 708 and exit the fountain spray hole 718 thus mixing with either ice cream or drink that is located in chamber 704 . it should be noted that several different types of check valves can be used for this application and could consist of silicone ring concave verses convex construction and the claim would indicate a one way valve that stops air from escaping the first fluid chamber housing lower cup 700 and exiting the funnel shaped inlet 707 when being pressurized and also allow fluid to enter the first fluid chamber housing lower cup when the pressure is not being applied into the first fluid chamber housing lower cup 717 . it should be noted that 733 and 734 are illustrating both air tight seals between first singular tube , pipe blow / sip straw 709 and secondary tube , pipe pump straw 708 between upper 700 and first fluid chamber housing lower cups 717 as described in detail per fig2 and fig7 straws and there interface with the upper and first fluid chamber housing lower cup .

US-92467910-A

a method of assembling an implant in one embodiment includes aligning the connection features of a first implant component with the connection features of a second an implant component , placing an implant engagement surface of an impactor device and the first implant component in contact , striking an impaction surface of the impactor device , transferring force from the impaction surface to an impactor shaft , diverting the transferred force within the shaft , focusing a portion of the diverted force , and transferring the focused force from the shaft to the first implant component which brings the connection features on the first implant component into engagement with the connection features on the second implant component .

with reference to fig3 - 5 , an impactor device 50 is disclosed . the impactor device 50 is provided as an elongated bar member 52 that includes a shaft portion 54 , a grip 55 , a first end 56 , and a second end 58 . the first end 56 provides an impaction surface and the second end provides a force distributing surface in the form of an implant engagement surface . a plurality of holes 60 are formed in the shaft portion 54 . in the embodiment of fig3 - 5 , the shaft portion 54 of the impactor device 50 is generally cylindrical in shape . the shaft portion 54 is hollow with a channel 62 extending axially along the center of the shaft portion . the channel 62 is surrounded by an exterior wall 62 . although the exterior wall 62 is cylindrical in the embodiment of fig3 - 5 , one of skill in the art will recognize that the exterior wall may be any of numerous other shapes , such as box - shaped . a plurality of holes 60 extend through the exterior wall 62 of the shaft portion 54 and into the axial channel 62 , resulting in a perforated shaft portion 54 . in the embodiment of fig3 - 5 , the plurality of holes 60 are arranged on the shaft portion 54 such that any given line passing axially along the surface of the exterior wall will intersect at least one of the plurality of holes 60 . to obtain this result , the holes 60 on the shaft portion 54 may be arranged in a staggered matrix around the shaft . fig1 shows an expanded polar coordinate view of the shaft portion 54 further displaying the staggered matrix arrangement of the holes . this view shows the shaft portion 54 “ unwrapped ” along the central axis such that the leftmost position is a zero degree position and the right most position is a three hundred sixty degree position radially relative to the central axis of the shaft . as shown in fig1 , the holes 60 are arranged in a staggered matrix such that the holes 60 in one row are offset from the holes in an adjacent row . in the disclosed embodiment , seven rows of holes 60 are provided with four holes in each row . the holes 60 overlap in the axial direction such that a line extending axially along the shaft portion , such as line 90 , will intersect one or more of the holes 60 . with this arrangement , the holes in each row are situated at ninety degree increments around the shaft , as can be seen from fig8 and 9 . in other words , the center of a hole in a row is ninety degrees removed from the center of an adjacent hole in the row . in the disclosed embodiment , the diameter of each hole is 0 . 379 inch . with reference again to fig3 - 5 , the grip 55 of the impactor device 50 is provided next to the shaft portion 54 , toward the first end 56 of the impactor device 50 . the grip 55 includes a plurality of fins 72 that extend axially along a length of the shaft surface . the fins 72 are separated by axial indentations 74 . the fins 72 and indentations 74 provide a knurled surface that provides an aid in gripping the impaction device 50 . the first end 56 of the bar member 52 provides the impaction surface and is configured to receive a blow from a mallet or other striking device . in the embodiment of fig3 - 5 , it can be seen that the impaction surface is generally flat . this flat surface helps prevent the surgeon or surgical assistant from hitting the impactor device off axis . fig6 - 9 show a similar embodiment to that of fig3 - 5 , and identical reference numerals are used to identify the same parts . however , in the embodiment of fig6 - 9 , the impaction surface on the first end 56 of the bar member is convex . in this embodiment , the force of striking tool used by the surgeon is generally concentrated on a smaller area of the impaction surface . the second end 58 of the bar member is positioned opposite the first end . the second end 58 of the bar member provides a force distributing surface . the force distributing surface is configured to engage an implant member , and thus serves as an implant engagement surface . if the implant member that will be contacted by the implant engagement surface is contoured , the implant engagement surface may be similarly contoured to mate with the surface of the implant member in a congruent fashion . the implant engagement surface shown in fig3 - 5 is designed to engage a convex rounded surface , such as the spherical humeral head of a humeral implant . thus , the implant engagement surface on the second end 58 of the bar member 52 provides a concave rounded surface . in one embodiment , the impactor device 50 is designed to be somewhere between five and nine inches in length . this length generally facilitates ease of handling by the surgeon along with a sufficient size for many human implant devices . in one embodiment for use with a humeral implant , the impactor device 50 is about seven inches in length . of course , one of skill in the art will recognize that the impactor device is not limited to a particular length and the impactor device may be designed to any number of different lengths . the impactor device 50 may be comprised of any of several different materials . preferably , the material will be moldable , offer high flexural fatigue strength , rigidity , low wear , toughness and resistance to repeated impact . in one embodiment , the impactor device 50 is comprised of an acetal copolymer such as celcon ®. the simplicity of the impactor device design and use of appropriate material will also allow the impactor device to be easily cleaned through autoclaving . the impactor device 50 is used by a surgeon or other surgical personnel to assemble a prosthetic device to be implanted in a patient . to this end , the surgeon first chooses an appropriate design and size for the various components of the implant device based on the size and needs of the patient . the implant device comprises a first implant component and a second implant component to be connected by a morse taper or similar arrangement where the implant components are configured for connection by forcing connection features on the first component into engagement with connection features on the second component . after selecting appropriate implant components , the surgeon selects an impactor device as set forth above . the impactor device includes a shaft portion , a grip portion , a first end with an impact surface and a second end with an implant engagement surface . a plurality of holes are formed in the axial wall of the shaft portion . the implant engagement surface of the impactor device is configured to engage a surface of the first implant component in a congruent fashion . the surgeon aligns the connection features of the first implant component with the connection features of the second an implant component . next , the surgeon holds the impactor device by the grip portion 55 and brings the implant engagement surface 58 into contact with the first implant component ( e . g ., the head 12 of the humeral implant of fig1 and 2 ). the axis of the impactor device is oriented on the first implant component such that a force transmitted through the impactor device will force the first implant component into full engagement with the second implant component . after properly aligning the impactor device , the surgeon strikes the impaction surface 56 on the impactor device , thus transmitting a force through the impaction device and to the first implant component ( e . g ., the plug 19 into engagement with the recess 28 in fig2 ). this force is intended to bring the connection features on the first implant component into engagement with the connection features on the second implant component . the surgeon may be required to strike the impaction surface 56 one or more times to bring the connection features on the first implant component into full engagement with the connection features on the second implant component . when the surgeon strikes the impactor device , the impactor device dissipates the force transmitted through the bar member and to the implant . in particular , the holes 60 in the impactor device 50 provide voids in the shaft portion 54 so that the shaft portion 54 can compress and expand to dissipate energy . furthermore , the orientation of the holes 60 not only limits the amount of force that is transmitted down the shaft portion , but also helps to maintain the integrity of the impactor device , such that the impactor device does not fracture , degrade or otherwise fail when struck with a mallet or other striking device . the staggered matrix orientation and size of the holes on the shaft portion can effectively dissipate about forty percent of the impaction force imparted by a striking device . thus , even if a five thousand pound force is delivered by a mallet strike , the impactor device 50 will reduce that force to around three thousand pounds , which would be more than enough force to cause the humeral head to engage the humeral insert for most implants . at the same time , the reduced force is much less likely to result in disengagement of or damage to the intermediate components in the implant device . although the present invention has been described with respect to certain preferred embodiments , it will be appreciated by those of skill in the art that other implementations and adaptations are possible . for example , the impactor may take the form of different shapes than those shown in the figures , may include different features , may be differently sized , or may be comprised of different materials than those disclosed herein . moreover , there are advantages to individual advancements described herein that may be obtained without incorporating other aspects described above . therefore , the spirit and scope of the appended claims should not be limited to the description of the preferred embodiments contained herein .

US-52695306-A

a male incontinence device comprises a condom which fits over the end of a penis and is secured by a band having overlapping ends with h & amp ; l fasteners . when the condom is filled with a quantity of urine , it can be removed and emptied . alternatively , the distal end of the condom has a valve thereat for manual emptying of the condom when it is in place . the valve may comprise a tubular housing fitted into an end of the condom and a plug which can be removably inserted into the housing . a brief - type undergarment has a pouch 33 for supporting the condom when filled with urine . in lieu of a separate housing , the end of the condom may be thickened and formed into a tube so that a plug can be inserted into the tube . alternatively , the end of the condom can be fitted with a ball - obturator valve which can be opened to empty the condom by squeezing it from outside to distort the valve seat and thus open the seal formed by the ball obturator .

fig1 show a urinary catheter or device 16 according to the invention . it has a large opening or rim 10 at its proximal ( right ) end and a wrap - around band 11 with multiple hook - and - loop fasteners adjacent the proximal end . a modified wrap - around band 19 &# 39 ; ( fig3 b ) has a wide loop end 25 which provides extra width for the fingers to hold while hook end 25 &# 39 ; is being attached . at the other end , the condom tapers to a neck 15 . positioned in neck 15 is a valve housing 12 with a plug valve 13 inserted into housing 12 . a binding thread 14 secures valve housing 12 to neck 15 to form a leak - proof seal . a plug valve cord 13 &# 39 ; is attached to plug valve 13 and valve housing 12 . fig2 shows condom 16 in a partly unrolled condition . its semen reservoir tip 20 is partially removed by cutting along broken line 18 . valve housing 12 preferably is made of rubber or vinyl and incorporates an annular groove 22 which is inserted into neck 15 about 1 . 3 cm ( 1 / 2 in ). about 15 to 20 cm ( 6 to 8 in ) of fine thread 14 is then wrapped tightly around annular groove 22 over neck 15 to force it into the groove to form a seal . removable plug 13 is then inserted into open valve end 26 . in addition , a cord 13 &# 39 ; is attached to plug 13 at one end and to valve housing 12 at its other end . this insures that plug 13 cannot be accidentally dropped or lost when it is removed during use . fig3 a shows wrap - around band 19 which is placed between rim 10 of condom device 16 ( fig1 ) and the head 17 of the penis to secure the catheter in place . band 19 has multiple hook - and - loop fasteners sold under the trademarks velcro and latchlock . fig3 b shows a wrap - around band 19 &# 39 ; made wider at end 25 , so as to provide extra width to hold while pulling and attaching narrow end 25 &# 39 ;. this assists the user in fitting it tightly enough to form a leak - proof seal and also in preventing the condom from slipping off the penis . fig4 shows a specially modified brief or undergarment 32 . a cut away portion 30 of brief 32 exposes condom 16 as worn by a user . during use , condom 16 will be expanded by urine 37 . brief 32 has a pouch 33 to house and support the expanded condom . brief 32 also has an opening 40 above pouch 33 . in use , to drain the catheter of urine , the user need only lift the catheter out of the pouch through opening 40 and withdraw valve plug 13 , while directing the released urine into a urinal or toilet . fig5 details undergarment brief 32 . it was made by modifying close - fitting commercial briefs , such as those sold under the trademark kangaroo . its pouch 33 has been formed by sewing in a gusset 34 ( fig6 ) which is made of similar material to the rest of the brief . fig5 shows how gusset 34 has been sewn into the brief along double broken line 35 after seam 36 has been partly undone . gusset 34 thereby enlarges the area of the brief so as to form pouch 33 and make it large enough to accommodate enlarged condom 16 ( fig4 ) even when expanded by as much as a pint of urine . however , as the user will become aware of the growing bulk of the condom and pouch , he will ordinarily will take the opportunity to empty it of urine before it becomes as heavily filled as is illustrated . the present invention has been made from large - sized commercial condoms , which have proven perfectly satisfactory over 18 months of daily testing . during this time the user has engaged in heavy , full - time physical labor , traveled extensively by a 4 - wheel drive vehicle through rough country , and also enjoyed dancing , swimming , and sports while wearing such condom catheters exclusively and continuously . nevertheless , it is preferred that production condoms be made of slightly thicker material and be made about 20 cm ( 8 in ) long . also , the distal end of condom 44 should be made even thicker -- 1 mm ( 1 / 32 in ) as illustrated at 42 in fig7 . production units can be made of rubber , latex , or any suitable material . additionally , it is preferred that a valve 43 ( fig7 and 8 ) and valve housing 41 of the plug type be integrally made with thickened end 42 of condom 44 . valve housing 41 is connected to plug 43 by a strap 45 . condom 44 is 4 . 5 mm ( 13 / 4 in ) in diameter and has a reduced diameter open end 46 of 3 . 5 mm ( 13 / 8 in ) diameter for a distance of about 4 to 5 cm ( 11 / 2 to 2 in ). when draining accumulated urine from condom 44 , plug 43 is removed with one hand while holding valve housing 41 with the other . fig9 and 10 shows an alternative valve , in which a ball obturator 47 is pressed against a seat 49 by a spring 50 . the user can operate this valve to release the urine by simply applying pressure with his forefinger and thumb in the direction of arrows e and f . this will cause obturator 47 to move away from seat 49 while at the same time elongating seat 49 , as shown clearly in the cross - sectional view ( fig1 ). this distortion of a round seat to an oval seat allows fluid to bypass obturator 47 . when finger and thumb pressure is released , the seat will return to round and spring 50 will return obturator 47 to its seat 49 , thus re - effecting a water - tight seal . one advantage of this valve is that it takes only one hand to operate the valve and drain the accumulated urine and replace the catheter into the pouch of the undergarment . this is a perfectly natural action by any person using a urinal and would not ordinarily be noticed by another person . in operation , the user unrolls or slips the condom over his penis into position as illustrated in fig1 . ordinarily , this does not present a problem . should a lubricant be required , water can be used . however , moisture tends to allow the condom to slip down the penis . this can be prevented by first applying a very thin film of denture adhesive cream around the upper part of the shaft of the penis before completing the unrolling of the condom . unlike the adhesives used generally in condom urinary devices , dental adhesive cream prevents slipping , without adhering like glue to the skin and without causing discomfort . it also washes off easily with water . once the condom is in place , the band is applied . the user places the loop end of the band just below the rim of the condom . he holds that end in place while simultaneously pulling the band snugly around the circumference of the penis . then he presses the hook end over the loop end , so that the hooks and loops mesh . the band should be tight enough to hold the condom firmly in place without exerting an uncomfortably degree of pressure on the penis . the user &# 39 ; s briefs are then drawn on the condom is guided into the enlarged pouch of the briefs . as urine accummulates , the condom will expand . the pouch will hold the condom and its contents comfortably and securely until it is convenient for the user to empty it . at that time , the user will ease the urine - filled catheter out through the opening in the pouch , open the valve , and aim the stream of urine into a urinal or toilet . when the urine has drained , he will close the valve and slip the condom back into the pouch . at least once a day , the user should remove the condom device , wash it in warm , soapy water , then rinse and dry it thoroughly before putting it back on . after two or three such washings , the condom should be discarded and replaced , as it will tend to weaken . ideally , for those who can afford it , a fresh condom device will be used each day . thus , the reader will see that the present invention has many advantages over prior - art male incontence device , i . e . the user enjoys normal and natural freedom , normal social activities , such as working , swimming , aerobics , driving , running , skiing , dancing , or riding horses or motorcycles . he enjoys freedom from feeling the weight of accumulated urine on his leg , from tacky adhesives , from the pain of excessive pressures , and from the dragging down of leg straps . he can dress in everyday street clothing , and his incontinence is completely inconspicious to all , even when standing side by side with other men at a public urinal . furthermore , he can drain the condom just as fast or faster than others can empty their bladders . not only is the condom easy to fit and secure , but it is also very convenient , simple to pack in quantity , takes up little room , is not bulky or heavy , nor is it costly . it is also not malordorous . used condoms can be disposed of like toilet paper , so that no bulky parcels in plastic bags and wrappers are left for disposal . the user can even enjoy long periods of driving with no urgency to get to a toilet when none is available . although most men will empty the condom when it contains no more than about 1 / 4 liter , the condom under test can hold at least a gallon . although the increase in bulk will alert the user to empty it in a timely manner , there is no sensation of weight . finally , the ease of use makes it highly advantageous for the elderly or partially disabled , in that it is easy to use , does not require rolling up one &# 39 ; s pants leg , and so spares them much embarrassment . while the above description contains many specificities , the reader should not construe these as limitations on the scope of the invention , but merely as exemplifications of preferred embodiments thereof . those skilled in the art will envision that many other possible variations are within its scope . for example , other forms of attaching the condom , such as with a tie band , an elastic band , or adhesive could be used . the attachment means should alone be sufficient to retain the condom when it contains about 100 grams of urine . the condom can be relatively short , covering just the distal end of the penis , or it can be made of relatively thicker , more expandable rubber in its proximal and middle portions , so that only its distal end can expand . the distal end portion should be able to expand enough to hold at least 100 grams of urine . it would also be possible to use an ordinary commercial condom , securing it by any of the above means , and simply removing and replacing it each time it became filled . also , the condom could be made longer , shorter , or bigger , or be fitted with any suitable valve , such as a rotary thumb - screw valve , a pressure screw - type valve , or a clamp pressure - type valve . also , the user could wear a regular , unmodified brief undergarment and a suitable athletic supporter or other dedicated pouch , separate from the user &# 39 ; s ungarment , and supported by its own attaching waist band in place of the modified brief . accordingly , the reader is requested to determine the scope of the invention by the appended claims and their legal equivalents , and not by the examples which have been given .

US-37910589-A

the present invention discloses novel stable oral pharmaceutical compositions comprising the active ingredient clopidogrel bisulfate and hydrophilic polymers along with pharmaceutically acceptable excipients . particularly , the said clopidogrel bisulfate is crystalline form 1 and the composition additionally comprises of one or more chelating agents and antioxidants . further the invention relates to a novel process for preparation of stable pharmaceutical compositions wherein the clopidogrel bisulfate form i is coated with a hydrophilic polymer thereby providing an increased physical and chemical stability to the composition .

the present invention describes a novel stable pharmaceutical composition comprising clopidogrel bisulfate form i and hydrophilic polymers along with pharmaceutically acceptable excipients wherein the clopidogrel bisulfate form i is coated with a hydrophilic polymer which provides a highly stable composition with improved dissolution . said compositions further comprises one or more antioxidants and chelating agents . the invention further describes a process for the preparation of the said compositions . clopidogrel bisulfate form i is unstable in the presence of moisture and elevated temperatures and gets converted spontaneously into form ii . this poses a major challenge in the development of stable pharmaceutical compositions using clopidogrel bisulfate form i . further , form i bulk solid is less compact and much more electrostatic than form ii and hence cannot be readily subjected to any treatment under the usual conditions of pharmaceutical technology . moreover , form i is practically insoluble in water and significant bioavailability can be a problem . despite the above mentioned drawbacks , the inventors of the present invention have successfully developed pharmaceutical compositions of clopidogrel bisulfate form 1 which provides both stability and improved solubility . according to one embodiment , the present invention provides novel stable oral pharmaceutical compositions comprising the active ingredient clopidogrel bisulfate and hydrophilic polymers along with pharmaceutically acceptable excipients ; wherein the composition additionally comprises of one or more chelating agents and antioxidants . according to another embodiment , the present invention provides novel stable pharmaceutical composition comprising clopidogrel bisulfate form i and hydrophilic polymers along with pharmaceutically acceptable excipients wherein the clopidogrel bisulfate form i is coated with a hydrophilic polymer . the resulting coated particles , storage granules or pellets exhibits improved stability at accelerated storage conditions . in the practice of the present invention , the active ingredient clopidogrel bisulfate form i is used in the range of about 20 . 0 % to about 70 . 0 % by weight of the total composition . for example , the composition comprises clopidogrel bisulfate form i in the range of about 30 . 0 % to about 50 . 0 % by weight of the total composition . clopidogrel bisulfate compositions of the present invention may be provided in dose strength of about 75 mg to about 300 mg and preferably in dose strength of 75 mg . according to the present invention , the hydrophilic polymers are selected from cellulose derivative polymers . cellulose derivative polymers that may be used are selected from a group consisting of one or more of hydroxypropyl methyl cellulose , hydroxypropyl cellulose and hydroxyethyl cellulose or mixtures thereof . polymers having viscosity in the range of 3 to 100 cps are used . in one embodiment , the polymer is hydroxy propyl methyl cellulose with a viscosity in the range of 3 to 50 cps . according to the invention , the hydrophilic polymer is present in the range of about 2 . 0 % to about 50 % by weight and preferably in the range of about 5 . 0 % to 25 . 0 % by weight of the total composition . hydrophilic polymers improves the solubility of the resultant formulation by reducing the contact angle and thus improves the dissolution of the formulation . additionally , the pharmaceutical compositions of the present invention comprises of one or more chelating agents and antioxidants . the presence of antioxidants and chelating agents helps to minimize the impurity formation caused by degradation of clopidogrel bisulfate and thus improves the stability of the formulation . in the practice of the present invention , water soluble and oil soluble antioxidants can be used . water soluble antioxidants used as per the present invention are selected from a group consisting of sodium salts of bisulphite , sulphite , metabisulphite , thiosulphate , formaldehyde sulphoxylate , l and d ascorbic acid , cysteine , acetylcysteine , thioglycerol , thioglycollic acid , thiolactic acid , thiourea , dithithreitol , glutathione , or mixtures thereof . oil soluble antioxidants are selected from a group consisting of propyl gallate , butylated hydroxy anisole , butylated hydroxy toluene , ascorbyl palmitate , nordihydroguaiaretic acid and alpha - tocopherol or mixtures thereof . the amount of antioxidant used is in the range of about 0 . 01 % to about 1 . 00 % by weight . the chelating or sequestering agents are selected from a group consisting of edetic acids and its salts such as sodium salt of ethylene diamine tetra acetic acid , beta - hydroxyethylenediamine triacetic acid , diethylene triaminepentaacetic acid and nitrilotriacetate or mixtures thereof . the amount of chelating agent used is in the range of about 0 . 01 % to about 1 . 00 % by weight . preferred chelating agent is sodium salt of ethylene diamine tetra acetic acid . compositions of the present invention may contain one or more pharmaceutically acceptable excipients selected from diluents , binders , lubricants , glidants , coating agents and the like . pharmaceutically acceptable carriers or diluents that are used for tabletting are selected from a group consisting of lactose monohydrate , lactose anhydrous , microcrystalline cellulose , mannitol and sugars or a mixture thereof . diluents that are used in the formulation are anhydrous with below 3 % moisture content which minimizes the chances of degradation . the pharmaceutical compositions of the present invention posses moisture content below 3 %. the amount of diluents used is in the range of about 20 . 0 % to about 90 . 0 % by weight . microcrystalline cellulose can be used as a diluent as it provides good compressibility ; for example , an anhydrous grade of microcrystalline cellulose can be used . lubricants that are used are selected from a group consisting of hydrogenated vegetable oil and siliconised talc , poloxomer 407 or a mixture thereof . siliconised talc is mixture of simethicone ( 3 . 0 % to 10 . 0 %) adsorbed on 90 . 0 % of talc . the amount of lubricants used is in the range of about 1 . 0 % to about 10 . 0 % by weight . disintegrants that may be used include , but are not limited to crospovidone , croscarmellose sodium , sodium starch glycolate , sodium alginate and the like . the polymer coated granules are further compressed with other pharmaceutically acceptable excipients and then film coated with a suitable coating agent . the amount of coating material used may be in the range from about 2 . 0 % to about 5 . 0 %. coating may be carried out using coating agents such as opadry . opadry contains hydroxypropyl methyl cellulose , plasticizers selected from triacetin , triethyl citrate , polyethylene glycol , opacifiers such as titanium dioxide . in one embodiment , the opadry is opadry pink which contains hydroxypropyl methyl cellulose , titanium dioxide , triacetin , iron oxide red , fd & amp ; c yellow / sunset yellow aluminum lake and iron oxide yellow . solvents that may be used for coating include isopropyl alcohol and methylene dichloride . pharmaceutical compositions of the present invention are stable even at accelerated conditions of stability . according to another embodiment , the invention provides a process for preparing clopidogrel bisulfate compositions , the said process comprising the steps of : ( a ) mixing clopidogrel bisulfate form i with one or more chelating agents and antioxidants and pharmaceutically acceptable excipients ; ( b ) preparing a coating solution of hydrophilic polymer by dissolving the polymer in a mixture of isopropyl alcohol and methylene dichloride ; ( c ) coating or granulating the above mixture in step ( a ) with the coating solution of step ( b ) to form wet mass ; ( d ) drying the wet mass and further sizing the dried mass to form granules ; ( e ) blending and lubricating the sized granules to form mixture ; ( f ) compressing the lubricated mixture ; and ( g ) further coating the compressed tablets . compositions may be formulated by dry granulation , wet granulation or even direct compression . the pharmaceutical composition of the present invention can be formulated into a tablet . in the practice of the present invention , the coating or granulation of clopidogrel bisulfate may be carried out in equipments such as a fluid bed processor . the use of a fluid bed processor is advantageous as both granulations and drying can be performed in the same equipment . sifting of the dried granules may be done using any sifter such as a vibro sifter . compression is done using any conventional compression machine like rotary compression machine . tablets may be compressed using suitable punches and dies to get tablets of required shape and size . the coating can be performed according to any of the conventional methods of coating using suitable coating agents and purified water or organic solvents . the process of preparation as described herein is advantageous as it is industrially feasible and further the process of preparation results in decreased tendency of the material sticking to the surface of tooling during compression resulting in ease of manufacture . pharmaceutical compositions of the present invention are useful as a medicine for prophylaxis and treatment of thrombotic events such as coronary artery disease , peripheral vascular disease and cerebrovascular disease as it acts as a platelet aggregation inhibitor . the present invention further provides the use of the pharmaceutical compositions in the prophylaxis and treatment of thrombotic events such as coronary artery disease , peripheral vascular disease and cerebrovascular disease by acting as a platelet aggregation inhibitor . according to one embodiment , the present invention provides a method for treating a patient suffering from thrombotic events such as coronary artery disease , peripheral vascular disease or cerebrovascular disease comprising administering a therapeutically effective amount of clopidogrel bisulfate composition prepared according to the present invention . as used herein , the term “ therapeutically effective amount ” refers to an amount sufficient to cause an improvement in a clinically significant condition in the patient or even prevent a disease , disorder or condition in a patient . as used herein , the term “ excipients ” refers to a pharmaceutically acceptable ingredient that is commonly used in the pharmaceutical technology for preparing , for example , granules or solid oral dosage formulations . as used herein the term “ tablet ” is intended to encompass compressed pharmaceutical dosage forms of all shape and size , whether coated or uncoated . the following examples are offered by way of illustration and not by way of limitation . the disclosures of all citations in the specification are expressly incorporated herein by reference . clopidogrel bisulfate ( form i ) ( 97 . 875 g ), sodium metabisulphite ( 1 . 000 g ) and disodium edetate ( 2 . 000 g ) were mixed in a suitable equipment . this mix was granulated or coated with a coating solution prepared by dissolving hydroxypropyl methyl cellulose ( 10 . 000 g ) in a mixture of isopropyl alcohol and methylene dichloride . the wet mass was then dried and sized . sized granules were then mixed with microcrystalline cellulose ( 106 . 625 g ) and crospovidone ( 15 . 000 g ). the blend was further lubricated with siliconised talc ( 10 . 000 g ) and hydrogenated vegetable oil ( 7 . 500 g ). the said blend was compressed into tablets on rotary tablet press and the compressed tablets were coated with opadry dispersion in water , hydro - alcoholic or organic solvents . clopidogrel bisulfate ( 97 . 875 g ), disodium edta ( 4 . 000 g ) and sodium metabisulfite ( 0 . 200 g ) were mixed in a suitable equipment . hydroxypropyl methyl cellulose ( 5 . 000 g ) was dissolved in a mixture of isopropyl alcohol and methylene dichloride and was used for coating / granulation of the above dry mix . the wet mass was dried in fluid bed drier and sized to get the granules . sized granules were mixed with microcrystalline cellulose ( 117 . 925 g ), sodium starch glycolate ( 15 . 000 g ) and lubricated using siliconised talc ( 10 . 000 g ) as lubricant . the lubricated blend was compressed on tablet press to get the tablets . the tablets were coated using non aqueous dispersion of opadry pink . clopidogrel bisulfate ( 97 . 875 g ), microcrystalline cellulose ( 176 . 825 g ), crospovidone ( 10 . 000 g ) were mixed in a suitable equipment . propyl gallate ( 0 . 100 g ), butylated hydroxyl anisole ( 0 . 200 g ) and hydroxypropyl cellulose ( 5 . 000 g ) were mixed in a mixture of isopropyl alcohol and methylene dichloride and was used for granulation of above dry mix . the wet mass was dried in fluid bed drier and sized to get the granules . sized granules were lubricated using poloxamer 407 ( 10 . 000 g ) as lubricant . the lubricated blend were compressed on tablet press to get the tablets . the tablets were coated using aqueous dispersion of opadry pink . clopidogrel bisulfate ( 97 . 875 g ), mannitol ( 181 . 825 g ) and crospovidone ( 10 . 000 g ) were mixed in suitable equipment . sodium metabisulfite ( 0 . 300 g ) and hydroxypropyl cellulose ( 5 . 000 g ) were mixed in a mixture of isopropyl alcohol and methylene dichloride and was used for granulation of above dry mix . the wet mass was dried in fluid bed drier and sized to get the granules . sized granules were lubricated using hydrogenated vegetable oil ( 5 . 000 g ) as lubricant . the lubricated blend was compressed on tablet press to get the tablets . the tablets were coated using aqueous dispersion of opadry pink . the tablets prepared according to the example no . 1 were analyzed for the impurities and the results obtained were compared with the plavix tablets and is shown in table 1 . dissolution was carried out in ph 2 . 0 acid buffer , 1000 ml and by using usp type ii method ( paddle ) at 50 rpm . the tablets prepared according to the example no . 1 were subjected to accelerated stability testing at 40 ° c ./ 75 % relative humidity and the impurities in the respective tablets were analyzed and the results obtained are as shown in table 2 . while the present invention is described above in connection with preferred or illustrative embodiments , these embodiments are not intended to be exhaustive or limiting of the invention . rather , the invention is intended to cover all alternatives , modifications and equivalents included within its spirit and scope , as defined by the appended claims .

US-57581309-A

apparatus for handling and cleaning contact lenses comprising a pair of tweezer arms connected at one end and biased apart at the other end , the connected end carrying a contact lens support pad . the free ends of the biased arms may advantageously be provided with removable sleeves for efficient grasping and handling of soft contact lenses .

referring now to fig1 which shows the preferred embodiment of our invention , the invented apparatus 10 is a unitized device having a pair of downwardly extending arms 12 connected at their upper ends , the free ends 14 preferably being tapered to a point or nearly so . fixed to and integral with the upper end of the apparatus 10 is a convex cleaning head or convex contact lens support pad 18 . advantageously , the convex surface of the contact lens support pad is a spherical segment , or a partially spherical segment . between the lens support pad 18 and the biased arms 12 is a connector 20 , which provides a finger grip for the user . the connector 20 is preferably flat , tapering toward a tapered lens support pad support 22 , which support 22 has a rounded , or circular cross - section . a tubular sleeve 28 may be affixed to each tip or free end 14 of arms 12 . the arms are preferably wider than they are thick , and taper from the widest point of their upper extremity to the narrowest point of their lower extremity . the arms also preferably bend or curve inwardly for from one - tenth to one - third of their length at their lower portion as shown in fig1 . the sleeves 28 preferably are affixed only to this lowermost portion of the arms . the tips of the arms may protrude through the sleeves , to such extent as desired by the user . the material from which the invented apparatus is made must be properly selected to minimize the possibility of damaging a contact lens . the material must have good resiliency and must return to its original configuration upon release of force thereon . preferred resilient plastic materials are : terpolymers , thermoplastics , elastomers , or any combination of these . especially well suited materials are polypropylene elastomers , polyisoprene elastomers , and silicon elastomers . the tweezer portion consists of a pair of arms connected at one end and biased into an open position at the other end to create a void between them . the arms may be straight or curved , but preferably have a short curved section near the free or open ends . the end of the apparatus opposite the free ends of the arms carries a convex lens - engaging surface , or anvil , shaped to mate with the concave surface of a contact lens . the convex surface supports the lens and is used to manipulate it against the palm of the user while the outer or front surface of the lens is being cleaned . the present invention is intended for use by placing the contact lens cleaner in the wearer &# 39 ; s hand , placing the contact lens on the convex surface of the invented apparatus and rubbing the lens into the palm of the user to effect proper cleaning . resilient sleeves , which can be made of a rubberized soft plastic or other resilient material , such as rubber - coated plastic , vinyl or nylon , elastomers , thermoplastics , or terpolymers , are adapted for placement over the tapered ends of the biased arms to provide a positive gripping surface . in operation , the cleansing solution is placed in the palm of the user &# 39 ; s hand , a soft contact lens is picked up by grasping with the resilient sleeves at the ends of the arms , placing the lens in the solution in the wearer &# 39 ; s palm and engaging the lens with the convex surface at the end of the apparatus opposite the resilient sleeves . from the foregoing , it is readily apparent that we have provided an apparatus for grasping and cleaning soft contact lenses , in particular , a small cleaning and grasping apparatus for contact lenses which is of sufficiently small size that a user can conveniently carry it with him at all times ; and which provides a positive grasp of the lens . while in accordance with the patent statutes , the best mode or preferred embodiment has been shown and described , it is readily apparent that modifications may be made without departing from the spirit of the invention . therefore , no limitations are to be inferred except as specifically set forth in the appended claims .

US-1661287-A

embodiments disclosed herein provide a method of implanting an intervertebral disk prosthesis that can be assembled and disassembled in a minimally invasive fashion . the prosthesis comprises a first fixing element having an anchoring first face and a co - operation second face ; a second fixing element having an anchoring first face and a co - operation second face ; a first prosthesis element having an active first face and a co - operation second face , the co - operation faces of the first fixing element and the first prosthesis element serving to fasten the two elements together ; a second prosthesis element having an active first face and a co - operation second face , the co - operation faces of the second fixing element and the second prosthesis element serving to fasten the two elements together ; and each of the active faces of the prosthesis elements defining at least a portion of a spherical cap that is respectively concave or convex .

with reference initially to fig1 , there follows a description of a first aspect of the intervertebral disk prosthesis . in this figure , there is shown in simplified manner a first vertebra v 1 and a second vertebra v 2 between which the intervertebral disk prosthesis 10 is to be put into place . the prosthesis 10 is constituted by a first prosthesis element 12 and a second prosthesis element 14 , and by a first fixing element 16 and a second fixing element 18 . the prosthesis element 12 has a co - operation face 12 a and an active face 12 b also referred to as a rubbing face or a contact face . this face 12 b is in the form of a convex spherical cap . the prosthesis element 14 also has an active face or contact face 14 b which is in the shape of a concave spherical cap and which is naturally designed to co - operate with the active surface 12 b of the prosthesis element 12 . as explained in greater detail below , the radii of curvature of the spherical caps 12 b and 14 b are not identical . the prosthesis element 14 also has a co - operation face 14 a . the fixing element 16 presents a co - operation face 16 a and an anchoring face 16 b . the anchoring face 16 b is provided with any suitable anchoring member 22 for fixing the fixing element 12 to the plate of the vertebra v 1 . the co - operation face 16 a of the fixing element 16 is provided with fasteners that co - operate with complementary fasteners of the face 12 a of the prosthesis element 12 to fasten the prosthesis element to the fixing element , at least in a horizontal plane . similarly , the fixing element 18 has a co - operation face 18 a and an anchoring face 18 b provided with an anchoring member 24 . it will be understood that in this first aspect of the invention , because the prosthesis elements proper and the fixing elements are distinct parts , it is easier to put the intervertebral disk prosthesis into place between the vertebrae while nevertheless ensuring that it is properly secured to the vertebrae . it will also be understood that since each prosthesis element has an active face in the form of a spherical cap , the ball - and - socket type mobility between the two vertebrae is indeed recreated . reference is now made to fig2 a and 2b for describing the intervertebral disk prosthesis in its second aspect . in these figures , there can be seen the vertebrae v 1 and v 2 between which the prosthesis is to be put into place . the prosthesis is constituted by a first prosthesis element 12 ′ and by a second prosthesis element 14 ′. each prosthesis element 12 ′ and 14 ′ is constituted by two distinct parts referenced 26 and 28 for the prosthesis element 12 ′ and 30 and 32 for the prosthesis element 14 ′. each part forming the prosthesis elements has both a fixing face referenced a , and an active face referenced b . the fixing faces a of the parts 26 to 32 are provided with fasteners for engaging the vertebrae v 1 and v 2 , these fasteners possibly being constituted by separate parts , as explained below and as shown in fig1 . the active faces a of the parts constituting the prosthesis elements are defined in such a manner that they form portions of spherical caps that are respectively concave and convex . when the parts 26 and 28 forming the prosthesis element 12 ′ are put into place on the vertebra v 1 , their active faces a are disposed on a concave spherical cap c . similarly , the active faces a of the parts 30 and 32 forming the prosthesis element 14 ′ are disposed on a spherical cap c ′. as mentioned above , these spherical caps c and c ′ may have different radii of curvature . it will be understood that because the two parts constituting the same prosthesis element together constitute a friction or contact surface that is in the form of a spherical cap , the same ball - and - socket mobility is obtained as in fig1 . in addition , because each prosthesis element is constituted by two distinct parts , it will be understood that it is easier for the surgeon to put the prosthesis element into place between the vertebrae . with reference to fig3 , 4 , and 5 , a first embodiment of the intervertebral disk prosthesis is described . in fig3 a and 3b , there can be seen a fixing element referenced 40 . the fixing element 40 is constituted by a plate 42 having an anchoring face 42 b provided with two transverse ribs 44 and 46 which constitute parts for anchoring in a vertebra . the co - operation face 42 a of the plate 42 is fitted with two locking members for locking to the prosthesis element . each of the locking members 48 and 50 is constituted by a strip 54 extending parallel to the ribs 44 . the right section of each strip 54 is generally t - shaped , the strip comprising two flanges 56 and 58 in its portion that is furthest from the plate 42 . in addition , in order to enable the strips to deform elastically to a certain extent , each of them has a longitudinal slot 60 . in fig4 a , 4 b , and 4 c , there can be seen a prosthesis element 62 which is constituted by two separate parts 64 and 66 . the active faces b of the parts 64 and 66 constitute portions of a spherical cap . thus , as explained above , when the parts 64 and 66 are fixed on a vertebra , the spherical cap portions b lie on the same spherical surface . the co - operation face a of each part 64 and 66 includes an anchoring groove 68 over a fraction of its length , the right section of the groove being generally t - shaped and being dimensioned to be capable of receiving the anchoring members 48 and 50 . the grooves 68 extend over a fraction only of the length of the parts 64 and 66 corresponding to the length of the anchor parts 48 and 50 . in addition , and preferably , the co - operation faces a of the parts 64 and 66 include respective setbacks 70 and 72 such that when these parts are fixed on a vertebra , the plate 42 of the fixing element 40 penetrates fully into said setback . as can be seen in fig4 c , the grooves 68 open out via their ends 68 a into end faces of the parts 64 and 66 so as to enable the locking members 48 and 50 to be inserted into the fixing element 40 . naturally , the prosthesis as a whole has a second fixing part 40 ′ identical to the part 40 and a second prosthesis element 62 ′ which differs from the prosthesis element 62 solely by the fact that its active surface b defines a spherical cap that is concave . fig4 shows the two prosthesis elements constituted by the parts 64 and 66 and two other analogous parts mounted on the fixing elements 40 and 40 ′. it can be seen that the fixing elements 40 and 40 ′ in this embodiment serve not only the fix each prosthesis element to the corresponding vertebra , but also to position the two parts constituting the same prosthesis element in such a manner that their active surface does indeed constitute a spherical cap . fig1 shows a variant of the first embodiment of the intervertebral disk prosthesis suitable for correcting a tendency to scoliosis . in this variant , when the prosthesis elements 64 ′ and 66 ′, and the fixing elements 40 and 40 ′ are assembled together , the plates 42 of the fixing elements form between them an angle a . in order to obtain this result , the co - operation faces a of the parts 64 and 66 forming the prosthesis element 62 are disposed in a plane pp ′, p 1 p 1 ′ which is not orthogonal to the common axis xx ′ of the spherical caps c and c ′ which are constituted by the active faces of the prosthesis elements . with reference now to fig6 , 7 , and 8 , there follows a description of a second embodiment of the intervertebral disk prosthesis . in this second embodiment , each prosthesis element is constituted by a single part and each prosthesis element is fixed to the corresponding vertebra by a separate fixing element . fig6 a and 6b show an embodiment of the fixing element 80 . the fixing element 80 is constituted by a preferably rectangular plate 82 that is relatively massive . the anchoring face 82 b of the plate 82 is provided with members for anchoring in the vertebra constituted , for example , by two ribs 84 and 86 identical to those fitted to the fixing element 40 shown in fig3 . as explained below , other anchoring elements could be used . as shown in fig6 b , the co - operation face 82 a is provided with a locking groove 88 . this locking groove has an insertion first portion 90 opening out into a long side of the plate 82 and a locking portion 92 which extends parallel to the long direction of the plate 82 . as shown in fig6 a , the groove 88 has a right section that is t - shaped . naturally , the complete prosthesis has a second fixing element 80 ′. fig7 a , 7 b , and 7 c show the prosthesis elements of the prosthesis constituting the second embodiment . the prosthesis element 100 is constituted by a massive part whose co - operation face a presents a shoulder 102 defining a setback portion 104 with the length of the setback portion 104 corresponding to the width of the plate 82 of the fixing element 80 . a locking member 106 projects from the setback portion 104 . the shoulder 102 corresponds to the thickness of the plate 82 . this locking member which is preferably circularly symmetrical about the axis xx ′ is constituted by a head 108 and a body 110 . the diametral section of the locking member 108 is of a shape which corresponds to the shape of the t - groove 88 formed in the plate 82 of the fixing element 80 . the active or contact face b of the prosthesis element 100 comprises a substantially plane portion 112 and a portion 114 in the form of a concave spherical cap . the second prosthesis element 120 is identical to the prosthesis element 100 with the exception of its active face b which comprises a substantially plane portion 122 and a portion in the form of a convex spherical cap 124 suitable for co - operating with the concave spherical cap 114 of the prosthesis element 100 . in fig8 , there can be seen the prosthesis elements 100 and 120 mounted on the two fixing elements 80 and 80 ′. as can be seen more clearly in this figure , in the assembled position , the prosthesis elements 100 and 120 are orthogonal to the fixing elements 80 and 80 ′. fig9 shows a variant embodiment of the anchoring element provided on the anchoring faces of the fixing elements 80 or 40 . in this embodiment , the anchoring elements given general reference 130 is constituted by two projecting triangular parts 132 and 134 each having one of its short sides connected to the short side of the other triangle to form an edge 136 , the angle between the triangles 132 and 137 being less than 180 . degree . this method of anchoring serves to prevent any displacement in the planes of the vertebral plates . in fig1 , there can be seen another variant embodiment of the anchoring element which is in this particular case consists in four generally cylindrical studs 140 terminating in conical portions . this figure also shows that the locking members 48 and 50 of the fixing element 40 are preferably spaced further apart than the locking members 48 ′ and 50 ′ of the fixing element 40 ′. this makes it possible for the two fixing elements 40 and 40 ′ to be placed in the configuration shown in the figure . the total thickness of the assembly constituted by the two fixing elements is thus reduced , thereby enabling them to be inserted simultaneously between the two vertebrae . the description above relates to two embodiments of the intervertebral disk prosthesis of the invention , together with variants thereof . as mentioned above , one of the advantages of these prostheses is that they can be put into place using a posterior technique . with reference initially to fig1 a and 12b , there follows a description of the method of putting the prosthesis shown in fig3 , 4 , and 5 into place by the posterior technique . as in the conventional posterior technique for putting intervertebral cages into place , the surgeon begins by providing posterior access to the vertebrae between which the prosthesis is to be placed : the surgeon must also move the two vertebrae apart and remove the natural disk . thereafter , the surgeon usually performs certain resections of portions of the two vertebrae onto which the prosthesis is to be fixed . these resections relate essentially to the epiphysis and to the facets of the vertebrae . functionally , the major resections are those enabling the fixing elements to be anchored to the vertebrae where that is necessary . these resections performed in the vertebral plate are of a shape that is adapted to the anchoring elements with which the fixing elements are fitted . for the rib - shaped fixing elements ( fig3 and 6 ), these resections consist in slots f 1 and f 2 formed in the posterior portions of the vertebral plates ( fig1 a ). for anchoring elements in the form of pegs ( fig1 ), the resections are in the form of holes t 1 , t 2 , . . . pierced in the vertebral plate ( fig1 b ). in other circumstances there is no anchoring element proper . fig1 a to 13g show a vertebral disk prosthesis of the shape shown in fig3 to 5 being put into place . initially , the bottom fixing element 40 ′ is inserted between the vertebrae v 1 and v 2 via their posterior portions ( fig1 a ) from one side or the other of the dura mater . then the fixing element 40 ′ is pushed to go round the spinal cord ( dura mater ) ( fig1 b ) by pivoting and come into position in such a manner that the anchoring ribs are in register with the slots f 1 and f 2 ( fig1 c and 13d ), after which the anchoring ribs are pushed into the slots f 1 and f 2 ( fig1 e ). the same process is used for putting into place the upper fixing element 40 under the upper vertebra v 1 . as shown in fig1 , it is also possible to introduce two fixing elements simultaneously between the vertebrae and then to put them into place separately in the resections . still using the posterior technique , the parts 64 and 64 ′ constituting the right - hand portions of the prosthesis elements are put into place round the right - hand side of the dura mater , going round the spinal cord . the fastening grooves 68 are engaged on the ends of the fastening strips 48 of the fixing elements . this engagement is made possible by the ability of the strips 48 to deform . the prosthesis elements are pushed until the plates 42 of the fastening elements 40 , 40 ′ penetrate into the setbacks 72 of the prosthesis parts 64 ( fig1 g ). finally , the same operation is performed on the parts 66 of the prosthesis elements by engaging them via the left side of the dura mater . fig1 a shows fixing elements being inserted when they are implemented as shown in fig1 . fig1 b shows subsequent placement of the prosthesis elements . fig1 a to 15c show the main steps in putting the intervertebral disk prosthesis shown in fig8 into place . fig1 a shows the bottom fixing element 80 ′ being put into place by being engaged using the posterior technique round one side of the dura mater , after which this part is turned so as to put into position beyond the dura mater . this operation ends with anchoring ribs being inserted into the slots f 1 , f 2 . fig1 a also shows in “ symbolic ” manner the upper fixing element 80 put into place . fig1 b shows the initial stage of putting the prosthesis elements 100 and 120 into place . in this stage , the prosthesis elements are inserted between the vertebrae on one side of the spinal cord , moving in their long direction . the locking members 106 are presented to the inlets to the first portions 90 of the locking grooves 88 in the fixing elements until they come into abutment . thereafter ( fig1 c ), the surgeon pushes the prosthesis elements sideways so that the locking members 106 come into abutment at the ends of the second portions 92 of the locking grooves 88 . the prosthesis elements are locked to the fixing parts by co - operation between the shoulders 102 and the edges of the fixing elements . as explained above , an important advantage of the intervertebral disk prosthesis is that it can be put into place by the posterior technique . nevertheless , this prosthesis can naturally also be put into place by the anterior technique . fig1 a to 16c show the prosthesis shown in fig5 being put into place by the anterior technique , and fig1 a to 17b show the prosthesis shown in fig8 being put into place by the anterior technique . firstly , it should be observed that the slots f ′ 1 and f ′ 2 are adapted to anterior placement so they open out into the periphery of the vertebral plate ( fig1 a ). thereafter , the fixing elements 40 and 40 ′ are put into place between the vertebrae and inserted into the slots f ′ 1 and f ′ 2 . finally , the parts 26 , 28 , 30 , and 32 forming the prosthesis elements are put into place on the fixing elements 40 and 40 ′. fig1 a shows fixing elements 80 and 80 ′ being put into place by the anterior technique , and fig1 b shows the prosthesis elements 100 and 120 being put into place on the fixing elements .

US-57531909-A

a compact continuous positive airway pressure apparatus and method provide a flatter profile and more compact thickness , including a larger lateral dimension in order to be accommodated in conventional luggage designed to stow laptop computers having a smaller aspect ratio of thickness to length or thickness to width . air tubing may be coiled within a case or coiled as about a spool - like configuration in the base unit of the device .

referring to fig1 , in one embodiment of an apparatus and method in accordance with the invention , a system 10 or device 10 may be configured to provide a continuous positive airway pressure to a user . in the illustrated embodiment , a housing 12 may contain the basic elements required to drive the air to an elevated pressure . in typical usage , a fraction of a pound per square inch or a fraction of a kilogram per square centimeter will be provided by the system 10 , to the airway of a user . typically , a drive system 14 provides the prime mover of air . the drive system 14 may draw air from the environment , through a filter , or without a filter , and pressurize it sufficiently to maintain a positive pressure against which a user breathes during sleep . from the drive system 14 , a delivery system 16 provides passageways to carry the air to an interface for delivery into the nostrils or mouth of a user , or both . typically , a control system 18 may be designed to be as simple or sophisticated as desired for the appropriate therapy . at a rudimentary level the system may be turned off and on . in a more sophisticated embodiment , a selection of the pressure , the net air flow , the profile of the increase of pressure of the air flow , or the like may be controlled in order to provide for the comfort and therapy of a user . a power system 20 provides a power source to drive the drive system 14 . in certain embodiments , a pneumatic power system may be provided . a convenient power system may rely on either wall current or battery power instead . to provide completely self - contained power , a power system 20 may be as simple as a rechargeable battery built into the system 10 . alternatively , a power supply that connects to a wall outlet may service the system equally well . in yet another alternative embodiment , both may be provided in order that a system may be recharged when the wall current is available , but may still be used when wall current is not available . referring to fig1 , the system 10 may include a base 22 to which to mount the other components of the system 10 . a console 23 may be provided in order to accommodate controls , user interface , and other access to the system during operation . the console 24 or console layer 24 may be positioned opposite the base 22 , each effectively forming a flange of a spool . thus , the base 22 and console 24 may actually act as flanges of a spool to receive therebetween the delivery system 16 . in certain embodiments , whether for protection , or simply for purposes of convenience , securement , or closing a display of information or the like , a cover 26 may be provided to close the console layer 24 . in certain embodiments the drive system 14 may be protected by a grid 28 in order to prevent entry of fingers or other small objects into the drive system 14 . downstream from the drive system 14 an aperture 30 may be provided to discharge air from the drive system into the delivery system 16 . a fitting 31 may be provided about the aperture 30 in order to accommodate connection and disconnection of the delivery system 16 . in certain embodiments , storage space 32 may be provided for a mask 34 or interface 34 . the storage space 32 may be formed as a recess in the console 24 of the apparatus . in other embodiments the recess 32 may be dispensed with in order to simply store the mask elsewhere . soft masks may be folded up or otherwise placed in a small space . in certain embodiments , it is desired that the mask 34 be of a substantially stiffer quality , in order to assure a firm seal against the face . thus , a mask 34 may need storage space 32 within the apparatus 10 . a storage space 36 for a power supply 38 may be provided in the console 24 as well . in the illustrated embodiment , a simple dc power supply 38 may provide the conversion of wall power ( alternating current ) to be converted to direct current to drive the drive system 14 . a recess 40 or space 40 may be provided between the base 22 and console 24 in order to wrap a hose 42 or tube there around . the hose 42 may be formed in any suitable manner . a convoluted hose may actually provide a very flexible , light , and still comparatively compact system for delivering air from the apparatus 10 to a user . in particular , the hose 42 will connect to the fitting 31 of the aperture 30 to receive air driven by the fan 50 . the fan 50 may be protected by the grid 28 at the inlet where air is received . accordingly , the fan 50 may blow air to a higher pressure and discharge it through the aperture 30 into the hose 42 for delivery to a mask 34 and ultimately to a user . in certain embodiments , a cord 52 may deliver power from a power supply or wall current into a plug 54 . the plug 54 may fit into a jack 55 formed within the base 22 , console 24 , or other part of the housing 12 in order to access the drive system 14 and power it . in embodiments where an internal battery is powering the apparatus 10 , the cord 52 and plug 54 may simply operate to power the battery during recharging . in certain embodiments , various buttons 56 or switches 56 may be provided for the system 10 . in the illustrated embodiment , various buttons 56 a , 56 b , 56 c , 56 d are shown . for example , a button 56 a may be a switch to turn the drive system 14 on and off . other buttons 56 c , 56 d may control the increase and decrease of the speed of the fan 50 . other buttons 56 d may control other factors , including the display 60 . a display 60 may include instructions , may provide feedback information regarding pressure , fan speed , or the like , and may include interactive selections for controlling the apparatus 10 by the user . in general , information and instructions by way of warning and basic set up may also be included in a label 58 simply printed and adhered to a portion of the apparatus 10 . in the illustrated embodiment , deployment of the apparatus 10 may include unwrapping the delivery system 16 including the hose 42 with its fittings 44 , 46 from the apparatus 10 , such as from a spooled location between the console layer 24 and the base layer 22 acting as flanges of a spool . accordingly , the fitting 44 may be connected to the output fitting 31 , and the fitting 46 to the mask 34 . a mask 34 may be formed in any suitable manner , typically of a flexible material in contact with the skin in order to form a good seal , with straps or other secure mechanisms to secure it to the face of a user . the mask 34 may cover only the nostrils , the nostrils and the mouth , or only the mouth . accordingly , the drive system 14 , and the fan 50 in particular , provides pressurized air through the aperture 30 into the tubing 42 for delivery into the mask 34 at an increased pressure above ambient pressure . meanwhile , the power supply 38 may be removed from its storage location 36 and plugged into outlet power in order feed the cord 52 and the plug 54 connected to power the motor driving the fan 50 . upon waking , a user may stow the system 10 by removing the fitting 44 from the aperture 30 with its retaining fitting 31 and removing the mask 34 , optionally , from the mask fitting 46 . in some embodiments , a more compact system may have a foldable or very flexible mask 34 . the mask fitting 46 may also be formed integrally between the tubing 42 and the mask 34 making removal of the mask 34 from the tubing 42 unnecessary . likewise , the fitting 31 , 44 need not be readily separable , nor separable at all , nor distinct from one another . in either mode , the tubing 42 , whether or not removed from the fitting 31 or mask 34 may be spooled around the space 40 between the base 22 and console 24 to stow it . detents may be provided by way of bosses , tabs , or simply a closer proximity to one another of the edges of the base 22 and console 24 in order to retain the tubing 42 therebetween . after final stowage of the power supply 38 in its storage location 36 , the lid 26 or cover 26 may be closed on hinges 48 against the console 24 in order to close the system up for travel . referring to fig2 , a view of the apparatus 10 of fig1 is illustrated showing only the base 22 with selected components located below the console 24 . in the illustration , a spool portion 62 or mandrel 62 for receiving the tubing 42 may be located between the base 22 and the console 24 . within the periphery of this spool portion 62 , or mandrel 62 , the fan 50 may operate . in the illustrated embodiment , the fan 70 represents a generic fan 50 of fig1 . in the illustrated embodiment , the fan 70 is a squirrel - cage type fan and the motor 68 is embedded within the confines of the fan 70 . a shroud 64 surrounds the fan 70 to direct the air to an output duct 66 . the spinning of the fan 70 about the motor 68 ( by the motor 68 ) causes the air to move radially away from the fan 70 , while also moving the air circumferentially with respect to the outer circumference of the fan 70 . accordingly , the duct 66 is filled with pressurized air , while the region within the circumference of the fan 70 is decreasing in pressure as it draws air through the grid 28 and through the fan 70 . referring to fig3 , the apparatus 10 in the illustrated embodiment may fold up with the cover 26 against the console 24 , forming a compact package between the base 22 and the cover 26 . meanwhile , the hose 42 or tubing 42 is spooled around the mandrel 62 in order to fit within the overall envelope defined by the juxtaposed base 22 and cover 26 . referring to fig4 , an apparatus 10 may have a housing 12 formed of a base 22 and a cover 26 . the base 22 and cover 26 may be connected by a hinge 48 pivotable between a closed and an open position . in fig4 , the apparatus 10 is shown in an open position with the tubing 42 removed from stowage along with the power supply 38 for use . in the illustrated embodiment , the delivery system 16 is constituted by the tubing 42 with its associated fittings 44 , 46 and mask 34 , having a strap 35 for securement to the face of a user . meanwhile , the drive system 14 is enclosed within a shroud 64 and the fan 50 is behind the grid 28 provided for protection . the aperture 30 is connectable to the fitting 44 to direct pressurized air from the duct 66 provided as an outlet from the shroud 64 delivering pressurized air from the fan 50 into the tubing 42 . in the illustrated embodiment , the control buttons 56 may be provided on the case 12 or housing 12 in any suitable location . in the illustration , the control buttons 56 are positioned on the base 22 . likewise , the jack 55 for receiving the plug 54 from the power supply 38 and cord 52 is located on the front face of the base 22 . accordingly , the power can be converted from wall power to dc current by the power supply 38 and delivered through the plug 54 and jack 55 to the motor 50 inside the shroud 64 . controls 56 may be used for controlling on , off , pressure , power , speed , or the like . the display 60 may provide instructions for monitoring of the operation of the apparatus 10 . referring to fig5 , the apparatus 10 of fig4 may be placed in a stowed configuration by wrapping the tubing 42 about the drive system 14 containing the fan 50 and shroud 64 . the fitting 44 may be disconnected from the aperture 30 or remain in it . likewise , the fitting 46 may be removed from the mask 34 or remain connected . the mask 34 in the illustrated embodiment may be stowed within the base 22 just as the tubing 42 or hose 42 . thus , closure of the lid 26 or cover 26 against the base 12 provides an envelope that is approximately that of a laptop computer and encloses the accompanying supporting peripheral elements of the apparatus 10 in a compact and easily transportable unit . various types of sealing mechanisms such as bosses , knobs , ridges or other detents within the hinge 48 , or between the cover 26 and base 22 may be implemented in accordance with principles or devices known in the art . referring to fig6 , an apparatus 10 in accordance with the invention may include a fan 50 connected directly to a motor 68 , or connected indirectly as illustrated . in the illustrated embodiment of fig6 the motor 68 is connected to the fan 50 by a set of pulleys 74 , 76 and corresponding shafts 75 , 77 . a belt 72 connects the pulleys 74 , 76 in order to drive the fan shaft 77 from the motor shaft 75 . in the illustrated embodiment , the axial direction 80 represents the direction of intake , while the radial directions 82 represent the direction that air moves in response the spinning of the fan 50 . a shroud 64 around the fan 50 may restrict the flow of air and directly into a particular duct 66 as described hereinabove . in response to the rotation of the fan , the space in the center of the fan 50 is evacuated or rather contains air at reduced pressure , while the area around the circumference of the fan represents air being driven in a radial 82 and a circumferential 84 direction . the shrouding 64 prevents air from escaping the fan 50 , while the ducting 66 provides a location or plenum for the air to accumulate at elevated pressure in order to be driven out the aperture 30 to the tubing 42 . referring to fig7 , in an alternative embodiment , a motor 68 may be embedded within the fan 50 in order to reduce the overall size of the system 10 . however , if the fan 50 is formed to be of a comparatively thin profile , then the motor may need additional space . meanwhile , the vanes 78 tend to drive the air in a circumferential direction 84 , resulting in acceleration in a radial direction 82 . as the air escapes from the vanes 78 or blades 78 of the fan 50 , it may have both a circumferential 84 and a radial 82 component of velocity . accordingly , it may be ducted as described hereinabove . in typical embodiments , the fan 50 may be formed of vanes 78 projecting ( for example , at right angles ) from a disk 79 or base 79 . typically , the base 79 will include a hub for receiving a shaft 77 on the motor 68 . any suitable attachment mechanism including keys , set - screws , friction , splines , and the like may be used to secure the shaft 77 to the fan 50 . referring to fig8 , in one embodiment of an apparatus 10 in accordance with invention , the fan 50 may actually be configured with vanes that taper toward the center hub 86 , having their greatest height from the frame 79 or disk 79 near the outer periphery thereof . accordingly , the vane 78 may actually act as trapezoidal or triangular vanes that are very short axially with respect to the disk 79 near the hub 86 , and very tall near the outer periphery of the disk 79 . thus , the air flow in 88 will be drawn in an axial direction into the fan while the blades 78 or vanes 78 rotate , the air moves in a circumferential direction 84 . a response of the air is to flow outwardly in a radial direction 82 such as the flow illustrated as flow 90 b . ultimately , however , the shroud 64 and duct 66 will permit escape of the air only in a circumferential direction 84 illustrated as the airflow 90 a exiting the fan 50 . the squirrel cage fan of 57 , and the vane fan of fig8 both tend to be centripetal or centrifugal fans . that is , the pressure comes as a result of the spinning of the air , and its tendency to want to escape radially 82 from the circumferential motion 84 . that is , any motion in a circumferential direction 84 is actually an acceleration toward the center shaft 77 , and the air preferentially migrates radially 82 . referring to fig9 , another embodiment of the fan 50 may include a shaft 77 and hub 86 from which various vanes 78 extend outward . in the embodiment of fig9 , air is actually inducted from one side of the fan 50 in an axial direction 80 , and is discharged out the other side in the same axial direction 80 . of course , in the illustrated embodiment , the direction of rotation in the circumferential direction 84 determines which direction or sense the air flow will actually take in the axial direction 80 . one of the advantages of a squirrel cage fan 50 or a vane fan 50 is a comparatively thin profile on the order of from about one half inch to about an inch and a half , or perhaps up to two inches . on a substantially larger radius of from about one and half to about four inches , the fan may provide a comparatively large flow rate ( e . g . 0 . 1 to about 2 cfm ), large pressure increase ( e . g . 5 to 30 cm of water ), or the like , into a comparatively smaller duct , such as the duct 66 , and the tube 42 . one benefit of the fan 50 illustrated in fig9 is that a comparatively quite fan with a minimal direction change may be implemented . many pancake fans 50 may actually include a motor within the hub 86 in the fan 50 of fig9 , thus forming a comparatively compact , axial drive system 14 . referring to fig1 , an apparatus 10 may include a housing 12 having a base 22 , console 24 , and cover 26 . likewise , a drive system 16 may include a fan 50 under a grid 28 to drive airflow into a tube 42 . in the illustrated embodiments , the console portion 24 actually becomes the bottom of the housing 12 , when stowed . nevertheless , the control buttons 56 may be provided on a panel 92 associated with the console layer 24 of the apparatus 10 . likewise , some type of power line 52 with its associated plug 54 may provide power into the system by any of the mechanisms discussed above or known in the art . meanwhile , the mask 34 may be stowed with the tubing 42 and its associated fittings 44 , 46 within the space available in the base 22 . in the illustrated embodiment of fig1 - 12 , retainers 94 may provide flexible or rigid restraints in order to hold the tubing 42 in place during stowage . in one embodiment , the retainers 94 may be formed of a flexible plastic or stiff rubber such that they may be easily deflected in order to place the tubing behind them . the retainers 94 may be replaced by belts , straps , or the like , securing to the base 22 in certain embodiments . by either means , the tubing 42 may be wrapped for stowage within the base 26 . meanwhile , the grid 28 covering the fan 50 may cover a squirrel cage fan 50 , a vane fan 50 , an axial fan 50 , or any other suitable mechanism . in the illustrated embodiment , an optional bellows 96 is included . the bellows provides an expansion space between the base 22 and the lid 26 in order to provide a plenum or expanse of space or volume in which a volume of air under pressure can be collected . the value of a plenum is that pressures are moderated somewhat in response to the breathing of an individual , or changes in output . for example , whenever an individual is breathing against the pressure of air within the tubing 42 , pressure rises behind the fan 50 . this effect may be somewhat ameliorated by providing a plenum that tends to have sufficient volume to absorb the instantaneous fluctuations in pressure and volume of air . any suitable support including the bellows alone , or flexible joints , struts , or the like may be used to support the cover 26 with respect to the base 22 . in such an embodiment , the system may actually expand to a larger size than its stowed size in order to create a plenum within the bellows 96 and the lid 26 . referring to fig1 , the apparatus of fig1 and 11 is illustrated in a stowed configuration . for clarity , the hose 42 has been removed from the housing 12 in order to illustrate an embodiment of how the fitting 44 may fit onto the cover 26 in the aperture 30 . when the fitting 44 is removed from the aperture 30 , and its associated fitting 31 , a cap 101 fitted to the fitting 31 may be inserted to prevent damage , dirt , and the like . in the illustrated embodiment , the lid closes against the bellows 96 , but may close over the bellows , in order to close up against the console 24 , which forms the outer shell of the housing 12 . meanwhile , the base 22 is fit down into the console portion 24 . in general , the hose 42 may be connected in any suitable manner . in the illustrated embodiment , the mask 34 may be secured permanently or temporarily to the hose 42 . the fitting 44 , typically permanently attached to the hose 42 , may include both a securement 100 and a stop 102 . the purpose of the securement 100 is as a detent to engage the fitting 31 . the purpose of the stop 102 is to prevent the fitting 44 penetrating further into the aperture 30 . any suitable mechanism may be used including threads , quick release couplings , interfering “ o ” rings , or the like . in general , the space 98 for storage of the hose 42 may actually be used as a plenum in certain embodiments . that is , for example , the space 98 may be configured on the opposite side of the base 22 , between the base 22 and the cover 26 in order to form a plenum after the hose 42 is removed therefrom . accordingly , the surface defined by the edges of the base 22 closest to the console 24 may be a solid surface except for the opening for the grid 28 . the bellows 96 is not required . thus , the illustration of fig1 shows the housing 12 in substantially the stowed configuration , but with the cap 101 removed . meanwhile , the hose 42 is illustrated in order to show its positioning and sealing with respect to the aperture 30 . referring to fig1 , the power system 20 for the apparatus 10 in accordance with the invention may be one of several possible configurations . for example , a power supply 38 may include the appropriate hardware to convert alternating current to direct current for convenience , and safety . thus , a cord 104 may come from wall power through a plug 106 to be connected by the adapter 108 to the power supply 38 . wall current may be converted from alternating current , at a comparatively higher voltage , to direct current , at a comparatively lower voltage , delivered through the cord 52 and subsequently the plug 54 into the apparatus 10 . typically , a plate 110 commonly called a rating plate or “ boiler plate ” may contain information concerning safety , ratings , instructions , warnings , connection requirements , and the like . referring to fig1 , a compact power supply may be used in many situations requiring comparatively lower power ( e . g . a few amps or less ). the apparatus 10 does not require large amounts of power ( e . g . typically less than an amp down to tenths of an amp ). a simple adapter 38 or power supply 38 may provide a plug 112 directly into a wall socket , feeding direct current through a cord 52 and a plug 54 into the apparatus 10 . referring to fig1 , in one embodiment , an apparatus 10 in accordance with the invention may use a battery 120 . the battery 120 may be identical to , or may be the same battery 120 as that of a laptop computer . accordingly , a charger 118 or cradle 118 may be used to charge the battery 120 , or the battery 120 may be charged within a laptop computer . a cpap apparatus 10 may be carried with a computer and may share the same battery 120 . in the illustrated embodiment , a battery 120 may be fitted into a cradle 118 connected to wall power or a power supply by a cord 114 , and secured electrically by a plug 116 in the cradle 118 . in the illustrated embodiment , the output cord 52 and the plug 54 may actually be connected to the apparatus 10 . in an alternative embodiment , a computer battery 120 may be embedded within the envelope of the apparatus 10 , and included in the space near the fan 50 of the drive system 14 within the housing 12 . a rating plate 110 or instruction plate 110 may provide the similar warnings , instructions , and connection details as discussed above . referring to fig1 , a case 130 for an apparatus 10 may include a region for holding the apparatus 10 , divided into compartments 137 . for example , a compartment 137 a may hold the apparatus 10 , while a compartment 137 b may hold a power supply 38 , a folded cord 104 , and the like . a closure 132 , or lid 132 may be secured to the case 130 by a zipper 134 or other suitable mechanism . typically , a handle 136 for carrying may be adapted to a hand of a user , a shoulder strap , or the like . in the illustrated embodiment , the case 130 may be a conventional case , borrowed from the laptop computer market , may be or a specially designed case adapted to the apparatus 10 . for example , the divider 136 may be moveable , and thus may be positionable within the case 130 in order to securely stow the apparatus 10 , and still accommodate the power supply 38 , cord 136 , or other accoutrements associated with the apparatus 10 . in certain embodiments , the cord 104 may actually be wrapped around a spooling mechanism before the tubing 42 . likewise , the power supply 38 may be replaced with a battery 120 actually embedded in the apparatus 10 . thus , not all embodiments of an apparatus in accordance with the invention will require separate storage for a power supply 38 and cord 104 . referring to fig1 , a case 130 suitable for holding the apparatus 10 may be a simple compartment 130 associated with other luggage 140 , such as a briefcase . for example , certain suitcases , briefcases , and the like may be configured as a separate piece of luggage 140 having a pocket 130 interior or exterior thereto for receiving a laptop computer or the like . accordingly , an apparatus 10 in accordance with the invention may be placed within the compartment 130 and closed by an appropriate lid 132 or cover 132 sealed by any appropriate mechanism . in the illustrated embodiment , hook - and - loop fasteners may be formed as a securement mechanism 142 on the flap 144 and the outer portion of the case 130 or compartment 130 in order to form a proper securement keeping the lid 132 closed on the apparatus 10 . zipper closures 134 may be formed as appropriate in any particular location , including as the sealing mechanism for the lid 132 of the compartment 130 . any suitable system of handles , shoulder straps , and the like may be associated with the luggage 140 as known in the art . referring to fig1 , one embodiment of an apparatus 10 in accordance with the invention may be fitted into a case 130 having a closure 132 sealed by a zipper 134 , or the like . typically , a zipper pull 135 or more than one , may secure the zipper 134 to itself in order to close the cover 132 over the apparatus 10 . similarly , a variety of carrying straps 138 or handles 136 may be secured on various sides in order to promote convenient carrying . meanwhile , the apparatus 10 may be fitted within the case 130 to be easily stowed , opened , inspected , and otherwise travel just as a laptop computer would . in certain embodiments , the tubing 42 may be configured to fit on a reel . the reel may be operated by a crank in order to wind up the tubing 42 into the housing 12 . in an alternative embodiment , the tubing 42 may be of a length selected to exactly fit with a single wrap or a few wraps about a spooling center portion 62 . the shape of a laptop computer may actually contain four or five feet of hose along its periphery . accordingly , in one method and apparatus in accordance with the invention , the system 10 may include a simple clip system around the outer periphery of the cpap apparatus 10 suitable for holding the tubing 42 therearound . in yet another embodiment , a computer battery may be fitted to the apparatus 10 in accordance with the invention . the power conditioning or the motor 50 may be sized to match the battery of an individual &# 39 ; s laptop computer . alternatively , a power supply , such as a battery of generic configuration having power conditioning for current , voltage , and the like may be adapted to power a laptop computer , the apparatus 10 , or both . thus , a computer battery may be matched to a user &# 39 ; s apparatus 10 , or vice versa . in yet another alternative embodiment , the housing 12 may be configured as a “ clam shell ” configuration , having a hinge 42 at the back of two substantially identical halves . the drive system 14 may be configured near the center of the housing 12 , with the delivery system 16 , principally the hose 42 or tubing 42 wrapped therearound . the present invention may be embodied in other specific forms without departing from its basic operational principles or essential characteristics . the described embodiments are to be considered in all respects only as illustrative , and not restrictive . the scope of the invention is , therefore , indicated by the appended claims , rather than by the foregoing description . all changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope .

US-201113080433-A

an electrosurgical handpiece that is bipolar or unipolar in operation and that is configured for use in mis . the bipolar operation confines the electrosurgical currents to a small active region between the active ends of the bipolar electrode and thus reduces the possibility that excessive heat will be developed that can damage patient tissue . the position of the active region can be controlled to avoid patient tissue that may be moire sensitive to excessive heat . in one embodiment , the handpiece is constructed with a flexible end controllable by the surgeon so as to allow the surgeon to manipulate the end as desired during the surgical procedure . this feature allows the surgeon to position the active electrode end at the optimum location within , say , a herniated disk to remove undesired regions and to provide controlled heat to shrink the tissue during surgery . in another embodiment , the handpiece is constructed to contain both a bipolar as well as a unipolar electrode , with provision made for selectively operating either of the electrodes . in still another embodiment , a replaceable element for the handpiece comprises scissors .

the mis procedures are well known in the art and need no further elaboration here except to state that the invention has to do with the construction of the electrosurgical electrode that is inserted into the cannula during the procedure for the purpose of shrinking or excising tissue . the use of electrosurgical procedures to chrink herniated sidks and other tissue is also well known in the art and also needs little elaboration here . it will suffice to state that the procedure with the novel handpiece of the present invention is similar to that using the unipolar electrode with the incorporated heat sensor , except that , with the bipolar handpiece of the invention , no complex temperature sensor and associated control circuit are needed , as , in the case of the bipolar electrode , electrosurgical currents are confined to the small active region between the electrode tips and will cause little if any heat generation at remote tissue locations . in a preferred embodiment of the invention , an electrode designed for mis is provided with an outer tubular housing that is stiff enough to be inserted into the cannula and has a straight end port ion that is capable of flexure when a bending force is applied but which end portion has inherent memory that will restore the tubular housing to its pre - flexed configuration when the bending force is removed . the tube may be made out of a plastic or a metal such as stainless steel . examples of suitable plastics with some flexibility and inherent memory that will keep the tubing straight when the bending flex is removed are delron , vinyls , and nylon . the location in the tubing where flexure occurs can be established in several ways , the preferred way being to weaken one side of the outer tubing , as for example by spaced slots , at an end region spaced from the tip where flexure is desired . in a preferred embodiment , a handle is provided for supporting the outer tubular housing and the handle is provided with a hand grip and a trigger that is connected to a mechanism to flex the tube end when squeezed . in a preferred embodiment , this result can be obtained by attaching a pull string or wire to the side of the tube that has been weakened by the cutting of slots but beyond the slots . the pull string or wire is attached to the trigger at the opposite end of the tube . when the trigger is squeezed against the grip , the tube end will flex in the direction of the weakened side of the tube . when the trigger is released , the tube due to its inherent memory returns back to its original straight position . referring now to fig1 one form of bipolar handpiece according to the invention is shown at 10 . it comprises a handle 12 having a grip 13 , a trigger 14 , and through a bore 15 at its top is mounted the outer first tubular member 16 . the latter has a small outside diameter that will allow it to be inserted into the standard cannula used for mis . a typical range is about 0 . 07 - 0 . 1 inches . a typical length is about 10 - 20 inches . the outer tubular member 16 is preferably supplied with an enlarged diameter end 18 ( see fig1 ) acting as a stop for the tubular member 16 when it is inserted into the handle bore 15 and secured therein by , for example , a set screw ( not shown ). this simple mounting allows the use of disposable assemblies of tubular member and electrodes if desired . inside the outer tubular member 16 is an inner electrically - insulating , for example , plastic , lumen ( second tubular member ) 20 that has an electrically - insulating wall 21 down its middle forming two electrically - insulated compartments 22 , 24 ( fig3 ). the inner tubular member 20 may be secured within the outer tubular member 16 by any convenient means , such as a set screw ( not shown ), which , as will be explained in greater detail below , allows replacement of the second tubular member 20 with its bipolar electrode by a another bipolar electrode or a similarly - configured unipolar electrode . fig1 illustrates this feature by showing an electrode 20 being plugged into the housing 12 via the opening 15 and extending into the outer tubular member 16 . two electrically - conductive wires 26 , 28 , for example of stainless steel , are each extended through one of the insulated compartments 22 , 24 , with the result that the wall 21 electrically separates the two conductive wires ( fig4 ). additionally , the circular wall 30 surrounding the separating wall 21 for a short distance at the tube end is stripped back ( fig5 ) leaving only the separating wall 21 projecting forward . this projecting wall 21 now becomes the insulation between two half - ball electrodes 30 , 32 connected as by welding to the projecting ends of the wires 26 , 28 ( fig6 ). [ 0036 ] fig4 shows the remote end of the assembly before the half - ball electrodes have been added , and fig6 shows the electrode wires 26 , 28 which were first pulled forward to provide extra room to attach the half - ball electrodes 30 , 32 to the wire ends , after which the wires are retracted pulling the half - ball electrodes back to their operative position , as shown in fig7 in which the ball electrodes 30 , 32 are fully spaced over their entire length ( the direction of the longitudinal dimension of the assembly ) by the center wall insulation 21 . the outer tubular member 16 is weakened at a location spaced a short distance from the remote end of the tubular member 16 , as by cutting a series of spaced slots 34 that extend through the outer wall 30 . a pull wire 36 is extended through the outer tubular member 16 along the bottom side of and outside of the inner tubular member 20 , i . e ., at the same side as the slots 34 , and anchored 38 ( fig4 ) to the outer wall 30 as by use of adhesive or by fusion if the outer tubular member is of plastic , or by welding if the outer tubular member is of metal . an opening 35 is made in front of the slots 34 on the top part to provide access to the pull wire end to allow this connection to be made during assembly . the opposite end of the pull wire 36 is attached 39 to the trigger 14 ( fig1 ). the outer tubular member 16 is held in a stationery position within the handle 12 , and the grip 13 is likewise stationery with respect to the handle 12 . hence , when the trigger 14 , which is pivotably mounted 41 on the handle 12 , is squeezed , illustrated in fig2 the pull wire 36 to which it is attached applies a pulling force on the remote end of the outer tubular member 16 which as shown at 44 causes it to flex downward about the weakened section 34 . when the trigger is released , the natural tendency of the outer tubular member 16 to return to its normal straight position restores it to the position shown in fig1 . if desired , a return spring 46 can be added to the trigger 14 to aid this motion . the inner tubular member 20 together with its insulated half - ball electrodes 30 , 32 positioned at the end of this flexible tip is the actual bipolar electrode . connected to the proximate ends of each of the wires 26 , 28 is a standard bipolar connector 42 ( fig1 ). when the latter is plugged into a like connector on the front panel of a conventional electrosurgical unit , shown schematically at 48 ( fig1 ), and the unit activated , bipolar electrosurgical currents flow along the wires 26 , 28 to the ball tips 30 , 32 and an electrosurgical discharge is generated that extends between the ball electrodes 30 , 32 around the end of the insulating wall separator 21 . while it is preferred for reduction of herniated disks to use the ball electrodes , in a bipolar arrangement to confine the discharge to the immediate vicinity of the electrode ends , it will be understood that other known electrode shapes can be substituted for the ball electrodes , such as straight wires , needles , hooks , or loops . in addition , a feature of the invention is that the dual tubular member assembly makes it particularly easy to accommodate other electrode ends , by sliding out the inner tubular member 20 ( see fig1 ) from the outer tubular member 16 and sliding in its place another inner tubular member 20 with a different electrode configuration . this can be done before the outer tubular member 16 is extended through the cannula in the patient or even while the cannula is in place within the patient . in addition , a bipolar assembly in its dual lumen arrangement can be replaced by a unipolar electrode in a lumen with only a single compartment , in which case , the unipolar electrode end , with one of the aforementioned electrode shapes , would project forward from the end of the inner tubular member 20 ′, which in this case would not require the center insulation present . this is illustrated in fig9 . when an electrode substitution is to be made , the surgeon can pull out the inner tubular member and replace it with another inner tubular member with a different electrode thereby enabling the surgeon to change electrodes during the procedure without removing the handle with its outer tubular member that has already been strategically placed in the surgical site . while a range of electrosurgical current frequencies can be employed , it is preferred that the frequency range employed be preferably in the range between 1 . 5 and 4 mhz . [ 0039 ] fig8 and 10 illustrate other active electrode configurations . fig1 shows a bipolar hook assembly 50 , which can also easily be made unipolar . fig8 shows a unipolar loop assembly 52 . fig9 shows a unipolar needle 54 or pointed electrode assembly . among the benefits of this invention is that it offers the surgeon control and flexibility during surgeries that require difficult placement of electrodes and also movement of the active end at the active surgical area while the electrode is within the cannula to perform precision surgery . the degree to which the surgeon actually needs to bend the flexible tip depends upon its location relative to the disk area to be cut or shrunk . the flexible tip provides the surgeon with an additional degree of freedom in finding the optimum electrode position before energizing the electrosurgical unit . the long nozzle 16 is needed because , typically , the cannula 50 is inserted from the patient &# 39 ; s side ( fig1 ), and the cannula 56 is positioned while the surgeon is observing the position of the cannula though the viewer . after the cannula is positioned properly , then the electrode 16 can itself be pushed through the cannula 56 until its flexible end 44 is outside the end of the cannula and further positioned within the disk surgical site by moving it forward or backwards and by flexing the electrode tip 44 . the connector 42 can be plugged directly into the electrosurgical mainframe 48 , and thus the electrosurgical energy furnished at the electrode working end will be determined by the mainframe controls and a conventional footswitch . however , most surgeons prefer hand control of the electrosurgical energy , as was explained in the earlier referenced patent , which is easily accomplished by using the finger switch activator described in that earlier referenced patent and which can be mounted on the cannula or handle . [ 0042 ] fig1 shows a variant 10 in which the inner tubular member 20 is replaceable , and also is provided with a suction tube 56 connected to the handle and to the clearance space 58 ( fig3 ) between the inner and outer tubular members . when suction is provided at the end 56 , it is delivered to the remote end of the outer tubular member 16 at the surgical site and thus will exhaust any fumes or smoke that may interfere with the surgeon &# 39 ; s vision as well as cool the surgical site . the variant 10 ′ of fig2 and 11 include a fixed inner tubular member 20 and lacks the suction feature . while the parts of the electrosurgical handpiece , made up of metal and if of plastic , of delrin for example , are autoclavable , the device is sufficiently simple that it can be manufactured at very low cost with a less expensive plastic and thus can be made disposable . the handpiece of the invention is generally useful for treating tissue and is useful in particular in the following situations . thermally induced radiofrequency for shrinkage of collagen , shrinkage and tissue denaturazation , and collagen contraction . for treating and producing profound shrinkage of capsular tissue , for example , due to denaturazation of collagen fibers . also to shrink and remodel collagen fibrils after exposure to high frequency radiowave energy . as a further example , shrinkage of collagen to promote capsular stability has been shown to be effective for shoulder dislocations and herniated discs , as examples . fig1 - 19 show a modification according to the invention comprising both a bipolar and a unipolar electrode , with the additional feature of allowing the surgeon to selectively choose and activate a bipolar or a unipolar electrode . this embodiment also includes as an additional feature electrodes with pre - configured ends such as pre - bent ends which are normally inside of a relatively stiff outer tube but which when extended outside of the outer tube will assume its pre - bent position . one form of this this embodiment comprises a handle 60 to which is attached a hand grip having a forward portion 62 affixed to the handle 60 and a rearward portion 64 which is secured to a slidable stiff member 66 comprising an upper part 68 and a lower part 70 . the upper part 68 is connected to a relatively stiff inner tube 72 which is slidable within the handle 60 and which is connected to and functions to push forward , when the grip is squeezed , a dual lumen 74 of the type illustrated in fig7 together with its wires 78 , 80 of a bipolar electrode 80 that may be of the half - ball type shown in fig7 which extend through the dual compartments 82 , 84 of the relatively stiff electrically - insulated inner first plastic tube 74 . the latter is slidably mounted within a stiff outer tube 75 . below the latter is mounted a stiff second tube 77 which slidably houses a slidable electrically - insulated tube 79 housing a wire 81 connected at its end to an unipolar electrode 88 . fig1 shows just the two side - by - side electrically - insulated tubes 74 and 79 without the outer housings 75 , 77 . normally , both the bipolar and the unipolar electrodes are in their retracted position shown in fig1 and 14 . when the grip is squeezed , the member 72 is pushed forward toward the working end causing the dual lumen 74 to which it is connected , together with its bipolar wires to which the bipolar electrode 80 is connected , to project forwardly out of their housing 74 as shown in fig1 and 17 . the surgeon can then activate the electrosurgical unit to supply via terminals 91 bipolar electrosurgical currents to the bipolar electrode end 80 . when the grip is released , the spring tension of the grip , or an additional spring ( not shown ) if needed , will cause the tube 74 to retract to the position shown in fig1 and 14 . when it is desired to operate the unipolar electrode , the surgeon presses a slide 90 on the side of the tube 70 , which slide is connected to the single tube 79 , which causes it to move forwardly from its retracted position ( fig1 ) to its extended position shown in fig1 and 19 . this action causes the unipolar electrode 88 to project forwardly . the surgeon can then activate the electrosurgical unit via wire 92 to supply unipolar electrosurgical currents to the unipolar electrode end 88 . the two electrode movements are separate from one another so that the surgeon can selectively choose which electrode to use inthe procedure . when the surgeon releases the slide 90 , a spring ( not shown ) causes the single tube 79 to retract within its outer hole 77 . preferably , at least the projecting end of one , preferably both , of the respective bipolar / unipolar tube is made of a material that can be pre - bent and has sufficient memory to retain its pre - bent shape when extended outwardly from its restraining outer tube . either a plastic can be used or a metal , such as stainless steel , which has been treated , as by tempering , to retain a pre - bent shape . this is well known in the art and suitable materials will be apparent to those in this art . if a metal is used for the inner tube , the electrode wires will have to be suitably insulated from one another or alternatively , the tube can be lined with an insulating layer . in this embodiment , with electrodes having a pre - bent and thus fixed shape , it is not possible to change their orientation , i . e ., whether straight or the angle of the bending . the only control that the surgeon has is over the length of the extension . a feature of the invention is a family of unipolar and bipolar electrodes with differently - oriented ends , some bent in one direction , others bent is still other directions , and some straight . fig1 shows one member of the family with an end that bends to the left . fig1 shows a member of the family with an end that is straight . typically , the family would contain either bipolar or unipolar electrodes or both with ends that are pre - bent in all four directions as well as straight . as in the fig1 embodiment , new electrodes 74 , 79 are easily plugged into the end of their respective tubular housing handle as needed , which can be done during the procedure . with the bipolar electrode , the replacement electrode telescopes through tube 68 , so that when the latter is moved relative to grip 62 , the entire tube 72 moves with it . with the unipolar electrode , as one example , the side can be provided with a rack ( visible through the side slot in fig1 ), with the slide 90 fitted with a suitable gear or other means to move the replacement tube 77 with the slide . the electrodes can be made at a relatively low cost and thus can be made disposable . the more expensive handle can be reused . other handle constructions that allow extension and retraction of replaceable electrodes will be apparent to those skilled in this art . another example according to the invention of a replacement element for the bipolar or unipolar housing is shown in fig2 . in this case , the new structure is the same as that of fig1 except that if desired the unipolar structure can be omitted . only the working end is shown in fig2 , which in this embodiment is a scissors 94 comprising bent stainless steel scissor elements 96 connected at the gun end to the tube 72 and at the remote end connected by a pivot 95 . as will be noted , the scissor elements 96 when extended out of their tube 75 are pre - configured to assume an open position . the grip 62 , 64 ( fig1 ) is spring loaded so that the surgeon can extend the scissor elements 96 as shown by squeezing the grip . when the grip is released , the spring action causes the scissor elements to be retracted , the confining action of the walls of the tube 75 forcing the scissor ends together cutting in a normal scissor action any tissue around which the scissor ends have been placed . the dual lumen 74 allows bipolar currents to be applied to the scissor ends if desired , in which case the pivot 95 would have to electrically - insulate the two scissor elements , as with washers for example . the scissors 94 can also be configured for mounting in the unipolar tube 77 in which case unipolar currents can be applied to the scissor elements 96 . it is also possible to have no terminals connected to the scissors 94 so that no electrosurgical currents can be applied thereto , in which case the scissors 94 can be operated just with a mechanical action . as before , the scissors 94 can have its own tubular housing 74 and thus be plugged into the gun of fig1 to replace a bipolar or unipolar electrode , all while the tubular structure remains within the cannula during the procedure . it is preferred that the scissor end is pre - configured as in the fig1 embodiment so that it can be caused to assume a particular orientation when extended , with the possibility of repalcing it with a scissors of a different orientation if needed . or if desired , it can be mounted as in the fig1 embodiment with means for flexing the remote end of the structure . other usable mechanical or electrical structures will be appreciated by those skilled in this art . while the invention has been described in connection with preferred embodiments , it will be understood that modifications thereof within the principles outlined above will be evident to those skilled in the art and thus the invention is not limited to the preferred embodiments but is intended to encompass such modifications .

US-84066601-A

the present invention is a miniature vein enhancer that includes a miniature projection head . the miniature projection head may be operated in one of three modes , afm , dbm , and rtm . the miniature projection head of the present invention projects an image of the veins of a patient , which aids the practitioner in pinpointing a vein for an intravenous drip , blood test , and the like . the miniature projection head may have a cavity for a power source or it may have a power source located in a body portion of the miniature vein enhancer . the miniature vein enhancer may be attached to one of several improved needle protectors , or the miniature vein enhancer may be attached to a body similar to a flashlight for hand held use . the miniature vein enhancer of the present invention may also be attached to a magnifying glass , a flat panel display , and the like .

referring to fig1 a - 1 d , preferred embodiments are shown that generate raster , lissajous and collapsing ellipse and spiral patterns . the drawings show the mirror ( e . g ., 1250 ) on top of the electrical wave form ( e . g ., 1258 ) that is applied to the mirror to control its motion . these sinusoidal wave forms move the mirror in a back and forth pattern with maximum deflection at the peak of the wave , rest at the center of the wave and the opposite maximum deflection at the opposite peak of the wave . also indicated in the drawing are the most preferred frequencies and the preferred ranges that would be used in an implementation of the invention . in fig1 a , a raster pattern 1257 is generated using two mirrors . mirror 1250 is mounted so that it has a single degree of freedom of motion at fulcrum 1251 / 1252 . a laser light source as described elsewhere strikes the mirror at an appropriate angle so that the angle of reflection is such that the light properly strikes the second mirror 1255 . mirror 1250 oscillates at a high frequency , for example , such as 20 khz 1258 . this generates the horizontal motion in the raster pattern 1257 . the now moving beam 1253 is projected on to the second mirror 1255 so that it is parallel to its axis of movement . mirror 1255 is mounted so that it has a single degree of freedom of motion at fulcrum 1254 / 1256 . mirror 1255 moves at a slower rate such as , for example , 60 hz as shown in waveform 1259 . the generated pattern is bi - directional , with the beam moving right to left and left to right as the fast mirror 1250 moves and top to bottom and bottom to top as the slow mirror 1255 moves . a preferred embodiment uses 20 khz for waveform 1258 and 60 hz for waveform 1259 . other preferred embodiments can use 7 khz to 35 khz for waveform 1258 and 45 hz to 90 hz for waveform 1259 . referring to fig1 e , a preferred embodiment for the generation of a lissajous pattern 1265 using a single mirror 1272 that can move on two axes is shown . an alternative embodiment would be to use two mirrors arranged as shown in fig1 a but modulated as described for the lissajous pattern . the mirror is capable of moving along the axes created by fulcrum pairs 1266 / 1269 and 1267 / 1268 . the mirrors are moved at different frequencies and in a specific phase relationship to generate this pattern . a lissajous pattern is mathematically described by the equations : the two axes are modulated based on this relationship where various values of a , b and the phase offset control the specifics and density of the projected lissajous pattern . waveform 1270 shows the x value over time and waveform 1271 shows the y value over time . in the equation , a is the amplitude of waveform 1270 and b is the amplitude of waveform 1271 . at and bt are the angle of the sine waves over time and phase is the phase shift ( angle offset ) between the two waveforms 1270 / 1271 . many values of these variables can be used for a scanning application , but a preferred embodiment would select values that move the mirror at its resonant frequencies so as to minimize power consumption . a preferred embodiment uses 400 hz for waveform 1270 and 60 hz for waveform 1271 . other preferred embodiments can use 300 khz to 35 khz for waveform 1270 and 45 hz to 90 hz for waveform 1271 . in fig1 i , the system is configured for a collapsing ellipse pattern 1286 where a series of loops are drawn across the target area with each circle either slightly smaller or slightly larger than the previously drawn circle . again , a single mirror 1287 is shown , but the same function can be performed with two moving mirrors . the mirror is capable of moving along the axes created by fulcrum pairs 1282 / 1284 and 1285 / 1283 . the mirrors are moved at identical frequencies and are 90 degrees out of phase to generate this pattern . the x direction of mirror movement is controlled by the waveform 1280 . the y direction of mirror movement is controlled by the waveform 1281 . this waveform 1281 is amplitude modulated so that each subsequent full wave is slightly changed in amplitude so that a different sized circle is drawn . a preferred embodiment uses 8 khz for waveform 1280 and 8 khz for waveform 1281 . other preferred embodiments can use 7 khz to 35 khz for waveform 1280 and 7 khz to 35 khz for waveform 1281 . the spiral pattern 1290 in fig1 m is shown generated by a single mirror 1297 but could be drawn with two mirrors as previously shown . the mirror is capable of moving along the axes created by fulcrum pairs 1291 / 1293 and 1292 / 1294 . the mirrors are moved at identical frequencies and are 90 degrees out of phase to generate this pattern . the x direction of mirror movement is controlled by the waveform 1295 . the y direction of mirror movement is controlled by the waveform 1296 . both waveforms 1295 / 1296 are amplitude modulated in a sawtooth pattern generating a spiral pattern . a preferred embodiment uses 8 khz for waveform 1295 and 8 khz for waveform 1296 . other preferred embodiments can use 7 khz to 35 khz for waveform 1295 and 7 khz to 35 khz for waveform 1296 . in addition to moving mirrors , one or more fixed mirrors may be used in the design of the invention . this allows many different arrangements of the light sources to minimize overall size or to otherwise optimize the positioning of the components of the device . referring to fig2 a , the laser source 10 is oriented to emit light 13 in a desired direction . a mirror 11 is placed in the path of the laser light at an angle to the light beam that is calculated to bounce the light beam 14 into the new desired direction . additional mirrors 12 can be placed in the path of the beam to further redirect the light beam 15 into a desired orientation . although two mirrors are shown in fig2 a , as many or as few mirrors as required can be used . additionally , although fig2 a is drawn in two dimensions and the angles shown are right angles ; these angles can be set so that the beam is reoriented at any angle required in three dimensions . in fig2 b , the laser source 20 is oriented so that the beam 21 strikes the mirror 22 at the appropriate angle and position . mirror 22 is a moving mirror with an axis of motion shown at 24 . in fig2 b , the mirror is presented as moving on a single axis and therefore projects a single line on the target surface . mirrors with two degrees of freedom are well known in the art and mirror 22 can be replaced by such a mirror so that it projects a two dimensional scan and projection field on the target area . alternatively , a second moving mirror can be used as will be described in fig2 d . note that the laser beam 21 can be redirected by one or more bounce mirrors as shown in fig2 b if necessary to the specific embodiment . such an implementation is shown in fig2 c . laser source 30 projects a beam of light 31 so as to strike the mirror at the desired position and angle . mirror 32 is oriented so that the reflected beam 33 strikes the appropriate position on the moving mirror 34 . again , the for ease of drawing , mirror 34 is shown moving on a single axis 35 , but can be replaced by a mirror with two degrees of freedom so as to project and scan a two dimensional area with only a single mirror . fig2 d shows a two mirror system that is used to project and image a two dimensional area . the laser source 50 is oriented so that the beam 51 strikes the mirror 52 at the appropriate angle and position . intermediate bounce mirrors could be placed in the beam path 51 to reorient the beam . mirror 52 is a moving mirror with an axis of motion shown at 53 . the now moving beam of light 54 is directed to moving mirror 55 . mirror 55 has an axis of motion 56 that is oriented at an angle such as 90 degrees from the axis of motion of mirror 52 shown at 53 . in this manner , the light reflected off of mirror 56 forms a two dimensionally shaped scanning pattern 59 on the target area 58 . different embodiments will use one or more laser colors and sources to perform detection and projection . one embodiment of the invention uses two lasers to perform its functions where one laser is selected to have optimum performance at blood detection ( e . g ., 740 nm ) and the second laser has optimum characteristics to project the resulting image to the user ( e . g ., 638 nm ). the major benefits of this embodiment include the ability to modulate the detection and visible lasers simultaneously , and the ability to select lasers that have ideal characteristics for the function to be performed ( rather than a trade off between detection and visibility as will be seen in a single laser embodiment ). the laser sources ( e . g ., fig2 d , 10 ), can be an assembly that provides one or more colors of laser light either arranged either coaxially side by side in parallel . a key element of this embodiment is a mirror system that in addition to moving the light spot as previously described provides a mechanism that causes the two laser beams to become coaxial so that both lasers strike the same point on the patients skin . there are many different ways to align co - axially the visible laser and the infrared laser including the use of dielectric mirrors . dielectric mirrors are specially coated mirrors that can reflect selected wavelengths ( or wavelength ranges ) of light while allowing other wavelengths to pass through the mirror . in this embodiment one or more coated mirrors are used in the optical path to make the separate laser sources coaxial so that when they strike the moving mirror subsystem , they then strike the same spot on the skin . furthermore , separate control systems are provided to modulate the intensities of the lasers . the laser intensities can be independently modulated to control the desired characteristics such as depth of detection and the brightness of the projected image providing a great degree of control over these desirable characteristics . additional embodiments are possible where additional lasers are added to provide for further refinement of the detection and presentation of the detected blood . for example an additional laser could be used to determine range to the surface of the skin so that finer control over the depth of detection can be performed . another example is the use of a second color of visible light so that additional information about useful attributes such as depth of the blood vessel can be presented to the user . fig3 depicts a dielectric mirror approach . the mirror is shown with the infrared laser placed behind the dielectric mirror . the dielectric mirror is selected so that the infrared laser ( e . g ., 740 nm ) passes through the mirror . the back side of the mirror can be coated with an anti - reflective coating 106 to minimize loss of intensity of the infrared light due to reflection from the back surface of the mirror . it also minimizes the shielding necessary for the back reflection of the infrared light . note that there is a refraction effect on the infrared laser that is adjusted for by the proper alignment of the lasers . the visible laser ( e . g ., 638 nm ) is directed to the front surface of the mirror which is coated with a material that reflects the light of that laser . the combination of the transmitted laser light and the reflected laser light is now aligned and exits the assembly coaxially . various implementations can be created that alternate the positions of the visible and infrared lasers . similar assemblies can be repeated multiple times for creating coaxial combinations of more than two lasers if needed for the specific marketing or technical requirements of the product . a characteristic of laser light is that it is polarized in a known orientation . by carefully controlling the orientation of the laser light , dielectric elements that reflect and pass light polarized in specific orientations can be used to coaxially align the lasers . with regard to the polarized approach , referring to fig3 and replacing the dielectric coated mirror with a polarized element as shown in fig4 . one laser is polarized in a first orientation and is placed behind the polarized element . the polarized element is selected so that the first polarized orientation passes through but the second polarized angle is reflected . the second laser is polarized to the second polarized angle and is aimed at the front of the polarized element and is angled and aimed so that the reflection of the first laser is coaxial with the second laser passing through the polarized element . in fig4 , the element 110 is shown with the infrared laser 111 placed behind the polarizing element . the laser 111 polarization ( orientation ) and the polarizer 113 orientation is selected so that the infrared laser 111 passes through the element . the back side of the element can be coated with an anti - reflective coating 116 to minimize loss of intensity of the infrared light due to reflection from the back surface of the element . it also minimizes the shielding necessary for the back reflection of the infrared light . note that there is a refraction effect on the infrared laser 115 that is adjusted for by the proper alignment of the lasers . the visible laser 112 is directed to the front surface of the element 113 polarized so that it is reflected by the element . the combination of the transmitted laser light and the reflected laser light is now aligned and exits the assembly coaxially . while element 110 shows a coating on the front surface , the coating may also be placed on the opposite surface . similar assemblies can be repeated multiple times for creating coaxial combinations of more than two lasers if needed for the specific marketing or technical requirements of the product . additionally , the visible and infrared lasers may be swapped if desired and the parameters of the assembly adjusted appropriately . laser diodes that combine more than one laser into a single package can also be used as the laser light source . this eliminates the need for additional beam combining elements in the system . for example , sanyo dl - 1195 - 251 provides both a red and an infrared laser in a single package . all the embodiments so far have related to a visible laser point source and a ir laser point source bouncing off multiple mirrors , or a single mirror moving in multiple directions , to create a two - dimensional scanning pattern where both the x and y axis of the two dimensional imaging area is scanned with the single coaxial source of laser light . rapid scanning causes the eye to integrate this into a single image . in such a system , the beams need to be actively steered in both the x and y directions in the desired pattern . since there is only reflection from the point at which the laser is currently striking , the photo detector sub system can make inferences about the presence of veins at that particular spot on the target . an alternative embodiment would be to use a linear array of visible laser sources and a linear array of ir laser sources which then are reflected off a single mirror moving on a single axis . the effect of putting these lasers side by side is to eliminate the need to move the laser point in both the x and y directions . an appropriate density of laser sources will be required so that the image presented to the user achieves a desirable resolution . these sources could be from individual lasers for each desired line of resolution or from a lower resolution array optically split into a sufficient number of sources to achieve the desired resolution . many laser arrays known in the art could be used including a vcsel array . using a laser array , you “ paint ” an entire field of view with the broad brush ( the array of laser sources ). an advantage of this approach is ( i ), the mirrors are less complex , and ( ii ) that the collection of the reflected ir light could also be by means of a retro collective mirror . a retro collective mirror has a field of view corresponding to the array of lasers , and moves in concert with the movement of the array of lasers . a retro collective unit has a significantly improved signal to noise ratio since it is only receiving signal input at any given time directly in a line of sight with the lasers , thereby minimizing the effect of ambient light and other noise sources . a retro collective mirror is inherently larger than a mirror that simply moves the beam . this is to allow for a large light collection area . however due to inertia , as the mirror is made larger , it can no longer be moved as fast as needed for a single laser . this arrangement of multiple lasers allows the system to eliminate the fast moving mirror . as shown in fig5 a , the array of laser light sources 400 / 408 / 403 , is arranged so that the beams strike the moving mirror 402 / 406 / 402 perpendicular to the axis of rotation 402 a / 407 so that as the mirror swings back and forth on its axis , the laser beams are scanned so that the emitted light forms a rectangle on the target surface 410 . fig5 b shows a side view of the arrangement , with the array of lasers 403 strike the moving mirror 402 and are reflected in a moving pattern 404 . in addition to the paired visible and ir lasers , the array of lasers could be a single wavelength array of sources that use one wavelength to detect and project as described elsewhere . in addition to lasers , if the distance to the object being scanned is tightly controlled , then leds could be used in place of lasers . a device called a grating light valve , such as those made by silicon light machines ( http :// www . siliconlight . com ), can be used in a similar manner to an array of laser sources . these light valves , typically based on mems technology , are basically mirrors that can be set to a reflective or non reflective state . they are typically packaged as an array of light valves 1506 as shown in fig6 . referring to fig6 , a light source 1500 generates a laser beam 1501 which is caused to strike a diffraction grating 1502 which spreads the beam into a line . since this line of light is divergent 1503 , lens 1504 is used to refocus the light 1506 onto the grating light valve 1506 . the light 1508 , with only a single element reflected from the grating light valve shown for clarity , is reflected off the grating light valve and is directed to a moving mirror 1509 , which moves along its axis 1510 , and is then modulated in the second axis by that moving mirror and is projected 1511 to the target area . by enabling a single light valve to reflect and all the rest to absorb in synchrony with the movement of mirror 1509 , a single scan line can be painted on the target area . two or more of the assemblies in fig6 can be bundled together so that one or more assemblies are used for visible light and one for infrared light , or a single assembly can be used for both projection and detection as will be described below . this embodiment can also be combined with a retro collective mirror system to enhance the collection of the reflected light . in another embodiment , the invention uses a single laser that emits light at a wavelength that is long enough that it is still differentially absorbed by blood but is still visible to the human eye . this embodiment is very important in that it enables building a system with only a single laser . all the complexity associated with aligning multiple lasers is eliminated thereby greatly reducing cost , engine size , unit size and power consumption . light emitted at 635 nm is one possible choice . in this embodiment , the laser spot performs the dual function of detecting the presence of blood and displaying that presence of blood to the user . it has been determined that a portion of a 635 nm laser penetrates into the tissue and is absorbed by the veins . accordingly the 635 nm laser can functions as did the infrared lasers for the purpose of imaging the veins . a portion of the 635 nm light does not penetrate the skin and is reflected off of the skin so that it is visible to the user . this portion of the light functions as did the visible laser in the dual laser system . a novel mechanism is used to allow the single laser to be used for both functions . in this embodiment the laser is never completely turned off . accordingly , even when the image to be displayed is black , the laser is still powered on at a very low level . the low level is strong enough that it can still be detected by the photo detectors so that the device can still image the veins , but not strong enough to create a distracting visible image ( so blacks may appear as a faint red color ). when the intensity of the 635 nm laser is subsequently increased to project a bright portion of the visible image , the gain of the analog circuitry associated with the received signal ( from the photo detectors ) is reduced in proportion . conversely , when the intensity of the 635 nm laser is subsequently decreased to project a darker portion of the visible image , the gain of the analog circuitry associated with the received signal is increased accordingly . in this manner , the received signal ( as measured after the analog circuitry ) remains relatively constant regardless of the intensity of the projected image . referring to fig7 a , a single laser source 70 is oriented so that its beam 71 is aimed into a steering assembly 72 . this assembly is constructed as described elsewhere in this patent out of a series of fixed and moving mirrors as appropriate to the specific embodiment . a moving light beam 73 is emitted from the device which then scans the targeted area of the body 74 in a pattern that is appropriate to the specific embodiment . typically in this configuration , neither repeatability nor knowledge of the specific beam position at a given time is required since the processing is done in real time as the light beam reads and paints the skin . however , the delay techniques that were discussed previously can be applied to a single laser configuration . the photo detector 76 is positioned to measure the light 75 reflected from the skin . since this is a scanning point source , the reflected light is an instantaneous representation of the reflection from a single point 82 on the body . note that the beam penetrates some distance into the body so the reflected signal is a composite of both surface and subsurface features . the output of the photo detector 77 is fed into a detection circuit 78 [ that uses techniques that are well known in the art ] to determine a change in the amplitude of reflected light and therefore detecting the relative amount of blood at the point 82 at which the laser is currently scanning . the detection circuit 78 provides an output 79 to the power supply 80 to the laser source 70 . as soon as a vein is detected at the point 82 , the power is increased to the laser source 70 which increases the output of the laser so that it is visible to the operator . as soon as the detection circuit 78 detects that the point 82 is no longer over a vein , then the control output 79 is changed so that the laser 70 outputs a light level that is sufficient for detection , but is no longer visible , or is dimly visible , to the operator . the detection circuitry includes the functionality to cancel out the increased reflection when the laser is brightened and the decreased reflection when the laser is dimmed so that the action of projecting the image does not interfere with the ability to detect the veins . if desired , the sense of on and off can be inverted , whereby the laser is brightly lit when no vein is detected and dim when a vein is detected . fig7 b - 7e provide a representation of the signals being used by the system . the reflected signal 90 - 94 is representative of what is seen at the inputs 75 and outputs 77 of the photo detector as well as the initial stages of the detection circuitry 78 . the corrected signal 95 , 96 represents what would be seen in later stages of the detection circuitry 78 once the variations in the laser amplitude 88 , 89 are canceled out . the detected vein 97 , 98 are representative of the logic in later stages of the detection circuitry 78 as well as the output signal 79 from the detection circuitry 78 to the input of the laser power supply 80 . the laser output amplitude 88 , 89 represent the output of the laser source 70 , 71 as it is increased and decreased to project the acquired image . following the reflected signal , at 90 the system is seeing a varying analog signal that is representative of a reflection pattern indicative of a beam that is not crossing a vein . since different individuals based on skin color , skin condition and place on the body will reflect different amounts of light as this baseline 90 , the detection circuitry is designed so that it can determine this baseline in real time . at 91 , there is an amplitude drop off as the beam crosses a part of the body where blood is absorbing sufficient light that the detection circuit 78 determines that the beam is over a vein . an internal representation or flag 97 that the beam is over a vein is set and the output to the laser power supply 79 is changed so that the laser amplitude is increased 89 to the bright condition thereby projecting the vein position . once the beam is brightened , there is a corresponding rise in the amplitude of the reflected light 92 . internally , the detection circuit 78 corrects for that amplitude 96 to eliminate false readings and to prevent saturation of the detection chain 76 , 77 , 79 . as the beam 73 continues to move , as long as the reflected level continues within the range for vein presence 92 , the laser will stay in its high state 89 . the beam will eventually move off of the vein and the reflection will increase once again 93 indicating that the beam has moved off of the vein . the detection circuitry 78 will then cause the laser power supply 80 to return to the dim state 88 . the reflected signal will now be reduced 94 , the detected vein flag will be turned off 98 . this process will continue to repeat for the duration of scanning . it is desirable in some embodiments to have greater control over the intensity of the beam when it is being used for detection . in a single laser system , it is required that the beam intensity be low enough in the dark areas of the image so that they appear clearly different from the lit areas . it would be desirable in certain circumstances such as different skin coloration or the desire to scan more deeply below the skin to bring the intensity of the light up for scanning . in this embodiment , the modulation of the laser between detection and projection can be in real time where the invention time slices the laser between detection and projection so that both functions are performed on the same pass of the laser over the skin . in fig8 a such a modulation scheme is shown . the signal 1350 shows the sample period for the photo detector . when the clock is high 1352 , the signal is sampled . when the clock is low 1351 , the signal from the photo detector is ignored . the laser output is switched between bright 1354 and dim 1359 . dim can also be off in some embodiments . as the beam passes over the body , the beam is kept at a bright intensity 1355 until a vein is detected during the period at 1360 . in this example , the vein is seen across two periods 1353 . in these periods , the output beam is dimmed 1356 / 1357 for the portion of the time period that is not used for sampling at the photo detector . it is brought back to its bright level 1361 during the sample period of the photo detector . many variations of this scheme are possible including working with multiple lasers of different colors , and changing the timing of the detection 1352 and projection 1351 intervals and allowing for multiple levels of bright 1354 and dim 1356 . in addition to modulation between detection and presentation modes as described , the laser can also be modulated within each of these domains to provide for variable detection characteristics such as changing the depth of penetration and detection through the skin and changing the intensity of the projection intensity to allow for variations in user preference , ambient lighting conditions and skin color . another embodiment of the single laser approach is to time slice the laser output so that very short pulses of high intensity are emitted followed by longer periods of projection intensity . projection intensity is the light output level that the system wishes the user to see . vein detection occurs at the bright pulses , but since they are very short , and the eye has a slow response time , they will not perceptibly interfere with the desired projection image . the advantage of this embodiment is that it allows higher intensity for the detection phase allowing for deeper structures to be imaged and allows the system to adjust for skin characteristics . the techniques discussed previously for alternating lines and frames between detection and presentation in a multiple laser system can also be applied in a single laser system . the use of these delay techniques allows all of the advanced vein detection techniques to be applied by allowing extra time between detection and projection as previously discussed as well as the improvements yielded by the additional control of laser intensity provided . as previously discussed a major benefit of lasers was that the beam remains a constant size over a very wide range of distances between the light source and the surface of the patient &# 39 ; s body . an alternative embodiment can be created that is of lower cost which uses tightly focused light emitting diodes ( leds ). in fig9 , a focusing scheme is shown for an led light source . the led 150 projects an unfocused beam of light 151 on a lens or assembly of lenses 152 which are designed to have a specific focal length so that the converging light 153 comes to a point 154 at a useful working distance . beyond the working distance the light begins to diverge 155 . the disadvantage is that the distance between the scanner and the body surface will need to be much more tightly controlled than in a laser embodiment . several controlling mechanisms are possible such as a physical device that is placed against the skin . one possible mechanism is shown in fig1 a . this approach uses a mechanical device that includes an open base 424 that is placed against the skin while allowing the image to be captured and projected through the opening 425 . the opening can be either closed as shown or open based on the design requirements of the specific embodiment . the base 424 is connected to the scan head 422 through one or more separation members 423 / 424 that are sized to ensure the proper distance is maintained between the scan head and the skin . the scan head 422 can be fixed to the positioning device or it can be a separate piece that is attached when needed and then removed . in an alternate construction , as shown in fig1 b , the mechanism can simply be a rod 430 of the appropriate length that projects from the scan head so that the distance is maintained when the end of the bar touches the skin 420 . 1 . a lighted crosshair or other pattern projected towards the skin that becomes crisply focused when the device is being held at the proper range 2 . an electronic ranging mechanism such as infrared or ultrasonic that measures the distance and then emits a set of tones that indicates that the device is at the appropriate distance . the tone feedback can be positive — only on when at the proper distance , negative — only on when outside of the proper distance or both with separate tones to indicate the two states . another useful embodiment of the invention is based on the use of led projection with alternative types of detection . given the need for tight control to be maintained of working distance , or to provide an auto focus mechanism in an led embodiment , the detection subsystem can be replaced with a camera element that is sensitive to ir light and an ir light source to illuminate the target area . in this embodiment , the image would be captured using the camera , processed to detect vein positions within the field of view and an led implementation as described earlier would be used to project the image back on the patient &# 39 ; s body . as discussed , a key benefit of using lasers is that they are inherently focused over a wide working range . as discussed above , since led &# 39 ; s do not remain focused over a long working range , the use of leds requires tight control of distance to the body area to be imaged . auto - focus lenses , such as those seen on cameras , could be integrated into the design so that a broader working range can be provided . typically however an led implementation is used to minimize cost so that normally the expense of auto - focusing would have limited application . however , other embodiments of vein enhancement systems such as that described in u . s . pat . nos . 5 , 969 , 754 and 6 , 556 , 858 would benefit from the use of auto - focus technology and have a cost basis that support such an implementation . fig1 shows an improvement to the device shown in fig1 from u . s . pat . no . 5 , 969 , 754 . in this figure , an auto - focusing feature has been added . computer controllable focusing lenses 1200 , 1201 , 1202 are placed in front of the key optical systems , typically replacing the existing lenses ( e . g . 14 ). these controllable auto - focus lens systems are controlled by either the main computing element of the system or a separate microprocessor dedicated to control functions such as and including auto focus . distance to the body is determined by a range detection system 1203 , many different types which are well known in the art . in addition to the subsystems that project the laser or laser spots on to the patient &# 39 ; s skin , a further subsystem provides the detection of the light that is reflected from both the skin and the subsurface features of the patient &# 39 ; s body . as previously mentioned , blood rich areas of the body such as veins absorb light in the infrared spectrum to a greater degree than surrounding tissues . the invention uses one or more photo detectors to measure the varying amount of reflection from the target . light sensitive devices including photo diodes , ccd camera elements and cmos camera elements and leds can be used as the photo detector to perform these measurements . the present invention can implement multiple photo detectors spatially separated so as to increase sensitivity , and reduce the interference associated with speckle , and specular reflection . however , as mentioned previously , one can achieve a reasonable result by using a single photo diode ; this will depend on the desired output and / or operating needs . the characteristics of the photo detector ( s ) will vary between embodiments . photo detectors can be selected with narrow band characteristics so that only the detection laser is received by the detector . this would also have the advantage of making the system less sensitive to ambient light . detector characteristics can be determined through selection of the photo detector itself or through the use of filter materials placed in front of the detector . another alternative approach would be to use a photo detector that is sensitive to a broad range of wavelengths and then by modulating the transmitted laser light , the system would be able to determine which laser , and therefore light wavelength , was being detected at a given moment in time . different embodiments may use different numbers of photo detectors based on the technical and business needs of the specific implementation . for example , a single photo detector might be used to minimize size or cost . multiple photo detectors may be implemented so that they are spatially separated so that the system is less sensitive to specular reflection . skin is somewhat shiny and causes unwanted specular reflection . in an embodiment where the photo detectors are separated , they each see the returned signal from a slightly different angle so that the effect of specular reflection is minimized . the larger the area of a photo diode ( one type of photo detector ) the lower the speckle noise seen by the system since the random pattern of speckles are integrated as a single reflection since they all strike the photo detector simultaneously . the larger area means that the small speckles are a smaller percentage of the total area and therefore have less of an impact on the signal . however , larger photo diodes have more capacitance and are therefore slower , which is undesirable in many embodiments of the invention . by using multiple photo diodes , the detector area is increased , providing the reduction in speckle noise , without the negative impact on the speed of the detector . this is due to the smaller capacitance of the smaller photo diode and the fact that each photo diode being able to have its own pre - amplifier circuit . a further benefit of having multiple photo diodes is that the received signal is increased without the need for additional amplifier gain and the associated noise that it would introduce into the system . a further benefit of having multiple photo diodes is that as the laser point moves across the human limb , the curvature of the limb causes an increasing amount of the light to be reflected away from the scanner as the beam moves to the sides of the limb . the addition of spatially separated photo detectors adds additional collection area nearer to the spot being scanned and allows more of the reflected light to be captured . in addition , having two separately placed photo detectors reduces the impact of specular reflection . as an alternative to the addition of a photo detector , collection mirrors can be used in the collection path so that light is collected from spatially separate points and are then reflected on to a single photo detector shared by two or more collection mirrors . fig1 shows an oscilloscope image of the signal received from the photo detectors . the large ‘ humps ’ 1700 are caused primarily by the change in angle as the laser scans across the arm . the amplitude of these humps will be affected by the angle at which the beam strikes the arm . a vein signal is also shown 1701 . in one embodiment , there is an array of smaller photo detectors arranged so that there is more collection area towards the outside of the detection area ( where the roll off of signal due to the curved body and the angle of the laser occurs ) and less towards the center where the reflection is more direct and intense . an example pattern is shown in fig1 . this could be implemented as a discrete photo detectors arranged in the appropriate pattern or as a monolithic semiconductor component . another technique to control the variation of reflection due to the change in laser angle across a scan line is to use specially configured lenses over the photo diodes . in this example a lens is cut from a standard fresnel lens in a pattern that increases the amount of collected light as the angle from the center of the photo diode increases thereby flattening the received signal . as shown in fig3 , a standard fresnel lens 1750 is cut in a pattern 1751 that when placed over the photo detector provides additional collection of light reflected from the edges of the scan line and then refracts that light into the photo detector . the frequency domain of the signal caused by the angle change as the laser sweeps is slightly different than the signal caused by the presence of a vein . through the use of electronic filters , well known in the art , such as switched cap filters , the impact of this signal can be reduced early in the signal processing chain , importantly prior to the vein detection circuitry . in the prior descriptions , a simplified model of the reflection of the laser light was presented . in fact , there are varying degrees of absorption of light from all of the structures illuminated including the skin , the blood vessels and other surface and subsurface structures of the body . additionally , since the body is a three dimensional structure , the range to the point on the surface being scanned varies in real time as the imaging point is scanned . for example , the curved shape of the arm would result in less returned reflection towards the edge of the arm as that surface curves away from the scanning device . the result is that these variable reflections off of these body structures add signals that must be filtered out to accurately detect the vein structure . furthermore , as the beam sweeps across the body , when the beam is at the center point of its sweep , the reflected light received at the photo detector is greater than when the angle of the beam is at its maximum deflection and therefore more light is reflected away from the photo detector . there many techniques that can be used to eliminate or cancel out these undesirable signals . the reflected signal received by the infrared photo detector is representative of both the veins and the surface topology of the patient &# 39 ; s body . put another way , the surface of the patient affects the reflected infrared signal . this is not desirable in that in most applications the user is only interested in the veins of the patient and not the surface topology . it has been observed that the short wavelength light such as blue and ultraviolet are reflected by the skin and is mainly representative of the surface topology of the patient and has no vein information contained therein . by utilizing a second coaxial laser light source at a short but visible wavelength and a second photo detector subsystem for receiving the short wavelength light reflected signal , the short wavelength light signal ( which contains information about the topology of the skin ) can be subtracted from the infrared signal ( topology + veins ) yielding a signal that is solely the veins ( topology + veins − topology = veins ). this works in that since the beams are coaxial , they will be affected by the topology of the target area symmetrically . this approach is particularly useful in a system that does not have a microcomputer for storing a complete image and for performing image processing on that image to enhance the veins ( and reject all other types of signals ) but also has benefit to a stored image system . referencing fig1 , the coaxial combination of the short wavelength and infrared laser 528 is projected on to the body surface . reflected light 530 is captured by the photo detectors 526 and 527 . detector 526 detects short wavelength light and detector 527 detects infrared light . these detection characteristics may be either a result of one of the signal modulation techniques described elsewhere herein , component selection or through the use of a filter 536 , 537 placed in the path of the reflected light . the output of the photo detectors 526 , 527 are amplified and conditioned by pre amplifier circuits 631 , 632 and then fed through the differential amplifier 534 which subtracts out the surface topology represented by the reflected short wavelength light yielding an output 535 that is primarily based on the reflected vein pattern . the simplest embodiment would use a red laser for both detection and projection as described earlier in conjunction with the short wavelength laser . as a further embodiment , a three laser system can be built to further enhance the captured and projected image . in this embodiment , three lasers are used : ultraviolet ( e . g ., 407 nm for imaging the skin topology ), visible ( e . g ., 630 nm providing the visible light for image projection ), and infrared ( e . g . 740 nm for imaging the veins ). two photo detectors are used . one is for receiving the ultraviolet , and one is for receiving the infrared light . the ultraviolet laser has absolutely no penetrating qualities into the skin and therefore the reflection very faithfully reflects the patient &# 39 ; s topology . this signal is then subtracted from the infrared signal to yield just the vein signal . this embodiment is further advantaged in that the wavelengths of the ultraviolet and infrared lasers are very far apart from each other , and therefore , there is no inadvertent signal pickup by the respective photo detectors . this implementation would operate in a substantially similar way to what was previously described for fig1 with the exception that the coaxial laser light source 528 would include three laser inputs : infrared for vein detection , ultraviolet for topology detection and a visible color for projection . photo detector 526 would be selected for ultraviolet detection characteristics and / or filtered by 536 to provide selective detection of the ultraviolet laser . many combinations of multiple lasers and detectors are possible that each provide optimizations based on the type and depth of structure being scanned for , for example adding additional visible lasers for additional projected information as described elsewhere . one goal of the photo detector design is to acquire only the desired signal such as the vein pattern without interference from the reflected light from other objects in view such as the topology of the body or ambient light . many techniques are possible . in some embodiments , a photo detector will be selected that is matched to the wavelength of the infrared laser . in another embodiment , a filter that has the ability to block all light other than the wavelength of the infrared laser can be placed in front of the photo detector so that only the infrared light passes into the photo detector . in a third embodiment , the amplitude of the laser light is modulated either in the time or frequency domain , thereby allowing the system to know which laser is being seen by the photodetectors . the third embodiment has the benefit of allowing a photo detector that is capable of detecting a broad spectrum of light ( e . g ., a photo detector that is responsive to both 638 nm laser and 740 nm lasers ). this allows a broader range of photo detector devices to be used that are selected for other desirable characteristics such as low cost , small size or greater sensitivity . as a mirror moves back and forth as it scans the laser beam it decelerates before it reaches a full stop then reverses direction and accelerates again . during some portion of the outer extremes of travel the mirror is moving too slowly for the information returned by the reflected laser to be used . in addition , the output power at these extremes is more dangerous because it is spread over a smaller area . therefore reducing or blocking laser power in these extremes helps to ensure that it stays within government mandated safety limits . furthermore , the laser current needed is proportional to the temperature of the laser . this is important in a battery powered device in that the amount of current needed to run a cooler laser is lower and therefore the battery lasts longer . in the preferred embodiment , one or more of the lasers are turned off during the unused portion at the ends of the scan lines . the benefits of this are : 1 . it saves power in the areas that are blind or unusable because of the slow movement of the mirror 2 . it reduces overall power used by the laser since it is now off a percentage of the time , reducing the temperature of the laser 3 . it extends battery life 4 . it is safer , due to less power during the slow moving portion of the scan 5 . the active area appears brighter since there is no bright edge to the pattern caused by the slow moving mirror an alternative embodiment would leave the laser on all the time , but change the size of the exit window aperture so that the brighter parts of the scan are clipped off by the window . this embodiment is safer than the preferred embodiment in that the failure mode is less likely to occur , but there is none of the power savings . there are useful benefits to the internal reflection cause by clipping the output however . these include : 1 . an internal photodiode can measure the reflected laser light for calibrating the lasers 2 . in the case of projecting an image stored in memory , convergence ( the need to know exact laser spot position between frames ) becomes critical . if the laser beam can hit an extra photodiode when it touches the shade , then that signal can be used for laser spot position sync . if the shade is also mirrored , then the extra photodiode can be placed on the top pc board , to catch the reflected beam . a further embodiment would be to proportionally reduce the power at the mirror slows so that the brightness is kept constant . this would be useful if a border demarking the edge of the image was desired or if some system data was to be displayed in this border area . in some embodiments , it is desirable to maximize the output of the laser so that a greater signal or greater penetration into the body is needed . all laser projection devices have governmental safety agency regulations dictating power output limitations . these limitations are typically expressed as a maximum output of the laser at a given distance from the eye over some period of time . therefore , a number of techniques that control power output and the time profile of the output can be used to ensure that the device meets these safety criteria . the balance between high power ( yielding brighter images or greater 3d penetration ) and safety are an important part of the design of the device . in one possible embodiment , physical barriers can be placed in the design of the product that prevents the user &# 39 ; s eye from getting close to the origin of the laser projections . if a user &# 39 ; s eye can not get close to the source of the laser , the laser power may be increased . for example , in an embodiment , protruding bars ( think of a football helmet cage ) can be placed in the direction of the optical path that prevents the user from placing an eye too close to the lasers . accordingly , the laser power can be increased . in an alternative approach , signal processing can be utilized to control the power output . by way of example , veins have a very distinctive pattern , ( e . g ., they are tubular shaped ). an embodiment can be created in which the acquired image pattern is stored in a computer memory , image processed to determine whether veins are present , and only upon confirmation of vein being present is the image projected . in this manner , the visible laser is not turned on if the unit is aimed at a user &# 39 ; s eye ( no vein pattern detected ). in a further embodiment , the power of the infrared laser can be set initially low to detect the presence of surface veins , and only after they are detected is the power of the infrared laser increased ( to image deeper veins ) and the visible laser turned on to project the vein pattern . an additional alternative method is to only turn on the device a when a proximity sensor determines the surface , or eye of a user , is a predetermined distance away from the origin of the lasers , for example an agilent hsdl - 9100 proximity detector . the power of the laser can be set so that it is safe at the threshold distance . there are many range detectors known in the art such based on optical and ultrasonic techniques that can be used in the invention . an additional alternative method is to turn the lasers on for a short duration to determine if a vein pattern is in view before turning the lasers on for an extended period to image the vein pattern . since the moving mirrors are subject to inertia , they will move more slowly towards the end of their movement than they do at the center of movement . therefore , the laser intensity over time is higher at the edges than it is in the middle . the system can be designed to manage the bright edges as follows : 1 . in some embodiments , it may be desirable to have the brighter edges since that helps demark the edge of the scan area 2 . the housing can be designed so that the exit window clips ( or blocks ) the edges of the pattern so the more intense light does not exit the device 3 . the electronics can be designed so that the amplitude of the transmitted laser is reduced near the edges 4 . the electronics can be designed so that the laser is turned off near the edges in all of these embodiments , these techniques can be applied to one or more of the lasers in the system . furthermore they can be done independently , for example , the visible laser is left on to show the border line , while the ir laser is shut off at the edges . the basic invention provides for the detection of and the projection of an image of the pattern of blood vessels directly on to the patient &# 39 ; s body . in this manner , the practitioner has a direct sense of where the veins are and where the center line of the vein is so that they may easily and accurately perform venipuncture . one intention of the invention is to be as easy to use as possible . one expression of ease of use is to ensure that the device enhances and doesn &# 39 ; t interfere with the normal work process of finding and accessing the vein . the integration of the detector and projector into a single device also improves on the crane patent . in crane , the vein enhancer implements two separate devices , one for illumination and / or trans illumination and a separate device used for detecting the low light . such a configuration is awkward and difficult to operate . in addition , having , two separate devices increases the likelihood losing one of them . several techniques can be applied to allow the user to control operating characteristics of the device such as on / off and gain . this user input is very important from both a safety and operational standpoint . the gain of the scanning system will need to be changed based on skin color and condition as well as the depth of detection desired by the operator . the gain of the projection will also need to be adjusted based on ambient light conditions and skin color and condition . 1 . a trigger or switch mounted on the handle of the device in proximity to the normal position of one of the fingers such as the thumb . such an implementation will be described later . a . a trigger or switch that has one position used for on and off b . a trigger or switch that has two positions , where the first position puts the device into an aiming mode and the second begins scanning . this type of implementation could be useful in an led or camera implementation where focal length is limited . c . a trigger or switch that has two positions , where the first position is for low gain , and therefore short penetration , and the second is for high gain . d . a trigger or switch with a single position that can be tapped multiple times to change the gain of the system 2 . a slide switch trigger , where multiple positions along its travel change settings on the device 3 . an analog trigger as in a video game joy stick , where the distance of the pull on the trigger is used to change settings of the device 4 . a pressure sensitive switch where pressure is used to change settings on the device 5 . a rolling thumb control where rolling the wheel in one direction reduces gain and the other direction increases gain 6 . any of the above implemented such that the switch stays in position when it is released and must be manually reset to an off position 7 . any of the above implemented as a dead man switch such that as soon as pressure is removed from the switch it returns to the off position . in the present invention there are described a number of novel mechanisms to automatically maintain the position of the imaged area as the practitioner moves the needle to perform venipuncture . it will be appreciated by those skilled in the art that the present invention is not limited to locating veins , arteries and other blood - rich structures and either implicitly or explicitly focused on placing a needle into the structure . there are many procedures , such as an intramuscular injection , where it is desirable not to puncture a vein . the invention can be used to avoid hitting a vein in this case . one such mechanism is to mount the imaging head on pivot - able mechanism mounted to the needle protector . the mechanism is arranged so that the force of gravity biases the projection angle at a predetermined angle to the earth &# 39 ; s surface . as the needle is moved , the field of view continues to remain at a constant angle to the surface of the earth . another mechanism would be to use electronic devices including tilt switches and / or accelerometers to monitor movement of the scanning element . a mechanism such as a switch press could be used by the practitioner to indicate that the scanner should go into a mode where it attempts to maintain the field of view on a fixed position on the body . as movement is detected , the device moves the scan area to compensate for the practitioners hand movement . several movement control mechanisms are possible . in one embodiment , positioning actuators can move the scan element in two dimensions thereby moving the imaging / projection area . in another embodiment , the internal mirror arrangement can be such that a bias is added or subtracted from the mirror &# 39 ; s travel , thereby changing where the projected image is placed . in another embodiment , a combination of both techniques can be used . in another embodiment , an engine with higher than necessary resolution for vein location can be used and a window is moved within the higher resolution space . the previous embodiment relies on the system detecting a change in its position by measuring the movement of the scan head . in another embodiment , as the image of the vein structure is captured , the system can identify unique patterns in the structure of the captured image . for example , the system could look at a cross point between two veins . in a frame to frame comparison , the change in position within the imaging field of this unique pattern can be determined and then the scan position can be moved by one of the techniques previously described so that the unique pattern is kept in a constant position within the imaging field of view . in the embodiments previously described , the projection of the image relies on repeated scanning of a visible light source over the area of the body being scanned . it is known in the art that there are materials that emit visible light when energized by a violet or ultraviolet light source . these materials can continue to emit light for a period of time , up to several minutes , after the energizing light source is removed . furthermore , these materials can be mixed into a gel , cream or liquid base so that it can be applied to the surface of the skin . in addition , the florescent material can be combined with the antiseptic that is already used in venipuncture . an embodiment of the invention can be made where a violet or ultra violet laser ( e . g ., 407 nm ) can replace the 630 nm laser . the practitioner can apply the florescent material to the surface of the skin and then the scanner can be passed over the area to scan the veins . the device uses the violet / uv laser to activate a pattern that matches the vein position on the treated skin . this embodiment is very useful and unique for several reasons . first , the image of the vein position is maintained even after the device is turned off and put away , thereby freeing both hands for the venipuncture . secondly , the size of the imaged area is now limited by the area that the florescent material is applied to , not by the projection area of the device . third , if the procedure is taking too long , the image can be reactivated by rescanning the area . still further , a three laser system can be built , comprising a visible laser for presenting the vein image and a near ir for detecting the position of the veins and a violet / ultra violet for energizing the florescent materials . all lasers are arranged to project along a single axis . without the violet / ultra violet laser turned on the system operates as described in previous embodiments . however , once an acceptable image is viewed ; the 407 nm can be energized to paint the same image as that projected by the 630 nm laser , thereby energizing the florescent material to emit the vein image . it is known in the art that there are chemical dyes that can change color by exposure to light . such a material can be substituted in the above embodiments in place of a florescent material . several control mechanisms that can be used to adjust various operating parameters for the unit are previously described . another embodiment is to use sensors well known in the art to determine distance to the body surface being scanned . for example , an irda module typically used in a laptop computer could be used to sense distance by using the amount of reflection from the ir led back to the photo sensor as a proxy for distance . these can be added to the device or in a preferred embodiment , the average intensity of one or more of the lasers already in the device can be used to approximate the distance based on the amount of light reflected . this average intensity would vary based on distance . when the scanner is close , say 6 ″, the scanning angle can be set to maximum and the ir power , signal gain and differentiation levels are set to medium . as the scanner moves away from the body , the scanning angle can be reduced in proportion to the distance . in this way , if the target were for example the arm , the scanned area would not grow as distance increases . this would prevent wasting detection area by preventing the imaged area from growing bigger than the arm . when unit is moved closer than 6 ″, the level of differentiation , and gain is increased . this is ok to do at close range but at far distances this would cause more false positives — veins would be indicated in places that they do not exist . however , at close range this will show deeper veins . this provides a very intuitive user experience . move closer — see deeper . other inventions that use fixed focal length systems and therefore must be kept at a single distance from the body cannot provide this user interface . in the system design , the photo detector can be selected or filtered so that it is responsive to the infrared laser but not the visible laser . in the manner both lasers can be on at the same time without having the visible laser couple into the photo detector . in some cases , useful attributes of a photo detector such as size or cost would make it preferable to use a photo detector which is responsive to both the visible laser and the infrared laser . in this embodiment , both of the lasers can be pulsed on and off at high rates without affecting the apparent quality of the image ( visible light projection ) or the quality of the acquired image ( the reflections of the ir laser ). by synchronizing the two lasers so that while one is on , the other is off , the image acquisition circuits ( photo diode and amplifiers ) can be arranged to only see signals from the appropriate laser . in this manner the other lasers do not interfere at all with the signal acquisition apparatus . through the use of amplitude modulation on the transmitted laser , simple filter circuits can be used in the photo detection subsystem to allow one or more laser signals to be differentiated from ambient light and from other laser signals in the system . in fig8 b , the laser output signal waveform is shown with two levels , bright 1370 and dim 1372 . for example , in a single laser system , the bright signal might be used to project and the dim signal would be used to scan . furthermore , the dim could also be an off state for the laser and this implementation would still be effective . in the photo detector subsystem , the output of the photo detector can be dc coupled so that no low frequency or dc bias signals pass through to the next stage in the circuit . in this manner , any light , including ambient light , that doesn &# 39 ; t exhibit the high frequency modulation , is not seen by subsequent stages of the circuit . another mechanism to differentiate between lasers is shown in fig8 c - 8e . in this embodiment , the lasers are amplitude modulated at different frequencies causing the reflected light received at the photo detector to also be frequency modulated . the visible laser 1380 is modulated at one frequency and the infrared laser 1383 is modulated at another . the light received at photo detector 1381 is a combination of the reflected light from both lasers . the received signal is fed through two different band pass filter circuits . the circuit at 1382 selects for one frequency and the circuit at 1385 selects for the other . therefore the signal at 1384 and 1386 are representative only of the light reflection from one of the lasers . this can be implemented in a single circuit so that only the infrared vein signal is seen or in two or more circuits where both an infrared vein signal is seen and a long wavelength topology - detection signal is received . a whole range of high pass , low pass , band pass , band block and notch filters can be used based on the technical and business needs of the specific embodiment . the system can be arranged as either a binary system or grayscale system . in a grayscale system , the infrared laser signal received by the photo detector is simply echoed and re - transmitted by the visible laser . in this manner , various levels of intensity can be shown . accordingly , the image of a vein may vary in intensity as a function of the magnitude of signal received . in a binary system , the projected image is either on or off . to determine whether the projected image should be on or off , a comparator with a trip point is placed after the photodiode . if the signal crosses the trip point the visible laser is turned on and when it falls below the trip point it is turned off . the system can set these parameters automatically based on built - in rule sets or a user input device like a dial , or push buttons , or any other means of user input could be placed on the device , and the user manually adjusts the trip point ( essentially making the device more or less sensitive .) some of the parameters that will often need to be controlled to deal with patient and environmental variability include : 2 . persistence of vein lock 3 . selection of vein size to detect 4 . working range and focus distance 5 . field of view size 6 . mirror amplitude throughout all the embodiments , when we discuss adjusting the power of a laser , such adjustment could be made by either adjusting the current to the laser , or alternatively , modulating the laser on and off at a rapid rate ( pulse width modulation or pwm ). depending upon the duty cycle , the average laser intensity will be changed . with respect to the visible laser , the human eye integrates the signal and , provided the frequency of the pwm is faster than the eye integration time , the laser will appear as if it was always on , but brighter or dimmer as the on cycle time increases respectively . the system will also need to adjust the power of the infrared laser . this can be done by adjusting the current to the laser , or alternatively , by pwm . provided that the pwm modulation is faster than the response time of the receiving means ( photodiode plus amplifiers ), the modulation will have the same effect upon the received signal as if you reduced the current to the laser . there are various methods that can be employed for creating a scanned laser pattern . in many embodiments , it is desirable for the scan pattern to be the same from frame to frame and for the system to be able to determine the instantaneous position of the lasers . such an implementation would allow time consuming processing and integration of data across frames to occur . in general however , the lower level of position precision that is required , the easier it is to produce the pattern , the lower the system complexity becomes and the lower the cost becomes . in an embodiment without image memory , since one does not need to remember the specific signal at a specific position over time , there is no need for a reproducible scan pattern . therefore , from frame to frame the laser scan lines do not need to fall reproducibly upon the scan lines of the prior frame and there is no need to know the instantaneous position of the laser . the reason one does not need a reproducible scan pattern or instantaneous position information is that the visible light is coaxially aligned to the infrared laser . the visible light is a function of the received image in real time . accordingly , whatever location is being imaged is instantaneously being projected . one such simplified modulation scanner which is well suited to this invention is amplitude modulated circular mirror . in this case a mirror is arranged to run at resonance in a circular or oval pattern . the magnitude of the circle is then amplitude modulated at a rate high enough to avoid appearance of flicker . accordingly , a scan pattern is formed which starts with small concentric circles and grows sequentially larger until reaching a limit and then collapses sequentially to the smallest circle . such a pattern has many advantages over a traditional raster scan pattern . rather than a rectangular shape which would be typical of a raster scan , this method can be used to generate circular or oval pattern shapes . the mirror in this design is always moving and the laser is always actively painting — there are no required off times as the mirrors move into position for the next scan line . the pattern can be adjusted so that it spends more time scanning near the center of the pattern so a brighter , denser , better defined image appears in the center of the scan area . additionally , the mirror operates at resonance which provides the lowest power dissipation , which is important in handheld battery operated devices . it is necessary to adjust the gain of the system during operation in order to ensure that the amount of reflected light is within the proper operating range of the photo detectors . one method of adjusting the gain is to maintain a constant output from the detection laser and adjust the gain of the photo diode amplification circuitry so as to get an appropriate signal that is neither too low for detection nor too high so that the photo detector or circuit saturates . this approach can become fairly complex due to the speed requirements of the gain adjustment . another method is to fix the gain of the photo detection circuitry but adjust the power output of the ir laser so that an appropriate signal is output from the photo detection circuitry ( once again not to low or saturated ). it is much easier to design circuits that adjust the ir laser due to the extremely high modulation bandwidth of the lasers . as previously discussed , the laser can be adjusted either by analog or digital means . a laser must be calibrated in that its intensity is sensitive to ambient conditions such as temperature . some laser diodes have internal mirrors to perform the calibration . an alternative technique is to use the housing of the scanner to block a portion of the light , perhaps an outer scan line and reflect that light back to the photo detector . that reflected light can be used for calibration . in some embodiments of the invention , the system will have a microprocessor and memory buffer so that the reflected light from the scanning laser will be kept as a representation in memory . by averaging the image over multiple scans , the system can form an image with greater resolution than it could have by only using a single pass of the laser . in order for this to be done , the system needs to ensure that the image elements being captured from scan to scan represent the same physical location on the patient . the benefit to the system design is that the gain of the photo detector and subsequent analog circuits can be reduced . there are several ways to do this . one is to provide a mechanical stabilization , similar to what was described for the led implementation ( fig1 ). many techniques for mechanical , analog and digital image stabilization are known in the art and can be applied to this invention such as best fit correlation . for example , you can identify a specific point or a group of points within the image in a single frame , for example the cross point between two veins . the system can then adjust the position of the image from frame to frame so that the image elements averaged together represent the same position on the body . since veins are linear structures , a novel technique can be used to accurately identify veins and to separately highlight one or more veins and ignore others without using image memory or signal processing techniques . referring to fig1 , a schematic representation of an arm 1809 , is shown along with a simplified pattern of veins 1802 / 1814 . as shown , veins are roughly linear structures . normally , depending on the part of the body the practitioner is attempting vein access , only veins that are oriented in a single direction are typically used to administer medicine or draw blood . for example , on the arm , the veins that run along the long axis of the arm are typically used . therefore scanning that favors vein detection along that axis is desirable . a series of scan lines are shown 1806 , 1810 and 1813 . each scan line occurs sequentially in time with 1806 first , 1810 second and 1813 last . this technique relies on the fact that once a vein &# 39 ; s position is found on a scan line , an assumption can be made where the vein is likely to be on a subsequent scan line . the vein signal can be expected to occur within a small distance to the right or left of the position seen on the previous scan line . therefore the system can apply a windowing technique wherein vein signals that occur outside the window are given a lower priority or are ignored completely referring to fig1 , a signal diagram to show the windowing approach is provided . 1804 , 1808 , and 1812 are the reflection signals from scan lines 1806 , 1810 and 1813 respectively . in this drawing , a high signal represents greater absorption of the laser light at that point on the body . 1807 , 1811 and 1813 are the “ windows ” calculated based on 1804 , 1808 and 1812 respectively . in this drawing , when the window signal is high , detection occurs , when it is low , no detection occurs . the signal 1800 is caused by vein 1814 and signal 1801 is caused by vein 1802 . this simplified example is for a system that is designed to only show the single largest vein in the field of view . by using a system capable of keeping track of multiple windows , multiple veins could be tracked . alternatively , the sense can be inverted and the vein within the window could be ignored . vein 1802 is selected as the vein of interest by some criteria , set in the system or by the user , such as size of vein or the central location of the vein in the field of view . based on the vein &# 39 ; s position as detected by the pulse 1801 on the reflection signal 1804 , a window signal 1807 is created that ignores vein reflections that occur outside of the detection window 1805 on the next scan line 1810 / 1808 . referring to signal 1808 , vein 1814 is ignored since it falls outside the window and vein 1802 is detected since it falls within the window . however , since the vein is traveling at an angle with relation to the scan pattern , the vein is now offset within the window . in order to track the vein on subsequent scan lines , the system now re - centers the window 1811 so that when it is applied to the next scan line 1813 / 1812 , the vein falls within the window . this process repeats for the entire field of scanning . a user interface can be implemented allowing the user to select a number of veins to detect simultaneously and to switch focus from vein to vein . also , the user could control the width of the window to optimize the detection of the vein . additionally , the user can turn this feature on and off so that they can either see all veins or just a specific vein or veins . since there is inherent directionality to the procedure , the user can rotate the scanner to see only those veins at a particular orientation . in fig1 through 22 , an embodiment of the device is presented . this implementation uses two lasers , one infrared and one red . the lasers are made coaxial through a series of bounce mirrors and are combined by a dielectric mirror . two moving mirrors are used to move the beam in a raster pattern which then exits the engine and strikes the patient &# 39 ; s body . the collection path includes two spatially separated photo diodes . the electronics use an analog , real time approach whereby the detection of a vein causes an immediate reduction in the projected visible light at the point at which the vein is detected . the operator sees this pattern of dark lines directly on top of the position of the veins . referring to fig1 , the scanning engine is shown as an assembly including a detector deck 1004 , an optical deck 1005 and a circuit board 1006 . both mechanical and electronic parts are mounted on these boards . the engine is oriented so that the laser scanning pattern 1000 projects perpendicular to the boards through an orifice in the detector deck 1004 . the photo detectors 1001 - 1002 are aimed along the same axis so that they have a clear view of the reflected light . in fig1 , the visible laser diode 1015 and infrared laser diode 1019 are arranged for best fit within a miniature form factor of the engine and therefore rely on a series of bounce mirrors to realign the beam . both laser diodes are mounted to holder assemblies 1023 / 1024 and heat sinks 1016 / 1018 . proper thermal management of the diodes extends their working life and increases the reliability of the engine . an optional connector 1017 is mounted to the side of the engine to allow it to be used in an embodiment of the device that allows the scan head to be removed from the portable handheld device and mounted on an alternative base such as a tabletop stand . the detector deck 1020 is a printed circuit assembly that holds the photo detectors 1021 / 1022 as well as other electronic components necessary for the operation of the engine . for example , the pre - amplifier circuitry for the photo detectors will typically be mounted in close proximity to the detectors 1021 / 1022 so that noise in the system is minimized . the photo detectors 1021 / 1022 are shown with integrated dome - shaped lenses to increase sensitivity in the direction of the reflected laser . various schemes both with and without lenses can be implemented in engine embodiments . in addition , filters can be placed in front of the photo detectors so that the wavelength of light they respond to can be specified . in fig1 a - c which is an illustrative example , several views of the bounce mirror assemblies are shown . since the intent of the design is to make two or more laser beams coaxial , proper alignment is critical . shown is one of the exit windows from the laser diode 1038 with the beam 1037 striking the mirror 1040 thereby reflecting the beam into the new desired orientation 1042 . the mirror is held in position by an adjustable holder 1041 . the holder assembly 1041 is comprised of a fixed platform 1031 that is fastened to the optical deck in a fixed manner . the mirror 1032 is attached to a wedge 1034 that is angled in the desired manner to reflect the beam in the appropriate direction . the wedge is fixed to a floating deck 1033 which is attached to the fixed platform 1031 through a number of screw 1035 and spring 1036 assemblies . the spring 1036 is placed around the screw 1035 and is compressed by the two platforms 1033 / 1031 so that the springs provide a constant force against the two platforms ensuring that they are held as far apart as the screws will allow . the screws ( e . g ., 1039 ) pass through an unthreaded hole in the floating deck and into a threaded hold in the fixed platform 1031 . by tightening or loosening the screws , the decks are moved closer or further apart . through the use of multiple screws , several degrees of freedom of adjustment are obtained , thereby allowing the beam to be properly aligned along the desired path . in this design , three of these bounce mirror assemblies are used . this design uses mechanical screws to fine tune the position of the mirrors and in practice would be locked in place once positioned with an adhesive material such as locktite . high volume configurations of the product could use robotic assembly and the mirrors would be positioned and then welded , epoxied or glued into place eliminating the cost and complexity of the screw / spring assembly . referring to fig2 , the path of the laser beams are shown . many parts have been removed from the diagram to allow the beam path to be easily seen . the laser diode 1080 emits a beam 1081 which strikes the angled mirror and is reflected along path 1083 which then strikes the dielectric mirror 1084 . the mirror &# 39 ; s characteristics are selected so that this beam passes through mirror 1084 and exits along path 1085 . the second laser 1088 emits its beam along path 1089 which then is reflected off of mirror 1090 along path 1091 . the beam 1091 strikes the dielectric mirror 1084 which as been coated to reflect the wavelength of light emitted by laser 1088 . therefore , the beam is reflected along path 1085 . at this point the two lasers are now coaxial . the beams 1085 are reflected off of mirror 1086 and are reflected along path 1087 so that it strikes the moving mirror that is part of assembly 1087 . this fast - moving mirror is oriented to provide the x - axis scanning . the light is reflected onto the mirror in assembly 1092 which is a slower moving mirror that provides the scanning in the y - axis . in this diagram , the resulting scanned beam pattern exits out towards the back of the drawing . in fig2 , which is an alternative view of the previous drawing , the scanned laser beam exit pattern 1095 is seen more clearly . in fig2 , additional novel features of the design are seen . the laser diode mounting bracket 1152 , is a split ring design . the screws 1159 pass through unthreaded holes in the bracket 1152 and into threaded holes on the optical deck 1160 . by tightening the screw on the split side of the bracket 1152 , the laser diode assembly 1158 is compressed and held in place . this allows the position of the diode to be locked in both an in / out orientation and in rotation . locking the rotation position is critical in designs that use the laser &# 39 ; s polarization rather than wavelength for beam alignment . the engine uses extensions 1153 , 1155 , 1157 on the circuit board to provide mounting features so that the entire engine assembly can be firmly mounted into a housing . the extensions could also have been on the detector deck or optical deck or on one or more of the mechanical components of the engine . holes such as 1154 are provided so that either a screw or a boss can be used to align and hold the engine in the housing . the extensions can be held in place with screws or by captivating them in a feature of the housing . the extensions can be made in a range of shapes so that they do not interfere with features in the housing . for example , the notch 1156 is designed so as not to interfere with a boss in the housing . in the current design , the high speed mirror 1111 is implemented with a texas instruments talp3400 and the low speed mirror 1111 is implemented with a texas instruments talp4500 . the red laser diode 1111 is a sanyo dl - ls 1148 and the infrared laser diode is a sanyo gh0781ja2c . the laser lens 1111 is a thorlabs , inc . 350150 - b and the photo diodes 1111 / 1111 are hamamatsu s6968 - 01 . referring to fig2 , one embodiment of a portable handheld vein scanner based on the engine described previously described . it will be appreciated that this device is just one example of the design of the present invention and that the shape and features can be altered to fit the end user &# 39 ; s needs while still employing the teachings of the present invention . this embodiment is typically a two piece design with a detachable head 1605 connected through a friction fit ; a snap on mechanism or other suitable means to a handle 1606 . the buttons 1610 , which are on both sides of the handle , are designed so that when they are pressed , latches that hold the scan head and the handle together are released and the user can separate the two pieces . screw holes 1600 on both sides of the handle are provided along with matching internal bosses in the scan head allow the handle and head to be permanently attached should the deploying organization wish to prevent the separation of the parts . the handle is composed of a top housing 1608 and a bottom housing 1609 that are snapped and screwed together to form a single unit . the battery door cover 1607 completes the handle package . this door cover 1607 is designed to be removed by the user with the latch 1607 . there is also provision for a screw hole in the battery door and a matching hole in the inner housing should the deploying organization wish to prevent the end user from accessing the battery . in the top portion of the handle , two led openings are provided 1603 , 1604 . these are illuminated by leds on a board inside the handle and provide important status information to the user . the openings at 1603 and 1604 can be filled with a light pipe or pipes to bring the light up to the top surface and can be covered either with a molded light pipe or with a label that fits into the opening at 1612 . an inset area is provided at 1602 that allows for a label to be positioned providing a company logo , a product model identifier or other user viewable indicia . since the top and bottom are separable , it may be desirable to repeat identical or other labeling information on the handle part as well . additional labels can be placed on the inside of the battery door , battery compartment or on or near the scanner opening on the other side of the scan head 1605 . as seen in the engine design discussions , thermal management of the laser is critical to minimizing power consumption and life of the laser . therefore , openings 1601 are provided on both sides of the scan head to allow convection cooling of the scan engine . in certain embodiments , it might be desirable to have a fully sealed unit . in this case , the openings will be eliminated and other techniques well know in the art will be used to cool the lasers . for example , the heat sinks on the engine can be continued on the outside of the housing . views of the handle 1620 separated from the head 1621 are shown in fig2 . 1630 / 1631 are the matching screw holes for the optional screws 1600 . these holes are designed to engage the threads on the screws . the holes 1627 / 1628 line up with these holes and do not engage the threads , but are designed so that the screw heads apply pressure against the head and handle thereby keeping them connected . further screw holes are seen at 1634 , 1633 , 1632 that hold the top and bottom plastic pieces of the scan head together . internal mating bosses are provided in the lower half of the scan head housing . mating latches 1626 / 1625 and holes 1623 / 1624 hold the scan head and handle together . the latches 1625 / 1626 are internally sprung so that when the buttons 1610 in fig2 are not pressed , they captivate the outside edge of the slots 1623 / 1624 . when the buttons 1610 are pressed , they no longer engage the slots 1623 / 1624 . two mating electrical connectors 1635 and 1622 are provided so that the battery , switch and other electronics in the handle 1620 connect to the electronics in the head 1621 . a shoulder 1637 and a matching inset 1636 are provided to ensure proper alignment of the connectors as the head and handle are separated and re - connected . in fig2 , the head and handle are shown attached . a trigger that allows the user to control the operation of the scanner is shown at 1655 and 1662 ( see fig2 ). this trigger is molded as part of lower housing 1653 and internally comes in to contact with an electrical switch . the hinged part of the lower housing that forms the trigger 1655 is designed so that it has an appropriate level of force so that the user doesn &# 39 ; t accidentally trigger the unit but doesn &# 39 ; t have to press to hard either . the mating electrical switch is selected so that the user gets positive tactile feedback of the switch closure . the lenses for the photo detectors are shown at 1650 . they are aligned in the same plane as the emitted laser path 1651 so that they can pick up the reflected light from the target area . in fig2 , the photo detectors 1660 / 1663 are shown arranged around the laser exit window 1661 . fig2 a is shown with the lower housing of both the handle and the head removed fig2 b showing the position of the scan engine 1670 , the paired electrical connectors 1674 and the electrical switch 1671 that were described earlier . a pcb 1676 is show holding the switch , the leds and the connectors 1674 previously described . a second pcb that mates to the battery connectors is at 1673 . the battery door spring mechanism is shown at 1675 . the loop in the mechanism provides force in the forward direction ( towards the head ) thereby engaging the latch . a second view of the door and the latch mechanism is shown in drawing 27 b with the tongue 1697 that engages the handle top housing 1698 and the clip on the latch 1700 that engages the handle top housing at the other end of the battery door . one of several screw bosses 1695 is used to connect the top and bottom halves of the housings . furthermore , an alignment standoff is shown at 1699 . referring to fig2 , which shows the cavity / rear housings of both the head 1685 and handle 1686 , several additional details are revealed . bosses 1691 and 1687 provide mounting for the mounting tabs on the scan engine described earlier . these can be secured with screws or can be captivated between the two halves of the housing . an alternative design could captivate the engine in shock absorbing materials to increase the ruggedness of the device . further detail of the spring latch mechanism described earlier can be seen at 1688 and the contact point / stud for the electrical switch from the trigger is shown at 1690 . ribbing that performs the multiple function of strengthening the housing and locating the battery is shown at 1689 and 1692 . referring to fig2 , a block diagram of the invention is presented . the electronics system 1747 can be based on discrete electronic components or can have one or more microprocessors and memories 1748 . in this embodiment , a small processor with on chip memory is dedicated to housekeeping functions including laser calibration , proximity sensing , and other system control and setup functions . additional processing and memory components can be added to perform higher level functions like image - based vein detection . in this embodiment , a raster pattern is implemented . a mirror drive subsystem 1738 / 1733 is controlled 1738 / 1735 by the electronics to drive the x mirror 1740 at a higher speed than the y mirror 1734 to create the raster pattern . the electronics will control mirror on and off , and the mirror will report back when it begins its scan . the mirror drive systems 1739 / 1733 provides the drive waveform to the mirrors 1740 / 1734 that cause them to oscillate at the proper speed and in synchrony . this consists of sine wave to the mirrors . the drive circuitry also contains detection circuitry that uses a feedback path 1737 / 1736 from the mirrors to detect that the mirrors are in motion . in this manner , if a mirror has failed to move , the engine can shut down the lasers to ensure user safety . the lasers are also controlled by the main electronics 1747 through a set of drive circuits 1746 / 1742 . these circuits provide the ability to set the intensity of the lasers 1744 / 1741 from off through maximum intensity . in this embodiment , the lasers contain internal mirrors for calibration and which are read back from the lasers 1745 / 1743 and through the drive circuits 1748 / 1750 into the main electronics . the reverse path is used to control the drivers and lasers . in this embodiment , a proximity sensor 1725 to detect that there is a surface within working range . the main electronics reads 1729 the sensor to ensure that the lasers are not turned on if there is an object either too close or no object within proximity of the front face of the scanner . the photo detection subsystem consists of a pair of photo diodes 1727 and an amplifier 1726 that is fed through 1730 the main electronics for vein detection . a control for setting gain is provided through 1730 . since this is a portable device , power is provided from a battery 1731 , which provides 1752 power to a control circuit 1732 which provides voltage regulation and delivers 1751 the appropriate voltages to the electronics

US-201414323259-A

a rollerskate carrier is disclosed , including an extensible member having flexible wheel retainers which , subsequent to an initial positioning of the member , permits a pair of rollerskates to be quickly and conveniently inserted and removed from the carrier in a single manual motion . the carrier is lightweight and fully adjustable , thereby accommodating virtually all wheel sizes and rollerskate styles .

referring to fig1 there is shown a rollerskate carrier 10 of the present invention composed generally of a base member 12 and an extensible member 14 , which cooperate with one another to mount a pair of rollerskates ( indicated by phantom lines in fig1 ) in a substantially vertical orientation . the base member 12 is preferably fabricated having an inverted t - shaped configuration formed by a horizontal plate portion 16 and an upright or vertical sleeve portion 18 , positioned midway along the length of the plate portion 16 . as is apparent from fig2 the upright portion 18 segregates the base member 12 into two sections or sides which are mirror images of one another . thus , hereinafter , the description of one section of the carrier 10 pertains equally as well to the other section . the horizontal portion 16 of the base 12 is provided with plural wheel blocks 20 , each located adjacent the distal corners of the horizontal portion 16 . the wheel blocks 20 are spaced from the upright portion 18 of the base 12 and include an inclined inboard surface 22 . as will become more apparent infra , the spacing of the blocks 20 from the upright portion 18 , as well as their inclined surfaces 22 , permit the carrier 10 to accommodate differing wheel diameter sizes and to self - register the rollerskates upon the carrier 10 . the upright portion or sleeve 18 of the base 12 is formed in a rectangular tube configuration , preferably being integrally formed with the horizontal portion 16 at its lower - most end . the interior dimensions of the upright portion 18 are sized to slidingly receive the lower end of the extensible member 14 , thereby permitting the member 14 to be telescoped toward and away from the base 12 . as best shown in fig1 and 3 , the extensible member is formed in a generally rectangular configuration , having a relatively thin central web portion 26 and an increased thickness flange portion 28 extending about its periphery . an elongate vertical slot 30 is located centrally within the web 26 , having raised side walls 32 extending on opposite sides thereof , having a height which is equal to or slightly less than the thickness of the peripheral flange 28 . a pair of wheel retainers 36 are integrally formed on the extensible member 14 adjacent its upper end . the retainers 36 are laterally spaced from one another and extend in a generally horizontal plane on opposite sides of the member 14 to reside over the base 12 . each of the retainers 36 includes a concave - shaped tip 38 at its outboard end . the wheel retainers 36 are strengthened at their inboard ends by plural support braces 42 , which are integrally formed with the web 26 of the extensible member 14 . the web 26 of the extensible member 14 preferably protrudes outward beyond the peripheral flange 28 in a localized area beneath the wheel retainers 36 , forming extensions 40 adapted to accommodate unusually wide wheel tracks of particular rollerskates . an opening 43 is additionally provided adjacent the upper end of the extensible member 14 to form a handle , thereby permitting the carrier 10 to be readily grasped and transported by a user . as best shown in fig3 the base 12 and extensible member 14 are assembled together by use of a fastener assembly , designated generally by the numeral 50 . the assembly 50 includes a threaded bolt 52 having a square shank portion 54 , adjacent its head , a star - shaped lock washer 56 , a bearing washer 58 , and a wing nut 60 . the bolt 52 is sized to be inserted within a pair of aligned apertures 62 and 64 , centrally located adjacent the upper end of the upright portion 18 of the base 12 . as shown , one of the apertures 62 is formed having a square configuration sized slightly larger than the dimensions of the square shank portion 54 of the bolt 52 . with the extensible member 14 inserted to reside within the upright portion 18 of the base member 12 , the bolt 52 may be inserted through the aperture 62 to extend through the elongate slot 30 , formed in the extensible member 14 . the lock washer 56 may then be positioned within the interior of the upright portion 18 to be aligned with the aperture 64 and abutted against the outboard edges of the raised side walls 32 of the elongate slot 30 . the bolt 52 is then inserted through the lock washer 56 and aperture 64 to extend outward a short distance on the opposite side of the upright portion 18 . completely inserted , the square shank 54 portion of the bolt 52 is tightly received within the square aperture 62 , formed on the upright portion 18 , thereby preventing rotation of the bolt 52 and the bearing washer 58 and wing nut 60 may be manually mounted to the bolt 52 in a conventional manner . by such a fastening arrangement , it will be recognized that , with the wing nut 60 loosened , the extensible member 14 may be freely telescoped vertically within the upright portion 18 . the extensible member 14 may then be selectively locked in place by tightening the wing nut 60 , thereby causing the lock washer 56 to tightly grip the raised side walls 32 of the elongate slot 30 . while the structure defined , the initial adjustment of the rollerskate carrier 10 of the present invention , to accommodate a pair of rollerskates , may be described , with specific reference to fig1 and 2 . initially , the wing nut 60 is slightly loosened and the extensible member 14 is raised vertically to a maximum elevation . as will be recognized , the extensible member 14 is prevented from being completely removed from the base 12 during this lifting movement , by the abutment of the bolt 52 with the lower end of the elongate slot 30 . the rear wheels of each of the rollerskates ( indicated by the phantom lines ) are then placed upon the base 12 between a respective pair of wheel blocks 20 and the upright portion 18 . due to the inclined surface 22 of the wheel blocks 20 , which , in the preferred embodiment , is approximately 40 degrees from vertical , the wheels of each of the rollerskates are biased inwardly or registered against opposite sides of the upright portion 18 . further , varying diameter size wheels are readily accommodated upon the inclined surface 22 of the wheel blocks 20 , with the larger or smaller wheel diameters merely being spaced at a shorter or longer distance vertically above the top surface of the horizontal portion 16 of the base 12 . subsequently , each of the rollerskates may be pivoted about their rear wheels to assume a generally parallel orientation with the extensible member 14 , whereby the front wheels of each skate contact the central web 26 of the extensible member 14 . variations in the track width of the front wheels is readily accommodated by the extending sections 40 , such that the front wheels of each of the skates tangentially contact the web 26 along a single abutment line . with the rollerskates maintained in this position , the extensible member 14 is telescoped downwardly , causing the wheel retainers 36 to engage or contact the front wheels of each of the rollerskates . as is evident in fig . 2 , the length of the wheel retainers 36 is preferably formed to extend outboard a short distance beyond the vertical center line of the front wheels , such that the concave tips 38 of the retainers 36 extend about a sufficient portion of the wheel circumference to urge the wheels tightly against the web 26 of the extensible member 14 . the downward pressure exerted during this lowering of the extensible member 14 should be firm enough to tightly press the front and rear wheels of the rollerskates between the base 12 and retainers 36 , yet not be of such a magnitude to cause the retainers 36 to flex or distort substantially upward . subsequently , the wing nut 60 may be manually tightened , causing the position of the extensible member 14 , relative the base 12 , to be fixed , and the pair of rollerskates to be maintained upon the carrier . with the pair of rollerskates mounted to the carrier in such a manner , the carrier may be easily grasped by use of the handle opening 43 and conveniently transported by the user . to eliminate the possibility of accidental slippage of the rollerskates from the carrier during transport , the surface of the carrier at the area of contact with the skate wheels is preferably roughened to increase frictional forces . further , due to the telescoping extensible member 14 , the carrier may be readily adjusted to accept all conventional sizes and styles of rollerskates . it is an important feature of the present invention that , once the carrier 10 is preadjusted to accommodate a particular pair of rollerskates in the manner previously described , the rollerskates may be selectively removed and remounted upon the carrier 10 without any additional adjustments . this specific feature is made possible by the construction and configuration of the wheel retainers 36 and the extensible member 14 , which flex or deform in response to a moderate , manually applied horizontal force to selectively release and engage the front wheels of the rollerskates . the detailed operation of the selective flexing of the wheel retainers 36 is schematically illustrated in fig4 . with the rollerskates mounted upon the carrier 10 , the user may remove the rollerskates by simply applying a moderate horizontal outward force ( in the direction indicated by the arrow o in fig4 ) to the upper portion or toe of the rollerskate . because the extensible member 14 is fixed relative to the base 12 , this applied force is resisted primarily by the resiliency of the wheel retainers 36 and extensible member 14 . further , since the inboard end of the wheel retainers 36 are strengthened by the support braces 42 , the wheel retainers 36 are weaker at their distan ends , i . e ., at their concave tips 38 . thus , as the magnitude of the applied horizontal force overcomes the resiliency of the retainer tips 38 , the tips 38 flex or deform a short distance upwardly , as indicated by the phantom lines in fig4 . during this upward flexing , the front wheels of the rollerskates rotate about their respective bearing axes ( not shown ) and travel horizontally outward beneath the retainers 36 . when the vertical center line of the wheels travel beyond the end of the tips 38 , the front wheels of the rollerskates are released from the carrier 10 and the rollerskates may thus be lifted off the wheel blocks 20 and be completely removed from the carrier . as such , each of the rollerskates may be conveniently removed from the carrier 10 in a single , manual , horizontal pulling motion which causes the wheel retainers 36 to flex upward and release the rollerskates therefrom . alternatively , the rollerskates can be remounted upon the carrier 10 by simply placing the rear wheels of the skates upon the wheel blocks 20 and pivoting the rollerskates upward so that the front wheels contact the tips 38 of the wheel retainers 36 . a moderate inward horizontal force may then be applied to the toe portion of the rollerskates ( in a direction opposite to the arrow o in fig4 ), causing the front wheels to cam against the tips 38 of the wheel retainers 36 . when the magnitude of this inward horizontal force exceeds the resiliency of the tips 38 , the retainer tips 38 flex or deform upwardly ( as indicated by the phantom lines in fig4 ) and permit the front wheels to rotate about their bearing axis and travel inwardly toward the extensible member 14 . when the front wheels abut the web 26 of the extensible member 14 ( as illustrated by the full line position in fig4 ), the tips 38 of the wheel retainers 36 return to their unstressed or relaxed position . in this relaxed position , the tips 38 engage a portion of the circumference of the front wheels to securely bias the skates downwardly and inwardly upon the carrier 10 . therefore , as in the removal process , the rollerskates may be rapidly and conveniently remounted upon the carrier 10 in a single , inwardly directed horizontal motion . it will be recognized that , during the removal and remounting of the rollerskates upon the carrier 10 , the application of the manually applied horizontal force upon the tips 38 of the retainers 36 , generates a moment force m adjacent the intersection of the wheel retainers 36 with the extensible member 14 . due to the relative thinness of the web 26 of the extensible member 14 , this moment force m causes the upper portion of the extensible member 14 to flex slightly inward in the direction of the arrow f in fig4 . this inward flexing of the top portion of the extensible member 14 is advantageous , in that it decreases the distance by which the tips 38 of the wheel retainers 36 need flex during the remount and removal operation . as such , the wheel retainers 36 are not subjected to severe stresses which could cause structural failure or fatigue during repeated operation . further , it will be noted that , because the wheel retainers 36 continuously bias the rollerskates downwardly against the base 12 and inwardly against the extensible member 14 , any minor dismounting force applied to the skates during transport is resisted by the wheel retainers 36 to maintain the skates upon the carrier 10 until such time as the user purposely removes them . thus , in summary , the present invention provides a significant improvement in rollerskate carrier devices which requires only a single , convenient adjustement to accommodate differing sizes and styles of rollerskates and wheels . further , once initially adjusted , the rollerskates can be conveniently removed and remounted upon the carrier 10 with a single , manual snapping motion , without the need for further adjustment or use of specialized tools . those skilled in the art will recognize that the present invention may be readily adapted to carry multiple pairs of rollerskates and include other base plate designs , without departing from the spirit of the present invention .

US-11000180-A

methods and apparatus monitor health by detection of sleep stage . for example , a sleep stage monitor may access sensor data signals related to bodily movement and respiration movements . at least a portion of the detected signals may be analyzed to calculate respiration variability . the respiration variability may include variability of respiration rate or variability of respiration amplitude . a processor may then determine a sleep stage based on a combination bodily movement and respiration variability . the determination of sleep stages may distinguish between deep sleep and other stages of sleep , or may differentiate between deep sleep , light sleep and rem sleep . the bodily movement and respiration movement signals may be derived from one or more sensors , such as non - invasive sensor .

fig1 is a diagram illustrating a use case scenario for the system . the sensor , processing and display means are all embodied in one unit , 100 . in this case , the sensing modality is totally non - contact , and operates through the means of transmitting electromagnetic waves towards the subject . the device is configured to be sensitive to movement within a distance of 1 . 2 m , but does not detect movement from more distant objects . this ensures that interference from a second person in the bed or nearby moving objects such as fans is minimised . in one embodiment the radiation used is in the microwave range , in which the sensor is of the type described in u . s . pat . no . 6 , 426 , 716 , the full contents of which are incorporated herein by reference . in another embodiment , the radiation is in the form of narrow virtual transmit pulses synthesized by differencing long - duration staggered pulse repetition interval ( pri ) transmit pulses . such a sensor is described in u . s . pat . no . 7 , 952 , 515 , the full contents of which are incorporated herein by reference . in the cases where these radio - frequency based sensors are used , they will produce so - called quadrature signals i and q which represent the detected movement observed from positions 90 ° apart in the phase space of the transmitter . an advantage of this approach is that it can help determine the direction of movement , and also smooth out the overall sensitivity of the system . fig2 shows the overall process and processing means used by the system . the sensor acquires at least one signal 200 which represents the movement of the body . in general , this movement will include components due to breathing effort and non - respiratory movements such as turning over , twitching , or adjusting position etc . such signals could be provided by a radio frequency bio - motion sensor , but could also be acquired by one or more respiratory inductance plethysmography , by pressure sensors embedded in a mattress , by a bioimpedance measurement system , by an end - tidal co2 respiratory monitor , by an ultrasonic sensor , or by an optical sensor . the first step of processing is to determine whether a person is present or absent using the presence - absence detector 201 . the means for determining presence or absence can be through measurement of the amplitude of the signal ( e . g ., the root mean square value of the signal ) or could involve more complex processing such as determining the spectral content of the signal relative to the expected noise floor of the sensor ( s ). in one embodiment the processing is performed in a manner as described in wo2007 / 143535 , the full contents of which are incorporated herein by reference . in another embodiment , periods of movement can be determined by taking the arctangent of the quadrature i and q signals mentioned above . in this case , the resulting signal will be related directly to the displacement of the object being observed , if normalization and phase unwrapping is correctly carried out . given the displacement signal , presence - absence can then be determined by seeing if the energy in the displacement signal is greater than a set threshold . the output of the presence - absence detector stage of processing will be a sequence of epoch labels such as “ aaaappp ”, where “ a ” is absent and “ p ” is present , and an epoch may represent a fixed period of time such as 30 seconds . the signal is then fed to a movement detector 202 which determines whether movement is present ( typically on a shorter time scale such as 1 second ). a means for determining movement may be through counting level - crossings of the signal , or by measuring the high frequency content of the signal . the detailed methodology of such measurement is described in wo2007 / 143535 . each second can then be associated with movement or non - movement . the outcomes of each 1 - second movement detector can be combined into an epoch - based activity count 203 . for example , if an epoch is 30 seconds , and each 1 - second period within an epoch has movement , then the overall activity count for that epoch is 30 . the amplitude of the movement detected can also be included in the activity count metric . based on the activity count , the sleep wake determination means 204 assigns labels based on the level of the activity count ( for example , an activity count greater than 20 may be considered as a wake epoch ). the activity counts of surrounding epochs may also be considered in making this determination . the post - processing rules 205 can be further used to enhance the accuracy of the sleep / wake determination , by for example removing single isolated epochs of sleep surrounded by wake . the overall output of the post - processing rules will be a sequence of labels ( which can combine the information from the presence /. absence detector ) which may look like ; “ aaaawwwwwssssss ”, where “ a ” is absent , “ w ” is wake , and “ s ” is sleep . in parallel to determining the sleep / wake status , further processing is used to determine the sleep stage . the respiration analysis block 206 is used to enhance the respiration signal , for example by filtering the raw signal using a low pass filter . using the information from the movement detector 202 , the respiration analysis may also label certain sections of signal as being too heavily contained by movement signals to provide reliable respiration rate estimates . the respiration rate calculation 207 is used to determine the breathing rate of the person , for example in breaths / minute or in hz . the respiration rate can be calculated using a power spectral density estimate , or by using an auto - regressive model of the signal . the detailed methodology of such calculation is described in wo2007 / 143535 . the calculation provides estimates of the respiration rate for example on a per - epoch basis , or alternatively on a shorter time scale ( e . g ., once / second ). these respiration rates are provided to the sleep stage determination means 208 which uses the respiration rates to determine sleep stage . in one embodiment , the respiration rate is used to distinguish deep sleep ( stage n3 ) from all other stages of sleep ( n1 , n2 and rem ). the relative amplitude of respiration can also be determined . for explanatory purposes , fig3 shows the output of the respiration rate block 207 from fig2 . in this , it is shown how the signal can be considered in epochs ( 30 seconds in this case ) and how each epoch could have a single respiration rate associated with it . this respiration rate is the rate associated with the maximum power spectral density of the epoch . the epochs can be labelled sequentially as epoch n , n + 1 , etc . for example , in this case epoch n − 5 might have a rate of 15 breaths / minute , n − 4 might be 14 . 5 breaths / min , etc . also , as an illustrative point , the respiration analysis block 206 might deem epoch n − 1 to have such large movement that it cannot supply a reliable respiration rate . in such cases , the epoch rate might be labelled as “ unavailable ” or “ not a number ”. fig4 shows in more detail a specific embodiment of a sleep determination means 208 from fig2 . the general principle of operation is to determine sequence of epochs where the respiration rate is quite stable . the set of sleep / wake labels for an entire recording is provided to the algorithm . the algorithm is initiated by assigning ( 301 ) the variable “ current epoch ” to be the first epoch in the series . . the system decides whether the current_epoch has a high amplitude signal ( representing good signal quality ). if the signal quality is good , then the algorithm can be very confident in the estimate of respiration rate . in this embodiment , an average signal amplitude of & gt ; 40 mv ( steps 302 , 303 , 304 ) is indicative of a high quality signal , and in this case we will use a stability threshold of 0 . 5 breaths / minute . for situations where the signal is lower quality we use a more tolerant limit of 1 . 5 breaths / minute for the allowed respiration rate variability . the algorithm then calculates ( 305 - 308 ) the respiration rate range by finding the minimum and maximum value of all the epochs &# 39 ; respiration rates between the current_epoch and the last epoch labelled as light_sleep . for example , if the last light_sleep was epoch n − 6 with a rate of 14 . 2 bpm , and the epochs [ n − 5 , n − 4 , . . . , n ] had rates =[ 14 . 4 , 14 . 8 , 15 . 1 , 14 . 9 , 14 . 7 , 14 . 6 ], then the breathing rate range is ( 15 . 1 - 14 . 4 )= 0 . 7 breaths / minute . if this breathing_rate_range is less than the stability threshold , then the current epoch is labelled as deep sleep ( 308 ). alternatively , if the breathing_rate_range is larger than the stability threshold , then the current epoch is labelled as light sleep ( 307 ). since very short sequences of deep_sleep are relatively uncommon , the algorithm also excludes ( 309 , 310 ) cases where there is a run of four or less deep sleep epochs . this is done by checking the current sequence length of the deep_sleep prior epochs when a light_sleep epoch is encountered . if there are four or less preceding epochs of deep_sleep encountered since the last light_sleep epoch , these epoch labels are converted ( 310 ) to light_sleep . since this condition makes it impossible to finish with deep_sleep count of less than 5 , in such a case by default the algorithm accepts ( 311 - 313 ) the wake or sleep labels for the last four epochs ( with sleep automatically treated as light_sleep ). as a further refinement of the embodiment described above , the stability threshold for “ stable breathing ” can be refined on a per - subject basis . for example , the default analysis may use a stability threshold of 0 . 5 breaths / minute , but if this threshold produces physiologically unreasonable values for deep sleep duration ( e . g ., & gt ; 40 % or less & lt ; 5 %), the threshold could be adaptively modified to a more suitable value . an alternative embodiment which uses respiration rate variability and amplitude to determine sleep stage is shown in fig5 . this is based on the observation that the variability of the respiration rate and amplitude can be used to distinguish rem sleep . a period of relatively high variation of the breathing rate is considered as an indication of a rem sleep period . a period of relatively low variation of the breathing rate is considered to be associated with a state of deep sleep . one embodiment for assessing the variability of a time series is the approximate entropy . the approximate entropy assumes lower values for predictable time - series , and higher values as the time - sequence becomes more variable . in this embodiment , the raw signal 200 is fed to a respiration analysis block . this respiration analysis block outputs a continuous respiration rate and respiration amplitude estimate ( pictured in fig6 ), e . g . on a 1 - second timescale . the respiration rate is then fed into two processing blocks in segments ( typically of duration 5 minutes , i . e . 300 samples of the respiration rate will be passed into the blocks labelled “ approximate entropy block ” 502 and the “ power spectral density ” 503 . the approximate entropy is a technique used to assess the predictability of a signal ( i . e . variability ) and is described in http :// en . wikipedia . org / wiki / approximate entropy . the block will output a single number for the 5 minute epoch entered , which is the approximate entropy of that section of the signal . for example , we can calculate the approximate entropy of five - minute segments of respiration rate , using parameters of m = 2 and m = 3 for the embedding dimensions , and a value of r equal to 0 . 2 the power spectral density block will estimate the power spectral density of the respiration rate , using a technique such as welch &# 39 ; s averaged periodogram . the psd estimate will then provide three measurements : the slope of the psd , the normalised high frequency power of the respiration rate variability and the low - frequency power of the respiration rate variability . the power spectral density block will be applied to the respiration amplitude signal also , and will output a low frequency ( lf ) power estimate . the values calculated from the processing blocks ( 502 , 503 and 504 ) will be fed to a classifier which will combine them to produce a number which is then used to estimate a sleep label ( drawn from n1 , n2 , n3 , rem or w ). an alternate embodiment to power spectral density which can also capture the short - term and long - term correlations of the respiration rate is to use detrended fluctuation analysis , a description of which can be found in “ establishing the relation between detrended fluctuation analysis and power spectral density analysis for stochastic processes ,” phys rev e stat phys plasmas fluids relat interdiscip topics . 2000 november ; 62 ( 5 pt a ): 6103 - 10 , by heneghan and mcdarby . fig6 illustrates an example of the respiration rate signal and the normalized respiration amplitude signals which are used in fig5 . the respiration rate signal is shown in fig6 ( a ); there are periods of missing signals where the signal quality is insufficient for a reliable respiration rate estimate . the normalized respiration amplitude signal is shown in fig6 ( b ); there are periods of missing signals where the signal quality is insufficient for a reliable respiration amplitude estimate . the respiration rate amplitude signal can be obtained by filtering the raw signal to the respiration rate range first and then applying a hilbert transform , or it could be taken from the amplitude of the peak in respiration rate estimation . fig7 shows some of the intermediate processing steps in fig5 . in fig7 ( a ), we illustrate the power spectral density estimate of a segment of 5 - minutes of respiration rate , plotted on a log - log plot . a line is then fitted to the slope , and the slope of this line is an output from the processing block . this is based on physiological observations of the long - term and short term control of respiration variability ( see rostig s ; kantelhardt j w ; penzel t et al . “ nonrandom variability of respiration during sleep in healthy humans .” sleep 2005 ; 28 ( 4 ): 411 - 17 .) in fig7 ( b ), we show the power spectral density of five minutes of respiration rate shown on a semi - log scale . power is represented at different frequencies . the “ high frequency - hf ” power of the respiration rate variability can be considered as the integral of the psd from 0 . 1 to 0 . 5 hz . this can be normalised by dividing by the entire power of the signal . the “ low - frequency lf ” power can be defined as the power between 0 and 0 . 1 hz . a schematic representation of how a scaled version of the output of the classifier block may vary is shown in fig8 as a smoother uninterrupted line . the breathing rate is visualised by the more variable line in the image . a threshold value may be used for classifying the sleep during a specific period . such a value is illustrated by the straight horizontal line crossing the breathing rate axis slightly below the value of 13 breaths per minute . if the classifier block output for the period is above the predetermined threshold value , the respective period may be classified as a rem sleep period . alternatively , if the classifier block output for the period is below the predetermined threshold value , the respective period may be classified as period of deep sleep . this is an alternative way of classifying a period as a deep sleep to that described with reference to fig4 fig9 shows a means for illustrating the time course of the sleep stages to a user by using color - coded vertical bars . bars extending above the main axis indicate a state of wake . bars extending below the axis indicate a sleep state . the amplitude of the bars corresponds to the stage of sleep , the shortest bars indicating light sleep , the medium length bars indicating deep sleep and the longest bars indicating a rem sleep . this disclosure has application in the field of sleep research and in providing quality - of - life metrics to individual users .

US-201314031553-A

a device for locating and distending the external jugular vein is provided by a wish - bone shaped apparatus designed to engage the neck of a patent and apply sufficient pressure on the neck that the external jugular vein becomes distended due to pressure placed on the patient &# 39 ; s neck . the device includes two distally placed flat portions that resiliently engage the patient &# 39 ; s neck without causing choking or hindrance in breathing .

the present invention 110 as shown in fig1 is effectively an ej tourniquet which , as shown in fig1 , has an offset wishbone - like appearance . the two end portions 112 , 114 of the wishbone , located distally of the portion of the tourniquet of handle 128 ( see fig2 ) are sized and shaped such that they engage the patient &# 39 ; s neck , as shown in fig7 and 8 to cause a distention of the ej vein so that iv access is made simply and effectively . while the shape of the ej in related applications 61 / 779 , 420 and 29 / 448 , 541 is more or less planar , that is , the handle 28 shown in fig2 of such disclosure is more or less co - planar with the two end portions 12 , 14 of fig1 of such disclosure , in the present application the respective handle and end portions are not substantially coplanar but rather are offset from one another for handling purposes and to be able to better bring contact to bear on a patient &# 39 ; s neck . as shown in drawing fig1 - 6 , the ej tourniquet is a simple device which can be placed on the patient &# 39 ; s neck area to cause a bulging of the ej veins . this is accomplished by having the minimum distance between the ends of the wishbone be less than the width of a patient &# 39 ; s neck . thus , to accommodate different patients &# 39 ; neck sizes and the physiology of the patient , the ej wishbone may be made in different widths and lengths to accommodate the very differing thicknesses of human anatomy necks . in its simplest form , the ej tourniquet is comprised of a single piece of resilient material such as plastic , by way of example only , that is placed on the patient &# 39 ; s neck area . it is also envisioned that the ej tourniquet , instead of being made of plastic or other resilient material such as stainless steel , may be made of a material which is sterilizable , and thus allow for multiple uses of the device . as can be seen best in fig2 , there are two flat surfaces 116 and 118 facing one another and inclined in a manner such that the distance between the flats decreases towards the point of joinder 120 . this inclination allows the physician to slide the ej tourniquet in direction 122 relative to the patient &# 39 ; s neck and adjust its position on the patient &# 39 ; s neck so that a desired degree of pressure is placed on the patient &# 39 ; s neck . thus , these flat surfaces 116 and 118 engage the ej in a secure manner and are sufficient width and size to cause distension of the ej . in addition , the flat inclined surface are not planar with one another , but rather angled with respect to one another , as illustrated in fig4 and 5 . the angular offsets 150 and 152 may range from 12 degrees to 50 degrees . although the flat surfaces are shown in fig1 and 2 to be in the shape of linear flat surfaces , it is envisioned that any number of shapes may be incorporated in the end portions of the wishbone so as to adequately engage and distend the ej vein . as shown in fig2 , the distance 126 at the most distal portion of the flat surfaces is greater than the distance less distal from the point of joinder 120 . this arrangement has the benefit that a wide range of neck widths may be accommodated , so that at some point along surfaces 116 and 118 the neck of the patient will be engaged sufficiently so as to cause the ej to become prominent . in particular , it has been found that the distances 124 and 126 ( as shown in fig2 ) between the flat surfaces on either side of the wishbone may range from about 50 mm to about 82 . 5 mm , as it is desirable to have a separation that provides sufficient pressure on the patient &# 39 ; s neck without in fact causing a lessening of or complete cut off of flow of blood . however , any suitable distance range may be used , so long as such distance range is sufficient to adequately engage a patient &# 39 ; s neck . in fact , just as persons have widely varying neck sizes , different size ej tourniquets may also be envisioned . in addition , wherein the ej tourniquet illustrated and described in application no . 61 / 779 , 420 is shown as substantially planar , in the embodiment of fig2 herein the edge portions 130 are raised in a rib - like fashion to impart strength to the structure of the ej tourniquet . a handle 128 as shown in fig2 is located at the closed end of the wishbone and enables the physician or other operator to position the ej tourniquet onto a patient &# 39 ; s neck . while shown in fig2 as being circular with a depression , it is understood that a handle or grab of any size may be incorporated . in operation , the patient may be either seated or lying in a flat or almost flat position . it has been found that the seated position is preferably used . this is especially important for elderly patients who may be more comfortable in a sitting position rather than in a flat , reclined position . in the seated position , it has been found that blood tends to collect in the vicinity of the point of contact of the ej tourniquet with the neck , thus causing an enlarging or distending of the ej . the doctor or operator then places the ej tourniquet on the patient &# 39 ; s neck in the vicinity of where he or she sees the ej or determines the ej should be located if not visible . fig8 and 9 show the ej tourniquet as placed onto a patient &# 39 ; s neck . in particular , as shown in fig9 , the flats 140 and 142 of the device 144 are illustrated as being in place near the ej veins 146 and 148 . also , as best illustrated in fig8 , preferably the ej tourniquet is oriented such that the ej tourniquet is in the orientation illustrated in fig8 , but this may be varied or reversed in accordance with the wishes of the physician or as dictated by the neck structure of the patient . the correct position of the ej tourniquet on the patient &# 39 ; s neck makes the ej vein stand out and thus eases the ability to introduce an iv into the patient &# 39 ; s vein . since patients &# 39 ; body physiologies and the location of the ej vary , the doctor or operator can easily move the ej tourniquet up , down , towards , and away from the patient &# 39 ; s neck until the external jugular vein is located . the ej tourniquet may be used in a variety of medical procedures . for example , it may be used in conjunction with ultrasound procedures . if , for example , the physician cannot find a suitable vein in the patient &# 39 ; s arm for iv cannulation , the physician can use the ej tourniquet to cause swelling or distention , apply ultrasound , then cannulate with a needle . thus , we have provided an external jugular tourniquet which is simple in structure and in operation , is inexpensive to make , may be disposable , and is sized to occlude the bilateral external jugular vein in a manner that is safe and comfortable for the patient without interrupting breathing or blood flow .

US-201414203736-A

a lifter includes a grasping device for grasping and holding a handle in the lane maintenance machine , vertically driving device for driving the grasping device in the vertical direction , horizontally driving device for driving the grasping device in the horizontal direction , and lifter moving device for moving the lifter . when the handle of the bowling lane maintenance machine is grasped by the grasping device and if the horizontally driving device , vertically driving device and lifter moving device are used step - by - step in a combination , the bowling lane maintenance machine can be safely and easily shifted from one position to the other position or vice versa .

referring now to fig1 and 2 , a lifter 1 comprises a base 2 , a slider 4 in the form of a wheeled carriage translatable relative to the base 2 in the horizontal direction , and a vertical support 3 fixedly mounted on the slider 4 . the base 2 comprises a main body formed of a steel sheet having a thickness between 1 . 6 mm and 3 . 2 mm , the main body including left - and right - side bent portions 2a , 2b of substantially c - shaped cross - section and a bottom having a rectangular opening formed therethrough with round corners , and two rod - like transverse members 2c and 2d of substantially c - shaped cross - section which are formed of similar material and screwed to the main body at its forward and backward ends ( also see fig3 and 5 ). the base 2 also comprises front wheels 5a , 5b and back wheels 5c , 5d which are used to move the lifter 1 on the floor . the base 2 further comprises at least one base stopper 9 which is temporarily used to fix the lifter 1 on the floor . referring now to fig3 the base 2 includes front and back stoppers 12a and 12b fixedly mounted on the left side 2a . when the front base stopper 12a is impacted by a t - shaped stopper 16 on the slider 4 which will be described later , the forward translation of the slider 4 is stopped . when the back base stopper 12b is impacted by the t - shaped stopper 16 , the backward translation of the slider 4 is stopped . the base 2 further comprises a temporal catch 13 fixedly mounted thereon adjacent the back wheel stopper 12b . when the temporal catch 13 is engaged by a hooked projection 14 which will be described later , the temporal catch 13 can temporarily hold the slider 4 against the back stopper 12b ( also see fig5 and 7 ). the slider 4 is formed by folding a steel sheet having a thickness between 1 . 6 mm and 3 . 2 mm ( see fig5 ). the slider 4 comprises a t - shaped stopper 16 and a hooked projection 14 fixedly mounted on the slider adjacent the t - shaped stopper 16 ( also see fig6 and 7 ). each of the opposite sides 4a and 4b in the slider carriage include two slider wheels ( 15a and 15c ; 15b and 15d , respectively ), which are located spaced away from each other along that side of the slider carriage 4 . the slider carriage 4 can be translated relative to the floor when the wheels 14a , 15b , 15c and 15d rotatably move within the left - and right - side c - shaped portions 2a and 2b of the main base body 2 ( also see fig5 and 7 ). the vertical support 3 is formed by folding a steel sheet having a thickness between 1 . 6 mm and 2 . 3 mm ( see fig9 and 13 ). referring again to fig1 and 2 , the top side of the support 3 includes a box - like handle base 8a from which a handle 8 extends backwardly . a handle grip 10 configured to grip the handle of the lane maintenance machine extends forwardly from the front side of the support 3 . when the handle 8 is manually rotated , the handle grip 10 can be moved vertically along the support 3 . the support 3 further includes hand grips 11a , 11b , 11c and 11d which are fixedly mounted on the opposite sides thereof . these grips are used to stabilize the lifter with operator &# 39 ; s hands and feet when the lifter 1 is to be moved on the floor or when the handle 8 is to be rotated . referring now to fig4 , 7 and 8 , compression springs 17 are located between the front axle 6 of the wheels 5a and 5b and the base 2 . the base 2 includes elliptical axle holes 18 formed therethrough for the front axle 6 of the front wheels 5b and 5a . tension springs 19 are located between the back axle 7 and the base 2 . the base 2 also includes elliptical axle holes 20 for the axle 7 for the back wheels 5d and 5c . with provision of the springs 17 and 19 , the load on the front and back wheels 5a - 5d can be relieved when the lane maintenance machine is received by the lifter 1 . the axle holes 18 , 20 and front and back wheels 5a - 5d are so sized and positioned that when the load exceeds about 10 kg , the base 2 is just seated against the floor 21 . more particularly , a center - to - center distance d between two circles defining the ellipse axle hole 18 ( see fig8 ) is equal to or slightly larger than a distance between the bottom of a protective member 38 ( fig4 ) described later and the floor . when the member 38 on base 2 is seated against the floor 21 , no load will be on the front and back wheels 5a - 5d . referring further to fig5 and 7 , a protective member 38 of plastic material is formed on the bottom of the base 2 . the protective member 38 can prevent the floor 21 from be damaged by the base 2 when the latter is seated on the floor 21 . referring to fig1 , the base stopper 9 comprises a stopper grip 22 , a stopper stem 23 , a stopper compression spring 25 and a non - slip 26 . the stopper stem 23 includes a stopper stem notch 24 formed therein . as shown in fig9 and 10 , the base 2 includes a stopper locking member 27 fixedly mounted thereon . the stopper locking member 27 includes a guitar - shaped opening 27a formed therethrough . the opening 27a consists of a larger aperture having a diameter larger than that of the stopper stem 23 and a smaller aperture having a diameter smaller than that of the stopper stem 23 but larger than that of the stopper stem notch 24 . under the normal condition , the non - slip 26 is seated against the floor by the biasing force of a compression spring 25 . when the stopper grip 22 is upwardly moved to engage the stopper stem notch 24 into the smaller aperture of the guitar - shaped opening 27a in the stopper locking member 27 , however , the non - slip 26 can be lifted separated from the floor . thus , the lifter 1 can be moved . when it is wanted to fix the lifter temporarily on the floor , such a procedure may be reversed to disengage the stopper stem notch 24 from the smaller aperture of the guitar - shaped opening 27a . referring now to fig1 , the hand grip 10 comprises a lower grip arm 10a and an upper grip arm 10b . the lower and upper grip arms 10a , 10b are pivotally connected to each other through a pivot 10d . the lower grip arm 10a is formed of a steel sheet having a thickness between 8 mm and 12 mm . the upper grip arm 10b is formed by two steel sheets of the same configuration having a thickness between 3 . 2 mm and 4 . 5 mm , which is screwed to each other with the lower grip arm 10a being sandwiched therebetween ( also see fig3 and 17 ). in such an arrangement , the hand grip 10 can bear the heavy weight of the lane maintenance machine . referring further to fig1 , the upper grip arm 10b can be rotated about the pivot 10d through 90 degrees in a direction shown by arrow a . when the upper grip arm 10b is engaged by the lower grip arm 10a , a grip space 10c will be produced therebetween . the grip space 10c can receive the handle 41 of the lane maintenance machine . the lower grip arm 10a has a base 10e including top and bottom recesses 10f and 10g of u - shaped cross - section . each of the top and bottom recesses 10f and 10g fixedly receives a chain anchoring pin 38a or 37b which is connected to a chain 32 at the corresponding end thereof . thus , the chain 32 can form a complete loop as described below . referring now to fig1 and 13 , the base 10e of the lower grip arm 10a is screwed to a carriage guide member 36 which moves within the cavity 33 of the support 3 . the carriage guide member 36 is formed by folding a steel sheet having a thickness between 1 . 6 mm and 2 . 3 mm into a substantially c - shaped cross - section . the carriage guide member 36 has a vertical height larger than that of the lower arm base 10e . the carriage guide member 36 includes four guide wheels , that is , a pair of upper guide wheels 35a , 35b and a pair of lower guide wheels 35c , 35d . each of the inner left - and right - side walls , 33b and 33a , respectively , of the support cavity 33 have a guide pillar 34b and 34a , respectively , fixedly mounted thereon . the guide pillars 34a and 34b extend substantially along the length of the support 3 and together with the side walls 33a and 33b and the front inside wall 33c of the cavity 33 , form a pair of u - shaped channels 50a and 50b running vertically along the inside walls 33a and 33b of the cavity 33 . the carriage guide wheels 35a and 35c roll within the channel 50a while the guide wheels 35b and 35d roll within the channel 50b . thus , the carriage guide member 36 with handle grip 10 secured thereto can be moved along the support 3 in the vertical direction . an upper sprocket 30 is supported by an upper sprocket shaft 30a and is located in the cavity 33 at a position adjacent the top of the support 3 ( fig1 ). the lower sprocket 31 is supported by a lower sprocket shaft 31a and is located in the cavity 33 at a position adjacent the bottom of the support 3 ( fig9 ). the chain connected to one of the anchoring pins 37a extends upwardly to the upper sprocket 30 within the support cavity 33 and around the upper sprocket 30 downwardly toward the lower sprocket 31 . the chain further extends upwardly from around the lower sprocket 31 and is then connected to the other anchoring pin 37b . as shown in fig1 , the handle 8 includes a worm gear 28 located within the handle base 8a . as shown in fig1 , the worm gear 28 of the handle 8 is operatively engaged by another worm wheel gear 29 which is fixedly connected to the upper sprocket 30 through an upper sprocket shaft 30a . in such an arrangement , as the handle 8 is manually rotated , the handle worm gear 28 is also rotated in the same direction . the rotation of the worm gear 28 causes the worm wheel gear 29 to rotate in the opposite direction with a reduced speed . this causes an increased force which in turn rotates the upper sprocket 30 in the same direction as that of the worm wheel gear 29 . the rotation of the upper sprocket 30 causes the chain 32 to move such that the hand grip 10 will be moved upwardly or downwardly . fig1 and 16 show one of the conventional lane maintenance machines 40 with which the lifter of the present invention is used . the top of the lane maintenance machine 40 includes such a handle 41 as previously described , which handle 41 had been manually grasped to stand the lane maintenance machine 40 upright ( fig1 ) or lay the same down upon its bottom 45 ( fig1 ), according to the prior art . the bottom 45 of the lane maintenance machine 40 has four steerable casters attached thereto , one near each of its four corners , of which only the near side two ( 42a and 42b ) are shown in fig1 . if the lane maintenance machine 40 was standing upright as shown in fig1 and the handle 41 of the lane maintenance machine 40 was manually grasped and pushed , the lane maintenance machine 40 could be moved in any direction , as indicated by arrow b . the working face 45 or bottom of the lane maintenance machine 40 may also include four ground wheels , one located near each of its four corners , only two of which ( 44a and 44b ) are shown in fig1 . these wheels permit the lane maintenance machine 40 to be moved in a direction shown by arrow c when positioned lying down as shown in fig1 . the lane maintenance machine 40 further includes a pair of pulling - out wheels 43 which are used only when the lane maintenance machine 40 is to be shifted from its running position to its moved and transported position . the pulling - out wheels 43 are adapted to engage the floor only when the position of the lane maintenance machine 40 is being shifted with both the ground wheels and casters being not engaged by the floor . with provision of the pulling - out wheels 43 , the lane maintenance machine can be smoothly shifted in position without damage to both the floor and lane maintenance machine . referring now to fig1 to 23 , there will be described the lifter 1 when the lane maintenance machine is shifted from its running position to its moved and transported position . first , the slider 4 is moved to its forwardmost position and the handle 8 is manually rotated to move the hand grip 10 to its lowermost position . under such a condition , the operator moves the lifter 1 to a position adjacent the lane maintenance machine 40 . the upper grip arm 10b is then stood up to bring the hand grip 10 into its graspable position . the upper grip arm 10b is thereafter returned to its original or lower position to sandwich the handle 41 of the lane maintenance machine 40 between the upper and lower grip arms 10b and 10a ( see fig1 ). second , the lifter handle 8 is manually rotated to move the hand grip 10 upwardly . as the hand grip 10 has been raised to such a height that the base 2 of the lifter 1 can be inserted between the working face 45 of the lane maintenance machine 40 ( see fig1 ) and the floor surface 21 , the manual rotation of the lifter handle 8 is stopped . such a height depends on the magnitude of the lane maintenance machine used , but may normally range between 10 cm and 15 cm ( see fig1 ). third , the grips 11a , 11b , 11c and / or lid of the support 3 are grasped to move the support and slider 3 , 4 to the backwardmost position . the temporal catch 13 is caused to engage the hooked projection 14 for temporal connection between the slider 4 and the base 2 . fourth , the lifter handle 8 is again rotated to move the hand grip 10 further in the upward direction . the hand grip 10 is then rotated until the lane maintenance machine 40 has been completely stood up , using the pulling - out wheels 49 ( see fig2 and 22 ). after the lane maintenance machine 40 has been completely stood up into its moved and transported position , the upper grip arm 10b is raised to disengage the hand grip 10 from the handle 41 . as a result , the lane maintenance machine 40 will be separated from the lifter 1 . the locus of the lifter handle 8 through the first to fourth steps is as shown by arrow in fig2 . the procedure through which the lane maintenance machine is shifted from its moved and transported position to its running position will be described . first , the support and slider 3 , 4 are moved to their backwardmost position wherein the temporal catch 13 is caused to engage the hooked projection 14 for temporal connection of the slider 4 with the base 2 . at the same time , the lifter handle 8 is rotated to move the hand grip 10 to its uppermost position . under such a condition , the lifter 1 is moved to a position near the lane maintenance machine 40 . the upper grip arm 10b is then raised to place the hand grip 10 in the open position . the upper grip arm 10b is then moved down to grasp the handle 41 of the lane maintenance machine 40 between the upper and lower grip arms ( see fig2 ). second , the operator grasps the grips 11a , 11b , 11c and / or 11d and pushes the lane maintenance machine 40 with his or her one leg while keeping the balance . at the same time , the operator rotates the lifter handle 8 to move the hand grip 10 in the downward direction ( see fig2 ). the hand grip 10 will be lowered to a position wherein the pulling - out wheels 43 of the lane maintenance machine can be used , that is , the pulling - out wheels 43 are spaced away from the floor by a distance between 10 cm and 15 cm ( see fig2 ). third , the temporal catch 13 is disengaged from the hooked projection 14 . the operator then grasps grips 11a , 11b , 11c and / or 11d and push the lifter 1 away from him or her such that the support and slider 3 , 4 will be moved to their forwardmost position ( see fig1 ). fourth , the operator again rotates the lifter handle 8 to move the hand grip 10 downwardly to a position wherein the ground wheels of the lane maintenance machine 40 completely seat on the floor while using the pulling - out wheels 43 ( see fig1 ). in such a position , the upper grip arm 10b is raised to disengage the hand grip 10 from the handle 41 of the lane maintenance machine 40 . thus , the lane maintenance machine 40 can be separated from the lifter 1 . the locus of the lifter handle 8 through the first to fourth steps is in the opposite direction as shown by arrow in fig2 . according to the aforementioned procedure , the lifter can be prevented from being fallen down when the lane maintenance machine is being shifted from one position to the other position . more particularly , when the load is to be applied to the front of the lifter , the support is positioned behind the lifter . further , the hand grip and two pulling - out wheels of the lane maintenance machine are located at three points a , b and c , as shown in fig2 . therefore , the lane maintenance machine can be shifted from one position to the other position while being stabilized . as described , the lifter of the present invention can be used to shift the lane maintenance machine from its running position to its moved and transported position or vice versa with a reduced force in an easy manner . since the lifter is of a strong structure , such a shifting process can be safely carried out . since the lifter is also of a simplified structure , it can be produced more simply and cheaply .

US-56672495-A

a drug mixing system including at least one receptacle port adaptor adapted to be inserted into a port of a fluid receptacle , at least one syringe adaptor adapted to be attached to a syringe and to the at least one receptacle port adaptor and at least one vial adaptor adapted for connection to a vial containing a drug and adapted for connection to the at least one syringe adaptor , the system being characterized in that at least one of the receptacle port adaptor , the at least one syringe adaptor and the at least one vial adaptor being vented to the atmosphere in a manner which prevents release to the atmosphere of possibly harmful contents of the vial in a liquid , solid or gaseous form .

reference is now made to fig1 a , 1 b , 1 c , 1 d , 1 e , 1 f , 1 g , 1 h , 1 i , 1 j , 1 k , 1 l and 1 m which are simplified pictorial illustrations of various stages of assembly and typical use of a drug mixing system constructed and operative in accordance with a preferred embodiment of the present invention . as seen in fig1 a , a conventional vial 10 , including a top portion 12 and a neck portion 13 , is pushed into engagement with a vial adaptor assembly 30 which is described hereinbelow with reference to fig4 - 6b . top portion 12 of vial 10 preferably has a septum 31 sealingly seated therein . fig1 a - 18b show a sectional view of the drug mixing system at this stage : alternatively , if a small vial 32 is used , small vial 32 is pushed into engagement with a vial head adaptor element 34 which is described hereinbelow with reference to fig2 - 3 as shown in fig1 b , and is then pushed into engagement with vial adaptor assembly 30 . the vials 10 and 32 typically contain a drug in a soluble powder form , in a solution or in other suitable form . as shown in fig1 c , a luer fitted hypodermic syringe 40 having a plunger 42 and a luer tip 44 is attached to a syringe adaptor element 50 which is described hereinbelow with reference to fig7 - 9b . fig1 a - 19d show planar and sectional views of the drug mixing system at this stage . fig1 d shows a spike port adaptor element 60 , as described hereinbelow with reference to fig1 - 11 , being inserted into a spike port 61 in a receptacle 62 containing a fluid . fig2 shows a partially pictorial partially sectional view of the drug mixing system at this stage . typically , receptacle 62 comprises a bag , and the fluid contained therein is sterile saline solution , water , or any other suitable sterile solution or pure fluid . alternatively , a needle port adaptor element 70 , as described hereinbelow with reference to fig1 a - 13b , is inserted into a needle port 64 in receptacle 62 . fig2 shows a sectional view of the drug mixing system at this stage . it will be appreciated by persons skilled in the art that the assembly steps shown in fig1 b - 1d may be performed in any suitable sequence . as seen in fig1 e , syringe adaptor element 50 , having syringe 40 attached thereto ( fig1 c ), is connected to a connection port in either of spike port adaptor element 60 or needle port adaptor element 70 of fig1 d . fig2 - 23 and 24 - 25 , respectively , show partially pictorial partially sectional views of the two alternate orientations of the drug mixing system at this stage . typically , plunger 42 of syringe 40 is fully pushed inward into syringe 40 before syringe adaptor element 50 is connected to either of spike port adaptor element 60 and needle port adaptor element 70 . as seen in fig1 f , a user retracts plunger 42 in either of the operative orientations of fig1 e , thus at least partially filling syringe 40 with fluid drawn from receptacle 62 . the fluid flows through the spike port adaptor element 60 or through the needle port adaptor element 70 directly into syringe 40 . this flow of fluid ensures that the fluid remains sterile , and that the user is not exposed to the fluid . subsequently , the syringe 40 and syringe adaptor element 50 are disconnected from the spike port adaptor element 60 or the needle port adaptor element 70 . the drug mixing system of the present invention also ensures that the user is not exposed to the fluid during disconnection thereof , as explained further hereinbelow . the user then connects syringe adaptor element 50 , which is attached to syringe 40 , to the vial adaptor assembly 30 having the vial 10 attached thereto , as shown in fig1 g . fig2 shows a sectional view of the drug mixing system at this stage . when the syringe 40 and vial 10 are connected and fluid can flow therebetween , the user pushes plunger 42 inward , with the vial positioned upright , thus injecting the fluid contained in syringe 40 into vial 10 and dissolving the drug contained therein . fig2 shows a sectional view of the drug mixing system at this stage . as seen in fig1 h , the user then shakes the drug mixing system of fig1 g to ensure that the drug in vial 10 is fully dissolved and that the resulting solution is homogenous . it is appreciated that when vial 10 contains a drug in a pre - dissolved form , the steps described hereinabove with reference to fig1 e - 1h may be obviated . as seen in fig1 i , the user turns the drug mixing system upside clown and retracts plunger 42 , thus drawing at least part of the solution from the vial 10 into syringe 40 . subsequently , syringe 40 and syringe adaptor element 50 are disconnected from vial 10 and vial adaptor assembly 30 , as shown in fig1 j . at this stage , if some of the drug solution is left in vial 10 , vial 10 and vial adaptor assembly 30 , joined thereto , may be stored in a suitable facility for further use . at a next stage , the drug solution contained in syringe 40 is prepared for delivery to a hospital ward for infusion into a patient . as shown in fig1 k , syringe 40 containing the drug solution is connected to spike port adaptor element 60 for transferring the drug into receptacle 62 . alternatively , syringe 40 may be connected to needle port adaptor element 70 . as a further alternative , the user may place a syringe protection cover 80 , which is described hereinbelow with reference to fig1 - 15 , onto the syringe adaptor element 50 which is attached to syringe 40 , prior to delivering it to a hospital ward . as seen in fig1 l , the user pushes plunger 42 of syringe 40 inward , thus injecting the drug solution into receptacle 62 and further diluting it prior to infusion into a patient . alternatively , syringe 40 may be covered by the syringe protection cover 80 and is ready for delivery to the appropriate hospital ward . fig2 is a sectional view of the drug mixing system at this stage . as seen in fig1 m , the receptacle 62 and spike port adaptor element 60 are connected via a standard infusion set 92 such as model ias which is commercially available from teva medical ltd . of ashdod , israel , to a patient &# 39 ; s intravenous cannula . the connection to the spike port adaptor element 60 is performed after the removal of a connection element which is placed at the end of the spike port adaptor element 60 . fig3 is a sectional view of the drug mixing system at this stage . alternatively , the syringe 40 and syringe adaptor element 50 may be connected via an infusion set adaptor element 90 , which is described hereinbelow with reference to fig1 - 17 , to an infusion set 92 including a port 93 and an intravenous cannula 94 which is placed at the injection site . before syringe adaptor element 50 is attached to the infusion set adaptor element 90 , the syringe protection cover 80 is removed from the end of the syringe adaptor element 50 . fig2 shows a partially pictorial partially sectional view of the drug mixing system at this stage . the structure of elements of the drug mixing system of fig1 a - 1m is described hereinbelow with reference to fig2 - 17 . reference is now made to fig2 , which is a simplified pictorial illustration of a vial head adaptor element 34 which forms part of the drug mixing system of fig1 a - 1m , and to fig3 , which is a sectional illustration taken along section lines iii - iii in fig2 . as seen in fig2 , vial head adaptor element 34 is preferably a side - to - side symmetric integrally formed element , which is preferably injection molded of plastic . vial head adaptor element 20 preferably includes a generally cylindrical main body portion 200 and has a central axis 201 . an inner cylindrical surface 202 of main body portion 200 preferably has four arms 204 extending therefrom , each arm 204 being arranged at generally right angles with respect to its neighboring arms . each of arms 204 terminates at an upper end thereof , in the sense of fig1 b , in an inwardly facing generally triangular tooth 206 having a forwardly facing inclined surface 208 and a bottom - facing engagement surface 210 extending generally perpendicular to aim 204 . at bottom surface of vial head adaptor element 34 , there are formed four inwardly protruding surfaces 212 , extending generally perpendicular to inner surface 202 of main body portion 200 . each of neighboring surfaces 212 is preferably arranged at a generally right angle with respect to its neighboring surfaces 212 . surfaces 212 and arms 204 are rotationally offset from one another about axis 201 . reference is now made to fig4 , which is a simplified exploded view illustration of a preferred vial adaptor assembly 30 which forms part of the drug mixing system of fig1 a - 1m , to fig5 , which is a simplified assembled pictorial illustration of the vial adaptor assembly 30 , and to fig6 a and 6b , which are sectional illustrations taken along respective section lines via - via and vib - vib in fig5 . as seen in fig4 - 6b , vial adaptor assembly 30 comprises a main body element 302 arranged generally about an axis 303 . main body element 302 is preferably integrally formed and preferably injection molded of plastic . main body element 302 is preferably side - to - side symmetric about axis 303 , and preferably includes a rear portion 304 , which is generally cylindrical and terminates in a forward wall 306 . rear portion 304 comprises a forward base section 308 , rearward of which are preferably foisted four tabs 310 each having a rectangular window 312 . rearward of rectangular windows 312 and on an inner surface 314 of each of tabs 310 there are preferably formed two radially extending inwardly facing protrusions 316 each having an inclined surface . protrusions 316 preferably terminate at a forward end thereof in an inwardly facing transversely extending protrusion 318 . rearward of protrusions 316 , each of tabs 310 preferably includes an outwardly tapered portion 320 . a hollow vial puncturing spike 322 extends rearwardly from a rearward surface 324 of forward wall 306 , and is surrounded by base section 308 and by tabs 310 . rearward surface 324 additionally includes a circular cylindrical protrusion 325 , surrounding puncturing spike 322 . two radially extending bores 326 and 327 extend through vial puncturing spike 322 . forward of forward wall 306 of rear portion 304 there is formed an intermediate portion 328 which is generally rectangular , and includes axial hollow tubular portion 330 which is in fluid flow engagement with bore 327 of vial puncturing spike 322 . at a top surface of intermediate portion 328 and slightly recessed with respect thereto there is formed a plastic membrane support surface 332 , having formed thereon a plurality of generally evenly distributed spherical protrusions 334 , which are adapted to support a hydrophobic membrane 336 and prevent it from excessive inflation and from cracking . membrane 336 is adapted to allow free passage of air into the main body element 302 , but to prevent passage therethrough of liquid and air - borne particles , microorganisms and aerosol . a preferred membrane 336 is model versapor r 0 . 2 micron which is commercially available from pall corporation of new york , u . s . a . membrane 336 is in fluid flow engagement with vial puncturing spike 322 via bore 326 and via a recess 337 formed in intermediate portion 328 . a rim 338 surrounding support surface 332 is adapted to support an optional carbon cloth filter 340 and maintain it in a raised position above and spaced from membrane 336 . carbon cloth filter 340 is adapted to prevent toxic vapors from escaping from main body element 302 , thus protecting users . a preferred carbon cloth filter 340 is model no . zorflex emi , which is commercially available from charcoal cloth international ltd . of houghton - le - spring , england . intermediate portion 328 terminates at a forward end thereof in a generally circular wall 342 . forward of circular wall 342 there is formed a hollow neck portion 344 , which is in fluid flow engagement with hollow tubular portion 330 and with hollow vial puncturing spike 322 . hollow neck portion 344 terminates at a forward end thereof in a generally circular wall surface 346 . forward of neck portion 344 there is formed a forward facing portion 348 , which is adapted to sealingly accommodate a generally circular septum 350 on a seat 352 which is located at a forward end of portion 348 . forward facing portion 348 defines a central bore 354 which communicates between tubular portion 330 and septum 350 . vial adaptor assembly 30 preferably additionally includes a covering element 360 which supports and covers membrane 336 and carbon filter 340 . covering element 360 is a generally cylindrical , generally side - to - side symmetric , element and is preferably formed with a central opening 362 at a forward end thereof through which forward portion 348 extends . a pair of outer side surfaces 364 of covering element 360 are each formed with ribbed grip regions 366 . an inner top surface 368 of covering element 360 is preferably flat , and is adapted to support the top surfaces of membrane 336 and carbon filter 340 and to prevent excessive inflation and cracking thereof . it is appreciated that the functionalities of membrane 336 and carbon cloth filter 340 , to allow free passage of air into the drug mixing system while preventing passage thereinto of liquid and air - borne particles , microorganisms and aerosol and preventing toxic vapors from escaping from the drug mixing system , may be incorporated , using similar elements , into any of syringe adaptor element 50 , spike port adaptor element 60 and needle port adaptor element 70 . reference is now made to fig7 , which is a simplified exploded view illustration of syringe adaptor element 50 which forms part of the drug mixing system of fig1 a - 1m , to fig8 , which is a simplified assembled pictorial illustration of syringe adaptor element 50 and to fig9 a , 9 b and 9 c , which are sectional illustrations taken along respective section lines ixa - ixa and ixb - ixb in fig8 . as seen with particular clarity in fig7 , syringe adaptor element 50 comprises a housing element 500 , which has seated therein a forward septum 502 and a rearward septum 504 . housing element 500 is preferably an integrally formed cylindrical hollow element made of plastic and is preferably side - to - side , top - to - bottom and forward - rearward symmetrical . preferably , a forward portion 506 of housing element 500 includes a seat 508 for forward septum 502 , and a rear portion 510 of the housing element includes a seat 512 for rearward septum 504 . an intermediate portion 514 of housing element 500 preferably includes on a top and a bottom surface thereof generally rectangular outwardly facing protrusions 516 . septa 502 and 504 are preferably formed to have a generally circular portion 518 with a partially spherical protrusion 520 at one side thereof . surrounding housing element 500 there is formed a body 522 , which defines a main body portion 523 , which is generally cylindrical , preferably side - to - side and top - to - bottom symmetrical , and preferably formed of plastic , and side surfaces 524 . extending from a forward portion of each of side surfaces 524 is an outwardly protruding arm 526 , defining at an inner facing forward end thereof a generally triangular tooth 527 having a transversely extending rearward facing surface 528 which is adapted to engage a forward facing surface of intermediate portion 514 of housing element 500 . rearward of each of arms 526 there is formed a generally rectangular aperture 529 . adjacent a rearward portion 530 of housing element 500 there is formed a circumferential protrusion 532 , forward of which is formed an additional circumferential protrusion 534 , having a slightly larger outer circumference than that of protrusion 532 . a compression spring 536 is seated within housing element 500 , on a shoulder 538 located between intermediate portion 514 and rear portion 510 of housing element 500 . a generally cylindrical rear sealing element 540 is located rearward of housing element 500 . rear sealing element 540 is preferably side to side symmetric , and is typically formed of plastic . rear sealing element 540 preferably defines a forward cowl 542 terminating at a rearward end thereof in a generally circular wall portion 544 . forward cowl 542 preferably includes a circumferential recess 546 , which is adapted to engage circumferential protrusion 532 of housing element 500 . a forward facing surface 547 of sealing element 540 is adapted to engage a rearward facing surface of additional circumferential protrusion 534 when the syringe adaptor element 500 is assembled . wall portion 544 preferably defines a rear spring seat for compression spring 536 . a tapered inner portion 548 of rear sealing element 540 , which has a smaller circumference than that of housing element 500 , is preferably therewithin at a rear portion thereof . inner portion 548 is formed forward of and immediately adjacent to wall portion 544 and lies within compression spring 536 . a radially extending bore 549 is preferably formed in inner portion 548 and a hollow needle 550 is sealingly mounted therein . inner portion 548 is preferably surrounded by a cylindrical portion 552 , which terminates at a rearward end thereof in wall portion 544 and which also has a circumference which is smaller than that of housing element 500 . needle 550 preferably extends axially within compression spring 536 and through the center of housing element 500 and rearward septum 504 . a sharpened tip of needle 550 is preferably placed between forward septum 502 and rearward septum 504 , thus maintaining the needle inaccessible to a user and to the atmosphere . two generally concave symmetric surfaces 554 forming a nearly complete cylinder , may extend rearwardly of wall portion 544 and preferably surround an inner rearward cylindrical portion 556 , which is adapted to engage the luer tip 44 of luer fitted syringe 40 , defining generally symmetric side - facing tabs 558 at rearward ends thereof . the rear portion of needle 550 preferably extends axially within inner cylindrical portion 556 . referring specifically to fig9 c , which illustrates an alternative embodiment of the syringe adaptor element of fig8 , it is seen that a needle protector 560 , preferably made of latex , at least partially covers needle 550 , thus protecting it from the surrounding atmosphere . reference is now made to fig1 , which is a simplified pictorial illustration of spike port adaptor element 60 which forms part of the drug mixing system of fig1 a - 1m and to fig1 a and 11b which are sectional illustrations taken along section lines xi - xi in fig1 . spike port adaptor element 60 preferably comprises a hollow flexible plastic tube 602 having associated therewith a standard clamp 604 , which is commercially available from various manufacturers , such as qosina of italy . at a forward end thereof , tube 602 is fitted with a hollow spike element 606 which is preferably side - to - side symmetric and formed of plastic . spike element 606 is preferably formed of a main body portion 607 which preferably defines at a forward end thereof a spike 608 , having formed therein apertures communicating with two axially extending bores 610 and 612 . rearward of spike 608 , main body portion 607 defines a generally semi - circular planar protrusion 614 adapted to define the location at which a user grips the spike . alternatively , as seen with particular clarity in fig1 b , main body portion 607 may have formed therein a single aperture , which communicates with a single axially extending bore 615 . the interior of tube 602 is in fluid flow communication with bore 612 . a bore 616 formed in a neck portion 618 which preferably extends transversely from main body portion 607 and communicates with bore 610 . hollow neck portion 618 preferably terminates in a forward facing cylindrical portion 620 , which sealingly accommodates a generally circular septum 622 located on a seat 624 which communicates with bore 616 . a sealing assembly 630 is preferably attached to a rear end of tube 602 . sealing assembly 630 preferably includes at a rearwardmost end thereof a selectably removable tapered sealing section 632 , forward of which there is formed a connecting tube portion 634 which is adapted to connect sealing section 632 to tube 602 . sealing assembly 630 is adapted to seal tube 602 during use of the drug mixing device , and may be removed from tube 602 when receptacle 62 is connected directly to an infusion set spike for infusion of the fluid contained therein to a patient . it is appreciated that the spike connector of connection assembly 630 of spike port adaptor element 60 may optionally be replaced by a luer connector . reference is now made to fig1 a and 12b , which are simplified pictorial illustrations of needle port adaptor element 70 which forms part of the drug mixing system of fig1 a - 1m and to fig1 a and 13b , which are sectional illustrations taken along respective section lines xiiia - xiiia and xiiib - xiiib in fig1 a . needle port adaptor element 70 preferably comprises a main body element 700 arranged generally about an axis 701 . main body element 700 is preferably integrally formed and preferably injection molded of plastic . main body element 700 is preferably side - to - side symmetric about axis 701 , and preferably includes a rear portion 702 which is generally cylindrical , terminating in a forward wall portion 704 having a bore 706 extending therethrough . each of side surfaces 708 of rear portion 702 preferably includes a ribbed engagement surface portion 710 . four axially extending slots 712 extend along rear portion 702 , each slot 712 being arranged at generally right angles with respect to its neighboring slots . defined between slots 712 at a rearward facing end of rear portion 702 are four outwardly tapering tabs 714 . each tab 714 includes an inwardly facing generally triangular tooth 715 and terminates in a transversely extending section 716 . rear portion 702 preferably surrounds a generally cylindrical portion 718 , which extends rearwardly from forward wall portion 704 . forward of wall portion 704 there is formed a neck portion 720 , defining a radially extending bore 722 . a hollow needle 724 is adhesively mounted in bore 722 and extends rearwardly thereof along axis 701 . forward of neck portion 720 there is formed a forward facing cylindrical portion 726 , which sealingly supports a generally circular septum 728 on a seat 730 which is located at a forward end of cylindrical portion 726 . a bore 732 preferably extends radially through forward facing cylindrical portion 726 . bore 732 is preferably in fluid flow engagement with the interior of hollow needle 724 . a generally conical cover element 740 which is generally side - to - side and top - to - bottom symmetric about axis 701 preferably is axially slidable with respect to main body element 700 for selectably surrounding rear portion 702 of main body element 700 . a rear portion 742 of cover element 740 is preferably outwardly tapered , and terminates in a transversely extending edge surface 744 . four outwardly facing radially extending protrusions 746 lie along an outer surface of cover element 740 , each protrusion 746 being arranged at generally right angles with respect to its neighboring protrusions . four outwardly facing generally circumferential protrusions 748 are preferably formed on an outer surface 750 of cover element 740 between protrusions 746 thus defining a grip region . at a forward end thereof , an inner surface 751 of cover element 740 includes an inwardly tapered section 752 , which is adapted to slidably engage ribbed engagement surface portion 710 of rear portion 702 of main body element 700 . four generally rectangular inwardly facing protrusions 754 extend from section 752 , each protrusion 754 being arranged at generally right angles with respect to its neighboring protrusions . protrusions 754 are adapted to slidably engage slots 712 of rear portion 702 of main body element 700 . reference is now made to fig1 , which is a simplified pictorial illustration of syringe protection cover 80 which forms part of the drug mixing system of fig1 a - 1m and to fig1 , which is a sectional illustration taken along section lines xv - xv in fig1 . syringe protection cover 80 is preferably integrally formed , and is generally side to side symmetric about an axis 800 . a generally circular locking element 802 is preferably formed at a bottom end of syringe protection cover 80 . locking element 802 preferably includes a flat generally circular base surface 804 , preferably extending along a plane which is perpendicular to axis 800 . surface 804 is integrally formed with a generally cylindrical portion 806 . cylindrical portion 806 terminates in a generally circular radially outwardly extending wall portion 808 , which lies in a plane parallel to that defined by surface 804 . wall portion 808 terminates in a generally cylindrical portion 810 , which generally surrounds cylindrical portion 806 . an elongate tab 812 extends from surface 804 along axis 800 . reference is now made to fig1 , which is a simplified pictorial illustration of infusion set adaptor element 90 which forms part of the drug mixing system of fig1 a - 1m and to fig1 , which is a sectional illustration taken along section lines xvii - xvii in fig1 . as seen in fig1 and 17 , infusion set adaptor element 90 is preferably integrally formed , and preferably is side - to - side symmetric along an axis 901 . infusion set adaptor element 90 preferably includes a forward facing cylindrical portion 902 , which is adapted to surround a generally circular septum 904 which is sealingly mounted onto a seat 906 which is located at a forward end of cylindrical portion 902 . a generally cylindrical intermediate portion 908 is formed rearward of cylindrical portion 902 , having an outer circumference which is slightly smaller than that of cylindrical portion 902 . at a rear end thereof , intermediate portion 908 tapers toward a cylindrical neck portion 910 , which has an outer circumference which is smaller than that of intermediate portion 908 . an axially extending bore 912 extends through neck portion 910 , intermediate portion 908 and cylindrical portion 902 , thus allowing fluid flow through infusion set adaptor element 90 when the septum 904 is suitably pierced . the assembled structure of the drug mixing system at various stages of use thereof is described hereinbelow with reference to fig1 a - 30 . reference is now made to fig1 a and 18b which are , respectively , a simplified planar illustration and a simplified sectional illustration of the drug mixing system of fig1 b during attachment of vial adaptor 30 , the sectional illustration being taken along lines xviiib - xviiib in fig1 a . as seen with particular clarity in fig1 b , vial puncturing spike 322 of vial adaptor assembly 30 punctures septum 31 located inside top portion 12 of vial 10 , thus enabling fluid flow between the main body of vial 10 and forward facing portion 348 of main body element 302 of vial adaptor assembly 30 . preferably , puncturing of septum 31 releases any vacuum in vial 10 by entrance of air into vial 10 through carbon filter 340 ( fig4 and 6b ) and membrane 336 ( fig4 and 6b ). engagement between vial adaptor assembly 30 and vial 10 is preferably maintained by snap engagement of protrusions 316 and 318 of rear portion 304 of main body element 302 with a neck portion 13 of vial 10 . the engagement of protrusions 316 and 318 with neck portion 13 ensures that vial adaptor assembly 30 is latched onto vial 10 and cannot be removed therefrom . tabs 310 and outwardly tapered portions 320 generally surround top portion 12 and neck portion 13 of vial 10 . reference is now made to fig1 a and 19b and to fig1 c and 19d which are , respectively , a top and a side view simplified planar illustration and a simplified sectional illustration of the drug mixing system of fig1 c during attachment of the syringe adaptor element 50 to syringe 40 , the sectional illustrations being taken along lines xixb - xixb in fig1 a and xixd - xixd in fig1 c . as seen in fig1 a - 19d , luer 44 of luer fitted hypodermic syringe 40 preferably engages inner rearward cylindrical portion 556 of sealing element 540 of syringe adaptor element 50 and tabs 558 formed thereon , such that needle 550 is in fluid flow engagement with the hollow body of syringe 40 . at this stage , the sharpened tip of needle 550 is preferably placed between septa 502 and 504 , and compression spring 536 is relaxed . preferably , when syringe 40 is connected to syringe adaptor assembly 50 , plunger 42 of syringe 40 is pushed fully inward with respect to the syringe . reference is now made to fig2 , which is a partially pictorial partially sectional illustration of the drug mixing system of fig1 d during attachment of spike port adaptor element 60 . as seen in fig2 , spike 608 of spike element 606 of spike port adaptor element 60 is preferably inserted into a spike port 61 of receptacle 62 . at this stage , receptacle 62 and tube 602 are in fluid flow engagement . however , clamp 604 is closed and prevents fluid from flowing out of the receptacle through bore 612 into tube 602 . additionally , bore 610 is in fluid flow communication with cylindrical portion 620 via bore 616 of neck portion 618 . reference is now made to fig2 , which is a partially pictorial partially sectional illustration of the drug mixing system of fig1 d during attachment of needle port adaptor element 70 . as seen in fig2 , needle 724 of needle port adaptor element 70 is preferably inserted into needle port 64 of receptacle 62 . preferably , teeth 715 of tabs 714 engage port 64 when needle 724 is inserted . additionally , after needle 724 is inserted , cover element 740 is preferably moved with respect to main body element 700 along ribbed engagement surface portion 710 ( fig1 b ). the axial displacement of cover element 740 preferably seals and locks the connection between main body element 700 and port 64 , by pressing on tabs 714 and pushing them inward . displacement of cover element 740 includes a corresponding axial displacement of protrusions 754 with respect to slots 712 of rear portion 702 of main body element 700 . the axial displacement terminates when sections 716 of tabs 714 engage inner surface 751 of cover element 740 . at this stage , receptacle 62 is preferably in fluid flow engagement with bore 732 of cylindrical portion 726 via intermediate portion 720 and needle 724 . however , fluid does not flow out of cylindrical portion 726 , as the cylindrical portion is sealed by septum 728 . reference is now made to fig2 , which is a partially pictorial partially sectional illustration of the drug mixing system of fig1 e and 20 prior to the attachment of syringe 40 and syringe adaptor element 50 to spike port adaptor element 60 . as seen in fig2 , syringe adaptor element 50 and syringe 40 joined thereto are placed in close proximity to cylindrical portion 620 of spike port adaptor element 60 . it is appreciated that at this stage compression spring 536 is relaxed and the sharpened tip of needle 550 is preferably placed between septa 502 and 504 . preferably , surfaces 528 of teeth 527 of arms 526 engage forward facing surfaces on either side of intermediate portion 514 of housing element 500 . throughout the engagement process , septum 622 of spike port adaptor element 60 and septum 502 of syringe adaptor element 50 are pushed into touching engagement by the biasing force of spring 536 , thus preventing exposure of the tip of needle 550 to the environment . reference is now made to fig2 , which is a partially pictorial partially sectional illustration of the drug mixing system of fig1 e and 20 following the attachment of syringe 40 and syringe adaptor element 50 to spike port adaptor element 60 . as seen in fig2 syringe adaptor element 50 and syringe 40 joined thereto are pushed into engagement with cylindrical portion 620 of spike port adaptor element 60 . preferably , surfaces 528 of teeth 527 of arms 526 snap into engagement with wall portion 618 , thus ensuring that the engagement between syringe adaptor element 50 and cylindrical portion 620 is secure . at this stage , spring 536 is in a compressed state , and housing element 500 is pushed rearwardly by the pressure from cylindrical portion 620 . the rearward motion of housing element 500 causes the sharpened tip of needle 550 to pierce septa 502 and 622 . as a result , needle 550 partially extends through the hollow space in cylindrical portion 620 , and is in fluid flow engagement with receptacle 62 via bore 610 of spike 608 of spiked element 606 and via bore 616 of neck portion 618 . due to the fluid flow engagement between luer 44 of syringe 40 and needle 550 of syringe adaptor element 50 , the syringe 40 is now in fluid flow engagement with receptacle 62 . it is appreciated that when using the syringe adaptor element described in fig9 c , needle protector 560 at least partially collapses , thus exposing the needle 550 . in order to draw fluid from receptacle 62 into syringe 40 via spiked element 606 , bore 616 of neck portion 618 , cylindrical portion 620 and needle 550 , a user retracts plunger 42 . in order to disengage syringe adaptor element 50 and cylindrical portion 620 , a user pushes slightly on arms 526 extending from side surfaces 524 of housing element 522 , causing teeth 527 to move outward and release a rearward facing surface of cylindrical portion 620 , thus disconnecting the cylindrical portion . throughout the disengagement process , septum 622 of spike port adaptor element 60 and septum 502 of syringe adaptor element 50 are pushed into touching engagement by the biasing force of spring 536 , thus preventing exposure of the tip of needle 550 to the environment . reference is now made to fig2 , which is a partially pictorial partially sectional illustration of the drug mixing system of fig1 e and 21 prior to the attachment of syringe 40 and syringe adaptor element 50 to needle port adaptor element 70 . as seen in fig2 , syringe adaptor element 50 and syringe 40 joined thereto are placed in close proximity to cylindrical portion 726 of needle port adaptor element 70 . it is appreciated that at this stage compression spring 536 is relaxed and the sharpened tip of needle 550 is preferably located between septa 502 and 504 . preferably , surfaces 528 of teeth 527 of arms 526 engage forward facing surfaces on either side of intermediate portion 514 of housing element 500 . reference is now made to fig2 , which is a partially pictorial partially sectional illustration of the drug mixing system of fig1 e and 21 following the attachment of syringe 40 and syringe adaptor element 50 to needle port adaptor element 70 . as seen in fig2 syringe adaptor element 50 and syringe 40 joined thereto are pushed into engagement with cylindrical portion 726 of needle port adaptor element 70 . preferably , surfaces 528 of teeth 527 of arms 526 snap to engage a rearward facing wall portion of cylindrical portion 726 , thus ensuring that the engagement between syringe adaptor element 50 and cylindrical portion 726 is secure . at this stage , spring 536 is in a compressed state , and housing element 500 is pushed rearwardly by the pressure from cylindrical portion 726 . the rearward motion of housing element 500 causes the sharpened tip of needle 550 to pierce septa 502 and 728 . as a result , needle 550 partially extends through bore 732 of cylindrical portion 726 , and is in fluid flow engagement with receptacle 62 via needle 724 of rear portion 702 , neck portion 720 of main body element 700 and bore 732 of cylindrical portion 726 . due to the fluid flow engagement between luer 44 of syringe 40 and needle 550 of syringe adaptor element 50 , the syringe 40 is now in fluid flow engagement with receptacle 62 . it is appreciated that when using the syringe adaptor element described in fig9 c , needle protector 560 at least partially collapses , thus exposing the needle 550 . in order to draw fluid from receptacle 62 into syringe 40 via needle 724 , bore 732 and needle 550 , a user retracts plunger 42 . in order to disengage syringe adaptor element 50 and cylindrical portion 726 , a user pushes slightly on arms 526 extending from side surfaces 524 of housing element 522 , causing teeth 527 to move outward and release a rearward facing wall portion of cylindrical portion 726 , thus disconnecting cylindrical portion 726 . throughout the engagement and disengagement process , septum 728 of needle port adaptor element 70 and septum 502 of syringe adaptor element 50 are pushed into touching engagement by the biasing force of spring 536 , thus preventing exposure of the tip of needle 550 to the environment . reference is now made to fig2 , which is a sectional illustration of the drug mixing system of fig1 g prior to drug dilution . as seen in fig2 , syringe adaptor element 50 and syringe 40 joined thereto are placed in close proximity to forward facing portion 348 of vial adaptor element 30 . it is appreciated that at this stage compression spring 536 is relaxed and the sharpened tip of needle 550 is preferably located between septa 502 and 504 . preferably , surfaces 528 of teeth 527 of arms 526 engage forward facing surfaces on either side of intermediate portion 514 of housing element 500 . at this stage , syringe 40 is preferably filled with a fluid drawn from receptacle 62 ( fig2 - 25 ) and therefore plunger 42 is at least partially retracted . reference is now made to fig2 , which is a sectional illustration of the drug mixing system of fig1 h following drug dilution . as seen in fig2 syringe adaptor element 50 and syringe 40 joined thereto are pushed into engagement with forward facing portion 348 of vial adaptor element 30 . preferably , surfaces 528 of teeth 527 of arms 526 snap to engage wall portion 346 of forward facing portion 348 , thus ensuring that the engagement between syringe adaptor element 50 and portion 348 is secure . at this stage , spring 536 is in a compressed state , and housing element 500 is pushed rearwardly by the pressure from forward facing portion 348 . the rearward motion of housing element 500 causes the sharpened tip of needle 550 to pierce septa 502 and 350 . as a result , needle 550 partially extends through a hollow section of portion 348 , and is in fluid flow engagement with vial 10 via bore 350 of neck portion 344 and vial puncturing spike 322 of main body element 302 . due to the fluid flow engagement between luer 44 of syringe 40 and needle 550 of syringe adaptor element 50 , the syringe 40 is now in fluid flow engagement with vial 10 . it is appreciated that when using the syringe adaptor element described in fig9 c , needle protector 560 at least partially collapses , thus exposing the needle 550 . at this stage , a user injects the fluid contained in syringe 40 into vial 10 via bore 350 of neck portion 344 and vial puncturing spike 322 by inwardly pushing plunger 42 of syringe 40 . a corresponding volume of air escapes from vial 10 via membrane 336 and optional carbon cloth filter 340 . it is appreciated that any drug containing aerosol is blocked by the membrane and any non - aerosolized drug vapor is adsorbed by the charcoal filter , thus protecting users and the environment from contamination . preferably , the user ensures that the drug contained in vial 10 is fully dissolved , and then draws at least part of the drug solution contained in vial 10 into syringe 40 by turning the system upside down and retracting plunger 42 ( not shown ). at this stage , a corresponding volume of sterile air enters vial 10 via membrane 336 and optional carbon cloth filter 340 . in order to disengage syringe adaptor element 50 and forward facing portion 348 , a user pushes slightly on arms 526 extending from side surfaces 524 of housing element 522 , causing teeth 527 to move outward and release a wall portion 346 of forward facing portion 348 , thus disconnecting the forward facing portion . throughout the engagement and disengagement process , septum 350 of vial adaptor element 30 and septum 502 of syringe adaptor element 50 are pushed into touching engagement by the biasing force of spring 536 , thus preventing exposure of the tip of needle 550 to the environment . reference is now made to fig2 , which is a sectional illustration of the drug mixing system of fig1 k and 1l in a protected , ready for delivery state , when syringe adaptor element 50 is covered by syringe protection cover 80 . as seen in fig2 , syringe adaptor element 50 is preferably covered at a forward end thereof by syringe protection cover 80 . at this stage , plunger 42 is preferably at least partially retracted with respect to syringe 40 , and the syringe contains a drug solution withdrawn from vial 10 ( fig2 ). the forwardmost circumference of main body portion 523 is preferably seated in the recess formed by wall portions 806 and 810 of syringe protection cover 80 and surface 804 of syringe cover element 80 preferably engages a forward surface of septum 502 . it is appreciated that at this stage compression spring 536 is relaxed and the sharpened tip of needle 550 is preferably located between septa 502 and 504 . preferably , surfaces 528 of teeth 527 of arms 526 engage forward facing surfaces on either side of intermediate portion 514 of housing element 500 . reference is now made to fig2 , which is a partially pictorial , partially sectional illustration of the drug mixing system of fig1 m and 28 when ready for injection . as seen in fig2 , syringe protection cover 80 has been removed from syringe adaptor element 50 , and syringe adaptor element 50 and syringe 40 joined thereto are pushed into engagement with cylindrical portion 902 of infusion set adaptor element 90 , while the infusion set adaptor element 90 is connected to a side port of an intravenous cannula located at an injection site . preferably , surfaces 528 of teeth 527 of arms 526 snap to engage a rearward facing wall portion of cylindrical portion 902 , thus ensuring that the engagement between syringe adaptor element 50 and cylindrical portion 902 is secure . at this stage , spring 536 is in a compressed state , and housing element 500 is pushed rearwardly by the pressure from cylindrical portion 902 . the rearward motion of housing element 500 causes the sharpened tip of needle 550 to pierce septa 502 and 904 . as a result , needle 550 partially extends through bore 912 of infusion set adaptor element 90 , and is therefore in fluid flow engagement with the injection site . due to the fluid flow engagement between luer 44 of syringe 40 and needle 550 of syringe adaptor element 50 , the syringe 40 is now in fluid flow engagement with the injection site . it is appreciated that when using the syringe adaptor element described in fig9 c , needle protector 560 at least partially collapses , thus exposing the needle 550 . in order to disengage syringe adaptor element 50 and cylindrical portion 902 , a user pushes slightly on arms 526 extending from side surfaces 524 of housing element 522 , causing teeth 527 to move outward and release a the rearward facing wall portion of cylindrical portion 902 , thus disconnecting the cylindrical portion . reference is now made to fig3 , which is a partially pictorial partially sectional illustration of the drug mixing system of fig1 m and 20 when ready for injection . preferably , receptacle 62 is connected via spike port adaptor element 60 to an infusion set 92 . the infusion set then connects to a standard intravenous cannula 94 such as a venolit model commercially available from teva medical ltd . of ashdod , israel which is located in an infusion site . typically , prior to connection of spike port adaptor element 60 to infusion set 92 , sealing element 630 is removed , and infusion set 92 is connected directly to tube 602 . alternatively , infusion set 92 may be connected to a new receptacle , not containing a drug , in which case the drug solution is injected directly into the infusion set . if this option is selected , syringe adaptor 50 having syringe 40 ( fig2 ) joined thereto is connected to port 93 after syringe protector cover 80 is removed , and the drug solution contained therein is injected into the infusion line . preferably , surfaces 528 of teeth 527 of arms 526 snap to engage a rearward facing wall portion of port 93 , thus ensuring that the engagement between syringe adaptor element 50 and port 93 is secure . at this stage , spring 536 is in a compressed state , and housing element 500 is pushed rearwardly by the pressure from port 93 . the rearward motion of housing element 500 causes the sharpened tip of needle 550 to pierce septum 502 and a sealing septum of port 93 . as a result , needle 550 partially extends into infusion set 92 , and is therefore in fluid flow engagement with the injection site . due to the fluid flow engagement between luer 44 of syringe 40 and needle 550 of syringe adaptor element 50 , the syringe 40 is now in fluid flow engagement with the injection site . in order to disengage syringe adaptor element 50 and port 93 , a user pushes slightly on arms 526 extending from side surfaces 524 of housing element 522 , causing teeth 527 to move outward and release a rearward facing wall portion of port 93 , thus disconnecting the port . reference is now made to fig3 a , 31 b , 31 c , 31 d , 31 e , 31 f , 31 g , 31 h , 31 i , 31 j and 31 l which are simplified pictorial illustrations of various stages of assembly and typical use of a drug mixing system constructed and operative in accordance with another preferred embodiment of the present invention . fig3 a shows a spike port adaptor element 1030 , as described hereinbelow with reference to fig3 - 35 , being inserted into a spike port 1031 in a receptacle 1032 containing a fluid . preferably , a luer connector of spike port adaptor element 1030 is sealed by a luer cover element 1034 . typically , receptacle 1032 comprises a bag , and the fluid contained therein is sterile salt solution , water , or any other suitable sterile solution or pure fluid . as shown in fig3 b , a luer - equipped hypodermic syringe 1040 , having a plunger 1042 and a luer tip 1044 , is connected to a syringe port of an adaptor assembly 1050 , which is described hereinbelow with reference to fig3 and 44 - 45 b . preferably , the syringe port is defined by a stopcock 1052 which is described hereinbelow with reference to fig3 - 38b and includes a removable protection cap 1054 . fig4 shows a sectional view of the drug mixing system at this stage . typically , plunger 1042 of syringe 1040 is pushed fully inward before the syringe is connected to the syringe port of stopcock 1052 . fig3 c shows spike port adaptor element 1030 and receptacle 1032 joined thereto being connected to a receptacle adaptor subassembly 1056 of adaptor assembly 1050 . subassembly 1056 is described hereinbelow with reference to fig3 - 40b . preferably , stopcock 1052 is in an operative orientation which enables fluid flow between receptacle adaptor subassembly 1056 and syringe 1040 . fig4 shows a sectional view of the drug mixing system at this stage . as seen in fig3 d , a vial 1060 , including a top portion 1062 and a neck portion 1063 , is pushed into engagement with a vial adaptor subassembly 1058 of adaptor assembly 1050 . top portion 1062 of vial 1060 preferably has a septum 1064 sealingly seated therein . subassembly 1058 is described hereinbelow with reference to fig4 - 42b . alternatively , if a small vial 1066 is used , small vial 1066 is pushed into engagement with a vial head adaptor element 1068 , which is described hereinbelow with reference to fig3 - 33 , as shown in fig3 e , and is then pushed into engagement with vial adaptor subassembly 1058 . vials 1060 and 1066 typically contain a drug in soluble powder form , in a solution or in other suitable four . fig4 shows a sectional view of the drug mixing system at this stage . it is appreciated that stopcock 1052 , receptacle adaptor subassembly 1056 and vial adaptor subassembly 1058 are preferably enclosed in a housing element 1070 of adaptor assembly 1050 , which is described hereinbelow with reference to fig4 a - 43b . it will be appreciated by persons skilled in the art that the assembly steps shown in fig3 c - 31e may be performed in any suitable sequence . as seen in fig3 f , a user retracts plunger 1042 while receptacle 1032 is upright and vial 1060 lies therebelow , thus at least partially filling syringe 1040 with fluid drawn from receptacle 1032 . the operative orientation of stopcock 1052 enables this fluid flow from receptacle 1032 to syringe 1040 via spike port adaptor element 1030 , receptacle adaptor subassembly 1056 and stopcock 1052 in a manner that ensures that the fluid remains sterile , and that the user is not exposed thereto . fig4 shows a sectional view of the drug mixing system at this stage . the user then rotates a handle 1080 of stopcock 1052 to enable fluid flow between syringe 1040 and vial adaptor subassembly 1058 , having joined thereto vial 1060 , as shown in fig3 g . when the syringe 1040 and vial 1060 are in fluid flow engagement , the user pushes plunger 1042 inward , thus injecting the fluid contained in syringe 1040 into vial 1060 and dissolving the drug contained therein . fig5 shows a sectional view of the drug mixing system at this stage . as seen in fig3 h , the user then shakes the drug mixing system of fig3 g to ensure that the drug in vial 1060 is fully dissolved and that the resulting solution is homogenous . as seen in fig3 i , the user turns the system upside down , so that the vial 1060 faces upward , and then retracts plunger 1042 , thus drawing at least part of the solution from vial 1060 into syringe 1040 . fig5 shows a sectional view of the drug mixing system at this stage . it will be appreciated by those skilled in the art that at this stage the drug mixing system of the present invention is preferably held such that vial 1060 lies above syringe 1040 , to allow smooth flow of the fluid from vial 1060 to syringe 1040 via vial adaptor subassembly 1058 and stopcock 1052 . as shown in fig3 j , handle 1080 of stopcock 1052 is oriented to enable flow of fluid between syringe 1040 and receptacle 1032 . the user then pushes plunger 1042 of syringe 1040 inward , thus injecting the drug solution into receptacle 1032 and further diluting it prior to infusion into a patient . fig5 shows a sectional view of the drug mixing system at this stage . subsequently , spike port adaptor element 1030 , having receptacle 1032 joined thereto , is disconnected from adaptor assembly 1050 , which remains connected to vial 1060 as shown in fig3 k . as seen in fig3 l , if some of the drug solution is left in vial 1060 , vial 1060 and adaptor assembly 1050 joined thereto may be stored in a suitable facility for further use . it is appreciated that at this stage syringe 1040 remains connected to the syringe port of stopcock 1052 of adaptor assembly 1050 . fig5 is a sectional view of the drug mixing system at this stage . the structure of elements of the drug mixing system of fig3 a - 31l is described hereinbelow with reference to fig3 - 43b . reference is now made to fig3 , which is a simplified pictorial illustration of a vial head adaptor element 1068 which forms part of the drug mixing system of fig3 a - 31l and to fig3 which is a sectional illustration taken along section lines xxxiii - xxxiii in fig3 . as seen in fig3 , vial head adaptor element 1068 is preferably a side - to - side symmetric integrally formed element which is preferably injection molded of plastic . vial head adaptor element 1068 preferably includes a main body portion 1200 which is generally cylindrical and has a central axis 1201 . an inner cylindrical surface 1202 of main body portion 1200 preferably has four arms 1204 extending therefrom , each arm 1204 being arranged at generally right angles with respect to its neighboring arms . each of arms 1204 terminates at an upper end thereof , in the sense of fig3 a , in an inwardly facing generally triangular tooth 1206 having a upwardly facing inclined surface 1208 and a bottom - facing engagement surface 1210 extending generally perpendicular to arm 1204 . at the bottom of vial head adaptor element 1068 , there are formed four inwardly protruding surfaces 1212 , extending generally perpendicular to inner surface 1202 of main body portion 1200 . each of neighboring surfaces 1212 is preferably arranged at a generally right angle with respect to its neighboring surfaces 1212 . surfaces 1212 and arms 1204 are rotationally offset from one another about axis 1201 . reference is now made to fig3 , which is a simplified pictorial illustration of spike port adaptor element 1030 which forms part of the drug mixing system of fig3 a - 31l and to fig3 which is a sectional illustration taken along section lines xxxv - xxxv in fig3 . spike port adaptor element 1030 preferably comprises a hollow flexible plastic tube 1302 having associated therewith a standard clamp 1304 , which is commercially available from various manufacturers such as quosina of italy . at a forward end thereof , tube 1302 is connected to a tube port 1305 of a hollow spike element 1306 which is preferably formed of plastic . spike element 1306 preferably includes a main body portion 1307 which defines at a forward end thereof a spike 1308 which includes an aperture communicating with an axially extending bore 1310 and an additional bore 1312 which extends partially through main body portion 1307 and communicates with a top portion of bore 1310 , thus facilitating complete priming before drug injection . rearward of spike 1308 , main body portion 1307 defines a generally circular planar protrusion 1314 adapted to define the location at which a user grips the spike . the interior of tube 1302 is in fluid flow communication with bore 1312 via tube port 1305 . bore 1310 preferably terminates in an aperture located in spike 1308 of main body portion 1307 , and fully extends through the body portion 1307 . main body portion 1307 preferably terminates in a connection port 1318 which is adapted to connect spike port adaptor element 1030 to receptacle adaptor subassembly 1056 . connection port 1318 preferably sealingly accommodates a generally circular septum 1320 on a seat 1322 . septum 1320 preferably engages the rear end of bore 1310 , thus sealing the rear end of the bore . forward of connection port 1318 , there is formed on main body portion 1307 a circumferential protrusion 1324 , forward of which is formed an additional circumferential protrusion 1326 , having an outer circumference which is slightly larger than that of protrusion 1324 . protrusions 1324 and 1326 are adapted to limit the movement of spike port adaptor element 1030 when it is connected to receptacle adaptor subassembly 1056 . a luer connector 1330 is preferably attached to a rear end of tube 1302 . luer connector 1330 preferably includes at a rearwardmost end thereof a narrow hollow port section 1332 , forward of which there is formed a connecting tube portion 1334 and a hollow neck portion 1336 which connects port section 1330 to tube 1302 . preferably , luer connector 1330 is sealed by luer cover element 1034 . it is appreciated that spike port adaptor element 1030 may alternatively be identical to spike port adaptor element 630 described hereinabove with reference to fig1 - 11b . reference is now made to fig3 , which is a simplified exploded view illustration of adaptor assembly 1050 which forms part of the drug mixing system of fig3 a - 31l . as seen with particular clarity in fig3 , adaptor assembly 1050 includes vial adaptor subassembly 1058 , onto which is placed a hydrophobic membrane 1402 , above which is optionally seated a carbon cloth filter 1404 . vial adaptor subassembly 1058 is connected at a forward portion thereof to a vial port 1082 of stopcock 1052 , which additionally includes a syringe port 1084 adapted for engagement with luer 1044 of syringe 1040 . stopcock 1052 additionally includes a receptacle port 1086 which is adapted for connection to a rear connection element 1406 of receptacle adaptor subassembly 1056 . preferably , when syringe 1040 is not connected to the syringe port of stopcock 1052 , the syringe port 1084 is sealed by protection cap 1054 . a needle holding element 1408 is preferably seated within rear connection element 1406 and supports a needle 1410 . a forward portion of needle 1410 is preferably protected by a flexible latex needle protection element 1412 . receptacle adaptor subassembly 1056 connects at a rearward end thereof to rear connection element 1406 , enclosing needle holding element 1408 , needle 1410 and needle protection element 1412 . the forward portion of vial adaptor subassembly 1058 as well as stopcock 1052 and the rear portion of receptacle adaptor subassembly 1056 are located within housing element 1070 . however , a handle 1080 of stopcock 1052 protrudes from housing element 1070 , thus enabling a user to change the operative orientation of the stopcock 1052 and thereby switch the fluid flow pathway . reference is now made to fig3 , which is a simplified pictorial illustration of stopcock 1052 which forms part of the adaptor assembly of fig3 and to fig3 a and 38b , which are sectional illustrations taken along respective section lines xxxviiia - xxxviiia and xxxviiib - xxxviiib in fig3 . stopcock 1052 , as noted hereinabove , has a vial port 1082 , a syringe port 1084 and a receptacle port 1086 , all of which are defined in a housing portion 1090 . user operable handle 1080 is fixed to a pathway defining element 1092 , which defines a three - way direction pathway , as seen with particularity in fig3 b . selectable rotational orientation of handle 1080 enables any two of ports 1082 , 1084 and 1086 to be placed in mutual fluid communication . stopcock 1052 is commercially available from elcam ltd . of baram , israel . reference is now made to fig3 , which is a simplified pictorial illustration of receptacle adaptor subassembly 1056 which forms part of the adaptor assembly of fig3 and to fig4 a and 40b , which are sectional illustrations taken along respective section lines xla - xla and xlb - xlb in fig3 . as seen in fig3 - 40b , receptacle adaptor subassembly 1056 includes a main body element 1600 which is arranged generally about an axis 1601 . main body element 1600 is preferably integrally formed of plastic , and is preferably side - to - side symmetric about axis 1601 . main body element 1600 preferably includes a generally cylindrical base portion 1602 terminating in a rear portion 1604 . top and bottom generally concave wall portions 1606 are formed at a forward end of base portion 1602 , each wall portion 1606 defining on an outer surface thereof an outwardly facing axially extending rib 1608 , which extends from a forwardmost end of each of wall portions 1606 and along base portion 1602 . a connection surface 1610 extending transversely from side surfaces 1612 of base portion 1602 connects an outwardly extending arm 1614 to each side surface 1612 . each arm 1614 preferably has a generally square rear portion 1616 , formed rearwardly of connection surface 1610 , and has a radially extending outwardly facing protrusion 1618 formed thereon . protrusion 1618 preferably extends onto an outer surface of a generally rectangular forward portion 1620 of each of arms 1614 , which extends forwardly of connection surface 1610 . an inwardly facing generally triangular tooth 1622 is formed adjacent a top end of each of forward portions 1620 . each tooth 1622 preferably includes a forwardly facing inclined surface 1624 and a rearwardly facing engagement surface 1626 . rear portion 1604 preferably includes a transversely extending generally circular portion 1630 which forms a base for ribs 1608 and which terminates at a rear end thereof in an axially extending generally cylindrical wall portion 1632 . wall portion 1632 preferably defines on a top and bottom surface thereof a small generally rectangular window 1634 , and two forwardly facing slots 1636 which are formed on either side of window 1634 . two generally symmetric side - facing tabs 1638 are formed on side surfaces 1640 of wall portion 1632 , each tab 1638 being formed forwardly of a generally rectangular forwardly facing slot 1642 . rear connection element 1406 preferably includes a forward disk 1652 defining a central bore 1654 . disk 1652 preferably functions as a terminating wall for a forward facing cylindrical portion 1656 . rearward of disk 1652 there is preferably formed a rear portion 1658 , having a narrow bore 1660 extend therethrough . bore 1660 preferably widens toward the rear end of rear portion 1658 , thus enabling rear portion 1658 to connect to an appropriate port . preferably , two generally symmetric tabs 1662 are formed on top and bottom surfaces of rear portion 1658 . cylindrical portion 1656 preferably has an outer circumference that is slightly smaller than that of wall portion 1632 , and is located therein . needle holding element 1408 preferably supports needle 1410 on a generally circular disk portion 1672 . needle 1410 extends axially through base portion 1602 of main body element 1600 and through bore 1660 of rear connection element 1650 . disk portion 1672 is preferably seated in cylindrical portion 1656 , and is locked into cylindrical portion 1656 by portion 1630 . reference is now made to fig4 , which is a simplified pictorial illustration of vial adaptor subassembly 1058 which forms part of adaptor assembly 1050 of fig3 and to fig4 a and 42b , which are sectional illustrations taken along respective section lines xliia - xliia and xliib - xliib in fig4 . as seen in fig4 - 42b , vial adaptor subassembly 1058 comprises a main body element 1702 arranged generally about an axis 1703 . main body element 1702 is preferably integrally formed and preferably injection molded of plastic . main body element 1702 is preferably side - to - side symmetric about axis 1703 , and preferably includes a rear portion 1704 , which is generally cylindrical and terminates in a forward wall 1706 . rear portion 1704 comprises a forward base section 1708 , preferably having four transversely extending outwardly facing protrusions 1709 extend therefrom , each protrusion being arranged at generally right angles with respect to its neighboring protrusions . rearward of base section 1708 there are formed four tabs 1710 each having a rectangular window 1712 . rearward of rectangular windows 1712 and on an inner surface 1714 of each of tabs 1710 there are preferably formed two radially extending inwardly facing protrusions 1716 each having an inclined surface . protrusions 1716 preferably terminate at a forward end thereof in an inwardly facing transversely extending protrusion 1718 . rearward of protrusions 1716 , each of tabs 1710 preferably includes an outwardly tapered portion 1720 . a hollow vial puncturing spike 1722 extends rearwardly from a rearward surface 1724 of forward wall 1706 , and is surrounded by base section 1708 and by tabs 1710 . rearward surface 1724 additionally includes a circular cylindrical protrusion 1725 , surrounding puncturing spike 1722 . two axially extending bores 1726 and 1727 extend through vial puncturing spike 1722 . forward of forward wall 1706 of rear portion 1704 there is formed an intermediate portion which is formed of two generally rectangular surfaces 1728 , and which includes an axial tubular portion 1730 having a bore 1731 extend therethrough , bore 1731 being in fluid flow engagement with bore 1726 of hollow vial puncturing spike 1722 . on the top rectangular surface 1728 and slightly recessed with respect thereto there is formed a plastic membrane support surface 1732 , having formed thereon a plurality of generally evenly distributed spherical protrusions 1734 , which are adapted to support hydrophobic membrane 1402 and prevent it from excessive inflation and from cracking . membrane 1402 is adapted to allow free passage of air to and from main body element 1702 , but to prevent passage of liquid and air borne particles , microorganisms and aerosol . a preferred membrane 1402 is model versapor r 0 . 2 micron which is commercially available from pall corporation of new york , u . s . a . membrane 1402 is in fluid flow engagement with vial puncturing spike via bore 1727 and via a recess 1737 formed in top rectangular surface 1728 . a rim 1738 surrounding support surface 1732 is adapted to support a carbon cloth filter 1404 and maintain it in a raised position above and spaced from membrane 1402 . carbon filter 1404 is adapted to prevent toxic vapors from escaping from main body element 1702 , thus protecting users . a preferred carbon cloth filter 1404 is model no . zorflex emi which is commercially available from charcoal cloth international ltd . of houghton - le - spring , england . rectangular surfaces 1728 of the intermediate portion terminate at a forward end thereof in a forward facing cylindrical portion 1748 , having a bore 1750 extend therethrough . preferably , bore 1750 is a continuation of tubular portion 1730 of the intermediate portion . it is appreciated that the functionalities of membrane 1402 and carbon cloth filter 1404 , to allow free passage of air into the drug mixing system while preventing passage thereinto of liquid and air - borne particles , microorganisms and aerosol and preventing toxic vapors from escaping from the drug mixing system , may be incorporated , using similar elements , into spike port adaptor element 1030 or receptacle adaptor subassembly 1056 . reference is now made to fig4 a and 43b , which are simplified pictorial illustrations of the housing element 1070 which forms part of the adaptor assembly 1050 of fig3 in closed and open orientations , respectively . as seen in fig4 a and 43b , housing element 1070 is preferably integrally formed about an axis 1800 and includes a top housing portion 1801 and a bottom housing portion 1802 . preferably , housing portions 1801 and 1802 are side - to - side symmetric about axis 1800 . preferably , each of housing portions 1801 and 1802 includes a semi - cylindrical forward portion 1804 and a semi - cylindrical rearward portion 1806 . top housing portion 1801 includes an inwardly recessed portion 1808 including a generally round aperture 1810 which extends forwardly into an elongate aperture 1812 . rearward of aperture 1810 there is preferably formed an elongate protrusion 1814 . preferably , apertures 1810 and 1812 lie below handle 1080 of stopcock 1052 when adaptor assembly 1050 is assembled . bottom housing portion 1802 includes an inwardly recessed portion 1816 which is generally symmetrical to recessed portion 1808 of top housing portion 1801 , and which includes a central generally round aperture 1818 . two elongate protrusions 1820 are formed on either side of aperture 1818 , such that rearward protrusion 1820 is generally symmetrical to protrusion 1814 of top housing portion 1801 . preferably , a bottom portion of pathway defining element 1090 of stopcock 1052 extends through aperture 1818 when adaptor assembly 1050 is assembled . top housing portion 1801 includes at forward and rearward ends thereof outwardly extending fingers 1822 terminating in a generally triangular teeth 1824 which include inclined outwardly facing surfaces 1826 and engagement surfaces 1828 . bottom housing portion 1802 preferably includes at forward and rearward ends thereof two generally rectangular windows 1830 which are placed generally below fingers 1822 and are adapted to engage engagement surfaces 1828 of fingers 1822 when housing element 1070 is assembled . an inner surface 1834 of housing element 1070 preferably includes at a rearward end thereof a circumferential recess 1836 which is adapted to engage protrusions 1709 of rear portion 1704 of vial adaptor subassembly 1058 . an outer surface of housing element 1070 which lies above recess 1836 preferably includes an outwardly facing protrusion 1840 which protrudes out of cylindrical forward portion 1804 . preferably , side surfaces of top housing portion 1801 and bottom housing portion 1802 include generally parallel generally rectangular slots 1842 , through which syringe port 1084 of stopcock 1052 extends when adaptor assembly 1050 is assembled . reference is now made to fig4 , which is a simplified assembled pictorial illustration of the adaptor assembly of fig3 and to fig4 a and 45b , which are sectional illustrations taken along respective section lines xlva - xlva and xlvb - xlvb in fig4 . as seen in fig4 - 45b , rear portion 1704 of vial adaptor subassembly 1058 extends from a rear portion of housing element 1070 . vial puncturing spike 1722 preferably extends out of housing element 1070 , and is accessible for connection of vial 1060 or of vial 1066 ( fig3 e ) thereto . preferably , circumferential recess 1836 of inner surface 1834 of housing element 1070 engages protrusions 1709 of rear portion 1704 of vial adaptor subassembly 1058 . preferably , forward facing cylindrical portion 1748 engages vial port 1082 of stopcock 1052 . a forward portion of main body element 1600 of receptacle adaptor subassembly 1056 preferably extends from a forward portion of housing element 1070 of adaptor assembly 1050 , and surrounds needle 1410 enclosed in needle protection element 1412 . main body element including needle 1410 and needle protection cover 1412 is preferably accessible for connection of spike port adaptor element 1030 ( fig3 - 35 ) thereto . preferably , rear portion 1658 of rear connection element 1406 engages receptacle port 1086 of stopcock 1052 . a rear end of needle 1410 at least partially extends through bore 1660 such that needle 1410 is in fluid flow communication with receptacle port 1086 . syringe port 1084 of stopcock 1052 preferably extends from housing element 1070 through slots 1842 formed in side surfaces thereof . preferably , pathway defining element 1092 extends from apertures 1810 and 1812 of top housing portion 1801 , and a bottom portion of stopcock 1052 extends through aperture 1818 of bottom housing element . housing element 1070 is preferably assembled such that top housing portion 1801 and bottom housing portion 1802 are connected by engagement of engagement surfaces 1828 of teeth 1824 of top housing portion 1801 and windows 1830 of bottom housing portion 1802 . reference is now made to fig4 , which is a sectional illustration of the drug mixing system of fig3 b during attachment of syringe 1040 to the adaptor assembly 1050 of fig4 - 45b . as seen in fig4 , luer tip 1044 of syringe 1040 is attached to syringe port 1084 of stopcock 1052 . at this stage , handle 1080 of stopcock 1052 is positioned such that fluid can flow from receptacle port 1086 to syringe 1040 thereof . it is appreciated that at this stage plunger 1042 of syringe 1040 is preferably pushed fully inward in the syringe . reference is now made to fig4 , which is a sectional illustration of the drug mixing system of fig3 c during attachment of spike port adaptor element 1030 and receptacle 1032 of fig3 a to the receptacle adaptor subassembly 1056 of the adaptor assembly 1050 of fig4 . as seen in fig4 , spike port adaptor element 1030 , having receptacle 1032 joined thereto , is connected to receptacle adaptor subassembly 1056 of adaptor assembly 1050 . spike 1308 is preferably previously inserted into spike port 1031 of receptacle 1032 , such that bore 1310 of spike element 1306 engages fluid content of receptacle 1032 . connection port 1318 of spike port adaptor element 1030 engages wall portions 1606 and base portion 1602 of main body element 1600 of receptacle adaptor subassembly 1056 . connection port 1318 is preferably locked into connection with receptacle adaptor subassembly 1056 by engagement of engagement surfaces 1626 of forward portions 1620 of arms 1614 ( fig4 b ) and a rearward facing wall portion of connection port 1318 . preferably , needle 1410 punctures needle protection cover 1412 and septum 1320 , resulting in a change to the structure of the needle protection cover . at this stage , receptacle 1032 is in fluid flow communication with syringe 1040 via bore 1310 of spike 1308 of spike port adaptor element 1030 , needle 1410 , bore 1660 and receptacle port and syringe port 1084 of stopcock 1052 . reference is now made to fig4 , which is a sectional illustration of the drug mixing system of fig3 d during attachment of vial 1060 to vial adaptor subassembly 1058 of the adaptor assembly 1050 of fig4 . vial 1066 and vial head adaptor element 1068 joined thereto ( fig3 e ) or vial 1060 is preferably pushed into engagement with vial puncturing spike 1722 of vial adaptor subassembly 1058 . typically , vial puncturing spike 1722 of vial adaptor subassembly 1058 punctures septum 1064 located inside top portion 1062 of vial 1060 , thus enabling fluid flow between the main body of vial 1060 and cylindrical portion 1748 of main body element 1702 of vial adaptor subassembly 1058 . preferably , puncturing of septum 1064 releases any vacuum in vial 1060 by entrance of air into vial 1060 through carbon filter 1404 ( fig4 b ) and membrane 1402 ( fig4 b ). engagement between vial adaptor subassembly 1058 and vial 1060 is preferably maintained by snap engagement of protrusions 1716 and 1718 ( fig4 a and 42b ) of rear portion 1704 of main body element 1702 with a neck portion 1063 of vial 1060 . the engagement of protrusions 1716 and 1718 with neck portion 1063 ensures that vial adaptor subassembly 1058 is latched onto vial 1060 and cannot be removed therefrom . tabs 1710 and outwardly tapered portions 1720 generally surround top portion 1062 and neck portion 1063 of vial 1060 . at this stage , the main body of vial 1060 is in fluid flow communication with syringe port 1084 via vial puncturing spike 1722 , bore 1750 of cylindrical portion 1748 and vial port 1082 of stopcock 1052 . reference is now made to fig4 , which is a sectional illustration of the drug mixing system of fig3 f and 48 during fluid drawing from receptacle 1032 into syringe 1040 . at this stage , plunger 1042 of syringe 1040 is preferably retracted , thus drawing fluid from receptacle 1032 into syringe 1040 . fluid drawn from receptacle 1032 reaches syringe 1040 via bore 1310 of spike 1308 of spike port adaptor element 1030 , needle 1410 , bore 1660 of receptacle adaptor subassembly 1056 , receptacle port 1086 , pathway defining element 1092 , syringe port 1084 and luer tip 1044 . reference is now made to fig5 , which is a sectional illustration of the drug mixing system of fig3 g and 48 during injection of fluid from syringe 1040 into vial 1060 . initially , the user rotates handle 1080 of stopcock 1052 , thus bringing syringe port 1084 into fluid flow engagement with vial port 1082 . preferably , the user pushes plunger 1042 of syringe 1040 inwardly with respect to syringe 1040 , resulting in injection of fluid from syringe 1040 to vial 1060 , thus dissolving the drug contained in the vial . the fluid injected from syringe 1040 flows to vial 1060 via luer tip 1044 of syringe 1040 , syringe port 1084 , pathway defining element 1092 , vial port 1082 , bore 1750 of cylindrical portion 1748 and vial puncturing spike 1722 . the user preferably shakes the drug mixing system of fig5 as shown in fig3 h , in order to ensure that the drug contained in vial 1060 is fully dissolved , and that the drug solution is homogenous . reference is now made to fig5 , which is a sectional illustration of the drug mixing system of fig3 i and 48 during drawing of fluid from vial 1060 into syringe 1040 . at this stage , the user positions the system such that vial 1060 is on top , and preferably draws at least part of the drug solution contained in vial 1060 , by at least partially retracting plunger 1042 of syringe 1040 . the fluid drawn from vial 1060 flows into syringe 1040 via vial puncturing spike 1722 , bore 1750 of cylindrical portion 1748 , vial port 1082 , pathway defining element 1092 and syringe port 1084 of stopcock 1052 and luer tip 1044 of syringe 1040 . reference is now made to fig5 , which is a sectional illustration of the drug mixing system of fig3 j and 48 during injection of fluid from syringe 1040 into receptacle 1032 . at a first stage , the user rotates handle 1080 of stopcock 1052 , resulting in syringe port 1084 being in fluid flow engagement with vial port 1082 . subsequently , plunger 1042 of syringe 1040 is preferably pushed inward with respect to the main body portion of the syringe . the inward displacement of plunger 1042 causes injection of fluid from syringe 1040 into receptacle 1032 . fluid drawn from syringe 1040 reaches receptacle 1032 via luer tip 1044 , syringe port 1084 , pathway defining element 1092 , receptacle port 1086 of stopcock 1052 , bore 1660 of receptacle adaptor subassembly 1056 , needle 1410 and bore 1310 of spike 1308 of spike port adaptor element 1030 . reference is now made to fig5 , which is a sectional illustration of the drug mixing system of fig3 l when ready for storage . as shown in fig5 , spike port adaptor element 1030 ( fig3 - 35 ) and receptacle 1032 joined thereto are disconnected from receptacle adaptor subassembly 1056 of adaptor assembly 1050 . typically , spike port adaptor element 1030 is disconnected from receptacle adaptor subassembly 1056 by slightly pushing arms 1614 extending from side surfaces 1612 ( fig3 - 40b ) of base portion 1602 , causing teeth 1620 to move outward and release the rearward facing wall portion of connection port 1318 ( fig3 - 35 ), thus disconnecting the connection port . typically , needle 1410 is released from connection port 1318 , and needle protection cover 1412 is deployed and once again fully encloses needle 1410 , thus preventing liquid spill and aerosol spray . adaptor assembly 1050 , including vial adaptor subassembly 1058 , stopcock 1052 , receptacle adaptor subassembly 1056 and housing element 1070 , is preferably stored in a suitable cooling facility . during cooling thereof , adaptor assembly is preferably connected to syringe 1040 , having plunger 1042 fully pushed inward , and to vial 1060 containing a drug solution therein . typically , pathway defining element 1092 of stopcock 1052 connects receptacle port 1086 to syringe port 1084 at this stage . reference is now made to fig5 a , 54 b , 54 c , 54 d , 54 e , 54 f , 54 g and 54 h which are simplified pictorial illustrations of various stages of assembly and typical use of a drug mixing system constructed and operative in accordance with yet another preferred embodiment of the present invention . fig5 a shows a spike port adaptor element 2010 , as described hereinbelow with reference to fig5 - 58 , being inserted into a spike port 2011 in a receptacle 2012 containing a fluid . preferably , a luer connector of spike port adaptor element 2010 is sealed by a luer cover element 2014 . typically , receptacle 2012 comprises a bag , and the fluid contained therein is sterile salt solution , water , or any other suitable sterile solution or pure fluid . as seen in fig5 b , a vial 2020 , including a top portion 2022 and a neck portion 2023 , is pushed into engagement with a vial adaptor subassembly 2044 of adaptor assembly 2040 . top portion 2022 of vial 2020 preferably has a septum 2024 sealingly seated therein . subassembly 2044 is described hereinbelow with reference to fig6 - 61b . alternatively , if a small vial 2026 is used , small vial 2026 is pushed into engagement with a vial head adaptor element 2030 which is described hereinbelow with reference to fig5 - 56 as shown in fig5 c , and is then pushed into engagement with vial adaptor subassembly 2044 . vials 2020 and 2026 typically contain a drug in soluble powder form , in a solution or in other suitable form . fig6 a and 67b show a sectional view of the drug mixing system at this stage . fig5 d shows spike port adaptor element 2010 and receptacle 2012 joined thereto , being connected to a receptacle adaptor subassembly 2046 of adaptor assembly 2040 , which is described hereinbelow with reference to fig6 - 63b . it is appreciated that receptacle adaptor subassembly 2046 and vial adaptor subassembly 2044 are preferably enclosed in a housing element 2050 of adaptor assembly 2040 , which is described hereinbelow with reference to fig6 a - 64b . it is appreciated by persons skilled in the art that the assembly steps shown in fig5 a - 54d may be performed in any suitable sequence . as seen in fig5 e , a user holds receptacle 2012 upright and squeezes the receptacle , thus at least partially filling vial 2020 with fluid squeezed out of receptacle 2012 . this flow of fluid ensures that the fluid remains sterile , and that the user is not exposed thereto . as seen in fig5 f , the user then shakes the drug mixing system of fig5 e to ensure that the drug in vial 2020 is fully dissolved and that the resulting solution is homogenous . as seen in fig5 g , the user reverses the direction of the receptacle 2012 , such that it is now facing downward , and then squeezes the receptacle . squeezing of the receptacle 2012 causes the drug solution contained in vial 2020 to be drawn into the receptacle , thus further diluting the solution . the user preferably repeats this action until vial 2020 is empty , thus diluting the entire content of the vial in a single receptacle . as shown in fig5 h , spiked receptacle adaptor element 2010 having receptacle 2012 joined thereto is disconnected from adaptor assembly 2040 , which remains connected to vial 2020 . it is appreciated that at this stage adaptor assembly 2040 and vial 2020 may be disposed of . the structure of elements of the drug mixing system of fig5 a - 54h is described hereinbelow with reference to fig5 - 64b . reference is now made to fig5 , which is a simplified pictorial illustration of a vial head adaptor element 2030 which forms part of the drug mixing system of fig5 a - 54h and to fig5 which is a sectional illustration taken along section lines lvi - lvi in fig5 . as seen in fig5 , vial head adaptor element 2030 is preferably a side - to - side symmetric integrally formed element which is preferably injection molded of plastic . vial head adaptor element 2030 preferably includes a main body portion 2200 which is generally cylindrical and has a central axis 2201 . an inner cylindrical surface 2202 of main body portion 2200 preferably has four arms 2204 extending therefrom , each arm 2204 being arranged at generally right angles with respect to its neighboring arms . each of arms 2204 terminates at an upper end thereof , in the sense of fig5 c , in an inwardly facing generally triangular tooth 2206 having a forwardly facing inclined surface 2208 and a bottom - facing engagement surface 2210 extending generally perpendicular to arm 2204 . at bottom surface of vial head adaptor element 2030 , there are formed four inwardly protruding surfaces 2212 , extending generally perpendicular to inner surface 2202 of main body portion 2200 . each of neighboring surfaces 2212 is preferably arranged at a generally right angle with respect to its neighboring surfaces 2212 . surfaces 2212 and arms 2204 are rotationally offset from one another about axis 2201 . reference is now made to fig5 , which is a simplified pictorial illustration of spike port adaptor element 2030 which forms part of the drug mixing system of fig5 a - 54h and to fig5 which is a sectional illustration taken along section lines lviii - lviii in fig5 . spike port adaptor element 2010 preferably comprises a hollow flexible plastic tube 2302 having associated therewith a standard clamp 2304 , which is commercially available from various manufacturers , such as qosina of italy . at a forward end thereof , tube 2302 is connected to a tube port 2305 of a hollow spike element 2306 which is preferably formed of plastic . spike element 2306 is preferably formed of a main body portion 2307 which preferably defines at a forward end thereof a spike 2308 , having formed therein an aperture communicating with an axially extending bore 2310 and an additional bore 2312 which extends partially through main body portion 2307 and communicates with a top portion of bore 2310 . rearward of spike 2308 , main body portion 2307 defines a generally circular planar protrusion 2314 adapted to define the location at which a user grips the spike . the interior of tube 2302 is in fluid flow communication with bore 2312 via tube port 2305 . bore 2310 preferably terminates in an aperture located in spike 2308 of main body portion 2307 and fully extends through the main body portion . main body portion 2307 preferably terminates in a connection port 2318 which is adapted to connect spike port adaptor element 2010 to receptacle adaptor subassembly 2046 . connection port 2318 preferably sealingly accommodates a generally circular septum 2320 on a seat 2322 . septum 2320 preferably engages the rear end of bore 2310 , thus sealing the rear end of the bore . forward of connection port 2318 , there is formed on main body portion 2307 a circumferential protrusion 2324 , forward of which is formed an additional circumferential protrusion 2326 , having an outer circumference which is slightly larger than that of protrusion 2324 . protrusions 2324 and 2326 are adapted to limit the movement of spike port adaptor element 2010 when it is connected to receptacle adaptor subassembly 2044 . a luer connector 2330 is preferably attached to a rear end of tube 2302 . luer connector 2330 preferably includes at a rearwardmost end thereof a narrow hollow port section 2332 , forward of which there is formed a connecting tube portion 2334 and a hollow neck portion 2336 which is adapted to connect luer connector 2330 to tube 2302 . preferably , luer connector 2330 is sealed by luer cover element 2014 . it is appreciated that spike port adaptor element 2010 may alternatively be identical to spike port adaptor element 630 described hereinabove with reference to fig1 - 11b . reference is now made to fig5 , which is a simplified exploded view illustration of adaptor assembly 2040 which forms part of the drug mixing system of fig5 a - 54h . as seen with particular clarity in fig5 , adaptor assembly 2040 comprises vial adaptor subassembly 2044 , onto which are placed a hydrophobic membrane 2402 , above which is optionally seated a carbon cloth filter 2404 . vial adaptor subassembly 2044 is connected at a forward portion thereof to a rear connection element 2406 of receptacle adaptor subassembly 2046 . a needle holding element 2408 is preferably seated within rear connection element 2406 and supports a needle 2410 . a forward portion of needle 2410 is preferably protected by a flexible latex needle protection element 2412 . receptacle adaptor subassembly 2046 connects at a rearward end thereof to rear connection element 2406 , enclosing needle holding element 2408 and needle protection element 2412 . the forward portion of vial adaptor subassembly 2044 as well as the rear portion of receptacle adaptor subassembly 2046 are located within housing element 2050 . reference is now made to fig6 , which is a simplified pictorial illustration of vial adaptor subassembly 2044 which forms part of adaptor assembly 2040 of fig5 and to fig6 a and 61b , which are sectional illustrations taken along respective section lines lxia - lxia and lxib - lxib in fig6 . as seen in fig6 - 61b , vial adaptor subassembly 2044 comprises a main body element 2502 arranged generally about an axis 2503 . main body element 2502 is preferably integrally formed and preferably injection molded of plastic . main body element 2502 is preferably side - to - side symmetric about axis 2503 , and preferably includes a rear portion 2504 , which is generally cylindrical and terminates in a forward wall 2506 . rear portion 2504 comprises a forward base section 2508 , preferably having four transversely extending outwardly facing protrusions 2509 extend therefrom , each protrusion being arranged at generally right angles with respect to its neighboring protrusions . rearward of base section 2508 there are formed a plurality of tabs 2510 each having a rectangular window 2512 . rearward of rectangular windows 2512 and on an inner surface 2514 of each of tabs 2510 there are preferably formed two radially extending inwardly facing protrusions 2516 each having an inclined surface . protrusions 2516 preferably terminate at a forward end thereof in an inwardly facing transversely extending protrusion 2518 . rearward of protrusions 2516 , each of tabs 2510 preferably includes an outwardly tapered portion 2520 . a hollow vial puncturing spike 2522 extends rearwardly from a rearward surface 2524 of forward wall 2506 , and is surrounded by base section 2508 and by tabs 2510 . rearward surface 2524 additionally includes a circular cylindrical protrusion 2525 , surrounding puncturing spike 2522 . two axially extending bores 2526 and 2527 extend through vial puncturing spike 2522 . forward of forward wall 2506 of rear portion 2504 there is formed an intermediate portion which formed of two generally rectangular surfaces 2528 , and includes an axial tubular portion 2530 having a bore 2531 extend therethrough , bore 2531 being in fluid flow engagement with bore 2526 of hollow vial puncturing spike 2522 . on the top rectangular surface 2528 and slightly recessed with respect thereto there is formed a plastic membrane support surface 2532 , having formed thereon a plurality of generally evenly distributed spherical protrusions 2534 , which are adapted to support hydrophobic membrane 2402 and prevent it from excessive inflation and from cracking . membrane 2402 is adapted to allow free passage of air to and from main body element 2502 , but to prevent passage of liquid and air borne particles , microorganisms and aerosol . a preferred membrane 2402 is model versapor r 0 . 2 micron which is commercially available from pall corporation of new york , u . s . a . a narrow bore 2537 connects membrane 2402 to bore 2531 , thus allowing pressure equalization in an evacuated drug vial 2020 upon connection of vial 2020 to the vial adaptor subassembly 2044 . when fluid first passes through the system during drug dilution , bore 2537 irreversibly fills with liquid , thus preventing air from escaping the system . prevention of the escape of air from the system is necessary for the reversible transfer of liquid from the receptacle 2012 to the vial 2020 and vice versa . air movement between vial 2020 and receptacle 2012 causes changes in pressure in the vial , thereby pushing liquid from the vial into the receptacle . a rim 2538 surrounding support surface 2532 is adapted to support an optional carbon cloth filter 2404 and maintain it in a raised position above and spaced from membrane 2402 . carbon filter 2404 is adapted to prevent toxic vapors from escaping from main body element 2502 , thus protecting users . a preferred carbon cloth filter 2404 is model no . zorflex emi which is commercially available from charcoal cloth international ltd . of houghton - le - spring , england . rectangular surfaces 2528 of the intermediate portion terminate at a forward end thereof in a forward facing cylindrical portion 2548 , having a bore 2550 extend therethrough . preferably , bore 2550 is a continuation of tubular portion 2530 of the intermediate portion . it is appreciated that the functionalities of membrane 2402 and carbon cloth filter 2404 , to allow free passage of air into the drug mixing system while preventing passage thereinto of liquid and air - borne particles , microorganisms and aerosol and preventing toxic vapors from escaping from the drug mixing system , may be incorporated , using similar elements , into any receptacle adaptor subassembly 2046 . reference is now made to fig6 , which is a simplified pictorial illustration of receptacle adaptor subassembly 2046 which forms part of the adaptor assembly 2040 of fig5 and to fig6 a and 63b , which are sectional illustrations taken along respective section lines lxiiia - lxiiia and lxiiib - lxiiib in fig6 . as seen in fig6 - 63b , receptacle adaptor subassembly 2046 includes a main body element 2600 which is arranged generally about an axis 2601 . main body element 2600 is preferably integrally formed of plastic , and is preferably side - to - side symmetric about axis 2601 . main body element 2600 preferably includes a generally cylindrical base portion 2602 terminating in a rear portion 2604 . top and bottom generally concave wall portions 2606 are formed at a forward end of base portion 2602 , each wall portion 2606 defining on an outer surface thereof an outwardly facing axially extending rib 2608 , which extends from a forwardmost end of each of wall portions 2606 and along base portion 2602 . a connection surface 2610 extending transversely from side surfaces 2612 of base portion 2602 connects an outwardly extending arm 2614 to each side surface 2612 . each arm 2614 preferably has a generally square rear portion 2616 , formed rearwardly of connection surface 2610 , and has a radially extending outwardly facing protrusion 2618 formed thereon . protrusion 2618 preferably extends onto an outer surface of a generally rectangular forward portion 2620 of each of arms 2614 , which extends forwardly of connection surface 2610 . an inwardly facing generally triangular tooth 2622 is formed adjacent a top end of each of forward portions 2620 . each tooth 2622 preferably includes a forwardly facing inclined surface 2624 and a rearwardly facing engagement surface 2626 . rear portion 2604 preferably includes a transversely extending generally circular portion 2630 which forms a base for ribs 2608 and which terminates at a rear end thereof in an axially extending generally cylindrical wall portion 2632 . wall portion 2632 preferably defines on a top and bottom surface thereof a small generally rectangular window 2634 , and two forwardly facing slots 2636 which are formed on either side of window 2634 . two generally symmetric side - facing tabs 2638 are formed on side surfaces 2640 of wall portion 2632 , each tab 2638 being formed forwardly of a generally rectangular forwardly facing slot 2642 . rear connection element 2406 preferably includes a forward disk 2652 defining a central bore 2654 . disk 2652 preferably functions as a terminating wall for a forward facing cylindrical portion 2656 . rearward of disk 2652 there is preferably formed a rear portion 2658 , having a narrow bore 2660 extend therethrough . bore 2660 preferably widens toward the rear end of rear portion 2658 , thus enabling rear portion 2658 to connect to an appropriate port . preferably , two generally symmetric tabs 2662 are formed on top and bottom surfaces of rear portion 2658 . cylindrical portion 2656 preferably has an outer circumference that is slightly smaller than that of wall portion 2632 , and is located therein . needle holding element 2408 preferably supports needle 2410 on a generally circular disk portion 2672 . needle 2410 extends axially through base portion 2602 of main body element 2600 and through bore 2660 of rear connection element 2650 . disk portion 2672 is preferably seated in cylindrical portion 2656 , and is locked into cylindrical portion 2656 by portion 2630 . reference is now made to fig6 a and 64b , which are simplified pictorial illustrations of the housing element 2050 which forms part of the adaptor assembly 2040 of fig5 in closed and open orientations , respectively . as seen in fig6 a and 64b , housing element 2050 is preferably integrally formed about an axis 2700 and includes a top housing portion 2701 and a bottom housing portion 2702 . preferably , housing portions 2701 and 2702 are side - to - side symmetric about axis 2700 . preferably , each of housing portions 2701 and 2702 includes a semi - cylindrical forward portion 2704 and a semi - cylindrical rearward portion 2706 . top and bottom housing portions 2701 and 2702 each include an inwardly recessed portion 2708 including a generally central elongate protrusion 2710 . top housing portion 2701 includes at forward and rearward ends thereof outwardly extending fingers 2722 terminating in a generally triangular teeth 2724 which include inclined outwardly facing surfaces 2726 and engagement surfaces 2728 . bottom housing portion 2702 preferably includes at forward and rearward ends thereof two generally rectangular windows 2730 which are placed generally below fingers 2722 and are adapted to engage engagement surfaces 2728 of fingers 2722 when housing element 2050 is assembled . an inner surface 2734 of housing element 2050 preferably includes at a rearward end thereof a circumferential recess 2736 which is adapted to engage protrusions 2509 of rear portion 2504 of vial adaptor subassembly 2044 . an outer surface of housing element 2050 which lies above recess 2736 preferably includes an outwardly facing protrusion 2740 which protrudes out of cylindrical rearward portion 2706 . reference is now made to fig6 , which is a simplified assembled pictorial illustration of the adaptor assembly 2040 of fig5 and to fig6 a and 66b , which are sectional illustrations taken along respective section lines lxvia - lxvia and lxvib - lxvib in fig6 . as seen in fig6 - 66b , rear portion 2504 of vial adaptor subassembly 2044 extends from a rear portion of housing element 2050 . vial puncturing spike 2522 preferably extends out of housing element 2050 , and is accessible for connection of vial 2020 or of vial 2026 ( fig5 b ) thereto . preferably , circumferential recess 2736 of inner surface 2734 of housing element 2050 engages protrusions 2509 of rear portion 2504 of vial adaptor subassembly 2044 . preferably , forward facing cylindrical portion 2548 engages rear portion 2658 of rear connection element 2406 . a rear end of needle 2410 at least partially extends through bore 2660 and through bore 2550 such that bore 2550 is in fluid flow communication with needle 2410 of receptacle adaptor subassembly 2046 . a forward portion of main body element 2600 of receptacle adaptor subassembly 2046 preferably extends from a forward portion of housing element 2050 of adaptor assembly 2040 , and surrounds needle 2410 enclosed in needle protection element 2412 . main body element 2600 including needle 2410 and needle protection cover 2412 is preferably accessible for connection of spike port adaptor element 2010 ( fig5 - 58 ) thereto . housing element 2050 is preferably assembled , such that top housing portion 2701 and bottom housing portion 2702 are connected by engagement of engagement surfaces 2728 of teeth 2724 of top housing portion 2701 and windows 2730 of bottom housing portion 2702 . reference is now made to fig6 a and 67b , which are sectional illustrations of the drug mixing system of fig5 b during attachment of vial 2020 to the vial adaptor subassembly 2044 of adaptor assembly 2040 of fig6 . vial 2026 and vial head adaptor element 2030 joined thereto ( fig5 c ) or vial 2020 is preferably pushed into engagement with vial puncturing spike 2522 of vial adaptor subassembly 2044 . typically , vial puncturing spike 2522 of vial adaptor subassembly 2044 punctures septum 2024 located inside top portion 2022 of vial 2020 , thus enabling fluid flow between the main body of vial 2020 and bore 2550 of cylindrical portion 2548 of main body element 2502 of vial adaptor subassembly 2044 . preferably , puncturing of septum 2024 releases any vacuum in vial 2020 by entrance of air into vial 2020 through optional carbon cloth filter 2404 ( fig6 a ) and membrane 2402 ( fig6 a ). engagement between vial adaptor subassembly 2044 and vial 2010 is preferably maintained by snap engagement of protrusions 2516 and 2518 of rear portion 2504 of main body element 2600 with neck portion 2023 of vial 2020 . the engagement of protrusions 2516 and 2518 with neck portion 2023 ensures that vial adaptor subassembly 2044 is latched onto vial 2020 and cannot be removed therefrom . tabs 2510 and outwardly tapered portions 2520 generally surround top portion 2022 and neck portion 2023 of vial 2020 . at this stage , the main body of vial 2020 is in fluid flow communication with needle 2410 via vial puncturing spike 2522 , bore 2550 of cylindrical portion 2548 and bore 2660 of cylindrical portion 2658 . reference is now made to fig6 , which is a sectional illustration of the drug mixing system of fig5 d - 54g during attachment of the receptacle port adaptor element 2010 and receptacle 2012 of fig5 a to the receptacle adaptor subassembly 2046 of adaptor assembly 2040 of fig6 , having vial 2020 attached thereto . as seen in fig6 , spike port adaptor element 2010 , having receptacle 2012 joined thereto , is connected to receptacle adaptor subassembly 2046 of adaptor assembly 2040 . spike 2308 is preferably previously inserted into spike port 2011 of receptacle 2012 , such that bore 2310 of spike element 2306 engages fluid content of receptacle 2012 . connection port 2318 of spike port adaptor element 2010 engages wall portions 2606 and base portion 2602 of main body element 2600 of receptacle adaptor subassembly 2046 . connection port 2318 is preferably locked into connection with receptacle adaptor subassembly 2046 by engagement of engagement surfaces 2626 of forward portions 2620 of awls 2614 and a rearward facing wall portion of connection port 2318 . preferably , needle 2410 punctures needle protection cover 2412 and septum 2320 , resulting in partial collapse of the needle protection cover . at this stage , receptacle 2012 is in fluid flow communication with the main body of vial 2020 via bore 2310 of spike 2308 of spike port adaptor element 2010 , needle 2410 , bore 2660 , bore 2550 of cylindrical portion 2548 , bore 2531 of tubular portion 2530 and vial puncturing spike 2522 . reference is now made to fig6 , which is a sectional illustration of the drug mixing system of fig5 h and 68 during disconnection of the spike port adaptor element 2010 and receptacle 2012 from the receptacle adaptor subassembly 2046 of adaptor assembly 2040 of fig6 . as shown in fig6 , spike port adaptor element 2010 and receptacle 2012 joined thereto are disconnected from receptacle adaptor subassembly 2046 of adaptor assembly 2040 . typically , spike port adaptor element 2010 is disconnected from receptacle adaptor subassembly 2046 by slightly pushing arms 2614 extending from side surfaces 2612 of base portion 2602 , causing teeth 2620 to move outward and release the rearward facing wall portion of connection port 2318 , thus disconnecting the connection port . typically , needle 2410 is released from connection port 2318 , and needle protection cover 2412 is deployed and once again fully encloses needle 2410 , thus sealing it to prevent leakage . reference is now made to fig7 which is a simplified exploded view illustration of a drug mixing system constructed and operative in accordance with a further preferred embodiment of the present invention . the embodiment of fig7 is a modification of the embodiments of fig3 a - 53 and 54 a - 69 . accordingly , for the sake of conciseness , it is described hereinbelow in somewhat abbreviated faun with reference to fig7 - 78 . in this embodiment the drug vial is enclosed in a protective housing used during storage and dilution , thereby preventing spills in case of breakage . as seen with particular clarity in fig7 , the drug mixing system comprises a vial adaptor subassembly 3000 , which preferably comprises an externally threaded vial support element 3010 , into which is placed a vial 3020 . a vial puncturing cover assembly 3030 comprises an internally threaded covering element 3032 , which connects at a forward end thereof to the externally threaded portion of vial support element 3010 . at a top end thereof , covering element 3032 engages a vial puncturing spike element 3034 , which supports a hydrophobic membrane 3036 . vial puncturing cover assembly 3030 connects at a forward end thereof to a connection port of a receptacle adaptor subassembly 3040 , which is adapted to engage a spike port receptacle adaptor element 3050 . spike port receptacle adaptor element 3050 is preferably inserted into a receptacle port 3051 of a receptacle 3052 . alternatively , vial puncturing cover assembly 3030 may connect at a forward end thereof to a vial port 3080 of a stopcock 3082 , and the connection port of receptacle port adaptor assembly 3040 connects to a receptacle port 3084 of stopcock 3082 . when this option is used , a syringe port 3086 of stopcock 3082 preferably engages a luer fitted syringe . it is appreciated that vial 3020 may be identical to either of vials 2020 and 2026 , and that receptacle 3052 may be identical to receptacle 2012 , described hereinabove with reference to fig5 a - 54c . receptacle adaptor subassembly 3040 may be identical to receptacle adaptor subassembly 2046 , described hereinabove with reference to fig6 - 63b . spike port adaptor element 3050 may be identical to spike port adaptor element 2010 , described hereinabove with reference to fig5 - 58 . reference is now made to fig7 which is a simplified pictorial illustration of a vial support element 3010 which forms part of vial adaptor subassembly 3000 of the drug mixing system of fig7 and to fig7 a and 72b which are , respectively , a sectional illustration and a pictorial sectional illustration taken along section lines lxxii - lxxii in fig7 . vial support element 3010 comprises a generally cylindrical body element 3100 arranged generally about an axis 3101 . body element 3100 is preferably integrally formed and preferably is generally side - to - side symmetric about axis 3101 . body element 3100 preferably includes a top portion 3102 , which is externally threaded and which is separated from a bottom portion 3104 by an outwardly facing circumferential protrusion 3106 . four axially extending outwardly facing protrusions 3108 are preferably formed on bottom portion 3104 , each protrusion 3108 being arranged at generally right angles with respect to its neighboring protrusions . body element 3100 preferably terminates in a transversely extending base wall portion 3110 , which includes a central spherical protrusion 3112 which is adapted to center vial 3020 in vial support element 3010 . as seen with particular clarity in fig7 b , an inner surface 3114 of body element 3100 may optionally include a plurality of axially extending inwardly facing generally rectangular protrusions 3116 , which are operative to adapt vial support element 3010 to support a smaller vial . different body elements 3100 , molded with protrusions 3116 of different sizes , may be used for different vial sizes . similarly , base wall portion 3110 may optionally be molded at various heights with respect to bottom portion 3104 , thus enabling different vial support elements 3010 to support vials of different heights . reference is now made to fig7 , which is a simplified pictorial illustration of vial support element 3010 of fig7 - 72b containing a vial 3020 and to fig7 , which is a sectional illustration taken along section lines lxxiv - lxxiv in fig7 . as seen in fig7 and 74 , vial 3020 is placed within vial support element 3010 , such that top portion 3022 , septum 3024 and at least part of neck portion 3023 extend above the vial support element and are accessible to a user . a base of vial 3020 is preferably seated on base wall portion 3110 and engages spherical protrusion 3112 . reference is now made to fig7 a and 75b , which are simplified pictorial illustrations of vial puncturing cover assembly 3030 which forms part of the vial adaptor subassembly 3000 of fig7 and to fig7 which is a sectional illustration taken along section lines lxxvi - lxxvi in fig7 a . vial puncturing cover assembly 3030 includes covering element 3032 , which comprises a generally cylindrical main body portion 3202 arranged generally about an axis 3203 . main body portion 3202 is preferably internally threaded and is adapted to engage the externally threaded top portion 3102 of vial support element 3010 . four axially extending outwardly facing protrusions 3204 are preferably formed on an outer surface 3205 of main body portion 3202 , each protrusion 3204 being arranged at generally right angles with respect to its neighboring protrusions . an outwardly facing radially extending wall portion 3206 extends from a bottom end of main body portion 3202 . main body portion 3202 terminates in a wall portion 3208 , which preferably extends transversely with respect to axis 3203 and includes a generally round aperture 3210 . an inner surface 3212 of wall portion 3208 preferably includes two semi - circular tracks 3214 . vial puncturing spike element 3034 preferably includes a vial puncturing spike 3220 extending through aperture 3210 of wall portion 3208 . vial puncturing spike 3220 preferably has two axial bores 3222 and 3224 extending therethrough . preferably membrane 3036 is in fluid flow engagement with cover element 3032 via bore 3224 of vial puncturing spike 3220 . spike 3220 preferably extends forwardly from a generally circular wall portion 3226 , which engages a top surface of wall portion 3208 . four generally rectangular wall portions 3228 extend radially from spike 3220 , each wall portion 3228 being arranged at generally right angles with respect to its neighboring wall portions . wall portions 3228 preferably define at top surfaces thereof four spherical protrusions 3230 , which engage tracks 3214 and are adapted to lock vial puncturing spike element 3034 with respect to covering element 3032 . a generally cylindrical portion 3232 , including an axial bore 3234 , preferably extends rearwardly from wall portion 3226 . cylindrical portion 3232 is preferably adapted to engage rear portion 3658 of receptacle adaptor subassembly 3040 . a second generally cylindrical portion 3236 preferably extends rearwardly of wall portion 3226 and adjacent cylindrical portion 3232 . portion 3236 preferably defines a seat 3238 which is adapted to support unidirectional breathing membrane 3036 and prevent it from excessive inflation and from cracking . membrane 3036 is adapted to allow free passage of air into the main body element 3032 , but prevent passage therethrough of liquid and air - borne particles , microorganisms and aerosol . a preferred membrane 3036 is model versapor r 0 . 2 micron which is commercially available from pall corporation of new york , u . s . a . reference is now made to fig7 , which is a simplified assembled pictorial illustration of the vial adaptor subassembly 3000 of fig7 and to fig7 , which is a sectional illustration taken along section lines lxxviii - lxxviii in fig7 . as seen in fig7 and 78 , vial puncturing cover assembly 3030 threadably engages vial support element 3010 , thus enclosing therein vial 3020 . the threaded engagement between vial support element 3010 and vial puncturing cover element 3032 causes puncturing spike 3220 to be pushed into engagement with vial 3020 . typically , vial puncturing spike 3220 of vial puncturing cover element 3030 punctures septum 3024 located inside top portion 3022 of vial 3020 , thus enabling fluid flow between the main body of vial 3020 and bore 3234 of cylindrical portion 3232 via bore 3222 of puncturing spike 3220 . preferably , puncturing of septum 3024 releases any vacuum in vial 3020 . reference is now made to fig7 , which is a pictorial illustration of the vial adaptor subassembly 3000 of fig7 when assembled to receptacle adaptor subassembly 3040 thus forming an adaptor assembly in accordance with a preferred embodiment of the present invention , and to fig8 , which is a sectional illustration taken along section lines lxxx - lxxx in fig7 . as seen in fig7 and 80 , cylindrical portion 3232 of vial cover element 3030 engages rear portion 3658 of receptacle adaptor subassembly 3040 . a rear end of needle 3410 at least partially extends through bore 3660 and through bore 3234 such that bore 3234 is in fluid flow communication with needle 3410 of receptacle adaptor subassembly 3040 . due to fluid flow communication between bore 3234 and the main body of vial 3020 , needle 3410 is in fluid flow communication with vial 3020 . a forward portion of main body element 3414 of receptacle adaptor subassembly 3040 preferably surrounds needle 3410 enclosed in needle protection element 3412 . main body element 3600 including needle 3410 and needle protection cover 3412 is preferably accessible for connection of spike port adaptor element 3050 thereto . it is appreciated that cylindrical portion 3232 of vial cover element 3030 may alternatively engage a stopcock 3052 , which additionally engages receptacle adaptor subassembly 3040 and a syringe as described hereinabove with reference to fig3 a - 53 . in such a case , the method of use of the system would be similar to that described in fig3 a - 31l . reference is now made to fig8 , which is a pictorial illustration of vial adaptor subassembly 3000 connected to receptacle adaptor subassembly 3040 of fig7 when connected to a spike port adaptor element 3050 and receptacle 3052 and to fig8 , which is a sectional illustration taken along section lines lxxxii - lxxxii in fig8 . as seen in fig8 and 82 , spike port adaptor element 3050 , having receptacle 3052 joined thereto , is connected to receptacle adaptor subassembly 3040 . a spike 3308 is preferably previously inserted into spike port 3051 of receptacle 3052 , such that a bore 3310 of a spike element 3306 engages fluid content of receptacle 3052 . a connection port 3318 of spike port adaptor element 3050 engages wall portions 3606 and base portion 3602 of main body element 3414 of receptacle adaptor subassembly 3040 . connection port 3318 is preferably locked into connection with receptacle adaptor subassembly 3040 by engagement of engagement surfaces 3626 of forward portions 3620 of arms 3614 and a rearward facing wall portion of connection port 3318 . preferably , needle 3410 punctures needle protection cover 3412 and septum 3320 , resulting in partial collapse of the needle protection cover . at this stage , receptacle 3052 is in fluid flow communication with the main body of vial 3020 via bore 3310 of spike 3308 of spike port adaptor element 3050 , needle 3410 , bore 3660 , bore 3234 of cylindrical portion 3232 and vial puncturing spike 3220 . reference is now made to fig8 , which is a simplified exploded view illustration of a drug mixing system constructed and operative in accordance with a still further preferred embodiment of the present invention . the embodiment of fig8 is a modification of the embodiment of fig5 a - 69 . accordingly , for the sake of conciseness , it is described hereinbelow in somewhat abbreviated form with reference to fig8 - 92 . as seen with particular clarity in fig8 , the drug mixing system comprises a receptacle adaptor subassembly 4000 which preferably comprises a receptacle adaptor housing element 4010 . receptacle adaptor housing element 4010 preferably engages a receptacle adaptor needle assembly 4020 . receptacle adaptor subassembly 4000 preferably engages a port such as a receptacle port 4031 of a receptacle 4032 . receptacle adaptor needle assembly 4020 connects at a rearward end thereof to a connection port of a vial adaptor subassembly 4040 , which is adapted to engage a vial 4050 . it is appreciated that vial 4050 may be identical to either of vials 2020 and 2026 , and receptacle 4032 may be identical to receptacle 2032 , described hereinabove with reference to fig5 a - 54c . vial adaptor subassembly 4040 may be identical to vial adaptor subassembly 2046 , described hereinabove with reference to fig6 - 61b . receptacle port 4031 may be identical receptacle port 2031 , described hereinabove . it is appreciated that receptacle adaptor subassembly 4000 may engage a spike port adaptor element such as spike port adaptor element 2030 described hereinabove with reference to fig5 - 58 . reference is now made to fig8 , which is a simplified pictorial illustration of receptacle adaptor housing element 4010 which fauns part of the drug mixing system of fig8 and to fig8 a and 85b , which are sectional illustrations taken along section lines lxxxva - lxxxva and lxxxvb - lxxxvb in fig8 . receptacle adaptor housing element 4010 comprises a body element 4100 , arranged generally about an axis 4101 . body element 4100 comprises a tube of generally rectangular cross - section , is preferably integrally formed and preferably is generally side - to - side symmetric about axis 4101 . body element 4100 preferably includes a rear portion 4102 which is formed with ribbed grip regions 4104 on an outer surface 4106 . two elongate windows 4108 are preferably formed on top and bottom surfaces of rear portion 4102 . a forward portion 4110 of body element 4100 has a slightly smaller outer circumference than that of rear portion 4102 , and includes a generally rectangular window 4112 on each of the surfaces thereof . forward portion 4110 preferably sealingly accommodates a septum 4114 in a seat 4116 . four axially extending tabs 4118 extend forwardly of forward portion 4110 , each tab 4118 being arranged at generally right angles with respect to its neighboring tabs . each tab 4118 preferably includes and an inwardly facing tooth 4120 and preferably terminates in an outwardly tapered portion 4122 . reference is now made to fig8 , which is a simplified pictorial illustration of receptacle adaptor needle assembly 4020 which forms part of the drug mixing system of fig8 and to fig8 a and 87b , which are sectional illustrations taken along section lines lxxxviia - lxxxviia and lxxxviib - lxxxviib in fig8 . receptacle adaptor needle assembly 4020 comprises a generally cylindrical body element 4200 , arranged generally about an axis 4201 . body element 4200 is preferably integrally formed and preferably is generally side - to - side symmetric about axis 4201 . body element 4200 preferably includes a rear connection port 4202 which is separated from a forward portion 4204 by a circumferential outwardly extending protrusion 4206 . protrusion 4206 is adapted to limit the extent to which receptacle adaptor needle assembly 4020 is inserted into receptacle adaptor housing element 4010 . forward portion 4204 preferably terminates in a forward wall portion 4205 from which extends a cylindrical portion 4210 having an outer circumference which is slightly larger than that of forward portion 4204 . cylindrical portion 4210 preferably has formed thereon four axially extending protrusions 4212 , each protrusion 4212 being arranged at generally right angles with respect to its neighboring protrusions . two outwardly extending arms 4214 are formed at a forward end of cylindrical portion 4210 , each aim 4214 being generally across from the other arm . protrusions 4212 and arms 4214 are preferably rotationally offset from one another about axis 4201 . each arm 4214 preferably defines at a forward most end thereof a generally triangular tooth 4216 including an engagement surface 4218 . a hollow needle 4220 is preferably sealingly mounted in a cylindrical portion 4222 which is formed within cylindrical portion 4210 of receptacle adaptor needle assembly 4020 . reference is now made to fig8 , which is a simplified assembled pictorial illustration of the receptacle adaptor subassembly 4000 of fig8 and to fig8 a and 89b , which are sectional illustrations taken along section lines lxxxixa - lxxxixa and lxxxixb - lxxxixb in fig8 . as seen in fig8 - 89b , cylindrical portion 4210 of receptacle adaptor needle assembly 4020 preferably engages a rearwardmost portion of rear portion 4102 of receptacle adaptor housing element 4010 . teeth 4216 of arms 4214 of cylindrical portion 4210 preferably extend through windows 4108 and maintain receptacle adaptor needle assembly 4020 locked in receptacle adaptor housing element 4010 . it is appreciated that a user may push receptacle adaptor needle assembly 4020 inward with respect to receptacle adaptor housing element 4010 . such inward motion of receptacle adaptor needle assembly 4020 is limited by protrusion 4206 . reference is now made to fig9 , which is a pictorial illustration of the receptacle adaptor subassembly 4000 of fig8 when assembled to a vial adaptor subassembly 4040 and to port 4031 of receptacle 4032 , prior to insertion of needle 4220 into the receptacle port 4031 and to fig9 , which is a sectional illustration taken along section lines xci - xci in fig9 . vial 4050 is preferably pushed into engagement with a vial puncturing spike 4522 of vial adaptor subassembly 4040 . typically , vial puncturing spike 4522 of vial adaptor subassembly 4050 punctures a septum 4014 located inside a top portion 4012 of vial 4050 , thus enabling fluid flow between the main body of vial 4050 and a bore 4550 of a cylindrical portion 4548 of main body element 4502 of vial adaptor subassembly 4050 . preferably , puncturing of septum 4014 releases any vacuum in vial 4050 by entrance of air into vial 4050 through a carbon filter 4404 and a membrane 4402 . engagement between vial adaptor subassembly 4040 and vial 4050 is preferably maintained by snap engagement of protrusions 4516 and 4518 of rear portion 4504 of main body element 4502 with neck portion 4013 of vial 4050 . the engagement of protrusions 4516 and 4518 with neck portion 4013 ensures that vial adaptor subassembly 4040 is latched onto vial 4050 and cannot be removed therefrom . tabs 4510 and outwardly tapered portions 4520 generally surround top portion 4012 and neck portion 4013 of vial 4050 . cylindrical portion 4548 preferably engages connection port 4202 of receptacle adaptor needle assembly 4020 , such that needle 4220 is in fluid flow communication with vial 4050 via forward portion 4204 , bore 4550 of cylindrical portion 4548 and vial puncturing spike 4522 . the sharpened tip of needle 4220 preferably partially extends through septum 4114 . teeth 4120 of arms 4118 preferably engage receptacle port 4031 of receptacle 4032 , or may alternatively engage any other suitable port such as a spike port adaptor element 4030 as described hereinabove . reference is now made to fig9 , which is a pictorial illustration of the receptacle adaptor subassembly 4000 of fig8 when assembled to a vial adaptor subassembly 4040 and to port 4031 of receptacle 4032 , following insertion of needle 4220 into receptacle port 4031 and to fig9 , which is a sectional illustration taken along section lines xciii - xciii in fig9 . as seen in fig9 and 93 , a user preferably pushes receptacle adaptor needle assembly 4020 inward , such that needle 4220 pierces septum 4114 , resulting in fluid flow communication between receptacle 4032 and vial 4050 . it will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove . rather the scope of the present invention includes both combinations and subcombinations of various features described hereinabove as well as modifications thereof which would occur to persons skilled in the art upon reading the foregoing specification and which are not in the prior art .

US-201213357004-A

a drug - eluting endocardial lead and method of manufacture . the silicone elastomer of the present invention is ideally suited to a manufacturing environment due to its extended pot life and decreased curing time . a preferred silicone elastomer is comprised of a multi - part mixture having at least a base portion and a curing portion . additionally , since curing does not begin until the base and curing portions are combined , the mixing can be physically undertaken closer to the location of the endocardial lead and the curing “ clock ” does not start until the mixing occurs and external heat is applied . since the silicone elastomer formed by base and curing components have improved the pot life and curing characteristics , the mixture is suitable for mixing with a steroid and then dispensing into an endocardial lead tip thus eliminating current design limitations imposed by current art while concomitantly minimizing manufacturing costs .

the following description is of the best mode presently contemplated for carrying out the invention . this description is not to be taken in a limiting sense , but is made merely for the purpose of describing the general principles of the invention . the scope of the invention should be determined with reference to the claims . fig1 shows a simplified diagram of the apparatus 10 of the present invention for forming a mixture of a drug , e . g ., a steroid , and a silicone elastomer and subsequently dispensing the mixture into a plurality of endocardial leads . although not shown in detail , the leads 34 and 34 ′ illustrated in fig1 represent implantable cardiac pacing leads , such as endocardial leads well known in the art . as was previously mentioned and also known in the art , upon implant of the lead in the heart , the heart tissue in contact with the leads distal tip electrode may become inflamed . heretofore , many attempts have been made to abate the inflammation at the implant site immediately upon implant . these attempts include placing a monolithic controlled release device ( hereinafter just “ mcrd ”) mixture in the leads tip electrode that comes in contact with the cardiac tissue . the efficacy of such mcrd mixtures is of course dependent upon the constituent parts or ingredients comprising the mcrd . the present invention attempts to greatly improve the efficacy of inflammation - reducing drugs with a new compound and method of manufacture that is intended among other things to be used in conventional cardiac pacing leads . each of the leads contemplated for use with the present invention includes a chamber for housing a drug dispensing means either in the form of a mcrd containing plug or a porous electrode at the leads distal tip . the silicone elastomer contemplated for the present invention is formed by mixing and curing multiple components , including at least a base component 12 and a curing component 14 . this silicone elastomer is used as a carrier for a drug 16 , which is concurrently mixed with the base 12 and curing 14 components . initially , the base component 12 is loaded into container a 18 , the curing component 14 is loaded into container b 20 and the drug 16 is loaded into container c 22 . the three components are fed , preferably with the assistance of pumps 24 , 26 , 28 to a first mixer 30 , e . g ., a static mixer , where they are combined into a drug / carrier mixture 31 , i . e ., a monolithic controlled release device ( mcrd ) mixture . ( the mixing process can be further improved with the use of additional components , as discussed further below .) the mcrd mixture 31 ( in a pourable form , e . g ., 0 – 2000 poise , until the curing process completes ) is then fed into a suitable dispenser 32 , such as a needle or equivalent , from which it is dispensed , either by injection or by forming droplets of the mixture into the distal end of an endocardial lead 34 . due to the large pot life , e . g ., 1 hour or more , the mixture may be dispensed into a plurality of such leads 34 . accordingly , a plurality of leads 34 may be held by a curing jig 36 ( described further below ) and the dispenser 32 ( or optionally the whole apparatus 10 ) may be repositioned so that the mcrd mixture 31 can be dispensed into a plurality of leads 34 within the pot life time . alternatively , one of ordinary skill in the art will readily recognize that the curing jig 36 may be repositioned relative to the dispenser 32 to accomplish the same function . this repositioning can be done via computer numerical control ( cnc ) type means ( not shown ) well known in the art , e . g ., servo motors , stepper motors , hydraulics , pneumatics , etc . once the mcrd mixture 31 has been formed and dispensed , the curing process begins . if left at room temperature , the curing process would take approximately 24 hours . however , elevating the temperature of the mcrd mixture 31 will significantly decrease the curing time and , accordingly , the manufacturing process time . preferably , the temperature of the mcrd mixture 31 is elevated by heating at least the distal end of the leads 34 to a temperature between 40 ° c . and 75 ° c ., preferably about 55 ° c . at the preferred temperature a curing time of approximately 2 hours is anticipated , while at 65 ° c ., the curing time can be further decreased to approximately 1 hour . to elevate the temperature , a heater controller 38 is used to heat the curing jig 36 ( preferably metallic ) via a heater 40 and preferably under feedback control of a temperature sensor 42 . the operation of such a heater controller 38 , e . g ., a pulse interval derivative ( pid ) controller , is well known in the art . depending upon the selected curing temperature , the mcrd mixture 31 is cured within the endocardial lead in approximately 1 to 2 hours . in a preferred variation of the aforedescribed process , a wetting fluid 44 , placed in container d 46 , is premixed with drug 16 ( typically in a powder form ) by a second mixer 48 to form a premixed fluid drug component that will mix easier with the base 12 and curing 14 components in the first mixer 30 . additionally , it is preferred that this premixed fluid drug component be fed via pump 28 to a third mixer 50 , e . g ., a static mixer , where it is mixed with the base component 12 before the curing component 14 is mixed in at the first mixer 30 . apparatus 10 may be used with active fixation leads 34 or may be used with passive fixation leads lead 34 ′. in the case of the active fixation leads 34 , the dispenser 32 is repositioned relative to each lead 34 and the mcrd mixture 31 is either injected or droplets are dripped into the distal tip 52 of the lead 34 and cured in a chamber 54 . in the case of a passive fixation lead 34 ′, the mcrd mixture is preferably injected , e . g ., via a syringe type nozzle at the end of the dispenser 32 into a chamber 54 ′ through the distal tip 52 ′ of each lead 34 ′. the mcrd mixture 31 is then cured in the chamber 54 ′. alternatively , a plurality of electrode tip portions 56 , e . g ., ones with sintered porous tips , may be positioned in the curing jig 36 and droplets 58 of the mcrd mixture can be dripped into the backside of the electrode tip 56 and cured . following curing , the distal electrode tip 56 may be attached , e . g ., welded , to the rest of the lead 34 ′ via conventional means . in each of these cases the mcrd mixture 31 cures into a plug 59 within the chamber 54 ′ and thus does not require a separate manufacturing insertion step as is typically found in the prior art . furthermore , there is little waste and many such leads can be manufactured in a single operation . accordingly , the material and manufacturing costs are reduced from that typically found in the prior art . various materials can be used in the above process . the currently preferred combinations ( drug 16 is dexamethasone sodium phosphate in each of these cases ) are described below : fig2 shows a simplified flow chart of the process used in forming , dispensing and curing the mcrd mixture into an endocardial lead 34 . initially in steps 60 , 62 , 64 and 66 , containers 18 , 20 , 22 and 46 are filled with the base component 12 , the curing component 14 , the drug component 16 , and the fluid component 44 , respectively . next , in step 68 , the drug and fluid , e . g ., wetting fluid , are mixed using the second mixer 48 . this wetted drug mixture is then mixed in step 70 with the base 12 and curing 14 components using the first mixer 30 and dispensed in step 72 used the dispenser 32 . optionally , the wetted drug mixture is first mixed with the base component 12 using the third mixer 50 before mixing with the curing component in the first mixer 30 . finally , the temperature of the dispensed mcrd mixture 31 is elevated in step 74 to reduce the curing time . while the invention has been described by means of specific embodiments and applications thereof , it is understood that numerous modifications and variations could be made thereto by those skilled in the art without departing from the sprit and scope of the invention . for example , while dexamethasone sodium phosphate is the preferred steroid drug to be used in forming the mcrd , other drugs and steroids could also be used , e . g ., glucocorticosteroid . furthermore , while the disclosed composition is particularly suitable for eliminating manufacturing steps , its improved curing properties can also be beneficially used to more quickly generate externally molded plugs for later insertion into endocardial leads . for example as shown in fig3 , the dispenser 32 may be used to dispense beads of uncured mcrd material 31 into one or more grooves 80 on a heated curing jig plate 82 . once the beads are cured , the mcrd material may be sliced into plugs and inserted into endocardial leads as in the prior art . however , this process will still be completed in less time and with less waste . alternatively , any curing jig having a plurality of curing cavities may be used . it is therefore to be understood that within the scope of the claims , the invention may be practiced otherwise than as specifically described herein .

US-73608203-A

for connecting the end of a supplemental vessel to the side of a body vessel , which has a greater diameter than the supplemental vessel , use is made of a sleeve whose one end portion is expandable for the forming of an annular end flange . as a result , the supplemental vessel , after being passed through the sleeve in the direction of the expandable end portion and folding back at least over the expandable end portion , is formable into a collar , both sides of which enclose the annular end flange inside the supplemental vessel and internally surround an opening formed therein . the distal portion of the sleeve to be inserted into the body vessel may comprise a memory material enabling the end flange to be formed without using the balloon .

the heart 1 shown in fig1 has two coronary vessels 2 , 3 each having a blocking 4 , 5 in the form of a stenosis or an occlusion . fig1 illustrates schematically how these blockings are bypassed by means of two vessels 6 , 7 which can be taken from the patient himself . more specifically , one end of the vessel 6 is connected after the blocking 4 , seen in the normal direction of flow in the vessel 2 , and its other end is connected to the aorta 8 , such that a sufficient quantity of oxygen - rich blood will be supplied to the already blocked coronary vessel 2 after the blocking 4 therein . the same applies to the vessel 3 . for effecting the connection of the vessel 6 to the coronary vessel 2 , a branching device according to international patent application no . pct / se97 / 00804 ( and corresponding to u . s . patent application ser . no . 09 / 192 , 895 which was filed on may 16 , 1997 ) can be used . the connecting apparatus according to the present invention concerns the connection of the other end 9 , 10 of the vessel 6 or 7 to a vessel , e . g . the aorta 8 , ( i . e . a supplemental vessel to a body vessel ) which thus should give a sufficient flow of blood to provide the coronary vessel 2 , 3 after the blocked point 4 , 5 with a sufficient supply of oxygen . as shown in fig2 the connecting apparatus according to the invention comprises a sleeve 11 of a metal or plastic that is not rejected by body tissue . the sleeve 11 comprises an end or distal portion 12 having a plurality of axial slots 13 and axially directed , intermediate ribs 14 . except for the end portion 12 , the sleeve 11 is relatively rigid . the ribs 14 of the end portion 12 are also relatively rigid , but flexible outwards from their axial direction in fig2 to a radial direction , as is best seen in fig5 . in the outwardly - flexed state , the ribs 14 form an annular radial end flange 15 , as is also best seen in fig5 . an alternative to the sleeve 11 in fig5 is shown in fig7 . instead of having the slots 13 and the ribs 14 , the sleeve 111 in fig7 is , at least at its end 112 , made of a net - like flexible material , e . g . of stent type , so as to give the flange 115 of the sleeve 111 the appearance which is schematically shown in fig7 . the connecting apparatus further utilises a balloon 16 , a locking ring 17 and a locking sleeve 18 . fig2 also shows part of the first blood vessel 6 adjacent to the end 9 thereof . more precisely , the blood vessel 6 is shown in the form it gets after being passed , end 9 first , through the sleeve 11 in the direction of the end portion 12 of the sleeve and subsequently has been folded back with its outer part at least over the end portion 12 of the sleeve 11 , preferably past the end portion 12 . the balloon 16 is made of an elastic material , but has an inlet tube 19 which is essentially nonelastic . the inlet tube 19 is adapted to be passed through the vessel 6 , for instance after the vessel 6 has been arranged on the sleeve 11 in the manner described above . the balloon 16 may also comprise an essentially nonelastic portion 20 adjacent to the inlet tube 19 for a purpose that will be described below . the locking ring 17 is an essentially planar ring having a plurality of axially directed pins 21 , which project in the same direction from one flat side of the ring . each pin 21 has one or more barbs 22 , which ensure that the pin 21 remains once it has been passed through a material , in this case the vessel 6 and the end flange 15 , as will be described in more detail below . the locking sleeve 18 serves to safely retain on the sleeve 11 that part of the vessel 6 which has been folded back over the sleeve 11 and past the end portion 12 . more specifically , the locking sleeve 18 is of such a design that it can be opened and be moved inwards laterally over that part of the vessel 6 which has been folded back over the sleeve 11 , and then be clamped , such that the interiorly of the locking part positioned part of the vessel 6 is locked against the sleeve 11 . alternatively , the locking sleeve 18 can be integrally formed with the locking ring 17 . a method for connecting the vessel 6 to the vessel 8 by means of an inventive apparatus will be described below with reference to fig3 and 4 . the end 9 of the vessel 6 is first passed through the sleeve 11 and folded back over the end portion 12 and somewhat past this . the folded - back part of the vessel 6 is fixed on the sleeve 11 by means of the locking sleeve 18 . the inlet tube 19 of the balloon 16 is moved through the vessel 6 , and the locking ring 17 is moved inwards over the vessel 6 from the end thereof which is opposite to the balloon 16 . after an opening has been made in the wall of the vessel 8 , the sleeve 11 with the vessel 6 pulled over and locked by means of the locking ring 18 and with the balloon 16 positioned within the sleeve 11 is moved so far into the vessel 8 that the end portion 12 is positioned completely inside the vessel 8 . the balloon 16 is then inflated via its inlet tube 19 , the balloon 16 being in such a position that the ribs 14 are bent outwards from their axial direction to a more or less radial direction . this deformation of the end portion 12 is permanent , and thus the end flange 15 is formed . the fact that the inlet tube 19 is not elastic makes it easy for the balloon 16 to affect the ribs 14 in the correct manner for the desired outwards bending thereof . the desired shape of a collar 23 formed from the vessel 6 around the end flange 15 , i . e . the shape of the end flange 15 , can be additionally guaranteed by the balloon portion 20 adjacent to the inlet pipe 19 also being formed essentially nonelastic . when inflating the balloon 16 , the shape of the sleeve 11 changes from the shape shown in fig3 to the one in fig4 ( and also fig5 ). the change of the shape is shown in more detail in fig6 a - c , where the sleeve 11 and the first vessel 6 are shown in a longitudinal cross - section , but where the balloon 16 is not included for the sake of clarity . [ 0048 ] fig6 a shows the starting position , where the first vessel 6 is passed through the sleeve 11 and is folded back practically to the end of the sleeve 11 opposite the end 12 , and where the locking ring 18 fixes the folded - back part of the first vessel 6 adjacent to the former end . [ 0049 ] fig6 b shows the position after the expansion of the end portion 12 of the sleeve 11 has begun . the first vessel 6 will , on the inside of the sleeve 11 , essentially abut on the inside of the end portion 12 , while on the outside of the sleeve 11 it will extend essentially straight between the locking ring 18 and the free end of the end portion 12 . since this free end is not fixed relative to the first vessel 6 , a relative movement will be possible , which is a requirement to enable expansion of the first vessel 6 without being damaged to a considerable extent . [ 0050 ] fig6 c shows the final position of the expansion of the end portion 12 of the sleeve 11 . also in this case , the first vessel 6 follows the inside of the end portion 12 but does not enter the angle between the sleeve 11 and the expanded end portion 12 on the outside of the sleeve 11 . this clearance between the vessel 6 and the outside of the sleeve 11 adjacent to the expanded end portion is advantageous for the necessary seal against the second vessel 8 since a pressure will thus be exerted on the inside of the edge of the opening formed in the vessel 8 . for the final fixing of the vessel 6 to the vessel 8 , the locking ring 17 is moved down coaxially on the outside of the sleeve 11 towards the end flange 15 , while the pins 21 penetrate at least the wall of the vessel 8 and the wall of that part of the vessel 6 which is folded back over the end portion 12 and forms one layer of the collar 23 . because of the barbs 22 , the desired locking is achieved . the pins 21 can advantageously also be made to penetrate the end flange 15 and the other layer of the collar 23 and outwards into contact with the balloon 16 , which , however , is so yieldable as not to be punctured by the pins 21 . once the vessel 6 is safely connected to the vessel 8 , the pressure in the balloon 16 can finally be relieved , thereby making it possible to pull out the balloon through the vessel 6 by means of the inlet tube 19 . an alternative embodiment of the sleeve 211 is illustrated in fig8 and comprises a stent 224 extending along a proximal portion 225 of the sleeve 211 . an end or distal portion 226 of the sleeve 211 has the same configuration as the sleeve 11 of fig2 i . e . a plurality of axially extending slots 213 alternating with a corresponding plurality of ribs 214 . the sleeve 211 has a continuous cover 227 made of a film of such material as ptfe , polyurethane and dacron , at least extending over the proximal portion 225 of the sleeve 211 . the continuous cover 227 may also be extended at least over a part of the end or distal portion 226 of the sleeve 211 . alternatively , the end or distal portion 226 of the sleeve 211 may be covered by flocks of ptfe or the like . the ribs 214 consist of a memory material , e . g . a memory metal such as nitinol , and are shown in a folded , axially extended state in fig8 in which state the ribs 214 must be retained by a positive bias , as described below . when released the ribs 214 will unfold to a radially extending state and form an annular end flange , as illustrated in fig5 without the need for any external force , such as that exerted by the inflating of a balloon . a further sleeve 311 is shown in fig9 in its unfolded state having an annular end flange 315 . this sleeve 311 is a combination of a proximal portion 325 corresponding to the proximal portion 225 of the sleeve 211 shown in fig8 and an end portion 326 corresponding to the end portion 112 of the sleeve 111 shown in fig7 . thus , this end portion 326 consists of a net - like flexible material , e . g . of stent type , which however also is a memory material such that the end portion 326 automatically will assume the shape of an annular end flange 315 when released , as shown in fig9 . further , the sleeve 311 has a stent 324 and also a cover 327 , which extends over the proximal portion 325 and the distal end portion 326 . the proximal ends of the slots 13 , 213 of each of the sleeves in fig2 and 8 lie in a common plane , which is perpendicular to the longitudinal axis of the sleeve 11 , 211 . the end flange formed by the unfolded ribs 14 , 213 will also lie in the same plane . thus , an end flange , which lies in a plane that is inclined towards the longitudinal axis of the sleeve , may be obtained by placing the proximal ends of the slots in that inclined plane , as illustrated by a sleeve 411 in fig1 . of course , it is possible to otain the same result with an end or distal portion having the configuration illustrated in fig7 and 9 , as also shown by a sleeve 511 in fig1 . referring to fig1 - 15 , a preferred method of releasing the ribs 214 will be described . as shown in fig1 , a frusto - conical cap 228 is pushed over the free ends of the ribs 214 to keep them in their folded position . more precisely the distal ends of the ribs are narrowed to each other so as also to give the end or distal portion 226 of the sleeve 211 a substantially conical shape . the cap 228 is kept over - the ends of the ribs 214 by a wire 229 , which is fixed to the cap 228 preferably at central point therein . the wire 229 extends through the sleeve 211 such that a positive tension applied to the wire 229 will keep the cap 228 fixed over the free distal ends of the ribs 214 . the cap 228 may have a central hole enabling the sleeve 211 to be pushed along a guide wire extending through that central hole . in order to release the memory material of the end or distal portion 226 of the sleeve 211 , a tube 230 may be pushed along the wire 229 , as shown in fig1 , and ultimately lift the cap 228 from the distal end of the end portion 226 of the sleeve 211 , as shown in fig1 . the memory material of the end portion 226 will consequently unfold and resume its unbiased state , as illustrated in fig1 for the type of sleeve illustrated in fig9 . eventually , the cap 228 and the tube 230 may . be withdrawn from the sleeve 211 together with the wire 229 . fig1 - 18 illustrate cross - sections of the sleeve 211 in fig8 and 12 . fig1 represent the cross - section view along lines a - a in fig1 , showing the cover 227 encircling elements of the stent 224 . fig1 represent the cross - section view along lines b - b in fig1 , showing the cover 227 encircling the ribs 214 . fig1 represent the cross - section view along lines c - c in fig1 , showing the uncovered distal tips of the ribs 214 encircled by the cap 228 . it should be noted that the cover 227 encircling the ribs 214 must be extremely flexible so as not to prevent the ribs 14 from unfolding when released from the cap 228 . referring to fig1 , the stent 224 of the proximal portion 225 of the sleeve 211 may have spikes 231 extending radially outwards from the peripheral surface of the sleeve 211 and through the cover 227 in order to fix the cover 227 relative to the stent 224 and also to fix an end portion of the vessel 6 relative to the stent 224 when pushed over the proximal portion 225 of the sleeve 211 . a method of using the apparatus illustrated in fig1 - 15 for connecting the vessel 6 to the vessel 8 will be described below with reference to fig2 and 21 . the proximal portion 225 of the sleeve 211 is inserted and fixed in the distal end of the vessel 6 , e . g . by dilating the stent 224 by means of a balloon or by allowing a self - expanding stent 224 to expand . the cap 228 is positioned over the distal tips of the ribs 214 of the distal portion 226 of the sleeve 211 and the wire 229 extends proximally from the cap 228 and through the vessel 6 . after an opening has been made in the wall of the vessel 8 , a sheath ( not shown ) may be used for introducing the sleeve 211 so far into the vessel 8 that the distal portion 226 is positioned completely inside the vessel 8 . the cap 228 is then pushed off the distal portion 226 by means of the tube 230 ( not shown ) whereby the ribs 214 are unfolded and form an end flange 215 approaching the inner surface of the wall of the vessel 8 around the opening therein . the cap 228 may then be withdrawn from the sleeve 211 and the vessel 6 by pulling the wire 229 proximally . finally , the vessel 6 is fixed to the vessel 8 by means of the locking ring 17 which is moved towards the end flange 215 while the pins 21 penetrate at least the wall of the vessel 8 and the covering film 227 of the end flange 215 . because of the barbs 22 , the desired locking is achieved . the pins 21 can advantageously also be made to penetrate the end flange 215 . the expert realises that several modifications of the above - described embodiments of a connecting apparatus are conceivable within the scope of the invention as defined in the appended claims . for example , the fan shape which the ribs 14 of the end flange 15 have according to fig5 can also be achieved without the slots 13 by folding the material of the end portion 12 like a fan . also , a sleeve of the type shown e . g . in fig8 but comprising ribs of a non - memory material could be used in combination with a balloon . however , it is also possible to combine a balloon with a sleeve having a distal portion , which comprises a memory material .

US-76974801-A

provided is a method for treatment and / or prophylaxis of a condition associated with t cell mediated chronic inflammatory disease by administration , to a patient , of a peptide comprising n ′- svteqgaelsneer - c ′ or an analogue thereof that inhibits t cell migration . also provided is the peptide or its analogue for use in the methods of treatment and / or prophylaxis of said condition . also provided is a method for the treatment of sjogren &# 39 ; s syndrome by administration of a peptide comprising n ′- svteqgaelsneer - c ′ to a patient in need thereof .

wo2007127935 relates to the histone deacetylase , hdac7 . it sets out to identify the phosphatase that dephosphorylates hdac7 and finds that a number of proteins bound to hdac7 , including the peptide described herein as seq id no no : 1 . the focus of the document is that a “ target subunit ” of the myosin phosphatase ( mypt1 ) also bound hdac7 and as such the teaching is directed to the interaction between hdac7 and myosin phosphatase via this subunit of myosin phosphatase . there is no mention that our peptide has any value , nor that it interferes with the hdac7 — myosin phosphatase interaction . us2002164668 ( a1 ) and us20030064411 ( a1 ) disclose our peptide and pharmaceutical preparations / compositions comprising it in relation to the treatment of alzheimer &# 39 ; s disease . us20040053309 ( a1 ) also discloses our peptide , but relates to the identification of proteins and protein isoforms that are associated with kidney response to toxic effectors . however , none of the prior art discloses the use of our peptide or analogues thereof . we have been interested in the ability of the adipocyte derived cytokine , adiponectin , to regulate the recruitment of human t cells to inflamed endothelium . previously , adiponectin deficient mice were shown to have a two - fold increase in leukocyte adhesion to endothelial cells and importantly , leukocyte recruitment was normalized by the addition of recombinant adiponectin . in our in vitro studies we used static transwell assays , as well as flow based adhesion assays , to track the migration of t cells ( which were in crude isolates of peripheral blood lymphocytes [ pbl ]) across tnf - α and ifn - γ stimulated endothelial cells . t cell migration was dose dependently blocked by adiponectin ( fig1 ). the effect of adiponectin on t cell transmigration was mediated by signalling through the adiponectin receptors ( ar1 and ar2 ). amp - activated protein kinase ( ampk ) is a crucial intermediate in the down stream signalling from ar1 and ar2 and when pbl were pre - treated for 30 minutes with the ampk inhibitor , compound c , the effects of adiponectin on the inhibition of t cell migration were ablated , i . e . t cell migration returned to the levels observed in the absence of adiponectin ( fig2 ). compound c did not have any effects on migration in the absence of adiponectin . importantly , we found that the adiponectin mediated inhibition of t cell migration was significantly compromised in patients with t1d i . e ., the ability of adiponectin to modulate t cell recruitment in our in vitro migration assays was lost when pbl isolated from t1d were used ( fig3 ). we have now shown that both ar1 and ar2 are significantly down regulated on lymphocytes in t1d ( fig4 ), and the levels of adiponectin mediated inhibition of t cell migration in vitro correlate exquisitely with expression of these receptors in t1d , to the extent that patient and healthy control cohorts cluster independently when receptor density is plotted against sensitivity to adiponectin in the endothelial cell transmigration assay ( fig5 ). we do not believe that adiponectin represents a suitable target for regulating t cell recruitment in t1d . its concentration in the circulation is not altered in t1d , indicating that aspects of adiponectin biology other than its bioavailability are important arbiters of function . moreover , adiponectin is a pleiotropic agent with important roles in metabolic homeostasis , raising the possibility of serious off target side effects . rather , we believe that targeting pathways down stream of adiponectin , which regulate t cell migration , would provide a therapeutic modality of greater precision . thus , we have now gone on to show unequivocally that adiponectin achieves its effects on t cell migration by the induction of a novel mediator , which we believe is a peptide inhibitor of trans - endothelial migration that is released from b lymphocytes . importantly , b lymphocytes express adiponectin receptors , so can respond in an appropriate manner to stimulation by this agent ( fig6 ). moreover , the inhibition of t cell migration by adiponectin is lost if b cells are removed from mixed lymphocyte preparations ( pbl ), and inhibition of t cell migration is regained if isolated b cells are added to purified preparations of t cells ( fig7 a ). interestingly , natural killer lymphocytes ( nk cells ), which also express high levels of adiponectin receptors ( fig6 ) are not capable of regulating the migration of t cells ( fig7 b ), indicating that the regulation of t cell migration is mediated exclusively by b lymphocytes and not other cellular components of the pbl population . b cells mediate their effects in this system by secretion of the peptide . thus , supernatants conditioned by adiponectin stimulated b cells , could effectively inhibit t cell migration ( fig8 ). moreover , the effects of conditioned supernatants were lost when brefeldine a , which is an inhibitor of b cell secretory pathways , was used to inhibit the release of the peptide from b cells in to the conditioned medium , see ( fig8 ). we have now definitively identified the secreted peptide released from b cells in response to adiponectin stimulation . using mass spectrometric analysis adiponectin conditioned b cell supernatant , as well as the relevant control supernatants were purified and analysed by lc - ms / ms . comparative analysis of a protein sequence database revealed a single candidate peptide unique to the adiponectin conditioned b cell supernatant , described in table 1 , below . due to the statistically stringent nature of the fragmentation analysis , the software was able to provide a definitive sequence with a high probability of accuracy and to identify the 14 . 3 . 3 zeta / delta ( 14 . 3 . 3 . ζδ ) protein as the precursor protein . indeed the peptide represents amino acids 28 - 41 of the 14 . 3 . 3 ζδ protein , which in turn is a 245 amino acid product of the ywhaz gen . stringent database searches demonstrate that the peptide sequence is unique to this protein and is not shared , even by the other six members of the 14 . 3 . 3 family of proteins ( fig9 ). the peptide is not a member of any known family of immuno - regulatory molecules and due to its chemistry , has attractive therapeutic potential . we have been able to successfully synthesise the peptide . comparative analysis of the b cell derived peptide and the synthetic version show identical mass : charge ratios in mass spectrometry analysis , showing that the native peptide has not been subject to post - translational modification prior to excision from the 14 . 3 . 3 . zeta / delta protein and secretion from b cells ( fig1 ). the peptide has efficacy both in vitro and in vivo . using the synthetic peptide we constructed a dose response curve in our in vitro assay of t cell migration ( fig1 ). the peptide has an ec50 of ≈ 20 pm in this assay . we have also utilised the peptide in an in vivo model of acute , zymosan induced peritonitis ( fig1 ). in this model we first showed that the knockout of b lymphocytes ( the cellular source of the peptide ) resulted in an increase in the recruitment of t lymphocytes into the peritoneal cavity . we then conducted the experiment after injection of the peptide into the blood and peritoneum cavity of the b cell knockout mice . the peptide was able to significantly reduce the recruitment of t cells to the peritoneum after challenge with zymosan ( fig1 ). without being bound by theory , we understand that the following represents the paradigm by which pepitem regulates t cell trafficking across endothelial cells during inflammation : adiponectin , operating through the receptors adipo - r1 and adipo - r2 ( ar1 / 2 ), stimulates the release the immune - regulatory peptide , pepitem , from b cells , which are recruited to the endothelial cell surface during inflammation . pepitem stimulates endothelial cells through its cognate receptor , promoting the formation and release of sphingosine - 1 - phosphate ( s1p ). s1p in turn stimulates t cells recruited to the endothelial cell surface during inflammation through the s1p - receptor ( s ) s1pr1 / 4 , a signal that inhibits the ability of t cells to traffic across the endothelial cell barrier and enter inflamed tissue . the following examples present experimental proofs for the function of this pathway in both in vitro and in vivo studies , demonstrate changes in pathway function associated with chronic auto - immune disease in humans , and describe the identity the pepitem peptide . adiponectin inhibits the transendothelial cell migration of peripheral blood lymphocytes ( pbl ). endothelial cells were cultured in low serum medium and stimulated with tnf - α / ifn - γ for 24 hours in the absence of adiponectin . pbl were isolated and treated with adiponectin at 0 . 0001 to 15 μg / ml for one hour . the results are shown in fig1 , where part ( a ) shows that pbl transmigration was significantly and dose dependently reduced by adiponectin in a static adhesion assay ; part ( b ) shows that adiponectin had an ec50 of 0 . 94 μg / ml as determined by linear regression ; and part ( c ) shows that adiponectin was equally effective at inhibiting pbl migration in a flow based adhesion assay . data is representative of at least three independent experiments and were analysed using t - test , one - way anova and dunnett &# 39 ; s multiple comparisons post - test . * p ≦ 1 . 01 , ** p ≦ 1 . 001 , *** p ≦ 1 . 0001 . endothelial cells were cultured in low serum medium and stimulated with tnf - α / ifn - γ for 24 hours . compound c was added to pbl at 10 μg / ml for 30 minutes prior to addition of adiponectin at 15 μg / ml for 1 hour . adiponectin treatment induced a decrease of transmigration , which was restored to normal , control levels in the presence of compound c . the results are shown in fig2 , where data is representative of three experiments and were analysed using one - way anova and dunnet &# 39 ; s multiple comparisons post - test . ** p ≦ 0 . 001 , *** p ≦ 0 . 0001 . pbl from t1d patients are released from the inhibitory effect of ddiponectin on transendothelial cell migration . endothelial cells were cultured in low serum medium and stimulated with tnf - α / ifn - γ for 24 hours in absence of adiponectin . the results are shown in fig3 . part a ) shows that adiponectin - mediated inhibition of pbl transmigration is lost in t1d ; and part b ) shows that the percentage of inhibition was calculated by dividing the percentage of transmigration with adiponectin treatment by the percentage of transmigration of untreated pbl . n = 13 for hc groups and n = 12 for t1d group . data was analysed using t - test and one - way anova and bonferonni &# 39 ; s multiple comparisons post - test . *** p ≦ 1 . 0001 . the expression of adiponectin receptors on pbl is reduced in patients with t1d . the frequency of pbl expressing adiponectin receptors ar1 or ar2 were determined for each healthy or diseased subject and are shown in fig4 a ) and 4 b ), respectively . data is represented as mean ± sem and was analysed using t - test or mann whitney t - test when data did not pass the kolmogorov - smirnov normality test . the expression of adiponectin receptors in t1d or healthy control subjects correlates with the inhibition of lymphocyte migration by adiponectin . fig5 a ) shows the correlation between the expression of ar1 and inhibition of lymphocyte migration , whilst fig5 b ) shows the correlation between the expression of ar2 and inhibition of lymphocyte migration . correlations were determined using linear regression analysis . fig6 a ) and b ) show the expression of ar1 ( fig6 a ) and ar2 ( fig6 b ) on different cell types . data is mean ± sem and are representative of seven healthy controls . data was analysed using one - way anova and bonferonni &# 39 ; s multiple comparisons post - hoc test . *** p ≦ 0 . 0001 . fig7 a ) shows that the migration of pbl is lost when they are depleted of b cells ( bs ) and regained when b cells are added back to isolated t cells . fig7 b ) shows that the migration of natural killer cells is not affected by adiponectin and addition of nks to t cells does not regulate the migration of the t cells . data is mean ± sem and are representative of at least three independent experiments . data was analysed using one - way anova and bonferroni &# 39 ; s multiple comparisons post - test . ** p ≦ 1 . 001 , *** p ≦ 1 . 0001 . b cells were isolated and incubated in presence or absence of adiponectin at 15 μg / ml . supernatant was taken after one hour and added to bs - ve pbl which significantly restored the adiponectin inhibition of pbl transmigration . for some experiments , b cells were treated with brefeldin a , an inhibitor of b cell secretion . these supernatants were not able to regulate the migration of t cells . this is shown in fig8 , where the data is shown as mean ± sem and is representative of three independent experiments analysed using one - way anova and bonferroni &# 39 ; s multiple comparison post test . *** p & lt ; 0 . 001 , ns = non - significant . the sequence of the peptide was determined and it is shown in fig9 together with the different isoforms of the 14 . 3 . 3 proteins . see also table 1 above . comparison of ms / ms parent ion m / z 774 . 88 from b cell supernatants and a synthetic version of the peptide . the ion m / z 774 . 88 is a fragmentation product of the analysis protocol and is generally only of use for identification using ms / ms , but can be an important parameter for comparison . a comparison of the mass spec profiles of parent ion m / z 774 . 88 from b cell supernatants and a synthetic version of the peptide analysis is shown in fig1 , revealing identical mass : charge ratios . this confirmed sequence identity and showed that the peptide is not subject to post - translational modification prior to secretion . the peptide inhibits t cell migration across endothelial cells in vitro . pbl were treated with adiponectin ( 15 μg / ml as positive control ) or the peptide at concentrations between 0 . 001 and 10 ng / ml , a scramble peptide was used as a negative control ( used 10 ng / ml ). other bioactive peptides were also used to demonstrate specificity of the peptide ( i . e . tetanus toxoid peptide ( ttp ) at 10 ng / ml and pro - insulin ( p1 ) at 10 ng / ml ). the results are shown in fig1 . fig1 a ) shows that pbl transmigration was dose - dependently reduced in presence of the peptide but not in the presence of the scrambled peptide , ttp or pi controls . fig1 b ) shows that the ec50 of the peptide ( 18 . 6 pm ) was calculated using non linear regression analysis . data is representative of three independent experiments and was analysed using one - way anova and bonferroni &# 39 ; s multiple comparison post test . * p ≦ 1 . 01 , ** p ≦ 1 . 001 , *** p ≦ 1 . 0001 . absolute number of t cells in the inflamed peritoneum of wild type or b cell knockout mice in the presence or absence of the peptide . leukocytes were collected from the peritoneum after 48 hours injection of zymosan ( or pbs as control ) with or without the peptide or a scrambled peptide . t cells were identified by expression of cd3 . the peptide or a scrambled peptide was injected at a final concentration of 300 μg / mouse . the results are shown in fig1 , where data for each group is the mean and was analysed using one - way anova and bonferroni &# 39 ; s multiple comparisons post - test . * p ≦ 0 . 01 . this example shows the results of further work undertaken and thus compliments example 1 . the effect of adiponectin ( aq ) on the transendothelial cell migration of peripheral blood lymphocytes ( pbl ). refer to fig1 . endothelial cells were cultured in low serum medium and stimulated with tnf - α / ifn - γ for 24 hours in the absence of adiponectin . pbl were isolated and treated with adiponectin at 0 . 0001 to 15 μg / ml for one hour . part ( a ) shows that pbl transmigration was significantly and dose dependently reduced by adiponectin in a static adhesion assay and that adiponectin had an ec50 of ˜ 40 nm as determined by linear regression ; and part ( b ) shows that adiponectin was equally effective at inhibiting pbl migration in a flow based adhesion assay ; and part ( c ) shows that adiponectin is effective on endothelial cells isolated from different tissues such as huvec ( umbilical cord ), hsec ( liver sinusoidal endothelial cells ) and dmec ( dermal microvascular endothelium ) but not hsavec ( saphenous vein ). in part ( d ), compound c , an amp - kinase inhibitor , was added to pbl at 10 μg / ml for 30 minutes prior to addition of adiponectin at 15 μg / ml for 1 hour . ampk is a signalling adapter that is required for adiponectin - receptor signalling . adiponectin treatment induced a decrease of transmigration , which was restored to normal control levels in the presence of compound c . these data indicate that adiponectin has a strong capacity to regulate the transmigration of lymphocytes through action on its receptors expressed on pbl . data is a pool of at least three independent experiments and were analysed using t - test , one - way anova and dunnett &# 39 ; s multiple comparisons post - test . ** p ≦ 1 . 01 , *** p ≦ 1 . 001 . the simplest interpretation of the previous experiment is that t cells are under the direct control of aq . however , t cells lack the appropriate receptors . however , other leukocytes do have adipo - r1 / 2 and both monocytes and b cells show high levels of expression . expression of both adiponectin receptors , adipor1 and adipor2 , was measured on pbmc by flow cytometry using rabbit anti - human adiponectin receptor 1 and 2 antibodies ( phoenix peptides ). adiponectin receptor expression is shown on the horizontal axis against pan markers of pbmc sub - populations ( vertical axis ). adipor1 and adipor2 are highly expressed on monocytes ( cd14 +) and on b cells ( cd19 +) but at very low levels on t cells ( cd3 +). this indicates that adiponectin cannot directly control t cell migration . b cells are required for the adiponectin mediated inhibition of t cell trafficking . refer to fig1 . endothelial cells were cultured in low serum medium and stimulated with tnf - α / ifn - γ for 24 hours in the absence of adiponectin . pbl transmigration was measured after removal of b cells using bead positive selection and after reconstitution with b cells that were isolated using bead negative selection in presence or absence of adiponectin ( 15 μg / ml ). supernatants from adiponectin - treated b cells or b cell treated with brefeldin a to block protein secretion were added to pbl . removing b cells form the peripheral blood lymphocyte preparation completely inhibited this response . this could be reconstituted using supernatants from adiponectin stimulated b cells that could also effectively inhibit lymphocyte migration , but this effect was lost when supernatants were prepared in the presence of brefeldin - a , an inhibitor of b cell secretion . these data demonstrate that a soluble mediator released form b cells is required . data is a pool at least three independent experiments and was analysed using one - way anova and bonferroni &# 39 ; s multiple comparison post test . * p ≦ 0 . 05 , *** p ≦ 0 . 001 . a 14 amino acid peptide released from b cells regulates t cell trafficking refer to fig1 . b cells were isolated using negative selection and incubated with adiponectin for an hour . supernatants were recovered and purified on a c18 columns to remove large size proteins and acquired by mass spectrometry . the proteomic analysis using mass spectrometry of supernatants from aq stimulated b cells revealed a 14 amino acid peptide with the sequence svteqgaelsneer . comparing this to an in silico library of published and predicted sequences , the peptide demonstrated exact sequence homology to a single human protein , and represents amino acids 28 - 41 of the 14 . 3 . 3 zeta / delta ( 14 . 3 . 3 . ζδ ) protein , which in turn is a 245 amino acid product of the ywhaz gene . the peptide is not a member , nor is it related to , nor does it have sequence similarity to , any of the known families of immune - regulatory peptides . analysis of synthetic peptide by mass spectrometry showed an identical mass : charge ratio to the native peptide ( m / z = 774 . 88 ), demonstrating that the b - cell derived product was not subject to any form of post translational modification prior to release . these data indicate that the 14 amino acid peptide identified is the mediator released by b cells under adiponectin stimulation . refer to fig1 . endothelial cells were cultured in low serum medium and stimulated with tnf - α / ifn - γ for 24 hours in the absence of adiponectin . pbl were treated with adiponectin ( 15 μg / ml as positive control ) or the peptide at concentrations between 0 . 001 and 10 ng / ml , a scramble peptide was used as a negative control ( 10 ng / ml ). other bioactive peptides were also used to demonstrate specificity of the peptide ( i . e . tetanus toxoid peptide ( ttp ) at 10 ng / ml and pro - insulin ( p1 ) at 10 ng / ml ). part ( a ) shows that pbl transmigration was dose - dependently reduced in presence of the peptide but not in the presence of the scrambled peptide , ttp or pi controls . part ( b ) shows that the ec50 of the peptide ( 18 . 6 pm ) was calculated using non linear regression analysis . the data indicates that pepitem is able to inhibit pbl transmigration similarly to adiponectin . data is a pool of at least three independent experiments and was analysed using one - way anova and bonferroni &# 39 ; s multiple comparison post test . * p ≦ 1 . 05 , ** p ≦ 1 . 01 , *** p ≦ 1 . 001 . pepitem inhibits t cell migration and promotes the recruitment of anti - inflammatory regulatory t cells refer to fig1 . endothelial cells were cultured in low serum medium and stimulated with tnf - α / ifn - γ for 24 hours in the absence of adiponectin . pbl and the different subsets and pepitem were added to different endothelial cells and transmigration was measured . the different subsets were isolated using negative selection for treg , cd4 + and cd8 + memory and naïve t cells . positive selection was used to isolate the different monocyte subsets . part ( a ) shows that pepitem inhibits t cell migration across ec with the same pattern as adiponectin on different endothelial cell type . part ( b ) shows that pepitem is effective at inhibiting the transmigration of memory cd4 + and cd8 + t cells , but it has no effect neutrophils , or monocytes ( including cd16 − and cd16 + subsets . naïve lymphocytes were not assessed in this analysis as they do not adhere to the endothelial cell monolayer . part ( c ) shows the efficiency of the migration of regulatory t cells ( treg ), which have anti - inflammatory functions , was increased by pepitem . these data indicate that pepitem is able to specifically modulate transmigration of memory t cells and treg . data is a pool of at least three independent experiments and was analysed using t - test and one - way anova and bonferroni &# 39 ; s multiple comparison post test . * p ≦ 0 . 05 , ** p ≦ 0 . 01 , *** p ≦ 0 . 001 . refer to fig1 . endothelial cells were cultured in low serum medium and stimulated with tnf - α / ifn - γ for 24 hours in the absence of adiponectin . pepitem was added with the pbl on the endothelial cells or endothelial cells were pre - treated with pepitem and pbl added after washes or pbl were pre - treated with pepitem , washed and added to the endothelial cells . when pbl were treated with pepitem and the agent was washed away prior to assay on endothelium , the efficiency of lymphocyte migration was not affected . however , pre - treating the endothelial cells with pepitem resulted in inhibition of lymphocyte trafficking . these data indicate that pepitem operates by stimulating endothelial cells to release an agent that inhibits t cell trafficking . data is a pool of three independent experiments and was analysed using paired t - test * p ≦ 1 . 05 , ** p ≦ 1 . 01 . the induction of sphingosine - 1 - phosphate ( s1p ) synthesis by endothelial cells inhibits t cell migration . refer to fig1 . pbl or b cell depleted pbl transmigration across ifn - γ / tnf - α treated huvec was measured after blockade of s1p signalling using s1pr antagonist ( w146 , 10 μm ) in presence or absence of ( part a ) adiponectin ( 15 μg / ml ) or ( part b ) pepitem . b cell depleted pbl were pre - treated with s1p at different concentrations ( 0 - 100 μm ) and transmigration across ifn - γ / tnf - α treated huvec was measured ( part c ). levels of sphk1 and sphk2 mrna expression determined by real - time pcr of rna from b cells and huvec ( part d , n = 2 ). pbl transmigration was measured across ifn - γ / tnf - α treated huvec pre - treated with sphk1 specific inhibitor ( 5 μm ) in presence of pepitem ( 10 ng / ml ) ( part e ). the data shows that antagonism of the s1p receptor on t cells results in loss of adiponectin and pepitem inhibition on t cell transmigration ( part a , b ). part ( c ) shows that addition of s1p to b cell depleted t cells restores the inhibition of transmigration ; and part ( d ) shows high expression of s1p kinase 1 and 2 in huvec ( sphk1 and 2 ); and part ( e ) shows that inhibition of sphk1 releases lymphocytes from the inhibitory effect of pepitem . these data indicates that pepitem stimulates endothelial cells to release s1p , which in turn inhibits lymphocyte transmigration . data is a pool of at least three independent experiments and was analysed using t - test and one - way anova and bonferroni &# 39 ; s multiple comparison post test . * p ≦ 0 . 05 , ** p ≦ 0 . 01 , *** p ≦ 0 . 001 . refer to fig2 . 96 well plates were coated with 50 μg / ml of recombinant icam overnight at 4 ° c . the plate was blocked using pbs 4 % bsa for an hour at room temperature and pbl treated with ip - 10 ( 10 ng / ml ) and / or s1p ( 10 μm ) were added for 30 minutes . excess of unbound pbl was washed and pbl were labelled for the intermediate affinity site of the lymphocyte integrin lfa - 1 ( cd11a / cd18 ; αlβ2 ) using the kim127 antibody ( 10 ug / ml ) and for the high affinity site using antibody 24 ( 10 ug / ml ) at 4 ° c . the expression of both affinity site was measured on memory t cells using mean fluorescence intensity ( mfi ). the data shows that the expression of both intermediate and high affinity sites increased upon ip - 10 stimulation is down - regulated in presence of s1p . the data indicates that s1p regulate lymphocyte transmigration by modulating the affinity of the integrin lfa - 1 that is essential to lymphocyte transmigration . data is a pool of two independent experiments . absolute number of t cells in the inflamed peritoneum of wild type or b cell knockout mice in the presence or absence of the peptide . refer to fig2 . in part ( a ), wild - type or b cell knock - out ( jh −/−) balb / c mice were injected with 100 ug zymosan . leukocytes were collected from the peritoneum after 48 hours injection of zymosan ( or pbs as control ) with or without the peptide or a scrambled peptide . t cells were identified by expression of cd3 . the peptide or a scrambled peptide was injected at a final concentration of 300 μg / mouse . the results are shown in part ( a ), where data for each group is the mean and was analysed using one - way anova and bonferroni &# 39 ; s multiple comparisons post - test . * p ≦ 1 . 01 . in part ( b ), wild - type or b cell knock - out c56bl / 6 mice were injected with salmonella typhirium . after 5 days , liver were collected and sections stained for t cells . the data in part ( b ) shows the number of t cells per infection loci in liver sections . the data shows that absence of b cells in mouse results in higher recruitment of t cells in the peritoneum upon zymosan - induced inflammation and salmonella infection . this is reduced in the zymosan treated b cell knock - out mice by pepitem but not by the scrambled control . these data indicates that b cells are essential to regulate recruitment of t cells during inflammation in vivo by release of pepitem at sites of inflammation . the adiponectin / pepitem pathway is altered in patients with type 1 diabetes refer to fig2 . the frequency of pbl expressing adiponectin receptors ar1 or ar2 were determined for each healthy or diseased subject by flow cytometry and are shown in part ( a ) and ( b ), respectively . data is represented as mean ± sem and was analysed using t - test or mann whitney t - test when data did not pass the kolmogorov - smirnov normality test . endothelial cells were cultured in low serum medium and stimulated with tnf - α / ifn - γ for 24 hours in the absence of adiponectin . pbl were isolated from healthy controls and patients with type 1 diabetes and treated with adiponectin 15 μg / ml for one hour . part ( c ) shows a correlation between the expression of adipor2 and inhibition of lymphocyte migration , correlations were determined using linear regression analysis . part ( d ) shows the transmigration of pbl from newly diagnosed patient with type 1 diabetes , pre - treated with adiponectin or pepitem ( n = 5 ). data was analysed using t - test ** p & lt ; 0 . 01 . the results show in part ( a and b ), lower expression of both adiponectin receptors ( adipor1 / 2 ) on pbl from patients with type 1 diabetes ; and part ( b ) shows that the lower expression of adipor2 , the lower is the capacity of adiponectin to inhibit lymphocyte transmigration ; and in part ( d ), pepitem was still able to inhibit lymphocyte transmigration . the data indicates that lymphocytes from patients with type 1 diabetes are released from the inhibitory effects of adiponectin because they express lower adiponectin receptors and this can be restored by exogenous addition of pepitem . this example shows the results of further work undertaken directed to sjogren &# 39 ; s syndrome . pepitem significantly reduces the number of infiltrating t cells into the salivary glands of sjogren &# 39 ; s syndrome primary sjogren &# 39 ; s syndrome ( pss ) is a chronic inflammatory autoimmune disease with a prevalence of 0 . 5 % in the general population . it is characterised by loss of function of salivary glands and autoantibody production . one third of the patients present signs of extra - glandular involvement that extend from cutaneous vasculitis to peripheral neuropathy or pulmonary involvement . systemic manifestations are most commonly observed in immunologically active patients characterised by high titres of autoantibody production . lymphocyte infiltration of the salivary glands and formation of organised inflammatory aggregates of t and b - lymphocytes represent the histological hallmark of the disease . acquisition of sjogren &# 39 ; s syndrome is associated with the formation of ectopic tertiary lymphoid organs ( tlo ) which are associated with a significant increase in the risk of developing lymphoma . c57bl / 6 mice were intraductally cannulated with 10 8 - 10 9 pfu of luciferase - encoding replication - defective adenovirus ( advs ) to virally induce tlo . a group of 5 mice were administered ( i . p injections ) 100 μg pepitem and another group of 5 mice were administered 100 μg scrambled peptide every day until day 5 post - cannulation . cannulated salivary glands were harvested and chopped into small pieces and digested for 20 minutes at 37 ° c . cells were filtered and washed , then stained for flow cytometry ( fig2 a ). salivary glands from mice were harvested , snap frozen , left to dry overnight at room temperature and then stored at − 80 ° c . until use . slides were immunofluorescently stained after being brought to room temperature ( figure b ). the data shows that pepitem administration significantly reduces the number of infiltrating t cells into the salivary glands of a mouse model of sjogren &# 39 ; s and their organisation into ectopic lymphoid structures ( tlo ). these data indicate that pepitem administration can be used to reduce the infiltration of t cells at sites of inflammation in sjogren &# 39 ; s syndrome . pepitem reduces the mrna for inflammatory cytokines in the salivary glands of a mouse model of sjogren &# 39 ; s syndrome salivary glands from the mice were removed and mrna isolated using standard protocols . qpcr analysis of the isolated mrna revealed that peptiem reduces the expression of cytokines which are inflammatory drivers of disease ( fig2 ).

US-201615354333-A

an improved implantable valve accumulator pump for the delivery of medication is disclosed . the implantable pump comprises a pressurized drug reservoir . the medication metering assembly comprises a fixed volume accumulator positioned between a pair of valves . the valves alternately open and close to admit medication from the reservoir into the accumulator and to dispense a precise volume pulse to an outlet catheter . in order to improve the pump &# 39 ; s accuracy and to increase pumping volume while optimizing the pump &# 39 ; s overall size and energy usage a two way diaphragm accumulator is used . the unit can be externally programmed or can be used in a fixed rate configuration that is never programmed but set at the factory or in the current programmable configuration .

as seen in fig1 , the infusion apparatus of the present invention includes a metering assembly having a programmable valve accumulator pump 30 , an infusate reservoir 10 that can be conventional and well - known in the art , and an external programmer 34 . those skilled in the art will appreciate that an external programmer is not necessary ; for example , the device could be used in a fixed rate configuration that is never programmed but is preset . the reservoir 10 is a sealed housing 14 that contains bellows 16 that includes an internal volume that contains the medicament or other fluid to be infused . the reservoir is preferably rechargeable , such as via septum 12 . external of the bellow is a chamber 20 that contains a fluid , such as a two - phase fluid having a significant vapor pressure at normal body pressure so that it compresses the bellows and causes the fluid in the bellows to exit the outlet of the housing 14 . the outlet communicates with the metering assembly , such as via a bacterial filter 24 , the metering assembly generally comprising an accumulator 30 and an inlet valve 26 and an outlet valve 28 in fluid isolation from the inlet valve . preferably the metering assembly is electronically controlled in accordance with convention . turning now to fig4 and 5 , accumulator 30 is shown . the accumulator 30 includes a housing 50 , that together with cap 51 defines a sealed gas chamber 52 . the cap 51 is attached to the housing 50 by any suitable means , such as laser welding . a suitable gas is sealed , under positive pressure , in the gas chamber 52 . the gas chamber 52 is in fluid communication with diaphragm chamber 57 via a port 55 in the housing 50 . the bottom surface of the housing 50 is configured and positioned to serve as a mechanical stop for the diaphragm 50 when the diaphragm 50 is in the up ( fill ) position . affixed to the housing 50 is a faceplate 56 . preferably the edges of the diaphragm 40 are sandwiched between the housing 50 and faceplate 57 as shown , and the assembly is sealed , such as by laser welding . the volume between the housing 50 and faceplate 57 , containing the diaphragm 40 , defines the diaphragm chamber 57 . the diaphragm 40 thus provides a barrier , separating the gas side ( e . g ., above the diaphragm ) from the fluid side ( e . g ., below the diaphragm ) in the accumulator 30 . faceplate 56 also includes a fluid inlet port 58 that provides fluid communication between inlet valve 26 and the diaphragm chamber 57 , and fluid outlet port 59 that provides fluid communication between outlet valve 28 and the diaphragm chamber 57 . turning now to fig2 , the operation of the accumulator assembly is shown schematically . a normally closed inlet valve 26 is in fluid communication with the inlet port 58 of the accumulator 30 ( and the outlet of the reservoir 10 via line 22 ). a normally closed outlet valve 28 is in fluid communication with the outlet port 59 of the accumulator 30 . miniature solenoid valves are suitable . preferably the valves 26 , 28 are controlled electronically , such as through a module programmed by an external programmer 34 ( fig1 ). the outlet of the accumulator 30 communicates with a catheter or the like via line 36 that delivers the infusate to the delivery site in the patient in a conventional manner . the diaphragm 40 , as illustrated in fig2 and 4 , is a circular disk of a thin metal sheet . preferably titanium may be used , although other materials also may be suitable as determined by those skilled in the art . the disk is selected to have a diameter and thickness of low spring rate over the desired range of deflection . thus , the diaphragm acts as a compliant , flexible wall which separates fluid from the environment behind it . the upward and downward motions of the diaphragm 40 are limited by the bottom surface of the housing 50 , and the top surface of the faceplate 56 , each of which serves as a mechanical stop for the diaphragm , depending on whether the diaphragm chamber 57 is filled with infusate or is empty of infusate . thus , these surfaces are provided with a shallow concave profile manufactured into its diaphragm contact surface . this surface acts as a contour stop for the diaphragm . dimensions of the contour are chosen to match the general profile of the diaphragm when it is deflected or biased by a predetermined fixed volume . this predetermined fixed volume is the volume desired to be metered from the accumulator ( e . g ., 2 μl ). deflection of the diaphragm 40 occurs in both the upward and downward direction . the fixed volume pumped is essentially twice that pumped by a diaphragm of the same size that is only deflected in one direction in the same accumulator package configuration . thus , the two way diaphragm permits the optimization of accumulator size and energy utilization to increase fixed volume pumping and to conserve battery energy . the first step in the fig2 pumping cycle shows the accumulator 30 in a state where both the inlet valve 26 and the outlet valve 28 are closed , and the diaphragm chamber 57 of the accumulator is empty ( i . e ., devoid of infusate fluid ). in this condition , preferably the diaphragm 40 is firmly held against the spacer 70 by the gas and is substantially flat ; it is not being urged or deflected in either an upward or downward direction ( it is noted that the accumulator pressure is generally less than the reservoir pressure and diaphragm spring force and greater than the catheter outlet pressure ). the second step in the cycle shows the accumulator 30 after the inlet valve 26 has been opened ( maintaining the outlet valve 28 closed ). the infusate fluid overcomes the bias of the pressurized gas against the diaphragm 40 , and deflects the diaphragm 40 upward , thereby filling the diaphragm chamber 57 with fluid from the reservoir 10 . the third step in the cycle is the closing of the inlet valve 26 once the diaphragm chamber 57 has been filled to its fixed or desired volume . the fourth step in the cycle is the opening of the outlet valve 28 ( while maintaining the inlet valve 26 in the closed position ) to empty the diaphragm chamber 57 through the catheter 36 , wherein the diaphragm 40 deflects downward as a result of the bias from the gas pressure in the gas chamber 52 and in the gas side of the diaphragm chamber 57 . accordingly , the diaphragm 40 deflects in a first direction during the filling operation of the accumulator 30 , as infusate fluid under pressure forces the diaphragm upwards against the mechanical stop of the bottom surface of the housing 50 , overcoming the pressure exerted by the gas in the accumulator . the diaphragm also deflects in a second direction during the emptying of the accumulator 30 , past its flat , resting point position , as the pressurized gas in the accumulator forces the diaphragm downward against the mechanical stop of the top surface of the faceplate 56 . the two - way deflection allows twice the volume to be delivered during a single pumping cycle compared to conventional designs , using the substantially same amount of energy . preferably the first and second directions of deflection of the diaphragm are opposite directions . the accumulator 30 thus stores and discharges predetermined volume spikes of infusate at a frequency defined by the cycling rate of the inlet and outlet valves . since the metering assembly controls the flow of fluid from the reservoir and does not rely on constant pressure to initiate flow , although a two - phase liquid can be used in the reservoir , a one - phase gas is suitable as well . suitable gasses include inert gases such as argon , helium and nitrogen , mixtures thereof , and air . fig5 a and 5b of the &# 39 ; 887 patent illustrate the details of the spacer plate utilized between the medication accumulation chamber and the accumulator valves . as disclosed in the &# 39 ; 887 patent , the continuous contoured surface desirable to use on the gas - filled side of the diaphragm is undesirable on the fluid side . intimate contact of two relatively flat surfaces with a liquid interface will create flow restrictions when the accumulator is emptied as the plates move toward each other and during filling when the plates move away from each other . this adverse effect was designed to be overcome by the addition of a checkerboard groove pattern as illustrated in fig5 b of the &# 39 ; 887 patent . additionally , a circumferential groove was incorporated in the design to establish fluid communication between the inlet and the outlet valves . objects of the design were to : permit complete free flow of fluid underneath the flattened diaphragm ; assist in washing of areas which might otherwise remain stagnant , and ; maintain the accumulator dead volume at a minimum level . u . s . pat . no . 5 , 049 , 141 introduced an improved spacer plate design as illustrated in fig5 a and 5b of that patent , the purpose of which was to reduce the diaphragm contact area with the plate . it was found that the prior art &# 39 ; s use of a checkerboard groove provided too much surface contact area and therefore large molecule drugs could be crushed at the plate and diaphragm contact points resulting in the creation of drug residue . the prior art checkerboard design also created areas where the drug could stagnate and particles and air bubbles could be trapped . the &# 39 ; 141 patent introduced an improved spacer plate design utilizing concentric circumferential grooves to establish fluid communication between the inlet and outlet valves and for fluid communication with the trough and a design that would reduce the diaphragm and plate contact area . the spacer 70 in accordance with certain embodiments of the present invention improves upon the prior art with a design that maximizes the wash out of fluid and minimizes dead volume . channels in the spacer are designed to create a flow path that allows the fluid to exit the accumulator quickly ( e . g ., the channel flow restriction is kept large enough to allow the accumulator to empty in a short period of time ). it was found that the multiple annular grooves of the prior art provided multiple sites for stagnant fluid and air encapsulation resulting in dead volume and a degradation of pumping accuracy . as seen in fig3 and 5 , the spacer 70 of the present invention includes an annular groove 54 intersected by ( and thereby in fluid communication with ) a trough 53 connecting the inlet and outlet valves wherein the volume of the space created by the annular and trough grooves permits the dead volume in the grooves and outlets to be equal to or less than about 5 % of the total volume discharged by the accumulator . preferably only a single annular groove 54 is provided , and it is interior to the inlet and outlet apertures respectively communicating with the inlet and outlet valves , such that the diameter of the annular groove 54 is smaller than the length of the trough 53 . the groove 54 thus provides an annular flow path , and the trough 53 provides a lateral flow path between the inlet and outlet of the accumulator . fluid in the groove 54 thus communicates with the inlet and outlet of the accumulator only through communication with the trough 53 . the remaining peripheral surface of the space plate 50 is preferably flat . the new design flow path configuration and placement also allows for the fluid to flow out of the accumulator without adversely affecting the empty time .

US-90682607-A

the invention is directed to a therapy apparatus for treatment with focussed ultrasound , comprising a cooled ultrasound source implemented as phased array and a preceding acoustic lens . the ultrasound source also comprises a base plate arranged between the lens and the ultrasound source on whose side facing away from the lens the ultrasound transducer elements of the phased array are attached , whereby the base plate is composed of a material with good thermal conductivity , whereby an ultrasound - conductive coolant that adjoins that side of the base plate facing toward the lens is situated between the lens and the ultrasound source , whereby the base plate , at least in the region of the ultrasound transducer elements , comprises a thickness that is equal to an odd - numbered multiple of a quarter of the wavelength of the ultrasound in the material of the base plate .

the therapy apparatus according to fig1 and 2 contains a therapeutic ultrasound source referenced 1 overall . this contains six annular ultrasound transducer elements 2 1 through 2 6 that are secured to the one side of a carrier 3 forming a base plate . the carrier 3 is composed of a light metal , for example aluminum or magnesium . the carrier 3 also has an essentially annular shape and comprises a flange 4 or , respectively , 5 both at its inner as well as at its outer circumferential edge . an acoustic lens implemented as fresnel lens , namely a positive lens 6 , is introduced between these . for reasons of clarity , the circumferential edges are only shown with respect to the outermost annular lens zone of the fresnel lens in fig1 . the ultrasound source 1 is accepted in a pot - shaped housing 7 that has its application end closed by a coupling membrane 8 . the housing 7 is filled with a fluid , for example water , suitable as acoustic propagation medium for the ultrasound . the corresponding shading is not entered for reasons of clarity . the therapy apparatus is pressed against the body surface of a patient p to be treated with the coupling membrane 8 in the way shown in fig1 in order to assure a good acoustic coupling for introducing the ultrasound emanating from the ultrasound source 1 into the body of the patient p . the space located between the positive lens 6 and the carrier 3 is also filled with the acoustic propagation medium . this assures a good cooling of the carrier 3 that absorbs a part of the waste heat arising during operation of the ultrasound source i and outputs it to the acoustic propagation medium , which thus acts as coolant at the same time . the annular ultrasound transducer elements 2 1 through 2 6 form a phased array implemented as annular array 2 . this is connected to a traditional drive means ( not shown ) via a multi - lead cable referenced 9 overall . when the ultrasound transducer elements 2 1 through 2 6 of the phased array are driven conphasally , i . e . without phase shifts between the drive signals supplied to the individual ultrasound transducer elements 2 1 through 2 6 , the emitted ultrasound is focussed onto a focus zone referenced f 0 in fig1 that lies on the middle axis m of the ultrasound source 1 . the focus zone can be displaced along the middle axis m between the two limit positions f 1 and f 2 by a suitably phase - offset drive of the ultrasound transducer elements 2 1 through 2 6 . the thickness of the ultrasound transducer elements is dimensioned such in a known way that resonance is present at the frequency with which the drive means drives the ultrasound source 1 . the drive , moreover , ensues such that either continuous sound of a constant frequency or ultrasound pulses are generated whose length respectively covers a plurality of cycles of the constant - frequency signal in view of the fact that a fresnel lens is provided as positive lens 6 . the constant frequency is selected taking the frequency for which the fresnel lens is designed into consideration . in order to be able to shift the focus zone within a region indicated in broken lines in fig1 that is rotational - symmetrical relative to the middle axis m and has a conical generated surface and two concentric , spherical end faces , the ultrasound source 1 together with the positive lens 6 is suspended cardanically swivellable in the housing 7 . to that end , the carrier 3 is connected to a ring 10 swivellable around a first axis a 1 lying in the plane of the drawing of fig1 said ring 10 being in turn connected to the housing 7 swivellable around an axis a 2 residing at a right angle to the plane of the drawing of fig1 . in order to be able to undertake the cardanic adjustment by motor , two linear drives 11 and 12 -- which can thereby by electrical , pneumatic or hydraulic linear motors -- are connected to the ring 10 or , respectively , the carrier 3 via articulated rods 13 or , respectively , 14 . in a schematically indicated way , the linear drives 11 , 12 are connected via lines 15 , 16 to a control device that is not shown in fig1 . in order to achieve an improved cooling effect , a cooling circulation path is provided for the acoustic propagation medium . to that end , the acoustic propagation medium is conducted with a pump 18 from the housing 7 via a first fluid conduit 17 through a cooling unit 19 and is conducted back into the housing via a second flexible fluid conduit 20 that discharges into the interspace between the carrier 3 and the positive lens 6 . the acoustic propagation medium flows out again from the interspace located between the carrier 3 and the positive lens 6 through an opening 21 that lies diametrically opposite the discharge point of the fluid conduit 20 . in the region of the ultrasound transducer elements 2 1 through 2 6 , the carrier 3 comprises a thickness d that is equal to an odd - numbered multiple of a quarter of the wavelength of the ultrasound in the material of the carrier 3 ( for example , aluminum with a speed of sound of 6 , 320 m / s or magnesium with a speed of sound of 5 , 790 m / s ). since the material of the carrier -- at least in the region of the ultrasound transducer elements 2 1 through 2 6 -- exhibits an acoustic impedance on the order of magnitude of 10 7 kg /( m 2 s ) ( for example , aluminum with an acoustic impedance of 17 . 1 · 10 6 kg /( m 2 s ) or magnesium with an acoustic impedance of 10 . 1 · 10 6 kg /( m 2 s )), the carrier 3 acts as resonance matching layer that assures an optimum acoustic impedance matching of the piezoelectric material of the ultrasound transducer elements 2 1 through 2 6 ( for example , pz 27 with an acoustic impedance of 35 · 10 6 kg /( m 2 s )) to the liquid ( for example , water with an acoustic impedance of 1 . 5 · 10 6 kg /( m 2 s )) provided as acoustic propagation medium . an ultrasound applicator 23 that contains a diagnostic ultrasound transducer 24 and belongs to an ultrasound locating means is introduced in a tubular component 22 introduced into the inner flange 4 of the carrier 3 . the arrangement is thereby undertaken such that ultrasound tomograms of a body slice of the patient p containing the middle axis m can be generated with the ultrasound applicator . in order to prevent the acoustic propagation medium from emerging from the housing 7 , a seal 25 is arranged , on the one hand , between the ultrasound applicator 23 and the tubular component part 22 ; on the other hand , the free end of the tubular component part 22 is connected fluid - tight via an accordion bellows 26 to the inner edge of the floor of the housing 7 , which comprises an opening . the accordion bellows is provided in view of the cardanic swivel of the ultrasound source 1 . if such a swivel of the ultrasound source 1 is not provided or is only provided to a limited extent , an accordion bellows seal can be provided in the region of the cardan ring 10 instead of the accordion bellows 26 . the part of the housing 7 facing away from the focus would then be free of fluid and the overall weight would be lower . the region portrayed in the ultrasound tomogram is at least so big that the entire region within which the focus zone of the ultrasound can be displaced is imaged . when the ultrasound applicator is a matter of a sector scanner , the region that can be imaged is schematically indicated dot - dashed in fig1 . in a known way , the ultrasound locating means comprises means that mix a mark corresponding to the momentary position of the focus zone of the ultrasound into the respectively generated ultrasound image . to that end and in a known way , the control means for the ultrasound source 1 supplies the ultrasound locating means with a signal corresponding to the momentarily set position of the focus zone and the control device for the linear drives 11 , 12 supplies signals with respect to the spatial alignment of the ultrasound source 1 . in a known way that is not shown , moreover , it can be provided that the ultrasound applicator is rotatable around the middle axis m . for the implementation of a treatment , one proceeds such that , with the assistance of the ultrasound locating means , the therapy device is first aligned such relative to the body of the patient that the region to be treated appears in the ultrasound tomogram ; by pivoting the ultrasound source 1 and by adjusting the position of the focus zone on the middle axis m of the ultrasound source , the mark indicating the position of the focus zone is then brought into coincidence with the region to be treated . following thereupon , the ultrasound source 1 is activated to output ultrasound in a way suitable for the respective therapy . given the ultrasound source 1 according to fig1 and 2 , the width of the ultrasound transducer elements 2 1 through 2 6 increases from the inside to the outside , namely such that the end faces of the ultrasound transducer elements 2 1 through 2 6 respectively exhibit the same area content . by contrast thereto , the ultrasound transducer elements 27 1 through 27 19 in the ultrasound source 1 according to fig3 and 4 likewise fashioned as annular array 27 exhibit the respectively same width . the width of the ultrasound transducer elements 27 1 through 27 19 is thereby selected such that they are arranged congruent with the annular zones of the positive lens 6 , which is again fashioned as fresnel lens . in the exemplary embodiment according to fig3 and 4 , the annular ultrasound transducer elements 27 1 through 27 19 are segmented such that segments 27 1a through 27 19f that are respectively 60 ° wide derive . since a 2d array is present because of the segmentation , the focus zone can thus be displaced not only along the middle axis m of the ultrasound source 1 as in the exemplary embodiment according to fig1 and 2 . on the contrary , a displacement transversely to the middle axis m is also possible ( see the positions f 3 and f 4 additionally entered in fig3 by way of example ), namely within a rotation - elliptical region indicated in fig3 . it is self - evident that , for displacing the focus zone transversely to the middle axis m , the . . . ! respectively . . . ! to an ultrasound transducer element 27 1 through 27 19 -- let the segments 27 19a through 27 19f provided with reference characters in fig4 be cited only by way of example -- must be driven with drive signals that are offset in phase relative to one another . the ultrasound source 1 of the exemplary embodiment according to fig5 and 6 is also implemented as 2d array 28 . it contains a total of 78 ultrasound transducer elements 28 1 through 28 78 that are attached mosaic - like to the carrier 3 . since the ultrasound transducer elements 28 1 through 28 78 are a matter of flat prisms with the crossection of an equilateral triangle , the focus zone of the ultrasound , as a result of the mosaic - like arrangement of the ultrasound transducer elements 28 1 through 28 78 , is displaceable within an approximately rotation - elliptical region ( see the positions of the focus zone f 0 through f 4 entered in fig5 ), as in the case of the above - described exemplary embodiment . the 2d array 29 of the exemplary embodiment according to fig7 through 9 differs from that described above in that the ultrasound transducer elements are divided again such that they exhibit the shape of flat prisms with the crossection of a right triangle , so that ultrasound transducer elements 29 1a through 29 78b are present . in addition , there is also room on the carrier 3 for ultrasound transducer elements 29 79a through 29 8ob . as a result of the further division of the ultrasound transducer elements , the number of ultrasound transducer elements per length unit is different measured in different directions transversely to the middle axis of the 2d array 29 . the focus can then be displaced more greatly transversely to the middle axis m in that direction in which more ultrasound transducer elements are present per length unit . this is clear with reference to fig7 and 9 . whereas , namely , no conditions deviating from the embodiment according to fig5 and 6 derive for the plane shown in fig8 more ultrasound transducer elements per length unit are present in the plane determinant for fig9 as a consequence of the subdivision of the ultrasound transducer elements , so that a greater displaceability of the focus zone derives transversely to the middle axis m ( see the positions of the focus zone f 5 and f 6 in fig9 ). in the exemplary embodiment according to fig7 through 9 , thus , the focus zone is displaceable within a region whose shape essentially corresponds to that of an ellipsoid ( not rotational - symmetrical ) with three principal axes of different length . as a result of the annular shape of the carrier 3 and of the positive lens 6 , the ultrasound source 1 of the inventive therapy apparatus comprises an opening 30 that forms an x - ray - transparent region into which an x - ray - transparent tube 31 can be introduced instead of the diagnostic ultrasound applicator 23 in the way illustrated in fig1 , so that there is the possibility of locating a region to be treated on the basis of an x - ray diagnostics means whose beam path proceeds through the x - ray - transparent region . only the x - ray tube 32 of the x - ray diagnostics means is schematically indicated in fig1 ; it is self - evident that a radiation receiver not shown in fig1 must be present , for example a x - ray image intensifier . according to fig1 , there is also the possibility of introducing a mr marker into the opening instead of the ultrasound applicator 23 or , respectively , the tube 31 . the mr marker 33 is a plastic cylinder or cone with central bore that is attached to a marker carrier tube 34 . given employment of the inventive therapy apparatus with a mr apparatus , it is thus possible to unambiguously determined the spatial position of therapy the apparatus and appertaining therapy focus with reference to the diagnostic image of the mr apparatus . the plastic produces only low mr contrast compared to the liquid in the bore and around the plastic part . the bore marks the middle axis of the ultrasound source 1 . mr - compatible materials are employed for the materials of the therapy apparatus if it is provided for employment with a mr apparatus . a fresnel lens is provided as acoustic lens in all described exemplary embodiments . however , a conventional acoustic lens can also be employed instead . the ultrasound sources of all described exemplary embodiments comprise a central opening into which a diagnostic ultrasound applicator , an x - ray - transparent tube or a mr marker can be partially introduced . within the scope of the invention , however , the ultrasound source can also be implemented without central opening . an x - ray - transparent region can thereby be nonetheless present , insofar as the ultrasound source exhibits the required transparency at least in the relevant region , whether on the basis of a correspondingly slight thickness of the component parts present there or on the basis of a corresponding selection of material . a cardanic suspension of the ultrasound source is not required in those exemplary embodiments that contain an ultrasound source executed as 2d array , since the focus zone can also be spatially displaced without this measure . when , however , the displaceability of the focus zone established by the fashioning of the ultrasound source as 2d array is insufficient , there is also the possibility of the cardanic suspension in such ultrasound sources . measures , moreover , can also be undertaken that allow a fluid other than the fluid otherwise present in the housing 7 to be provided in the space located between the positive lens 6 and the carrier 3 . when the two fluids differ in terms of their critical acoustic properties , however , this must be taken into consideration in the design of the positive lens 6 .

US-89498097-A

a balloon catheter having a long shaft with an inflatable balloon connected to its distal end with a pressure source connected to the shaft at an invivo point which operates to inflate and deflate the balloon . the balloon catheter may be a fixed - wire type , an over - the - wire type , or an single - operator - exchange type catheter . the pressure source may include a piston and a chamber with an actuation member attached to the piston . the actuation member may be a solid rod or a hollow robe . in the case where the actuation member is a hollow tube , the tube may be used to introduce inflation fluid into the pressure source and the inflation lumen . a receptacle such as a reel or tubular hoop may be used to contain the actuation member when pulled proximally . a pressure sensor / gauge and a balloon sizing scale may be incorporated into the catheter assembly to assist the treating physician in monitoring the procedure . a longitudinally oscillating drive , such as a solenoid , may be operatively connected to the pressure source .

the following detailed description should be read with reference to the drawings in which like elements in different figures are numbered identically . the drawings , which are not necessarily to scale , depict selected embodiments and are not intended to limit the scope of the invention . examples of constructions , materials , dimensions and manufacturing processes are provided for selected elements . all other elements employ that which is known to those skilled in the field of the invention . those skilled in the art will recognize that many of the examples have suitable alternatives which may also be utilized . referring to fig1 a schematic view of an embodiment of the present invention is shown . generic catheter 20 includes a shaft 22 , a balloon 25 and a generic pressure source 21 connected to the shaft 22 at a location proximal of the balloon 25 and distal of the proximal end of the shaft 21 . the pressure source may include a piston or plunger 24 disposed inside a chamber 23 . an actuation member 26 may be connected to the piston 24 and extend proximally substantially parallel with the shaft 22 . the generic catheter 20 may take the form of any balloon catheter and used in a variety of medical procedures . for example , the generic catheter 20 may take the form of a soe , fw or otw type balloon catheter ( fig2 a and 2b , 3 , 4 respectively ) and may be used in coronary , peripheral , cerebral , and urethral applications . in addition , the catheter 20 may incorporate other clinically significant features such as perfusion or drug delivery capabilities . for the purpose of the following discussion , the exemplary embodiments are directed to a catheter system which is particularly suitable for ptca procedures . however , with simple modifications in construction , the generic catheter 20 may be used for other medical applications not fully discussed herein . the balloon 25 may also take on a variety of constructions . the material of the balloon 25 may be selected from polymers including , but not limited to , polyolefin copolymer , polyester , polyethylene teraphthalate , polyethylene , polyether - block - amide , polyamide , polyimide , nylon , latex and urethane . the balloon 25 may be made by blow molding a polymer extrusion into the desired shape . a number of ancillary processes may be used to affect the material properties of the balloon 25 . for example , the polymer extrusion may be exposed to gamma radiation which alters the polymer infrastructure to provide uniform expansion during blow molding and additional burst strength when in use . in addition , the molded balloon 25 may be exposed to a low temperature plasma field which alters the surface properties of the balloon 25 to provide enhanced adhesion characteristics . those skilled in the art will recognize that other materials and manufacturing processes may be used to provide a balloon 25 suitable for use with the present invention . similarly , the shaft 22 may be made of a several different constructions , materials and dimensions , depending on the performance characteristics desired . the shaft 22 may be made of , for example , an extruded polymer tube , a stainless steel hypotube , or a composite material such as stainless steel braid encased in polyimide . to impart different characteristics along the length of the catheter 20 , the shaft 22 may incorporate changes in diameter or combine different constructions . for example , the shaft 22 may have a composite proximal section combined with a polymer distal section . those skilled in the art will recognize that the shaft 22 can take on a wide variety of constructions not fully discussed herein but well known in the art . pressure source 21 is generic in form and may vary without departing from the scope of the invention . specific embodiments of the pressure source 21 are discussed in more detail with reference to fig5 and 6 . the generic pressure source 21 as shown in fig1 is in fluid communication with the balloon 25 and when actuated , causes the balloon 25 to inflate or deflate . with the pressure source 21 located close to the balloon 25 , the effective inflation lumen 29 is substantially shortened as compared to a conventional balloon catheter . the shortened inflation lumen reduces both the resistance to fluid flow and the compliance of the fluid path . both these effects reduce the time required to inflate or deflate the balloon . the reduced deflation time allows the physician to more quickly relieve aschemia and other adverse reactions to prolonged balloon inflation . eliminating a significant amount of the fluid system compliance allows the treating physician to better &# 34 ; feel &# 34 ; the response of the vascular restriction to the inflation of the baboon . in addition , pressure source 21 provides more immediate balloon response which is particularly effective for the pulsating balloon technique . the incorporation of the pressure source 21 also eliminates the need to use a bulky inflation device . eliminating the need for an inflation device reduces the number accessory devices needed in a procedure , reduces the number prepping procedures required , reduces the necessary storage space , and reduces the amount of medical waste generated in a procedure , all of which would ultimately save a significant amount of time and expense . the generic pressure source 21 includes a piston or plunger 24 disposed in a chamber 23 . pressure source 21 may operate much like a conventional syringe insofar as the general principles of fluid displacement and fluid pressure are concerned . the piston 24 may be virtually any given geometry sized to movably and sealingly fit into chamber 23 which is preferably incorporated into the shaft 22 . the piston 24 may be displaced by several mechanisms including simple longitudinal actuation ( e . g . a push member ), rotational actuation ( e . g . a threaded piston ), or by magnetic actuation ( e . g . a solenoid ). as such , piston 24 may include an operably connected actuation member 26 which extends in a proximal direction from the piston 24 to a point where the treating physician has access to it and may actuate it to inflate or deflate the balloon 25 . the actuation member 26 can function as a push member to longitudinally displace the piston 24 inside the chamber 23 , the actuation member 26 can function as a rotating shaft to rotationally actuate a threaded piston ( not shown ), or the actuation member 26 can function as an electrical path to actuate a solenoid type piston ( not shown ). in addition , the actuation member 26 may be solid or tubular ( shown ) to provide a prep lumen 69 to carry inflation fluid to the pressure source 21 , inflation lumen 29 , and balloon 25 prior to use in - vivo . the inflation fluid may also be introduced by way of a syringe and needle insertable into the pressure source 21 or inflation lumen 29 . referring now to fig2 a , a first soe embodiment of the present invention is shown . a more detailed description of a known soe catheter can be found in u . s . pat . no . 5 , 156 , 594 to keith et al . a difference between the keith &# 39 ; 594 and the soe embodiments of the present invention is the use of the pressure source 21 with the associated components and necessary modifications . another difference is the length of the guide wire lumen as compared to the length of the inflation lumen . in conventional soe catheters , the length of the guide wire lumen is substantially shorter than the length of the inflation lumen . by contrast , the length of the inflation lumen in the present invention is essentially the same as the length of the guide wire lumen . the soe catheter 30a includes a guide wire tube 31 which extends from a point just distal of the balloon to a guide wire exit port 32 which is located proximal of the balloon 25 and near the location of the pressure source 21 . similarly , the inflation lumen 29 extends from a point adjacent the pressure source 21 to the interior of the balloon 25 . thus , as differentiated from conventional soe catheters , the guide wire tube 31 is essentially the same length as the inflation lumen 29 . the pressure source 21 and the guide wire exit port 32 are preferably positioned between 25 and 30 cm from the balloon 25 . soe catheter 30a further includes shaft 22 which may be formed by conventional methods known to those skilled in the art . since the primary function of the shaft 22 is to transmit longitudinal forces and not to carry inflation fluid , the shaft may have a non - integral structure . for example , it is contemplated that the shaft may be in the form of a plurality of braided wires , a hypotube with either longitudinal or helical slots , a loosely wound helical wire , or a closely wound wire coil . in the above examples , the shaft 22 may partially surround the actuation member 26 . however , as discussed with reference to fig2 b , the shaft 22 may also extend along side the actuation member 26 . a manifold 34 and corresponding strain relief 37 are connected to the proximal end of the shaft 22 by conventional methods . manifold 34 provides a means for the treating physician to more easily grip and manipulate the shaft 22 . a crimp segment 38 is connected to the distal end of the shaft 22 by conventional methods and provides a transitional connection to the distal portion of the catheter including the guide wire tube 31 and the inflation tube 39 . a coil strain relief 36 provides additional transitional support to reduce the potential for kinking the guide wire tube 31 and the outer tube 39 . balloon 25 is connected at its proximal end to the distal end of the outer tube 39 by conventional means . similarly , the distal end of the balloon 25 is connected to the distal end of the guide wire tube 31 . a radiopaque marker band 35 is secured to the guide wire tube 31 at a mid point inside the balloon 25 . the radiopaque marker band 35 facilitates proper placement of the balloon 25 in - vivo . soe catheter 30a utilizes pressure source 21 which includes piston 24 , actuation member 26 and chamber 23 as discussed in detail with reference to fig1 . pressure sources 60 and 70 as shown in fig5 and 6 respectively may be used in place of pressure source 21 . actuation member 26 may extend inside the shaft 22 ( shown ) or adjacent the shaft as mentioned above and discussed in detail with reference to fig2 b . a prep manifold 33 is connected to the proximal end of the actuation member 26 and is discussed in more detail with reference to fig8 . however , the proximal assembly as shown in fig2 a may take the form of any of the embodiments discussed with reference to fig7 - 13 . now turning to fig2 b , a second soe embodiment of the present invention is shown . the discussion with respect to soe catheter 30a shown in fig2 a is equally applicable to soe catheter 30b shown in fig2 b with the following exceptions . as stated previously , the primary function of the shaft 22 in fig2 a is to transmit longitudinal forces and not to carry inflation fluid . thus , the shaft 22 may be replaced with shaft extension 27 which extends along side the actuation member 26 . the shaft extension 27 provides a means to transmits longitudinal forces which facilitates manipulation of the catheter 30b and stabilization of the chamber 23 relative to the actuation member 26 and piston 24 . the shaft extension 27 may be formed of 304v sst and may have a diameter of about 0 . 020 to 0 . 040 inches . an extension handle 28 is rigidly connected to the proximal end of the shaft extension 27 and provides a means for the treating physician to more easily grip and manipulate the shaft extension 27 . referring now to fig3 a fw embodiment of the present invention is shown . a more detailed description of a known fw catheter can be found in u . s . pat . no . 4 , 943 , 278 to euteneuer et al . a difference between euteneuer &# 39 ; 278 and the embodiment shown in fig3 is the use of the pressure source 21 with the associated components and necessary modifications . fw catheter 40 utilizes pressure source 21 which includes piston 24 , actuation member 26 and chamber 23 as discussed in detail with reference to fig1 . pressure sources 60 and 70 as shown in fig5 and 6 respectively may be used in place of pressure source 21 . actuation member 26 may extend inside the shaft 22 ( shown ) or adjacent the shaft as discussed with reference to fig2 b . a prep manifold 33 is connected to the proximal end of the actuation member 26 and is discussed in more detail with reference to fig8 . however , the proximal assembly shown in fig3 may take the form of any of the embodiments discussed with reference to fig7 - 13 . fw catheter 40 includes a core wire 41 which includes a spring tip 42 connected at its distal end . the proximal end of the core wire 41 may be connected to the distal end of the chamber 23 by a conventional means . an inflation tube 43 is connected at its proximal end to the distal end of the chamber and connected at its distal end to balloon 25 . a radiopaque marker band 35 is secured to the core wire 41 at a mid point inside the balloon 25 . the radiopaque marker band 35 facilitates proper placement of the balloon 25 in - vivo . a manifold 34 and corresponding strain relief 37 are connected to the proximal end of the shaft 22 by conventional methods . manifold 34 allows the treating physician to more easily grip and manipulate the shaft 22 . referring now to fig4 an otw embodiment of the present invention is shown . a more detailed description of a known otw catheter can be found in u . s . pat . no . 5 , 100 , 381 to burns . one significant difference between the device disclosed in burns &# 39 ; 381 and the otw catheter 50 shown in fig4 is the use of the pressure source 21 with the associated components and necessary modifications . as with soe catheter 30a and fw catheter 40 , otw catheter 50 utilizes pressure source 21 which includes piston 24 , actuation member 26 and chamber 23 as discussed in detail with reference to fig1 . pressure sources 60 and 70 as shown in fig5 and 6 respectively may be used in place of pressure source 21 . actuation member 26 may extend inside the shaft 22 ( shown ) or adjacent the shaft as discussed with reference to fig2 b . a prep manifold 33 is connected to the proximal end of the actuation member 26 and is discussed in more detail with reference to fig8 . note , however , that the proximal assembly shown in fig4 may take the form of any of the embodiments discussed with reference to fig7 - 13 . otw catheter 50 includes a guide wire tube 51 which extends the full length of the catheter 50 . the distal end of the guide wire tube 51 is secured to the distal end of the balloon 25 by a conventional means . the proximal end of the balloon 25 is connected to a distal portion of the guide wire tube 51 and to the distal end of inflation tube 56 . the proximal end of the inflation tube 56 is connected to the chamber 23 to provide a fluid path from the pressure source 21 to the balloon 25 . the proximal end of the guide wire tube 51 is connected to a fairly conventional otw manifold 52 . guide wire tube 51 is sized to slidably receive a guide wire by way of guide wire port 53 on manifold 52 . the manifold 52 includes an actuation member port 54 which guides the actuation member 26 into the interior of the shaft 22 . the manifold 52 may be connected to the shaft 22 and the guide wire tube 51 which allows fie treating physician to more easily grip and manipulate the catheter 50 . the manifold 52 may also incorporate a strain relief 37 to reduce the potential for kinking the shaft 22 and the guide wire tube 51 adjacent the manifold 52 . the shaft 22 , the guide wire tube 51 and the inflation tube 56 may be connected along their length by several methods such as adhesive and / or an outer sheath 55 . alternatively , the entire shaft assembly could be made of a dual lumen extrusion with one lumen for a guide wire and the other lumen for the actuation member 26 , the chamber 23 and the inflation lumen 29 . while the above description contemplates a construction wherein the guide wire tube 51 is adjacent ( i . e . not coaxial ) to the shaft 22 and the inflation lumen 56 , it is also contemplated that a coaxial otw catheter ( not shown ) may be made to incorporate a pressure source 21 . in the coaxial construction , the guide wire tube would extend inside the actuation member , and the actuation member would in turn extend inside the shaft . the actuation member and the shaft would have a larger relative diameter than discussed in the non - coaxial embodiment in order to accommodate the guide wire tube . the chamber of the coaxial pressure source would be annular in cross section as defined by the outside surface of the guide wire tube and the inside surface of the shaft . the piston would be ring - shaped and sealingly slide around the guide wire tube and inside the shaft . the distal end of the guide wire tube would be connected to the distal end of the balloon and the shaft distal of the chamber would be connected to the proximal end of the balloon . a support connection may be desired between the guide wire tube and the shaft which would prevent relative longitudinal movement therebetween while allowing inflation fluid to pass through . now referring to fig5 a preferred embodiment of a pressure source is shown . the generic pressure source 21 as seen in fig1 may take the form of pressure source 60 shown in fig5 . pressure source 60 provides all the advantages discussed with reference to generic pressure source 21 . pressure source 60 includes a piston head 62 disposed in a chamber 64 and connected to an actuation member 61 . the piston head 62 includes an o - ring 63 to fluidly seal the piston inside the chamber 64 while permitting relatively free longitudinal movement . it is contemplated that more than one o - ring 63 may be desirable to provide a more effective fluid seal . the actuation member 61 may either be a solid rod or a hollow tube ( shown ) to facilitate the introduction of inflation fluid into the inflation lumen 29 and to facilitate pressure monitoring by a fluidic pressure gauge as discussed with reference to fig9 . assuming inflation fluid is already disposed inside the pressure source 60 and the entire inflation lumen 29 , longitudinal displacement d actuating member 61 by the treating physician causes corresponding longitudinal displacement of piston head 62 . the displacement of piston head 62 and the sealing action of the o - ring 63 in turn causes fluid to be displaced into or out of the balloon , depending on the direction of the displacement . it is preferred that the piston head 62 be located at a position allowing for slight proximal displacement ( creating a vacuum in the balloon ) and substantial distal displacement ( creating high positive pressures in the balloon ). the piston head 62 , o - ring 63 , and actuation member 61 may be manufactured as follows . note that the dimensions and materials may be altered to achieve the desired performance characteristics . the actuation member 61 may be made of 304v stainless steel ( sst ) with an outer diameter of about 0 . 023 inches which is small enough to fit inside the shaft 22 but large enough to provide sufficient column strength to actuate the piston to high pressures . the inside diameter may be about 0 . 017 inches which is large enough to provide an adequate path for the introduction of inflation fluid into the inflation lumen 29 and the interior of the balloon . the inside diameter also affects the column strength of the actuation member 61 and should be sufficiently small relative to the outside diameter to reduce the potential for buckling . the length of the actuation member 61 should be sufficient to extend from a point outside the body to the pressure source 60 which is preferably located near the balloon to minimize the inflation fluid path . it is contemplated that the position of the pressure source be approximately 25 - 30 cm from the balloon for ptca applications such that the pressure source remains substantially inside the guide catheter . as such , the length of the actuation member for ptca applications is preferably about 115 cm . the piston head 62 and the o - ring 63 may be mounted on the actuation member 61 by sequentially sliding parts onto the actuation member 61 and securing the parts at opposite ends . for example , the proximal end of the parts may be secured by soldering a short hypotube collar to the actuation member 61 . a proximal polymer ( e . g . polycarbonate ) ring is slid on , followed by the o - ring 63 , which is followed by a distal polymer ring . as mentioned previously , it may be desirable to utilize more than one o - ring to provide a more effective high pressure seal . the distal polymer ring may be secured with a suitable adhesive . the polymer rings are sized to provide a close fit in the chamber 64 . the o - ring is sized to provide an interference fit in the chamber and thus provide a fluid seal , while permitting relatively free longitudinal displacement . the ends of the parts may be secured by other means , provided the proximal end is secured to withstand the high forces associated with distal actuation ( inflating the balloon ) and the distal end is secured to withstand relatively low forces associated with proximal actuation ( deflating the balloon ). the chamber 64 may be formed of 304v sst , a high strength polymer such as polyimide , or a composite structure such as sst braid encased in polyimide . the chamber 64 may be a separate element ( shown ) secured at its ends to the shaft 22 by a suitable adhesive or it may be formed integrally with the shaft 22 . the length and inside diameter of the chamber 64 must be sufficient to allow for both proximal actuation to generate a vacuum in the balloon ( i . e . deflate the balloon ) and distal actuation to inflate the balloon to high pressures ( e . g . 300 psi .). for example , if a conventional ptca balloon ( 20 mm length ) is used , the resulting dimensions would be as shown in table 1 . table 1______________________________________balloon distal proximal chamber chamberdiameter stroke stroke length diameter ( mm ) ( inches ) ( inches ) ( inches ) ( inches ) ______________________________________1 . 5 2 . 75 1 . 0 3 . 75 0 . 0302 . 0 3 . 75 1 . 0 4 . 75 0 . 0352 . 5 5 . 0 1 . 0 6 . 0 0 . 0403 . 0 5 . 75 1 . 0 6 . 75 0 . 0453 . 5 6 . 5 1 . 0 7 . 5 0 . 0504 . 0 7 . 25 1 . 0 8 . 25 0 . 055______________________________________ with reference now to fig6 another embodiment of a pressure source is shown . the pressure source 70 shown in fig6 enjoys the same advantages discussed with reference to pressure source 21 as shown in fig1 and is similar to pressure source 60 shown in fig5 except for the following differences . essentially , the pressure source 70 combines the plurality of parts of pressure source 60 into a single plunger 71 . the shaft in turn functions as a chamber 72 . the plunger 71 may be made of solid 304v sst and is preferably sized to provide a close fit inside the chamber 72 which thus provides an essentially fluid tight seal . the plunger 71 may continue proximally to a point outside the body to function as an actuation member . to reduce friction , it is contemplated that only the distal portion of the plunger 71 have a close fit with the inside of the chamber 72 . alternatively , to provide additional column strength , the diameter of the plunger may remain substantially constant along its entire length . an alternative embodiment is contemplated in which a proximal seal is used to seal about the plunger 71 such that when the plunger 71 is inserted into the shaft 22 , it displaces a volume of fluid into the balloon . this embodiment would not require a fluid tight fit between the distal end of the plunger 71 and the chamber 72 . a seal located at the proximal end of the catheter would allow the plunger to be moved longitudinally while preventing fluid from escaping the system . the balloon would be inflated with a volume of fluid that is equal to the volume of the plunger 71 inserted into the shaft 22 . it is also contemplated that a magnetic solenoid ( not shown ) can be used to drive a pressure source similar to pressure source 60 or pressure source 70 . the solenoid may either be located at the proximal end of the catheter assembly , incorporated into the catheter shaft 22 , or incorporated into the pressure source . if the solenoid were incorporated into the pressure source , for example , the piston could be made of a magnetically responsive material and the chamber could incorporate a wire coil electrically connected to a control system and a power source . the power source and associated control system are substantially known in the art and may be modified to suit this particular application . by supplying the coils with an appropriate electrical signal , the coils would generate a magnetic field to longitudinally displace the piston in the desired direction . the longitudinal displacement would in turn cause the balloon to either inflate or deflate depending on the signal and the coil wind direction . it is also contemplated that a spring may be incorporated into the chamber to provide a force causing the magnetically actuated piston to return to its original position , such as a position generating a vacuum in the inflation lumen and balloon . alternatively , a secondary coil ( wound in the opposite direction as the primary coil ) may be incorporated into the chamber to longitudinally displace the piston in the opposite direction as the primary coil . with a similar arrangement , the solenoid may be located more proximally in the catheter shaft and the actuation member would serve as the solenoid core rather than the piston as mentioned above . the coils would be incorporated into or surrounding the shaft and would be operably connected to a driver circuit and power source . the solenoid may also be incorporated into the proximal assembly to avoid the size restrictions imposed by locating the solenoid into the pressure source or actuation member which are located inside the body during use . the solenoid at the proximal end would function substantially the same as described above , but a relatively large solenoid core connected to the actuation member may be utilized rather than the piston or actuation member as described above . relatively large solenoid coils may be driven by a similar power source and control system , but a more powerful driver circuit and electrical source may be used since the circuitry is outside the body . it has been shown that solenoid model number 9219 available from lucas ledex driven by an harris 7667 integrated circuit ( separated in series by a irf531 mosfet ) and triggered by a stanford research ds335 signal generator provides an oscillatory force to the pressure source when rigidly ( or releasably ) connected to the actuation member . in particular , with this arrangement , frequencies between 1 hz ( approximate displacement of 0 . 313 inches at low frequencies ) and 60 hz have been obtained . the corresponding dynamic response is discussed in detail with reference to fig2 and 21 . it should be noted that the solenoid drive system is not the only means to impart longitudinal oscillation to the actuation member and / or piston . other oscillation methods such as a cam drive may be employed . also , it is contemplated that drives capable of generating sonic frequencies may be desirable in order to match the natural resonance of the obstruction being dilated . fig7 shows a first embodiment of a proximal assembly of the present invention . proximal assembly 80 includes a reel 81 which functions as a receptacle for the actuation member 26 . the reel includes a handle 82 which rotates the reel 81 and thus winds or unwinds the actuation member 26 depending on the direction of rotation . the reel 81 is held stationary relative to the catheter shaft 22 and chamber 23 by way of arm 83 which is rigidly connected to the manifold 34 . as mentioned previously , the actuation member 26 may be either solid or hollow to accommodate a prep lumen 69 for the introduction of fluid into the pressure source 21 and the inflation lumen . if a hollow actuation member is used , a prep port 84 located on the reel 81 may be utilized for access to the prep lumen 69 . the prep port 84 is preferably equipped with a cap to seal off the prep lumen 69 during use . fig8 shows a second embodiment of a proximal assembly of the present invention . proximal assembly 90 includes a prep manifold 33 connected to the actuation member 26 which allows for fluid to be introduced into the prep lumen 69 prior to in - vivo use and also allows the prep lumen 69 to be closed off prior to in - vivo use . the prep manifold 33 includes a female luer fitting 91 for connection to a conventional prepping syringe . the prep manifold 33 also includes threads 94 so that compression seal 93 closes the prep lumen 69 when the fitting 91 is turned relative to the hub 92 . fig9 shows a third embodiment of a proximal assembly of the present invention . proximal assembly 100 includes a prep manifold 102 connected to the actuation member 26 which includes a fluidic pressure gauge 101 ( e . g . bourdon gauge ). the fluidic pressure gauge 101 is in fluid communication with the prep lumen 69 which in turn is in fluid communication with the inflation lumen 29 and the interior of the balloon . with this arrangement , the pressure inside the balloon can be directly monitored by the fluidic pressure gauge 101 . manifold 102 also includes a fitting 105 for connection to a conventional prepping syringe and a cap 105 for closing the prep lumen 69 during use . the fluidic pressure gauge 101 may be replaced with an electronic pressure transducer and corresponding digital read out . it is also contemplated that the electronic pressure transducer may be mounted inside the chamber 23 and the actuation member could carry electric leads to the proximal end of the catheter for connection to a digital readout . fig1 shows a forth embodiment of a proximal assembly of the present invention . proximal assembly 110 may include the prep manifold as s discussed with reference to fig8 . the proximal assembly 110 also includes a spring pressure gauge 111 which correlates the compression of the spring 112 to the pressure inside the chamber 23 and thus the pressure inside the balloon . the actuation member 26 is advanced or retracted by gripping the actuator handle 113 rather than the prep manifold 33 . the actuator handle 113 is slidably disposed about the actuation member 26 and is rigidly connected to the proximal end of the spring 112 . the distal end of the spring 112 is rigidly connected to the actuation member 26 . a viewing window is cut into the actuator handle 113 to allow visualization of the indicator arrow 115 disposed on the actuation member 26 . as the actuator handle 113 is advanced , the force is transmitted through the spring 112 to the actuation member 26 to the pressure source 21 . as pressure builds inside the pressure source 21 and the balloon , the actuation member 26 resists advancement . the resistance to further advancement is felt in the spring 112 which responds by compressing a certain distance . the compression of the spring 112 may be noticed by the change of position of the actuation handle 113 relative to the indicator arrow 115 on the actuation member 26 . knowing the spring constant , the pressure inside the pressure source 21 and inside the balloon may be correlated to the distance the spring 112 is compressed . the correlation may be reflected in the pressure scale 114 disposed on the actuation handle 113 , and thus the pressure inside the balloon and pressure source 21 is shown by the position of the indicator arrow 115 relative to the pressure scale 114 . the exact same principles may be applied to correlate a vacuum inside the pressure source 21 and balloon to the expansion of the spring 112 . fig1 shows a fifth embodiment of a proximal assembly of the present invention . the proximal assembly 120 may include the prep manifold 33 as discussed with reference to fig8 . the proximal assembly 120 includes a shaft manifold 121 similar to the manifold 34 as discussed with reference to fig2 a , except that a viewing window 122 is cut into the side to permit viewing of an indicator arrow 124 disposed on the actuation member 26 . as the actuation member 26 is displaced either proximally or distally , the piston 24 inside the pressure source 21 displaces a certain volume of fluid which may be correlated to the size increment of the balloon . as such , as the actuation member 26 is displaced , the indicator arrow 124 moves relative to the shaft manifold 121 and the correlated size of the balloon may be shown by balloon sizing scale 123 . it should be noted that other similar structures may obtain the basic concept of indicating the size of the balloon by correlating the longitudinal displacement of the actuation member 26 to the size of the balloon . for example , the sizing scale may be located on the actuation member 26 and the indicator may be located on the shaft 22 or the shaft manifold 121 . fig1 shows a sixth embodiment of a proximal assembly of the present invention . this embodiment combines some of the features shown in fig9 and 11 . in particular , the proximal assembly 130 includes the pressure gauge manifold 102 as discussed with reference to fig9 and the balloon size manifold 121 as discussed with reference to fig1 . the combination allows the treating physician to monitor both the balloon size and the inflation pressure without the need for any ancillary equipment . similarly , fig1 shows a seventh embodiment of a proximal assembly of the present invention . this embodiment combines some of the features shown in fig8 and 11 . in particular , the proximal assembly 140 includes the prep manifold 33 as discussed with reference to fig8 the spring pressure gauge 111 as discussed with reference to fig1 , and the balloon size manifold 121 as discussed with reference to fig1 . this combination also allows the treating physician to monitor the balloon size and the inflation pressure without the need for any ancillary equipment . it should be noted that fig1 and 13 represent mere examples of possible combinations . the individual features of any of the proximal assemblies may be combined to achieve the desired device . in addition , it is contemplated that the pressure gauges and / or the balloon size indicators described above may be either rigidly or releasably attached to the catheter . furthermore , it is contemplated that the pressure gauge and sizing scale may be at a remote position within view of the treating physician but away from the device . the various embodiments of the present invention may be used in a variety of ways . the steps associated with inserting the device in - vivo and positioning the balloon across the treatment site are essentially the same as with conventional balloon catheters . however , the steps for prepping the catheter and inflating the catheter are very different . the pressure source , inflation lumen and balloon may be filled with fluid prior to final packaging or may be filled just prior to use by utilizing the prep lumen discussed previously . after the pressure source , inflation lumen and balloon are filled with fluid , the catheter is prepared (&# 34 ; prepped &# 34 ;) for use and does not require conventional ancillary devices such as an inflation device . with the balloon in position invivo , the balloon may be inflated by actuating the actuation member . as discussed previously , this may be done by longitudinal displacement , rotation or magnetic actuation . in the case of longitudinal displacement , the actuation member is pushed distally while holding the shaft and chamber relatively fixed . similarly , in the case of rotational actuation , the actuation member is rotated while the shaft and chamber are held relatively fixed . magnetic actuation may be accomplished by activating a solenoid drive which is set to the desired amplitude and frequency . the balloon is inflated to the desired size and / or pressure as indicated by the lo previously described pressure gauges and balloon size indicators . the balloon size may also be monitored by conventional angiography . when desired , the treating physician may deflated the balloon by reversing the actuation steps . in the case of the solenoid drive , the balloon is automatically inflated and deflated in rapid succession . the frequency and or amplitude may be modified during the oscillation or between oscillations . after the treatment is complete , the catheter system is removed substantially the same as conventional balloon catheters . refer now to fig1 and 15 which show the balloon response of the present invention versus the a prior art system to a single inflation and deflation . the balloon response was measured by positioning the balloon in a fixture including a lucas schaevitz model 250 dce linear transducer electrically connected to a tek 2232 oscilloscope . the linear transducer was positioned to abut one side of the balloon and a stop plate was positioned to abut the other side of the balloon . with this arrangement , changes in balloon diameter caused displacement of the linear transducer as recorded by the oscilloscope . the pressure of both the inflation device ( prior art ) and the pressure source ( present invention ) were measured by a lucas nova model npc - 102 pressure sensor electrically connected to the tek 2232 oscilloscope by way of frequency devices model 9002 filter instrument . the prior art device included a scimed cobra 14 3 . 5 mm × 20 mm balloon catheter operably connected to a scim ed encore inflation device . the embodiment of the present invention utilized a 0 . 054 diameter piston inside a 6 . 0 inches long chamber which was positioned 30 cm from a 3 . 5 mm × 20 mm balloon . the prior art device was inflated by manually actuating the handle on the inflation device to a specified pressure . the present invention embodiment was inflated by manually pushing the actuation member and holding it at a specified pressure . fig1 shows the balloon response of the prior art system to a single inflation and deflation . the pressure curve of the inflation device is denoted by the letter a and the balloon - response curve is denoted by the letter b . fig1 shows the balloon response of the present invention to a single inflation and deflation . the pressure curve is denoted by the letter c and the balloon response curve is denoted by the letter d . the balloon response graphs of fig1 and 15 demonstrate the increased responsiveness of the present invention as compared to the prior art . the prior art device has a inflation time lag of approximately 1 . 0 seconds from inflation pressure initiation to balloon response and a deflation time lag of approximately 2 . 0 seconds from deflation pressure initiation to full balloon deflation . by contrast , the present invention has a inflation time lag of approximately 0 . 1 seconds from inflation pressure initiation to balloon response and a deflation time lag of approximately 0 . 5 seconds from deflation pressure initiation to full balloon deflation . thus , in this experiment the inflation response improved 900 % and the deflation response improved 300 %. referring now to fig1 and 17 , the balloon response to cyclic inflation and deflation is shown for a prior art system and an embodiment of the present invention . the same test arrangement and test specimens as discussed with reference to fig1 and 15 were used for the test corresponding to fig1 and 17 . the inflation device of the prior art system was manually oscillated as was the actuation member on the present invention embodiment . fig1 shows the balloon response of the prior art system to a cyclic inflation and deflation . the pressure curve of the inflation device is denoted by the letter a and the balloon response curve is denoted by the letter b . fig1 shows the balloon response of the present invention to a cyclic inflation and deflation . the pressure curve is denoted by the letter c and the balloon response curve is denoted by the letter d . the balloon response graphs of fig1 and 17 demonstrate the increased responsiveness of the present invention as compared to the prior art and in particular the benefits of reduced system compliance . the prior art device has an essentially non - responsive balloon to oscillating inflation pressures with an amplitude of approximately 3 - 4 atm at a frequency of about 2 . 2 hz . by contrast , the present invention embodiment has a noticeably responsive balloon to oscillating inflation pressures with an amplitude of approximately 3 - 4 atm at a higher frequency of about 2 . 75 hz . thus , the compliance of the prior art system is sufficiently high to dampen the effect of the inflation pressure , whereas the compliance of the present invention system is sufficiently low to permit effective balloon response to cyclic inflation pressure . this feature may be of particular significance when the pulsating balloon technique is used to atraumatically dilate difficult lesions . similar results are demonstrated in fig2 and 21 which show the dynamic balloon response of the present invention to a solenoid driven pressure source . the solenoid drive system used for this test is described in detail with reference to alternative embodiments of fig5 and 6 . in particular , the test specimen utilized solenoid model number 9219 available from lucas ledex driven by an harris 7667 integrated circuit ( separated in series by a irf531 mosfet ) and triggered by a stanford research ds335 signal generator to provide an oscillatory force to the pressure source when rigidly ( or releasably ) connected to the actuation member . the same balloon response measurement and pressure measurement apparatus as described with reference to fig1 and 15 was used for the test reflected in fig2 and 21 . fig2 shows the dynamic balloon response ( curve labeled y 1 ) of an embodiment of the present invention to a solenoid driven at 20 hz square wave with an amplitude of approximately 5 volts which corresponds to a solenoid displacement of about 0 . 313 inches ( curve labeled x 1 ). the dynamic balloon response has a matched frequency at an amplitude of approximately 0 . 30 mm . this response results in what essentially feels like a vibrating balloon , which may be used to effectively massage a vascular lesion during dilation and thus perhaps dilate at lower pressures and reduce the potential for abrupt closure or restenosis . fig2 shows the dynamic balloon response ( curve labeled y 2 ) of an embodiment of the present invention to a solenoid driven at 30 hz square wave with an amplitude of approximately 5 volts which corresponds to a solenoid displacement of about 0 . 313 inches ( curve labeled x 2 ). the dynamic balloon response has a matched frequency at a relatively large amplitude of approximately 0 . 65 mm . thus , without increasing the solenoid amplitude , the balloon response has more than doubled because the input frequency matches the resonance of the catheter system . this can be used to focus significant vibratory energy at the location of the lesion which may improve the ability to dilate difficult lesions such as calcified lesions at relatively low pressures . it is further contemplated that a drive system operating at higher frequencies ( e . g . sonic ) may be employed to cause correspondingly higher frequency response of the balloon . with this arrangement , it is believed possible to match the natural resonance of the lesion . matching the natural resonance of the lesion would allow the treating physician to dramatically affect even the most calcified lesion without disrupting the native vasculature . this allows the physician to effectively treat only the diseased portion of the vessel regardless of the physical integrity of the lesion . now refer to fig1 and 19 which demonstrate the response of a synthetic arterial lesion to balloon dilation . the same test apparatus as described with reference to fig1 and 15 is used in this experiment except that a synthetic calcium carbonate annular lesion is placed around the balloon . as shown in fig1 , the inflation pressure ( curve labeled a ) of the prior art system is gradually increased by rotating the handle on the inflation device . at approximately 10 . 4 atm , the synthetic lesion cracks and the balloon diameter jumps from 2 . 5 mm to 3 . 5 mm ( curve labeled b ). thus , when the lesion cracks , the balloon continues to grow primarily due to the excessively high stored compliance of the fluid system . by contrast , the balloon diameter ( curve labeled b ) of the present invention shown in fig1 does not continue to grow more than 0 . 1 mm . the significantly reduced compliance of the present invention reduces the potential for dissection or crack propagation after the lesion is cracked which in turn increases the potential for favorable clinical results . another embodiment of the present invention is contemplated ( not shown ) which utilizes pressurized gas and a corresponding pressure source in place of the actuation member . a piston and chamber arrangement may be used as described previously but the piston is actuated by the pressurized gas rather than the actuation member . alternatively , a flexible membrane may be used in place of the piston and chamber . since the pressurized gas has a relatively low viscosity as compared to conventional inflation liquids , the response of the piston to pressurized gas is almost immediate . by contrast to the actuation means described previously , the overall compliance of this system is higher because gas is relatively compliant . however , the use of gas actuation may in some circumstances increase the responsiveness of the balloon . while the specification describes the preferred constructions , materials , dimensions , methods of manufacture and methods of practice , those skilled in the art will appreciate the scope and spirit of the invention with reference to the appended claims .

US-61937596-A

dental liner and primer compositions having improved adhesion to dentin and containing a metal dissolved in a polar organic solvent , said metal being selected from fe , cu , mn , co , sn , cr , ni , and zn .

in the practice of the present invention , the polymerizable phosphorus compound ( viz ., component ( a ) above ) is preferably an organic ester of one or more acids of phosphorus ( hereafter referred to as &# 34 ; phosphorus acid esters &# 34 ;), said ester having chlorine or bromine bonded directly to phosphorus , and the organic radical of said ester containing at least one polymerizable functional group . said phosphorus acid esters can be characterized by the formulas ( i ) and ( ii ): ## str2 ## wherein m is 1 to 3 , n &# 39 ; and n &# 34 ; are independently zero to 4 and are the same or different , with the proviso that n &# 39 ; and n &# 34 ; are both not zero , p , p &# 39 ;, and p &# 34 ; are zero or 1 and are the same or different , r 1 is a monovalent olefinic organic radical ( preferably alkenyl , alkenoxy , cycloalkenyl , aralkenyl , or alkenaryl , having 2 to 40 carbon atoms ) which can be straight chain , branched , or cyclic , can contain skeletal hetero atoms , i . e ., atoms other than carbon ( e . g ., oxygen , sulfur , or non - basic nitrogen atoms ), and can be unsubstituted or substituted with non - interfering moieties , e . g ., moieties which do not interfere with free - radical polymerization of said phosphorus acid esters , r 2 and r 3 are divalent olefinic organic radicals ( preferably alkenylidene , oxyalkenylidene , cycloalkenylidene , arylenealkenylidene , or alkenylidenearylene , having 2 to 40 carbon atoms ) which can be straight chain , branched , or cyclic , can contain skeletal hetero atoms , can be unsubstituted or substituted with non - interfering moieties , and are the same or different , and x is cl , br , or r 4 , where r 4 is an aliphatic or oxyaliphatic radical having 1 to 12 carbon atoms , and each x is the same as or different from other x , with the proviso that at least one x is cl or br . compounds of formula i and ii contain trivalent or pentavalent phosphorus atoms . in compounds of formula i , phosphorus is bonded to at least one chlorine or bromine atom . in compounds of formula ii , at least one phosphorus atom is bonded to at least one chlorine or bromine atom . preferably phosphorus is bonded to chlorine . the preferred phosphorus acid esters desirably contain at least one double bond between phosphorus and oxygen or sulfur , with a double bond to oxygen being preferred . most preferably two or more polymerizable functional groups per phosphorus atom are contained in the preferred phosphorus acid esters . also , the phosphorus acid esters are preferably liquids at room temperature . the polymerizable functional group in the preferred phosphorus acid esters is a free - radically polymerizable group , such as an olefin , and is most preferably a monofunctional or difunctional acryl or methacryl radical . other polymerizable functional groups include monofunctional or difunctional vinyl , allyl , crotyl , and cinnamyl radicals . representative preferred phosphorus acid esters include : ## str3 ## as well as mixtures of more than one of the above compounds . the preferred phosphorus acid esters can be used individually or in the form of adducts containing more than one phosphorus acid ester . preferably , the phosphorus acid esters are prepared by combining a chlorine - or bromine - containing phosphorus acid ( e . g ., phosphorus oxychloride , pocl 3 , also known as phosphoryl chloride ) with a polymerizable monomer having at least one reactive hydroxyl group ( e . g ., bis - gma and isomers thereof , sometimes referred to collectively hereafter as &# 34 ; bis - gma &# 34 ;, such as those isomers obtained by replacement of one or both of the 2 - hydroxypropylene moieties of bis - gma with 2 - hydroxymethylethylene moieties ). such polymerizable monomers having at least one reactive hydroxyl group will be hereafter referred to as &# 34 ; hydroxylated monomers &# 34 ;. when the hydroxylated monomer has a high initial viscosity , it is preferable to mix the phosphorus acid with the hydroxylated monomer and a suitable diluent ( which diluent is preferably said component ( f ), above ), e . g ., triethyleneglycol dimethacrylate . the phosphorus acid and hydroxylated monomer will react at low temperature , e . g ., at room temperature , and the reaction mixture will increase in viscosity , preferably reaching an equilibrium state that is stable over time . the reaction product of such a mixture will generally be an adduct , the phosphorus acid esters of which are the product of reactions between some or all of the various hydroxyl groups of the hydroxylated monomer and available chlorine or bromine atoms of the phosphorus acid . sufficient phosphorus acid should be added to the hydroxylated monomer to provide good bonding and handling performance in liner and primer compositions prepared therewith . for an adduct prepared by combining phosphorus oxychloride and bis - gma , about 0 . 25 to twenty percent by weight phosphorus oxychloride , and preferably about one to ten percent by weight phosphorus oxychloride should be used , based on the weight of bis - gma . because bis - gma contains two hydroxyl groups per molecule , the above weight percentage values represent equivalent ratios of pocl 3 to bis - gma of about 0 . 025 : 1 to 1 : 1 , preferably about 0 . 05 : 1 to 0 . 5 : 1 . suitable adjustment of such equivalent ratios should be made when the phosphorus acid esters are prepared from hydroxylated monomers having other hydroxyl functionality , e . g ., monofunctionality or trifunctionality . also , suitable adjustment of such equivalent ratios should be made when the phosphorus acid esters are prepared from phosphorus acids other than phosphorus oxychloride . expressed in terms of the ratio of halogen atoms in the phosphorus acid to hydroxyl groups in the hydroxylated monomer , the phosphorus acid and hydroxylated monomer should be combined in a ratio of halogen atom to hydroxyl group between about 0 . 0375 : 1 to 1 . 5 : 1 , preferably about 0 . 075 : 1 to 0 . 75 : 1 . if lesser amounts of phosphorus acid than those amounts sufficient to provide good bonding and handling performance are used , the resulting adduct may have low adhesion to dentin and enamel when polymerized therewith . if larger amounts of phosphorus acid than those sufficient to provide good bonding and handling are used , the resulting adduct will tend to homopolymerize , thereby having inadequate shelf life . other phosphorus acids which can be reacted with hydroxylated monomers to prepare the preferred phosphorus acid esters used in this invention include ch 3 pocl 2 , pcl 3 , pcl 5 , c 6 h 5 pocl 2 , c 6 h 5 opocl 2 , and pbr 3 . such phosphorus acids can be used singly or in combination . phosphorus oxychloride is a preferred phosphorus acid for use in the preparation of the preferred phosphorus acid esters used in this invention . other hydroxylated monomers which can be used to prepare the preferred phosphorus acid esters used in this invention include hydroxyethyl methacrylate , pentaerythritol triacrylate , glycerol dimethacrylate , methyl vinyl alcohol , vinyl benzyl alcohol , allyl alcohol , crotyl alcohol , and cinnamyl alcohol . the mixing of phosphorus acid and hydroxylated monomer can be carried out at room temperature . the attainment of equilibrium between the phosphorus acid and hydroxylated monomer can be determined by observing the viscosity of the adduct over time , with equilibrium being indicated by a leveling off of such viscosity . other polymerizable phosphorus compounds which can be used as said component ( a ) include compounds containing olefinic functionality and at least one ## str4 ## moiety , such as glycerophosphate dimethacrylate and the polymerizable phosphorus compounds described in u . s . pat . nos . 4 , 182 , 035 , 4 , 222 , 780 , 4 , 235 , 633 , and 4 , 259 , 075 , o . l . s . nos . 2711234 and 2818068 , and japanese laid - open application nos . 77 - 113089 , 78 - 30193 , 78 - 39331 , 78 - 67740 , 78 - 69494 , 78 - 110637 , 78 - 113843 , 78 - 134037 , 78 - 144939 , 78 - 138441 , 79 - 21438 , and 79 - 28339 . of the polymerizable phosphorus compounds described therein , the compound ## str5 ## is a preferred polymerizable phosphorus compound for use in the present invention . said solution of a metal , hereafter sometimes referred to as the &# 34 ; metal solution &# 34 ; ( viz ., component ( b ) above ) enhances the adhesion of the other components of the dental bonding composition to dentin upon polymerization thereof . metal solutions containing ions such as fe + 3 , cu + 2 , mn + 2 , and co + 2 ions are preferred , and metal solutions containing fe + 3 ion are most preferred . metal solutions containing more than one metal ( e . g ., solutions containing fe + 3 ion and mn + 2 ion ) can be used if desired . the metal solution can be prepared by dissolving a salt of the desired metal in a suitable polar organic solvent . suitable metal salts include fecl 3 , fe ( no 3 ) 3 , cucl 2 , cu ( no 3 ) 2 cuso 4 , mncl 2 , mnf 2 , cocl 2 , sncl 4 , crcl 3 , nicl 2 , zncl 2 , hydrates thereof , and mixtures thereof . the polar organic solvent preferably is a solvent for both the metal and for the polymerizable phosphorus compound . suitable polar organic solvents include alcohols ( e . g ., ethanol ), ketones ( e . g ., acetone ), polar heterocycles ( e . g ., tetrahydrofuran ), said diluent ( f ), above ( also described in greater detail below ), and mixtures thereof . other substances which are poor solvents for the polymerizable phosphorus compound ( e . g ., water ) can be used as the polar organic solvent if desired , but preferably such other substances are not used or are excluded . absolute ethanol is a preferred polar organic solvent . other adjuvants , such as buffering agents , fungicides , dyes , pigments , indicators , and the like can also be added to the metal solution if desired . the concentration of metal in the metal solution should be sufficient to provide an effective amount of metal in the dental bonding composition . an &# 34 ; effective amount &# 34 ;, as used herein , is an amount sufficient to provide improved adhesion to dentin of dental restorations prepared with the dental bonding compositions of the invention , compared to dental restorations prepared with corresponding dental bonding compositions which do not contain said metals . an effective amount of metal in the dental bonding composition is a non - toxic amount , preferably between about 5 . 2 × 10 - 5 and 1 . 9 × 10 - 2 weight percent of metal based on the weight of said polymerizable phosphorus compound ( a ). the &# 34 ; concentration of metal &# 34 ;, as used herein , is based upon the equivalent weight of elemental metal present , although , of course , a substantial portion of the metal in the metal solution may be in ionic form . the concentration of metal in the metal solution can range between trace amounts and the limit of solubility ( when mixed with any other components of the metal solution ) of the metal cation . preferably , the concentration of metal in the metal solution is chosen such that mixing a given volume ( e . g ., one drop ) of the metal solution with an equal volume ( s ) of solution ( s ) containing said components ( a ), ( c ), ( d ), ( e ), and ( f ) will provide the desired concentration of metal in the resulting dental bonding composition . for metal solutions containing fe + 3 ion in ethanol , the preferred concentration of iron is between about 3 . 2 × 10 - 4 and 1 . 2 × 10 - 1 grams of iron per liter of ethanol , and most preferably is between about 3 . 2 × 10 - 3 and 3 . 2 × 10 - 2 grams of iron per liter of ethanol . similar concentration ranges are preferred for other metals and other solvents , and range between about 2 to 700 parts per million by weight (&# 34 ; ppm &# 34 ;) of metal in solvent , and most preferably between about 20 to 200 ppm . said sulfur compound having sulfur in the + 2 or + 4 oxidation state , hereafter sometimes referred to as the &# 34 ; sulfur compound &# 34 ;, ( viz ., component ( c ) above ) acts as an activator for polymerization of the dental bonding compositions of this invention . &# 34 ; oxidation state &# 34 ;, as used herein , is defined according to hendrickson et al ., organic chemistry , third edition , pps . 796 - 799 ( mcgraw hill co ., 1970 ). suitable sulfur compounds are ordinarily alkali metal salts , such as potassium or sodium salts , or ammonium salts , of sulfur - containing anions such as sulfinate or sulfonate anions . additional sulfur compounds which can be used in this invention include the salts of sulfurous acid having the following formulas ( iii ), ( iv ), ( v ), and ( vi ): ## str6 ## wherein m is a metal from group i of the periodic table of the elements , or a cation of the formula n ( r 5 ) 4 + where r 5 is a hydrogen atom , a monovalent alkyl or cycloalkyl radical having about 1 to 8 carbon atoms , or two r 5 taken together with the nitrogen atom to which they are joined combine to form a 5 to 7 membered ring , each r 5 is the same as or different from other r 5 , and r 5 can contain hetero atoms which do not interfere with the functioning of the salt of sulfurous acid as an aid to polymerization of the polymerizable liquid monomer , such as oxygen , sulfur , or nitrogen . such salts of sulfurous acid are ordinarily alkali metal salts , such as potassium or sodium salts or ammonium or alkylammonium salts , of bisulfite , metabisulfite , hydrosulfite , or sulfite anions . suitable sulfur compounds include c 6 h 5 so 2 na , ch 3 c 6 h 4 so 2 k , c 6 h 5 so 3 na , lihso 3 , nahso 3 , khso 3 , nh 4 hso 3 , li 2 s 2 o 5 , k 2 s 2 o 5 , na 2 s 2 o 5 , ( nh 4 ) 2 s 2 o 5 , na 2 s 2 o 4 , k 2 s 2 o 4 , ( nh 4 ) 2 s 2 o 4 , li 2 so 3 , na 2 so 3 , k 2 so 3 , ( nh 4 ) 2 so 3 , and mixtures thereof . sodium benzene sulfinate is a preferred sulfur compound . the amount of sulfur compound used is an amount sufficient to provide good bonding and handling performance ( e . g ., good shelf life and working time ) in dental bonding compositions of the invention prepared therewith . a preferred amount is between about 0 . 5 to 10 weight percent sulfur compound based on the total weight of the dental bonding composition . the sulfur compound is preferably dissolved in a suitable solvent , such as an alcohol ( e . g ., ethanol ), so that the desired amount of sulfur compound can be readily combined with the other components of the dental bonding composition . said tertiary amine , ( viz ., component ( d ) above ) acts as a polymerization accelerator for the dental bonding compositions of this invention . suitable tertiary amines include dhpt , n , n - dimethyl - para - toluidine , n , n - bis ( 2 - hydroxyethyl )- 3 , 5 - xylidine , and the like . dhpt is a preferred tertiary amine . the amount of tertiary amine used is an amount sufficient to provide good bonding and handling performance in dental bonding compositions of the invention prepared therewith . a preferred amount is between about 0 . 1 to 10 weight percent tertiary amine on the total weight of the dental bonding composition . the tertiary amine is preferably dissolved in a suitable solvent , such as an alcohol ( e . g ., ethanol ), so that the desired amount of tertiary amine can be readily combined with the other components of the dental bonding composition . said polymerization catalyst ( viz ., component ( e ) above ) promotes polymerization of the dental bonding compositions of this invention . suitable polymerization catalysts include free - radical initiators such as peroxides , e . g ., benzoyl peroxide , acetyl peroxide , lauroyl peroxide , and t - butyl hydroperoxide . benzoyl peroxide is a preferred free - radical initiator . photoinitiators ( i . e ., light - activatable catalysts ) such as monoketals of aromatic 1 , 2 - diketones or a combination of benzil and a dialkylamino acrylate or methacrylate can also be used . the amount of polymerization catalyst is an amount sufficient to provide good bonding and handling performance in dental bonding compositions of the invention prepared therewith . a preferred amount is between about 0 . 05 to 5 weight percent polymerization catalyst based on the total weight of the dental bonding composition . the polymerization catalyst preferably is dissolved in a suitable solvent ( e . g ., said diluent ( f ), above ), and preferably is combined with said polymerizable phosphorus compound prior to shipment thereof to the user . said diluent ( viz ., said component ( f ), above ) serves to reduce the viscosity of the dental bonding compositions of the invention , and thereby enhance the penetration thereof into the microstructure of the tooth treatment site ( e . g ., into the dentin tubules ). also , the diluent preferably copolymerizes with and increases the crosslink density of the dental bonding composition , thereby increasing the hardness and strength ( e . g ., diametral tensile strength ) thereof . suitable diluents include triethyleneglycol dimethacrylate ( hereafter referred to as &# 34 ; tegdma &# 34 ;), 1 , 4 - butanediol dimethacrylate , 1 , 6 - hexanediol dimethacrylate , 1 , 8 - octanediol dimethacrylate , trimethylolpropane trimethacrylate , tetraethyleneglycol dimethacrylate , neopentylglycol dimethacrylate , hydroxyethyl methacrylate , bisphenol a dimethacrylate , glycidyl methacrylate , styrene , vinyl acetate , and mixtures thereof . preferred diluents have methacrylic functionality . tegdma and 1 , 6 - hexanediol dimethacrylate are most preferred diluents . the amount of diluent should be sufficient to lower the viscosity of the dental bonding composition to a level sufficient to provide good bonding and handling performance ( e . g ., ease of mixing ). if the diluent is mixed with the polymerizable phosphorus compound ( without addition of other components of the dental bonding composition ), the viscosity of the resulting mixture preferably is between about 5 and 5000 cps at 25 ° c ., and most preferably is less than about 3500 cps at 25 ° c ., and the diluent preferably is between about 25 to 75 percent by volume of said mixture . addition of solutions containing the remaining components of the dental bonding composition will typically further reduce the viscosity of the dental bonding composition below the preferred upper limits for viscosity stated above . the dental bonding compositions of this invention can contain other adjuvants such as surfactants , pigments , inhibitors , stabilizers against oxidation , and the like . the amounts and types of such adjuvants , and their manner of incorporation in the dental bonding compositions of this invention , will be essentially the same as currently used in existing dental liner and primer compositions familiar to those skilled in the art . the dental bonding compositions of the invention are preferably put up in multiple - part packages . maximum shelf life is obtained if the metal of the metal solution is kept separate from the polymerizable phosphorus compound , the sulfur compound , and the tertiary amine until the time of use , as the metal may have a tendency to form insoluble complexes with the above - mentioned other components , thereby diminishing the bonding performance of dental restorations prefered therewith . also , the polymerizable phosphorus compound and the sulfur compound are preferably kept separate until the time of use , as addition of the sulfur compound to the polymerizable phosphorus compound can promote homopolymerization of the latter upon standing . however , the use of multiple - part packaging for the dental bonding compositions of the invention is not a drawback , because the individual components can be readily dispensed and mixed due to their low viscosity and the small quantity of dental bonding composition typically required for a dental restoration . for example , polymerizable phosphorus compound , polymerization catalyst , and diluent can be combined in a first part , a suitable first solvent ( e . g ., aqueous ethanol ), sulfur compound , and tertiary amine can be combined in a second part , and a suitable second solvent ( e . g ., aqueous ethanol ) and soluble salt of the desired metal ( e . g ., fecl 3 or hydrate thereof ) can be combined in a third part . while uncombined , the resulting three - part package will remain in a stable , uncured state . when the three parts are mixed together , e . g ., by spatulation , stirring , or other means , the resulting liner composition will be ready for use . also , a polymerizable phosphorus compound , polymerization catalyst , and diluent can be combined in a first part , a suitable first solvent ( e . g ., aqueous ethanol or water ) and sulfur compound can be combined in a second part , a suitable second solvent ( e . g ., aqueous ethanol or water ) and tertiary amine can be combined in a third part , and a suitable third solvent ( e . g ., aqueous or absolute ethanol ) and soluble salt of the desired metal can be combined in a fourth part , and the four parts later mixed together for use . the amount of each ingredient in such multiple - part packages should be adjusted to allow sufficient working time for the practitioner to mix and apply the dental bonding composition as desired , together with attainment of the desired physical properties in the cured dental restoration . if desired , other combinations of polymerizable phosphorus compound , desired metal , sulfur compound , tertiary amine , polymerization catalyst , diluent , and any other desired adjuvants can also be employed in multiple - part packages of dental bonding compositions of this invention . preferably , a multiple - part dental bonding composition package offers ease of mixing , good shelf life , and desirable physical properties after cure . in addition , where desired , one or more of said components ( c )-( d ) can be omitted from the dental bonding composition , provided that the omitted component ( s ) are present in an adjacent layer of uncured dental restorative , composite , or adhesive and can migrate into the dental bonding composition during polymerization thereof . however , this packaging method may diminish clinical reproducibility of bonding results obtained therewith . the dental bonding compositions of the invention can be used to line prepared dentin and enamel surfaces of a dental restoration . the dental bonding compositions of the invention are applied in a manner similar to that used for existing dental liner compositions . however , cavity preparation is simplified . excavation can be limited to the removal of damaged or defective tooth structure . undercutting of the cavity is generally not required for retention of the restorative in the cavity . if desired , acid etching of the cavity can be omitted . this invention therefore shortens the time required for completion of a dental restoration and reduces trauma to healthy tooth structure . following application of the dental bonding composition , the thus - treated dentin and enamel surfaces of the area to be restored can be covered with conventional restorative or composite compositions , which are hardened and finished using conventional techniques . the dental bonding compositions of the invention can also be used as primers for the fastening of dental devices ( e . g ., orthodontic brackets and crowns ) with dental adhesives . the dental bonding compositions of the invention are applied in a manner similar to that used for existing dental adhesive primers . however , application technique can be simplified . satisfactory results can often be obtained in the absence of acid etching , thereby reducing damage to tooth enamel . where desired , e . g ., to obtain very high bonding strength when dental devices are bonded to tooth enamel , acid etching of the exposed tooth enamel can be employed . the following examples are offered to aid understanding of the present invention and are not to be construed as limiting the scope thereof . 10 g of phosphorus oxychloride was dissolved in a polymerizable monomer mixture ( identified hereafter as &# 34 ; resin a &# 34 ;) containing 96 g bis - gma , 2 . 0 g of benzoyl peroxide , 96 g tegdma , 0 . 13 g of butylated hydroxytoluene , 0 . 34 g phenyl salicylate , and 0 . 24 g glycidyl methacrylate . the resulting mixture was allowed to stand at room temperature for 5 days . this reaction product was labeled as part &# 34 ; a &# 34 ; and was used as the first part of a three - part dental bonding composition ( hereafter sometimes referred to as the &# 34 ; bonding agent &# 34 ;). a solution of 3 percent by weight sodium benzene sulfinate and 1 percent by weight dhpt in absolute ethanol was prepared . this solution was labeled as part &# 34 ; b &# 34 ; and was used as the second part of the bonding agent . a solution containing 4 . 1 × 10 - 4 weight percent iron in absolute ethanol was prepared using ferric chloride hexahydrate , fecl 3 . 6h 2 o . this solution was labeled as part &# 34 ; c &# 34 ; and was used as the third part of the bonding agent . adhesion of the bonding agent to unetched dentin was evaluated using the following procedure . four bovine teeth of similar age and appearance were partially embedded in circular acrylic disks . the exposed portion of each tooth was ground flat and parallel to the acrylic disk using 120 grit silicon carbide paper - backed abrasive mounted on a lapidary wheel , in order to expose the tooth dentin . during this and subsequent grinding and polishing steps , the teeth were continuously rinsed with water . further grinding and polishing of the teeth was carried out by mounting 400 grit silicon carbide paper - backed abrasive and 600 grit silicon carbide paper - backed abrasive on the lapidary wheel . the teeth were stored in distilled water , and dried with oil - free compressed air immediately prior to use . one drop of each part of the bonding agent was placed in a mixing tray . the drops were mixed together by hand spatulation for about 5 seconds , and the resulting mixture was then painted onto the polished tooth surface and blown into a thin film with compressed oil - free air . a conventional orthodontic bracket adhesive (&# 34 ; concise 1960 &# 34 ;, commercially available from 3m ) was placed on the pad surface of an orthodontic bracket ( bracket no . 007 and pad no . 065 , commercially available from american orthodontics , inc .) and the adhesive - coated bracket pad was then applied to the bonding agent - treated dentin surface . the tooth and bracket were allowed to stand for about 10 minutes at room temperature , then stored in distilled water at 37 ° c . for 24 hours . adhesion of the bonding agent to the polished , unetched bovine dentin was evaluated by placing the tooth mounting disk in a holder and clamping the holder in the jaws of an &# 34 ; instron &# 34 ; apparatus with the layer of bonding agent parallel to the direction of pull . a loop of orthodontic wire ( 0 . 44 mm diameter ) was placed around the bracket . the ends of the orthodontic wire were clamped in the pulling jaws of the instron apparatus , thereby placing the bonding agent bond in shear stress . at a crosshead speed of 5 mm / min , the average measured shear strength of the bonding agent - dentin bond was 49 . 3 kg / cm 2 . using the above technique , the bond strength on polished bovine enamel was also evaluated , without use of acid etching . bond strength on unetched enamel was an average of 64 . 1 kg / cm 2 . in a comparison run , parts a and b were combined in a two - part liner composition without the use of part c . when the liner composition was evaluated using the above - described procedure , the average bond strength on unetched dentin was 38 . 6 kg / cm 2 and the average bond strength on unetched enamel was 63 . 3 kg / cm 2 . this comparison run shows that use of the metal solution of part c improved adhesion to dentin by approximately 27 percent and improved adhesion to enamel by approximately 1 percent . in a further comparison run , an isotonic ferric chloride mordant solution containing 1 . 41 percent by weight fecl 3 . 6h 2 o was prepared and applied to polished dentin using the procedure of example 3 of u . s . pat . no . 4 , 251 , 565 , but using a 1 minute application time ( instead of the thirty second application time shown therein ) and with rinsing of the mordant solution from the tooth ( rather than removal by suction as shown therein ). next , the above - described parts a and b ( but not part c ) were mixed to form a two - part liner composition . when this composition was evaluated for adhesion to dentin using the above - described technique , the average bond strength on unetched dentin was 30 . 1 kg / cm 2 . this comparison run shows that use of the &# 34 ; mordant &# 34 ; prewash technique of u . s . pat . no . 4 , 251 , 565 actually decreases adhesion to dentin when used with the two - part liner composition containing the above - described parts a and b . in yet a further comparison run , the &# 34 ; mordant &# 34 ; prewash procedure of the preceeding paragraph was repeated , but using a prewash solution containing 20 parts per millon by weight fecl 3 . 6h 2 o in absolute ethanol in place of the isotonic 1 . 41 weight percent fecl 3 solution used previously . the average bond strength on unetched dentin was 39 . 8 kg / cm 2 . this further comparative example shows that an improvement in adhesion to dentin could be obtained with a prewash solution containing a very small amount of fecl 3 ( a much more dilute solution than that suggested in said u . s . pat . no . 4 , 251 , 565 ), but the improvement in adhesion to dentin amounted to only about 0 . 5 percent . the procedure of example 1 was repeated , using other compositions in place of the three - part dental bonding composition containing parts a , b , and c of example 1 . set out below in table i are the example no ., composition of each part of the dental bonding composition , and the adhesion to polished , unetched dentin and to polished , unetched enamel obtained using the dental bonding composition of each example . also set out below are comparison examples showing the effect of omission of the metals used in this invention . the notes following table i show the composition of each part of the dental bonding compositions referred to therein . the notation &# 34 ; ppm &# 34 ; refers to parts per million on a weight basis . table i______________________________________ dental bonding composition bond strength bond strengthex . no . or part part part on dentin , on enamel , comp . ex . no . one two three kg / cm . sup . 2 kg / cm . sup . 2______________________________________ 2 a b c1 46 . 2 -- 3 a b c2 44 . 1 -- 4 a b c3 41 . 4 -- 5 a b c4 30 . 9 -- 6 a b c5 39 . 1 -- 7 a b c6 41 . 7 -- 8 a b c7 41 . 1 -- 9 a b c8 49 . 8 65 . 210 a b c9 24 . 6 -- 11 a b c10 39 . 8 56 . 012 a b c11 39 . 2 66 . 113 a b c12 47 . 1 66 . 114 a b1 c13 47 . 6 66 . 115 a b2 c13 45 . 4 48 . 216 a b3 c13 63 . 8 53 . 217 a b4 c13 40 . 5 39 . 818 a b5 c13 56 . 0 51 . 719 a b6 c13 65 . 5 34 . 220 a b7 c13 65 . 0 49 . 821 a b8 c13 58 . 2 -- 22 a b8 c14 57 . 7 -- 23 a1 b9 c 51 . 0 21 . 324 a1 b9 c5 15 . 1 -- 25 a1 b9 c6 26 . 9 -- 26 a1 b9 c7 57 . 6 -- 27 a1 b9 c8 25 . 9 -- comp . ex . 1 a b8 c15 42 . 0 47 . 3comp . ex . 2 a b10 -- 36 . 4 54 . 6comp . ex . 3 a1 b9 -- 17 . 0 32 . 7______________________________________notes : a is &# 34 ; part a &# 34 ; of example 1 . a1 is &# 34 ; clearfil &# 34 ; catalyst resin , commercially availablefrom kuraray co ., ltd ., and believed to contain ## str7 ## and about 2 wt . % benzoyl peroxide . b is &# 34 ; part b &# 34 ; of example 1 . b1 is 3 wt . % sodium benzene sulfinate in absolute ethanolb2 is 5 wt . % sodium bisulfite in water . b3 is b2 plus 0 . 1 wt . % &# 34 ; triton x - 100 &# 34 ; surfactant ( commercially available from rohm and haas co .). b4 is 5 wt . % ammonium bisulfite in water . b5 is b4 plus 0 . 1 wt . % &# 34 ; triton x - 100 &# 34 ;. b6 is 5 wt . % sodium metabisulfite in water . b7 is b6 plus 0 . 1 wt . % &# 34 ; triton x - 100 &# 34 ;. b8 is 5 wt . % sodium bisulfite in 50 % aqueous ethanol . b9 is &# 34 ; clearfil &# 34 ; universal liquid , commercially availablefrom kuraray co ., ltd ., and believed to contain about3 wt . % sodium benzene sulfinate and about 1 wt . % dhptin ethanol . b10 is b plus 0 . 1 wt . % &# 34 ; triton x - 100 &# 34 ;. c is &# 34 ; part c &# 34 ; of example 1 . c1 is 20 ppm cucl . sub . 2 in absolute ethanol . c2 is 20 ppm sncl . sub . 4 in absolute ethanol . c3 is 20 ppm mncl . sub . 2 in absolute ethanol . c4 is 1 ppm fecl . sub . 3 in absolute ethanol . c5 is 2 ppm fecl . sub . 3 in absolute ethanol . c6 is 5 ppm fecl . sub . 3 in absolute ethanol . c7 is 50 ppm fecl . sub . 3 in absolute ethanol . c8 is 200 ppm fecl . sub . 3 in absolute ethanol . c9 is 1000 ppm fecl . sub . 3 in absolute ethanol . c10 is 20 ppm fecl . sub . 3 in tegdma . c11 is 20 ppm fecl . sub . 3 in a 50 / 50 ( by volume ) mixture ofbis - gma and tegdma . c12 is 200 ppm fecl . sub . 3 in a 50 / 50 ( by volume ) mixture ofbis - gma and tegdma . c13 is 20 ppm fecl . sub . 3 and 1 . 5 wt . % dhpt in absolute ethanol . c14 is 200 ppm fecl . sub . 3 and 1 . 5 wt . % dhpt in abosoluteethanol . c15 is 1 . 5 wt . % dhpt in absolute ethanol . these examples show that use of the metal solutions in dental bonding compositions of this invention provided increased adhesion to dentin and , in some cases , increased adhesion to enamel as well . these examples also show that the degree of improvement in adhesion was dependent upon the concentration of the metal solution , with adhesion values increasing , then decreasing , as the concentration of the metal solution was increased above trace concentration levels . various modifications and alterations of this invention will become apparent to those skilled in the art without departing from the scope and spirit of this invention , and it should be understood that this invention is not limited to the illustrative embodiments set forth herein .

US-33929082-A

a device for weaning an addiction includes a housing , an indicator , a processor , and an actuator . the processor is configured to deliver a state signal to the indicator under control of an algorithm . the state indicates either an armed state or a wait state . the actuator is supported by the housing and is communicatively coupled to the processor . in response to actuation of the actuator , the algorithm delivers the state signal indicative of the wait state until the timing signal satisfies a threshold value . if actuated after the timing signal satisfies the threshold value , the algorithm delivers the state signal indicative of the armed state and increases the threshold value . a method for weaning an addiction such as a smoking habit includes the steps of providing a device as above , enabling the user to seek permission from the device , and selectively indicating permissions to the user .

by way of overview and introduction , this invention concerns a device for weaning an addiction , which , in the exemplary embodiment , is discussed in connection with breaking a smoking habit . the device is reactive to user requests . in response to a user request , permissions are selectively granted to the user , allowing the user to engage in the habit that is being weaned , in this example , smoking . the time period between permissions gradually increases with “ successful ” actuations from a ( preferably , prescribed ) initial wait period . the device does not proactively notify the user when it is time to smoke again ; instead , the user must do something to the device in order to request permission to smoke again . the device is always in one of two states during normal operation : it can indicate that the user has to wait additional time for a permission , which is the wait state , or it can indicate that it is o . k . to smoke , which is the armed state . this approach provides an elegant solution to weaning a habit because , if the user does not actuate the device as soon as the device has changed to the armed state , the user will not be notified of the fact that it is now permissible to smoke . instead , the user will go for an additional , undefined time period without being made aware that a successful request could be made . thus , the user “ discovers ” that the device 100 was in the armed state when the urge to smoke or otherwise engage in a habit arises . once in the armed state , the moment that the user actuates the device , it will grant permission immediately and enter the next wait state . critically , the wait interval between such successful requests progressively increases to further the weaning process . referring now to fig1 , an embodiment of the invention is shown which is designed to help wean a smoking habit . the illustrated housing 110 has a cylindrical form , the interior not being shown . one end 120 is preferably attached to the housing 110 by a threaded or other connection 140 which allows the end 120 to be removed for battery replacement , and , optionally , to reset or change settings of the device 100 . in this embodiment , the end 120 is adorned to resemble the end of cigarette , such as the filter end of a cigarette . so , visually , the illustrated device 100 insinuates a cigarette and handling a so - constructed device provides a degree of psychological comfort to the user ; however , the appearance of the device 100 is not important to the invention . an actuator 150 is also provided which , in this embodiment , is a button that protrudes from one end of the housing 110 . the actuator is pressed to close a circuit contained within the housing . the user of the device 100 presses the actuator 150 to seek permission to engage in the habit being weaned . the actuator can be a capacitive or inductive switch , if desired , and can be positioned elsewhere on the house 110 . the indicator 160 preferably comprises an led . the indicator advises the user whether the device 100 is in a wait state or armed state in response to requests that are accepted by the device 100 using the actuator 150 as an input device . the actuator 150 preferably supports and contains , at least partially the indicator 160 . when the actuator 150 is pushed , the user can clearly and quickly be informed of the state of the device 100 . the led can be positioned elsewhere . other examples of the indicator can be an electroluminescent device , a light bulb , a buzzer , a flashing display of an icon , or a vibrator . regardless of the indicator type , when the actuator 150 is pressed , the wait state and armed state are distinguished . in the preferred embodiment , the indicator is a flashing led so that the user knows that the device 100 is working and the battery is functioning . other forms for the housing can be used if desired . for example , the housing 110 ′ can comprise a watch casing with the actuator 150 ′ comprising a button protruding from the case and the indicator 160 ′ being positioned on the face of the watch . another form can be that of a pager in which the actuator button 150 ′ comprises a button on the pager and the indicator 160 ′ is part of the standard display panel ( or is the pager &# 39 ; s vibrator ). yet another example is a personal information manager ( pim ) or personal digital assistant ( pda ) in which the actuator comprises a keyboard button or touch - sensitive icon on the display panel and in which the standard display panel serves as the indicator 160 ′. fig2 illustrates the circuit details of a governor circuit 200 that can be contained within the housing 200 . a processor 210 delivers a state signal 220 to the actuator 160 when the actuator 150 is pressed . a clock 260 delivers to the processor 210 a timing signal indicative of that time since the last wait state was initiated ( t n ). a wait state is initiated in response to a user pressing the actuator 150 when the device 100 is in an armed state . the timing signal can be obtained by other means such as a crystal oscillator , 555 timer circuit , an rc timing circuit or through an embedded timer or software included on - board the processor 210 itself . the memory 270 is used by the processor to store the current value of the wait state , or the threshold value ( t n ). the threshold value of this embodiment changes with every subsequent wait state , in accordance with the invention , to progressively wean the addictions by increasing successive wait intervals . optionally , the memory can also store configuration settings for the device 100 and also data concerning the number of attempted actuations by a user while the device was still in the wait state . such data can be used to control the transition ( i . e ., the time of the change over ) to the armed state . an algorithm 250 is executed by the processor 210 and governs the comparison between the current threshold value ( t n ) stored in memory 270 and the current elapsed time ( t n ) from the clock 260 . if the current threshold value ( t n ) is greater than the elapsed time value ( t n ), the difference is the amount of time still required in order for the device to enter the armed state . the processor will deliver a wait state signal 220 to the indicator 160 if the actuator 150 is pressed and if the algorithm determined that the timing signal does not yet satisfy the threshold value . on the other hand , if the elapsed time value ( t n ) satisfies ( that is , exceeds or equals the current threshold value ( t n ), the difference in time is the amount of time that the user lost to have been able to smoke ( l n ), but the processor will deliver an armed state signal 220 to the actuator under control of the algorithm 250 . when the elapsed time value exceeds the current threshold value , the lost time is referred to herein as lapsed time ( l n ). lapsed time is the amount of time that the device 100 has been in an active state and the user would have been permissioned to smoke if the actuator 150 had been pressed . the time left and the time lost will generally not be shown to the user , but can be retained in a memory 270 ( optionally together with the algorithm ) for statistical purposes utilized by the governor circuit 200 . the processor 210 also uses the algorithm 250 to increment the wait state &# 39 ; s current threshold value t n . the threshold value is increased each time a new wait state is triggered t n while the device 100 is already in an armed state . an incremental increase in the current threshold value is used to slowly increase the intervals at which a user can smoke , and therefore weans the user of the addiction over time . in this embodiment , the processor 210 uses the same algorithm 250 for both the function of determining whether to deliver the state signal and for updating the threshold valve . in addition , the timing signal is reset so that the newly computed current threshold value is compared against a new timing signal starting with the moment that a successful activation has been made ( that is , a press of the actuator 150 that was made while the device is in the armed state ). the device is either in a wait state or in an armed state , depending on timing issues as described below . different indications are provided to the user in response to pressing the actuator 150 , as a function of the present state of the device 100 . while in the wait state , there may be no indication at all , or the indication may be a flashing light . however , while in the armed state , a steady light can be the indication to the user . no matter how many times the button 150 is pushed in the wait state , there is preferably no effect on the duration of the waiting state or advancement / delay of the next armed state . other configurations are possible in which the user is penalized with a longer wait for “ unsuccessful ” button presses . in the illustrated embodiment , the processor delivers the wait state signal 220 such that the indicator 160 displays a flashing light . the armed state signal 220 can comprise a steady output at the indicator 160 . optionally , an amplifier circuit 240 is provided to boost the state a signal to a voltage magnitude sufficient to drive the selected indicator device . the amplifier can be on - board the processor 210 . fig3 is a timing and state diagram which illustrates the algorithm of the exemplary embodiment . in this diagram , the current value for the amount of time necessary to satisfy the wait state is indicated by t n and is called the current threshold value . the time period during which the threshold value is not exceeded is called the wait state 330 , and each subsequent wait state is indicated by a letter ( e . g . 330 a , 330 b , wherein the designation for the first wait state is 330 a ). once the current threshold value has been exceeded , the device 100 enters into an armed state 340 , and each subsequent armed state is indicated by a letter ( 340 a , 340 b , etc .). depending on the present state of the device , presses of the activator 150 have different results . presses 310 of the button 150 while the device 100 is in the wait state 330 are indicated differently in the diagram from presses 320 of the button 150 while the device 100 is in the armed state 340 . when the urge arises , a user presses 310 the button 150 to get permission , say , to smoke . if the device 100 is in the wait state , the indicator 160 will indicate to the user that it is not yet time ( e . g . by doing nothing or by blinking , etc .). when the user presses 320 the button 150 when the device 100 is in an armed state , however , the user gets a different indication than when the device was in the wait state ( e . g ., a steady light for 1 second ). further , because the elapsed time has satisfied the algorithm 250 , that activation causes a triggering event which places the device in the next wait state with ( optionally ) a new timing signal starting from that moment . each subsequent press 320 of the button 150 while in the armed state is indicated on the diagram as event t n , which indicates a successful actuation that delivers a permission to the user and starts a new wait state t n + 1 . the initial start time is indicated by t 0 , which is that time at which the user pushed the button 150 for the first time on the device 100 and was permitted to smoke a cigarette . the device 100 enters into a wait state 330 a for a duration of the first ( current ) threshold value t 1 . since the device 100 does not indicate to the user the current state , the user presses the activator 150 at various times 310 to learn if the next cigarette is allowed . the device indicates back to the user that it is still in a wait state 330 a and the user must wait to smoke a cigarette . the device 100 will be in that wait state 330 a until the timing signal from the clock has arrived at the ( current ) threshold value t 1 . at that time , the device 100 will enter the armed state 340 a . when the user next presses the activator 150 he or she shall discover a permission has been issued by virtue of the processor delivering the state signal indicative of the armed time . once the threshold value t 1 has been exceeded , the device 100 goes into an armed state 340 a , during which the elapsed time l 1 is lost until the user presses the button 150 indicated by 320 a . since the device 100 is passive and does not affirmatively alert the user to the fact that it is already in an armed state 340 a and is ready to grant permission to engage in the habit being weaned , that elapsed time l 1 defines a window during which the user could have had another cigarette . in this circumstance , the device 100 does not trigger a new state t n + 1 until the user has depressed the button 150 . therefore , there will be a time period for which the user loses the ability to smoke forever , indicated in fig3 by l 1 , l 2 and l 3 . the elapsed time l n can be very extremely small , e . g ., if the user presses the button 150 at the moment the device 100 exceeds the threshold value t n and goes into the armed state 340 a , 340 b or 340 c . at time t 1 + l 1 , the user has just pressed 320 a the button 150 while the device 100 was in the armed state 340 a . as a result , the device 100 enters the wait state 330 b for a duration of t 2 . the current threshold time duration t 2 is calculated using the algorithm 250 in the processor 210 by taking the previous threshold time duration value t 1 and incrementing it by incremental value d n . d n is a predetermined percentage increase value that will assist the user in slowly weaning the cigarette habit . preferably , the percentage increase is small so that it is reasonable for the user to slowly get acclimated to the fewer number of cigarettes being smoked over time . it is anticipated that the device will be able to assist a 4 - pack - a - day cigarette smoker wean down to 1 - cigarette - a - day during , say , a 5 - month period . the percentage rate increase is given as an example , there could be different permutations of incremental value d n available in different devices 100 or it could be a configurable , different predetermined increment . after the time duration for threshold value t 2 has been reached , the device 100 again enters the next armed state 340 b and waits for the user to press 320 b the button 150 . the threshold value t 2 , and more generally , t n + 1 , is larger than the prior threshold period . this cycle continues . when the user presses 320 b the button 150 while the device 100 is in the armed state 340 b , the device 100 enters the wait state 330 c for a duration of t 3 . once again , the next threshold time duration t 3 is be calculated using the algorithm 250 by taking the previous threshold time duration value t 2 and incrementing it by incremental value d n . after the time duration for threshold value t 3 has been reached , the device 100 enters the next armed state 340 c and waits for the user to press 320 c the button 150 , until which time the elapsed time l 3 indicates the time lost in which the user could have smoked had the user known . as a result , the increase in the current threshold value has a compounding effect on the magnitude of the timing signal that is necessary to deliver an armed state signal . the invention can be embodied other than described in the foregoing detailed description and is defined solely by the claims appended hereto .

US-23667502-A

this operative technique allows for an alternative treatment for patients with diagnoses of hernias or other symptoms in various regions within the body . the proposed approach has the benefit of providing the surgeon faced with the lack of long - term treatment solutions for conditions and symptoms including neuromuscular disorders . the proposed prosthetic device and method presents surgeons with a multi - functional device for stimulus control , operative procedure and surgical technique to achieve results to relieve a variety of patient symptoms . this system provides an accurate robotic surgical technique allowing a minimally invasive procedure .

this bioproshetic may be standard size , configured with nanocomposites and have customized seamless design for specific patient needs . each prosthetic has a number of variable or fixed length flexible and elastic connectors ( 2 ). each connector end may have variable cross - section along its &# 39 ; length such as oval for band - like extensions . the connector and ends which connect to the chosen tissue may use conventional sutures , stem cells , semi - absorbable grafts , resorbable materials or utilize bio - nanotechnology connections comprised of any of the latest methods to connect tissues with prosthetics . the typical configuration is represented by the perspective shown in fig1 , showing a sample prosthetic shape with connectors . the application of the bioprosthetic allows for a thickness to be established in the region were desired and may contain preformed shapes . these spaces are both shape and volume changing . the principle of utilizing prosthetics having a flexible and elastic external shell is two - fold . first , is the need for the prosthetic volume to compress . secondly , the permanent prosthetic positioning demands prosthetic shell to contain flexible twisting characteristics similar to the actions of the human or animal torso . each prosthetic may be rolled , twisted or folded and put into a sheath . each prosthetic surface ( 1 ) may be impermeable or permeable thickness , woven and have layers comprised of synthetic polymers , pdms , platinum , natural biomaterials or biocompatible materials . each surface may contain an internal insulating layer to establish a membrane potential . the prosthetic device may have internal diaphragms forming a space and cavities which may be filled with collagen or other appropriate material or fluid for the beneficial purpose of conducting electrical impulses and controlled with a micro - circuit and processor . each of these prosthetic surfaces may also be used as a smaller membrane size as needed with or without internal cavities for impulse control including neuromuscular disorders . this method to autonomously regulate stimulus and secretions optimizes treatment efficacy . for those prosthetic surfaces which require capability to control electrical impulses to and from the adjacent plasma - membrane , the membrane potential may be activated by electrical excitation by containing an intracellular conductive ion fluid control system . layers may be biocompatible materials , utilize nanotechnology , polymers or nanocrystals having switch controlled surface conductivity characteristics across and along each side of the prosthetic layer . multiple membrane layers may be used to achieve the desired ion flow , collection and to conduct electrical charge in the milli - volt range across membrane surfaces . membrane edges may be connected in any way known to the art . these membranes may also form prosthetic connector ends of various sizes required to establish a pseudo - synaptic cleft and thus the needed nervous system control to transmit desired stimulus to achieve treatment of symptoms . each of the membrane &# 39 ; s resting potential is designed to be balanced . histology has been established for the individual membranes and cells being connected to . conductance may be reversible through the known extracellular spaces , openings , electrochemical channels , gates or the membrane . these surfaces may be used as smaller membranes , suitable attached at the distal ends of connectors and further connected to the affected organ requiring stimulus control through robotic surgical techniques . the prosthetic may be fabricated to fit contours to shape desired surfaces of internal spaces which are unique to each surgical procedure . an additional prosthetic mesh layer ( s ) or other prosthetic cross - section may extend from the edge of the prosthetic edge , be attached or be as one in an integrally fabricated structure using suitable manufacturing methods and techniques . this prosthetic structure may additionally act as a module for housing of collecting electrical impulse energies with the use of capacitors and have circuits containing transducers , microchips and relays for release of said energy according to body orientation . prosthetic structure walls may be comprised of conductive materials as a matrix to collect adjacent sensory electrical impulses and internally store energy potential into capacitors . to achieve sensory control , electrical impulses may be collected and controlled for any viscera timing objectives . timing control for the nighttime function of sleeping and daytime functions of both emptying bladder and moving bowels may be modulated . a ground may be utilized internally and the electrical energy stored in capacitors that may then be released in a controlled method through connectors and possibly into heat internally via a heat transfer method device to then stimulate organ functions . contact points may be used as a network with polarity control by any manner known in the art including extending and attaching said connector ends to the natural sensory positions of desired organs . wake and rest periods are optimized with stimulus control . highly precise bio - nanotechnology prosthetics with suture methods may be robotically implanted and attached allowing for connecting various devices . this is highly advantageous for each connector the prosthetic has to attach to an organ or to establish a fixed position within the abdominal or other region . each connector may have a cross - section containing at least a central core for transmission with at least one internal conductive sensory impulse element . from the internal micro - circuits , connectors may extend to transmit electrical impulse delivery or collection to points or through graded potential membrane surfaces using an interconnected layered conductor series . this action potential across membranes allows for polarization control with voltage energy to affect ion flow transfer . internal conductive elements may be a fluid to transmit charges through connectors and across membranes . energy may be recharged and stored in an internal battery or be released externally with a controlled pulse with known resistance and timing sequence such as a transcutaneous energy transfer ( tet ) device . use of a grounding pad may also be used . stored electrical energy may then be control released with microcircuits programmed for daily cycles of electrochemical collection and or release . control may be established as well with horizontal and vertical orientation detection such as a micro - gyro or other suitable device . these electrical energy releases , diffusion and electrical gradient functions may be programmed externally by any wireless remote control method available in the art to modify and control function timing and release characteristics . this programming allows for the prosthetic device to automatically assist in daily organ and or muscular functions . as another embodiment this prosthetic device may additionally house and control chemical absorption therapies to regulate the release for hormone therapy as a dosing mechanism or any other deficiency or surplus level where dosing with biochemical reaction agents are needed . this includes the use of permeable wall materials . internal cavities may form a compartment for different functions including but not limited to dosing regulation and sensory assisting modules with connector networks . each cavity may have a time release function internal to the prosthetic to provide needed ion transfer capability throughout the desired prosthetic surface utilizing microchannels , layers or other available methods known in the art . in this way the prosthetic allows for several applications to function in one prosthetic . modern nanotechnology fabrication methods may be used to make customized prosthetic shapes including internal circuitry , microchips , solenoids , pumps , magnets , the attachment of connectors and ends with internal conductive elements . this shall provide one or multiple solutions for homeostasis of chronic problems involving any of the organ functions in the abdominal area or other area for improved daily living such as for metabolism regulation and hormone secretions . in another embodiment , each cavity in the prosthetic may contain a specific volume of hormone or other fluid . the prosthetic may be positioned adjacent to the organ in need of supplemental control or stimulus added . the cavity volume may be activated for release by a micro - pump through the use of a computer . internal diaphragms may compensate for volume contraction and expansion within the prosthetic cavities . for circumstances where the connector must deliver the stimulus or secretion , the connector element may have a central porous core to deliver required dosages along the connect length or to an end . any method known in the art may be used as a gate or valve or switch to control either fluid or stimulus flow . one such method proposed is for use of proportionately sized in the prosthetic exterior wall or internal cavity wall having an internal passage size with passage gate which may be sensor activated which is sized to allow for precise flow based on the fluid &# 39 ; s viscosity . in another embodiment , prosthetics may be structures shaped and stiffened with biocompatible materials to form the needed dimensions for internal placement and to be externally attached and interconnected for articulating and extending modular robotic functions such as limbs , hands or devices for sensory collection and delivery processes and movements . this operative technique proposes combining new and conventional laparoscopic entry methods , insufflation and new biologic prosthetic design possibly comprising a module with microchips in order to achieve successful treatment . it is important to distinguish the point of the bioprosthetic to be inserted is not a conventional mesh as used and available in current hernia surgery procedures . these space prosthetic devices may be inserted via trocar anywhere for the benefit to implant internal electronic devices which may control organ and muscular actions . the details of laparoscopic operative procedures vary for the position and size of prosthetic needed . as a primary feature of design to the biologic prosthetic , the in - situ insertion includes the capability to expand in the peritoneum during insufflation through a removal from sheath process . as the surgeon has control of the prosthetic from both ends of the sheath , the position is held in place with the forceps and removed . open repair surgery methods may be used as well . the connectors may be predesigned and arranged for use with resorbable or semi - absorbable ends and are then attached as planned for the final location of the biologic prosthetic . cavities may be refilled by an injection orifice ( 3 ) on the prosthetic surface or into a connector end . post - operative treatment is required to establish both physiological normalization and psychological conditioning from the surgery &# 39 ; s secondary effects such as closing issues of entry sites , surgical site infections ( ssi ), re - establishing activity , sleep restriction and a nutrition plan in order to develop new stability of the lower abdominal gastro - intestinal function . patients must maintain daily and nightly eating and sleeping schedules to retrain the local internal gastro - intestinal organs which are adjusting to new orientations . the post - operative affect shall vary depending on the prosthetic options used and the severity of the existing conditions and for an adjustment period of adjacent viscera functioning in displaced positions . the most common adverse events for all surgical repair of hernias are pain , infection , hernia recurrence , scar - like tissue that sticks tissues together ( adhesion ), blockage of the large or small intestine ( obstruction ), bleeding , abnormal connection between organs , vessels , or intestines ( fistula ), fluid build - up , seroma at the surgical site and holes in adjacent tissues or organs ( perforation ). the proposed prosthetic device and system provide surgeons a multi - functional device and operative procedure to achieve results and relieve a variety of patient symptoms . multiple sensor elements within each connector and between more than one prosthetic device may be utilized for interconnection of devices to establish an internal feedback system to calibrate timing and allow for mnemonic data to be computed used for improved autonomous synergistic effects . all embodiments , features and methods may be combined in any way to establish the desired device . this application description describes an apparatus , device and methods to control stimulus and perform surgical methods . specific embodiments of this invention allow for numerous combinations for numerous additional advantages . modifications and changes will readily occur to those skilled in the art without departing from the spirit and scope of this invention . this invention and its broader aspects are not limited to a specific detail and various modifications may be made without departing from the spirit or scope of the general inventive concept as defined by the appended claims and their equivalents .

US-201615083004-A

a container for manually transporting a pet having a litter box , food container and water container therein and sliding doors accessible from the exterior of the container for selectively closing the litter box , food container and water container to prevent inadvertent spillage . the container may include a single compartment or two detachably connected compartments in order that a litter box compartment may be selectively separated from a food and water compartment . detachable handles are provided in order that each separate compartment of the dual compartment embodiment may be carried separately or as a unified compartment .

referring to the drawings for a clearer understanding of the invention , it should be noted in fig1 - 6 that a first embodiment of the present invention contemplates the use of a substantially rectangular compartment 1 having a first end panel 2 , a second end panel 3 , a top panel 4 , a bottom panel 6 , a left panel 7 and a right panel 8 . an opening 9 is defined in the second end panel 3 for inserting a pet ( not shown ) within the compartment 1 . as shown in fig2 , 4 and 6 , a litter box 11 is partially defined by the first end panel 2 , the left panel 7 , the right panel 8 and a vertical litter box panel 12 connected to the left panel 7 , right panel 8 , top panel 4 and bottom panel 6 in substantially parallel planar relation to the first end panel 2 . a portal 13 is defined by the litter box panel 12 to provide the pet passage to the litter box 11 . a horizontal litter door slot 14 is defined by the first end panel 2 for receiving a litter door 15 therethrough . the litter door 15 , when inserted through the litter door slot 14 , is slidably received between a rectangular first litter box runner 16 , connected to and extending along the left panel 7 , the first end panel 2 , the right panel 8 and the litter box panel 12 , and between a rectangular second litter box runner 17 , connected to and extending along the right panel 8 , the first end panel 2 , the left panel 7 and the litter box panel 12 in parallel relation to the first litter box runner 16 . the first and second runners 16 and 17 are connected to the first end panel 2 and spaced on opposite sides of the litter door slot 14 . a quantity of pet litter 18 is contained in the litter box 11 and may be selectively isolated from the interior of the compartment 1 by inserting the litter door 15 through the litter door slot 14 , along the left and right pairs of runners 16 and 17 and in abutment with the litter box panel 12 . a latch 19 is rotatably connected to the first end panel 2 and may be rotated across the litter door slot 14 to secure the litter door 15 within the compartment 1 . as shown in fig1 - 4 and 6 , ventilation slots 20 are defined by the left panel 7 , the right panel 8 and first end panel 2 . as shown in fig2 , 4 and 5 , a food container 21 is formed within the compartment 1 adjacent to the opening 9 . the food container 21 is partially formed by the second end panel 3 , the bottom panel 6 and the right panel 8 . the food container 21 is further formed by a first food container panel 22 connected to the bottom panel 6 and left panel 8 in substantially parallel planar relation to the second end panel 3 . the food container 21 is further formed by a second food container panel 23 connected to the first food container panel 22 , the bottom panel 6 and the second end panel 3 in substantially perpendicular relation to the first food container panel 22 . a horizontal food door slot 24 is defined by the second end panel 3 , adjacent to the food container 21 , for receiving a food container door 26 therethrough . the food container door 26 , when inserted through the food door slot 24 , is slidably received between a rectangular first food container runner 27 , connected to and extending along the second end panel 3 , the right panel 8 , the first food container panel 22 and the second food container panel 23 and a rectangular second runner 28 , connected to and extending along the first food container panel 22 , the right panel 8 , the first food container panel 22 and the second food container panel 23 in parallel relation to the first runner 27 . the first and second runners 27 and 28 are connected to the second end panel 3 on opposite sides of the food door slot 24 . a quantity of pet food 29 is contained in the food container 21 and may be selectively isolated from the interior of the compartment 1 by inserting the food container door 26 through the food door slot 24 , along the first and second runners 27 and 28 , and in abutment with the first food container panel 22 . a latch 31 is rotatably connected to the second end panel 3 and may be rotated across the food door slot 24 to secure the food container door 26 within the compartment 1 . as shown in fig3 and 5 , a water container 32 is formed within the compartment 1 adjacent to the opening 9 and opposite the food container 21 . the water container 32 is partially formed by the second end panel 3 , the bottom panel 6 and the left panel 7 . the water container 32 is further formed by a first water container panel 33 connected to the bottom panel 6 and left panel 7 in substantially parallel planar relation to the second end panel 3 . the water container 32 is further formed by a second water container panel 34 connected to the first water container panel 33 , the bottom panel 6 and the second end panel 3 in substantially perpendicular relation to the first water container panel 33 . a horizontal water door slot 36 is defined by the second end panel 3 , adjacent to the water container 32 , for receiving a water container door 37 therethrough . the water container door 37 , when inserted through the water door slot 36 is slidably received between a rectangular first water container runner 38 , connected to and extending along the second end panel 3 , the left panel 7 , the first water container panel 33 and the second water container panel 34 , and a second water container runner 39 , connected to and extending along the first water container panel 33 , the left panel 7 , the first water container panel 33 and the second water container panel 34 in parallel relation to the first water container runner 38 . the first and second water container runners 38 and 39 are connected to the second end panel 3 and spaced on opposite sides of the water door slot 36 . a quantity of water 41 is contained in the water container 32 and may be selectively isolated from the interior of the compartment 1 by inserting the water container door 37 through the water door slot 36 , along the first and second water container runners 38 and 39 , and in abutment with the first water container panel 33 . a latch 42 is rotatably connected to the left panel 7 and may be rotated across the water door slot 36 to secure the water container door 37 within the compartment 1 . a wire frame gate 43 is pivotally connected to the second end panel 3 for selectively opening and closing the opening 9 . a latch 44 is connected to the gate 43 and to the second end panel 3 for securing the gate 43 in a closed position . two handle connectors 46 are connected to the top panel 4 . a handle 47 is detachably connected to the handle connectors 46 by two clips 48 connected to the handle 47 . during manual transport or during such other times that the compartment 1 may be subjected to slipping , tipping , jolting or other external influences during travel , the litter door 15 , the food container door 26 and water container door 37 will be inserted within the compartment 1 to prevent spillage . when the compartment 1 is in a stable position , the doors 15 , 26 and 37 may be removed to provide the pet access to the pet food 29 , water 41 and pet litter 18 provided . after the pet has utilized the pet litter 18 , the litter door 15 can be reinserted within the compartment 1 to isolate the pet litter 18 and thereby contain any unpleasant odor generated by the pet &# 39 ; s use thereof . the litter box panel 12 provides some separation between the litter box 11 and the pet &# 39 ; s food , water and general living space 49 . a second embodiment of the present invention is shown in fig7 - 12 , wherein the singular compartment 1 of the first embodiment is divided into a substantially cubicle litter box compartment 51 and a substantially cubicle living compartment 52 . as shown in fig9 and 12 , the litter box compartment 51 includes the first end panel 2 , the litter box 11 , litter box panel 12 , portal 13 and ventilation slots 20 . the living compartment 52 includes the second end panel 3 , the food container 21 , the water container 32 , and has a third end panel 53 formed opposite the second end panel 3 . the litter box compartment 51 is detachably connected to the living compartment 52 by a plurality of lever and post fasteners 54 connected to the litter box compartment 51 and the living compartment 52 . the third end panel 53 defines a passage 56 which allows the pet to move to and from the living compartment 52 and litter box compartment 51 . a cross - sectionally l - shaped guide 57 is connected to the third end panel 53 and extends along the left , right and bottom edges of the third end panel 53 for receiving a compartment divider 58 . a divider panel slot 59 is defined by the living compartment 52 , adjacent the third end panel 53 , to facilitate insertion of the compartment divider 58 within the living compartment 52 and the guide 57 . as shown in fig7 - 9 , two of the aforedescribed handle connectors 46 are connected to the living compartment 52 and two handle connectors 46 are connected to the litter box compartment 51 . when the living compartment 52 and litter box compartment 51 are connected , as is shown in fig7 and 9 , the handle connectors 46 are disposed in linear relation and each are spaced an equal distance from the adjacent handle connectors 46 . when the living compartment 52 is disconnected from the litter box compartment , as shown in fig8 a first handle 47a having clips 48 connected thereto is detachably connected , by the clips 48 , to those connectors 46 attached to the living compartment 52 . a second handle 47b having clips 48 connected thereto is detachably connected to those connectors 46 attached to the litter box compartment 51 . the living compartment 52 may be connected to the litter box compartment 51 , as shown in fig7 and 9 , with the compartment divider 58 removed from the guide 57 to provide a combined pet carrying unit . as shown in fig7 and 9 , one of the handles 47 is disconnected and the other handle is connected to the connectors 46 closest to the litter box panel 12 and third end panel 53 in order that the detachably connected compartments 51 and 52 may be easily carried as a unit . alternatively , the compartments 51 and 52 may be disconnected with the compartment divider 58 received within the guide 57 , and the handle 47a connected to the living compartment 52 , as shown in fig8 such that the living compartment 52 may be easily carried as a separate unit . the second embodiment of the present invention can be used to satisfy the functions of the first embodiment of the present inventions and , additionally , allows the advantage of transporting the pet in the smaller , lighter living compartment 52 . further , the pet may be contained in the living compartment 52 with the litter box 11 distanced and completely separated from the pet &# 39 ; s food and water . this advantage is particularly realized by owners of finicky pets which will not eat or sleep near their litter box . while i have shown my invention in two forms , it will be obvious to those skilled in the art that it is not so limited but is susceptible of various changes and modifications without departing from the spirit thereof .

US-33066494-A

devices for collecting fluids from a patient are disclosed . the present invention includes a first sheet of liquid impervious material having an opening . the first sheet is attached to a bottom sheet of liquid impervious material having a fenestration for access to the patient . a bendable section disposed along the inner perimetric edge of the first sheet retain the edge in a particular defined shape , improving fluid collection and access . the bendable section preferably includes a wire covered by a pliable plastic material , which are encased by providing a second sheet of liquid impervious material and placing the bendable section between the first second sheets . the sheets are then preferably secured by heat sealing . in certain preferred embodiments adhesive is provided on the patient facing side of the fenestration section and drainage ports for transmitting fluids are affixed to the bottom sheet . the present invention also provides a surgical drape including a sheet of drape material having an opening for access to the patient and having a device for collecting fluids as described above attached to it . such drapes may also include a pad of absorbent material overlying the drape material and a device for retaining a drainage tube . methods of manufacturing a fluid collecting device are also disclosed .

referring to fig1 an isometric view of fluid control apparatus 100 made in accordance with the present invention is shown . the fluid control apparatus is comprised of a top sheet 102 , which is preferably thin pliable sheet of fluid impervious material , which is most preferably substantially transparent . the top sheet 102 has an opening , thus creating both an outer perimetric edge and an interior perimetric edge 104 , the latter defining the opening . affixed to the top sheet 102 near the interior perimetric edge is at least one elongated , flexible , bendable support element 106 adjacent to and substantially completely surrounding the interior perimetric edge . the thin bendable element 106 is preferably comprised of a plastic encased wire , similar to the construction of a twist tie typically used as a closure device for various types of bags . as shown in fig1 in a preferred embodiment , a second thin bendable element 108 is also provided . the bendable elements 106 , 108 are preferably placed in contact with one of the surfaces of the top sheet 102 and are held in place by a number of techniques , for example , they may be affixed using adhesives , or by heat sealing the bendable elements 106 , 108 to the top sheet or to the top sheet 102 and a second sheet 103 of similar material . the bendable elements 106 , 108 are constructed from a wire having a sufficiently heavy gauge to maintain the edge of the opening in the top sheet in place and in a configuration which promotes fluid collection . by manipulating the bendable elements , it is possible to form the edge of the top sheet into an upwardly depending lip and the bendable means will retain it in such a position , preventing fluid from flowing over this edge on to the top sheet 102 . the present invention thus keeps the fluid contained within the top and bottom sheets , which are sealed together in a liquid tight relationship to form container , i . e ., a pouch . however , unlike a more rigid structure , the bendable elements do not substantially inhibit the characteristics of the surrounding thin pliable sheets 102 , 110 and further provide a structure which adds very little bulk when the device is folded and packaged . the bendable elements 106 , 108 of the present invention create a relatively more rigid and shape retentive section along the inner perimetric edge 104 of this section of the fluid collection device . numerous materials and constructions can be substituted to achieve a similar effect . for example , certain shape retentive foam materials could be formed in thin strips or narrow annular sections and disposed in the manner of the bendable elements 106 , 108 shown . it is preferred , however , that a plastic encased wire as described be used . as will be explained in further detail below , the fluid control apparatus of the present invention also comprises a bottom sheet 110 , preferably is also comprised of a thin pliable sheet of material . the bottom sheet 110 also has a fenestration section 112 which is placed into contact with the patient . the fenestration section has an interior perimetric edge 114 which defines the fenestration through which the surgeon may access the patient during a procedure . preferably , the side of the fenestration section which contacts the patient is coated with an adhesive material 112a . in certain embodiments , either the fenestration section or the entire patient facing bottom sheet may be coated with an anti - microbial coating 110a . this coating may be in addition to an adhesive or may be used alone , for example , only the fenestration section might be coated with adhesive , while the fenestration section 112 and the rest of the bottom sheet , i . e ., the entire bottom sheet 110 may be coated with an anti - microbial product . one such coating is micro - side ™ which is comprised of polyhexamethylenebiguanide ( phmb ). also , one or more drainage ports 120 are provided in the bottom sheet 110 in order to facilitate the removal of the collected fluid from the fluid collection device 110 illustrated . in ceratin embodiments , the fenestration section 112 may be integral with the bottom sheet 110 . further details of the construction of the fluid collection device depicted in fig1 are seen in the cross - sectional view of fig2 . as shown , the top sheet 102 also preferably comprises a second sheet of thin pliable material 103 . in a preferred embodiment , the top sheet 102 and second sheet 103 are thermally bonded in the region of the interior perimetric edge to retain the bendable elements 106 , 108 in place and also at the outer edge of the device thereby creating a liquid tight seal between the top sheet 102 , the second sheet 103 and the bottom sheet 110 . the construction of the region near the interior edge 104 of the top sheet is shown in the enlarged view of fig2 a . the bendable means 106 , 108 are spaced apart from each other and the edge 104 of the opening , and are sealed between the top sheet 102 and second sheet 103 . in certain embodiments , it may be preferable to use a single bendable means or to replace the encased wire depicted with other shapes or materials . the design of the bendable means will depend largely upon the material characteristics and thickness of the top sheet 102 and second sheet 103 , as well as the overall size of the fluid collection device 100 and the opening . referring again to fig2 the construction of the lower section of the fluid collection device of the present invention is shown . the bottom sheet 110 preferably surrounds an adhesive fenestration section 112 . the bottom sheet 110 and fenestration section 112 are preferably heat sealed or otherwise affixed to provide a liquid tight seal at their juncture . in a preferred embodiment , the bottom sheet 110 is comprised of a substantially opaque portion , while the fenestration section 112 and the adhesive disposed thereon are substantially transparent . a protective covering , such as release paper 115 overlies the adhesive on the fenestration section 112 and is removed prior to use , as shown by the arrow in fig2 . a top plan view of a preferred embodiment of the fluid collection device 100 of the present invention is depicted in fig3 . the device 100 shown is particularly adapted for use in a procedure such as a caesarean section delivery , during which a relatively large quantity of fluids and other materials are released and must be channeled away from the incision and collected . accordingly , the present invention provides the capability to collect fluids around the entire perimeter of the incision -- that is , 360 degree collection . the device 100 is most preferably in the substantially square or rectangular , having two corners removed at about a 45 degree angle , resulting in the shape shown . numerous other overall shapes will be useful , however , depending upon the application for a particular surgical procedure . in use , the fenestration section 112 will be placed into substantially fluid tight contact with the portion of the patient surrounding the incision site . fluids will flow from all directions on to the top surface of the fluid impervious sheet which comprises the fenestration section 112 and the bottom sheet 110 . most preferably , the drainage ports 120 are located to take best advantage of gravity when the fluid collection apparatus is placed on the patient . in the case of the preferred embodiment shown , the drainage ports 120 are located in the corners of one side of the device , where the fluids and materials will collect and be drained . although visible in this view because the top sheet 102 is preferably transparent , the drainage ports 120 are disposed on the bottom sheet 110 . also , in the preferred embodiment shown , the fenestration section 112 is slightly offset from the opening in the top sheet . this design is preferred since the incision made for a caesarean section is typically offset from the central medial plane of the patient , therefore the fenestration is disposed at an offset position while the collection device itself remains substantially atop the patient . referring to fig4 a bottom plan view of a preferred embodiment of a fluid collection device 100 made in accordance with the present invention is shown . as set forth above , the drainage ports 120 which are located on the bottom sheet 110 are seen in this view . the fenestration section 112 , upon which adhesive is preferably applied is also shown . since the fenestration section 112 is preferably transparent , the second sheet 103 and the top sheet 102 , as well as the bendable elements 106 , 108 are all visible in fig4 . the placement of the components which form the preferred embodiment of the fluid collection device made in accordance with the present invention are shown in the exploded isometric view of fig5 . preferably , bendable means 106 , 108 are disposed between the top sheet 102 and second sheet 103 , which are then preferably bonded together by heat sealing or applying adhesives in at least the region of the bendable means 106 , 108 , thereby embedding them in place . the bottom section is formed by affixing the fenestration section 112 to one side of the bottom sheet 110 , again preferably by heat sealing or applying an adhesive . the side of the fenestration section 112 placed into contact with the bottom sheet 110 is the side which preferably has adhesive disposed thereon . accordingly , release paper 115 is placed over the adhesive and removed prior to use . the drainage ports 120 are also installed on the bottom sheet 110 . the upper and lower sections are then joined and a liquid impervious seal is formed about the outer perimetric edges of the top sheet 102 , the second sheet 103 and the bottom sheet 110 , resulting in a complete fluid collection device , substantially as depicted in fig1 . a side view of the construction described in fig5 taken along line 6 -- 6 , is shown in fig6 . as shown by the single connecting lines , the fist sheet 102 , second sheet 103 and bendable means 106 , 108 are disposed atop one another and form an upper section of the device . the bottom sheet 110 , fenestration section 112 and cover paper 115 form a lower section . as indicated by the double connecting lines , the upper section and lower section are preferably then joined and sealed around their outer perimetric edges to form a complete fluid collection device 100 . although the fluid collection device 100 described above with reference to fig1 - 6 may be used alone as a fluid control product , it is also a preferred embodiment of the present invention to incorporate the fluid collection device 100 into a drape or other structure which covers the patient . as shown in isometric view in fig7 an obstetric drape 200 for use during procedures such as a caesarean sections is provided by the present invention . a fluid collection device 100 is disposed upon and attached to the surface of a drape 210 . as well known to those of ordinary skill , numerous materials can be utilized as surgical drapes including woven and nonwoven fabrics and polymeric materials . in a preferred embodiment an instrument pad 220 is also disposed upon the top surface of the drape 210 . the instrument pad provides a reinforced section and preferably absorbent surface upon which instruments or other objects may rest during the procedure . the instrument pad 220 is also provided with one or more means for retaining a drainage tube 222 . preferably , while in use , a tube will connect the drainage ports 120 with a remote collection receptacle ( not shown ). the retaining means 222 are provided to keep the tube in proper position and away from the area of the incision . the fluid collection device 100 is preferably affixed to the drape 210 substantially along the along the dashed line 230 shown in fig7 . by affixing the fluid collection device 100 to the drape surface 210 in this manner , the characteristics of the drape material are not affected by the fluid collection device . in other words , the drape material retains the same degree of conformability to the patient , except in a small area near the fenestration section 112 . as easily envisioned by those of ordinary skill , such a construction is advantageous , particularly as the fluid collection device becomes filled with fluid , since it may move relative to the drape material 210 and , thus will not substantially shift or otherwise affect the position of the drape . as seen by the upturned corner illustrated in fig7 the drainage port protrudes from the bottom sheet 110 and is preferably located over the instrument pad 220 when in use . as an alternative to the construction disclosed above with reference to fig1 - 6 , the top section may be formed as shown in fig8 . as shown in a partial exploded isometric view , similar to fig5 the bendable means 106 , 108 may be contained between the top sheet 102 and an annular layer 105 , which replaces the second sheet 103 described above . in this embodiment , the top section will therefore comprise two layers only in the region surrounding the interior perimetric edge where the bendable means 106 , 108 are disposed . the desirability of this type of construction is again determined by the thickness and other characteristics of the materials used , and the particular application for the drape being designed . referring to fig9 and alternate design of the fluid collection device 100 of the present invention is shown in a top plan view , similar to that of fig3 . in this embodiment , the interior perimetric edge 104 of the top sheet 102 and second sheet 103 ( or annular section 105 ), as well as the bendable means 106 , 108 are substantially octagonally shaped . in certain applications , this design might be preferred because the sides of the opening in the top section are substantially parallel to five of the sides of the outer perimetric edge of the device . therefore , improved draping characteristics and improved stability and uniformity in the performance of the bendable means to keep the opening properly positioned above the bottom sheet 110 and fenestration section 112 are obtained . numerous variations to the invention disclosed above will present themselves to those of ordinary skill . accordingly , reference should be made to the appended claims in order to determine the scope of the present invention .

US-49356790-A

a strap and carry system for cradling and transporting flat and generally rectangular objects such as a body board . the system comprises three flexible loose straps secured to each other forming an adjustable flexible cradle which can be folded for storage and held open with one hand so that an object such as a body board can be inserted and secured for carrying .

fig1 shows the strap and carry system on a body board 22 . the strap and carry system comprises a horizontal strap 2 which adjusts to various lengths with an adjustable buckle 10 . the strap 2 can then hold body board 22 without damaging the board . a flexible rope ring 8 is secured to the horizontal strap through two metal grommets . a vertical front shoulder strap 4 is secured to the flexible ring 8 at connection 6 . the front strap 4 is affixed to a back strap 16 with an adjustable buckle assembly 12 . the back strap passes through the indent portion 24 of the body board 22 and is connected to the horizontal strap 2 at a point diametrically opposite the flexibe rope ring 8 . a loop strap 20 of the back strap 16 connects the back strap to the horizontal strap 2 . the loop strap is affixed to the horizontal strap using stitching , hook and loop fasteners or as flexible rope ring . the loop strap 20 forms a handle and can serve to attach other objects , such as surf fins , wet suits or other related items , to the strap and carry system . the back strap 16 can also be directly fastened to the horizontal strap 2 using stitching or a flexible rope ring . extra long strap material 14 provided after adjustment of buckle 12 can be used to carry the body board 22 by hand . in its preferred form , the strap and carry system is constructed from soft nylon webbing which is 1 / 2 to 2 inches in width . once the body board 22 and other objects such as wet suit 30 and surf fins 24 have been secured to the strap and carry system , the front vertical strap 4 is passed over the shoulder of the user and is oriented on the user &# 39 ; s body as illustrated in fig2 and 3 . in fig4 another embodiment of the invention is illustrated . front vertical strap 4 is secured to horizontal strap 2 via stitching 64 . the front strap 4 is connected to an adjustable buckle 12 which is affixed to a short strap 68 . the short strap 68 is attached to a plastic or metal c - clamp 70 which slips under and holds up board 22 . c - clamp 70 may be padded to prevent damage to the board . in fig5 another embodiment of the invention is illustrated . front vertical strap 4 is secured to horizontal strap 2 via stitching 64 . there is no extra long strap material provided after adjustment of buckle 12 and no loop strap 20 is provided . in fig6 another embodiment of the invention is illustrated for use with a surfboard 32 or any other similar item . the strap and carry system comprises a nose strap 34 attached to a long strap 36 having an adjustable buckle 38 . the long strap 36 is also affixed to a tail fin strap 40 . in fig7 a strap and carry system is illustrated in use with a set of folding beach chairs 42 . horizontal strap 44 wraps around and holds the chairs together . the strap 44 is adjusted using adjustable buckle 46 . a vertical strap 48 is secured to the horizontal strap 44 and includes an adjustable buckle assembly 50 . the vertical strap 48 provides a cradle for the chairs 42 . strap 48 is placed over the shoulder of a user to secure the device in place . in fig8 the strap and carry system of fig1 is shown in a position to facilitate loading of the board into the system . in operation , the user grasps the horizontal strap 2 such that the rope ring 8 permits the strap 2 to fold . a vertical passageway is formed by the grasped strap 2 and the depending vertical straps 4 and 16 such that the body board 22 can be inserted . vertical strap 16 contacts the undersurface 24 of the board 22 . the horizontal strap 2 can then be returned to its normal position whereby adjustable buckles 10 , 12 can be tightened and strap 4 can then be placed over the shoulder . it should be understood that the foregoing description of the invention is intended merely to be illustrative thereof and that other modifications and embodiments may be apparent to those skilled in the art without departing from its spirit .

US-63670091-A

a photo acoustic trace gas detector is provided for detecting a concentration of a trace gas in a gas mixture . the detector comprises a light source for producing a light beam and a light modulator for modulating the light beam into a series of light pulses for generating sound waves in the gas mixture . the light modulator is arranged for modulating the light beam between a non - zero lower intensity level and a higher intensity level . an amplitude of the sound waves being a measure of the concentration . an optical cavity contains the gas mixture and amplifies a light intensity of the light pulses . a transducer for converts the sound waves into electrical signals . a feed back loop with a photo detector for measuring the light intensity of the light pulses regulates the amplification of the light intensity in the optical cavity .

fig1 a shows a typical photo acoustic trace gas detector 100 according to the invention . a light source 101 provides a continuous wave laser beam and is modulated into a series of light pulses at a certain ‘ chopping ’ frequency by , e . g ., a chopper 103 , shutter or acousto - optic modulator . alternatively , the light source 101 itself may provide the light pulses at a fixed frequency . the light pulses are sent into an optical cavity , which is defined by two semi - transparent mirrors 104 a and 104 b . an optical isolator 102 is optionally placed between the light source 101 and the input mirror 104 a to reduce the reflectance of light from the cavity mirror 104 a into the light source 101 . the light pulses enter the optical cavity through input mirror 104 a and are reflected many times between the two cavity mirrors 104 a and 104 b . if the distance between the two mirrors 104 a and 104 b is in resonance with the wavelength of the laser , standing waves occur and the light intensity is amplified . the light that is transmitted by the output mirror 104 b is measured with a photo detector 110 . the signal from the photo detector 110 is used as a feedback signal for the laser wavelength or the length of the optical cavity . in a locked cavity scheme the laser and cavity operate at the same fixed wavelength . in most designs either the laser wavelength or cavity length is modulated and the transmission or reflection of the laser through the cavity is monitored with a photo detector 110 . the change in transmission is then used as a feedback signal that is used to either drive an actuator , e . g . a piezo driver , attached to one of the cavity mirrors 104 a , 104 b ( cavity length modulation ) or to set the laser frequency ( laser wavelength modulation ). the wavelength of the laser is typically scanned on the flank of a cavity resonance if it is locked to the cavity . when the laser wavelength gets out of resonance with the cavity ( not including the small wavelength modulation of the laser ) the transmitted intensity changes . a feedback signal is then sent to the laser diode 101 to correct the wavelength and bring the transmission back towards the desired level . note that at maximum cavity transmission the wavelength modulation of the laser does typically not result in a change in transmission . therefore the cavity should preferably be operated just below maximum transmission . when the laser intensity changes ( due to laser instability ) the height of the resonance peak changes with a consequent change of the feedback amplitude as a result . the locking mechanism will move the laser to another frequency on the new resonance curve until a new equilibrium is achieved . inside the optical cavity a gas cell 106 is situated for containing the gas sample to be examined . alternatively , the optical cavity is enclosed by the gas cell 106 . optionally , the gas cell 106 comprises a gas inlet 107 and a gas outlet 108 for allowing a gas flow through the gas cell 106 . if the laser wavelength is tuned to a molecular transition , i . e . e i → e k , some of the gas molecules in the lower level el will be excited into the upper level e k . by collisions with other atoms or molecules these excited molecules may transfer their excitation energy into translational , rotational , or vibrational energy of the collision partners . at thermal equilibrium this causes an increase of the thermal energy , resulting in a local rise of the temperature and pressure inside the gas cell 106 . every pulse of light will cause an increase in pressure after which the pressure can reduce again , before the next pulse arrives . this increase and decrease of pressure will result in an acoustic wave at the chopping frequency . centered in the middle of the gas cell 106 is a transducer 109 , e . g . a microphone that can pick up the acoustic wave generated by the absorbed light in the gas . preferably , the transducer 109 is a crystal oscillator , e . g . a quartz tuning fork , with a resonance frequency that can pick up the acoustic wave generated by the absorbed light in the gas . the use of a crystal oscillator may make the acoustic cell unnecessary . fig2 a shows the light intensity ( y - axis ) of the modulated light as a function of the progress of time ( x - axis ) in a prior art detector . in , for example , the trace gas detector according to rossi et al . the light beam is blocked periodically in order to create light pulses from the continuous wave laser beam from the laser source . as a result , the light intensity of the modulated light is zero during the periods between two pulses and the feedback signal is interrupted . the interruption period can not be easily shortened , because a detector using a higher chopping frequency would require an acoustic cell with so small dimensions that it becomes inefficient . fig2 b shows a time dependence of the light intensity of the modulated light according to an embodiment of the invention . here , the light is modulated in such a way that the light intensity never drops to zero . the light is modulated between a higher and a lower intensity level , the lower level being substantially higher than zero . in this way , the feedback signal is never interrupted and the response time of the feedback loop may be much shorter than in the prior art situation . fig3 shows two choppers 103 which are arranged for use with the trace gas detector 100 according to the invention . the choppers 103 are used for modulating the light beam into a series of light pulses . the choppers 103 in fig3 are rotatable discs with first segments 301 with a lower transmission coefficient and second segments 302 with a higher transmission coefficient . the lower transmission coefficient is substantially higher than zero . the higher transmission coefficient is higher than the first transmission coefficient and preferably equal to or approximately 1 . in operation , the chopper 103 is rotated at a constant angular velocity . when the light beam shines on a segment 301 with a lower transmission coefficient , most of the light is blocked . behind the chopper 103 , a low intensity light beam does not excite many molecules in the gas , but provides sufficient light for the photo detector 110 to provide a feedback signal . when the light beam shines on a segment 302 with a higher transmission coefficient , all or most of the light is transmitted . behind the chopper 103 , a high intensity light beam excites many molecules in the gas ( if available ) which causes an increase of the thermal energy , resulting in a local rise of the temperature and pressure inside the gas cell 106 . the transmission coefficients of the segments may be realized by using absorption filters or reflection filter . the second embodiment shown in fig3 uses plates with an array of small hole 303 and large holes 304 to modulate the intensity between the low level and the high level , correspondingly . slits may be used instead of holes . alternatively , the density of the holes or slits can be varied instead of their size . the total area of the holes or slits is proportional to the required transmission . to achieve a relatively constant intensity in either modulation state , the holes or slits should be much smaller than the beam diameter . if necessary this can be achieved with a beam expander followed by a collimator . the frequency of the light pulses and the resulting acoustic waves depends on the angular velocity of the chopper 103 and the number of segments on the disc . the strength of the acousto - optic signal is proportional to the difference between the high intensity level of the pulses and the low intensity level during the darker periods . instead of the choppers 103 , other kinds of modulators like , e . g ., a shutter or acousto - optic modulator may be used . fig4 shows a time dependence of the light intensity of the modulated light according to a further embodiment of the invention . the light intensity has a low frequency chopping component for photo - acoustic detection and a high frequency modulation for cavity locking . the high frequency modulation may be provided by modulating the laser wavelength around an average wavelength . alternatively the cavity length can be modulated using , e . g ., piezo drivers attached to one of the cavity mirrors 104 a , 104 b . the wavelength of the laser is typically scanned on the flank of a cavity resonance if it is locked to the cavity . when the laser wavelength gets out of resonance with the cavity ( not including the small wavelength modulation of the laser ) the transmitted intensity changes . a feedback signal is then sent to the laser diode 101 to correct the wavelength and bring the transmission back towards the desired level . note that at maximum cavity transmission the wavelength modulation of the laser does not result in a change in transmission . therefore the cavity should be operated just below maximum transmission . when the laser intensity changes ( due to laser instability ) the height of the resonance peak changes with a consequent change of the feedback amplitude as a result . fig5 shows a wavelength dependence of the modulated light according to an embodiment of the invention . the modulation of the light intensity at the chopping frequency results in a small wavelength shift as shown in fig5 . the high frequency wavelength modulation over a small wavelength interval 51 results in an intensity modulation along the slope of the cavity resonance with a certain amplitude 52 . when the transmission changes from low to high , the height of the resonance peak increases in amplitude . consequently , the slope of the resonance curve and the feedback amplitude are changed . since the feedback amplitude 53 has to remain constant a feedback signal is sent to the laser to change the center wavelength of the laser to achieve the same feedback amplitude . this will result in a small wavelength shift 54 . this unwanted wavelength shift 54 does not occur with the embodiment described below with reference to fig6 . fig1 b shows a preferred embodiment of a photo acoustic trace gas detector 100 according to the invention . this embodiment uses a polarization dependant modulator 103 , which results in the modulation of the polarized beam used for photo - acoustic excitation of trace gas molecules , but does not modulate the orthogonally polarized beam used for feedback . this may be accomplished by placing an alternating series of ‘ p ’ polarizers and open blades along the perimeter of a mechanical chopper . the ‘ s ’ beam is blocked by the ‘ p ’ polarizer , while the ‘ p ’ beam is not affected by any of the blades of the chopper and therefore has a constant amplitude . the laser is mounted under an angle such that the output beam contains both a ‘ p ’ and an ‘ s ’ component . the beam then enters the whole gas analysis system , as shown in figure la , and is split by a polarizing beam splitter 82 downstream of the optical cavity . the transmitted ‘ s ’ polarized beam may then be measured by a first photo detector 83 to serve as a reference signal to the photo - acoustic signal . the transmitted ‘ p ’ polarized beam is detected by second photo detector 84 and is demodulated using electronic system 111 where its amplitude is used to lock the laser to the cavity . the purpose of the modulator 103 is to modulate the ‘ s ’ beam for photo - acoustic excitation of the trace gas , while simultaneously achieving a constant transmission for the ‘ p ’ beam for cavity locking . because of this constant transmission , this embodiment does not show the wavelength shift 54 of the embodiment described shown in fig5 and is therefore not very stable . in a preferred embodiment , the detector comprises a polarization rotator 81 , placed between the light source 101 and the light modulator 103 , for enabling varying a ratio of the intensity of the light with the different polarizations . in stable conditions , when the feedback is not very important , the intensity of the light used for the feedback loop is decreased and the intensity of the light used for the photo acoustic detection is increased . fig6 shows two time dependences of the light intensity of the modulated light according to an embodiment of the invention comprising a polarization rotator 81 and a polarization dependent modulator 103 . in the situation shown in fig6 a , the ‘ s ’ polarized component is relatively large . fig6 a shows the total light intensity ( the sum of ‘ s ’ and ‘ p ’) behind the modulator . the relatively high difference 61 between the high intensity level and the low intensity level 62 results in a strong photo acoustic signal . fig6 b shows the total light intensity behind the modulator for less stable situations , e . g . when the detector is subject to large shocks ( e . g . when someone is walking with the detector in his hands ). the polarization rotator 81 rotates the polarization of the light beam , such that more light with the polarization that is not affected by the modulator (‘ p ’ component ) is sent to the modulator . the difference 63 between the high intensity level and the low intensity level 64 is now much smaller , but the intensity level 64 of the light that is used for the feedback loop is increased . as a result the photo acoustic signal will be less strong , but the cavity locking feedback loop will perform much better . fig7 shows a time dependence of the light intensity for modulated light for both different polarizations downstream of the cavity according to an embodiment of the invention comprising a polarization dependent modulator . these intensities may be measured separately by placing a polarizing beam splitter 82 behind the optical cavity and providing two separate photo detectors 83 , 84 for measuring the intensity of the light with the corresponding polarizations . fig7 shows the light intensities of both polarizations downstream of the cavity . the ‘ s ’ polarized beam has both a low frequency modulation for photo acoustic signal generation and a high frequency component of the laser wavelength modulation . the ‘ p ’ polarized beam only has the high frequency wavelength modulation . locking the ‘ p ’ polarized beam to the cavity can be done very stable because the large difference in intensity , as was present in the embodiment shown in fig5 , is absent . the wavelength shifts 54 are no longer present since the feedback beam is separated from the photo - acoustic beam . the amount of feedback signal can be simply adjusted by a further rotation of the laser polarization . it is assumed that the coupling of ‘ s ’ and ‘ p ’ polarized light to the cavity is equal , a fair assumption for an axially symmetric cavity . it is to be noted that the advantageous combination of an optical cavity and a crystal oscillator could , in principal , also be achieved in trace gas detectors using different feedback loops and / or modulation schemes . when crystal oscillators are used instead of microphones it is important to use a chopping frequency that matches a resonance frequency of the crystal oscillator . it should be noted that the above - mentioned embodiments illustrate rather than limit the invention , and that those skilled in the art will be able to design many alternative embodiments without departing from the scope of the appended claims . in the claims , any reference signs placed between parentheses shall not be construed as limiting the claim . use of the verb “ comprise ” and its conjugations does not exclude the presence of elements or steps other than those stated in a claim . the article “ a ” or “ an ” preceding an element does not exclude the presence of a plurality of such elements . the invention may be implemented by means of hardware comprising several distinct elements , and by means of a suitably programmed computer . in the claims enumerating several means , several of these means may be embodied by one and the same item of hardware . the mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage .

US-43857307-A

this invention is in the general field of surgical instruments . it relates specifically to catheters which may be used in cardiovascular and endovascular procedures to deliver diagnostic , therapeutic , or vaso - occlusive agents to a target site within a human or animal body which is accessible by a system of natural passageways within that body . the catheters are coated in such a way that they are exceptionally slippery and the coating is very durable . the invention also relates to methods of coating the catheters and to methods of applying lubricious coatings by forming a sheet of the coating on the substrate and simultaneously drying and crosslinking through heat and radiation .

this invention is a catheter , optionally including a guidewire , having discrete sections of varying flexibility . in each variation of the invention , the catheter has a relatively stiff proximal section and a less stiff mid portion . for devices intended for use as flow - directed catheters , the distal end section is quite flexible ; for devices intended for use with guidewires , the distal end section need not be quite as flexible since it need only follow the path of the guidewire without substantial disturbance of that predetermined path . at least the distal portion of the catheter is coated with a polymeric material to increase its lubricity and to minimize the potential for trauma as it moves through the body lumen . the mid or transition section of the catheter may also be coated with the polymeric material . the proximal section may also be coated although most desirably a small proximal end portion is left uncoated for increased control particularly suitable as coatings in the catheter assembly of this invention are polymers or oligomers of monomers selected from ethylene oxide ; 2 - vinyl pyridine ; n - vinylpyrrolidone ; polyethylene glycol acrylates such as mono - alkoxy polyethylene glycol mono ( meth ) acrylates , including mono - methoxy triethylene glycol mono ( meth ) acrylate , mono - methoxy tetraethylene glycol mono ( meth ) acrylate , polyethylene glycol mono ( meth ) acrylate ; other hydrophilic acrylates such as 2 - hydroxyethylmethacrylate , glycerylmethacrylate ; acrylic acid and its salts ; acrylamide and acrylonitrile ; acrylamidomethylpropane sulfonic acid and its salts , cellulose , cellulose derivatives such as methyl cellulose ethyl cellulose , carboxymethyl cellulose , cyanoethyl cellulose , cellulose acetate , polysaccharides such as amylose , pectin , amylopectin , alginic acid , and crosslinked heparin . these monomers may be formed into homopolymers or block or random copolymers . the use of oligomers of these monomers in coating the catheter for further polymerization is also an alternative . preferred monomers include ethylene oxide ; 2 - vinyl pyridine ; n - vinylpyrrolidone and acrylic acid and its salts ; acrylamide and acrylonitrile each polymerized ( with or without substantial crosslinking ) into homopolymers , or into random or block copolymers . additionally , hydrophobic monomers may be included in the coating polymeric material in an amount up to about 30 % by weight of the resulting copolymer so long as the hydrophilic nature of the resulting copolymer is not substantially compromised . suitable monomers include ethylene , propylene , styrene , styrene derivatives , alkylmethacrylates , vinylchloride , vinylidenechloride , methacrylonitrile , and vinyl acetate . preferred , because of their propensity for ease of linkage to the typical polymeric catheter substrates , are ethylene , propylene , styrene , and styrene derivatives . polymers or oligomers applied using the procedure described below are activated or functionalized with photoactive or radiation - active groups to permit reaction of the polymers or oligomers with the underlying polymeric surface . suitable activation groups include benzophenone , thioxanthone , and the like ; acetophenone and its derivatives specified as : ## str1 ## where r 1 is h , r 2 is oh , r 3 is ph ; or r 1 is h , r 2 is an alkoxy group including -- och 3 , -- och 3 , r 3 is ph ; or r 1 ═ r 2 = an alkoxy group , r 1 is ph ; or r 1 ═ r 2 = an alkoxy group , r 3 is h ; or the polymeric coating may then be linked with the substrate using known and appropriate techniques selected on the basis of the chosen activators , e . g ., by ultraviolet light , heat , or ionizing radiation . crosslinking with the listed polymers or oligomers may be accomplished by use of peroxides or azo compounds such as acetyl peroxide , cumyl peroxide , propionyl peroxide , benzoyl peroxide , or the like . a polyfunctional monomer such as divinylbenzene , ethylene glycol dimethacrylate , trimethylolpropane , pentaerythritol di - ( or tri - or tetra -) methacrylate , diethylene glycol , or polyethylene glycol dimethacrylate , and similar multifunctional monomers capable of linking the polymers and oligomers discussed above is also appropriate for this invention . the polymeric coating may be applied to the catheter body or other polymeric substrate by any of a variety of methods , e . g ., by spraying a solution or suspension of the polymers or of oligomers of the monomers onto the catheter or by dipping the catheter into the solution or suspension ( after sealing the open ends , if so desired ). initiators may be included in the solution or applied in a separate step . the catheter may be sequentially or simultaneously dried to remove solvent after application of the polymer or oligomer to the polymeric body and crosslinked . the solution or suspension should be very dilute since only a very thin layer of polymer is to be applied . we have found that an amount of oligomer or polymer in a solvent of between 0 . 25 % and 5 . 0 % ( wt ), preferred is 0 . 5 to 2 . 0 % ( wt ), is excellent for thin and complete coverage of the resulting polymer . preferred solvents for this procedure when using the preferred polymers and procedure are water , low molecular weight alcohols , and ethers , especially methanol , propanol , isopropanol , ethanol , and their mixtures . other water miscible solvents , e . g ., tetrahydrofuran , methylene dichloride , methylethylketone , dimethylacetate , ethyl acetate , etc ., are suitable for the listed polymers and must be chosen according to the characteristics of the polymer ; they should be polar because of the hydrophilic nature of the polymers and oligomers but , because of the reactivity of the terminal groups of those materials , known quenching effects caused by oxygen , hydroxyl groups and the like must be recognized by the user of this process when choosing polymers and solvent systems . particularly preferred as a coating for the catheter bodies discussed below are physical mixtures of homo - oligomers of at least one of polyethylene oxide ; poly 2 - vinyl pyridine ; polyvinylpyrrolidone , polyacrylic acid , polyacrylamide , and polyacrylonitrile . the catheter bodies or substrates are preferably sprayed or dipped , dried , and irradiated to produce a polymerized and crosslinked polymeric skin of the noted oligomers . the lubricious hydrophilic coating is preferably produced using generally simultaneous solvent removal and crosslinking operations . the coating is applied at a rate allowing &# 34 ; sheeting &# 34 ; of the solution , e . g ., formation of a visibly smooth layer without &# 34 ; runs &# 34 ;. in a dipping operation for most polymeric substrates noted below , the optimum coating rates are found at a linear removal rate between 0 . 25 and 2 . 0 inches / sec , preferably 0 . 5 and 1 . 0 inches / sec . the solvent evaporation operations may be conducted using a heating chamber suitable for maintaining the surface at a temperature between 25 ° c . and the glass transition temperature ( t g ) of the underlying substrate . preferred temperatures are 50 ° c . to 125 ° c . most preferred for the noted and preferred solvent systems is the range of 75 ° to 110 ° c . ultraviolet light sources may be used to crosslink the polymer precursors onto the substrate . movement through an irradiation chamber having an ultraviolet light source at 90 - 375 nm ( preferably 300 - 350 nm ) having an irradiation density of 50 - 300 mw / cm 2 ( preferably 150 - 250 mw / cm 2 ) for a period of three to seven seconds is desired . passage of a catheter through the chamber at a rate of 0 . 25 to 2 . 0 inches / second ( 0 . 5 to 1 . 0 inches / second ) in a chamber having three to nine inches length is suitable . when using ionizing radiation , a radiation density of 1 to 100 krads / cm 2 ( preferably 20 to 50 krads / cm 2 ) may be applied to the solution or suspension on the polymeric substrate . exceptional durability of the resulting coating is produced by repetition of the dipping / solvent removal / irradiation steps up to five times . preferred are two to four repetitions . fig1 shows an infusion catheter ( 100 ) constructed according to one embodiment of the invention . the catheter ( 100 ) has an elongate tubular body ( 102 ) with proximal ( 104 ) and distal ( 106 ) ends and an open inner lumen ( 108 ) extending between the ends . the elongate tubular body ( 102 ) has three segments ; a relatively flexible and strong distal segment ( 120 ), a relatively stiff tapered proximal segment ( 122 ) and a transition section or segment ( 124 ) between the proximal and distal segments that is less flexible than the distal segment ( 120 ) but more flexible than the proximal segment ( 122 ). the elongate tubular body ( 102 ) has a strong distal segment ( 120 ) which is desirably relatively flexible such that the catheter can easily navigate a tortuous vessel pathway . by &# 34 ; relatively flexible &# 34 ; is meant that a force of about 1 × 10 4 pounds corresponds to a deflection of the material that is 10 ° from horizontal , or only about 5 × 10 4 pounds of force to deflect the material about 800 from horizontal . by &# 34 ; relatively strong &# 34 ; is meant that the material has a burst pressure of greater than 195 psi , more preferably , the burst pressure is between about 195 and 220 psi . the flexible distal segment ( 120 ) has an open end which allows for the infusion of diagnostic , therapeutic , or vaso - occlusive agents into the target site . when the catheter is a flow - directed infusion catheter , the flexible distal segment ( 120 ) preferably is made of a polymer that is springy and biologically compatible such as low density polyethylene , polyurethane , a block copolymer of polyamide , polyvinyl chloride , or silicone or blends of the above . the flexible distal segment ( 120 ) may carry one or more radiopaque bands ( 130 ) or may be doped with a radiopaque material such as barium sulfate , bismuth trioxide , bismuth carbonate , tungsten , tantalum or the like so that the location of the distal region of the catheter within the vessel may be visualized radiographically . the distal segment ( 120 ) typically makes up between about 5 and 25 % of the total length of the tubular member and is between about 5 and 40 cm long , preferably between about 10 and 20 cm long . the inner diameter of the distal segment ( 120 ) may be between about 0 . 25 and 0 . 50 mm , more preferably between about 0 . 25 and 0 . 35 mm . the outer diameter of the distal segment may be between about 0 . 50 and 0 . 80 mm , more preferably between about 0 . 60 and 0 . 70 mm . the wall thickness of the distal segment 120 is between about 0 . 1 and 0 . 3 mm . the proximal segment ( 122 ) of the elongate tubular body ( 102 ), when used as a flow - directed infusion catheter , is relatively stiff such that it can be easily pushed thus eliminating the need for guidewire support . the proximal segment ( 122 ) may be made of a polymeric or metallic material that is relatively stiff and biologically compatible such as high density polyethylene , polypropylene , nylon , polyurethane , polyimides , polyvinyl chloride , polysulfones , polyfluorocarbons , polyethylene terephthalate , their mixtures , copolymers ; or polyester elastomers or a braided shaft ( a polymer outer core with a metallic mesh inner core ). the proximal segment ( 122 ) may comprise a tapered proximal section ( 134 ) for attachment to the proximal end fitting ( 150 ) and a distal section ( 132 ). the proximal section ( 134 ) of proximal segment ( 122 ) may make up between about 60 % and 80 % of the total length of the tubular member ( 102 ) and typically is between about 90 and 130 cm long , preferably between about 100 and 120 cm long . the largest inner diameter of the proximal section ( 134 ), measured at the proximal end ( 104 ) of the tubular member 102 , is often between about 0 . 40 and 0 . 60 mm , more preferably between about 0 . 45 and 0 . 55 mm . the outer diameter of the proximal section ( 134 ) at the proximal end ( 104 ) of the tubular member ( 102 ) is between about 0 . 8 and 1 . 2 mm . the wall thickness of the proximal section ( 134 ) of proximal segment ( 122 ) is between about 0 . 1 and 0 . 4 mm , more preferably between about 0 . 2 and 0 . 3 mm . the distal section ( 132 ) of proximal segment ( 122 ) makes up between 10 and 20 % of the total length of the tubular body ( 102 ) and is between about 20 and 40 cm long , preferably between about 20 and 30 cm long . the inner diameter of the distal section ( 132 ) of proximal segment ( 122 ) may be between about 0 . 20 and 0 . 50 mm , more preferably between about 0 . 25 and 0 . 35 mm . the outer diameter of the distal section ( 132 ) of proximal segment ( 122 ) is between about 0 . 60 and 0 . 90 mm , more preferably between about 0 . 60 and 0 . 70 mm . the wall thickness of the distal section ( 134 ) of proximal segment ( 122 ) is typically between about 0 . 1 and 0 . 3 mm . the transition section ( 124 ) of the elongate tubular body ( 102 ) is less stiff than the proximal segment ( 122 ) but more stiff than the distal segment ( 120 ). a suitable material that is biologically compatible is a polymer such as polyurethane , a block copolymer of polyamide , polyvinyl chloride or silicone with greater durometer reading ( i . e . that is stiffer ) than the flexible distal segment ( 120 ). the transition section ( 124 ) may be radiopaque and thus observable in the event that the catheter becomes lodged in a particular portion of the vasculature or buckles . the polymeric material may be doped with a radiopaque material such as barium sulfate , bismuth carbonate , bismuth trioxide , tungsten , tantalum or the like . the transition section ( 124 ) may make up between about 10 and 20 % of the total length of the tubular member ( 102 ) and is between about 20 and 40 cm long , preferably between about 25 and 35 cm long . the transition section ( 124 ) may be of constant diameter or may be tapered . the inner diameter of the transition section ( 124 ) may be between about 0 . 20 and 0 . 50 mm , more preferably between about 0 . 20 and 0 . 35 mm . the outer diameter of the transition section ( 124 ) may be between about 0 . 50 and 0 . 90 mm , more preferably between about 0 . 60 and 0 . 70 mm . the wall thickness of the transition section ( 124 ) may be between about 0 . 1 and 0 . 3 mm . the proximal segment ( 122 ), transition section ( 124 ), and distal segment ( 120 ) are joined at junctions ( 140 ) and ( 142 ), respectively . the junctions may be formed - by flaring , overlapping , and heat fusing the materials of the proximal segment ( 122 ) and transition section ( 124 ) and the transition section ( 124 ) and distal segment ( 120 ). other methods for forming the junction , e . g ., heat welding , solvent welding , etc . are also suitable . the distal segment ( 120 ), transition section ( 124 ) and distal section ( 132 ) of proximal segment ( 122 ) may all have approximately the same outside diameter orthe transition section ( 124 ) and the distal section ( 132 ) of the proximal segment ( 122 ) may be tapered . a standard proximal end fitting ( 150 ) is attached to the proximal end ( 134 ) of the proximal segment ( 122 ) often by heat fusion with reinforcing tubing . fig2 shows an embodiment of the distal segment ( 120 ) of the catheter where the tip ( 160 ) of the catheter is pre - shaped by heating with steam so that the distal end ( 106 ) points towards the wall of the vessel rather than in the direction of blood flow to increase the ease of manipulation through the tortuous vessel pathway . the particular embodiment shown is an &# 34 ; s &# 34 ; shape , but the tip may be any shape that allows for access to the particular vasculature being treated . one additional shape is that of a hockey stick . in this way , if the catheter becomes lodged against the vessel wall , the infusion of liquid through the catheter propels the distal end ( 106 ) of the catheter away from the vessel wall . since the stiff proximal segment ( 122 ) is pushed , the distal segment ( 120 ) will be carried by the blood flood to the target site . the catheter described above is useful in delivering diagnostic , therapeutic , or vaso - occlusive agents and devices to deep tissue , usually without need for a guidewire . fig3 shows a catheter assembly ( 200 ) for placing the infusion catheter ( 100 ) at the target site . an appropriate guiding catheter ( 202 ) is inserted into the vasculature using standard placement techniques . a rotating hemostatic valve ( 204 ) may be utilized by connection to the guiding catheter luer adapter ( 206 ). the guiding catheter ( 202 ) is continuously flushed with saline . the thumb - screw of the valve ( 204 ) is opened and the infusion catheter ( 100 ) is inserted through the rotating hemostatic valve ( 204 ). optionally , as shown in fig3 a - teflon - coated stainless steel stylet ( 208 ) is first inserted into the flow - directed infusion catheter ( 100 ) in order to prevent kinking of the infusion catheter ( 100 ) within the valve ( 204 ). the distal end ( 106 ) of the infusion catheter ( 100 ) is advanced proximal to the tip of the guiding catheter ( 202 ). the stylet ( 208 ) is then removed from the infusion catheter ( 100 ). once the stylet ( 208 ) is removed , the infusion catheter ( 100 ) is pushed out of the guiding catheter ( 202 ). the flow - directed infusion catheter ( 100 ) is gently guided by the flow of blood in the vasculature to the target site . optionally , gentle pushing and pulling and injection of saline or contrast medium through the catheter lumen ( 108 ) may aid in the placement of the catheter at the target site . once at the target site , the desired agent is injected . such agents may include radiopaque agents for viewing blood vessel anatomy and blood flow characteristics in the target region , vaso - occlusive agents which can be used to produce small - artery vaso - occlusion in the tissue region supplied by the target vessel , and pharmacological agents , such as anti - tumor drugs or sclerosing agents such as alcohols , which are effective against identified disease states at the target site . vaso - occlusive agents useful in the treatment of arteriovenous malformations include polymers that are activated in the presence of polar solvents such as water and include materials such as n - butylcyanoacrylate . other types of vaso - occlusive agents useful in the treatment of arteriovenous malformations include polymer solutions that coagulate by diffusion of the solvent when in contact with blood . polyvinyl acetate dissolved in dimethylsulfoxide is one such agent . alternatively , vaso - occlusive coils may be injected into the infusion catheter and delivered to a target site to occlude the blood flow at that site . fig4 shows a variation of the invention in which the catheter is guided to its intended site by the use of a guidewire rather than through the use of blood flow . as with the device described above , the catheter assembly ( 400 ) includes an elongate member ( 402 ) having a proximal end ( 404 ) and a distal end ( 406 ) and an inner lumen which extends between those two ends . the elongate tubular body ( 402 ) has three segments ; a relatively flexible distal segment ( 408 ), a relatively stiff proximal segment ( 410 ) and a transition section or middle segment ( 412 ) ( separated at junction ( 414 ) from the proximal segment ) between the proximal and distal segments that is less flexible than the distal segment ( 408 ) but more flexible than the proximal segment ( 410 ). found within the lumen of the catheter assembly is guidewire ( 414 ) often having a bent tip ( 416 ) to allow ease of passage through the vasculature . typically , such a catheter will have a small radiopaque band ( 418 ) of gold , platinum , palladium , or the like to permit monitoring of the catheter tip &# 39 ; s position in relation to the tip of the guidewire or , when the guidewire is not in the catheter , to the vasculature itself . a standard proximal end fitting ( 420 ) may attached to the proximal end ( 404 ) of the proximal segment ( 410 ) often by heat fusion with reinforcing tubing . as is described in u . s . pat . no . 4 , 739 , 768 , to engelson , the variation of flexibility may be introduced into the catheter assembly by use of sections of discrete coaxial tubing , e . g ., by use of an inner stiff tube of polypropylene or high density polyethylene covered by a flexible tube of low density polyethylene or silicone in the proximal section ( 410 ) with the inner tubing junction found at ( 410 ). a thinner wall inner tubing of the same polymer as found in the proximal section ( 410 ) may be used as the inner tubing in middle section ( 412 ) to provide decreased stiffness in the middle section ( 412 ). in such an instance , the outer coaxial layer could be of the same composition and dimensions from proximal end ( 404 ) to distal end ( 406 ). other methods of varying the stiffness to provide for strength at the proximal end , extreme flexibility at the distal end to allow conformance to the contortions of the guidewire through multiple flexions , and a middle section of strength sufficient to transmit pressure and torque from proximal end to distal end without buckling or compression . the various sections ( particularly the inner section ) may be tapered to provide variable stiffness through at the section or throughout the catheter . two sets of catheters were made , one according to the invention and one with a silicone coating , for comparison of the resulting slipperiness and durability of the coating . the catheters had three discrete sections : a proximal section of low - density polyethylene laminated over polypropylene tubing ( having 0 . 022 &# 34 ; i . d . and 0 . 039 &# 34 ; o . d .) of 115 cm . length , a transition section of low density polyethylene laminated over polypropylene tubing ( having 0 . 022 &# 34 ; i . d . and 0 . 036 &# 34 ; o . d .) of 15 cm ., and a distal section of low density polyethylene of 20 cm . the low density polyethylene outer covering was a single piece covering throughout the length of the catheters . a ) catheters were dipped into a dilute polymeric solution of xx % polyvinylpyrrolidone and xx % polyacrylamide ( each having photoactive groups ) in a solution of isopropanol and water , and removed from the solution at a rate of 0 . 7 &# 34 ;/ sec ., b ) the coating was dried using heated air at 100 ° c ., c ) the coated catheter was exposed to ultraviolet light ( 100 mw / cm 2 ) for seven seconds to bond the coating to the catheter substrate and to crosslink the polymers in the solution , and the comparative silicone catheter coating was applied using the following procedure : a ) catheters were dipped into a silicone solution of 1 . 5 ml dowcorning mdx 4 - 4159 , 160 ml freon , and 40 ml isopropanol . c ) the catheters were then coated with a silicone fluid solution ( 15 ml dow 360 in 160 ml freon ), and the catheters were separately introduced into a usci angiographic systems berenstein j - tip guiding catheter in a test rig allowing measurement of the force . needed to push and to pull the catheters through the guiding catheter . each of the catheters was tested through 20 pulls and pushes of 2 inches pushed and pulled at a rate of 1 inch / minute . in this way both absolute force needed to introduce the catheter may be recorded as well as the magnitude of all deterioration in the slipperiness . the measurements were taken for both the midsection and for the distal sections of the two catheters . table______________________________________ force ( in lbs .) pull . no . comparative invention______________________________________midsection 1 0 . 044 0 . 02520 0 . 054 0 . 025distal section 1 0 . 023 0 . 01320 0 . 027 0 . 013______________________________________ it is apparent that the force needed to move the inventive catheter through the guiding catheter was only about half of that needed to move the comparative device . additionally , the amount of force needed to move the comparative catheter increased substantially during the repetitive testing indicating that the coating was failing . in contrast , the inventive coating did not degrade during the test . although preferred embodiments of the invention have been described herein , it will be recognized that a variety of changes and modifications can be made without departing from spirit of the invention as found in the claims which follow .

US-60450096-A

a golf bag of variable configuration includes a tubular pillar to which are hinged two compartments each having a triangular cross - section . the compartments extend parallel to the tubular pillar and are open at one end . the two compartments are movable angularly between an open position in which they are spaced from each other and define with the tubular pillar a longitudinal outwardly - open v - shaped seat and a closed position in which they are side by side . an auxiliary container having a shape substantially complementary to that of the longitudinal seat can be fitted removably into the seat when the two compartments are in the open condition .

with reference initially to fig1 and 2 , a bag according to the invention is generally indicated 1 and can be used , for example , as a golf bag . the bag 1 comprises essentially a carrying structure 2 , illustrated in greater detail in fig3 to 7 , two casings 3 fitted to the carrying structure 2 in the manner explained below and defining therewith two club - carrying compartments 4 which are side by side , and an auxiliary container 5 which can be fitted selectively to the carrying structure 2 in the manner made clear below . with reference in greater detail to fig3 to 5 , the carrying structure 2 comprises essentially an axially elongate , rigid tubular pillar 6 having dimensions of length and width such as to accommodate a closed umbrella . at the top , at the base and in the middle region of the tubular pillar 6 are fitted three pairs of annular elements 7 , of which the lower ones are closed by means of respective rigid base covers 8 which are conveniently perforated . according to the preferred embodiment of the bag , the annular elements 7 have a cross - sectional profile which is substantially triangular with rounded corners , conveniently a right - angled isosceles triangle . the annular elements 7 of each pair are articulated to each other and to the tubular pillar 6 in the manner clearly illustrated in fig4 and 5 , and the homologous annular elements 7 of the two pairs are rigidly interconnected by respective rods 9 parallel to the tubular pillar 6 . the casings 3 are tubular in shape and are fixed independently of each other to the homologous annular elements 7 of the two pairs . in this way , each of the two compartments 4 is defined in practice by the tubular pillar 6 and the three annular elements 7 situated on the same side , with their connection rods 9 , and by the corresponding casing 3 which is closed at the bottom by its respective base cover 8 and is open at the top . it should be noted that , although in the case of the illustrated example , the carrying structure 2 is rigid and the casings 3 are flexible , a solution is also envisaged in which the tubular pillar 6 is flexible but the casings 3 are rigid . in this case , the interconnecting rods 9 between the annular elements 7 may be omitted . by virtue of the articulated connection illustrated , the annular elements 7 can rotate like compasses between a spaced - apart open position , illustrated in fig6 in which the catheti of the elements 7 are parallel to each other , and a side - by - side closed position , illustrated in fig7 in which the hypotenuses of the elements 7 are next to each other . identical configurations are obviously assumed by the two compartments 2 , as illustrated in fig1 and 8 and in fig9 respectively . in the first configuration , that is , the open one , the two compartments 4 define , between the hypotenuses of the annular elements 7 and the tubular pillar 6 , a substantially v - shaped longitudinal seat 10 which is open outwardly along one side of the bag 1 . with the two compartments 4 in the side - by - side configuration illustrated in fig9 this seat 10 is eliminated so that the bag 1 has a substantially square shape in cross - section . the longitudinal seat 10 is adapted to house the auxiliary container 5 , in the manner illustrated in fig1 and 2 . as can better be seen in fig1 and 11 , this auxiliary container 5 is conveniently constituted by a flexible bag of triangular section , having a length corresponding to that of the tubular pillar 6 and provided with pockets 11 with zip fasteners . this bag 5 is conveniently divided into two longitudinal sections 5a , 5b of equal length which can be kept one as an extension of the other , as illustrated in fig1 , or folded one against the other , as illustrated in fig1 . this bag 5 is provided with rapid connection means , not illustrated , constituted , for example , by press - studs , zip fasteners , or similar means , for its separable connection to the tubular pillar 6 and / or the outside of the two compartments 4 . these connection means enable it to be fixed both in the extended configuration of fig1 ( fig1 and 2 ) and in the folded configuration of fig1 , as illustrated in fig8 . the second case allows access to a rain hood 12 , normally folded into the upper region of the seat 10 , which can be fitted by rapid connection means ( studs , zip fasteners , or the like ) to the tops of the two compartments 4 , as indicated with a broken line in fig8 . the bag is completed by various accessories , such as a carrying handle 13 , a shoulder - strap 14 and any other attachments fixed to the tubular pillar 6 , and by further pockets 15 formed in the casings 3 and adapted to contain small items . in the complete configuration of fig1 and 2 , the bag 1 formed by the two compartments 4 and by the auxiliary container 5 has a generally rectangular cross - sectional shape . in this configuration , which is the one with the maximum useful volume , the bag 1 may easily be fixed to a normal transporting trolley usually used for golfing . the compartments 4 are adapted to house the golf clubs , whilst the tubular pillar 6 can house an umbrella . the auxiliary container 5 can house any additional bulky equipment , such as shoes , articles of clothing , etc ., whilst the pockets 15 of the casing 3 can contain small items used frequently during play . when the accessories in the container 5 are not required during play and the player has to carry the bag 1 by the shoulder - strap , the container 5 is removed by simple and rapid operations and the two club - carrying compartments 4 brought alongside each other to obtain the least bulky configuration of fig9 . in this case , the auxiliary container can be folded into the configuration of fig1 and perhaps carried separately . fig1 to 18 illustrate possible variants of the sectional shape of the bag 1 corresponding to different profiles of the annular elements 7 articulated to the tubular pillar 6 . fig1 corresponds to the preferred embodiment described above , in which the annular elements 7 and therefore the two compartments 4 have a right - angled isosceles triangular section . in the case of fig1 and 14 , the two compartments 4 have quadrangular , trapezoidal and parallelogram shapes respectively . in the case of fig1 , the two compartments 4 are substantially semi - circular and , in this case , the auxiliary container 5 may conveniently have the shape of a circular sector . fig1 shows an irregular polygonal configuration of the two compartments 4 and fig1 shows a lobe - shaped configuration thereof . finally , in the case of fig1 , the two compartments 4 have a flattened , elongate profile . furthermore , although specific reference has been made to the use of the bag according to the invention as a golf bag in the example illustrated , it is clear that the same utility and advantages of the invention also extend to different uses of the bag , for example , to its use as a travelling bag or suitcase .

US-20677388-A

a system and method for acquiring an image of a region of interest of subject using a computed tomography system includes a ) performing a scout scan of the subject using the ct system to yield scout data related to the roi and b ) determining an initial contrast volume form at least the scout data . the method also includes c ) prescribing a scanning protocol to be implemented using the computed tomography system to image the roi and d ) determining a size of the subject about the roi . the method further includes e ) determining a computed tomography dose related to volume based on at least the size determined at step d ) and f ) adjusting the scanning protocol prescribed in step b ) to match at least one of a desired radiation dose and a relative intravenous contrast dose to a reference ctdivol . the method includes g ) acquiring imaging data from the roi using the ct system by using the adjusted scanning protocol .

with initial reference to fig1 a and 1b , a computed tomography ( ct ) imaging system 110 includes a gantry 112 representative of at least a “ third generation ” ct scanner . in the illustrated example , the gantry 112 has a pair of x - ray sources 113 that each project a fan beam or cone beam of x - rays 114 toward a detector array 116 on the opposite side of the gantry 112 . the detector array 116 is formed by a number of detector elements 118 that together sense the projected x - rays that pass through a medical patient 115 . during a scan to acquire x - ray projection data , the gantry 112 and the components mounted thereon rotate about a center of rotation 119 located within the patient 115 to acquire attenuation data . the rotation of the gantry 112 and the operation of the x - ray source 113 are governed by a control mechanism 120 of the ct system 110 . the control mechanism 120 includes an x - ray controller 122 that provides power and timing signals to the x - ray sources 113 and a gantry motor controller 123 that controls the rotational speed and position of the gantry 112 . a data acquisition system ( das ) 124 in the control mechanism 120 samples analog data from detector elements 118 and converts the data to digital signals for subsequent processing . an image reconstructor 125 , receives sampled and digitized x - ray data from the das 124 and performs high speed image reconstruction . the reconstructed image is applied as an input to a computer 126 that stores the image in a mass storage device 128 . the computer 126 also receives commands and scanning parameters from an operator via console 130 that has a keyboard . an associated display 132 allows the operator to observe the reconstructed image and other data from the computer 126 . the operator supplied commands and parameters are used by the computer 126 to provide control signals and information to the das 124 , the x - ray controller 122 , and the gantry motor controller 123 . in addition , computer 126 operates a table motor controller 134 that controls a motorized table 136 to position the patient 115 in the gantry 112 . in ct scans , image noise is highly correlated to the dose of radiation delivered to the subject . similarly , when a contrast agent , such as iodine is employed , the signal - to - noise ratio of the resulting image is correlated to the dose of contrast agent administered . thus , higher snr in a resulting image is achieved when more x - ray photons and / or a large dose of iv contrast agent are used to create the image . if a clinician were able to prospectively determine and consider whether the decreased snr noise associated with a decreased dose of radiation or contrast agent would be acceptable to a given clinical application , the clinician would be empowered to determine whether additional dose reductions would be acceptable to the given clinical application . the present invention provides a system and method for achieving this objective . the term “ low kv ct ” typically refers to imaging with ct at 100 kv , or in some cases 70 kv or 80 kv , rather than at 120 kv as is usual in ct . low kv ct has been widely used for radiation dose reduction , especially in smaller patients , because of the benefit of increased iodine signal at lower x - ray energies . with low kv imaging , image quality equivalent to that acquired at 120 kv can be achieved with a reduced radiation dose in patients with body size less than a certain threshold . selection of the most appropriate kv for each patient size and diagnostic task is the subject active debate and investigation . however , taking advantage of the greater iodine signal with lower kv , the present invention makes it possible to reduce the dose of intravenous ( iv ) iodine contrast instead of reducing radiation dose , whilst maintaining adequate contrast . without decreasing the radiation dose , the noise level can be controlled or maintained . therefore , the same level of iodine contrast - to - noise ratio ( cnr ) can be obtained at low kv with a reduced dose of iv iodinated contrast material . patients who may benefit from this include those with renal insufficiency or those with poor venous access , in whom only a small iv cannula with a decreased contrast flow rate can be used . cost savings can also be achieved from the use of low intravenous contrast dose . in addition , an age - appropriate ct imaging method , which is designed to reduce radiation dose for younger patients and intravenous contrast dose for older patients , is provided . the present invention allows one to determine a desired radiation dose reduction in routine abdominal and pelvic ct , while maintaining sufficient diagnostic image quality . furthermore , the present invention provides scan protocols to use in clinical practice that allow either the reduction of iv contrast dose or reduction of radiation dose , while maintaining image quality and iodine contrast - noise ratio (“ icnr ”). the reduction in iv contrast dose (“ ivcd ”) and radiation dose may be quantified , and the icnr and iq obtained with the new scan protocols may also be measured . to develop the scientific basis for the present invention , a two - stage study was performed . first , the lowest acceptable radiation dose was determined . 25 lymphoma follow - up ct scans using routine dose levels ( 240 quality reference mas , 120 kv ) had noise inserted to simulate images at 25 %, 50 % and 75 % dose levels . two radiologists evaluated 4 image sets ( 1 randomized dose level / patient , 25 patients / set ) for image quality ( iq ) ( scale 1 - 5 ; 3 = more noise without loss of confidence , 5 = normal noise , excellent iq ). the dose level yielding iq score of 3 was selected . second , two lymphoma follow - up ct protocols were implemented . a first protocol was developed to reduce intravenous contrast dose ( ivcd ) while keeping the original radiation dose ( used in patients 50 and older ). the amount of ivcd reduction was determined from the lowest radiation reduction to maintain the same iodine contrast - noise ratio ( icnr ). the second protocol was developed to reduce radiation dose ( used in patients under 50 years ). the processes used to develop both protocols employed a size - specific kv selection . 60 patients underwent follow - up ct with either reduced radiation dose ( if & lt ; 50 years ) or reduced iv contrast dose ( if 50 years ). noise , liver and aortic icnr , and iq ( same scale ) were compared to prior studies . in the first phase , we determined by how much we could reduce radiation dose in routine ct scans of the abdomen and pelvis scans , while still maintaining diagnostic image quality . the lowest acceptable radiation dose corresponds to the icnr that was sufficient to reliably result in diagnostic image quality . in the second phase , we developed ct acquisition protocols that allowed us to reduce radiation dose or iv contrast amount whilst maintaining this icnr , then evaluated these protocols in our clinical practice . for both phases of the study , we selected the diagnostic task of “ lymphoma follow - up ” ct , as numerous exams are often performed in the same individuals for this purpose . to develop new low - dose protocols for following patients with lymphoma , we first needed to determine how much radiation dose we could reduce in routine ct scans of the abdomen and pelvis scans while still maintaining sufficient diagnostic image quality . in order to develop new scan protocols , in the first phase of the study , we first took 25 abdomen / pelvis scans that had been scanned with routine abdomen / pelvis technique ( 120 kv , 240 quality reference mas ). raw data was exported to an off - line workstation and noise was inserted to simulate 75 %, 50 %, and 25 % of the original radiation dose level , using a previously validated noise insertion tool . images at different dose levels were reconstructed with 5 mm slice thickness and b40 kernel . this resulted in a total of 100 data sets , consisting of 25 patients each with 4 dose levels . these were formed into 4 groups of 25 cases , with one randomly chosen data set from each of the 25 patients being put into each of the 4 groups , so that each group consisted of 25 patients with scans from any 1 of the 4 dose levels . the cases were stripped of patient identifiers , coded and transferred to an independent workstation for viewing . the cases were independently read by 2 radiologists , reading no more than 50 cases at a time ( 2 groups of 25 ), with at least 2 weeks between reading the first 50 and the second 50 cases to minimize recall bias . readers were blinded to the technical parameters of each scan , as well as to the clinical data and final radiologic diagnosis . for each case , the readers recorded their assessment of image quality on a 5 point scale , reflecting the readers ability to confidently diagnose or rule out pathology in the liver , spleen , kidneys , pancreas , aorta , and lymph nodes , as follows : 2 : suboptimal image quality , worse than routine dose images with excessive image noise , may miss lesions or mischaracterize lesions , confidence affected negatively ; 3 : markedly increased noise but acceptable image quality for diagnostic interpretation , confidence not affected ; 4 : good image quality , with only mild noise increase / texture change compared to routine dose images ; and objective evaluations of image noise were performed by region - of - interest ( roi ) analysis on the standard - dose scans and simulated ct data sets . the objective image noise ( sd of mean ct number ) was measured by placing circular rois of 20 - 48 mm 2 area in the subcutaneous fat and the fluid within the urinary bladder in patients in whom the urinary bladder was not collapsed or in the gallbladder in patients in whom the urinary bladder is collapsed . the roi locations on the standard ct scans was carefully matched to the rois on the corresponding simulated ct data set . the lateral width of each patient &# 39 ; s abdomen was measured skin to skin in cm at the level of mid portion of the liver , in order to help understand the impact of patient body habitus on dose reduction and image quality . while the lateral width information is useful , the analysis on the impact of patient body habitus on dose reduction and image quality is not required for the first phase . using a validated noise insertion program , noise was inserted into 25 contrast - enhanced abdomen / pelvis scans using our routine technique ( 120 kv , 240 quality reference mas ) to simulate 75 %, 50 %, and 25 % of the original radiation dose level . two radiologists , blinded to dose level and diagnosis , independently evaluated 4 randomized image sets ( 1 randomized dose level / patient , 25 patients / set ) and recorded their assessment of image quality ( iq ) on a 5 point scale reflecting the reader &# 39 ; s ability to confidently diagnose or rule out pathology in the liver , spleen , kidneys , pancreas , aorta , and lymph nodes , as follows : 1 , poor iq , not acceptable for interpretation ; 2 , suboptimal iq , excessive noise , may miss or mischaracterize lesions , confidence affected negatively ; 3 , markedly increased noise but acceptable iq for diagnostic interpretation , confidence not affected ; 4 , good iq , mild noise increase ; 5 , excellent iq , normal noise . objective noise measurements ( sd of mean ct number ) were also taken using region - of - interest ( roi ) analysis . the roi &# 39 ; s on the routine dose exam were carefully matched to the roi &# 39 ; s on the corresponding lower - dose simulated ct exam . at 50 % radiation dose reduction from baseline , radiologists rated 100 % and 90 % of cases to have iq score ( median 4 and 3 ), as illustrated in fig2 . we chose a 40 % dose reduction to represent the iodine contrast - to - noise ratio ( icnr60 %) that should be maintained , based on the logistic regression curve showing a 94 % probability of an iq score with this dose level , as illustrated in fig3 . the first protocol developed was focused on reducing or lowering intravenous contrast dose ( ivcd ), with no change to original radiation dose . the amount of intravenous contrast dose ( ivcd ) reduction was determined from the lowest radiation reduction necessary to maintain the same icnr , as outlined in table 1 below . baseline ivcd was calculated according to our default weight - based protocol using iohexol 300 ( omnipaque 300 , ge healthcare inc , princeton n . j .). instead of reducing radiation dose ( which increases noise ), we reduced the iodine contrast dose administered so as to maintain the predicted iodine contrast - noise ratio that would have been achieved had we used a low radiation dose . this protocol was used in patients 50 and older , as in these patients radiation dose is less of a concern , and because patients with renal insufficiency who would benefit from a reduced ivcd usually come from this age group . the older age group (& gt ; 50 ) was chosen for this protocol as they are the patients most likely to have renal insufficiency or diabetes and are most likely to benefit from the lower iv contrast dose . 42 patients greater than or equal to 50 years of age were scanned with a mean ctdivol of 18 . 4 +/− 3 . 0 mgy , not significantly different from the mean reference ctdivol of 19 . 8 +/− 3 . 0 that would have been given had a routine scan protocol been performed at 120 kv . mean ivcd administered in this group was 99 . 6 ± 18 . 3 ml , versus 133 . 8 +/− 22 . 3 ml had they received routine contrast dose . this represents a mean dose reduction of 26 % ( p - value & lt ; 0 . 001 ), as illustrated in fig4 . mean iq for this group was 4 . 6 , versus 4 . 7 in the prior comparison scan performed with routine ivcd ( p = 0 . 273 ). there was no significant difference in liver icnr between the study scans and the prior scans , and a 12 % decrease in aorta icnr ( p = 0 . 026 ) on the study scans versus the prior scans , as illustrated in fig5 . it was demonstrated that satisfactory image quality can be obtained with lower radiation dose and / or lower dose of iv contrast in some groups of patients , including those being followed up for lymphoma . by lowering the kv in patients & lt ; 42 cm lateral width , even greater dose savings can be achieved . in patients aged 50 and older , lower dose of iv contrast is likely to be more beneficial than lower radiation dose . therefore , it was concluded that this information could serve as the basis for a protocol that should be used in patients 50 years and older . referring to fig6 , a process in accordance with the present invention and relevant to protocol 1 is illustrated . the process starts at process block 600 with the acquisition of scout data using a scout scan , for example a topogram , and is followed thereafter at process block 602 by prescribing scan protocols at 120 kv and 240 quality reference mas and adjusting or reducing pitch if necessary to avoid under - estimation of ctdivol . the ctdivol is recorded . then , at process block 604 , the size of the subject is measures , for example , by measuring a maximum lateral width at the level of , for example , mid liver . at process block 606 , the ctdivol is determined and compared against a predetermined set of measurements , such as provided above in table 1 or input into a model consistent with the such measurements to determine the optimal kv and the value of the lowest relative iv contrast . at process block 608 , the scanning parameters are adjusted to the optimal kv , along with adjusting the quality reference mas and pitch to match the recorded ctdivol . at process block 608 , the clinician may consider the projected scanning time and , if too long , adjust the kv to a higher value and repeat the preceding steps for determining optimal kv at process block 606 . at process block 610 , a new iv contrast volume is calculated by multiplying the original iv contrast volume by the relative iv contrast value determined at process block 606 . a standard 50 cc saline chaser will follow at the same rate . by using a size - based kv analysis and keeping the original ctdivol in the reference technique , iv contrast dose can be lowered to the relative volume shown in the chart above . the potential radiation dose that would result in icnr60 % was calculated , taking potential selection of lower kv into account , depending on patient size , such as addressed above in table 1 . no change to iv contrast dose . low kv and the lowest possible radiation dose , with full iv contrast dose . the younger age group was selected for this protocol as they would benefit the most from the lower radiation dose 17 patients under the age of 50 were scanned with the low radiation dose protocol . the mean ctdivol was 12 . 5 ± 4 . 1 mgy , versus a mean reference ctdivol of 20 . 5 ± 4 . 5 mgy in these patients had they been scanned with routine protocol at 120 kv , with a mean dose reduction of 39 % ( p & lt ; 0 . 001 ). 11 patients received a dose reduction in excess of 40 % and 3 smaller patients received a dose reduction of approximately 50 % or more . mean liver icnr was 8 . 6 ± 1 . 9 versus 9 . 0 ± 2 . 1 on the prior scans . mean aortic icnr was 13 . 0 ± 2 . 7 versus 12 . 2 ± 2 . 9 on the prior scans . mean iq score was 4 . 3 , versus 5 . 0 on the prior scans ( p - value = 0 . 0005 ). this protocol is built off evaluation results from lymphoma patients that showed we can reduce radiation dose by 40 %. by further utilizing the dose reduction potential offered by optimal kv , additional radiation dose reduction can be used . this chart and protocol should be used in patients less than 50 years of age . referring to fig7 , a general process for protocol 2 is illustrated . the process is similar to that described above with respect to fig6 , but relies upon different data or models , such as described above and which is represented by the exemplary embodiment shown in table 2 . the process starts at process block 700 with the acquisition of scout data from a scout scan , such as a topogram , as described above , and is followed thereafter at process block 702 by prescribing scan protocols at 120 kv and 240 quality reference mas and adjusting or reducing pitch if necessary to avoid under - estimation of ctdivol . the ctdivol is recorded . then , at process block 704 , the size of the subject is measures , for example , by measuring a maximum lateral width at the level of , for example , mid liver . at process block 706 , the ctdivol is determined and compared against a predetermined set of measurements , such as provided above in table 2 or input into a model consistent with the such measurements to determine the optimal kv and the value of the lowest relative iv contrast . at process block 708 , the scanning parameters are adjusted to the optimal kv , along with adjusting the quality reference mas and pitch to match the recorded ctdivol . by using a size - based kv reference or model and applying the dose reduction estimated from an evaluation study on simulated low - dose images , radiation dose can be lowered to the relative dose shown in table 2 . thus , at process block 710 , a new iv contrast volume is calculated for the two low - dose protocols , baseline ivcd was calculated according to a default weight - based protocol using omnipaque 300 ( ge healthcare inc , princeton n . j .). contrast was injected at 3 cc / second , with a scan delay of 70 seconds . contrast dose ( in the over 50 age group ) was then altered according to our low - dose protocol , but injection rate and scan delay were not changed . the scans were read in a routine fashion by the radiologist of the day . there are two parts of possible radiation dose reduction : one is determined from the first phase of the study by evaluating the lowest possible radiation dose from the original protocol at 120 kv ; the other is from the optimal kv selection . together they represent the total amount of radiation dose that can possibly be reduced while still maintaining the diagnostic quality . the optimal kv was determined by using a kv technique chart referred to as autokv . the percentage of radiation dose reduction relative to 120 kv were obtained . since our purpose was not to reduce the radiation dose , we didn &# 39 ; t implement this predicted radiation dose reduction in the scan for these patients . instead , we used the original radiation dose while converting the total amount of allowable radiation dose reduction to iv contrast reduction . one assumption that is noted is that the iodine cnr given by the lowest - acceptable dose technique established in phase 1 is diagnostically acceptable . instead of reducing radiation dose ( which increases noise ), we reduced the dose of iodinated contrast while still maintaining the iodine cnr given by the lowest - acceptable dose technique established in phase 1 . the amount of iv contrast dose reduction can be estimated by calculating the noise decrease due to keeping the original radiation dose relative to the predicted reduced radiation dose . the fundamental assumption is that icnr60 % results in diagnostically acceptable images . the amount of iv contrast dose reduction can be estimated by calculating the noise decrease due to keeping the original radiation dose relative to the predicted reduced radiation dose . if the original ctdivol at 120 kv is d 0 and the estimated ctdivol after radiation dose reduction is d , then the relative noise for example , if the estimated total radiation dose reduction is 40 %, then the iv contrast reduction is ( 1 −√{ square root over ( 0 . 6 )})× 100 = 22 . 5 %. size - specific charts that took potential changes in radiation dose by changing kv into account were developed , such as provided in the example represented by table 1 . optimal kv was determined by patient size . image quality was measured using the scale used in phase 1 , with quantitative noise and ct number measurements additionally performed . actual iv contrast dose , flow rate , % change in ivcd ( from usual protocol ), ctdivol actual , and ctdivol if 120 kv scanning was performed , were recorded . in making our comparison with prior scans , we assumed that the iv contrast dose given at the prior scan was the routine dose and flow rate according to our usual contrast protocol . had the patient &# 39 ; s weight or renal function been considerably different at the time of the prior scan , they may have received a greater or lesser dose than the dose we assumed . it is contemplated that modifications to the low - ivcd protocol and the low - radiation dose protocol may be desirable in some circumstances . for example the low dose technique works better in scanners with larger detector rows and larger generators , as the tube limit is less likely to be encountered , allowing the use of 100 kv in more patients . also , on a 128 - slice or dual source scanners , 100 kv is used on patients of up to 41 cm width , whereas on a 64 - slice scanner 100 kv is used only on patients of & lt ; 39 cm width . protocols have been customized for use on siemens and ge scanners ( ge protocol not shown ). different customization may be desirable for other vendors . of 17 patients receiving the low radiation dose protocol , 11 patients received a dose reduction in excess of 40 % and 3 smaller patients received a dose reduction of approximately 50 % or more . the reason that the mean dose reduction was only 39 % is at least in part due to human error ; in several cases , the technique was not lowered to the full extent allowed . with greater patient numbers , appropriate patient selection and greater technologist experience , we believe that we could more consistently achieve dose reductions of 40 - 50 %. finally , we believe that addition of noise reduction methods to these images will result in additional incremental radiation dose or intravenous contrast dose savings . in conclusion , we have demonstrated that with optimized scan protocols and the use of patient size - based low - kv selection it is possible to perform ct of the abdomen and pelvis with substantially lower doses of intravenous contrast or lower radiation doses . although we chose to implement these studies in patients with lymphoma undergoing follow - up scans , the same protocols could also be used for other clinical indications . knowing that additional dose reduction can be achieved by lowering the scan kv , two new body scan protocols were developed , both using a size - specific kv selection . with irb approval , the following data were recorded on all patients who were scanned with the low dose protocols in whom there was a research authorization in place : age , width skin - to - skin at the level of the mid - portion of the liver , measured from the ap topogram , optimal kv as determined by the protocol , actual kv used ( in some cases actual kv was higher than optimal kv because scanning with the optimal kv would have exceeded the tube limit of ma ). the width skin - to - skin may be measured at the dome of the liver . for patients & lt ; 50 , the ctdivol at the original reference technique ( 120 kv , 240 reference mas ) and the ctdivol using the new protocol was recorded . for patients & gt ; 50 with the low ivcd protocol , the following were recorded : reference iv contrast dose , actual iv contrast dose , flow rate , percent change in ivcd . attenuation measurements were made from each scan and from the most recent prior scan . attenuation was measured in the aorta at the level of the diaphragm and in the right hepatic lobe at the level of the bifurcation of the main portal vein , avoiding inclusion of hepatic vessels . a region of interest was placed in the anterior subcutaneous fat to measure noise . icnr was calculated for the aorta and liver according to the formula icnr = attenuation ( hu )/ noise in subcutaneous fat ( hu ). one reader reviewed each abdomen / pelvis scan in random order , blinded to whether is was a study scan or the compare scan , and rated it for image quality on the same 5 - point scale that was used in the first phase of the study . 60 patients underwent ct with either reduced ivcd ( n = 43 ; patients & gt ; 50 years ) or reduced radiation dose n = 17 , age & lt ; 50 ). 1 patient was excluded from the & gt ; 50 year group because their prior scan had been performed elsewhere , and the scanning technique was not consistent with our reference protocol . the 42 patients & gt ; 50 years were scanned with a mean ctdi vol of 18 . 4 +/− 3 . 0 mgy , not significantly different from the mean reference dose of 19 . 8 +/− 3 . 0 that would have been given had a routine scan protocol been performed . mean iv contrast dose administered in this group was 99 . 5 ± 18 . 5 ml , versus 133 . 7 +/− 22 . 6 cc had they received routine contrast dose . this represents a mean dose reduction of 34 %. mean iq for this group was 4 . 6 , versus 4 . 7 in the prior comparison scan performed with routine iv contrast dose ( p - value = 0 . 273 ). there was no significant difference in liver icnr between the study scans and the prior scans , and a 12 % increase in aorta icnr ( p = 0 . 026 ) on the study scans versus the prior scans . 17 patients under the age of 50 were scanned with low radiation dose . the mean ctdi vol was 12 . 5 ± 4 . 1 mgy , versus a mean reference ctdi vol of 20 . 5 ± 4 . 5 mgy in these patients had they been scanned with routine protocol at 120 kv , with a mean dose reduction of 39 %. mean liver icnr was 8 . 6 ± 1 . 9 versus 9 . 0 ± 2 . 1 on the prior scans . mean aortic icnr was 13 . 0 ± 2 . 7 versus 12 . 2 ± 2 . 9 . on the prior scans . mean iq score was 4 . 3 , versus 5 . 0 ( p - value = 0 . 0005 ). we have shown that with the use of the age - specific protocols , there can be substantial reductions in either iv contrast dose or radiation dose , whilst maintaining diagnostic image quality . we had several reasons for electing to implement the low dose protocols in outpatients with lymphoma undergoing follow - up rather than in other patient groups . firstly , the lymphoma patients have prior scans available against which we could compare the low dose scans . they tend to be scanned frequently , often at 3 - 12 month intervals , so they potentially have more to gain from being scanned with either lower radiation dose or lower iv contrast dose than patients undergoing a single scan for an indication such as abdominal pain or weight loss . we chose follow - up scans in lymphoma outpatients rather than other oncology outpatients as we were looking to detect lymphadenopathy and changes in size of lymph nodes , rather than looking for subtle low attenuation lesions in organs such as the liver . we have demonstrated that with the low dose protocols there is satisfactory hepatic enhancement , icnr and iq . the protocols are readily amenable to being implemented into routine practice for many indications . particular instances where the low ivcd protocol are advantageous are any patients at greater risk of contrast induced nephropathy such as patients with renal insufficiency and diabetes , and patients with poor iv access in whom we need good hepatic enhancement yet only a small iv cannula can be placed and a slow injection flow rate used . we made certain assumptions regarding iv contrast dose . we have standard weight based iv contrast protocols in our practice . when calculating the contrast dose savings on the study scans versus the prior routine full - dose scan , we assumed that the dose given at the prior scan was the routine dose that would have been given according to our usual contrast protocol . had the patient &# 39 ; s weight or renal function been considerably different at the time of the prior scan , they may have received a greater or lesser dose than the dose we assumed . similarly , it is possible that a patient could have received their injection on the prior scan at a rate slower than our default 3 cc / sec because of poor iv access , and this could negatively impact the enhancement on their prior scan . we elected to use a saline chaser in the low ivcd patients , whereas in our routine practice we do not use a chaser . it is arguable that we saw no decrease in aortic and hepatic enhancement in our low ivcd patients at least in part due to use of the chaser . however , had we not used a saline chaser our injection duration in the low - ivcd patients the scan duration would have been on average 11 seconds shorter ( mean decrease in contrast dose 34 cc / 3 cc per sec flow rate ), so we may have needed to adjust either our injection rate or scan delay or both to give comparable aortic and hepatic enhancement . by giving the saline chaser we did not need to alter our scan delay . it has been estimated that a saline chaser may result in “ savings ” of 12 - 20 ml of contrast in a routine clinical setting , which is somewhat less than the mean 34 ml that we saved . further , in a recent review of the literature on the use of saline chasers , it was found that a saline chaser does not improve contrast enhancement of the liver in clinical images , and although there was a tendency for improved aortic enhancement , it was not statistically significant . based on the findings of the study , it may be desirable to make slight modifications to the low - ivcd protocol for some settings . the protocol works better in scanners with larger detector rows and larger generators , as with these scanners the tube limit is less likely to be encountered , allowing the use of 100 kv in a greater number of patients . for example , on the 128 - slice or dual source scanners , we can use 100 kv on patients of up to 41 cm width , whereas on a 64 - slice scanner 100 kv is used only on patients of under 39 cm width . our protocols were customized for use on siemens scanners and ge scanners ( protocol not shown ). different customization may be needed for other vendors . in patients receiving the low dose protocol , we achieved a mean dose reduction of 39 %. this almost equates to the lower dose we could have achieved merely by tolerating more noise , as concluded in the first phase of the study . by making the additional protocol modifications , in particular , lowering the kv , we would have expected a greater mean dose reduction , of 46 - 50 %. that we did not achieve this much dose reduction is at least in part due to human errors . in several cases , the technologists did not correctly lower the technique to the full extent allowed so the patients did not receive the dose reduction that they could have . we elected not to exclude these patients because our study numbers are small , and because the difficulty experienced by the technologists may accurately reflect the challenge of applying the protocol in a real life situation . with greater patient numbers , appropriate patient selection and greater technologist experience , dose reductions of 40 - 50 % can be achieved more consistently . in conclusion , we have demonstrated that with optimized scan protocols and the use of patient size - based low - kv selection it is possible to perform ct imaging , for example , of the abdomen and pelvis with substantially lower doses of intravenous contrast or lower radiation doses . the present invention has been described in terms of one or more preferred embodiments , and it should be appreciated that many equivalents , alternatives , variations , and modifications , aside from those expressly stated , are possible and within the scope of the invention .

US-201213654496-A

a biological information sensing device capable of minimizing the variations of the support for a sensor portion or the displacement thereof despite the exposure of the device to accelerative motion during exercise or regardless of the size of a neck - like portion of a user is provided . a biological information sensing device applied to a neck - like portion , including a predetermined measurement area , of a living organism as holding a sensor body thereof in intimate contact with the predetermined area for sensing biological information of a living organism , the device comprises a flexible sensor structure including the sensor body and a flexible strap - like sensor holder for holding the sensor body ; and a strap for fastening the sensor structure to the neck - like portion of the living organism , and is characterized in that an engaging portion of the strap or an engaged portion of the sensor holder extends along a longitudinal direction of the strap for permitting the engaged portion of the sensor holder of the sensor structure to be engagedly secured to the engaging portion of the strap at an optional position along the longitudinal direction of the strap .

some of the preferred modes of the invention will be described with reference to the preferred embodiments thereof shown in the accompanying drawings . as shown in fig1 a , an arterial pulse wave detector 1 as the biological information sensing device of a preferred embodiment of the invention comprises a flexible sensor structure 30 including a sensor body 10 and a sensor holder 20 in the form of a flexible strap serving to hold the sensor body 10 ; and a strap 40 for fixing the sensor structure 30 to a wrist a . the flexible strap - like sensor holder 20 of the sensor structure 30 is provided with a hook fastener 23 on an outside surface 22 of a flexible strap piece 21 , the hook fastener 23 extending a length l1 along a longitudinal direction or an extension direction l of the strap piece . the strap 40 includes a flexible strap body 50 , and a fastening hardware structure 60 . the strap body 50 is provided with a loop fastener 52 on an inside surface 51 thereof , the loop fastener formed in complementary relation with the hook fastener 23 for engagement therewith and extending a length l2 along the longitudinal direction or extension direction l of the strap body . the pair of hook and loop fasteners 23 , 52 in face - to - face relation are pressed against each other along respective directions f1 , f2 and secured to each other , thereby securing the sensor structure 30 to the strap 40 including the strap body 50 . the hook and loop fasteners 23 , 52 extend the respective lengths l1 , l2 along the longitudinal direction l . thus , within a range between a position where an la - wise end 23 a of the hook fastener 23 opposes an lb - wise end 52 b of the loop fastener 52 and a position where an lb - wise end 23 b of the hook fastener 23 opposes an la - wise end 52 a of the loop fastener 52 , the hook fastener 23 is at least partially engageable with the loop fastener 52 even though the hook fastener 23 is shifted relative to the loop fastener 52 . therefore , the hook fastener 23 can be secured to the loop fastener 52 . accordingly , the sensor structure 30 is fixable to the strap 40 with its position adjusted generally in the range of l1 + l2 along the l - direction . in the illustrated example , the hook fastener 23 is disposed at a place shifted from a back side of the sensor body 10 along the l - direction . however , the hook fastener 23 may be so located as to overlap the back side of the sensor body 10 , so long as a pressure for pressing the sensor body 10 against the wrist portion a can be constantly maintained within a predetermined range . it is noted that the pair of hook and loop fasteners 52 , 23 may be replaced by another desirable pair of engagement means so long as the engagement means permit the sensor holder 20 of the sensor structure 30 to be engaged with and fixed to the strap 40 at any practically optional position along the longitudinal direction l of the strap 40 . such a pair of engagement means may be a combination of , as shown in fig6 a and 6 b , an engaging portion 110 having a mushroom - like projection 113 including a column - like shaft 111 having a disc - like head of a greater diameter 112 at its distal end , and an engaged portion 120 having a plurality of engaged hole 123 arranged along the longitudinal direction l , the engaged hole 123 including a circular hole 121 for disengageably receiving the greater - diameter head 112 of the mushroom - like projection 113 , and a notch 122 formed at place of a circumference of the circular hole 121 for fittingly receiving the column - like shaft 111 . in a case where a portion formed with the hole 123 ( the strap body 50 of the strap 40 , for example ) has a thickness g practically smaller than a height h of the shaft 111 , the greater - diameter head 112 of the projection 113 of the engaging portion 110 may be inserted into the circular hole 121 of the engaged hole 123 of the engaged portion 120 to bring the column - like shaft 111 into fitting engagement , and then the engaging portion 110 may be moved along a wr - direction relative to the engaged portion 120 thereby bringing the column - like shaft 111 of the projection 113 of the engaging portion 110 into engagement with the notch 122 of the engaged portion 120 . it is noted herein that either one of the pair of components engaging with each other or locking to each other is referred to as “ the engaging portion ”, while the other is referred to as “ the engaged portion ”. in this case , a typical practice is to form the engaged portion 120 at the strap 40 and to form the engaging portion 110 at the sensor holder 20 of the sensor structure 30 . however , in a case where a slit is formed at a portion of the sensor structure 30 in the direction of its thickness , the engaged portion 120 including the engaged hole 123 may be formed in the sensor structure 30 . it is noted that the shape and distribution of the projection 113 constituting the engaging portion 110 as well as the shape and distribution of the hole 123 constituting the engaged portion 120 may be changed as desired . in the example shown in fig1 and the like , the fastening hardware structure 60 of the strap 40 has a fastening hardware 63 including a pair of pins or shafts 61 , 62 . one 61 of the shafts of the fastening hardware 63 is engaged with a loop - like end 53 of the strap body 50 whereas the other shaft 62 thereof is engageable with the other end 54 of the strap body 50 . a pair of hook and loop fasteners 57 and 58 are also provided on surface portions 55 and 56 of the end 54 of the strap body 50 . the hook fastener 57 on the surface portion 55 is pressed against the confronting loop fastener 58 on the surface portion 56 thereby fixing the end 54 of the strap body 50 . cylindrical peripheries of the shafts 61 , 62 are typically rotatable about respective axes of the shafts . when the arterial pulse wave detector 1 is used on the wrist a of the user , the following procedure may be taken to assemble the arterial pulse wave detector 1 as shown in fig1 b , for example . the sensor structure 30 , shown in fig1 a , is fixed to the strap 40 at a desired position with respect to the l - direction according to the size of the user &# 39 ; s wrist a ( fig1 c ) by means of the hook and loop fasteners 23 , 52 . subsequently , as shown in fig1 c , the sensor structure 30 is positioned in a manner that the sensor body 10 is pressed against a surface area a1 of the wrist a where the radial artery b is close to the wrist surface . then , after threading the end 54 of the strap body 50 through the fastening hardware 63 , the detector 1 is so positioned as to bring the shaft 62 into contact with a bump area a2 corresponding to the cubitus d . subsequently , the strap 40 is tightened by pulling the end 54 of the strap body 50 , and the hook and loop fasteners 57 , 58 at the end 54 are pressed against each other thereby fixing the strap body 50 . the l - direction position of the sensor structure 30 relative to the strap 40 may be selectively set such that with the sensor body 10 positioned to confront the surface area a1 of the wrist near the radial artery b , the rotary shaft 62 may correspond to the bump area a2 at the cubitus d . this provides for an easy and positive fastening of the strap 40 . although the sensor structure 30 of the example shown in fig1 a to 1 c has a length of about less than a half of an outside circumference of the wrist portion a , the sensor structure 30 may have a greater length than this . as shown in fig1 d , for instance , the sensor structure may have a length of about ¾ or more of the outside circumference of the wrist portion a . in the case of a sensor structure 30 a of the greater length as shown in fig1 d , the elongate flexible sensor structure 30 a is disposed in a manner to overlap the strap body 50 except for a region where the fastening hardware structure 60 of the strap 40 exists . specifically , of the wrist a substantially of an elliptic or oval section , an area a3 having a relatively great curvature near the radius b1 as well as areas a4 , a5 on both sides thereof having smaller curvatures are used as portions along which the sensor structure 30 extends , so that the area a2 of a great curvature near the bubitus d may be utilized for fastening the strap to place by means of the fastening hardware structure 60 . this permits the strap 40 to be effectively fastened to place . as indicated by a phantom line 40 b in fig1 d , for example , a part of the strap 40 may comprise an elastic strap piece 40 b such as of a rubber material in order that the strap 40 may present a generally constant fastening force . it goes without saying that such a strap including the elastic strap piece may also be used for securing the sensor structure 30 shown in fig1 a to 1 c . where the sensor structure 30 is the sensor structure 30 a having the length to surround the most part of the wrist a as shown in fig1 d , a circuit portion 70 of the sensor structure 30 a comprises , as shown in fig2 a for example , the following components arranged in blocks in addition to an arterial pulse wave sensor portion 15 comprising the sensor body 10 including a supersonic transmitter 11 and a supersonic receiver 12 , the components including an oscillating / actuating portion 72 for the supersonic transmitter 11 of the sensor body 10 ; an arterial pulse wave receiving portion 74 for extracting an analog arterial pulse signal from a supersonic signal received by the supersonic receiver 12 of the sensor body 10 ; a digital signal processing portion 76 for converting the arterial pulse signal extracted by the arterial pulse wave receiving portion 74 into a digital signal and processing the resultant digital signal ; and a display portion 78 for displaying the processing results given by the digital signal processing portion 76 ( incidentally , the sensor structure 30 shown in fig1 a to 1 c typically includes the same circuit portion 70 , as well ). the circuit components 72 , 25 , 74 , 76 and 78 constituting the circuit portion 70 of the sensor structure 30 each comprise a circuit board and a circuit device incorporated in the circuit board . the circuit components are each connected with the respective adjoining circuit component 15 , 74 , 76 or 78 via a respective flexible cable 81 , 82 , 83 or 84 . it is noted here that each of the circuit boards may be a printed wiring board such as formed of a resin or ceramic , or a circuit board per se forming an integrated circuit board . in the examples shown in fig2 a , 2b and 1 d , the circuit boards are typically rigid , but the circuit boards themselves may have flexibility . the sensor holder 20 of the sensor structure 30 is formed of a flexible strap material such as a urethane resin , and includes , for example , strap forming bases 24 , 25 , 26 , 27 and 28 individually serving to support their respective circuit components 72 , 15 , 74 , 76 and 78 , and interconnection portions 29 for interconnecting the forming bases 24 to 28 . fig2 a and 2b illustrate the example where the sensor holder 20 is formed of a material having a greater rigidity than that of the sensor holder shown in fig1 d . the degree of flexibility of the sensor holder 20 may be selected according to requirements with the proviso that the sensor holder 20 is soft or flexible enough to permit the sensor body 10 to be positioned / fixed . the strap forming bases 24 , 25 , 26 , 27 and 28 of the sensor holder 20 have the corresponding circuit components 72 , 15 , 74 , 76 and 78 laid thereon or embedded therein . in this connection , the strap forming bases 24 , 25 , 26 , 27 and 28 are previously formed with recesses or openings on either one surface or both surfaces thereof for receiving therein the corresponding circuit components 72 , 15 , 74 , 76 and 78 such that the circuit components 72 , 15 , 74 , 76 and 78 maybe disposed / fixed therein . for instance , the sensor body 10 may be so disposed on the associated portion 25 of the sensor holder 20 as to project from an inside surface of the sensor holder 20 , whereas the circuit component 78 including the display portion may be so disposed on the associated portion 28 as to be visually recognized from an outside surface of the sensor holder 20 . such a structure may be constructed , for example , by placing the circuit components 72 , 15 , 74 , 76 , and 78 in the corresponding recesses and then interconnecting the adjoining circuit components by means of the respective flexible cables 81 , 82 , 83 and 84 . if desired , of course , at least some or all of the circuit components 72 , 15 , 74 , 76 and 78 may be formed integrally with the corresponding strap forming bases 24 , 25 , 26 , 27 and 28 at the forming of the strap forming bases 24 , 25 , 26 , 27 and 28 so that the circuit components are embedded in the corresponding strap forming bases 24 , 25 , 26 , 27 and 28 of the sensor holder 20 . as shown in fig5 for example , the sensor portion 15 comprises a common substrate 14 incorporating therein the sensor body 10 including the supersonic transmitter 11 and the supersonic receiver 12 individually including a piezoelectric device . in the arterial pulse wave detector 1 , as shown in fig3 a , the supersonic transmitter 11 of the sensor body 10 is actuated to transmit a supersonic signal p 1 under the control of the oscillating / actuating circuit portion 72 including a high - frequency oscillator circuit 72 a and a sensor actuating circuit 72 b while the signal p 1 is reflected as impinging upon blood components , such as blood cells or the like , in blood flowing through the radial artery b . the supersonic signal emitted from the supersonic transmitter 11 is typically the signal p 1 practically having a constant frequency and amplitude , as shown in fig4 a , for example . a supersonic signal p 2 reflected by the blood components in blood as a pulsing stream through the radial artery b and received by the supersonic receiver 12 is modulated in frequency due to the doppler effect associated with the pulse of the blood components as the reflector of the transmitted supersonic signal p 1 . hence , the signal p 2 assumes a form as shown in fig4 b , for example . the arterial pulse wave receiving portion 74 for extracting an analog arterial pulse signal p 4 from the supersonic signal p 2 received by the supersonic receiver 12 of the sensor body 10 includes , for example , a doppler signal detector circuit 74 a , a filter / amplifier circuit 74 band an arterial pulse signal detector circuit 74 c , as shown in fig3 a . an output from the doppler signal detector circuit 74 a is , for example , an electrical signal of a similar wave form p 2 to that of the received supersonic signal p 2 . the filter / amplifier circuit 74 b amplifies an amount of variation of the doppler signal p 2 ˜ sin {( ω + δω ) t } using the original transmission signal p 1 ˜ sin ( cot ) as a reference or a reference signal , so as to extract a differential amplification signal p 3 ˜{ sin ( δω / 2 ) t }· sin {( δω / 2 )} t as shown in fig4 c . it is noted here that ω denotes an angular frequency of the supersonic signal p 1 , and that δω = δω ( t ) denotes a modulated angular frequency dependent upon time t due to the doppler effect . in the arterial pulse wave receiving portion 74 , the arterial pulse signal detector circuit 74 c extracts , as the arterial pulse signal p 4 , an amplitude modulated component from the differential amplification signal p 3 . in the case of a square law detection , the arterial pulse component p 4 can be extracted as sin {( δω ) t }. although fig4 show the arterial pulse wave p 4 quite in a simple wave form , the arterial pulse wave p 4 actually presents much more complicated time - dependent wave form than that of fig4 d . particularly in a state where the cardiopulmonary circulatory system is overtaxed during or after exercise , the arterial pulse wave assumes a much more complicated and irregular wave form containing a wide range of high frequency components . in the case of an arterial pulse wave detector 1 shown in fig3 a , the digital signal processing portion 76 includes an analog / digital ( a / d ) converter circuit 76 a for converting the analog signal p 4 indicative of the arterial pulse wave into a digital signal p 5 indicative of the arterial pulse wave ; a central processing unit ( cpu ) 76 b for receiving the digital arterial pulse signal p 5 ; and a low - frequency oscillator circuit 76 c for supplying the cpu 76 b with a reference signal for processing . in this case , the cpu 76 b includes a memory for storing a frequency - of - pulse operation program and a microprocessor for executing the program , thus forming a frequency - of - pulse operating portion 76 d for operating the frequency of pulse based on the digital arterial pulse signal p 5 with reference to the low - frequency signal from the low - frequency oscillator circuit 76 c . typically , the cpu forms a digital signal processor ( dsp ) wherein a part of the frequency - of - pulse operation program including a fast fourier transformation ( fft ) process is incorporated in a digital signal processor circuit . it is noted that the cpu 76 b further includes a device operation portion 76 f for receiving an operation command from an operation command input portion 76 e such as a push - button switch . according to fig3 a , the display portion 78 comprises a display unit for displaying the operation result or frequency of pulse q determined by the frequency - of - pulse operating portion 76 d of the cpu 76 b . in a case where the sensor structure 30 or 30 a includes the display portion 78 , the strap forming base 28 including the display portion 78 may be provided with the display portion 78 at place near one end thereof with respect to a width - wise direction w thereof as shown in fig2 c or at a central portion thereof with respect to the width - wise direction w thereof as shown in fig2 d . in the former case , as shown in fig2 c for example , a region of the strap 40 , that is overlapped by the strap forming base 28 , is formed in an adequately smaller width w2 than a width w1 of the strap forming base 28 in order to permit the view of the display on the display portion 78 . alternatively , the strap 40 may be formed in a width equal to or greater than that of the strap forming base 28 and a side edge portion of the strap forming base 28 , that is overlapped by the display portion 78 , maybe formed of a transparent material . in the latter case , the strap 40 includes an opening 40 a at its region overlapped by the display portion 78 of the strap forming base 28 in order to permit the view of the display on the display portion 78 disposed centrally with respect to the width - wise direction w of the strap , as shown in fig2 d . of course , the opening 40 a may be formed of a transparent material . according to the foregoing description , the a / d converter circuit 76 a , the operation command input portion 76 e and the like belong to the digital signal processing portion 76 . however , the a / d converter circuit 76 a may belong to , for example , an output circuit portion of the arterial pulse wave receiving portion 74 for processing the analog signal . further , the operation command input portion 76 e like a push - button switch may be integrally formed with the display unit 78 as an article . similarly , the other components may be freely combined into blocks , as desired , so long as such combinations contribute to the mass distribution as a whole . needless to say , the cpu 76 b may perform other operations during spare - time when the frequency of pulse q is not operated or at an interval between the operations of the frequency of pulse q . one example of the other operations include a time counting operation as a clock . specifically , the cpu 76 b is , for example , capable of performing the time counting operation as a timer and hence , the display portion 78 is also capable of functioning as a display of a digital clock . the arterial pulse wave detector 1 of the above construction may be worn on the wrist a as follows . the arterial pulse wave detector 1 is placed around the wrist a in a manner to bring the sensor body 10 of the sensor portion 15 into abutment against the wrist surface area a1 near the radial artery b of the wrist a . with the fastening hardware 63 of the fastening hardware structure 60 positioned at the wrist bump area a2 near the cubitus d , the strap piece 54 is threaded through the fastening hardware 63 and pulled along a j - direction . then , the strap piece 54 is fixed by means of the hook and loop fasteners 57 , 58 . when the arterial pulse wave detector 1 is wrapped around the wrist in this manner , the sensor structure 30 of the arterial pulse wave detector 1 has substantially uniform mass distribution along the longitudinal direction thereof . therefore , even when the wrist a is subjected to the accelerative motion due to exercise or the like , such a great inertia force as to bring the arterial pulse wave detector 1 into mono - directional rotation about the wrist a will not actually occur . accordingly , the sensor body 10 of the sensor portion 15 of the arterial pulse wave detector 1 is maintained in intimate contact with the measurement area a1 , thus achieving the precise measurement of the arterial pulses . since the sensor body 10 and the display portion 78 , as a part of the circuit portion 70 , are unified as one piece , mediation of a sliding contact and the like is dispensed with . thus , there is no fear of noises during the signal processings . another approach may replace the direct display of the frequency of pulse q on the display portion 78 shown in fig3 a . as shown in fig3 b , a transmitter portion 78 a including an antenna or coil is adapted to transmit the data on the frequency of pulse q , obtained by the frequency - of - pulse operating portion 76 d , in the form of an electromagnetic signal r such as of an electromagnetic wave or variable magnetic field , whereas a separate receiver portion 78 b receives the electromagnetic signal r , from which the frequency of pulse q is extracted to be displayed on a display unit 78 c . in this case , the arterial pulse wave detector worn on the wrist of one arm takes the form of a headless strap while , for example , the frequency of pulse q may be displayed on the display unit 78 c with a clock function which is worn on the other arm . this permits the whole body of the display unit 78 c prone to heavy weight to be mechanically separated from an arterial pulse wave detector 1 b , contributing to the weight reduction and mass distribution of the arterial pulse wave detector 1 b . as a result , the possibility of variations of the pressure for pressing the sensor body 10 of the arterial pulse wave detector 1 b against the wrist a or displacement of the sensor body 10 of the detector 1 b relative to the area al of the wrist a can be reduced . in this case , as well , the display unit 78 c having the clock and other functions may be adapted to be worn on the wrist a by means of the strap 40 having a pair of pins 91 , 92 pivotally movable about their axes , as shown in fig1 e for example . the arterial pulse wave detectors shown in fig1 a to 1 c and 1 e are practically constructed the same way as the arterial pulse wave detectors shown in fig1 d , 2a and 2 b , except that the sensor structure has a smaller length than that of the arterial pulse wave detectors of fig1 d , 2a and 2 b , and that the circuit boards constituting the sensor structure are generally unified into one piece by a more flexible sensor holder 20 . if desired , however , a greater part of the circuit portion involved in the signal processings and the like may be separated from the sensor structure 30 so that the sensor structure 30 may have a relatively smaller size .

US-34988603-A

a patient &# 39 ; s body temperature is regulated by using an enclosure to enclose a portion of the patient &# 39 ; s body in an isolated environment . in accordance with one embodiment , the patient &# 39 ; s entire body below his head is enclosed . once enclosed , the patient is surrounded by heated vapor that is injected into the enclosure . the heated vapor condenses on the patient &# 39 ; s skin to warm the patient quickly , efficiently and safely . this embodiment is well suited for the treatment of hypothermia patients . in accordance with alternative embodiments , only a portion of the patient &# 39 ; s head is enclosed . in these embodiments , an enclosure is placed on the patient &# 39 ; s head , and heated vapor is fed into the enclosure . excess air and vapor are preferably dissipated by vents in the cap , whereas excess condensate is preferably absorbed by an absorbent layer provided in the cap . these embodiments are well suited for regulating a patient &# 39 ; s body temperature in a surgical setting . tympanic temperature is monitored and thus vapor dew point temperature is controlled to less than 47 ° c . but greater than tympanic temperature . heated vapor may heat other articles such as intravenous supply bags . the heated vapor for many locations in a building may be supplied from a central steam generator .

the present invention provides a means of regulating body temperature . this strategy employed in the present invention has particular applications in surgical environments and in the treatment of hypothermic patients . both of these embodiments rely on enclosing a portion of a patient &# 39 ; s body and surrounding the enclosed portion with heated vapor . the heated vapor condenses on the patient to bring about heating of the enclosed portion of the patient and in some instances , of the patient as a whole . the primary benefits of this approach are that it is quick ; it does not cause harm to tissue exposed to the heated vapor ; and it is very efficient . fig1 depicts the first embodiment of the present invention . this embodiment is ideally suited for treating patients that are suffering from hypothermia . in accordance with this embodiment , the hypothermic patient 10 is placed inside an enclosing body bag 12 . this body bag 12 covers the patient 10 from the head down . portions of the patient &# 39 ; s neck are likely to be exposed . the enclosing body bag 12 provides an enclosure that is non - porous and that isolates the patient 10 from the surrounding environment . the material is preferably made from a thermally insulative material so that heat inside the enclosure does not escape to the surrounding environment . once the patient 10 is properly placed within the enclosing body bag 12 , a tympanic monitor 14 is placed in the patient &# 39 ; s ear . a preferred monitor is disclosed in u . s . patent application , ser . no . 07 / 666 , 744 . the tympanic monitor 14 determines the temperature at the patient &# 39 ; s tympanic membrane . research has indicated that such a measurement is an extremely accurate indicator of the patient &# 39 ; s core temperature . the core temperature is widely regarded as the best available measurement of true body temperature . the tympanic monitor 14 is coupled to a controller 20 of a vapor generator 18 . the vapor generator 18 is utilized to generate heated vapor that is injected along with air as a saturated mixture into the enclosing body bag 12 . in particular , vapor mixture produced by the vapor generator 18 travels through a conduit 22 into the enclosing body bag 12 . the vapor mixture is distributed throughout the enclosing body bag 12 so as to surround the patient 10 . because the temperature of the heated vapor is higher than the temperature of the patient 10 , condensation occurs at the patient &# 39 ; s skin . this condensation brings about heat transfer from the heated vapor to the patient &# 39 ; s body 10 . the resulting heat transfer produces a quick and efficient increase in the patient &# 39 ; s body temperature . a temperature of about 110 ° fahrenheit provides sufficient heat transfer without injury . a controller 20 directs the activity of the vapor generator 18 . the vapor generator 18 responds to the body temperature measurements sent from the tympanic monitor 14 . specifically , it adjusts the temperature of the air / vapor mixture that is being produced . circulation of the vapor and air is aided by a fan 17 provided within the vapor generator 18 . the vapor generator 18 operates by bubbling hot air through a volume of water . the bubbling brings about evaporation of the water into the air . sufficient water and air interface , in area and time , should be provided so that the air is fully saturated with water ( i . e . 100 % relative humidity ). less than fully saturated will provide the required condensation so long as the dew point of the vapor is greater than the blood temperature . the temperature of the air that is bubbled through the water and / or the temperature of the water may be adjusted to produce a mixture of water and air having a suitable temperature ( i . e . 43 ° c .) for application to the patient . an alternative approach that may be adopted for the vapor generator 16 is to generate steam and to mix the steam with air to produce a fully saturated mixture of air and vapor having a suitable temperature controlled by the relative amounts of air and steam . it should be noted that each approach is equally viable , and both are intended to be embodied within the present invention . as mentioned above , the exposure of the heated vapor to the patient 10 results in a certain amount of condensation . this embodiment provides a means for gathering the condensation so that it may be recycled by the vapor generator 18 . specifically , the patient 10 is preferably oriented at a slight slope relative to the horizontal plane so that the condensation and air flow towards the condensation and air return 24 . the resulting condensate and air are already heated to some extent and , thus , do not need to be heated as greatly when they are recycled . they - travel via the return 24 to the vapor generator 16 wherein the condensate passes through the heat generator 18 to be heated and vaporized . the heated air continues along to the conduit 22 where it , once again , entrains additional heated vapor . the inclusion of the condensation and air return 24 increases the efficiency of the system . for reasons of contamination control , the system could be constructed without condensate or air return , by providing suitable venting for spent air / vapor mixture , and suitable condensate storage or drainage . benefits provided by this embodiment include that it is quicker than other embodiments . the vapor can be generated essentially instantaneously , whereas in the water bath strategy time is wasted in preparing the warm bath . secondly , because this embodiment utilizes a tympanic monitor 14 with feedback and because the heat delivered by the vapor can be quickly controlled , this invention is a far more controlled strategy than mere submergence in a water bath . the second approach of the present invention concerns a body temperature regulating means that maintains a patient &# 39 ; s body temperature without a body bag . this particular embodiment is designed for use in a surgical environment . all of the components of this embodiment can be readily sterilized . in the embodiment of fig2 and 3 , instead of entirely encapsulating the patient 10 with an enclosing body bag 12 , a cap 26 is provided to cover the top surface of the patient &# 39 ; s head . it is similar to its enclosing body bag counterpart in that it isolates a portion of the patient &# 39 ; s body . it is also similar in use of the vapor generator 18 . the heated vapor mixture is forwarded to the cap 26 via a conduit 22 . the system is designed so that the vapor generator 16 can be placed in close proximity to the patient 10 in a surgical environment . the system maintains a patient &# 39 ; s body temperature during a surgical procedure . the cap 26 is placed on the patient 10 at the initiation of a surgical procedure . a tympanic monitor 14 is inserted into the patient &# 39 ; s ear to furnish continuous data regarding the patient &# 39 ; s body temperature . like the previously described embodiment , the tympanic monitor 14 is coupled to the controller 20 of the vapor generator 18 . this feedback is especially important in the surgical environment where it is desirable to maintain a steady body temperature . this embodiment , however , does not have the condensation and air return 24 . exposure to the patient &# 39 ; s body contaminates the condensation and air . it is , therefore , undesirable to recycle the contaminated condensation and air back through the vapor generator 18 because the recycling could contaminate the vapor generator 18 . although the condensation air return 24 is not utilized in this embodiment , there are still certain features provided in this embodiment that address the issues of excess condensation and air . to remove unwanted condensation , a liquid collector may be provided within the cap 26 . a primary candidate for such a collector is an absorbent band 27 of material as shown in fig3 filled with an absorbent gel . as condensation begins to accumulate on the patient &# 39 ; s head , the absorbent band 27 soaks up the condensation . preferably , an absorbent material which in the presence of moisture becomes a dry gel is provided in the band 27 . such material is currently employed in products such as baby diapers ( e . g . in ultra - pampers plus ®). the gel filled material adequately removes the condensation because only a small amount of liquid ( i . e . on the order of 8 ounces ) need be vaporized and condensed to transfer significant amounts of heat , on the order of 500 btus . with respect to excess air and vapor , they are allowed to escape through vents 29 provided in the cap 26 . fig4 a - 4c illustrate an alternative embodiment particularly suited to the surgical environment . in this embodiment , only the forehead is heated . the vapor is directed through a supply tube 42 to a manifold 40 having a lower surface contoured to fit over the forehead as a vapor enclosure . that lower surface is perforated with small vapor spray holes 44 . due to the high efficiency of the condensation heat transfer mechanism , only a small amount of vapor flow is required , so small holes are preferred to restrict flow and thus minimize the vapor generation requirements . to collect the condensate , pads of absorbent material extend from beneath the ends of the manifold alongside the patient &# 39 ; s head . any condensation on the forehead flows into the two absorbent pads 46 . the pads also serve to support the manifold 40 above the forehead to permit spraying of the vapor onto the skin . any noncondensed vapor passes freely from under the spaced manifold . the surgical embodiments utilize the fact that a great amount of heat transfer naturally occurs through the human head . in particular , there is a great deal of blood flow through the human head , and the blood that flows through the head is in close thermal communication with the external environment . typically , about 40 % of the heat transferred from the body is through the head , so a much more compact heat transfer unit may be used . on the other hand , if heat is applied to the human head , it is absorbed by the blood that is flowing through the head . the resulting heated blood travels throughout the rest of the patient &# 39 ; s body and keeps the patient &# 39 ; s body at a standard temperature . with heating , the natural response of the body is to increase blood flow and , thus , further improve heat transfer and distribution . by heating an area such as the forehead , only a very limited portion of the patient &# 39 ; s overall surface area need be heated . efficient heating can be obtained by a heating member applied to less than 5 % of the patient &# 39 ; s overall surface area . in fact , a typical patient has a total surface area of about ten square feet and an area of the forehead of only about fifteen square inches ( 1 % of the total ) may be heated to regulate the entire body temperature . by using such a strategy , the patient is kept warm without the problems of interference with the surgical procedure that have traditionally confronted medical personnel . heating of the forehead is particularly advantageous because it is generally exposed during surgery . furthermore , the strategy is very efficient and requires minimal amounts of water to generate sufficient vapor to maintain the patient &# 39 ; s body temperature . a model of the human circulatory system is illustrated in fig5 . blood pumped from the heart 50 is circulated through one principal loop which includes the brain 52 and , in parallel with flow through the brain , through the skin of the head and neck illustrated at 54 . a second principal loop services the rest of the body illustrated at 56 . blood returning from the head and body is mixed and pumped by the heart 50 through the lungs 58 and then again through the head and body . the tissue of the head loop has only about 5 % of the total mass of the body and 10 % of the total surface area ; however , about 20 % of the blood flow is through the head . thus , any heating through the skin of the head is quickly returned to the heart and lungs . with the brain , the heart and lungs are the critical organs in treating a hypothermic patient or in maintaining a patient &# 39 ; s temperature . tympanic temperature is the monitorable temperature which is closest to that of the brain . thus , the tympanic monitor 60 provides the most critical temperature feedback . that criticality is illustrated by fig6 . if a patient &# 39 ; s temperature were decreasing along the line 62 and the blood heated through the skin of the head , that heated blood would quickly reach the pulmonary artery and thus increase the temperature t pa . soon thereafter , the blood flow would reach the tympanic area and thus increase the tympanic temperature t t . only much later would the remainder of the body 56 increase in temperature due to the significantly lesser ratio of flow to mass . thus a rectal temperature t r would significantly lag the tympanic temperature . with the present invention , with feedback control of the vapor source , the tympanic temperature can be clamped at a desired level 64 . if one were monitoring the rectal temperature , it can be seen that the feedback system would cause excessive heat to be applied to the body even after the tympanic temperature had reached the desired level . fig5 illustrates yet another advantage of heating through the head rather than the main body . as noted , it is of primary interest that the heart , lungs and brain be properly heated . when one heats the blood through the main body 56 , vasodilation in the body results in a greater mass of blood at the skin . when heating the skin of the head , the skin vessels present a much lower mass even with dilation . thus , there is little remote storage of heated blood and the heart and lungs are promptly warmed . the model of fig5 illustrates an advantage of heating the patient through the forehead rather than through a body bag even in such applications as hypothermia . where heat is delivered through the large mass of the body with vasodilation , there is the risk of initially starving the heart of blood and also a risk of initially sending a large amount of not yet heated blood to the heart . by delivering the heat through the forehead , one does not substantially change the circulation path to which the body has limited itself , and the patient &# 39 ; s heart is heated before the main body . with the heart temperature up , the heart rate will increase . heart rate is the temperature control mechanism for the peripheral parts of the body , so heating of the main body will follow heating of the heart . once the tympanic temperature has reached normal , a peripheral temperature sensor can be used to check the sufficiency of blood volume . if , for example , the temperature of a toe does not increase , there is an indication that insufficient blood is being delivered through the body . additional liquid could then be added intravenously . to maximize heat flow to the blood , the blood flow rate should be maximized . that flow rate is controlled to a large extent by the local skin temperature . as illustrated in fig7 as saturated vapor temperature increases to about 42 ° c ., blood flow and thus the heat transfer per unit area increases . however , when the saturated vapor temperature exceeds about 42 ° c . the body initiates a defense mechanism to minimize injury due to excessive heat . above that temperature , vasoconstriction substantially reduces blood flow and thus heat transfer . thus , not only is it desirable to maintain a vapor dew point temperature of less than 43 ° c . to avoid injury , to maximize heat transfer it is preferred that the temperature be about 42 ° c . from fig7 a preferred range of temperature is 40 ° c . to 43 ° c . as illustrated in fig8 principles of the invention can be applied to inanimate bodies as well . in this example , a single vapor generator 80 is used not only to heat a patient 82 through a forehead enclosure 84 as previously described , but also to heat an intravenous supply bag 86 . the intravenous supply bag 86 is positioned in a simple enclosure 88 such as a vented plastic bag . a vapor / air mixture is delivered to that enclosure through a separate delivery tube 90 . as before , absorbent material 92 is provided in the bag 88 to collect any condensation . the thus heated blood or other liquid is then delivered to the patient through an intravenous tube 94 . as illustrated in fig9 the vapor generator need not be local to the patient or other body being heated . as illustrated , a steam generator 100 is located in a remote room of the building . that steam generator provides steam at 100 ° c . to each of several operating rooms , each having a valved steam outlet 102 . the steam generator 100 may be located in the same area as oxygen tanks 101 typically found in a hospital . the steam piping would then follow the same routing as the oxygen supply and be delivered to individual operating rooms in the same fashion as oxygen is delivered . an air mixer 104 mixes ambient air with the steam to create a vapor / air mixture of , for example , 42 ° c . for delivery to a headpiece 106 on a patient 108 . control of the vapor / air mixing is preferably in response to a tympanic temperature monitor 110 . wherein the present invention has been shown with reference to the preferred embodiments thereof , it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the spirit and scope of the invention as defined in the appended claims . for example , the system can be readily modified to provide cooling of a patient . in that case , a fine spray of cool water would be sprayed on the forehead and air would be blown on the forehead to evaporate the cool water . although much less desirable , heating may in some cases be obtained by a small water bottle covering a small area of the patient such as the forehead .

US-17953894-A

herein is disclosed a probe , including a first electrode disposed at least partially on the probe surface , a second electrode disposed at least partially on the probe surface , a first conductor electrically coupled to the first electrode , a second conductor electrically coupled to the second electrode , and a reactive element electrically coupling the first conductor and the second conductor .

the disclosed systems and methods in an embodiment use mri to allow multi - functional catheters to be placed without radiation , and provides very accurate localization of catheter tips in 3d space . with current mri scanners , resolution is limited by the distance the rf coil is from the volume of tissue being imaged . the signal from any particular imaging volume is picked up by an external detector coil . the gradients select a volume inside the body for imaging , but the coil outside the body picks up the signal from the imaging volume as well as the noise from all of the sample regions that are within its range . the farther the surface coil is from the imaging volume , the more noise can be present . mri has been proposed as an alternative imaging modality for guiding and monitoring ep procedures and offers several advantages over other modalities for electrophysiologic intervention . for example , the heart and endocardial landmarks can be visualized throughout the procedure . this anatomical information facilitates the identification of ablation sites for arrhythmias such as atrial flutter and fibrillation . in addition , cardiac motion and flow dynamics can be monitored during the procedure . this enables acute assessment of cardiac function as the intervention is performed . furthermore , mri does not employ ionizing radiation , such as x - rays , and is generally considered to be a minimal risk procedure . mri can facilitate the visualization of ablated tissue during the procedure . because lesions are typically invisible under x - ray fluoroscopy , it is currently difficult to discern whether tissue has been completely ablated , is only temporarily stunned ( i . e ., has been subjected to reversible thermal injury ), or indeed has not been treated at all . by actually visualizing the tissue lesion , mri enables positive confirmation of tissue treatment . this can be especially important for procedures that benefit from continuous lines of ablation , such as treatment for atrial flutter , atrial fibrillation , and isolation of pathologic tissue in the pulmonary veins . imaging of ablated tissue may allow what are now long and difficult procedures to be performed on a more routine and efficient basis . in an embodiment , an internal catheter receiving coil / antenna may be incorporated into an electrophysiologic rf ablation catheter that also includes electrodes for recording bio - potentials . because the receiving coil / antenna is closer to the imaging volume being targeted for ablation and may have a limited range of detection , the mri signal is increased and the noise from remote regions reduced , thereby providing an enhanced signal - to - noise ratio ( snr ), which enables higher strength mri gradients to be applied , thereby improving resolution where it is needed most . in an embodiment , mri can be used to facilitate catheter ablation of atrial fibrillation by guiding creation of continuous linear ablation lesions , and confirming that a complete linear lesion has been created ( line of block ) in combination with measurements of bio - potential . the visualization of areas of ablation and measurements of bio - potential may allow a reduction in the number of lesions needed , and may also reduce the number of recurrences , by more accurately ablating the arrhythmias . a reactive element can include an electrical component such as a capacitor , a resistor , an inductor , a diode , or various combinations of these . a reactive element can be a filter , such as a lowpass filter , a highpass filter , a bandpass filter , or a bandstop filter . a reactance can be a reactive element . a high frequency signal or high frequency energy can include energy that has a frequency of 10 megahertz ( mhz ) or higher . it can include energy that has a frequency of 60 mhz or higher . it can include energy that has a frequency of about 63 . 9 mhz . a low frequency signal or low frequency energy can include energy that has a frequency of less than 10 mhz . it can include energy that has a frequency of 500 kilohertz ( khz ) or less . it can include energy that has a frequency of 100 khz or less . it can include energy that has a frequency of 1 khz or less . it can include energy that has a frequency of 100 hertz ( hz ) or less . ablation frequency energy can include energy that has a frequency of less than 10 mhz . it can include energy that has a frequency of 500 kilohertz ( khz ) or less . it can include energy that has a frequency of 100 khz or less . it can include energy that has a frequency of 1 khz or less . it can include energy that has a frequency of 100 hertz ( hz ) or less . biopotential recording frequency energy can include energy that has a frequency of less than 10 mhz . it can include energy drat has a frequency of 500 kilohertz ( khz ) or less . it can include energy that has a frequency of 100 khz or less . it can include energy that has a frequency of 1 khz or less . it can include energy that has a frequency of 100 hertz ( hz ) or less . it can include energy that has a frequency between about 100 hz and about 1 khz . medium frequency energy can include energy that has a frequency of less than 10 mhz and greater that 50 khz . it can include energy that has a frequency between 500 kilohertz ( khz ) and 50 khz . it can include energy that has a frequency between 200 khz and 50 khz . it can include energy that has a frequency of 100 khz . in an embodiment , a lubricious material can include at least one of polyvinylpyrrolidone , polyacrylic acid , hydrophilic substance , or silicone . fig1 a depicts the physical structure of a probe or catheter according to an embodiment . a probe 10 can be about 10 cm to about 1000 cm long . the probe 10 can be from about 50 cm to about 200 cm long . the probe can be 100 cm long . the probe 10 can be a catheter . the probe 10 may have two surface electrodes 14 , 15 . the surface electrodes 14 , 15 may be ring electrodes . the , are located at the distal end , 15 , and two wire leads , 4 and 5 , run the length of the catheter . the electrical structure of a conventional electrophysiology catheter is shown in fig1 b . note that the electrical leads 4 and 5 , terminate in respective surface electrodes , 14 and 15 . this arrangement can be less preferred for mri studies because of ( i ) potential safety issues arising from heating induced in the wires and electrodes by the mri excitation field ; ( ii ) application of rf energy for ablation may result in significant degradation and interference during mri scanning ; and ( iii ) the elements are not tuned to the mri frequency and generally will not provide improved snr and mri resolution performance . interfering signals and noise not related to mri detection should be limited , as should be currents induced directly in the conductors by the time - dependent mri fields . mri tracking may be facilitated be creating a small , configured region of high snr . it is known to those skilled in the art that long , flexible loop antennas produce local regions of high signal and are therefore ideal for active catheter tracking ( for example , see atalar e , bottomley p a , ocali o , correia l c , kelemen m d , lime j a , zerhouni e a . high resolution intravascular mri and mrs by using a catheter receiver coil . magn reson med . 1996 ; 36 : 596 - 605 ). for a catheter structure with two electrical leads , a loop antenna configuration can be produced by short - circuiting the distal end of the catheter . while this solution may be theoretically ideal , it is unacceptable for electrophysiology interventions because in order to perform ablation and to record of bio - potentials , multiple , electrically isolated wire leads are preferred . in an embodiment , a capacitor 20 , is placed at the distal end 11 , of the catheter ( fig1 c ). in another preferred embodiment , in addition to the capacitor 20 at the distal end of the catheter , rf reactances 24 and 25 are applied in series with each of the surface electrodes 14 and 15 , in order to improve the safety of the device for mri applications . the component values of the reactances 24 and 25 are adjusted or tuned such as to produce a high impedance at the mri frequency , but low impedance at the frequency used for rf ablation and / or measuring bio - potentials . more specifically , in one embodiment each of the reactances 24 and 25 may include a non - magnetic rf inductor . in another preferred embodiment , each of the reactances 24 and 25 may include an rf inductor - capacitor pair , preferably non - magnetic , connected in parallel to form a parallel resonant lc circuit with resonant tuned to substantially equal to the mri frequency , for example , 63 . 9 mhz with a static magnetic field of 1 . 5 tesla . by this means each lc pair provides a high impedance at the mri frequency . the lc circuit can be formed by winding a wire coil around a ceramic chip capacitor . for maximum effectiveness , the lc circuit should be shielded with conducting foil or the like . to understand the function of the catheter , it is useful to consider the electrical appearance of the device at both low and high frequency ranges . first , at low frequencies , the capacitor has a large impedance and behaves approximately as an open circuit . the rf inductors have low impedance and appear as short circuits . therefore , the low frequency structure ( fig1 d ) of the catheter behaves the same as the conventional structure ( fig1 a ). the electrodes can thus be used for monitoring bio - potentials , and applying rf ablation at frequencies , for example , that are lower than the mri frequency ( for example , less than about 15 mhz for rf ablation vs 63 . 9 mhz for mri at 1 . 5 tesla ). however , at high frequencies or at the mri frequency , the structure is quite different . the impedance of the capacitor at high frequencies is small and is depicted as a short circuit , 21 in fig1 e . the rf inductors have a large impedance , behaving approximately as open circuits 34 , 35 . note that the use of lc resonant reactances 24 and 25 can provide a much higher impedance at the mri frequency , depending on the circuit quality factor ( q ). the net result is that rather than a two - lead catheter , the catheter now acts as a long loop mri receiver , 40 , which is ideal for tracking . furthermore , the two catheter electrodes , 14 , 15 have been decoupled from the rest of the circuit as depicted in fig1 e . note that the two electrical structures shown in fig1 d and fig1 e exist simultaneously , but at different frequency ranges . therefore , this structure enables the same leads to be used for high resolution mr imaging , the recording of physiological potentials , and / or rf ablation . in the preferred embodiment , the proximal ends 4 and 5 of the catheter are connected to an mri tuning , matching and decoupling circuit 99 and signal splitting circuit 100 as exemplified in fig2 . fig2 a shows a photograph of the circuitry in a prototype system . in the mri tuning , matching and decoupling circuit 99 ( fig2 b ), reactive elements 70 , 71 , 74 , and 77 are providing such that the catheter loop 40 shown electrically in fig1 e and which has an electrical inductance , is tuned to resonate at the mri frequency when the catheter is engaged in the sample of interest such as the body . in addition , the reactive elements are adjusted so that time impedance at the catheter mri output connections 84 and 85 is matched approximately to the characteristic impedance of the transmission cable used to connect the catheter to the receiver input of the mri system . for example , 50ωcoaxial cable with bnc type connectors . alternatively , the catheter mri output connections 84 and 85 can be connected directly to the receiver input of the mri system , for example , to the input of a preamplifier . in this case , the impedance should be adjusted to the value that corresponds to the preamplifier input impedance that results in an optimum or near - optimum preamplifier noise figure . it will be understood that the matching circuit shown in fig2 b has the advantage of providing a balanced input , analogous to that provided by a balun transformer , by virtue of the two capacitors 74 and 75 connected to both sides of the catheter leads . suitable tuning and matching circuits for catheter devices are known to those skilled in the art , for example , as described in atalar et al cited above , and in ocali o , atalar e . entitled “ intravascular magnetic resonance imaging using a loopless catheter antenna ” in magn reson med . 1997 ; 37 : 112 - 8 , and it will be understood that other matching and tuning circuits that are routinely used for matching and tuning mri detector coils may be alternatively used and are within the scope of , and forseen by , the disclosed systems and methods . in addition , the mri tuning , matching , decoupling and signal splitting circuit ( fig2 b ) shows , e . g ., decoupling element 90 including a low noise pin diode , connected across the output conductors 84 and 85 . during mri excitation by an external transmit coil , a dc bias voltage is provided by the mri scanner across the coil input causing the pin diode to conduct . during conduction , the tuning elements are shorted - out , which results in detuning of the catheter loop 40 , and high impedance , thereby limiting those rf currents induced at the mri frequency in the loop . in previous studies , concerns have been raised about the safety of using metallic structures in mr scanners . radiofrequency energy ( mhz )— transmitted from the scanner in order to generate the mr signal — can be deposited around the interventional device . this results in high electrical fields around the instrument and local tissue heating . this heating tends to be most concentrated at the ends of the electrical structure . this safety issue can be addressed using the disclosed systems and methods . the concern is that the surface ring electrodes , which directly contact the tissue , can cause local tissue burns . the electrodes need to be cut / removed from the circuit in the megahertz frequency range . this can be accomplished with an inductor circuit element ( placed in series ) between the lead wires and the surface electrodes . with this design , the electrical end of the leads ( in the megahertz range ) are buried inside of the catheter and as a result , the concentrated electric fields are also located inside of the catheter , instead of in the tissue . this results in a significant reduction in unwanted tissue heating . a more effective way to ‘ cut ’ the surface electrodes from the rest of the circuit could be to use a resonant circuit in place of the inductors . this resonant circuit could include an inductor in parallel with a capacitor ( an ‘ lc circuit ’). if this lc circuit is tuned to the mr frequency , it can present a very high impedance at this frequency . this can effectively cut the surface electrodes and reduce unwanted heating . for maximal effectiveness , the lc circuit should be shielded . the lc circuit may be placed distal to the electrodes and allowing the electrodes to be visualized . in order to monitor physiologic bio - potentials and / or deliver rf energy for ablation , a splitting circuit is required . in fig2 b , leads 64 and 65 of splitting circuit 100 are connected across the catheter output leads 4 and 5 . these leads are connected via rf filters 67 and 68 to either the bio - potential monitoring device and / or the rf energy source for ablation at 94 and 95 . the purpose of rf filters 67 and 68 is to prevent spurious electrical noise signals that are at least at or near the mri frequency , from passing from either the bio - potential monitoring device or the rf energy source for ablation to the catheter system 40 . in addition the rf filters can stop rf signals induced by the mri scanner , for example during excitation , from being input to the bio - potential monitoring device or the rf ablation energy source . the rf filters 67 and 68 can be of a number of types known to those skilled in the art , including but limited to those described in u . s . patent application ser . no . 09 / 428 , 090 , filed nov . 4 , 1999 , of which this application is a continuation in part , and in lardo a c , mcveigh e r , jumrussirikul p , berger r d , calkins h , lima j , halperin h r , “ visualization and temporal / spatial characterization of cardiac radiofrequency ablation lesions using magnetic resonance imaging ”, circulation 2000 ; 102 : 698 - 705 . for example , rf filters 67 and 68 can be low pass filters with a cut - off frequency chosen to lie between the mri frequency of the catheter loop 40 , and a lower rf frequency of the rf ablation device so that any signals that arise at the mri frequency on lines 64 and 65 are significantly attenuated and effectively eliminated . alternatively , in another preferred embodiment as illustrated in fig2 b , filters 67 and 68 are parallel lc resonant circuits with resonant frequencies adjusted to substantially match that of the mri frequency . by this means , the impedance of each filter can be rendered a very high value at the mri frequency depending on the q of the circuit , thereby stopping or substantially eliminating signals arising on lines 64 , 65 , 94 , 95 . in summary , it will be seen that , with the filtering and connections in place as described , low frequency physiological bio - potentials can pass unimpeded from surface electrodes 14 and 15 to bio - potential measuring device connected at outputs 94 and 95 . similarly rf energy for ablation applied at a frequency that is different from the mri frequency to leads 94 and 95 , can be delivered unimpeded to electrodes 14 and 15 when they are used for ablation . any noise or other signals present at the mri frequency can be substantially attenuated or effectively eliminated from lines 64 , 65 , 94 , 95 . from the mri standpoint , electrodes 14 and 15 are deactivated and disconnected . the catheter behaves as a loop antenna 40 tuned to the mri frequency and matched to the mri system input , 84 and 85 . during mri excitation , or in fact at any point during the procedure when it is desirable to do so , the antenna can be deactivated by a dc bias voltage applied across inputs 84 , 85 , by virtue of the decoupling means 90 . in this embodiment it will be apparent also that the entire area of the loop antenna 40 extending from the distal portion of the catheter 11 near the electrodes , to the points where the catheter is connected to the mri tuning , matching , decoupling and splitting circuits 99 and 100 , is mri active . however , a number of situations may arise where it is desirable to limit the length of sensitivity and / or improve the tuning properties of the loop antenna . in particular , the loop 40 is tuned by capacitor 20 in conjunction with the tuning and matching elements 71 , 74 , and 75 in tuning and matching circuit 99 at each end of a catheter that may be 100 cm or more long . the extended length of this loop may render it susceptible to stray capacitance arising between the leads of the catheter , 4 and 5 , and the surrounding sample and / or environment . the effect of this stray capacitance is generally to add capacitance to the effective lc resonant circuit formed by the loop antenna . if the detuning produced by this effect is significant , it is preferably offset by re - adjustment of the tuning and matching circuit 99 . under situations where the catheter is inserted to different lengths in the sample , different amounts of stray capacitance may occur resulting in variable performance and / or a need for retuning which is not convenient during a procedure or study . in addition there are losses associated with the stray capacitances which can degrade performance as an mri antenna . in an embodiment , the effect of the stray capacitance is reduced relative to the total capacitance needed to tune the circuit by adding additional capacitance at other locations . in order not to impede passage of bio - potential and / or rf ablation signals , the capacitors are placed between leads 4 and 5 analogous to capacitor 20 . in one embodiment , depicted in fig2 c , tuning capacitor 20 ′ is connected across 4 and 5 creating distal portions 4 ″ and 5 ″ and proximal portions 4 ′ and 5 ′. the entire loop 40 is tuned to resonance via circuitry 99 as above , but now with the 2 capacitors , 20 and 20 ′ present . in another preferred embodiment the placement of capacitor 20 ′ is used to shorten the effective length of loop 40 to a smaller loop 40 ″ of working length l , thereby improving mri performance by reducing stray capacitance effects and the amount of noise picked - up from the sample . in this embodiment , a section of shielded cable , such as coaxial cable 41 may be used to form the proximal portion 40 ′ of the loop 40 . by this means , stray capacitance and noise pick - up associated with the loop section 40 ′ is substantially eliminated . this has no effect on the measurement of bio - potentials or application of rf ablation . in yet another exemplary embodiment shown in fig2 d , additional capacitors 20 b , 20 c , 20 d are connected between the catheter leads 4 and 5 to further distribute the mri tuning capacitance along the mri - active portion of the catheter l with shielded cable portion 41 connecting this portion to circuitry 99 and 100 described above . in an embodiment , at least one tuning capacitor is provided . in this embodiment , loop 40 ″ is tuned as before . the number of capacitors that can be added in this way is limited by the inability to tune the circuit if the capacitance becomes too large . in addition the capacitance is preferably limited such that bio - potential and / or rf ablation signals are transmitted without significant impediment between electrodes 14 and 15 , and input / output connections 94 and 95 . while the catheter devices that are illustrated , in fig1 and fig2 c and fig2 d are depicted with two electrodes 14 and 15 , this is not intended to be a limitation . conventional catheters with different numbers of electrodes , for example with 1 - 7 electrodes for intra - cardiac use , are available . the multi - functional mri probe or catheter disclosed herein can be extended to catheters with tips with different numbers of electrodes by placing the capacitor 20 immediately proximal to the plurality of electrodes , in the case of two or more electrodes . in such embodiments , the capacitor is connected across the lead 4 a that goes to the proximal electrode 15 a , and to any of the leads connected to a more distal electrode such as 14 b , as depicted in fig2 c . a loop - antenna is thereby formed from leads 4 a and 5 a , which are connected to the circuitry 99 and 100 shown in fig2 b , as above . because the other leads , e . g ., leads 7 , 8 , can be used for measuring bio - potentials , and / or delivering rf energy for ablation thereby they may be filtered and each connected to a filter circuit 100 . in addition , performance and safety are improved by providing reactances 24 a , 24 b , 25 a , 25 b etc , one for each electrode , of the same form and design as reactances 24 and 25 in fig1 c 3 , 1 f , or 1 g . fig2 f depicts an embodiment in which a probe or catheter may have a single electrode , 15 b . a loopless antenna , as described by and atalar cited above , is formed by providing a shielded coaxial cable length 41 ″ for the catheter section , with an unshielded central conductor portion extending to the single electrode 15 b as shown in fig2 f . in this single electrode embodiment , the active or “ whip ” portion of the antenna extends from the electrode over the extending portion 4 b , with the proximal end of 4 b , and the shield of the coaxial cable fed to inputs 4 and 5 of circuits 99 and 100 shown in fig2 b . in an embodiment , the electrophysiology catheter can be made to function in the mode of a loopless antenna described by ocali and atalar cited above , with catheters employing a plurality of electrodes . in a preferred embodiment represented by fig1 b , the distal end 4 a of the catheter and distal electrode 14 form the mri active end of a loopless antenna , and the connecting portions 4 and 5 form a cable portion of same . in this embodiment leads 4 and 5 are preferably formed by a shielded cable section which extends from tuning / matching / decoupling / splitting circuitry 99 and 100 to proximal electrode 15 , analogous to the use of cable section 41 used in fig2 d described above . in particular , lead 5 is formed by the outer shielding of the coaxial cable and is terminated by the ring electrode 15 . the outer shielding of the coaxial cable is insulated from the sample and is only exposed to the sample at ring electrode 15 . similarly , section 4 a connected to electrode 14 is electrically insulated so that it is only exposed to the sample via contact electrode 14 . tuning of the loopless antenna via circuitry 99 is as described by ocali and atalar cited above , and the splitting circuitry remains unchanged . note that in this embodiment reactive elements 23 - 26 may be omitted . in another embodiment , capacitor 20 may be omitted also . during mri the conducting loops formed by electrodes 14 and 15 in loopless antenna embodiments of the disclosed systems and methods , may introduce decoupling artifacts , or give rise to local heating due to currents induced in the loops by the mri excitation field . this problem is mainly limited to distal electrode 14 because electrode 15 is attached to the cable shield . in a further embodiment these problems are minimized by electrically cutting the circular electrodes so that they cannot make continuous loops while maintaining continuous connections between the electrode and lead 4 a and 5 . this will not curtail their performance for measuring bio - potentials or rf ablation . in another embodiment , these problems are minimized by reducing the diameter of the electrodes and by forming the electrodes with a solid area of conductor covering the electrode diameter . loopless antenna embodiments have an advantage of shielding essentially the entire length of the catheter up to the proximal electrode , from stray capacitance and noise pick - up from the sample . in addition it provides the advantage of an mri capability with an improved range beyond the proximal electrode 15 to the most distal portion of the catheter , the distal electrode , thereby improving image quality and resolution even closer to the target area . embodiments wherein the catheter electrodes are split to form rings as described above and which share the advantages of shielding a substantial portion of the catheter length and maximizing the imaging capability at the distal end of the catheter are further described and illustrated in fig2 g , 2 h , and 2 i . in these embodiments , the electrode rings themselves form loop antennas , and a portion of the catheter is formed by a section of coaxial cable 41 ″, analogous to fig2 d and 2 f . a tuning capacitor 20 a is connected across the distal end of the coaxial cable section 41 a . in this case , the value of the capacitor is chosen , in conjunction with capacitor ( s ) 29 ( a , b , etc ), such as to tune the loop formed by the distal electrode ( s ) to resonate at the mri frequency . one end of each split catheter ring is connected to the next electrode via capacitors , 29 , 29 a , 29 b etc , so that the electrodes together effectively form a helical solenoid with turns that are spaced by the separation of the electrodes . the end of the split ring of the distal electrode is connected back to the other conductor of the coaxial cable , depicted as 5 b . fig2 g depicts a single electrode loop antenna of this form for use as a multi - functional device . fig2 h depicts a two - electrode device . the capacitor 29 can block low frequency currents so that bio - potentials can be measured between the electrodes without being shorted out . for rf ablation , the capacitor is chosen to have a high impedance at the rf ablation frequency , winch is preferably much lower than the mri frequency ( eg , & lt ; 10 mhz compared to about 64 mhz for mri at 1 . 5 tesla ) to avoid interfering with mri signals detection . fig2 i exemplifies a four electrode device . in this case , the two center electrodes are connected via additional leads 7 a , 8 a , which need to be connected to filter circuitry 100 , as described for fig2 e . in fig2 g , 2 h , 2 i , reactances are preferably connected on the dc lines connecting each electrode , as in 24 a , 24 b , 25 a , etc in fig2 e and described above in reference to fig1 c 3 , 1 f , and 1 g . while these examples are described in detail some embodiments , it will be seen that this arrangement can be extended to other numbers of electrodes on the catheters , of which it is the intent of the present application to include by reference herein . the multi - functional catheter or probe systems and methods disclosed herein may be constructed so as to be fully mri - compatible . specifically , it &# 39 ; s design and materials are selected such that ( 1 ) the image is not significantly distorted by the device ; ( 2 ) the mri electromagnetic fields do not alter the normal functioning of the device ; ( 3 ) cardiac arrythmias or other nerve stimulation affects are not produced by the device , and ( 4 ) no damage to the tissue is produced by rf energy received from the mri scanner . the presence of even small amounts of magnetic material in the imaging fields can produce substantial amounts of image distortion . this distortion is caused by perturbation of the imaging magnetic field . the most distortion is caused by ferromagnetic materials ( iron , nickel , cobalt ). little if any distortion is produced by materials that do not become significantly magnetized ( low magnetic susceptibility ) by the mri magnetic field . metals which do not produce significant magnetization include copper , gold , platinum and aluminum among others . many plastics and synthetic fibers are entirely non - magnetic and do not distort the images . fig1 c shows an embodiment in which the catheter or probe is constructed based on gold - tipped , 1 - 15 french , most likely 7 french , mri - compatible two - electrode ablation catheter . mri - compatible electrode components 14 and 15 , such as those used in commercial ablation catheters , or electrodes including , e . g ., safe , bio - compatible , minimally corrosive materials such as gold , platinum and the like are suitable for this purpose . leads 4 and 5 are formed from insulated conducting wire , an insulated section of flexible printed circuit board , or twin lead cable . the conductor separation should be maintained substantially constant along the length of the catheter shaft in order to promote uniform signal sensitivity and to minimize variability in tuning , which can be accomplished by twin lead cable and flexible printed circuit board , bonding an insulated wire pair together , using a twisted pair , by a multi - lumen tube to house the electrodes , by a composite tube formed with multiple lumens for the electrodes , or by separating the pair with spacers at fixed intervals with mechanisms known in the art . the conductor leads can generally be fixed to the electrodes and / or the electrical components by standard soldering or welding techniques . ceramic chip capacitors and ( non - ferrite ) rf inductors wound from small diameter copper wire are preferably used for the electrical components throughout . the shaft of the catheter is typically formed of a polymer tubing that is flexible and can be torqued within the body cavities , such as teflon , polyolefin , polyethylene , pebax , polyurethane , or ptfe . the properties of the materials are such that the enable the device to be easily steered under mri guidance . the diameter of the tubing should be in the range 0 . 8 - 5 mm used typically for electrophysiology procedures , or in the range 1 - 15 french . the total length of the catheter is in the range 0 . 6 - 2 m , but typically at least 1 m . in embodiments designed for cardiac ablation applications , the length of the invasive portion of the device is preferably at least 1 . 2 m long so that the tip can be placed into the heart from the femoral artery or vein , and the diameter of the device is approximately 2 . 5 mm . in the embodiment shown in fig2 c and fig2 d , section 41 corresponding to loop 40 ′ can be formed from coaxial cable of diameter less than that of the shaft , and connected to circuitry 99 and 100 via standard small gauge rf - type connectors as are known and used by those skilled in the art . in the loopless antenna embodiment corresponding to fig1 b wherein the entire proximal length of leads 4 and 5 up to electrode 15 are formed by a coaxial cable type configuration , similar coaxial cable of diameter less than that of the shaft , and connected to circuitry 99 and 100 via standard small gauge rf - type connectors can be used . alternatively , the leads can be formed by flexible , torqueable insulated cable replacing the shaft altogether . in this version of the loopless antenna embodiment , the insulating shaft 10 ( fig1 a ) is replaced by the external insulation on the shaft . in yet another preferred embodiment , torqueability and maneuverability are enhanced by using coaxial cable formed by a nitinol hypotube . similarly , the shaft that forms the coaxial cable may be constructed with an inner core that is formed from nitinol , and plated with alternating layers of gold and silver . a layer of insulation made out of fep or pet could be used to separate the inner core from the outer conductor . fig3 shows a block diagram illustrating the operation of an mri scanner system which may be used in connection with the disclosed systems and methods . a magnet is provided for creating the magnetic field for inducing magnetic resonance . within the magnet are x , y , and z gradient coils for producing a gradient in the static magnetic field in three orthogonal directions . within the gradient coils is an external rf excitation coil . the external rf excitation coil produces the magnetic field to excite the mri signals in the body . a computer is provided for controlling all components in the mri scanner . this includes the rf frequency source , spectrometer and pulse programmer . the pulse programmer generates a carefully - controlled time - sequence of shaped and / or phase or frequency - modulated rf pulses that are delivered to the rf power amplifier . the rf power amplifier has pulse power of 1 - 20 kw which is applied to the external rf excitation coil . the computer also controls the gradient magnetic field by providing a sequence of modulated pulses that are synchronous with the rf pulse sequence , to gradient power amplifiers , which in turn activate the x , y , and z gradient magnetic field coils in the magnet . signals detected by receiver coils in response to the applied rf / gradient imaging sequences , including those detected in the aforementioned multi - functional mri catheter system , are first input to a receiver preamplifier . these signals are amplified , phase sensitive detected , for example , by converting to digital signals and being fed to a digital receiver . the digital image data are then reconstructed in the computer and displayed as images on a monitor or the like . it is important that the location of the tip of the catheter can be accurately determined by mri . a number of modes of localization can be used . because the catheter is a receiver it can be used to directly image the tissue around it . this image can be viewed on with high resolution employing a probe or catheter as disclosed herein , or , it can be viewed at low resolution as an overlay on a large field - of - view “ scout ” image obtained with an auxiliary coil outside the body . the location of the catheter in the body can be tracked by the bright line of signal moving in the scout image . the scout image can be updated at an interval set by the user to compensate for patient motion . an interactive control can allow the physician to “ zoom in ” towards the bright catheter , finally resulting in a high - resolution image in the area of the distal catheter and tip . the “ zoom ” function can be achieved with interactive control of the imaging gradients . some exemplary embodiments may include a combined multi - functional mri catheter ; a multi - functional mri catheter connected and used in conjunction with matching / tuning / decoupling circuit means and splitting circuit means ; a multi - functional mri catheter used with said circuit means in conjunction with a bio - potential monitoring device and / or a standard rf generator for use in ablation connected at inputs 94 and 95 of fig2 b ; and any of a combined multi - functional mri catheter and said circuit means used in conjunction with one or more of a bio - potential monitoring device , an rf generator for ablation , and an mri scanner . in such a system embodiment , the mri scanner has a receiver whose inputs are connected to inputs 84 and 85 . the probe or catheter disclosed herein can be used in combination with an mri scanner such that rf energy can be delivered to selected areas of tissue with the electrodes of the multi - functional catheter , bio - potentials measured with the electrodes , the tissue imaged with the antenna portion of the catheter . rf lesions , target tissue , catheter location and tracking may thus be visualized with the use of external detector coils or the catheter - antenna , or using external detector coils in conjunction with the catheter - antenna . this image visualization and bio - potential measurements can be used for ( 1 ) precise titration of therapy , ( 2 ) the ability to test the length and depth of lesions from new ablation - energy sources , and ( 3 ) accurate assessment of the success of making lines of ablation that block conduction . mri can also be used to guide other procedures . in cardiology , accurate anatomic information , combined with electrical measurements , allows improved study of the pathophysiology of arrhythmias , stunning , remodeling , and tachycardia - induced myopathy . outside of cardiology , mri - guided ablation of tumors such as metastatic liver disease , brain tumors , and prostate cancer , may allow treatment with less morbidity and less cost than conventional open surgery . as an example of the embodiment depicted in fig1 c , a 100 cm long prototype catheter device for use in a 1 . 5 tesla mri system was constructed from electrode components taken from a gold - tipped , 7 french , mr - compatible two - electrode ablation catheter ( bard inc ., murray hill , n . j .). the two wire leads were formed from 30 gauge insulated copper wire ( 0 . 25 mm wall thickness — alphawire co . elisabeth , n . j .) with a conductor separation held constant at 1 . 3 mm . for the shaft of the catheter , polyolefin tubing ( 3 . 36 mm diameter with 0 . 5 mm wall thickness — alphawire co . elizabeth , n . j .) was used yielding a final catheter size of 10 french . a 500 pf chip capacitor ( 1 . 4 × 1 . 4 × 1 . 45 mm ) was placed between the catheter leads 2 cm from the catheter tip ( american technical ceramics corp . huntington station , n . y .). rf tip chokes 24 and 25 were not used in this implementation . this catheter was connected to circuitry shown in fig2 b . the catheter and circuitry are pictured in fig2 a . capacitors could have values in the range of about 1 - 1000 pf . inductors could have values in the range of about 100 - 1000 nh . in an embodiment , the capacitor c and inductor l values can be related by the equation l = 1 /( w 2 c ), where w = 2πb , and where b is the resonance frequency , for example , about 64 mhz . fig4 shows the snr performance of this example . snr curve 300 represents that of a probe or catheter used as a standard electrophysiology catheter as in fig1 c . snr curve 310 represents that of a probe with an open circuit such as in fig1 b . snr curve 320 represents that of a probe in which the loop 40 is shorted , as in fig1 e . these data suggest that use of the example probe or catheter described above can produce a large gain in snr compared with a standard catheter . in addition , the prototype catheter has comparable performance to the design model , fig1 e , which , unlike the prototype , cannot be used for electrophysiology applications . fig5 exemplifies visualization and tracking of a prototype catheter . shown are selected images from a 10 - second catheter push acquired with 10 frame / sec , real - time mri and overlaid on a static , slice - selective roadmap image obtained with a conventional external mri coil . the location of the catheter is readily visualized by the bright line of signal . annotations indicate the left ventricle ( lv ), right ventricle ( rv ), chest wall , and the superior vena cava ( svc ). the catheter starts in the right ventricle and is then pulled up into the right atrium ( panels a & amp ; b ). as the catheter is subsequently pushed , the tip stays in the atrium and the catheter body flexes ( panel c ). the catheter is pulled back further ( panels d & amp ; e ). in panels f - g , the catheter is pushed once again , the tip stays in the right atrium , and the catheter shaft flexes . note that the full length of the catheter can be easily visualized . fig6 demonstrates the multifunctional operation of a prototype catheter , in the form of intracardiac electrogram recordings acquired concurrent with catheter tracking by mri . shown are selected images from a 15 - second catheter push acquired with a 7 frame / sec , real - time mri sequence . annotations indicate the left ventricle ( lv ), right ventricle ( rv ), chest wall , and the superior vena cava ( svc ). the catheter is initially advanced from the jugular vein down the superior vena cava toward the heart ( panels a & amp ; b ). once the catheter arrives in the right atrium , the catheter tip gets stuck and the catheter body begins to flex ( panel c ). the catheter is withdrawn several centimeters , the shaft is torqued , and then advanced again ( panels d & amp ; e ). as the tip is now angled anteriorly , it slips through the right atrium and into the right ventricle ( panels f & amp ; g ). note that once the catheter arrives in the ventricle , a large bipolar spike is seen in the intracardiac electrogram . bipolar endocardial recordings typically show only electrical activation of the myocardium ( in the ventricle , these spikes are concurrent with the qrs complex in the body surface ecg ). in panel h , the catheter is positioned and stable in the ventricle . note that a strong bipolar signal is recorded once the catheter tip arrives in the right ventricle ( lower amplitude signal is also seen from the right atrium ). mri data can be used to construct 3d map or images of the areas in the heart or other organs being treated , that have undergone ablation , and the surrounding organ or tissue . areas of ablation can typically be marked by elevated mri transverse relaxation time values ( t2 ), or decreased longitudinal relaxation values ( t1 ) during infusion of an mri contrast agent wherein contrast is enhanced by alteration of such relaxation times . a composite 3d rendering of the organ being targeted can be updated after each ablation and displayed with an appropriate rendering technique . the guidance of the catheter tip to the next site of ablation and / or bio - potential measurement , can be assisted by mri wherein the physician uses the images to manipulate and steer the catheter , or automatic tracking and feedback could assist that physician to steer the catheter . this feature is facilitated by the current availability of mri frame rates of 10 frames / s or more , which enables real - time catheter placement , bio - potential measurements and intervention . the lesions may be visualized using standard imaging techniques including the use of contrast agents , as discussed in u . s . patent application ser . no . 99 / 25858 , filed nov . 4 , 1999 , entitled “ system and method for magnetic resonance guided electrophysiologic and ablation procedures ” of which this application is a continuation on part . electrical activation timing information obtained from bio - potential measurements with the catheter , when combined with catheter localization information , enables accurate activation maps that are most useful in determining , for example , the site of origin of an atrial or ventricular tachycardia in the heart . activation maps can be superimposed and / or color rendered on anatomically accurate reconstructions of cardiac structure . spatially accurate voltage data is available from knowledge of the location of each electrode in contact with the myocardium in 3d , as derived from mri . thus , electrical data originating from each known electrode position allows generation of activation and voltage maps on true anatomic structures . this provides significant advantages beyond the capabilities of the non - fluoroscopic electroanatomic mapping systems that do not provide accurate anatomic information . when the ablation / imaging catheter is used for the delivery of ablative radio - frequency energy , the high - resolution image obtained via the present catheter system enables visualization of the ablation lesion and of lesion growth . again , directional orientation , as web as location , of the catheter lip can be determined in 3d space , and the high - resolution image data can be displayed in any plane , and in particular , in the plane orthogonal to the catheter . since the image is obtained with the same catheter that is delivering the ablative energy , the orthogonal - plane image displays the lesion at its maximal radius , reducing the chances of underestimation as often occurs with ultrasound . high - resolution visualization of ablative lesions by the multi - functional mri catheter or probe as disclosed herein allows for documentation of whether or not rf application resulted in successful lesion development and of where lesions have and have not yet been made . this facilitates efficient catheter placement so that rf is applied only to tissue not previously ablated . the combination of the high - resolution visualization , bio - potential measurements and / or rf ablation functionality in a single catheter as discussed above makes high - resolution mri guidance ideal for visualization and verification of ablative lesion lines , particularly in atrial tissue . this is useful for ablation of the re - entrant circuit in typical atrial flutter and is crucial for successful ablation of atrial fibrillation . it has been shown that atrial fibrillation can be eliminated with multiple lines of ablative lesions placed in the right and left atria to emulate the surgical maze procedure . failures of the ‘ percutaneous maze ’ procedure have resulted primarily from incomplete lesion lines . mri guidance should allow rapid confirmation of lesion line continuity and avoidance of unnecessary repetition of rf application where tissue has already been successfully ablated . the mri - guided catheter bio - potential / ablation system offers advantages in ablation of ischemic and idiopathic ventricular tachycardias , ectopic atrial tachycardias , atrial flutter , and atrial fibrillation . unlike av node reentry and accessory pathway mediated tachycardia , these other arrhythmias have lower ablation success rates and longer ablation procedure durations , primarily due to difficulties in accurate activation mapping or confirmation of lesion development with conventional equipment . procedure durations and risk of complications should thus be reduced substantially with the mri - guided catheter ablation system . while the disclosed systems and methods have been described in connection with embodiments shown and described in detail , various modifications and improvements thereon will become readily apparent to those skilled in the art . accordingly , the spirit and scope of the present disclosure is limited only by the following claims .

US-201414326183-A

axial stress or similar properties in a stressed tendon or ligament are measured by mechanical excitation of a shear wave in the tendon or ligament measured using ultrasonic displacement techniques at least two different longitudinal positions to derive a shear wave propagation speed . this shear wave propagation speed may be equated to an axial stress on the tissue using a model . rapidly repeated measurements allow dynamic axial stress measurements to be obtained for clinical study .

referring now to fig1 , a sensor / stimulator unit 10 , constructed according to one embodiment of the present invention , may provide a housing 11 having a front face 12 sized and shaped to place against skin 14 of a patient proximate to a tendon or ligament ( henceforth tissue 18 ) extending along a longitudinal axis 20 . the housing 11 may be held against the skin by means of an elastic cuff 13 or the like . for example , the housing 11 may be applied with its front face 12 against the rear of a patient &# 39 ; s ankle adjacent to and vertically aligned with the achilles tendon . exposed at a lower edge of the front face 12 of the housing 11 is a stimulator probe 22 attached to piezoelectric element 24 . the stimulator probe 22 is shaped to press against the skin overlying the achilles tendon to conduct force from the piezoelectric element 24 through the skin to apply a periodic transverse stimulation pressure 26 to the tissue 18 inducing a longitudinally traveling shear wave pulse 28 traveling vertically upward therefrom . as is understood in the art , piezoelectric materials are those which change dimension under the influence of the electric field and thus can be used to provide mechanical motion under electrical control . also exposed at the front face 12 of the housing 11 are multiple ultrasonic transducers 30 arrayed generally in a vertically extending longitudinal line . in a simplest case , two spaced apart ultrasonic transducers 30 a and 30 b may be positioned at predetermined locations in longitudinal separation from the stimulator probe 22 as discussed . these ultrasonic transducers 30 may emit ultrasonic waves 33 and measure returning echoes 35 in the manner of conventional ultrasound imaging transducers . each of the stimulator probe 22 and the ultrasonic transducers 30 communicate with a local signal processing circuit 32 which may provide signals to the stimulator probe 22 and the ultrasonic transducers 30 from electronic computer 34 and may sample and digitize the data from the ultrasonic transducers 30 for transmission to the electronic computer 34 . generally , signals from each of the ultrasonic transducers 30 a and 30 b provide a time series of ultrasound re data . the electronic computer 34 may include one or more processors 36 communicating with a memory 38 holding a program 43 as will be described below . in addition , the electronic computer 34 may communicate with the signal processing circuit 32 to send data to the stimulator probe 22 and ultrasonic transducers 30 and to collect data from the ultrasonic transducers 30 that may also be stored in memory 38 for processing . as will be described below , the electronic computer 34 may further change the particular ultrasonic transducers 30 selected as ultrasonic transducers 30 a and 30 b or may control mechanical elements to scan the transducers 30 a and 30 b in an alternative embodiment also discussed below . the electronic computer 34 communicates with a graphics display 39 of a type known in the art as well as human input controls 40 such as a keyboard , mouse , touchscreen or the like , allowing a human operator to input data and control the acquisition of data using the present device . referring now also to fig2 and 3 as well , the sensor / stimulator unit 10 operating with the electronic computer 34 may make repeated measurements of shear wave propagation speed , for example , at a repetition frequency of greater than 20 hertz and at rates from 50 to 100 hertz . at the beginning of each periodic measurement , stimulation pressure 26 is applied to the tissue 18 as indicated by process block 42 , for example , providing an impulse signal to the piezoelectric element 24 ( for example , a short square wave pulse or sine pulse ) and then quieting the piezoelectric element 24 for the remainder of the measurement . it will be understood that this pulse provides a range of frequencies of stimulation as a result of its short duration . typically the duty cycle of the transducer operating in this fashion will be less than ten percent , meaning that the piezoelectric element 24 remains quiet without motion for most of the time during operation of the sensor / stimulator unit 10 . the transverse stimulation pressure 26 passes through a gel or ultrasound conducting pad layer 44 then through the skin 46 and into the superficial tendon 48 ( gastrocenemius ) and then through the deep tendon 50 ( soleus ) and then into other muscle and tissue 52 . the result of the transverse stimulation pressure 26 is to produce a shear wave pulse 28 in the superficial tendon 48 ( and 28 ′ in the deep tendon 50 ) traveling upwardly and longitudinally ( along the y - axis as shown ) along the tissue 18 . it will be appreciated that some shear waves will also pass up the other layers including the gel layer 44 , skin layer 46 , and muscle 52 such as may be distinguished from the pulses 28 a by intensity , speed , or depth . the shear wave pulses 28 arrive first at ultrasonic transducer 30 a longitudinally displaced from the stimulator probe 22 and positioned to direct ultrasound waves 33 transversely along a first transverse axis 31 a ( also indicated as the x - axis ) through each of the layers 44 , 46 , 48 , 50 , and 52 and receive return echo signals 35 at various points along that path , for example , from tissue interfaces and other elements providing “ speckle ”. the result is a series of time domain raw ultrasound radiofrequency signals 60 ( shown distinguished by index i and each providing a “ frame ” of data ) having time domain defined by portions corresponding to each of the layers 44 , 46 , 48 , 50 and 52 and more generally providing an echo signal amplitude as a function of time reference to a corresponding timing of the emission of the ultrasound wave 33 . the shear waves 28 next arrive at the second ultrasonic transducer 30 b displaced longitudinally along axis 20 to a second transverse axis 31 b further beyond the ultrasonic transducer 30 a of first transverse axis 31 a . typically the first transverse axis 31 a and second transverse axis 31 b will have longitudinal separation of 1 to 2 centimeters . ultrasonic transducers 30 a and 30 b may be single element transducers or multielement transducers . like ultrasonic transducer 30 a , ultrasonic transducer 30 b are positioned to direct ultrasound wave 33 transversely through each of the layers 44 , 46 , 48 , 50 , and 52 and received return echo signals 35 in return providing raw ultrasound signal 60 ′. the acquisition of this set of echo signals 60 i and 60 ′ i is indicated by process block 66 and may be stored in memory 38 for later processing . the signals 60 and 60 ′ may be acquired at an extremely high rate based on the simple transducer structure of the present invention providing in excess of at least 8000 frames per second and typically in excess of 14 , 000 frames per second for each transducer 30 a and 30 b . it will be appreciated that for a given elapsed time after generation of the emitted ultrasound wave 33 associated with each signal 60 , the signal 60 will indicate echoes returned from different depths within this tissue 18 unique to different of layers 44 , 46 , 48 , 50 , and 52 along transverse axis 31 a . accordingly , a time window 68 may be applied to each signal 60 being a predetermined fixed time delay after the excitation signal 29 of the emitted ultrasound wave 33 to isolate signal portions relevant to particular layers . for example , a time window 68 a may provide for corresponding depth signal portion 70 among the different signals 60 relevant to the layer 48 and time window 68 b may provide for signal portion 70 ( not shown ) among the different signals 60 relevant to layer 50 . similar windows 68 a and 68 b may be applied to the signals 60 ′ to generate depth signal portion 70 for corresponding layers positioned along axis 31 b . at process blocks 72 , signal portions 70 for each window 68 a and 68 b for each of signal 60 and 60 ′ are correlated ( i . e ., between sequentially acquired signals 60 for corresponding windows 68 of corresponding depths , and independently between sequentially acquired signals 60 ′ for corresponding windows 68 of corresponding depths ) to determine separately the relative transverse motion of the tissue 18 along the transverse axes 31 a and 31 b . this transverse motion will be determined from the timeshift necessary for maximum correlation times the approximate sound speed of ultrasound transversely through the tissue 18 . it will be appreciated that precision with respect to knowing the transverse displacement is not required and that the instrument may be used for revealing relative changes as well as providing absolute quantitative measurements . successively calculated displacements for successive signals 60 yield transverse motion signals 76 being a set of displacements over time indicating the transverse motion of the particular tissue element of layer 48 or 50 at axis 31 a . similarly , successively calculated displacements for successive signals 60 yield transverse motion signals 76 ′ being a set of displacements over time indicating the transverse motion of the particular tissue element of layer 48 or 50 at axis 31 b . the motion signals 76 and 76 ′ describe the evolution of transverse tissue deformation caused by the propagation of shear wave pulse 28 as it propagates along the tissue 18 . accordingly , two motion signals 76 and 76 ′ may be then compared , as indicated by process block 78 , to determine a δt value being equal to time it took the shear wave pulse 28 to travel between the axes 31 a and 31 b . it will be understood that this δt value is inversely proportional to the shear wave speed and that shear wave speed may be determined simply by knowing the longitudinal separation between axes 31 a and axis 31 b . the processes of process block 66 , 72 and 78 makeup process block 80 shown in fig2 . the speed of propagation of a shear wave is typically much lower than the speed of propagation of a compression wave through the tissue 18 , for example , with compression waves traveling at 1800 to 2000 meters per second and shear waves traveling from approximately 10 to 100 meters per second depending on the stress applied to the tendon . accordingly , it will be appreciated that high spatial and temporal accuracy is necessary to resolve shear wave speed differences over the short distance of the separation of the transducers 30 at axes 31 a and 31 b . shear wave speed is substantially more sensitive to tissue stress ( above speeds of over approximately 15 meters per second ) than measurement of compression wave speed . this measurement of shear wave propagation speed may be repeated by looping back to process block 42 to apply a new stimulation pulse between measurements of process blocks 66 , 72 and 78 indicated generally by process block 82 . the shift at process block 82 is optional and the repeated measurements may be made at the same location for example under dynamic loading . during or subsequent to the process of process blocks 42 , 80 , and 82 , stress measurements may be determined from the shear wave speeds as indicated by process block 83 . in one embodiment , stress on the tissue 18 may be derived according to the following equation modeling the tissue 18 as a timoshenko beam as follows : where υ is shear wave longitudinal speed determined by knowledge of the separation of the axes 31 discussed above ; k ′ is a shear correction factor empirically determined for a particular tissue and geometry being studied ; μ is the shear elastic modulus ( that may be determined empirically for a particular tissue type ); ρ is the effective tissue density ( generally known for a particular tissue type and its surroundings ); and the inventors have determined that axial stress dominates this equation ( 1 ) when even moderate stresses are applied to tendon tissue allowing the equation to be simplified to : alternatively , a measurement may be made using equation ( 1 ) at zero axial stress to deduce a constant this value may then be output as indicated , for example , by process block 85 of fig4 . in addition to or alternatively various shear wave speed derived parameters may be output including but not limited to shear wave delay , shear elastic modulus and density . these latter two measures may be determined simply by making assumptions about shear wave speed ( for example , by empirical measurement ) and solving equation ( 1 ) for different variables . it will be appreciated that the present technique may provide not only quantitative axial stress but qualitative axial stress in cases where only qualitative indications of stresses are required , for example , as provided by the shear wave speed itself . such measures may be useful for qualitative displays of tissue properties . referring now to fig1 and 2 , at the conclusion of each measurement of process block 80 , and prior to the repetition of process block 82 , the location of the ultrasonic transducers 30 a and 30 b may be shifted along the tissue 18 ( with or without shifting the stimulator probe 22 ) to measure stress - related properties at different longitudinal portions of the tissue 18 . these properties may include changes in stress in the tissue or changes in the other properties described above . in cases where the stress along the tissue 18 may be assumed to be substantially constant , insight and other tissue properties such as elastic modulus may be better revealed . referring to fig1 , this movement of the location of transducers 30 a and 30 b may be performed by simply selecting among different pairs of ultrasonic transducers 30 in a longitudinal array of ultrasonic transducers 30 only some of which are activated . alternatively , as shown in fig4 , a pair of individual ultrasonic transducers 30 a and 30 b may be mounted on a movable carriage 84 translated by electrically controlled actuator 86 such as a stepper motor or the like driving a lead screw 88 to physically translate the ultrasonic transducers 30 along the axis 20 . this actuator 86 may be controlled by the computer 34 through the signal processing circuit 32 . referring now to fig5 , the motion signals 76 and 76 ′ as described above may be further analyzed to determine a change in the shape of the shear wave pulse 28 as it progresses through the tissue such as may reveal a damping effect of the tissue , for example , caused by tissue viscosity or the like . accordingly process block 78 may be supplemented to provide not only a δt value indicating the propagation delay of the shear wave pulse 28 through the tissue 18 but also a decrease in amplitude or a change in spectral content represented by the shear wave pulse 28 , for example , produced by a fourier transform of the motion signals 76 and 76 ′ or a similar measure such as power spectra difference . referring to fig6 , repeated execution of process blocks 42 , 80 and 83 ( without necessarily shifting the position of the transducers 30 ) may be used to create a dynamic stress plot 100 showing a representation of the stress on the tissue 18 over time , for example , with a patient walking or performing other activity . this stress plot 100 may be displayed on the display 39 for analysis , for example , together with a video image 102 of the patient showing a frame of the patient activity such as walking coordinated with a cursor 104 moving over the stress plot 100 to a corresponding time . referring now to fig7 and 9 , in one embodiment , the sensor / stimulator unit 10 may make use of an array 105 of ultrasonic transducers 30 having columns extending along the longitudinal axis 20 . depth information is obtained using the known speed of ultrasound transmission from to determine the depth at which tissue structures generated the ultrasound echo . this depth information is obtained for each element , allowing for the acquisition of a two dimensional b - mode image 108 . this b - mode acquisition may occur before or after the processing of shear wave propagation speed measurement . portions 111 of the b mode image may be shaded or colored to reflect tissue properties determined by the present mention , for example , by matching the data determined from process block 85 with a shifting of the transducers 30 a and 30 b corresponding to longitudinal location in the b - mode image . this shear wave speed - related data may also be displayed in addition to or alternatively along only a single dimension per plot line 113 , and quantitative information 114 may also be provided as derived above with respect to process block 82 of fig2 and 5 . a key 115 may be provided to decode the shading to quantitative values or ranges . during the determination of shear wave speed , ultrasound is collected at a small number of ( two or more individual ultrasonic transducers ) 30 may be actuated to obtain high frame rate information . alternatively , planar wave imaging may be used to achieve for high - frame rate data acquisition . referring now to fig9 , the ability to rapidly measure axial stress in multiple tissue layers ( for example , tissue layers 48 and 50 ) of fig3 allows simultaneous display of axial stress or a similar quantity for each of the different tissue layers . in this way depth - related differences in tissue properties may be determined , for example , showing a deviation between axial stress 110 for superficial tendon layers versus axial stress 112 for deeper tendon layers . referring now to fig1 , in an alternative embodiment , the ultrasound transducers 30 a and 30 b may be replaced with skin - mounted accelerometers 116 a and 116 b , each providing an axis of sensitivity along respective axes 31 as described above . the accelerometers 116 , for example , may be microelectromechanical devices having low mass and high sensitivity , for example , the adx l212 accelerometer from analog devices of massachusetts having sensitivity of +/− 2 g with the z - axis aligned with axis 31 . a signal from the z - axis accelerometers 116 a and 116 b may provide motion signals 76 and 76 ′ as discussed above and these motion signals 76 and 76 ′ may be processed as described above , for example , with respect to fig2 , and 5 , to provide the measurements also discussed above . in this respect , it will be understood that transducers 30 and accelerometers 116 both provide a function of motion sensors of transverse motion . generally , the signals from the accelerometers 116 will indicate a second derivative of position of the tissue 18 and will measure a position that is a combined effect of shear waves moving through multiple layers of tissue 18 as opposed to the transducers 30 which may distinguish between motion at different layers and measure motion directly . this second derivative signal can be integrated twice to provide a position or may be used directly as if the acceleration signals were position signals , either of which will provide an indication of shear wave speed . in one embodiment , the accelerometers 116 may be precisely spaced in a supporting housing ( not shown ) including damping elements to prevent the communication of vibration through the housing between the accelerometers 116 or between the stimulator probe 22 and the accelerometers 116 . close coupling of the accelerometers 116 to the skin of the patient may be provided a pressure sensitive adhesive ( not shown ) or by an elastic cuff 118 holding the accelerometers 116 a and 116 b in a fixed longitudinal separation and biased against the skin . the same cuff 118 may support the stimulator probe 22 operating as discussed above to be spaced from the lower accelerometer 116 b . the material of the cuff 118 may be selected to provide very little coupling between the stimulator probe 22 and the accelerometers 116 , for example , by using a material that is relatively compliant and that has high damping measured in the longitudinal direction . multiple accelerometers 116 may be arrayed longitudinally along axis 20 to provide for the ability to make shear wave measurements at different longitudinal locations along the tissue 18 as discussed above with respect to the ultrasound transducers 30 . alternatively , two accelerometers 116 a and 116 b may be mounted as shown in fig4 in place of the ultrasound transducers 30 a and 30 b and moved mechanically along the surface of the skin , coupled to the mechanical carriage 84 by a motion damping material and by using a lubricating medium between the face of the accelerometers 116 and the skin to permit this motion . in other respects , this embodiment may make use of the components and techniques described above with respect to the ultrasonic transducer system . certain terminology is used herein for purposes of reference only , and thus is not intended to be limiting . for example , terms such as “ upper ”, “ lower ”, “ above ”, and “ below ” refer to directions in the drawings to which reference is made . terms such as “ front ”, “ back ”, “ rear ”, “ bottom ” and “ side ”, describe the orientation of portions of the component within a consistent but arbitrary frame of reference which is made clear by reference to the text and the associated drawings describing the component under discussion . such terminology may include the words specifically mentioned above , derivatives thereof , and words of similar import . similarly , the terms “ first ”, “ second ” and other such numerical terms referring to structures do not imply a sequence or order unless clearly indicated by the context . when introducing elements or features of the present disclosure and the exemplary embodiments , the articles “ a ”, “ an ”, “ the ” and “ said ” are intended to mean that there are one or more of such elements or features . the terms “ comprising ”, “ including ” and “ having ” are intended to be inclusive and mean that there may be additional elements or features other than those specifically noted . it is further to be understood that the method steps , processes , and operations described herein are not to be construed as necessarily requiring their performance in the particular order discussed or illustrated , unless specifically identified as an order of performance . it is also to be understood that additional or alternative steps may be employed . references to “ a controller ” and “ a processor ” can be understood to include one or more microprocessors that can communicate in a stand - alone and / or a distributed environment ( s ), and can thus be configured to communicate via wired or wireless communications with other processors , where such one or more processor can be configured to operate on one or more processor - controlled devices that can be similar or different devices . furthermore , references to memory , unless otherwise specified , can include one or more processor - readable and accessible memory elements and / or components that can be internal to the processor - controlled device , external to the processor - controlled device , and can be accessed via a wired or wireless network . “ diameter ” as used herein should not be understood to require a cylindrical or circular element but to simply describe a diameter of a circumscribing cylinder closely conforming to the element . it is specifically intended that the present invention not be limited to the embodiments and illustrations contained herein and the claims should be understood to include modified forms of those embodiments including portions of the embodiments and combinations of elements of different embodiments as come within the scope of the following claims . all of the publications described herein , including patents and non - patent publications are hereby incorporated herein by reference in their entireties .

US-201514839448-A

a system for delivering a supply of pressurized gas to a user may include a blower and a noise suppression portion . the blower may include an intake portion and an outlet portion for supplying the pressurized gas to the user . the noise suppression portion may define a conduit therethrough having an intake portion and an outlet portion in communication with the intake portion of said blower . the noise suppression portion may be moveable between a first configuration and a second configuration such that at least one exterior dimension of the device is reduced when the noise suppression portion is moved from the first configuration to the second configuration .

selected embodiments of the disclosure may be understood by reference , in part , to fig1 - 19 . although the following discussion focuses on a noise suppression device or system for an assisted breathing device , e . g ., a cpap device , it should be understood that the disclosed subject matter may be used in connection with any medical or therapeutic device for transporting gas ( e . g ., air and / or oxygen ), where sound reduction and / or compact size may be relevant considerations . according to an embodiment of the disclosure , a system 100 may include an acoustic dampening design that reduces the transport size of a device . as illustrated in fig2 , 4 , and 5 , system 100 may include a noise suppression portion 110 , a body portion 120 , and a port 130 for connecting to an gas hose which may supply the pressurized gas to the nasal mask ( not shown ). the noise suppression portion 110 may be moveable between a compressed configuration useful during transport ( see , fig4 ) and a relaxed or uncompressed configuration during system use ( see , fig2 and 5 .) as can be seen by comparison with prior devices , system 100 may provide a substantial reduction in the overall size of the device ( for example , compare the devices shown in fig3 and 4 ). as discussed herein above , a prior device , e . g ., the puritan bennett gk 420 cpap has overall dimensions of 7 . 5 ″× 5 . 5 ″× 3 ″. in comparison , in certain embodiments , the noise suppression system disclosed herein may permit devices to be relatively smaller and also maintain low noise levels during use . for example , an example system 100 including a noise suppression system described herein may have dimensions of approximately 5 ″× 4 . 5 ″× 2 . 5 ″. in some embodiments , system 100 may be provided with a noise suppression portion 110 that may be compressible to reduce the travel size of system 100 . referring to fig4 and 5 , compression of the noise suppression portion 110 may result in the reduction of one or more exterior dimensions of system 100 . for example , the height 112 of system 100 in the uncompressed configuration , e . g ., about 4 . 75 inches as shown in fig5 , may be reduced to a height 114 in the compressed configuration , e . g ., about 3 . 5 inches . in some embodiments , the noise suppression portion 110 may include a compressible foam ( or other ) structure 150 within a collapsible conical shell 160 , as shown in fig6 . as discussed with reference to fig7 - 14 , foam structure 150 may define a noise - suppressive conduit that channels gas from the ambient environment ( e . g ., adjacent aperture 250 , as shown in fig7 ) to the intake of the blower 310 ( shown in fig1 ). as generally used herein , a “ noise suppressive conduit ” may provide noise suppression through the use of the acoustic foam ( or other noise suppressing ) material forming the conduit walls , which absorb at least a portion of the sound generated by the blower . fig7 - 12 are top views of components of noise suppression portion 110 in accordance with an embodiment of the present disclosure . fig1 and 14 are sectional side views of noise suppression portion 110 taken though line 13 - 13 and line 14 - 14 , respectively , of fig7 - 12 . as shown in fig7 - 12 , in some embodiments , foam structure 150 may include a stacked structure including a plurality of foam disks 180 , 190 , 200 , 210 , 220 , and 230 manufactured from an acoustic foam material selected for its ability to absorb sound waves in the audible range . in some embodiments , one or more of the foam disks may be manufactured from a material such as , for example , soundfoam absorption foam , which is a polyester and urethane based material , manufactured by soundcoat company , which foam may have a density of 2 lb . per cubic foot . other appropriate acoustic foam materials which may be compressed and which absorb sound in the audible range may also be used . in certain embodiments , the foam disks may have a thickness of about 0 . 5 inch and diameters that vary from about 3 . 25 inches to about 4 . 25 inches in diameter . when stacked as illustrated in fig1 and 14 , foam structure 150 may define a spiral - like conduit 240 extending from an aperture 250 in disk 180 , through a c - shaped channel 260 in disk 190 , through an aperture 270 in disk 200 , through a c - shaped channel 280 in disk 210 , and through an aperture 290 in disk 220 , which may be in communication with a blower 310 ( indicated in dashed line ). the blower , as known in the art , may provide a pressurized supply of gas to the user . one example blower useful in connection with some embodiments is the blower used with puritan bennett gk 420 cpap . the airflow through foam structure 150 is indicated with arrows passing through the conduits in the foam structures , entering foam structure 150 as indicated by arrow a ( see fig1 ), and exiting foam structure 150 into the blower 310 as indicated by arrow b ( see fig1 ). foam disks 180 , 190 , 200 , 210 , 220 , and / or 230 may be attached together with an adhesive as is known in the art , or may be otherwise attached in any other suitable manner . as illustrated in fig1 - 15 , foam structure 150 may be compressed , such that the noise suppression portion 110 may be reduced from an uncompressed height 330 ( fig1 ) to a compressed height 340 ( fig1 ). in an example embodiment , uncompressed height 330 may be approximately 3 . 0 inches and compressed height 340 may be approximately 1 . 5 inches . it may be understood that foam structure 150 may include more or fewer foam disks than illustrated in fig7 - 15 . moreover , in some embodiments , foam structure 150 may be manufactured from a single piece of foam in which a conduit has been formed . the conduit may be substantially spiral in shape , serpentine , or may any other appropriate configuration . as illustrated in fig1 - 17 , foam structure 150 may be positioned over the blower such that the gas conduit may be in communication with the intake of the blower . in one embodiment , the lowest foam disk 230 may include an aperture 300 configured to be positioned over the blower 310 . as illustrated in fig1 , foam disk 220 ( illustrated with dashed lines ) may be positioned over blower 320 , such that aperture 290 aligns with the intake 320 of the blower 310 . as illustrated in fig6 and 13 - 15 , foam structure 150 may be encased by a shell 160 . fig1 - 19 illustrate that shell 160 may include a plurality of concentric rings 350 , 360 , 370 , 380 , 390 and a cap 400 that may serve as a sound barrier between foam structure 150 and the environment . in addition , the shell 160 may provide mechanical support for foam structure 150 . in one embodiment , shell 160 may also provide a mechanism for compressing foam structure 150 into the compressed configuration and / or to lock foam structure 150 in the compressed configuration ( as illustrated in fig1 ). one or more of the conical rings 350 , 360 , 370 , 380 , and 390 may be designed to be longitudinally slidable with respect to adjacent rings and may have an interference ( e . g ., frictional ) fit with adjacent rings , which may allow the shell 160 to form a rigid structure and / or to be compressible when the noise suppression portion 110 is in the uncompressed and compressed configurations , respectively . cap portion 400 may include an inlet 410 . as illustrated in fig6 and 13 , inlet 410 may align with aperture 250 in foam disk 180 , and may allow gas to be drawn into the gas conduit in the foam structure 150 with relatively little flow resistance . decreasing the flow resistance may reduce the work required by the blower . the shell 160 may be manufactured from any rigid or semi - rigid material that can be formed in a ring or similar structure and which reflects sound waves , e . g ., metals , plastics , and composites . it may be understood that the shell 160 may include more or fewer rings than illustrated herein . moreover , shell 160 may alternatively include other collapsible structures , e . g ., accordion configurations or flexible walls including struts or other supporting members when the foam is in the relaxed configuration . fig2 illustrates a breathing assistance system including a system 100 including a noise suppression portion 110 , a patient 500 , and a tube 502 connected at one end to a port 130 of system 100 and at to the other end to a patent nasal mask 504 . while there have been described what are believed to be the preferred embodiments of the present disclosure , those skilled in the art will recognize that other and further changes and modifications may be made thereto without departing from the spirit of the disclosure , and it is intended to claim all such changes and modifications as fall within the true scope of the disclosure .

US-34009406-A

the invention comprises a device for treating presbyopia . a stretch segment is provided for implantation into the region extending between the outer circumference of the lens and extending to the sulcus region at the intersection of the iris and ciliary body . the stretch segment engages the equatorial zonules spanning between the lens and ciliary body . the segment is designed to take up slack in the equatorial zonules in the presbyopic eye , such that their effective working distance is enhanced . this aids in the accommodation process which affects the curvature of the lens for near viewing . the segment may a closed ring , or may be open ended .

under the theory of accommodation followed by the inventor , it is a pulling effect of the equatorial zonules that causes the change in shape necessary to refract incident light rays traveling through the eye into proper alignment on the retina . fig1 diagrammatically shows the basic anatomy of the human eye 10 . the cornea 12 permits the transfer of light into the eye , and the iris 14 regulates the amount of light which passes through the lens 16 . a framework of radially arrayed zonules 18 support the lens in place behind the iris . the zonules span between the lens 16 and ciliary body 20 . while it is understood that anterior , equatorial and posterior zonules make up the framework , for diagrammatic purposes , only the equatorial zonules are discussed . furthermore , under the theory of accommodation followed , it is primarily the equatorial zonules that are critical in affecting the lens shape change . as the ciliary body 20 contracts , as shown in the lower drawing of fig1 it exerts an outward pulling force on the zonules 18 , which in turn pull outwardly on lens 16 at its periphery . this causes the central bulge 15 in the lens with a greater degree of curvature which permits the passing light rays to refract appropriately to focus on the retina . in the eye of a person having presbyopia , the spanning zonules 18 have become slack and have lost their tautness between ciliary body 20 and lens 16 , as shown in fig2 . in such a case , the contraction of the ciliary body 20 is only effective in drawing out the slack in the zonules . the full range of the contraction does not adequately translate through the zonules , and therefore , only a minimal , if any , stretching effect is placed on lens 16 . accordingly , lens 16 does not undergo a significant change in curvature , as seen in the lower drawing of fig2 and light can not refract appropriately as it passes through the lens for near viewing . although the zonules have lost their tautness , they have not lost the ability to exert a pulling force . the zonules could again become effective in pulling and stretching the lens if their slack was reduced . by means of the instant invention , a stretch member capable of being inserted into the region outside the equator of the lens is provided for placing tension against the equatorial zonules spanning between the lens and the ciliary body . as shown in fig3 a stretch segment member 22 , which may comprise a closed or open - ended ring , is inserted in the circumferential region 24 surrounding the lens 16 . segment member 22 , acting as a cam , pushes against zonules 18 in a direction transverse to their length which shortens the effective length of the zonules between the ciliary body and the lens , effectively removing the slack in the zonules . by doing so , the translational effect of the contraction of the ciliary body through the zonules is increased . accordingly , the capability of the presbyopic eye to control the shape of the lens for near viewing can be regained . the stretch segment is preferably made of a biocompatible materials such as polymethyl methacrylate ( pmma ), although those skilled in the art would recognize that other biocompatible materials suitable for implantation into the eye may be used . the diameter of the stretch segment when inserted into the eye should be in the range of 6 - 20 millimeters . this approximates the dimensional range available in the region 24 between the outer equatorial circumference of the lens 16 extending to the sulcus 26 defining the border between the anterior aspect 28 of ciliary body 20 and iris 14 of a typical patient . the cross - sectional dimension of the stretch segment should be in the range between 10 microns to 3 millimeters , and preferably 0 . 5 to 1 . 5 millimeters , but must have a great enough size to effectively engage and transversely displace the zonules to a sufficient degree such that slack is removed . fig3 and 6 show one embodiment of the stretch segment 22 having a diameter slightly larger than the circumference of the lens . in this embodiment , the segment resides in the gap 24 between the lens and ciliary body . although not shown , it is to be understood that the segment may generally be disposed between the equatorial zonule bundles , and therefore , displacement may occur on either side of the segment . for diagrammatic purposes and ease of understanding the intended function of the invention , the drawings only show one side of the segment engaging the zonules . [ 0024 ] fig4 and 5 show another embodiment of a stretch segment 30 having a diameter approximating that of the sulcus 26 . in this embodiment , the segment resides snugly in the sulcus . in both of these embodiments , the respective stretch segments are adapted to directly engage the equatorial zonules . in yet a further embodiment ( not shown ), the stretch segment has a dimension slightly larger than the sulcus 26 . the segment engages the distal , anterior aspect of the ciliary body with a radially outwardly extending force which does not directly engage the zonules , but indirectly provides a supplementary stretching effect on the zonules . one embodiment of the stretch segment may form a closed ring having a fixed diameter . another embodiment contemplates an open , semi - circular member designed for optimal placement in the sulcus as shown in fig7 . the stretch segment may provide effective therapeutic benefit by engaging less than all the equatorial zonules , so long as a majority of the equatorial zonules are engaged . the segment may reach around to between 180 ° to approximately 360 °, and more preferably to between 270 ° to 360 ° of a circle , and is constructed to have a slight resistance to flexion so that it will fit snugly into the sulcus and provide an outward force against the ciliary body . this embodiment provides for custom fitting into a patient &# 39 ; s eye , and a segment can be constructed according to precise measurements depending on the degree of zonular stretching desired . the radius of curvature of a stretch segment can be configured to be slightly larger than the radius of the curvature of the patient &# 39 ; s sulcus region , so that the resultant diameter of the segment will be greater than that of the sulcus for a snug fit . it may be necessary to secure the ends of the semi - circular stretch segment member , either together or to a part of the eye , once it is placed within the eye . fig8 and 9 show two embodiments which provide the ability to draw and secure the two ends of the stretch segment together . fig8 shows stretch segment 40 having apertures 42 at each end . a fastening member , such as a suture filament , clip , or other device known to those skilled in the art , may be inserted in the apertures . the double - ended apertures provide for adjusting the effective diameter of the stretch segment as necessary . also , the apertures permit one or both ends to be sutured to a supporting surface within the eye . fig9 shows open ended stretch segment 50 having an end formed with aperture 52 and a complementary clasp 54 formed at the other end . clasp 54 has a shape enabling it to be manipulated to pass through aperture 52 in a sideways orientation and be secured therein by a retaining flange member at the end of clasp 54 . the apertures may also assist in the insertion and removal of the stretch segment . the stretch segment may be inserted in place using techniques similar to the implantation of similar devices such as lens capsular tension rings . the stretch segment can be inserted with a forceps through a 1 . 0 to 4 . 0 mm corneal incision . alternately , an inserting device such as that provided by ophtec bv ( easycontro ™ micro inserter ) may be used . the micro inserter is a hollow tube with a hook which can engage the open end of the stretch segment . the tube is inserted through a corneal incision into the anterior chamber of the eye . the distal end of the tube is placed near the sulcus region where the segment will be implanted . the plunger holding the segment in the tube is manipulated to push the segment out of the tube , causing the segment to glide into the sulcus . the stretch segment is placed in the anterior aspect of the zonular framework to engage the front surface of the equatorial zonules . various changes and modifications may be made within this invention as will be apparent to those skilled in the art . such changes and modifications are within the scope and teaching of this invention as defined in the claims appended hereto .

US-46494703-A

in the preferred embodiment , the invention is a system for creating micropores in the skin for transdermal drug delivery through the micropores and includes : a chemical that dissolves or breaks down superficial layers of skin ; a chemical delivery element that holds and delivers controlled volumes of the chemical to skin , creating micropores ; and a base that is able to temporarily couple to skin , contains the chemical delivery elements , and may activate the chemical delivery elements to administer the chemical to skin . in the preferred embodiment , the invention is a method for delivering drugs transdermally that includes providing a carrier containing a chemical delivery element with a chemical to break down superficial layers of skin ; placing the carrier into contact with skin ; activating the chemical delivery element ; allowing the chemical to break down superficial layers of skin and creating micropores ; and providing a drug to be delivered transdermally through the micropores .

the following description of preferred embodiments of the invention is not intended to limit the invention to these embodiments , but rather to enable any person skilled in the art to make and use this invention . as shown in fig1 and 2 , the system 10 of the preferred embodiments includes a chemical 16 , a series of chemical delivery elements 14 that hold and deliver the chemical 16 , and a base 12 that contains the chemical delivery elements 14 . when the base 12 is coupled to an outer layer of skin of a patient , the chemical delivery elements 14 are activated and function to deliver the chemical 16 to the outer layer of skin of the patient ( the stratum corneum ). the chemical 16 functions to create a series of micropores 18 , as shown in fig3 and 4 , in the outer layer of skin of the patient . because nerve endings do not reach the outer layer of skin , the patient does not feel pain from the creation of the micropores 18 . the system 10 of the preferred embodiment is preferably designed to enable transdermal drug delivery , and more specifically , to create a series of micropores 18 in an outer layer of skin of the patient . the micropores 18 preferably increase skin permeability of the patient , enabling a drug 22 ( shown in fig5 ) to reach the body of the patient . the system 10 of the preferred embodiments , however , may be alternatively used in any suitable environment and for any suitable reason . as shown in fig3 - 5 , the chemical 16 of the preferred embodiments functions to create a series of micropores 18 in the outer layer of skin ( the stratum corneum ) of the patient , which preferably increase skin permeability of the patient and enable a drug 22 to reach the body of the patient . the chemical 16 is preferably an agent that does not pose a threat if it is taken up by the vasculature and / or deposited in another location in the body of the patient . the chemical 16 is preferably one of several suitable agents such as acids , bases , lipid , and / or enzymes , but may alternatively be any other suitable chemical to dissolves , or otherwise breaks down , the skin and to create micropores 18 in outer layer or stratum corneum of the skin . in a first variation , the chemical 16 is preferably 10n potassium hydroxide ( 10n koh ), but may alternatively be any other concentration up to approximately 10n of potassium hydroxide . although 10n koh is relatively strong , the combination of the small volume held by each chemical delivery element and the small area of skin that the chemical 16 is contacting enables the chemical 16 to form precise micropores 18 in the superficial layers of the skin . in addition , as the chemical 16 diffuses through the skin and creates the micropores , the chemical 16 is subsequently diluted and loses its original ability to break down tissue such as vaculature or nerves once it has gone past the superficial layers of the skin . in alternative variations , the chemical 16 is preferably an acid such as hydrochloric acid ( hcl ), a base such as sodium hydroxide ( naoh ), an enzyme such as papain , bromelain , actinidin , ficin , or any other suitable agent such as esters . as shown in fig5 , the micropores 18 created by the chemical are preferably spaced such that they produce microscale , invisible channels into the skin through which drug molecules may diffuse or pass . the creation of the micropores 18 by the chemical 16 is preferably pain free and invisible to the eye . the micropores 18 are preferably in the range of approximately 10 μm to 300 μm in diameter , but may alternatively be of any appropriate size to allow a macromolecular drug ( preferably greater than 1 kda ) to diffuse through the outer layer of skin , while at the same time small enough such that the skin of the patient can naturally heal and / or close the pores . as shown in fig1 , the series of chemical delivery elements 14 of the preferred embodiments functions to hold and deliver the chemical 16 to the outer layer of skin of the patient . the series of chemical delivery elements 14 preferably function to focus a series of small volumes of a chemical 16 to a portion of the outer layer of skin of the patient . each chemical delivery element 14 is preferably on the order of 100 μm by 100 μm , but may alternatively have any other suitable dimension . the dimensions of the chemical delivery element 14 may also be specific to the drug 22 that is to be delivered by the system . to prevent overlap of the created micropores 18 because of diffusion of the chemical 16 through the skin , each chemical delivery element 14 is preferably spaced at least 50 μm ( center to center ) from one another . in the preferred embodiments , each chemical delivery element 14 is preferably spaced about 500 μm ( center to center ) from one another , but may alternatively have any other suitable spacing . each chemical delivery element 14 preferably holds a volume of 0 . 5 to 2 . 5 nl of the chemical 16 , but may alternatively hold any other suitable amount of chemical appropriate to create the desired micropores 18 while accommodating for variation in thicknesses of the superficial layers of skin . the series of chemical delivery elements 14 preferably holds a total volume of the chemical 16 of about 1 μl , but may alternatively hold a volume approximately of the range from 0 . 1 μl to 100 μl . however , the series of chemical deliver elements 14 may hold any other total volume suitable for creating miropores over the area necessary to transmit an appropriate dosage of transdermal drug 22 . the series of chemical delivery elements 14 is preferably one of several variations . in a first variation , as shown in fig2 and 3 , the series of chemical delivery elements 14 is a series of wells that function to hold a volume of the chemical 16 . each well is preferably cube - shaped , 100 μm × 100 μm horizontally and about 250 microns deep , but may alternatively have any suitable geometry of any suitable dimension . the material of the series of wells is preferably the same material a material that may be made temporarily hydrophilic and is otherwise hydrophobic . the material is preferably a polymer such as polydimethylsiloxane ( pdms ), which is a hydrophobic material that can be made temporarily ( less than 30 minutes ) hydrophilic when exposed to oxygen plasma . this property enables the wells to be loaded with the chemical 16 . a vacuum may be used to facilitate filling the wells with the chemical 16 . when the hydrophobic property of the material of the wells returns , it will form a tight interface between the chemical 16 and the wells , such that the chemical does not spill outside of the well . the hydrophobic property of the material also facilitates the deposition of chemical 16 onto the skin upon application to the skin . alternatively , a vacuum may be used to fill the wells without using oxygen plasma . however , any other suitable method for loading the delivery elements 14 with the chemical 16 may be used . in a second variation , as shown in fig6 , the series of chemical delivery elements 14 is a series of columns 26 that function to hold the chemical 16 such that when the base 12 is coupled to the outer layer of skin of the patient , the columns 26 function to deliver the chemical 16 to the outer layer of skin of the patient by “ stamping ” the chemical 16 onto the skin . in a third variation , as shown in fig7 , the series of chemical delivery elements 14 is a series of electrode sites 38 , electrochemically coated with a polymer having the chemical 16 . when the base 12 is coupled to the outer layer of skin of the patient , the chemical 16 will preferably leech out of the polymer coating into the outer layer of skin of the patient . the coating is preferably a thin coating , preferably on the order of 50 μm , but may alternatively be any other suitable thickness . the series of chemical delivery elements of this variation is preferably fabricated as shown in fig8 , but may alternatively be fabricated in any other suitable fashion . although the series of chemical delivery elements 14 is preferably one of these three variations , the series of chemical delivery elements 14 may be any suitable element to hold and deliver a chemical 16 . as shown in fig1 and 2 , the base 12 of the preferred embodiments includes the series of chemical delivery elements 14 and functions to couple to an outer layer of skin of a patient . when coupled to the skin of the patient , base 12 functions to activate the delivery elements 14 to deliver the chemical 16 . the base 12 is preferably of the same material as the chemical delivery elements 14 and is preferably made of a polymer such as polydimethylsiloxane ( pdms ), but may alternatively be made of any suitable material . the material of the base 12 is preferably inert and non - toxic , such that it is biocompatible . the base 12 is preferably removably fixable to the skin . the base 12 preferably includes an adhesive that is removably fixable to the skin , but may alternatively be removably fixable to the skin in any other suitable fashion . the base 12 preferably has dimensions of about 5 cm × 5 cm × 1 cm , and more preferably has dimensions of less than 2 cm × 2 cm × 0 . 5 cm , but may alternatively have any other dimension suitable to enable the appropriate dose of drug 22 to be delivered transdermally to the body . as shown in fig9 , the system 10 of the second embodiment is nearly identical to the system 10 of the first embodiment . the difference between the two embodiments , however , is that the system 10 of the second embodiment further includes a chemical reservoir 14 ′. in this embodiment , the chemical reservoir 14 ′ preferably includes an additional volume of the chemical 16 , which can ensure that the system 10 includes enough volume of the chemical 16 to create appropriately sized micropores 18 . the chemical reservoir 14 ′ preferably holds an additional total volume of chemical 16 of about 30 to 50 μl , but may alternatively hold any other suitable total volume . as shown in fig1 , the system 10 of the third embodiment is nearly identical to the system 10 of the first embodiment . the difference between the two embodiments , however , is that the system 10 of the third embodiment further includes a hydration reservoir 32 . in this embodiment , the hydration reservoir 32 preferably maintains the hydration level of the chemical 16 , which can prevent dehydration of the chemical 16 after the system has been packaged and while it is being stored . this arrangement may be quite useful in certain environments , such as to increase the “ shelf life ” of the system 10 . as shown in fig5 , the system 10 of the preferred embodiments also includes a drug delivery element 20 . the drug delivery element 20 functions to hold a drug 22 and functions to deliver a drug 22 to the micropores 18 created in the outer layer of skin of the patient . the drug delivery element 20 is preferably any suitable drug infused patch that functions to hold a drug 22 and functions to deliver a drug 22 to the skin . the drug 22 is preferably any suitable drug and more preferably any suitable macromolecular drug that functions to enter a patient &# 39 ; s body through a series of micropores 18 created by the system 10 . one specific example of a suitable drug is botulinum toxin , or botox . other examples of suitable drugs include enoxaparin ( lovenox ), caspofungin ( cancidas ), etanercept ( enbrel ), somatostatin ( sandostatin ), or any other high molecular weight pharmaceuticals . the drug 22 may further include a buffer to neutralize the chemical 16 in the body of the patient before the drug 22 enters the body of the patient . as shown in fig1 , the system 10 of the fourth embodiment is nearly identical to the system 10 of the first embodiment . the difference between the two embodiments , however , is that the system 10 of the fourth embodiment further includes a drug reservoir 34 , that functions to store and deliver drug 22 , and at least one pillar 36 that functions to simultaneously lift the base 12 off of the surface of the skin and compress the drug reservoir 34 such that the drug 22 exits the drug reservoir 34 . in this embodiment , the chemical 16 is preferably applied to the skin to create the series of micropores 18 . the pillars 36 are then activated such that they lift the base 12 off of the surface of the skin and compress the drug reservoir 34 . the pillars are preferably activated by gas expansion . the gas expansion may be activated by the user , but may also be an automatic gas expansion that expands at a rate that allows the chemical delivery elements 14 to administer the appropriate amount of the chemical 16 for the appropriate length of time before fully lifting the base 12 off the surface of the skin . however , the pillars may alternatively be activated by any other suitable mechanism . once the base 12 is lifted off the surface of the skin , and the drug 22 exits the drug reservoir 34 , the drug 22 preferably seeps below the lifted patch and enters the micropores 18 in the skin . the drug 22 in this embodiment preferably includes a buffer to neutralize the chemical 16 in the body of the patient before the drug 22 enters the body of the patient . the system 10 may alternatively include a drug reservoir 34 that supplies the drug 22 to the micropores 18 in any other suitable arrangement . the system 10 of the preferred embodiment is preferably micro - machined using standard microfabrication techniques , but may alternatively be fabricated in any other suitable fashion . as shown in fig1 , the method of the preferred embodiments includes the steps of providing a wafer s 100 , building up the mold material s 102 , masking a portion of the mold material s 104 , removing a portion of the mold material s 106 , adding the base material to the mold s 108 , and removing the base 12 , which has a series of chemical delivery elements 14 , from the mold s 110 . the method is preferably designed for the manufacture of system 10 for transdermal drug delivery . the method , however , may be alternatively used in any suitable environment and for any suitable reason . one specific example of the method of the preferred embodiments uses photolithography or photolithographic patterning to create the mold . in step s 100 , a bare silicon wafer is first cleaned in acetone and isopropyl alcohol ( ipa ) to remove any organics or surface impurities . ap300 is then preferably spun onto a clean four - inch wafer at 500 rpm for 5 seconds , followed immediately by 4000 rpm for 30 seconds . ap300 functions to improve su8 adhesion . in step s 102 , the mold material , su8 - 2075 ( microchem corp . ), is preferably spun onto the wafer . the thickness of the mold material is preferably of 250 μm , but may alternatively be any other suitable thickness . the mold material is preferably su - 8 , but may alternatively be any other suitable material , which functions well with the chosen material for the base 12 . the spread cycle in this variation preferably lasts 12 seconds at 500 rpms ( a = 100 rpm / s ) while the spin cycle is preferably 1 , 200 rpm spin for 30 seconds ( a = 300 rpm / s ). after settling for 30 minutes , the wafer is preferably soft baked initially at 65 ° c . for 7 minutes followed immediately by a second bake at 95 ° c . bake for 45 minutes . deep edge bead removal is then preferably performed by washing the edge of the wafer with acs soaked 10 mm brush while the wafer was spinning at 500 rpm . the edge is then preferably cleaned with developer while the wafer is preferably spun at 500 rpm . in step s 104 , a mask 24 is preferably applied to the surface of the wafer using a glass sheet . as shown in fig1 , a specific example of the mask 24 is a square grid of 25 by 25 chemical delivery elements over a 1 . 4 cm × 1 . 4 cm area . each chemical delivery element is 100 μm width and 100 μm height with 500 μm spacing ( center - to - center ). the mask 24 may alternatively have any other suitable geometry with any other suitable dimensions . the mask 24 , on the mold material , is then preferably exposed for 15 seconds with 60 second pauses , repeated 5 times for an approximate total exposure of approximately 450 mj / cm2 and put through a post exposure bake at 65 ° c . for 5 minutes , immediately followed by at 95 ° c . for 15 minutes . in step s 106 , the excess mold material is removed by soaking the wafer in developer for 17 minutes with agitation , and , after removing the wafer , it is preferably sprayed by a developer for 10 seconds , then ipa for 10 seconds , followed by a rinse with dih 2 o . after air - drying the wafer , it is preferably hard baked at 150 ° c . for 5 minutes to prepare the mold . the patterned su - 8 layer then preferably serves as a mold for the base 12 , as shown in step s 108 in fig1 . the mold is then preferably incubated in a chamber with 1 ml of methyltrichlorosilane for 30 minutes at room temperature . the material for the base 12 is then preferably prepared by mixing pre - polymer and curing agent in a 10 : 1 ratio . the mixture is degassed in a vacuum changer to remove bubbles for 30 minutes , and then poured onto the wafer without forming bubbles . the wafer is then baked at 80 ° c . for 30 minutes . however , any other suitable process may be used to create a mold and the base 12 . as shown in fig1 , the base 12 , removed from the mold , is preferably plasma oxidized , making it hydrophilic ( step s 200 ). step s 202 shows the chemical 16 deposited over the surface of the base 12 and chemical delivery elements 14 . in s 204 , a vacuum is preferably applied to fill the chemical delivery elements with the chemical 16 . as shown in fig1 , the system 10 may alternatively be filled with the chemical 16 by use of a channel system 28 such that the chemical 16 may be inserted into the base 12 from the opposite side of the chemical delivery elements 14 . in this variation , oxygen plasma may be similarly used to make the chemical delivery elements 14 and channel system 28 to be hydrophilic and a vacuum is then preferably applied to fill the channel system 28 and the chemical delivery elements 14 with the chemical 16 . once the chemical 16 is inserted into the base 12 , and the chemical delivery elements 14 are filled with the chemical 16 , the channel system 28 is preferably sealed with any suitable cap or sealant 30 . in both variations , a vacuum may be used alone to fill the chemical delivery elements 14 ( and the channel system 28 ) without the assistance of oxygen plasma . however , any other suitable type of method or catalyst for filling the chemical delivery elements 14 with chemical 16 may be used . although omitted for conciseness , the preferred embodiments include every combination and permutation of the various bases 12 , chemical delivery elements 14 , chemicals 16 , drug delivery elements 20 , drugs 22 , and methods of making these elements . as a person skilled in the art will recognize from the previous detailed description and from the figures and claims , modifications and changes can be made to the preferred embodiments of the invention without departing from the scope of this invention defined in the following claim .

US-33437908-A

the present invention relates to a nano - enhanced device for substance transfer between the device and a tissue . the device comprises a substrate with substantially aligned carbon nanotubes anchored within the substrate , and with at least one end of the carbon nanotubes protruding from the substrate . the protruding nanotube ends may be coated with a drug for delivery of the drug into body tissue . the present invention may be incorporated into an angioplasty catheter balloon or into a patch that is worn on the skin . the carbon nanotubes can be grouped in clusters to effectively form nano - needles which can transfer fluid to or from the subdermal tissue . the nano - needles can be used in conjunction with a sensor to ascertain body fluid information such as ph , glucose level , etc .

referring to fig1 and 2 , the preferred embodiment of the inventive medical method can be shown . the medical method is performed laparoscopically in 90 % of the cases . in fig1 , the organs of the esophagus 10 , stomach 14 , duodenum 16 , small intestine 18 and gall bladder 20 are shown . the focus of the medical method is upon the modifications made to the esophagus 10 , stomach 14 and small intestine 18 . as first shown in fig1 , a gastric pouch is manufactured by preferably separating the esophagus 10 and part of the lesser curvature 22 of the stomach from the remainder of the stomach 14 at point a . the small intestine 18 is bisected at point b . the location of point b is preferred because it results in the duodenum 16 being completely bypassed along with the stomach 14 . bypassing the duodenum results in selective fat malabsorption which results in more weight loss than in prior art gastric bypass methods . the duodenum remains fully functional and continues to receive liver bile from the hepatic ducts 24 and enzymes from the pancreatic duct 26 . referring now to fig2 , the formation of the gastric pouch and the re - connection of the small intestine can be described . the proximal stomach is bisected on the lesser curvature 22 just below the esophagus 10 , leaving a small stomach segment 28 that is connected to the proximal jejunum 18 , this esophogeal and small stomach segment is what will eventually form the gastric pouch 30 having a size of between 20 - 30 cc . the bottom section of the small intestine ( proximal jejunum ) 18 below the duodenum 16 is connected to the small stomach segment 28 through a hand sewn closure to form an anastomosis ( not shown ) that is 1 . 5 to 2 cm wide . the anastomosis is impervious to air and water and allows direct entry of the contents of the gastric pouch 30 into the small intestine 18 , which causes the release of satiety stimulating chemicals known as enterokinins . this release of enterokinins is even induced by the obese individual &# 39 ; s salivary secretions that go from the gastric pouch 30 to the small intestine 18 . this feeling of satiety , or “ fullness ” results in anorexia and enhances initial weight loss as well as the maintenance of weight loss over time . above the anastomosis and above the bottom of the pouch 30 , about 2 cm , is placed the inventive gastric bypass band device 32 . the gastric band device acts as a restrictor valve which controls the emptying of partially digested food materials from the gastric pouch 30 . the gastric band 32 is preferably placed at the distal portion of the gastric pouch 30 . when the inventive gastric band is in place , the portion of the pouch above the gastric band is 15 to 20 cc in capacity and the portion of the pouch below the band is about 8 to 10 cc in capacity . this compared to the normal 2000 - 3000 cc capacity of the stomach illustrates the restriction in food intake provided by the gastric pouch . once the gastric pouch is full of food materials , a feeling of satiation is experienced , resulting in anorexia . the gastric band device 32 preferably ranges in size between 5 . 5 - 7 . 0 cm in inner circumference . in addition to its function as a restrictor valve , the gastric band 32 prevents stomach dilation , meaning that the restricted opening provided by the band never expands in size due to the expansion - resistant construction of the device . moreover , the pouch 30 is more resistant to expansion than the stomach . the relative size of the pouch ensures that excessive expansion does not occur . patients that have been x - rayed five years post - surgery show that the pouch has not expanded by much . moreover , the small size of the pouch insures that if a patient over - eats , the food will back up into the esophagus , thereby causing the patient to regurgitate the food . this factor operates as a self - regulating feature , and for this reason , patients are counseled to keep their food intake to a minimum . the duodenum 16 is re - joined to the small intestine 18 to form a y - limb 34 , with one deviation of the limb going upward to the duodenum and the other deviation proceeding upward to the gastric pouch 30 . the intestine - intestine connection 36 forms an anastomosis ( not shown ) of approximately 2 cm , that is wide enough to allow food to pass through easily . at the point of anastomosis , pancreatic juices and liver bile from the duodenum can now come into contact with the partially digested food that travels down the second section of the intestine from the pouch . liver bile begins fat digestion for the first time , and as a result , fats are only partially absorbed , thereby helping contribute to weight loss . sugars are absorbed , but discouraged as part of the patient &# 39 ; s diet , because with the stomach disconnected , they go directly into the intestines , causing some patients to have “ dumping syndrome .” this is a very uncomfortable feeling of cramps , flushing , fast beating heart , weakness and sometimes watery stools . the stomach 14 , although disconnected , remains fully functional , and if necessary can be reactivated by reversing the surgery and re - connecting the stomach segment 28 and small intestine 18 to their prior , natural , state . the stomach 14 can also be reactivated by placing a temporary gastrostomy tube 38 , as shown , through which food can be routed , should this be necessary . to facilitate the reactivation of the stomach 14 , the stomach opening 40 can be marked with a radiopaque marker band 42 or disk , that is sutured to the abdominal wall , thereby making it clearly visible to allow the surgeon to find the stomach entry site 40 on an x - ray , to allow easy reactivation . the inventive gastric bypass band device 32 that was introduced previously , as being crucial to the successful result of the inventive surgical method , will now be described in terms of its preferred embodiment . referring to fig3 , the gastric bypass band 32 is comprised of an expansion - resistant section 44 mated to a latch 46 , which locks upon full engagement , thereby preventing the device 32 from opening up while positioned within the body . the latch 46 is of a one - way variety and can only be released through the application of a specialized surgical tool ( not shown ). the expansion - resistant section 44 prevents the device from expanding too far , thereby restricting the amount of food traveling from the gastric pouch 30 to the small intestine 18 . it is important for the device to retain food within the pouch long enough for the patient to feel sated , thereby reducing hunger and preventing further eating . the expansion - resistant section 44 is preferably made from implant grade silicone rubber surrounding a monofilament core . the monofilament can be polypropylene suture material , which is resistant to expansion . the latch is preferably made from surgical - grade plastics such as polypropylene or acetal , which gives both strength and lubricity to the latch . fig4 shows a transverse cross section of the expansion - resistant section 44 which illustrates the monofilament core 48 surrounded by silicone material 50 . alternatively , the silicone material can be a silicone tube having a monofilament core therein . the expansion - resistant section 44 preferably has a flat - faced inner side 52 as shown . this flat face 52 continues longitudinally along the length of the expansion - resistant section 44 . the flat face 52 forms a flat - sided inner circumference when the latch of the device is engaged , as shown in fig3 . it has been found that the flat face prevents the expansion - resistant section from migrating into the patient &# 39 ; s tissue and prevents tissue erosion . also crucial with regard to preventing leakage caused by the device eroding into the internal lumen of the gastric pouch is that the cross - sectional diameter of the expansion - resistant section 44 is kept to 0 . 125 ″, or less . if erosion occurs , it has been found that if the cross section is kept to these approximate dimensions the pouch tissue will form a scar around the band device 32 , and in essence seal off the device , thereby preventing any leakage . erosion is caused by tissue necrosis , where tissue dies when the supply of blood to the area is cut off . prior art larger , thicker , band devices , have been known to necrose when the food pouch begins to sag , making a deep sack out of which food has difficulty being passed . this food begins to decay in the pouch , which can lead to necrotic complications . the larger , thicker , prior art devices penetrate the necrosed area in time , creating a break in the gastric pouch , which can lead to leakage of the pouch contents into the interior of the body cavity . in the worst cases this can lead to death ; in the minor cases , additional surgery is necessary to repair the breached pouch . contrastingly , fewer pouch breaches are experienced with the present invention than with the prior art devices . referring now to fig5 a , 5b and 5c the latch 46 can be examined . the latch is preferably a one - way latch employing a one - way male - female engagement . the opposite ends 54 , 56 of the expansion - resistant section 44 are each mated to one - half of the male - female latch as shown in fig3 and a preferred method of mating is further described below . as shown in fig5 a , the female portion 58 of the latch 46 is illustrated in detail . the female portion has an exterior body 60 and an interior lumen 62 for receiving the male portion 64 of the latch . the lumen 62 is sized to compress the lateral prongs 66 of the male portion 64 . under surgical conditions , engagement of the male and female portions is performed with a forceps , laparoscopically . the preferred interior lumen 62 dimensions are approximately height = 0 . 082 ″× width = 0 . 190 × length = 0 . 300 ″. a pair of openings 68 are placed in each side 70 of the female portion 58 to allow for the expansion of the lateral catches 72 of the male portion 64 . the lateral catches 72 engage fully and laterally within the side openings 68 , in a one - way fashion . side openings 68 have top , bottom , rear and front walls , which engage catches 72 . the engagement is such that the latch can be released only after applying a special surgical tool ( not shown ) to disengage the latch 46 , by placing inward force upon catches 72 through side openings 68 . the lumen 62 opens outward and the face 74 of the opening of the lumen is inwardly beveled so as to receive the outward bevels 76 of the male portion 64 . the corner facings 78 of the female portion 58 are rounded so as to present a non - irritating surface to the patient . still referring to fig5 a , the body 60 of the female portion 58 is longitudinally curved 80 . the curvature of the female portion 58 mates with the longitudinally curved male portion 64 to form the device 32 into a radial shape as shown in fig6 . this radial shape is crucial for preventing the device from becoming ingrown within a patient &# 39 ; s tissue , as this shape applies equal pressure to the enclosed tissue at every point along the inside circumference of the device 32 . shapes that are non - circular ( e . g . oblong shapes ) tend to apply unequal pressure along their inside circumference , thereby resulting in a cutoff of blood supply , necrosis , and eventual tissue erosion and leakage as discussed previously . for each graduation in inner circumference of the inventive device 32 , a corresponding radius of curvature applies which contributes to the forming of the proper radial shape in each case . the radii of curvature in inches is listed after each graduation in inner circumference ( centimeters ) as follows : 5 . 5 cm = 0 . 398 ″; 6 . 0 cm = 0 . 422 ″; 6 . 5 cm = 0 . 460 ″ and 7 . 0 cm = 0 . 492 ″. also , for the same graduations , the following diameters apply : 5 . 5 cm = 1 . 75 cm dia ; 6 . 0 cm = 1 . 91 cm dia ; 6 . 5 cm = 2 . 07 cm dia ; 7 . 0 cm = 2 . 23 cm dia . the inner circumference that is used is open to the discretion of the surgeon , but generally , men require 6 . 5 and 7 . 0 cm sizes while women require 5 . 5 and 6 . 0 cm devices . referring now to fig5 b , the male portion of the latch is shown as comprising a pair of lateral prongs 66 , the prongs being longitudinally curved to mate efficiently within the lumen 62 of the female portion 58 . preferably , prongs 66 are approximately 0 . 076 ″ thick , by 0 . 040 ″ wide . the prongs terminate at their front with lateral catches 72 which are molded integrally with the prongs 66 . lateral catches 72 are angled longitudinally along their side face 84 , the angled attitude allowing easy entry of the prongs 66 into the lumen 62 of the female portion 58 , which is an important feature under surgical conditions . side faces 84 having steeper angles give a mechanical advantage when locking . the preferred angle of side faces is 36 degrees or less . the catches 72 further comprise lateral catch faces 86 , which engage the front walls of the side openings 68 of the female portion 58 . when the catches 72 of prongs engage , it is preferred that they remain engaged under a pulling stress of at least 5 pounds of force . the prongs 66 are separated by inner space 88 , which allows the prongs to travel inward and outward . the prongs 66 terminate rearwardly at prong body 90 , which provides a base of structural integrity from which prongs can confidently travel inward and outward as they engage the interior walls of lumen . prong body 90 migrates further rearward to become outwardly beveled face 76 which mates with inwardly beveled face 74 of the female portion 58 . the beveled face 76 migrates further rearward to become hilt 92 . hilt 92 is where the front opening of the female portion 58 fully engages against . this engagement is shown in fig5 c which illustrates lateral catches 72 seated in the side openings 68 of female portion 58 , the hilt being 92 engaged with the front opening of female portion . the circumference of the body 60 of female portion 58 and the circumference of the hilt 92 of the male portion 64 are preferably identical so as to provide a fairly uninterrupted surface traveling from one to the other . also shown in fig5 a and 5b are anchor arms 94 , which are used to attach the male and female portions of latch to the expansion - resistant section 44 . anchor arms 94 retain the curved theme of the male and female portions , 58 , 64 of the latch 46 . anchor arms 94 are molded integrally with their corresponding latch portion and curve rearwardly so as to retain the radii of curvature of the inventive device noted previously . the expansion - resistant section which is comprised of surgical grade silicone and monofilament is attached to the anchor arms as follows . referring again to fig5 b , the front opening 96 of lumen 98 is shown , and its rearward path of travel through anchor arm is shown in phantom . a similar arrangement exists for female portion . monofilament 48 enters the rear of anchor arm and is fed through lumen until it protrudes through the front opening of lumen . the monofilament 48 is then tied off in a manner so as to anchor it in place along with the silicone material as seen in phantom , in fig3 . as fig7 a - 7b show , the body 60 of female portion 58 may also be fitted with a disposable cover 100 so as to reduce its potential to snag upon tissue as it is being fed through and positioned around the gastric pouch 30 during laparoscopic surgery . as the device is fed through the tissue and around the new pouch , it is led by the female portion 58 . cover 100 provides a streamlined shape which can be grasped by a forceps and easily led through the tissue . fig7 a is a side view showing the female end 58 positioned in the cover 100 , with the remainder of the device trailing out the back end 102 of cover 100 . back end 102 of cover includes a lumen ( see fig7 b ) 104 for receiving female end 58 , the lumen being sized to snugly grasp female end without coming loose during surgical placement . the sides of lumen are preferably ringed with small ridges 106 to reduce the frictional engagement between female portion 58 and the cover 100 to a level that allows easy removal of the cover once the device is in place . as seen in fig7 b , cover 100 further comprises a blunt front end 108 which extends into an elongate portion 110 . the blunt front end 108 facilitates easy movement through tissue . the elongate portion 110 is for grasping by the surgeon &# 39 ; s forceps to allow the cover to be threaded through tissue . past the elongate portion 110 , the cover 100 has a gently tapered region 112 , which , again contributes to easy movement through tissue . at its widest point , the cover is about . 250 to allow easy movement through a trocar during laparoscopic surgery . the cover is preferably made from a radiopaque material for easy sighting on an x - ray . the cover is removed and discarded once the device has been positioned around the gastric pouch . referring now to fig8 , the radiopaque marker band 42 previously shown in fig2 can be more precisely described . the band &# 39 ; s inside diameter is approximately 0 . 8 ″ and the outside diameter is approximately 1 ″ with a thickness of approximately 0 . 06 ″. the band is preferably flat along its major surfaces 114 , 116 . the marker band 42 can be made from polyester mesh that is coated with surgical grade silicone . also , it is envisioned by the inventor that the inventive device 32 can be combined with the radiopaque marker band 42 shown in fig8 , as well as with the disposable cover 100 to form a surgical kit . this kit can then be installed surgically using the method previously described . finally , although the description above contains many specificities , these should not be construed as limiting the scope of the invention but as merely providing illustrations of some of the presently preferred embodiments of this invention . other modifications by those skilled in this art are possible and are included within the scope of the appended claims .

US-201615170831-A

a method for reducing sunburn cells in human skin includes applying a topical preparation comprising an amount of an agent effective to reduce the formation of sunburn cells in human skin , and exposing the skin to ultraviolet radiation . the agent includes idebenone or a derivative of idebenone .

chemical derivatives of idebenone may also be suitable for use in a method according to the present invention . such derivatives may include , for example , esters and salts of idebenone , or protein bound forms , or other derivatives . examples of idebenone derivatives include esters of idebenone where idebenone is esterified using glycosaminoglycans and / or their salts , for example hyaluronic acid having a molecular weight of 1 to 1 , 000 , 000 and its salts or hyaluronidase inhibitors , such as for example inter - alpha - trypsin inhibitor . an example of a hydrophilic idebenone ester ( separate synthesis ) is idebenone sulphonic acid , characterized by the following structural formula : an exemplary synthesis of idebenone sulphonic acid was performed as follows : idebenone was reacted with pyridine - so 3 and the reaction was then stopped using 1 n hydrochloric acid . after shaking out the organic phase using ethyl acetate , the organic phase was dried and concentrated under vacuum . the residue was dissolved in water and insoluble products centrifuged off . the hydrophilic idebenone ester thus recovered is suitable for application according to the invention in aqueous cosmetic and dermatological preparations . compositions according to the present invention may contain a concentration of idebenone or a derivative of idebenone of about 0 . 001 - 30 %, 0 . 01 - 10 . 0 %, 0 . 1 - 2 . 0 %, or 0 . 5 % to 1 . 0 % by weight of the composition . the compositions may be cosmetic , dermatologic , or pharmaceutical preparations or compositions , and may exist in a wide variety of forms , such as emulsions , suspensions , solutions and the like . in certain embodiments , the compositions are in the form of lotions , creams , and other types of cosmetic compositions . for administration , the cosmetic and dermatological preparations of the invention may be applied to the skin in adequate quantity in the manner conventional for cosmetics . cosmetic and dermatological preparations of the invention may exist in various forms . hence , they may be , for example a solution , an anhydrous preparation , an oil - free preparation , an emulsion or microemulsion of the type water - in - oil ( w / o ) or of the type oil - in - water ( o / w ), a multiple emulsion , for example of the type water - in - oil - in - water ( w / o / w ), a gel , a solid stick , an ointment or even an aerosol . it is also advantageous to administer idebenone and / or its derivatives in encapsulated form , for example in collagen matrices and other conventional encapsulation materials , for example as cellulose encapsulations , in gelatine , wax matrices or liposomally encapsulated . it is also possible and advantageous within the scope of the present invention to add idebenone and / or its derivatives , such the sulphate of idebenone , for example , to aqueous systems or surfactant preparations for cleansing the skin . the cosmetic and dermatological preparations of the invention may contain cosmetic auxiliaries , as are used conventionally in such preparations , for example preservatives , bactericides , perfumes , substances for preventing foaming , dyestuffs , pigments which have a coloring effect , thickening agents , surfactant substances , emulsifiers , softening , moisturizing and / or moisture - retaining substances , fats , oils , waxes or other conventional constituents of a cosmetic or dermatological formulation , such as alcohols , polyols , polymers , foam stabilizers , electrolytes , organic solvents or silicone derivatives . in particular , idebenone and its derivatives may also be combined according to the invention with one or more traditional or other anti - oxidants and / or free - radical absorbers that are suitable or conventional for cosmetic and / or dermatological applications . such anti - oxidants include , for example , one or more of the following : antioxidant enzymes ( for example superoxide dismutase , catalase , glutathione peroxidase , glutathione s - transferase , glutathione reductase ), antioxidant botanical extracts ( for example green tea , white tea , black tea , licorice , grape , bilberry ), plant growth factors ( for example n - furfuryladenine ), amino acids ( for example glycine , histidine , tyrosine , tryptophan ) and their derivatives , imidazoles ( for example urocanic acid ) and their derivatives , peptides , such as d , l - carnosine , d - carnosine , l - carnosine and their derivatives ( for example anserine ), carotinoids , carotenes ( for example alpha - carotene , beta - carotene , lycopene ) and their derivatives , chlorogenic acid and its derivatives , lipoic acid and its derivatives ( for example dihydrolipoic acid ), aurothioglucose , propylthiouracil and other thiols ( for example thioredoxin , glutathione , cysteine , cystine , cystamine and their glycosyl , n - acetyl , methyl , ethyl , propyl , amyl , butyl and lauryl , palmitoyl , oleyl , gamma - linoleyl , cholesteryl and glyceryl esters ) and their salts , dilauryl thiodipropionate , distearyl thiodipropionate , thiodipropionic acid and their derivatives ( esters , ethers , peptides , lipids , nucleotides , nucleosides and salts ) and sulphoximine compounds ( for example buthionine sulphoximines , homocysteine sulphoximine , buthionine sulphones , pentathionine sulphoximine , hexathionine sulphoximine , heptathionine sulphoximine ) in very low , acceptable doses ( for example pmole to μmoles / kg ), also ( metal ) chelating agents ( for example alpha - hydroxy fatty acids , palmitic acid , phytic acid , lactoferrin ), alpha - hydroxy acids ( for example citric acid , lactic acid , malic acid , mandelic acid , gluconolactone , lactobionic acid ), humic acid , colic acid , colic extracts , bilirubin , biliverdin , edta , egta and their derivatives , unsaturated fatty acids and their derivatives ( for example gamma - linolenic acid , linolic acid , oleic acid ), folic acid and their derivatives , ubiquinone and ubiquinol and their derivatives , vitamin c and derivatives ( for example ascorbyl palmitate , mg - ascorbyl phosphate , ascorbyl acetate ), tocopherols and derivatives ( for example vitamin e acetate ), vitamin a and derivatives ( for example vitamin a palmitate ) and coniferyl benzoate of benzoin resin , rutinic acid and their derivatives , butylhydroxy toluene , butylhydroxy anisole , nordihydroguaiacic acid , nordihydroguaiaretic acid , trihydroxybutyrophenone , uric acid and its derivatives , mannose and its derivatives , sesamol , sesamolin , zinc and its derivatives ( for example zno , znso 4 ), selenium and its derivatives ( for example selenium methionine ), stilbenes and their derivatives ( for example stilbene oxide , trans - stilbene oxide ) and suitable derivatives ( salts , esters , ethers , sugars , nucleotides , nucleosides , peptides and lipids ) of these said active ingredients . the quantity of the aforementioned anti - oxidants ( one or more compounds ) in the preparations may be , for example , 0 . 0001 wt . % to 30 wt . %, 0 . 05 wt . % to 20 wt . %, or 1 to 10 wt . %, based on the total weight of the preparation . emulsions according to the invention may contain , for example the said fats , oils , waxes and other adipoids , and water and an emulsifier , as is used conventionally for such a type of formulation . also any mixtures of such oil and wax components can be used advantageously within the scope of the present invention . it may also optionally be advantageous to use waxes , for example cetyl palmitate , as the single lipid component of the oil phase . gels according to the invention may contain alcohols of low c number , for example ethanol , isopropanol , 1 , 2 - propane diol , glycerine and water or an above - mentioned oil in the presence of a thickening agent ,- which for oily - alcoholic gels is preferably silicon dioxide or an aluminium silicate , for aqueous - alcoholic or alcoholic gels is preferably a polyacrylate . conventional highly volatile , liquefied propellants , for example hydrocarbons ( propane , butane , isobutane ), which may be used alone or mixed with one another , are suitable as propellants for preparations which can be sprayed from aerosol containers according to the invention . compressed air can also advantageously be used . preparations of the invention may also contain filter substances that absorb uv radiation , or sunscreens , wherein the total quantity of filter substances is , for example 0 . 1 wt . % to 30 wt . % or 0 . 5 wt . % to 10 wt . %, based on the total weight of the preparation . the preparations may also serve as sunscreen agents for the skin . such uv filter substances include , for example , the following : avenobenzene , cinoxate , dioxybenzone , homosalate , menthyl anthranilate , octocrylene , octyl methoxycinnamate , octyl salicylate , oxybenzone , padimate o , phenylbenzimidazole sulfonic acid , sulisobenzone , titanium dioxide , trolamine salicylate , and zinc oxide . a preparation according to the invention may be an oil and water , water and oil , a water and oil , or a water emulsion including , for example , by weight of the preparation : from about 10 % to about 90 % of water ; from about 0 % to about 20 % of at least one humectant ; from about 0 % to about 20 % of at least one emollient ; from about 0 % to about 20 % of at least one ester ; from about 0 % to about 10 % of at least one thickener ; from about 0 % to about 2 % of at least one preservative ; from about 0 % to about 1 % of color ; and from about 0 % to about 1 % of fragrance . a preparation according to the invention may be an oil and water , water and oil , a water and oil , or a water emulsion including , for example , by weight of the preparation : from about 50 % to about 90 % of water ; from about 1 % to about 10 % of glycerin ; from about 1 % to about 5 % of cetyl ricinoleate ; from about 1 % to about 5 % of isohexadecane from about 1 % to about 5 % of ceresin ; from about 0 . 5 % to about 2 . 5 % of sericin ; from about 0 . 1 % to about 1 % of glycosaminoglycans ; from about 0 . 1 % to about 1 % of dimethicone ; and from about 0 . 001 % to about 30 % of idebenone . in the method according to the invention idebenone - containing compositions are applied to human , skin . the compositions may be applied once or more times per day depending on the activities the particular individual is engaged in . for example , an individual engaging in normal workday activities may wish to apply the compositions twice a day , once in the morning , and once in the evening , in conjunction with normal grooming . on the other hand , if the individual plans outdoor activities such as sunbathing and athletics , the compositions may be applied prior to , and during , such activities , much like a sunscreen composition is applied periodically during the day . the compositions may be used to reduce sunburn cell formation on the face and neck , by applying appropriate idebenone compositions to the face and neck areas . however , the idebenone compositions may also be applied to the entire body , particularly areas which are not covered by clothing , such as the arms , neck , and lower legs . it has been found the application of idebenone - containing compositions in this manner significantly reduces the number of sunburn cells which are formed upon exposure to uv radiation , particularly uvb radiation . referring to example 2 below , generally , the extent of sunburn cell formation is determined by obtaining slide preparations of skin cells according to well known histological techniques . the slides are then stained with hematoxylin - eosin , and the number of dyskeratotic cells per high power field ( generally 100 × magnification ) is counted . generally a number of high power fields are counted , for example 25 to 100 high power fields per sample , to ensure relability of results . mean sunburn cell counts from skin areas treated with the idebenone - containing composition are compared with the sunburn cell counts from untreated skin and placebo treated skin are compared . the idebenone used in the examples according to the present invention presented below was obtained from alpin chemical company , although idebenone is available from other sources . the invention will be described in connection with the following examples which are set forth for the purposes of illustration only . w / w % formula : 1 2 3 idebenone 1 . 0 0 . 10 0 . 01 sd alcohol 40b 75 . 0 75 . 00 75 . 00 di water 24 . 0 24 . 90 24 . 09 to prepare formulas 1 , 2 and 3 , the idebenone was added directly to the sd alcohol 40b while stirring until dissolved . di water was then added to the solution with continued stirring . the idebenone - containing formulas 1 , 2 , and 3 of example 2 and a non - treated control ( nt ) were applied to human skin in a 2 - week human sunburn cell assay study . the panel composition was six different healthy adult volunteers between the ages of 18 and 53 . all were in excellent health , and without any significant internal or dermatological diseases . the subjects were carefully screened to ensure they were not taking any medications . all had a clear back free of blemishes or a tan and were of skin types ii and iii according to the following classification scheme : type i : always burns easily , never tans ( sensitive ) type ii : always burns easily ; tans minimally ( sensitive ) type iii : burns moderately ; tans gradually — normal skin ( light brown ) the subjects were given detailed instructions to avoid any direct exposure to sunlight and to minimize any incidental exposure to their backs for the entire duration of the study . no other topical products were allowed , and no medications including over - the - counter ( otc ) products were to be used except for acetaminophen ( e . g ., common tylenol ®) for the relief of transient pains or headaches . individual test sites were delineated over the midback region . the test products were randomly allocated amongst the test sites according to a randomization schedule prepared by the investigator . the subjects came in once daily to the laboratory and received supervised applications of the test products to the allocated test sites . all test products were dispensed by a technician using 1 cc disposable plastic tuberculin syringes . each site received 100 μl ( 2 μl / square cm ) of , as appropriate , formula 1 , 2 or 3 of example 3 , or no formula ( normal , untreated skin site ). the test product was then spread uniformly throughout the 5 × 10 cm rectangular test site using a finger cot . the subjects received once daily application for two consecutive weeks ( except on weekends ). the light source used was a 150 watt xenon arc solar simulator equipped with a uv reflecting diachronic mirror and a 1 mm thick schott wg - 320 filter to produce simulation of the solar spectrum . a 1 mm thick ug5 filter was added to remove reflected heat and remaining visible radiation . warm up time of the lamp before use was 20 - 25 minutes . total irradiance at skin level was measured with a calibrated eppley thermopile and the uvb component was monitored with a uvb radiometer ( international light inc , newburyport , mass .). the size of the irradiated field was approximately a 1 cm diameter circle . two days prior to the end of the study , the med ( minimal erythema dose ) for each subject was determined by exposing several normal untreated skin sites over the midback area to a series of exposures in 25 % dose increments from the solar simulator . the med was defined as the time of exposure required to produce a minimally perceptible erythema 20 ± 4 hours after exposure . visual grading of the med was done under standardized lighting conditions when the subjects returned to the testing facility approximately 24 hours after irradiation . the med was recorded in the appropriate case record form . approximately ten minutes after the last topical application of the test products , a circular area measuring 1 cm in diameter within each treated test site was exposed once to a signal does of 1 . 5 med &# 39 ; s . the med was based on the determination in the nearby normal skin site using the solar stimulator . 20 ± 2 hours later , shave biopsy ( approximately 4 × 4 mm ) was obtained from each irradiated site following injection of a local anesthetic ( xylocaine ). the skin specimens were immediately fixed in 10 % buffered formalin . histology : the fixed specimens were processed routinely , embedded in paraffin and then sectioned and stained with hematoxylin - eosin . the numbers of sun burn cells ( sbc ) were determined in at least 12 sections at 50 u intervals . a minimum of 70 high power fields ( hpf ) was counted from each biopsy and the average number of sbcs per hpf determined . all specimens were counted in a blinded manner by the investigator , where all slides were identified only by subject number and test code . it has been found that the method of the invention provided between a 31 % to a 44 % reduction ( depending on the concentration tested ) in the number of sunburn cells formed when compared to untreated skin which is exposed to the same degree of uv radiation . the mean number of sunburn cells ( sbc ) for each subject is set forth below in table i . table i mean number of sbc per high power field subject number formula 1 formula 2 formula 3 nt site 1 0 . 33 0 . 46 0 . 29 0 . 69 2 0 . 32 0 . 36 0 . 29 0 . 19 3 0 . 39 0 . 30 0 . 24 0 . 33 4 0 . 70 1 . 05 1 . 43 2 . 05 5 0 . 20 0 . 17 0 . 13 0 . 21 mean 0 . 39 0 . 47 0 . 48 0 . 69 delta % 44 . 00 33 . 00 31 . 00 n / a formula 1 ( 1 . 00 wt . % idebenone ) formula 2 ( 0 . 10 wt . % idebenone ) formula 3 ( 0 . 01 wt . % idebenone ) nt site - normal untreated skin exposed to uv conclusion : formulas 1 , 2 and 3 ( 1 . 0 wt . %, 0 . 1 wt . %, and 0 . 01 wt . % idebenone ) respectively produced a 44 %, 33 %, and 31 % reduction in the number of sunburn cells when compared with normal , untreated skin . thus , the application of idebenone and its derivatives containing compositions to skin prior to exposure to uv radiation reduces the formation of sunburn cells in human skin . referring now to examples 3 and 4 below , it has also been found that the method of the invention provides a 100 % reduction in the increase in the number of sunburn cells formed in skin treated with glycolic acid ( neutralized to ph 3 . 8 ) and exposed to uv radiation . an idebenone - containing formula 4 and a formula 5 ( placebo ) were prepared as follows : w / w % formula : 4 5 idebenone 0 . 5 — sd alcohol 40b 67 . 5 67 . 5 di water 22 . 0 22 . 5 ammonium glycolate 10 . 0 10 . 0 and glycolic acid ( neutralized to 3 . 8 ) to prepare formula 4 , the idebenone was added directly to the sd alcohol 40b while stirring until dissolved . di water was then added to the solution with continued stirring followed by 10 % ammonium glycolate and glycolic acid ( neutralized to 3 . 8 ). to prepare formula 5 , the same procedure was followed except that idebenone was not added to the composition . the idebenone - containing formula 4 and the placebo formula 5 of example 3 were applied to human skin in a 2 - week human sun burn cell assay study . the panel composition was six different healthy adult volunteers between the ages of 18 and 53 . all were in excellent health , and without any significant internal or dermatological diseases . the subjects were carefully screened to insure they were not taking any medications . all had a clear back free of blemishes or a tan and were of skin types ii and iii according to the following classification scheme : type i : always burns easily , never tans ( sensitive ) type ii : always burns easily ; tans minimally ( sensitive ) type iii : burns moderately ; tans gradually — normal skin ( light brown ) the subjects were given detailed instructions to avoid any direct exposure to sunlight and to minimize any incidental exposure to their backs for the entire duration of the study . no other topical products were allowed , and no medications including over - the - counter ( otc ) products were to be used except for acetaminophen ( e . g ., common tylenol ®) for the relief of transient pains or headaches . individual test sites were delineated over the midback region . the test products were randomly allocated amongst the test sites according to a randomization schedule prepared by the investigator . the subjects came in once daily to the laboratory and received supervised applications of the test products to the allocated test sites . all test products were dispensed by a technician using 1 cc disposable plastic tuberculin syringes . each site received 100 μl ( 2 μl / square cm ) of , as appropriate , formula 4 or 5 of example 3 , or neither formula ( normal , untreated skin site ). the test product was then spread uniformly throughout the 5 × 10 cm rectangular test site using a finger cot . the subjects received once daily application for two consecutive weeks ( except on weekends ). the light source used was a 150 watt xenon arc solar simulator equipped with a uv reflecting diachronic mirror and a 1 mm thick schott wg - 320 filter to produce simulation of the solar spectrum . a 1 mm thick ug5 filter was added to remove reflected heat and remaining visible radiation . warm up time of the lamp before use was 20 - 25 minutes . total irradiance at skin level was measured with a calibrated eppley thermopile and the uvb component was monitored with a uvb radiometer ( international light inc , newburyport , mass .). the size of the irradiated field was approximately a 1 cm diameter circle . two days prior to the end of the study , the med ( minimal erythema dose ) for each subject was determined by exposing several normal untreated skin sites over the midback area to a series of exposures in 25 % dose increments from the solar simulator . the med was defined as the time of exposure required to produce a minimally perceptible erythema 20 ± 4 hours after exposure . visual grading of the med was done under standardized lighting conditions when the subjects returned to the testing facility approximately 24 hours after irradiation . the med was recorded in the appropriate case record form . approximately ten minutes after the last topical application of the test products , a circular area measuring 1 cm in diameter within each treated test site was exposed once to a signal does of 1 . 5 med &# 39 ; s . the med was based on the determination in the nearby normal skin site using the solar stimulator . 20 ± 2 hours later , shave biopsy ( approximately 4 × 4 mm ) was obtained from each irradiated site following injection of a local anesthetic ( xylocaine ). the skin specimens were immediately fixed in 10 % buffered formalin . histology : the fixed specimens were processed routinely , embedded in paraffin and then sectioned and stained with hematoxylin - eosin . the numbers of sun burn cells were determined in at least 12 sections at 50 u intervals . a minimum of 70 high power fields ( hpf ) was counted from each biopsy and the average number of sun burn cells per hpf determined . all specimens were counted in a blinded manner by the investigator , where all slides were identified only by subject number and test code . it has been found that the method of the invention prevented an increase in sun sensitivity , as demonstrated by prevention of increase in sunburn cell formation , normally caused by a product containing 10 % glycolic acid when applied topically and exposed to the same degree of uv radiation . the mean number of sunburn cells ( sbc ) for each subject is set forth below in table ii . table ii mean number of sbc per high power field subject number site a site b site c 1 4 . 86 9 . 28 3 . 16 2 1 . 03 3 . 18 0 . 75 3 0 . 78 1 . 22 2 . 18 4 0 . 13 0 . 21 0 . 36 5 2 . 17 1 . 32 1 . 68 6 3 . 33 3 . 06 4 . 24 mean 2 . 05 3 . 50 2 . 06 delta % 0 . 00 − 70 . 0 n / a site a : formula 4 ( 0 . 5 wt . % idebenone + 10 wt . % glycolic acid ) site b : formula 5 ( 10 wt . % glycolic acid ) site c : normal untreated skin conclusion : formula 4 ( 0 . 5 wt . % idebenone + 10 wt . % glycolic acid ) prevented the sun sensitivity produced by a 10 wt . % glycolic acid - containing composition when compared with normal , untreated skin . thus , the application of idebenone and / or its derivatives containing compositions to skin prior to exposure to uv radiation prevents the increase in formation of sunburn cells in human skin that can be produced by glycolic acid - containing compositions and the like . while the invention has been described in connection with preferred embodiments , the description is not intended to limit the scope of the invention to a particular form set forth , but , on the contrary , it is intended to cover such alternatives , modifications and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims .

US-82526504-A

fire fighting apparatus for generating air compressed foam having both a water and a surfactant metering device for dispensing controlled and discrete quantities of both into a mixing conduit where they combine into a foam solution . the foam solution is combined with air prior to being injected within a compression chamber of an air compressor device . foam is generated by compression of the air - foam solution and then is discharged through a discharge device . the air compression device is also controlled to dispense a discrete quantity of foam therefrom in correlation with the discrete quantities dispensed from the other two metering devices . the quantitative dispensing coordination of the air compression device with the two metering devices makes all three devices both relational and proportional in the cooperative generation of compressed air foam , and thus ensures prompt production of constant quality foam . the relational and proportional condition is achieved in a preferred mechanical embodiment by incorporating a common , concentric drive shaft driving all three dispensing devices , each of which is a rotary vane pump . in an electrical embodiment , the relational and proportional condition is achieved by an electric drive motor driving each dispensing device at a pre - set r . p . m ., each motor being , connected to and controlled by a programmable control device mechanical and electrical embodiments have devices for monitoring and controlling a variety of operational parameters to further enable prompt production of constant quality air compressed foam .

reference is now made to the drawings wherein like parts are designated with like numerals throughout . referring to fig1 , 3 and 7 , the presently preferred embodiments of the present invention are illustrated and designated generally at 10 . the compressed air foam apparatus 10 includes a drive means 12 which operates to rotate a drive shaft 14 which extends from the drive means 12 . the drive means 12 can be of any type , including a d . c . motor , a diesel or gasoline operated engine , or hydraulic drive . a means for delivering fluid ( such as water ) from a fluid source 15 to the compressed air foam apparatus 10 is required . alternatively and in place of fluid source 15 , the fluid delivery means can be of any type that supplies fluid under pressure , including a standard fire hydrant or a water pump located on a standard fire engine . the fluid is delivered to the compressed air foam apparatus via a first fluid conduit 16 . the first fluid conduit 16 is connected to a first meter injection port 18 located on a first metering means 20 . preferably , the first metering means 20 is a rotary vane pump , but may be of any similar metering type device as will be apparent to one skilled in the art . the first metering means 20 meters a predetermined volume of fluid present in the first fluid conduit 16 to the first meter discharge port 22 with each revolution of the drive shaft 14 . connected to the first meter discharge port 22 is a second fluid conduit 24 . as shown in fig1 and positioned in communication with the first meter discharge port 22 is a first metering means exhaust port pressure sensing and response means 172 with a first metering means exhaust port pressure sensing and response control cable 174 attached thereto . such a pressure sensing and response means can be mechanical , electrical , or electromechanical , with a function of creating a signal in proportion to the pressure sensed thereat and then communicating that signal to the pressure sensing and response control cable for the purpose discussed below . for example , a mechanical embodiment may be a spring device and the electrical embodiment may be a piezoresistive pressure transducer , while the electromechanical embodiment may be a spring with electrically controlled switching . also connected to the drive shaft 14 is second metering means 26 , which is also preferably a rotary vane pump . the second metering means 26 has a second meter injection port 28 through which is passed a foaming agent surfactant , accessed from a foaming agent surfactant source 30 ( illustrated in fig2 ) via a foaming agent conduit 32 . the second metering means 26 meters a predetermined volume of foaming agent surfactant from the foaming agent surfactant source 30 to the second meter discharge port 34 with each revolution of the drive shaft 14 . the second meter discharge port 34 is also then connected to the second fluid conduit 24 . positioned in communication with the second meter discharge port 34 is a second metering means exhaust port pressure sensing and response means 176 with a second metering means exhaust port pressure sensing and response control cable 178 attached thereto . such a pressure sensing and response means can be mechanical , electrical , or electromechanical , with a function of creating a signal in proportion to the pressure sensed thereat and then communicating that signal to the pressure sensing and response control cable for the purpose discussed below . for example , the pressure sensor may be a spring device , a piezoresistive pressure transducer , or a spring with electrically controlled switching . with reference now to fig1 and 7 , it is illustrated how the foaming agent surfactant discharged from the second metering means 26 into the second fluid conduit 24 ultimately meets , and is intermixed with , fluid discharged from the first metering means 20 into the second fluid conduit 24 . this mixture takes place at a mixture point 36 within the second fluid conduit 24 . the second fluid conduit 24 then proceeds to enter a water jacket heat sink 38 which is encased about an air compressor means 40 . as the second fluid conduit 24 proceeds through the heat sink 38 , the foam solution mixture is heated with the heat absorbed by the heat sink 38 from the air compressor means 40 . the second fluid conduit 24 then exits the heat sink 38 and enters the air compressor means 40 at a compressor injection port 42 . in communication with the compressor injection port 42 is an air inlet port 44 which is illustrated as having an air filter thereat . the apparatus illustrated in fig2 operates by the air compressor means 40 , also preferably a rotary vane pump compressor , introducing and mixing a predetermined volume of air at the air inlet port 44 and foam solution mixture present at the compressor injection port 42 with each revolution of the drive shaft 14 . this predetermined volume of air and of foam solution mixture is then pressurized within the air compressor means 40 thereby producing an air - foam mixture , which is then discharged under pressure out the compressor discharge port 46 . connected to the compressor discharge port 46 is a hose 48 and a nozzle 50 for directing the foam to a fire . fig1 , and 7 all show a preferred embodiment of the invention in which the drive shaft 14 makes one rotation for every one rotation of each metering device 20 , 26 , 40 . fig7 shows a cut - away of the inside of the metering devices 20 , 26 , 40 each of which has the same number of rotary vanes , the rotary vanes being mutually aligned in planes normal to the drive shaft 14 . particularly , the air compressor rotary vanes 40a form a combination of metering and compression chambers 40b . the first and second metering means 20 , 26 have respective rotary vanes 20a , 26a and respective metering chambers 20b , 26b . the embodiment shown in fig7 features eight ( 8 ) metering chambers on each of the metering devices 20 , 26 , 40 . the relative volume differences of metering chambers 20b , 26b , and 40b are a function of the dimensions of the respective metering means 20 , 26 , 40 . in the preferred embodiment shown in fig1 , and 7 , the dimensions of each metering means 20 , 26 , 40 is based upon the intended respective ratios of fluid from fluid source 15 , surfactant from surfactant source 30 , and air from air source 44 . thus , as the drive shaft 14 makes one revolution , each of the metering means 20 , 26 , 40 has six ( 6 ) respective metering chambers 20b , 26b , and 40b that open to respective discharge ports 22 , 34 , and 46 . positioned in communication with the compressor discharge port 46 is a air compressor means exhaust port pressure sensing and response means 170 with an air compressor means exhaust port pressure sensing and response control cable 166 attached thereto . such a pressure sensing and response means can be mechanical , electrical , or electromechanical , with a function of creating a signal in proportion to the pressure sensed thereat and then communicating that signal to the pressure sensing and response control cable for the purpose discussed below . for example , the pressure sensor may be a spring device , a piezoresistive pressure transducer , or a spring with electrically controlled switching . a key 13 fits both into the drive shaft 14 along an axial longitudinal surface thereof and into separate central keyways of the first metering means 20 , the second metering means 26 , and the air compressor means 40 so as to enable relational and simultaneous revolutions of the respective rotary vanes journaled on the drive shaft 14 within the illustrated meters 20 , 26 , 40 housings . the drive shaft 14 is driven by drive means 12 under the control of power transmission means 164 ( as seen in fig1 and is hidden in fig2 ). power is transmitted to drive shaft 14 from drive means 12 by engaging these two together by clutch means 160 . clutch means 160 is also controlled by power transmission means 164 through transmission control cable 162 . the transmission control cable 162 can transmit signals to the clutch 160 that are electrical , mechanical , pneumatic , or the like . the power transmission means 164 has connected thereto the first and second metering means exhaust port pressure sensing and response control cables 174 , 178 as well as the air compressor means exhaust port pressure sensing and response control cable 166 . the signals from cables 166 , 174 , 178 enable the drive power taken from drive shaft 14 to be controlled by the power transmission means 164 as a function of the respective signals from pressure sensors 170 , 172 , 176 . signals sent , as described above for the transmission control cable 62 , through these cables set a condition within the power transmission means 164 to engage or to disengage clutch means 160 via clutch cable 162 so as to respectively start or stop the generation of foam . clutch engagement and disengagement is desirable when the fluid or surfactant supplies have been depleted , when the system is being initialized for start - up , when the hose or discharge device is temporarily shut - off by a system user , or when the system has a malfunction which necessitates a system shut down . for example , when either surfactant or fluid is not being discharged ( e . g . due to source depletion ) from respective first and second discharge ports 22 , 34 , the respective first and second metering means exhaust port pressure sensing and response means 172 , 176 will so indicate by generating a signal respectively through first and second metering means exhaust port pressure sensing and response control cables 174 , 178 to transmission means 164 . in turn , transmission means 164 responds to the received signals by transmitting a reaction to clutch cable 162 to disengage clutch means 160 from drive shaft 14 . alternatively , cables 166 , 174 , and 178 can be wired to switches in series that will open when pressure is detected as less that predetermined pressures at the various pressure sensing means 170 , 172 and 176 . when any of the switches in series are open , the transmission means 164 is signaled to disengage clutch means 160 as described above . the transmission means 164 must also be able to keep the clutch means 160 engaged during the low pressure conditions occurring at the various pressure sensing means 170 , 172 , and 176 during system start - up . as one example , the transmission means 164 may be provided with an override switch which overrides all of the aforementioned switches that are wired in series , so that the open status of the series - wired switches during system start - up will not causes the drive shaft 14 to be disengaged from the drive means 12 . once the proper pressures at sensing means 170 , 172 , and 176 are achieved , the series - wired switches will close and the override switch will open -- which switch status will continue during proper system operation . by controlling the transmission of power to the drive shaft 14 , the compressed air foam pump apparatus 10 will halt the production compresses air foam in response to the discharge device being closed off by a system user ( such as closing off the hose ) so that any resumed generation and discharge of foam will be prompt and even in consistency , e . g . being free of slugs of fluid or air . a second preferred embodiment of the present invention , also illustrated in fig2 functions as the first preferred embodiment but further features a first adjustable valve means 52 which is disposed after the first meter discharge port 22 and within the second fluid conduit 24 , as well as a second adjustable valve means 54 disposed after the second meter discharge port 34 and within the second fluid conduit 24 . each of the valves may be adjustable by combined solenoid / relay devices , equivalents thereof , or other devices known to the artisan . preferably , each of the valves are operable electrically whereby the amount of fluid / surfactant that is allowed to pass through each valve is selectively variable as a function of a variation of the operating input voltage or variation of the electrical current supplied to the valves 52 , 54 . the excess of substances not passing further into the second fluid conduit 24 through each valve 52 , 54 are shunted or passed respectively into exhaust conduits 17 , 33 . each valve 52 , 54 is independently connected electrically , via respective first and second adjustable valve control cables 64 , 66 , to a programmable control means 56 in fig3 . which preferably comprises a system user input means , such as a keyboard 55 , a standard display means 57 , and a standard digital microprocessor including data memory means and program memory means . the programmable control means 56 in fig3 is connected to valves 52 , 54 by control cables 64 , 66 , as is illustrated by fig2 by respective off - page connectors a and b . the programmable control means 56 , which may be a general purpose microcomputer , is preprogrammed to function as an expert system for proper valve adjustment for fire fighting according to parameters input by a system user at the key board associated with programmable control means 56 . a third preferred embodiment of the present invention is illustrated in fig3 . this embodiment of the invention is operates primarily as does the first and second preferred embodiments with the exception that there is no common drive shaft to relate the proportioning of substances through the various rotary vane pumps . unlike the first and second preferred embodiments , the requirement for the common drive shaft is eliminated . in the third embodiment , the first metering means 20 , the second metering means 26 and the air compressor means 40 are each rotary vane pumps respectively having rotors 21 , 27 , and 41 journaled therethrough , and are respectively driven by separate and controllable drive motors 60 , 62 , and 58 . these drive motors each individually operate the respective rotors 21 , 27 , 41 of the associated respective metering devices and air compressor device , 20 , 26 , 40 , and are each controlled via electric signals through respective control cables 61 , 63 , and 59 generated by the programmable control means 56 so that each metering device and air compressor , 20 , 26 , 40 is operated individually and independent of the other . independent operation of drive motors 60 , 62 provide the capability to independently vary the amount of fluid and the amount of foaming agent surfactant that is metered through the first and second metering devices 20 , 26 and fed into the air compressor 40 , thus allowing for the production of different foam qualities . similarly , the amount and pressure of air - foam that is discharged from the air compressor 40 is also dependent on the operating speed and is thus controllable via the operation of its drive motor 58 . the air being fed to the air compressor at 44 can also have thereat an air pressure measuring means which feeds a detected air pressure value back to the programmable control means 56 via control cable 91 . as in the second preferred embodiment , the third preferred embodiment features adjustable valves 52 , 54 that are in communication with the programmable control means 56 respectively by a first adjustable valve control cable 100 and a second adjustable valve control cable 102 . positioned in communication with the first meter discharge port 22 is a first metering means exhaust port pressure sensing and response means 130 with a first metering means exhaust port pressure sensing and response control cable 132 attached thereto . such a pressure sensing and response means 130 is preferably electrical , or electromechanical , with a function of creating a signal in proportion to the pressure sensed thereat and then communicating that signal to the pressure sensing and response control cable 132 to programmable control means 56 for the purpose discussed below . for example , the electrical embodiment may be a piezoresistive pressure transducer , while the electromechanical embodiment may be a spring with electrically controlled switching . the first metering means drive means 60 has a first metering means drive means tachometer 182 that measures the r . p . m . of the first metering means 20 and creates a signal in proportion thereto that is sent to programmable control means 56 via control cable 61 . positioned in communication with the second meter discharge port 34 is a second metering means exhaust port pressure sensing and response means 140 with a second metering means exhaust port pressure sensing and response control cable 142 attached thereto . such a pressure sensing and response means 140 is preferably electrical , or electromechanical , with a function of creating a signal in proportion to the pressure sensed thereat and then communicating that signal to the pressure sensing and response control cable 142 to programmable control means 56 for the purpose discussed below . for example , the electrical embodiment may be a piezoresistive pressure transducer , while the electromechanical embodiment may be a spring with electrically controlled switching . the second metering means drive means 62 has a second metering means drive means tachometer 184 that measures the r . p . m . of the second metering means 26 and creates a signal in proportion thereto that is sent to programmable control means 56 via control cable 63 . the air compressor means drive means 58 has a air compressor drive means tachometer 180 that measures the r . p . m . of the air compressor means 40 and creates a signal in proportion thereto that is sent to programmable control means 56 via control cable 59 . all of the aforementioned tachometers 180 , 182 , and 184 can be known devices that measure the r . p . m . of the respective metering means 40 , 20 , and 26 , for example , by optical recognition , by inductance , or by other devices known to those of skill in the art . the programmable control means 56 is preprogrammed to both monitor parameters and to control parameters in order to automatically operate the system so as to produce foam to specifications that are input by a system user at the keyboard of the programmer controller 56 or are pre - set by the system manufacturer . specifically , the monitored parameters are the foam solution mixture temperature , the temperature of the surfactant , the air temperature , the air flow rate , the temperature of the fluid , the ambient air pressure , the pressure of the fluid at the exhaust port 22 of the first metering means 20 , the pressure of the surfactant at the exhaust port 34 of the second metering means 26 , the pressure of the foam at the compressor discharge port 46 of the air compressor 40 , the ambient air humidity , and the quality of the produced foam with respect to electrical conductivity , and the measured rpm of the various metering means 20 , 26 , and 40 . the parameters that are controlled by the programmable control means 56 include the r . p . m . of the various metering means 20 , 26 , and 40 , the temperature of the surfactant , and the temperature of the foam solution mixture within the second fluid conduit 24 . in order to accomplish the monitoring and controlling of parameters of the foam producing system , the system further comprises several hardware mechanisms detailed below . the first drive means control cable 61 enables the programmable control means 56 to both monitor and control the r . p . m . of the first drive means 60 and the flow rate of the fluid going into the system . further , the fluid flow rate is controlled by the programmable control means 56 sending a signal to the first adjustable valve 52 via control cable 100 , based upon pre - set and programmed instructions within the programmable control means 56 . similarly , the second drive means control cable 63 enables the programmable control means 56 to both monitor and control the r . p . m . of the second drive means 62 and the flow rate of the surfactant from surfactant source 30 into the system . likewise , the surfactant going into the system is controlled by the programmable control means 56 sending a signal to the second adjustable valve 54 via control cable 102 , based upon pre - set and programmed instructions within the programmable control means 56 . additionally , the air compressor drive means control cable 59 enables the programmable control means 56 to both monitor and control the r . p . m . of the air compressor drive means 58 , and the pressure of the compressed air foam out of the system . it is advantageous to quality foam production that the surfactant within the surfactant source 30 be pre - heated to a controlled temperature point . to do so , both a surfactant temperature sensing means 84 and a surfactant heating means 72 are provided within surfactant source 30 . thus , the temperature of the surfactant is monitored and controlled by the programmable control means 56 via surfactant temperature sensing means 84 through surfactant temperature control cable 70 using surfactant heating means 72 . in a variation of the third preferred embodiment , the water jacket heat sink 38 may be omitted from the relative portion of the second fluid conduit 24 encasing around the air compressor means 40 . in place thereof ( or alternatively , in addition thereto ) is a foam solution mixture containing means 74 having therein a foam solution heating means 76 and a foam solution temperature sensing means 80 , both of which are in communication with the programmable control means 56 via a foam solution temperature control cable 78 so as to respectively control and monitor the temperature of the foam solution that is to be injected into the air compressor means 40 . the fluid source 15 is also monitored for the fluid temperature therein using a fluid temperature sensing means 86 in communication with the programmable control means 56 via fluid temperature sensing mean control cable 92 . atmospheric monitoring is also important to quality foam production . to this end , there are provided an air temperature / humidity / pressure sensing means 88 in communication with the programmable control means 56 via ambient air temperature / humidity / pressure sensing means control cable 90 . in order to have direct monitoring of both the exhaust pressure of the foam from the air compressor as well as the quality of the foam that is being produced by the system , monitoring means 96 is positioned in communication with the output of the air compressor means 40 , which is in communication with the programmable control means 56 via monitoring means control cable 98 . in one embodiment of the monitoring means 96 , a combined pressure transducer ( to monitor the output pressure thereat ) and dual conductive electrodes ( to monitor electrical conductivity of the output foam ) are contained therein . by monitoring the electrical conductivity of the output foam , the quality or consistency of the foam being produced can be deduced , given that the type of fluid being used is a parameter that is input to the programmable control means 56 at the keyboard 57 by a system user , as well as other parameters . thus , by so positioning the air compressor monitoring means 96 sequentially within the system after the air compressor means 40 , the system is able to gauge , by this as well as other hardware techniques well known in the art , the output pressure and the electrical conductivity of the foam being produced . as shown in fig1 through 3 , most , if not all , of the control and monitoring cables ( 59 , 61 , 63 , 64 , 66 , 70 , 78 , 90 , 98 , 100 , 102 , 132 , 162 , 166 , and 174 ) for communication with the clutch means 160 or the programmable control means 56 can be within a wiring harness 82 routed to the programmable control means 56 . the programmable control means 56 performs both monitoring and controlling functions of the system according to a pre - programmed set of instructions . one example of the pre - programmed set of instructions , which performs a series of steps in the control and monitoring of the system , is shown in fig4 through 6 . as shown in fig4 step 100 is a starting step that is preferably initiated by a system user throwing a system start - up switch or a smoke or heat detector triggering such a switch . at step 102 , the programmable control means 56 goes through an initial program load or ` boot ` step . this step also includes such diagnostic routines as determining if all control leads in wire harness 82 , and the devices to which they are attached , are in communication with the programmable control means 56 . at step 110 , the pass / fail status of the initialization step 102 is output to a communication port of the programmable control means 56 for subsequent display upon a display means 57 associated with the programmable control means 56 . the status data output at step 110 is tested at step 120 . if the start - up has failed three times , as indicated at step 125 , the program will exit and move to shut down the system through step 255 , as indicated at step 127 , and then to termination at step 1000 . otherwise , the program will try to re - initialize at step 102 a maximum of three times . if the self - test at step 120 passes , control will move to step 130 where the display means 57 of the programmable control means will output a test - passed message to the system user . at step 140 , the system user is prompted upon the display means 57 for input , which may have pre - set default values , of operating parameters comprising : the orientation of the hose 48 as deck gun , vertical , up hill , level , or downhill ; the hose diameter size ; the hose length ; a desired surfactant to fluid ratio ; surfactant and fluid types ; and a parameter representing desired foam quantity which is electrical conductivity of the foam to be produced . the input parameters are verified by look - up tables in the programmable control means 56 . the system user may also choose to exit the system and shut the system down at this stage by inputting a pre - set response at step 150 which causes control to be passed to step 255 and then to termination at step 1000 . should the system user choose to continue the system &# 39 ; s operation ( or the system is in a pre - set automatic control mode ), in fig5 control passes to step 160 where all the monitoring aspects of the system are tested to obtain current values . specifically tested are the foam solution mixture temperature at 80 , the temperature of the surfactant at 84 , the air temperature at 88 , the air flow rate at 91 , the temperature of the fluid at 86 , the ambient air pressure at 88 , the pressure of the fluid at the exhaust port 22 of the first metering means 20 , the pressure of the surfactant at the exhaust port 34 of the second metering means 26 , the pressure of the compress - air foam at the exhaust port 46 of the air compressor means 40 , the ambient air humidity at 88 , the measured r . p . m . of all metering means including the air compressor means 40 , the second metering means 26 , and the fluid metering means 20 , and the quality of the produced foam with respect to electrical conductivity at 96 . the signals from the various monitoring means involved at step 160 may be transformed from analog signals into digital signals by a peripheral a - d means associated with the programmable control means 56 so as to arrive at discrete values . after step 160 , the instruction set passes on to step 170 where the resultant value of the temperature parameters , including fluid , surfactant , and foam solution are tested . if the temperature is not within a look - up table range , then appropriate adjustments are made at step 175 to the respective heaters 72 , 76 . similarly , at step 210 in fig5 the resultant value of the pressure parameters are tested , including fluid , surfactant , and air compressors at the respective exhaust ports . if respective detected pressure is not within a respective look - up table range , then appropriate adjustments are made at step 215 to the r . p . m . of the respective drive means 58 , 60 , 62 . in fig6 the electrical conductivity of the compressed air foam , as measured at 96 is looked - up against the input at step 140 and against a look - up table , as indicated at step 230 . if there is a need , as indicated from the look - up , differentials are calculated and the appropriate adjustments derived therefrom are computed at step 235 . the adjustments derived by the instruction in the programmable control means 56 may be adjustments to the adjustable valves 52 , 54 , the heaters 72 , 76 , and / or the drive means 58 , 60 , 62 . at step 250 , if the fluid pressure detected at either of the exhaust ports 22 , 34 is less than a pre - set pressure for a pre - set duration , a diagnostic at step 255 will display upon display means 57 ( e . g . &# 34 ; low fluid pressure &# 34 ; or &# 34 ; low surfactant pressure &# 34 ;) and the system will shut down by the routine at step 1000 . at step 260 , the system determines if a system user has closed off the flow of foam out of the discharge device . such as condition is indicated by a higher than a pre - set pressure detected at the exhaust port 46 of the air compressor means 40 . if such a pressure is detected at step 260 , drive means 58 , 60 , and 62 are adjusted to zero r . p . m , as indicated at step 265 , until the pressure drops below the pre - set maximum pressure and the system resumes producing foam at step 260 . a general house - keeping diagnostic routine is performed at step 270 to check for problems in the programmable control means 56 operational capability , and if it has a failure , the system shuts down through a diagnostic display at step 255 . otherwise , the program re - cycles through step 150 in fig4 as above . the present invention may be embodied in other specific forms without departing from its spirit or essential characteristics . the described embodiments are to be considered in all respects only as illustrative and not restrictive . the scope of the invention is , therefore , indicated by the appended claims rather than by the foregoing description . all changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope .

US-99812092-A

systems and methods introduce a tissue fastener applier to apply tissue - piercing fasteners to a prosthesis sequentially along a path established by the directing device that , between fastener applications , is manipulated into orientation with different desired fastening sites , until a plurality of tissue - piercing fasteners are placed , one - at - a - time , in the prosthesis .

fig1 depicts an endovascular graft delivery catheter 10 being positioned within an abdominal aortic aneurysm 11 over a guidewire 12 . fig2 depicts the initial stage of graft deployment within a vessel . the delivery catheter 10 has a movable cover 13 over the graft . when the cover is pulled proximally the graft 14 expands to contact the internal walls of the vessel . it is contemplated that the graft could be self - expanding or utilize an expanding member such as a balloon or mechanical expander . the process of graft deployment is continued until the graft is fully deployed within the vessel . it is contemplated that the graft could be in either a straight or bifurcated form . fig3 depicts a completely deployed straight graft 14 and fig4 depicts a completely deployed bifurcated graft 15 . the guidewire 11 used to deliver and position the graft remains within the vessel for access of the fastener attachment system . one embodiment of the graft scaffolding 16 ( stent ) is illustrated in the area broke away in fig4 . the stent is in the form of a simple zigzag pattern , however it is contemplated that the stent design could involve more complex patterns 17 as depicted in fig5 . although only one stent structure within the graft is depicted , in fig4 and 5 , it is contemplated that multiple independent stent structures could be incorporated into the graft . 1391 fig6 depicts one embodiment of the directing device 18 with an obturator 19 positioned within the lumen of the directing device and extending past the distal of the tip of the directing device . the obturator has a lumen to allow for delivery over a guidewire . fig7 depicts the directing device being positioned within the deployed endovascular graft over a quidewire 12 . the directing device has an incorporated stabilizing device 20 to aid in maintaining position of the directing device within the vessel . in one embodiment , the stabilizing device 20 is spring - loaded and is positioned for use when the obturator in the directing device is removed fig8 . the directing device is activated though a control assembly 21 as seen in fig8 . in one embodiment the control assembly 21 features a movable wheel or lever 22 , which deflects the distal tip 23 of the directing device 18 to the desired location as seen in fig9 . it is contemplated that the control assembly for the directing device could be activated mechanically , electrically , hydraulically or pneumatically . the control assembly has a through lumen to allow for the passage of the obturator and fastener applier . fig1 depicts another embodiment the stabilizing device as a movable strut assembly 24 . the movable strut assembly is activated through a lever 25 on the control assembly fig1 . in both embodiments ( fig7 and 10 ) the stabilizing device is distal to the end of the directing device . in another embodiment the stabilizing device could be in the form of an expandable member 26 adjacent to the distal tip of the directing device fig1 . in one embodiment , the expandable member 26 is shown activated through a lever 25 on the control assembly fig1 . however it also contemplated that this type of stabilizing device could also be inflatable . in all embodiments the stabilizing device could be use to stabilize the directing member either concentrically or eccentrically within the vessel . in another embodiment of the invention a separate tubular device could be used in cooperation with the directing device and to access the vessel . this separate tubular device could incorporate the stabilizing devices used above with the directing device . fig1 depicts one embodiment of the fastener applier 27 . fig1 a is a detail view of the distal end of the fastener applier . fig1 depicts the fastener applier being positioned through the lumen of the directing device to the site where a fastener will be installed . fig1 is an enlarged cross - sectional view of fastener applier 27 and directing device 18 . in one embodiment of the fastener applier the helical fastener 28 is rotated via a fastener driver 29 through a drive shaft 30 that is connected to the control assembly 31 . the drive shaft 30 can be made of any material that allows for both bending and rotation . the drive shaft is connected to the fastener driver 29 , which engages and imparts torque to the helical fastener . fig1 illustrates the coils of the helical fastener 28 engaged with internal grooves 32 within the fastener applier . it is contemplated that the grooves could be positioned along the entire length of the fastener or within a portion of its length . fig1 is an enlarged cross - sectional view of the fastener applier 27 with a cross - section of the fastener driver 29 depicting one embodiment of engagement between the fastener driver and helical fastener 28 . in this embodiment the proximal coil of the helical fastener is formed to produce a diagonal member 33 , which crosses the diameter of the helical fastener . similar helical fasteners are described in u . s . pat . no . 5 , 964 , 772 ; 5 , 824 , 008 ; 5 , 582 , 616 ; and 6 , 296 , 656 , the full disclosures of which are incorporated herein by reference . fig1 depicts one embodiment of the helical fastener 28 showing the diagonal member 33 . fig1 depicts one embodiment of the fastener applier 27 during activation of the fastener applier control assembly . activation of the control assembly rotates the drive shaft , faster driver and helical fastener . this rotation causes the helical fastener 28 to travel within the internal grooves 32 of the fastener applier and into the graft 14 and vessel wall 34 fig2 . it is contemplated that the control assembly for the fastener applier could be activated mechanically , electrically , hydraulically or pneumatically . fig2 illustrates a completed helical fastener 28 attachment of the graft 14 to the vessel wall 34 . it is contemplated that one or more fasteners will be required to provide secure attachment of the graft to the vessel wall . fig2 illustrates a perspective view of a graft prosthesis attached to the vessel wall both proximally and distally . it is contemplated that the present invention can be used for graft attachment of both straight and bifurcated grafts 15 within the aorta and other branch vessels . it will be appreciated that the components and / or features of the preferred embodiments described herein may be used together or separately , while the depicted methods and devices may be combined or modified in whole or in part . it is contemplated that the components of the directing device , fastener applier and helical fastener may be alternately oriented relative to each other , for example , offset , bi - axial , etc . further , it will be understood that the various embodiments may be used in additional procedures not described herein , such as vascular trauma , arterial dissections , artificial heart valve attachment and attachment of other prosthetic device within the vascular system and generally within the body . the preferred embodiments of the invention are described above in detail for the purpose of setting forth a complete disclosure and for the sake of explanation and clarity . those skilled in the art will envision other modifications within the scope and sprit of the present disclosure .

US-97875207-A

an adapter for an introducer comprises a medical device having a tubular port on a proximal end such as a splittable hemostatic valve . a tubular fitting is provided on a proximal end of the introducer . an elastomeric member is disposed between the port of the medical device and the tubular fitting of the introducer for providing a fluid tight and mechanically secure connection therebetween . the introducer and valve are manually connectable and reconnectable with each other while maintaining the fluid tight connection between them . a side port may communicate with the hemostatic valve , the side port having a controllable valve ending . in the preferred embodiment the introducer comprises a splittable introducer . in the illustrated embodiment the elastomeric member provides a slip fit between the medical device and the tubular fitting of the introducer . a tab extends from the tubular fitting of the introducer to facilitate manual manipulation of the tubular fitting . in the preferred embodiment , the introducer is torqueable and the tab is used to rotate the introducer .

as shown in side elevational view of fig1 a cardiac or endovascular apparatus 10 is shown in the illustrated embodiment as comprised of a splittable and preferably , a rigid hemostatic valve 12 with an introducer 14 . introducer 14 is comprised of an elongate hollow tubular member 18 , which is coupled with tapered fitting 16 on its proximal end . any type of introducer 14 now known or later devised may be used in the claimed combination of the invention . for example , introducer may be reinforced or unreinforced so that it is torqueable or torsionally flexible . introducer 14 may be splittable , slittable , tearable or separable by some means or may be integral and inseparable . introducer 14 may be straight , curved , biased , unbiased , moldable , unmoldable or characterized variations in length , diameter , stiffness , resiliency , softness , hardness or composition along its longitudinal extent . in other words , introducer 12 should be understood in the present specification to be generally inclusive of all and any type of introducer structure or characterization . tapered fitting 16 is comprised of a thin walled cylindrical hollow proximal portion 20 , which tapers down through a funnel - shaped portion 24 to connect with or integrally extend into or with tubular member 18 . in the illustrated embodiment , tapered fitting 16 includes a molded tab 22 extending from its lower portion in a generally perpendicular direction . tab 22 is firmly connected to fitting 16 and provides a convenience means for manually holding , pushing , pulling , and turning fitting 16 . tapered fitting 16 slip fits or is snugly telescopically disposed in a fluid tight sealing relationship with distal end 26 of valve 12 . distal end or portion 26 of valve 12 is provided with an elastomeric collar 28 which serves to enhance the slip fit with fitting 16 and provide the fluid tight seal . elastomeric collar 28 may be composed of any material now known or later devised to provide quick , fluid tight engagement with the interior walls of fitting 16 , such as silicone rubber or any rubberized plastic or polymer . collar 28 can be coated with a lubricant such as silicone fluid or any other medical grade lubricant that facilitates the insertion and removal of collar 28 into a mating fitting , such as tapered fitting 16 . except for its modification at its distal end 26 , valve 12 is conventional and may also include any type of hemostatic valve now known or later devised . in the illustrated embodiment a splittable or slittable valve 12 is employed which is molded or formed from two valve halves 30 a and 30 b . valve 12 is held or manipulated by means of a pair of opposing upper tabs 34 a and 34 b extending at right angles to the axis of longitudinal symmetry of valve 12 . tabs 34 a and 34 b can be used to snap or tear valve 12 apart . while valve 12 is shown as splittable , it is to be expressly understood that valves comprised of separate halves , which are resiliently opened or closed like a clam shell , are also contemplated . alternative constructions , such a valves which open against a resilient spring mechanism , are cut apart , break apart on weakened seams , or any other means for separating or opening the body of the valve are deemed to be equivalent to the illustrated embodiment . the proximal portion of valve 12 is provided with a conventional splittable or separable hub 36 having an elastomeric sealing membrane 38 therein . again hub 36 may be provided with any type of design desired or needed to connect with other medical devices or tubing . in the illustrated embodiment , fitting 16 has a smooth interior bore or surface 44 with which collar 28 makes intimate contact . the outer diameter of collar 28 and the inner diameter of fitting 16 are such that given the elasticity of both collar 28 and fitting 16 , a tight sealing fit is achieved through which not only is a fluid tight seal made , but valve 12 and introducer 14 are mechanically coupled together with sufficient strength so that they will not easily be disconnected from each other by the forces encountered in normal handling . however , their coupling is not so strong , that the physician has any substantial difficulty in either making or disconnecting the coupling between valve 12 and introducer 14 . hence , collar 28 of valve 12 and fitting 16 of introducer 14 may be coupled and uncoupled multiple times without losing the ability to make a fluid tight and mechanically secure connection . [ 0023 ] fig2 is a side elevational view of the invention which illustrates apparatus 10 in an assembled configuration . collar 28 is telescopically forced or inserted into fitting 16 deeply enough to cause circular circumferential hard ridge 46 on valve halves 32 a and 32 b to be inserted into the upper portion of fitting 16 to provide a compression fit . collar 28 is illustrated in fig1 and 2 as fixed to the distal end or port of valve 12 , but it is entirely within the scope of the invention that collar 28 may be fixed within proximal portion 20 of fitting 16 , or may be a free piece which is alternatively slip fit either on distal end or port of valve 12 or into proximal portion 20 of fitting 16 according to user choice . fitting 16 can be forced further up valve halves 32 a and 32 b until its upper proximal edge 20 comes into contact with a circular circumferential hard stop 48 . this serves to limit the degree of insertion and to avoid overstressing fitting 16 , which has a slight inner tapering or cone shape . while the illustrated embodiment is shown as being coupled together by slip fit elastic members , it is also to be understood that similar couplings using luer lock structures or other positive screw or locking structures can be added or combined with the disclosed fitting / collar combination . in other words , the coupling of a cylindrical or slightly conical elastomeric plug into a cylindrical or slightly conical hollow tube end may be further modified to include additional structure such as locking structures , threading , rings , keyways , guides , collars and any other type of connection mechanism . the inner chamber within valve 12 may be communicated with a side port 40 , which terminates in a conventional three - way valve 42 . valve 42 communicates with tubular ports 50 for connection to external tubing and is operated by manually turning a cylinder valve element ( not shown ) by means of a lever 52 . this allows the infusion of fluids into valve 12 and ultimately introducer 14 . further details of the design of valve 42 is immaterial to the scope of the invention . thus , it can now be readily appreciated that introducer 14 with fitting 16 is provided with an adapter which allows introducer 14 to be quickly and securely connected to multiple alternative medical devices according to the medical application at hand . for example , in the simplest embodiment introducer 14 may be combined with a splittable valve 12 and a pacemaker lead implanted into a patient through valve 12 and introducer 14 . in such a procedure , valve 12 would normally be broken open after the pacemaker lead was implanted . after implantation if for any reason it should be desired to remove the first pacemaker lead and replace it with a second lead , then a new valve 12 can be inserted into introducer 14 , which might be left in place , and the procedure repeated . in prior art embodiments where the valve and introducer were integral , such a replacement procedure would require subcutaneous reinsertion of the introducer with the attendant risk of additional tissue trauma and complication . [ 0028 ] fig3 is a simplified side elevational view of another embodiment where valve 12 is connected to introducer 14 by a slip fit of a hard plastic distal port 54 that wedges into the proximal end of a hard plastic fitting 16 . the distal port 54 is shown as generally tubular or conical and as slip fitting into a conforming tubular or conical bore 56 defined in the proximal end of a hard plastic fitting 16 without the mediation of any elastomeric gasket or seal between them . it is within the scope of the invention that the relationship may be reversed , i . e . the proximal end of a hard plastic fitting 16 may be formed as a male - type tubular or conical port which inserts into a female - type tubular or conical port of valve 12 . the medical device may be any type hemostatic valve now know or later devised . while splittable and nonsplittable valves have been described above , the invention expressly contemplates being used as an adapter for translatable or slideable valves which are moved or rotated into and out of an operative position , such as shown in u . s . pat . no . 5 , 441 , 504 or pct publication wo 02 / 05867 , both of which are incorporated herein by reference . many alterations and modifications may be made by those having ordinary skill in the art without departing from the spirit and scope of the invention . therefore , it must be understood that the illustrated embodiment has been set forth only for the purposes of example and that it should not be taken as limiting the invention as defined by the following claims . for example , notwithstanding the fact that the elements of a claim are set forth below in a certain combination , it must be expressly understood that the invention includes other combinations of fewer , more or different elements , which are disclosed in above even when not initially claimed in such combinations . the words used in this specification to describe the invention and its various embodiments are to be understood not only in the sense of their commonly defined meanings , but to include by special definition in this specification structure , material or acts beyond the scope of the commonly defined meanings . thus if an element can be understood in the context of this specification as including more than one meaning , then its use in a claim must be understood as being generic to all possible meanings supported by the specification and by the word itself . the definitions of the words or elements of the following claims are , therefore , defined in this specification to include not only the combination of elements which are literally set forth , but all equivalent structure , material or acts for performing substantially the same function in substantially the same way to obtain substantially the same result . in this sense it is therefore contemplated that an equivalent substitution of two or more elements may be made for any one of the elements in the claims below or that a single element may be substituted for two or more elements in a claim . although elements may be described above as acting in certain combinations and even initially claimed as such , it is to be expressly understood that one or more elements from a claimed combination can in some cases be excised from the combination and that the claimed combination may be directed to a subcombination or variation of a subcombination . insubstantial changes from the claimed subject matter as viewed by a person with ordinary skill in the art , now known or later devised , are expressly contemplated as being equivalently within the scope of the claims . therefore , obvious substitutions now or later known to one with ordinary skill in the art are defined to be within the scope of the defined elements . the claims are thus to be understood to include what is specifically illustrated and described above , what is conceptionally equivalent , what can be obviously substituted and also what essentially incorporates the essential idea of the invention .

US-27747602-A

a pair of spaced , resiliently tired wheels are mounted on a base for axial rotation in a common plane , the spacing between the wheels being less than the diameter of a ball to be thrown and the rotational speed of each wheel being adjustable independently of the other . the base is supported on a universal mounting ball by means of a socket located on the base at the center of gravity of the assembly of base and components supported thereon . the universal mounting ball is supported at the upper end of an angularly bent support arm , whereby to afford angular adjustment of the rotational plane of the wheels infinitely in all directions about the common pivot of the mounting ball , between horizontal and vertical positions . electrical controls are provided for controlling the speed of rotation of the coacting wheels . a ball infeed chute is mounted on the base for rotational adjustment about the ball projecting line between the spaced wheels , for maintaining the feed chute in a vertical , gravity feeding position irrespective of the angular disposition of the common plane of the ball projecting wheels .

the ball throwing device of this invention includes a laterally elongated base member 10 provided with forwardly offset end portions 12 having openings 14 for receiving the output shafts 16 of electric motors 18 the housings of which are secured to the base member as by bolts in tapped bores 20 . the output shafts of the electric motors mount hubs to which are secured by bolts 22 the wheels 24 which mount pneumatic or solid tires 26 . the electric motors drive the wheels in opposite directions of rotation , as indicated by the arrows , and in a substantially common plane p which is parallel to the plane of the base member 10 , 12 . the spacing between the confronting surfaces of the wheels is slightly less than the diameter of a ball b to be thrown . accordingly , the ball is gripped between the rotating wheels and ejected forwardly therefrom , as explained more fully hereinafter . the drive motors are preferably of the electric type illustrated . further , the motors preferably are of the variable speed type in order to accommodate adjustment of the rotational speed of each wheel independently of the other . the base member 10 , 12 is supported in a balanced condition , explained in detail hereinafter , by a universal pivot ball 28 mounted on the top end of an obliguely angularly bent support arm 30 . the lower end of the support arm has an enlarged cylindrical pivot 32 ( fig3 ) welded or otherwise secured to it . the cylindrical pivot is contained rotatably in a bearing socket 34 provided at the top of a base support 36 . the lower end of the base support is flared outwardly and provided with three leg sockets 38 spaced 120 ° apart and diverging downwardly . the hollow center of the lower end of the base support receives a clamp member 40 of truncated conical shape , configured for clamping the upper ends of three support legs 42 . this clamping is effected by a clamp screw 44 having a reduced diameter inner section 46 threaded for the reception in threaded bore 48 in the base support 36 . a shoulder 50 at the juncture of the clamp screw body 44 and inner section 46 abuts the lower end of the clamp member 40 to move the latter upward toward the base support 36 , whereby to clamp the legs securely but removably to the base support . the clamp screw 44 is turned by means of a t - handle 52 . the bent support arm 30 is secured in either of two positions 180 ° apart by means of a lock screw 54 ( fig3 ) having a reduced diameter threaded inner end 56 for releasably engaging one of two threaded bores 58 which extend in pivot 32 on a common diametrical line . a chamfered shoulder 60 between the lock screw body 54 and threaded inner end 56 cooperates with a tapered bore 62 in the base support 36 to ensure precise rotational positioning of the arm 30 . a t - handle 64 on the lock screw facilitates turning . the base member 10 , 12 is provided with a socket 66 for the pivot ball 28 . the socket has a diameter smaller than the pivot ball 28 and is provided about its circumference with an annular sleeve 68 of nylon or other material having a suitable low coeffecient of friction . this sleeve bears against the pivot ball a spaced distance above the center plane of the ball . a clamp member 70 ( fig2 ) also is provided adjacent its forward end with a socket 72 for the pivot ball 28 . this socket also has a diameter smaller than the diameter of the pivot ball and is provided with an annular sleeve 74 similar to sleeve 68 for providing a low friction contact with the ball . the socket 72 communicates through a rearwardly extending slot 76 with an entrance opening 78 which is larger in diameter than the ball 28 . the opening 78 serves to receive the pivot ball 28 upwardly therethrough and the slot 76 serves to receive the support arm 30 , for positioning the pivot ball in the socket 72 , below the center of the ball . the front end of the clamp member 70 is connected adjustably by bolts 80 to the forward , central portion of the base member 10 . the rearward end of the clamp member 70 is provided with a downwardly extending flange 82 by which to mount the forward side of control box 84 . this box contains the electrical control unit for varying the speeds of rotations of the tires 26 . for this purpose the electrical control unit includes potentiometers having control knobs 86 disposed at the top of the control box . the rear side of the control box supports the vertical section 88 of a clamp bar , as by screws 90 . the horizontal section 92 of the clamp bar is provided with a threaded opening for receiving the reduced diameter threaded shank 94 of a clamp screw 96 . the upper end of the clamp screw is provided with a hand knob 98 to facilitate its manipulation . the threaded shank 94 extends freely through an opening at the juncture of the cross bar 100 of a t - handle the leg 102 of which extends forwardly for attachment to the base member 10 . in the embodiment illustrated , this attachment is provided by a clamp plate 104 arranged to be releasably tightened against the leg 102 as by bolts 106 . by rotating the clamp screw 94 to move it into or out of the horizontal section 92 , the rearward end of clamp member 70 and leg 102 are moved toward or away from each other , to clamp or release the base member 10 and clamp member 70 to or from the pivot ball 28 . this allows readjustment of the rotational plane p of the ball projecting tires 26 . the clamp plate 104 also preferably mounts a ball feeder . this feeder includes a delivery section which is secured to the upper surface of the clamp plate and is provided with a rear tubular portion 108 the inner bore of which is slightly larger in diameter than a ball b . extending forwardly of the tubular portion are elongated top and bottom fingers 110 and 112 , respectively . these fingers extend forwardly between the tires 26 and have curved inner surfaces to confine a ball b against both horizontal and vertical displacement . by adjusting the bolts 106 to pivot the clamp plate 104 about the leg 102 , the ball is delivered to the exact centerline between the tire treads where it is gripped frictionally and ejected forwardly therefrom . the top finger 110 preferably is narrower in width than the spacing between the tires . this allows removal of one of the tires for repair or replacement , without the necessity of removing the ball feeder . the ball feeder also includes a ball infeed section provided at its forward end with a tubular connector portion 114 configured to rotatably engage the rear tubular portion 108 . the connector portion is secured releasably in rotational adjustment relative to the tubular portion 108 means of a clamp screw 116 secured to the tubular portion 108 . a hand knob 118 is threaded to the clamp screw 116 and the latter is engagable in a 180 ° slot 120 in the connector portion 114 . the clamp screw is accessible to the slot by means of an access slot 122 which communicates with the 180 ° slot from the forward end of the connector portion 114 . extending angularly rearward from the connector portion 114 is a ball feed chute 124 which is open at its top side to receive a ball b for delivery to the space between the rotating tires 26 . as explained more fully hereinafter , the ball feeder section is adjustable rotationally relative to the delivery section so that the ball feed chute 124 may remain pointing angularly upward for maximum effeciency of gravity feeding of balls , regardless of the angular disposition of the ball throwing wheels . as mentioned hereinbefore , the base member 10 , 12 is supported in a balanced condition by the universal pivot ball 28 . it is more accurate to state that it is the base member and all of the components supported by it that is supported in balanced condition on the pivot ball . thus , the assembly of base member , driven wheels 26 , clamp member 70 , t - handle 100 , 102 and ball feeder has its balance point on the axis 66 &# 39 ; ( fig1 ) of the socket 66 and its center of gravity at the center 28 &# 39 ; ( fig2 ) of pivot ball 28 . accordingly , manipulation of the assembly by grasping the cross bar 100 of the t - handle is achieved with maximum precision and mimimum physical effort . in this regard , the earlier ball throwing device disclosed in u . s . pat . no . 3 , 774 , 584 is significantly off - balance in the direction of the control handle , whereby care must be exercised in unclamping the assembly for readjustment to prevent the assembly from swinging sharply downward at the handle end , with consequent hazard to the operator and possible damage to the assembly . although the aforementioned earlier ball throwing device provides a substantial degree of adjustment of the rotational plane of the ball projecting wheels , the structural arrangement prevents adjustment of the rotational plane of the wheels infinitely to all positions between horizontal and vertical . this latter greater degree of adjustment is afforded by the provision in the present invention of the angled support arm 30 . for example , fig8 of the drawings shows the device adjusted to the position in which the rotational plane p of the wheels is horizontal and with the line of delivery of the ball b disposed to the left of the vertical axis of the base support 36 . by rotating the support arm 30 through 180 °, as afforded by removal of the lock screw 54 , the ball projecting wheel assembly may be positioned with the ball projecting line disposed to the right of the vertical axis of the base support . it is to be noted in fig8 that the ball feed chute 124 is angled vertically upward for the optimum gravity feed of balls to the rotating wheels . fig9 and 10 show the ball projecting wheel assembly adjusted so its rotational plane p is disposed vertically for throwing a fast ball or a drop curve . fig4 is a side elevation as viewed from the left in fig9 and shows the ball infeed chute 124 rotated 90 ° from its position in fig8 so as to incline vertically upward as in fig8 again to provide optimum gravity feed of balls to the rotating wheels which now are disposed vertically . fig1 and 12 show the ball projecting wheel assembly adjusted to an angular position intermediate the horizontal and vertical positions of fig8 and 10 . it is to be noted in these views that the ball infeed chute is adjusted to its optimum , vertically inclined position as previously described . fig1 shows the ball projecting wheel assembly titled forwardly downward , with the rotational plane p of the wheels disposed on a horizontal axis . this position may be utilized for throwing ground balls to the infield or outfield . the same practice may be achieved with different ball spin by the adjusted position illustrated in fig5 wherein the rotational plane of the ball projecting wheels is vertical but the line of ball projection is tilted forwardly downward . in both adjustments , the ball infeed chute is adjusted to the optimum ball gravity feed position . fig1 illustrates the adjustment of the rotational plane p of the wheels on a horizontal axis but tilted forwardly upward as for throwing fly balls to the infield or outfield . the ball may be given side spin to curve it laterally . as in the previous illustrations , the ball infeed chute is angled vertically upward for optimum gravity feed of balls to the wheels . fig6 illustrates the rotational plane of the ball projecting wheels disposed vertically but the line of projection of a ball inclined forwardly upward at an angle greater than that illustrated in fig1 . the ball may be given over spin or under spin , as desired . at this angle the ball infeed chute 124 is inoperative and hence the infeed section has been removed to facilitate hand feeding of balls to the delivery section of the feeder . in fig7 the rotational plane of the ball projecting wheels is once again disposed on a horizontal axis but adjusted to vertical for the throwing of practice pop - up balls . as in fig6 the feed chute has been removed to facilitate the hand feeding of balls vertically upward into the delivery section . as in the earlier ball throwing device of u . s . pat . no . 3 , 774 , 584 the foregoing angular adjustments of the rotational plane p of the ball projecting wheels , together with adjustments in relative rotational speeds of the wheels , provides a wide range of types , directions and speeds of throws and pitches . for example , referring to fig1 , the rotational plane of the wheels is shown inclined upwardly toward the right as viewed , for example , by a batter during batting practice . by rotating the upper wheel faster than the lower wheel a baseball pitched from between the wheels takes the same curved trajectory as a left handed overhand curve thrown by a pitcher . when the plane of rotation of the wheels is adjusted to the position shown in fig1 , and the upper wheel rotated faster than the lower wheel , the pitched ball takes the same trajectory as a right handed overhand curve delivered by a pitcher . with the rotational plane of the wheels disposed as in fig1 and 12 and both wheels rotating at the same speed , the degree of curvature of the pitch is reduced both horizontally and vertically . by rotating the lower wheel faster than the upper wheel , the trajectory of the pitch is both horizontal and upward . when the plane of rotation of the wheels is adjusted to horizontal , as in fig8 and one of the wheels is rotated faster than the other , the curve has a lesser degree of vertical component . with the rotational plane of the wheels disposed horizontally and with one of the wheels rotating only slightly faster than the other , a substantially straight fast ball will be delivered to the batter . the speed of the pitch may be varied by increasing or decreasing the rotational speed of the wheel , as will be understood . when both wheels are rotated at exactly the same speed , the pitch is a knuckler . the provision of the bent support arm 30 rotatable to opposite , 180 ° positions by the diametrically opposite threaded bores 58 and lock screw 54 , allows the device to throw any type of pitch with maximum stability by keeping one leg 42 facing the operator and the other two legs facing forward toward the batter . this arrangement best absorbs the recoil that takes place when a ball is thrown , thereby inhibiting the device from moving around on the ground from its preset position . this results in the device throwing more accurate and reproducible pitches over the course of many throws , without the need to reposition the device . as in the earlier patent , the simplified construction described hereinbefore affords transport of the device to and from an operating site but with greater stability and ease than the earlier construction . in this regard , the device may be tipped to one side , such as in fig9 with the tires 26 resting on the ground and the handle 100 , 102 extending upward . in this position the device may be grasped by the rearwardly inclined leg 42 and rolled from a site of operation to an automobile . because of the angled support arm 30 , this maneuver is accomplished with greater ease and stability than is afforded by the construction of the earlier patent by positioning the operator behind and in line with the wheels . then , by simply loosening the single clamp screw 44 to loosen the clamp member 40 , the legs 42 may be removed from the base support 36 . the remaining assembly is of sufficiently light weight that it may be lifted by one person and deposited in the trunk of the automobile , together with the legs . from the foregoing it will be appreciated that the present invention provide a ball throwing device which overcomes certain limitations and affords other advantages over the ball throwing device disclosed in the aforementioned u . s . pat . no . 3 , 774 , 584 . principal among these is the provision of the balanced assembly mounted on the universal pivot ball 28 ; the angularly bent support arm 30 which allows adjustment of the plane p of rotation of the ball projecting wheels infinitely to all positions between horizontal and vertical ; and the rotationally adjustable ball infeed chute 124 which allows adjustment of the chute to a vertical plane for optimum delivery of balls by gravity to the ball projecting wheels , regardless of the angular disposition of the wheels . it will be apparent to those skilled in the art that various changes may be made in the size , shape , type , number and arrangement of parts described hereinbefore . for example , although the illustrated embodiment of the invention utilizes two rotating tires for projecting a ball from between them , other forms of ball projecting mechanisms may be utilized . for example , the arrangement of a single fixed pad in association with one rotary wheel as disclosed in commonly owned u . s . pat . no . 4 , 080 , 950 may be substituted for the two rotary wheels illustrated . the spacing between the ball projecting components , such as the tires 26 illustrated , may be changed to accommodate the throwing of tennis balls , soft balls , and the like , it being understood that the dimensions of the ball feeder delivery and infeed sections will also be changed accordingly . these and other changes may be made , as desired , without departing from the spirit of this invention and the scope of the appended claims .

US-79265485-A

a method for treating stenosis in a spine comprises percutaneously accessing the epidural space in a stenotic region of interest , compressing the thecal sac in the region of interest to form a safety zonem , inserting a tissue removal tool into tissue in the working zone , using the tool to percutaneously reduce the stenosis ; and utilizing imaging to visualize the position of the tool during at least a part of the reduction step . a tissue excision system for performing percutaneous surgery , comprises a cannula comprising a tissue - penetrating member having a distal end defining an aperture on one side thereof , an occluding member slidably received on or in the cannula and closing the aperture when the occluding member is adjacent the cannula distal end , means for engaging adjacent tissue via the aperture , and cutting means for resecting a section of the engaged tissue .

the epidural space is the space between the ligamentum flavum and the thecal sac . this space is filled with blood vessels and fat . the nerves contained within the thecal sac are normally surrounded by cerebrospinal fluid ( csf ). when the ligamentum flavum hyperitrophies , the blood vessels that supply the nerves of the cauda equina are compressed . this results in ischemic pain termed spinal claudication . the nerve roots may also be compressed resulting in back and / or leg pain . referring again to fig1 the posterior border of the normal epidural space 30 is formed by the normally thin ligamentum flavum 26 and posterior epidural fat ( not shown ). ligamentum flavum 26 extends from the lamina above the interspinous space to the lamina below the interspinous space . the dural sleeve ( thecal sac ) 32 contains nerve roots 34 surrounded by cerebrospinal fluid . the nerve roots 34 normally comprise only a small proportion of the thecal sac volume . in fig2 , spinal stenosis is present . ligamentum flavum 26 is markedly thickened , compressing the posterior margin of dural sleeve 32 . as shown in fig2 , the posterior margin of the dural sleeve 32 is apposed to the ligamentum flavum and the epidural space is only a potential space . because more than 90 % of the volume of the thecal sac in the lumbar region is filled by csf , the thecal sac is highly compressible . thus , even though stenosis may be causing compression of the thecal sac ( and associated pain or discomfort ), in most instances it will be possible to temporarily compress the thecal sac further . thus , according to preferred embodiments of the invention , thecal sac 32 is compressed in a region of interest by applying pressure to the outside of the sac so that at least a portion of the csf is forced out of the region of interest . according to certain embodiments , thecal sac 32 is compressed by injecting a standard radio - opaque non - ionic myelographic contrast medium or other imagable or non - imagable medium into the epidural space in the region of interest . this is preferably accomplished with a percutaneous injection . the result is illustrated in fig3 . the presence of the fluid gently compresses and displaces the dural sleeve 32 in the region of interest ) creating a safety zone 40 between thecal sac 32 and ligamentum flavum 26 . sufficient injectable fluid is preferably injected to displace the csf out of the region of interest and compress the thecal sac to at least a desired degree . the injected medium is preferably substantially contained within the confines of the epidural space extending to the margins of the nerve root sleeves . the epidural space is substantially watertight and the fatty tissues and vascularization in the epidural space , combined with the viscous properties of the preferred fluids , serve to substantially maintain the injected medium in the desired region of interest . this novel method for protecting the neural column may be referred to hereinafter as “ contrast - guided dural protection .” once a safety zone 40 has been created , a tool 100 , such as the tissue excision devices and tissue retraction devices described below , can be inserted into the ligamentum flavum 26 , as illustrated in fig4 . while it is preferred that the tip of the tool remain within the ligament as shown , the presence of safety zone 40 ensures that the thecal sac will not be damaged even if the tool breaks through the anterior surface of ligament 26 . for insertion of the tool , a fluoroscopic window of access ( fwa ) is defined by the inferior margin of the lamina ( contra lateral to the point of instrument entry in the soft tissues ) and the dorsal margin of the contrast material that defines the epidural space . this fwa is roughly orthogonal to the long axis of the cutting instrument , which parallels the inferior surface of the lamina as in fig4 . the fluoroscopic plane of projection is preferably but not necessarily oriented 20 - 45 degrees from normal ( ap projection ). because the present techniques are preferably performed percutaneously , certain aspects of the present invention can be facilitated by imaging . in this context , the spine can be imaged using any suitable technology , including but not limited to 2d , 3d fluoroscopy , ct , mri , ultrasound or with direct visualization with fiber optic or microsurgical techniques . stereotactic or computerized image fusion techniques are also suitable . fluoroscopy is currently particularly well - suited to the techniques disclosed herein . fluoroscopic equipment is safe and easy to use , readily available in most medical facilities , relatively inexpensive . in a typical procedure , using direct biplane fluoroscopic guidance and local anesthesia , the epidural space is accessed adjacent to the surgical site as described above . if the injected medium is radio - opaque , as are for example myelographic contrast media , the margins of the expanded epidural space will be readily visible using fluoroscopy or ct imaging . thus , the safety zone created by the present contrast - guided dural compression techniques can reduce the risk of damage to the spinal cord during procedures to remove or displace portions of the ligamentum flavum and / or laminae in order to treat spinal stenosis . if desired , the injected medium can be provided as a re - absorbable water - soluble gel , so as to better localize the safety zone at the site of surgery and reduce leakage of this protective layer from the spinal canal . an injectable gel is a significant improvement on prior epidural injection techniques . the gel is preferably substantially more viscid than conventional contrast media and the relatively viscid and / or viscous gel preferably tends to remain localized at the desired site of treatment as it does not spread as much as standard liquid contrast media that are used in epidurography . the injected gel is preferably sufficiently viscous that it remains substantially within the local epidural space . this results in more uniform compression on the thecal sac and less leakage of contrast out of the canal . in addition , preferred embodiments of the gel are re - absorbed more slowly than conventional contrast media , allowing for better visualization during the course of the surgical procedure . in some embodiments , a contrast agent can be included in the gel itself , so that the entire gel mass is imagable . in other embodiments , an amount of contrast can be injected first , followed by the desired amount of gel , or an amount of gel can be injected first , followed by the desired amount of contrast . in this case , the contrast agent is captured on the surface of the expanding gel mass , so that the periphery of the mass is imagable . any standard hydrophilic - lipophilic block copolymer ( pluronic ) gel such as are known in the art would be suitable and other gels may be used as the injectable medium . the gel preferably has an inert base . in certain embodiments , the gel material is liquid at ambient temperatures and can be injected through a small bore ( such as a 27 gauge needle ). the gel then preferably becomes viscous when warmed to body temperature after being injected . the viscosity of the gel can be adjusted through the specifics of the preparation . the gel or other fluid is preferably sufficiently viscid or viscous at body temperature to compress and protect the thecal sac in the manner described above and to remain sufficiently present in the region of interest for at least about 30 minutes . thus , in some embodiments , the injected gel attains a viscosity that is two , three , six or even ten times that of the fluids that are typically used for epidurograms . in certain embodiments , the injected medium undergoes a reversible change in viscosity when warmed to body temperature so that it can be injected as a low - viscosity fluid , thicken upon injection into the patient , and be returned to its low - viscosity state by cooling . in these embodiments , the injected medium is injected as desired and thickens upon warming , but can be removed by contacting it with a heat removal device , such as an aspirator that has been provided with a cooled tip . as a result of localized cooling , the gel reverts to its initial non viscous liquid state and can be easily suctioned up the cooled needle or catheter . an example of a suitable contrast medium having the desired properties is omnipaque ® 240 available from nycomed , new york , which is a commercially available non - ionic iodinated myelographic contrast medium . other suitable injectable media will be known to those skilled in the art . because of the proximity to the spinal nerves , it is preferred not to use ionic media in the injectable medium . the preferred compositions are reabsorbed relatively rapidly after the procedure . thus any residual gel compression on the thecal sac after the mild procedure resolves relatively quickly . for example , in preferred embodiments , the gel would have sufficient viscosity to compress the thecal sac for thirty minutes , and sufficient degradability to be substantially reabsorbed within approximately two hours . the injected contrast medium further may further include one or more bioactive agents . for example , medications such as those used in epidural steroid injection ( erg . depo medrol , celestone soluspan ) may be added to the epidural gel to speed healing and reduce inflammation , scarring and adhesions . the gel preferably releases the steroid medication slowly and prolongs the anti - inflammatory effect , which can be extremely advantageous . local anesthetic agents may also be added to the gel . this prolongs the duration of action of local anesthetic agents in the epidural space to prolong pain relief during epidural anesthesia . in this embodiment the gel may be formulated to slow the reabsorption of the gel . the present gels may also be used for epidural steroid injection and perineural blocks for management of acute and chronic spinal pain . thrombin or other haemostatic agents can be added if desired , so as to reduce the risk of bleeding . in some embodiments , the gel may also be used as a substitute for a blood patch if a csf leak occurs . the gel may also be used as an alternative method to treat lumbar puncture complications such as post - lumbar puncture csf leak or other causes of intracranial hypotension . similarly , the gel may be used to patch postoperative csf leaks or dural tears . if the dural sac were inadvertently torn or cut , then gel could immediately serve to seal the site and prevent leakage of the cerebral spinal fluid . after safety zone 40 has been created , the margins of the epidural space are clearly demarcated by the injected medium and can be visualized radiographically if an imagable medium has been used . as mentioned above , percutaneous procedures can now safely be performed on the ligamentum flavum and / or surrounding tissues without injuring the dural sac or nerves and the spinal canal can be decompressed using any of several techniques . suitable decompression techniques include removal of tissue from the ligamentum flavum , laminectomy , laminotomy , and ligament retraction and anchoring . in some embodiments , all or a portion of the ligamentum flavum and / or lamina are excised using a percutaneous tissue excision device or probe 100 , which may hereinafter be referred to as the mild device . as shown schematically in fig4 , a device 100 may be placed parallel to the posterior and lateral margin of the safety zone 40 with its tip in the ligamentum flavum 26 . preferred embodiments of the present tissue excision devices and techniques can take several forms . in the discussion below , the distal ends of the tools are described in detail . the construction of the proximal ends of the tools , and the means by which the various components disclosed herein are assembled and actuated , will be known and understood by those skilled in the art . by way of example , in the embodiment shown in fig4 and as illustrated in fig5 , device 100 may be a coaxial excision system 50 with a sharpened or blunt tip that is placed obliquely into the thickened ligamentum flavum 26 posterior to safety zone 40 under fluoroscopic guidance . the needle is preferably placed parallel to the posterior margin of the canal . excision system 50 is preferably manufactured from stainless steel , titanium or other suitable durable biocompatible material . as shown in fig5 - 10 , an outer needle or cannula 51 has an opening or aperture 52 on one side that is closed during insertion by an inner occluding member 54 . aperture 52 is readily visible under imaging guidance . once needle 51 is positioned in the ligamentum flavum or other tissue removal site , inner occluding member 54 is removed or retracted so that it no longer closes aperture 52 ( fig6 ). aperture 52 is preferably oriented away from the epidural space so as to further protect the underlying structures from injury during the surgical procedure . if it was not already present in the tool , a tissue - engaging means 56 is inserted through outer needle 51 to aperture 52 so that it contacts adjacent tissue , e . g ., the ligamentum flavum , via aperture 52 . tissue - engaging means 56 may be a needle , hook , blade , tooth or the like , and preferably has at least one flexible barb or hook 58 attached to its shaft . the barb 58 or barbs may extend around approximately 120 degrees of the circumference of the shaft . barbs 58 are preferably directed towards the proximal end of the tool . when needle 56 is retracted slightly , barbs 58 allow it to engage a segment of tissue . depending on the configuration of barbs 58 , the tissue sample engaged by needle 56 may be generally cylindrical or approximately hemispherical . once needle 56 has engaged the desired tissue , inner occluding means 54 , which is preferably provided with a sharpened distal edge , is advanced so that it cuts the engaged tissue section or sample loose from the surrounding tissue . hence occluding means 54 also functions as a cutting means in this embodiment . in alternative embodiments , such as fig1 - 14 discussed below , a cylindrical outer cutting element 60 may extended over outer needle 51 and used in place of occluding member 54 to excise the tissue sample . referring still to fig5 - 9 , once the tissue sample has been cut , tissue - engaging needle 56 can be pulled back through outer needle 51 so that the segment of tissue can be retrieved and removed from the barbs ( fig8 ). the process or engaging and resecting tissue may be repeated ( fig9 ) until the canal is adequately decompressed . referring briefly to fig1 - 14 , in other embodiments , a tissue - engaging hook 64 can be used in place of needle 56 and an outer cutting member 60 can be used in place of inner occluding member 54 . hook 64 may comprise a length of wire that has been bent through at least about 270 °, more preferably through 315 °, and still more preferably through about 405 °. alternatively or in addition , hook 64 may comprise nitinol ™, or any other resilient metal that can withstand repeated elastic deflections . in the embodiment illustrated , hook 64 includes at least one barb 58 at its distal end . in some embodiments , hook 64 is pre - configured in a curvilinear shape and is retained within tool 100 by outer cutting member 60 . when cutting member 60 is retracted , the curved shape of hook 64 urges its outer end to extend outward through aperture 52 . if desired , hook 64 can be advanced toward the distal end of tool 100 , causing it to extend farther into the surrounding tissue . in some embodiments , hook 64 is provided with a camming surface 66 . camming surface 66 bears on the edge of opening 52 as hook 64 is advance or retracted and thereby facilitates retraction and retention of hook 64 as it is retracted into the tool . in these embodiments , hook 64 may not extend through aperture 52 until it has been advanced sufficiently for camming surface 66 to clear the edge of the opening . hook 64 may alternatively be used in conjunction with an inner occluding member 54 in the manner described above . as above , hook 64 can be used to retrieve the engaged tissue from the distal end of the tool . in still other embodiments , the tissue - engaging means may comprise a hook or tooth or the like that engages tissue via aperture 52 by being rotated about the tool axis . in such embodiments ( not shown ) and by way of example only , the tissue - engaging means could comprise a partial cylinder that is received in outer cannula 51 and has a serrated side edge . such a device can be rotated via a connection with the tool handle or other proximal device . as the serrated edge traverses aperture 52 tissue protruding into the tool via the aperture is engaged by the edge , whereupon it can be resected and retrieved in the manner disclosed herein . in preferred embodiments , the working tip of tool 100 remains within the ligamentum flavum and does not penetrate the safety zone 40 . nonetheless , safety zone 40 is provided so that even an inadvertent penetration of the tool into the epidural space will not result in damage to the thecal sac . regardless of the means by which the tissue is engaged and cut , it is preferably retrieved from the distal end of the tool so that additional tissue segments can be excised without requiring that the working tip of the tool be repositioned . a tissue - removal device such as that described below is preferably used to remove the tissue from the retrieval device between each excision . each piece of tissue may be removed from barbs 58 by pushing tissue - engaging means 56 through an opening that is large enough to allow passage of the flexible barbs and supporting needle but smaller than the diameter of the excised tissue mass . this pushes the tissue up onto the shaft , where it can be removed with a slicing blade or the like or by sliding the tissue over the proximal end of the needle . alternatively , needle 56 can be removed and re - inserted into the tool for external , manual tissue removal . it is expected that in some embodiments , approximately 8 - 10 cores or segments of tissue will be excised and pushed up the shaft towards the hub during the course of the procedure . alternatively , a small blade can be used to split the tissue segment and thereby ease removal of the segment from the device . if desired , a blade for this purpose can be placed on the shaft of needle 56 proximal to the barbs . in an exemplary embodiment , shown in fig1 - 18 , the tissue removal device may include a scraper 120 that includes a keyhole slot having a wide end 122 and a narrow end 124 . to remove a tissue sample from needle 56 or hook 64 , the tissue - engaging device with a mass of excised tissue 110 thereon can be retracted ( pulled toward the proximal end of the tool ) through wide end 122 of the slot and then re - inserted ( pushed toward the distal end of the tool ) through narrow end 124 of the slot . narrow end 124 is large enough to allow passage of the barbed needle , but small enough to remove the tissue mass as the needle passes through . the removed tissue can exit the tool through an opening 113 in the tool body . by shuttling the tissue - engaging device through scraper 120 in this manner , each excised segment of tissue 110 can be removed from the device , readying the device for another excision . in an alternative embodiment shown in fig3 , the tissue removal device may be constructed such that tissue is removed from the tissue - engaging device by retracting the tissue - engaging device through narrow end 124 of the slot . as above , narrow end 124 is large enough to allow passage of the shaft of the tissue - engaging device , but small enough to remove the tissue mass as the needle passes through . if the tissue - engaging device is constructed of a tough material , the barbs or the like will cut through the tissue and / or deform and release the tissue . as above , the removed tissue can exit the tool through an opening 113 in the tool body . by shuttling the tissue - engaging device through scraper 120 in this manner , each excised segment of tissue 110 can be removed from the device , readying the device for another excision . in another alternative embodiment ( not shown ) an alternative mechanism for removing the tissue segment from needle 56 includes an adjustable aperture in a disc . after the tissue - bearing needle is pulled back through the aperture , the aperture is partially closed . needle 56 and flexible hooks 58 then can pass through the partially closed aperture but the larger cylinder of tissue cannot . thus the tissue segment is pushed back onto the shaft . the tissue segment can either be pulled off the proximal end of the shaft or cut off of it . a small blade may be placed just proximal to the barbs to help cut the tissue segment off the shaft . the variable aperture can formed by any suitable construction , including a pair of metal plates with matching edges that each define one half of a central opening . the two pieces may be held apart by springs . the aperture may be closed by pushing the two edges together . in other embodiments , this process can be mechanically automated by using a disc or plate with an opening that is adjustable by a variety of known techniques , including a slit screw assembly or flexible gaskets . other cutting and / or grasping devices can be used in place of the system described above . for example , embodiments of the grasping mechanism include but are not limited to : needles with flexible barbs , needles with rigid barbs , corkscrew - shaped needles , and / or retaining wires . the corkscrew - shaped needle shown in fig1 works by screwing into the ligamentum flavum in the manner that a corkscrew is inserted in a cork . after the screw engages a segment of tissue , outer cutting element 60 slides over the needle , cutting a segment of tissue in a manner similar to that of the previous embodiment . in some embodiments , the cutting element can be rotated as it cuts . in other embodiments , shown in fig2 - 22 , cannulated scalpel 5 houses a grasping device 70 that includes at least one pair of arcuate , closable arms 72 . closable arms 72 may be constructed in any suitable manner . one technique for creating closable arms is to provide a slotted sleeve 74 , as shown . slotted member 74 preferably comprises an elongate body 75 with at least one slot 76 that extends through its thickness but does not extend to either end of the body . slot 76 is preferably parallel to the longitudinal axis of the sleeve . on either side of slot 76 , a strip 77 is defined , with strips 77 being joined at each end of sleeve 74 . it is preferred that the width of each strip 77 be relatively small . in some embodiments , it may be desirable to construct slotted member 74 from a portion of a hollow tube or from a rectangular piece that has been curved around a longitudinal axis . the inner edge of each strip that lies along slot 76 forms an opposing edge 78 . the width of the piece is the total of the width of strips 77 and slot 76 . advancing one end of sleeve 74 toward the other end of sleeve 74 causes each strip 77 to buckle or bend . if strips 77 are prevented from buckling inward or if they are predisposed to bend in the desired direction , they will bend outward , thereby forming arcuate arms 72 , which extend through aperture 52 of cannulated scalpel 51 , as shown in fig2 . as they move away from the axis of body 75 , arms 72 move apart in a direction normal to the axis of body 75 . likewise , moving the ends of sleeve 74 apart causes arms 72 to straighten and to move together and inward toward the axis of the device , as shown in fig2 . as the arms straighten , opposing edges 78 close and a segment of tissue can be capture between them . tissue within the grasping device may then be resected or anchored via the other mechanisms described herein closable arms 72 may include on their opposing edges 78 ridges , teeth , or other means to facilitate grasping of the tissue . in other embodiments , edges 78 may be sharpened , so as to excise a segment of tissue as they close . in these embodiments , closable arms 72 may also be used in conjunction with a hook , barbed needle , pincers or the like , which can in turn be used to retrieve the excised segment from the device . once arms 72 have closed on the tissue , if arms 72 have not cut the tissue themselves , the tissue can be excised using a blade such as cutting element 60 above . the excised tissue can be removed from the inside of needle 51 using a tissue - engaging hook 64 or other suitable means . the process of extending and closing arms 72 , excising the tissue , and removing it from the device can be repeated until a desired amount of tissue has been removed if desired , this cycle can be repeated without repositioning the device in the tissue . alternatively , the tool can be rotated or repositioned as desired between excisions . it is possible to rotate or reposition the tool during an excision , but it is expected that this will not generally be preferred . furthermore , it is expected that the steps of tissue excision and removal can be accomplished without breaching the surface of the ligament , i . e . without any part of the device entering the safety zone created by the injected fluid . nonetheless , should the tool leave the working zone , the safety zone will reduce the risk of injury to the thecal sac . in some embodiments , the spinal canal may also be enlarged by retracting the ligamentum flavum , either with or without concurrent resection . retraction is preferably but not necessarily performed after dural compression has been used to provide a safety zone . in addition , the dural compression techniques described above have the effect of pressing the ligamentum flavum back out of the spinal canal and thereby making it easier to apply a restraining means thereto . thus , in preferred embodiments , after a safety zone is created by epidural injection of contrast medium or gel , a retraction device 90 as shown in fig2 is used to retract and compress the thickened soft tissues around the posterior aspect of the spinal canal , thereby increasing the available space for the dural sac and nerves . in the embodiment shown , retraction device 90 is a double - headed anchor that includes at least one distal retractable tissue - engaging member 91 and at least one proximal tissue - engaging member 92 , each of which are supported on a body 94 . retraction device 90 is preferably constructed from an implantable , non - biodegradable material , such as titanium or stainless steel , but may alternatively be polymeric or any other suitable material . in certain preferred embodiments , body 94 is somewhat flexible . in some instances , flexibility in body 94 may facilitate the desired engagement of barbs 91 , 92 . barbs 91 , 92 may comprise hooks , arms , teeth , clamps , or any other device capable of selectively engaging adjacent tissue . barbs 91 , 92 may have any configuration that allows them to engage the ligamentum flavum and / or surrounding tissue . similarly , barbs 91 , 92 may be covered , sheathed , pivotable , retractable , or otherwise able to be extended from a first position in which they do not engage adjacent tissue to a second position in which they can engage adjacent tissue . fig2 shows schematically the distal and proximal retractable arms 91 , 92 of a preferred ligament anchor 90 . the proximal end of the anchor preferably includes a threaded connector 96 or other releasable mechanism that attaches to a support rod 100 . ligament anchor 90 may be attached to a support shaft 112 and sheathed in a guide housing 114 . the distal and proximal barbs 91 , 92 are prevented by guide housing 114 from engaging surrounding tissue . housing 102 is preferably a metal or durable plastic guide housing . the distal end of the device is preferably positioned in the ligamentum flavum under fluoroscopic guidance . if desired , an accessway through the lamina may be provided using an anchored cannula or the like . the device is held in position by support shaft 112 . distal barbs 91 are unsheathed and optionally expanded by pulling back guide housing 102 , as shown in fig2 . distal barbs 91 are secured in the ligamentum flavum by pulling back on the support shaft 112 . with barbs 91 engaging the tissue , the ligamentum flavum is retracted posteriorly by pulling back on support shaft 112 . while maintaining traction on the now - retracted ligament , proximal barbs 92 are uncovered and expanded by retracting guide housing 114 , as shown in fig2 . barbs 92 are preferably positioned in the soft tissues 116 in the para - spinal region so that the device is firmly anchored behind the posterior elements of the spinal canal . once the proximal end of the anchor is engaged , support shaft 112 may be detached from body 94 as shown in fig2 . in this manner , the posterior margin 95 of the ligamentum flavum can be held in a retracted position , thereby expanding the canal . the procedure can then be repeated on adjacent portions of the ligamentum flavum until it is sufficiently retracted . in an alternative embodiment , the proximal end of ligament anchor 90 may be adapted to engage the lamina . this may be accomplished by having the arm posterior to the lamina or by using the laminotomy and suturing the device to the lamina there . a knotted or knotless system or a suture plate can be used . a second embodiment of the present method uses a plurality of retraction devices 90 . in this embodiment , the retraction device is inserted through one lamina in an oblique fashion , paralleling the opposite lamina . after the distal anchor is deployed , the retraction device is pulled back and across the ligamentum flavum , thereby decompressing the opposite lateral recess of the spinal canal . this is repeated on the opposite side . this same device can also be deployed with a direct approach to the lateral recess with a curved guide housing . while retraction device 90 is describe above as a double - headed anchor , it will be understood that other devices can be used . for example sutures , barbed sutures , staples or the like can be used to fasten the ligament in a retracted position that reduces stenosis . using the percutaneous methods and devices described herein , significant reductions of stenosis can be achieved . for example , a dural sac cross - sectional area less than 100 mm2 or an anteroposterior ( ap ) dimension of the canal of less than 10 - 12 mm in an average male is typically considered relative spinal stenosis . a dural sac cross - sectional area less than 85 mm2 in an average male is considered severe spinal stenosis . the present devices and techniques are anticipated to cause an increase in canal area of 25 mm2 per anchor or 50 mm2 total . with resection and / or retraction of the ligamentum flavum , the cross - sectional area of the dural sac can be increased by 10 mm2 , and in some instances by as much as 20 mm2 or even 30 mm2 . likewise , the present invention can result in an increase of the anteroposterior dimension of the canal by 1 to 2 mm amid in some instances by as much as 4 or 6 mm . the actual amount by which the cross - sectional area of the thecal sac and / or the anteroposterior dimension of the canal are increased will depend on the size and age of the patient and the degree of stenosis and can be adjusted by the degree of retraction of the ligament . the minimally invasive ligament decompression ( mild ) devices and techniques described herein allow spinal decompression to be performed percutaneously , avoiding the pain and risk associated with open surgery . through the provision of a safety zone , the present devices and techniques offer reduced risk of spinal cord damage . in addition to improving nerve function , it is expected that decompression of the spinal canal in the manner described herein will result in improved blood flow to the neural elements by reducing the extrinsic pressure on the spinal vasculature . for these reasons , it is believed that spinal decompression performed according to the present invention will be preferable to decompression operations performed using currently known techniques . in some embodiments ( not shown ), a mechanical device such as a balloon or mechanical shield can also be used to create a protective guard or barrier between the borders of the epidural space and the adjacent structures . in one embodiment a durable expandable device is attached to the outside of the percutaneous laminectomy device , preferably on the side opposite the cutting aperture . the cutting device is inserted into the ligamentum flavum with the expandable device deflated . with the aperture directed away from the spinal canal , the expandable device is gently expanded via mechanical means or inflated with air or another sterile fluid , such as saline solution , via a lumen that may be within or adjacent to the body of the device . this pushes the adjacent vital structures clear from the cutting aperture of the device and simultaneously presses the cutting aperture into the ligament . as above , the grasping and cutting needles can then be deployed and operated as desired . the balloon does not interfere with tissue excision because it is located on the side opposite the cutting aperture . the cutting needle may be hemispherical ( semi - tubular ) in shape with either a straight cutting or a sawing / reciprocating blade or may be sized to be placed within the outer housing that separates the balloon from the cutting aperture . in another embodiment , a self - expanding metal mesh is positioned percutaneously in the epidural space . first the epidural space is accessed in the usual fashion . then a guide catheter is placed in the epidural space at the site of the intended surgical procedure . the mesh is preferably compressed within a guide catheter . when the outer cover of the guide catheter is retracted , the mesh expands in the epidural space , protecting and displacing the adjacent dural sheath . at the conclusion of the surgical procedure , the mesh is pulled back into the guide sheath and the assembly removed . the mesh is deformable and compresses as it is pulled back into the guide catheter , in a manner similar to a self - expanding mesh stent . there are many commercially available self - expanding stents approved and in use in other applications . however , using a self expandable mesh as a device within the epidural space to protect and displace the thecal sac is novel while preferred embodiments of this invention have been shown and described , modifications thereof can be made by one skilled in the art without departing from the scope or teaching of this invention . for example , the means by which the safety zone is formed may be varied , the shape and configuration of the tissue excision devices may be varied , and the steps used in carrying out the technique may be modified . accordingly , the invention is not limited to the embodiments described herein , but is only limited by the claims that follow , the scope of which shall include all equivalents of the subject matter of the claims . likewise , the sequential recitation of steps in a claim , unless explicitly so stated , is not intended to require that the steps be performed in any particular order or that a particular step be completed before commencement of another , step .

US-38038206-A

a position - finding device for locating the position of a working edge , especially the edge of a crop , wherein the position - finding signal therefrom is supplied in the form of a steering adjustment value to an electrically controlled steering device in an agricultural machine , and wherein the device comprises a first sub position - finding device including a transmitter and a receiver whose zone of reflection extends mainly over the field that has not yet been worked , especially the not yet harvested field , and a second sub position - finding device including a further transmitter and a further receiver whose differing reflection zone is aligned such as to overlap both sides of the working edge , wherein the two reflection zones partially overlap and the two transmitters are simultaneously triggered by a pulse whereby the two receivers accordingly receive overlapping partial reception signals originating from the two transmitters and reflected by the unworked field .

fig1 shows a moveable machine in the form of a self - propelled combine harvester 1 incorporating , at its front , a cutter bar or cutter bar mw which is intended to travel along an edge gk of standing grain in a grain field gf . preferably the machine 1 is automatically controlled to stay close to the grain edge by allowing it to deviate only slightly from a predefined position gks located laterally thereof . a height adjustable position - finding device ov includes two sub position - finding devices ov 1 , ov 2 and is arranged above one end of the cutter bar mw and advantageously at the front corner of that end . the sub position - finding devices ov 1 , ov 2 are advantageously in the form of ultrasonic transmitter - receiver assemblies . the sub position - finding devices ov 1 and ov 2 emit ultrasonic position - finding beams ost 1 and ost 2 , respectively . beam ost 1 is directed at the grain field gf , while beam ost 2 is generally directed toward the edge gk of the grain so as to be oriented on both the stubble field and the grain field gf so as to provide differing , partially overlapping reflection zones rg 1 , rg 2 , rg 2 *. the beams ost 1 and ost 2 provide reflected signals os 1 and os 2 , respectively . signal os 1 is derived from the grain field gf and is utilized for defining the normalized range thereby providing a reference value ; whereas the signal os 2 from the stubble field and the grain field at the edge gk provides a steering signal after processing . the received position - finding signals os 1 , os 2 are supplied to a control device st . ideally , these position - finding signals are digitized and converted into a normalized position - finding signal nos . further , the first position - finding signal os 1 is specified as a reference value for a component of the second position - finding signal os 2 which is derived from the second partial reflection zone rg 2 located in the near region in the grain field gf . in the illustrated embodiment , the control device st is connected via a normalized data bus can to a central processor zp which also monitors other control processes of the machine 1 . the central processor zp is provided with an input keyboard et and an output device av for this purpose . further , the central processor zp advantageously receives a speed indicating signal vs from front wheels vr . a hydraulic steering mechanism lh is electromagnetically controlled from the control device st by means of a left - hand control valve lv and a right - hand control valve rv whose hydraulic outputs are connected to the existing hydraulic steering mechanism lh for turning rear wheels hr . a signal rws representing the angular turn - out position of the steering wheels hr is derived from the steering device and supplied to the control device st . the steering valves lv , rv are conveniently spring - loaded to provide a measure of self - protection in that they close in the event of a power failure . should this happen , steering is effected directly by the steering wheel r via a known hydraulic control system . moreover , a manual switch hs , a foot switch fs and a security switch ns are provided in the operator &# 39 ; s cab . the signals from these switches are supplied to the assembly of steering valves and they are also made available to the control device st so as to activate it when these signals are complete . the distance from the position - finding device ov to the forward point at which the position - finding beam ost 2 scans the edge of the grain gk advantageously corresponds approximately to the spacing between the front wheels vr and the rear wheels hr . via this relationship , an angular change between the axis of the combine harvester 1 and the elongate edge of the grain gks can be determined and this angle is represented in the position - finding signal in the form of a partial component , an equivalent to the signal indicating the angular position of the wheels . this angular component of the position - finding signal overlies the component for the lateral deviation of the directional axis of the combine harvester from the predefined , preferred path i . e . the component which furnishes its lateral position from the grain edge gks . the position - finding device ov preferably supplies its normalized position - finding signal nos to the control device st . other sensors producing other input values are distributed around the combine harvester 1 and pass their signals to the control device st , for example via appertaining digitizing and calculating means . their appertaining normalizing means could of course also be installed directly in the vicinity of these sensors . a steering wheel position sensor lss , whose wheel angle representing signal rws is used in appropriate manner as yet another input signal for the steering control means , is provided on the steered rear wheels hr . it has proved propitious to logically combine , in compensatory manner , the normalized position - finding signal nos and the wheel angle representing signal rws taken with reference to the normalizing signal , and to supply the result to a tolerance comparator which produces appropriate steering adjustment values lsg . the steering adjustment value lsg is converted into a left - or right - hand hydraulic setting signal shl , shr and supplied to the left - or right - hand control valve lv , rv . fig2 shows a side view of the cutter bar mw of the combine harvester 1 in the vicinity of the grain edge gk and also shows the position - finding beam ost 2 . the appertaining sub position - finding device ov 2 together with the other sub position - finding device ov 1 are arranged on a support ha , at the front , above a crop lifter 12 of the cutter bar mw and are adjustable in height h , h 1 between 1 . 5 and 2 . 5 meters above the ground . the inclined position - finding beam ost 2 is incident partially on the ground and the stubble and partially on the standing crop adjacent the grain edge gk . the included angle of the position - finding beam ost 2 will provide about 50 % of the signal component when the angle is approximately 7 ° about 90 % of the signal component when the angle is approximately 14 °. the angle of inclination is selected such that the reflection zone rg 2 on the standing grain gf produces a separable earlier echo than that produced by the ground or stubble reflection zone rg 2 *. it should be ensured that there is a fully detectable echo from both reflection zones rg 2 , rg 2 * even when travelling over uneven ground , such as a knoll , so that the ultrasonic beam does not simply disappear . the position - finding head is lowered in height h 1 when the upper edge of the grain is lower , as shown at gk 1 in fig2 . its inclination will then be somewhat flatter so that the two appertaining reflection zones will produce approximately the same echo transit times and the echo signals will have approximately the same amplitude . since both of the sub position - finding devices ov 1 , ov 2 are adjusted in height and appertaining inclination in the same manner , the temporal and magnitude relationships of the received signals will always be virtually the same . also , since the echo zones of the two sub position - finding devices ov 1 , ov 2 partially overlap and are otherwise directly adjacent , their reflection characteristics will , to a large extent , be the same independently of whether a strong reflection occurs from a whole crop aligned with the ultrasonic beam , or whether a weak reflection occurs from a few stalks inclined away from the sensor . for this reason , the echo signal for the first sub position - finding device ov 1 originating mainly from the grain field gf serves as the 100 % normalized signal for the earlier signal component in the second sub position - finding device ov 2 which likewise originates from the grain field . where the predefined alignment of the position - finding device relative to the grain edge gk is being maintained i . e . when the steering is correct , then the earlier echo expected from the ultrasonic beam directed at the edge will have a magnitude that is approximately ½ to ⅔ that of the reference echo from the other receiver . the echo signals are integrated during an appropriate time window in order to compensate for signal fluctuations occurring due to the heterogeneous structure of the echo zone and to make them more readily comparable . preferably , upper and lower limiting values for the relative amplitudes of the integrated earlier echo signals are specified , whereby any under - or over - shooting of these limits will then be used for producing the steering adjustment signals . in the simplest version of the steering system , these under - or over - shooting signals are used directly as right - or left - hand setting signals for the electromagnetically actuated valves lv , rv in the hydraulic lines leading to the hydraulic steering mechanism lh . in a more precisely operative , two - stage control device , it is preferred that the deviation of the normalized echo signal from a specified fraction of the reference signal be supplied in the form of a preferred signal to a subsequent control stage to which the actual wheel angle signal is also supplied . if the resultant difference signal under - or overshoots a lower or upper threshold value then the relevant over - shooting signal is used for differentially controlling the hydraulic steering mechanism lh or other hydraulic adjustment device . in known manner , the hydraulic adjustment device is preferably provided with a further subregulating device having a proportional characteristic . if the control device st is in the form of a digital computer , this will allow the steering system to be fully integrated into the usual digital control system of the combine harvester 1 . the relevant parameters , especially the threshold values , are preset in the computer by a simple parameterization process by means of signals sent from the control console of the harvesting machine 1 . the basic structure of the control device itself is completely neutral . the height adjusting device for lifting the position - finding device ov up to a maximum height h and for lowering it to a lower height h 1 is illustrated in fig2 . a swivel arm sa is mounted on the fixed supporting arm ha and is also connected to a height adjusting device hsv . the height adjusting device hsv may be a length adjusting device or an angle adjusting device which is located on the end of the supporting arm ha . one leg of the swivel arm forms part of a four - bar linkage . the position - finding device ov is mounted on a member vg at the front of the linkage . the four - bar linkage is designed such that the downward inclination of the axis of the position - finding device ov on the member vg will become steeper as the device is set higher . this can be done for example by making a lower control arm ul of the four - bar linkage shorter than an upper control arm ol thereof . in the dashed - line lower position illustrated in fig2 a clamp sc holding the position - finding device ov is aligned with the lower grain edge gk 1 . the adjustment ratios for the height and the inclination of the position - finding device are selected such that the first echo from the upper reflection zone rg 2 arrives in approximately the same time period independently of the setting , and the ground level reflection zone rg 2 * is always spaced from the position - finding head ov by at least a distance ae which is markedly greater than the greatest spacing of the higher reflection zone rg 2 so that the ground echo can be masked out over time . fig4 shows a section through the position - finding device ov which is detachably mounted in tiltable manner by means of the clamp sc on a horizontal supporting tube hr . the two sub position - finding devices ov 1 , ov 2 are housed in a housing g and diverge slightly from one another . a variant of the control circuit is illustrated in fig3 . the two position - finding signals os 1 , os 2 are integrated in the integrator circuits i 1 , i 2 during a time window t 1 in which the earlier echo signal is expected . the integrated values are then accepted by the buffer circuits hs 1 , hs 2 at a clock rate t 2 . the reference signal coming from the first buffer circuit hs 1 is divided in a three stage voltage divider r 1 , rt , r 2 . a relative upper limiting value go and a relative lower limiting value gu are provided at the central resistor rt , which defines the tolerance range , and these values are respectively supplied to the positive and negative inputs of two comparators v 1 , v 2 . the respective signals from the two buffer circuits hs 1 , hs 2 are supplied to the other inputs of the comparators v 1 , v 2 . this input circuit is in the form of an adding circuit including a resistance network r , sr 1 , sr 2 . the wheel angle signal rws , which is supplied to a steering position sensor lss that is fed with the negated reference signal from the first buffer circuit hs 1 in the form of a reference signal , is taken from the second input sr 2 . consequently , the position - finding signal os 2 will be reduced by the wheel angle signal rws in the comparators v 1 , v 2 . said wheel angle signal rws is normalized with respect to the first position - finding signal os 1 and compared with the respective threshold values go , gu . should this sum signal exceed the upper limiting value go which indicates that the alignment into the stock is too great , then the steering control signal shl is supplied by the first comparator v 1 to the first control valve lv . if the lower threshold gu is undershot i . e . the position - finding device is aligned too much towards the stubble field , then the other comparator v 2 sends the other steering control signal shr to the other control valve rv . the wheel setting angle is thereby controlled in proportion to the amount of deviation found by the position - finding process . while a preferred embodiment of the invention has herein been illustrated and described , this has been done by way of illustration and not limitation , and the invention should not be limited except as required by the scope of the appended claims .

US-41266899-A

this invention is directed to a balloon dilatation catheter which comprises a first , inflation lumen extending therethrough and having distal and proximal ends , the distal end of said first lumen opening into and being in fluid communication with the interior of an expandable dilatation balloon having distal and proximal ends , and a second lumen extending coextensively with the first lumen and having proximal and distal portions , wherein the proximal portion of the second lumen has an opening adjacent or distal to the proximal end of the first lumen , the distal section of the second lumen is exterior to the balloon , the distal end of the second lumen is open , and the second lumen is capable of receiving a guidewire in a sliding fit . the proximal end of the guidewire may have a removedly mounted slitter , and optionally there may be a hub means in fluid communication with the distal end of the second lumen .

according to the invention , a balloon dilatation catheter comprises two substantially longitudinal coextensive lumens wherein the distal portion of one lumen terminates in a dilatation balloon . the other , second lumen is open at its proximal and distal ends to provide a passageway for a guidewire that extends distally through the open distal end of the second lumen . moreover , the second lumen optionally comprises a pushing wire that extends from the proximal portion of the catheter to a point adjacent or proximal to the distal end of the catheter . the invention can perhaps be better appreciated by making reference to the drawings . fig1 depicts a cross - sectional view of a balloon dilatation catheter 1 having substantially coextensively extending inflation lumen 2 and guidewire lumen 3 . lumen 2 terminates in a dilatation balloon 4 which is inflated and deflated through lumen 2 . lumen 3 optionally contains a stiffening or pushing wire 5 , which extends from the proximal end of catheter 1 to a position 7 proximal or adjacent to balloon 4 or optionally to position 7a adjacent to the distal end of the catheter . the pushing wire 5 is secured along its length by suitable means , such as adhesive or heat fixation to the interior surface 8 of lumen 3 . also , the distal portion of pushing wire 5 is preferably tapered distally to provide a smooth transition in axial stiffness . the pushing wire 5 will become less stiff as the diameter of pushing wire 5 narrows in the distal direction . the tapering is substantially linear over the distal 1 to 30 cm of the pushing wire 5 . pushing wire 5 may optionally be located in the inflation lumen 2 as shown in fig1 a . the distal portion of a guidewire 9 is threaded through opening 10 into the proximal end of lumen 3 . as the guide - wire 9 is threaded through lumen 3 , it exits through distal opening 11 . fig2 represents a cross - sectional view in the distal direction showing how lumens 2 and 3 relate to one another and how pushing wire 5 can be positioned within lumen 3 . lumen walls 12 and 13 can each have a thickness of from about 0 . 5 to 3 mil and may be of different thicknesses . fig2 a represents an alternative embodiment wherein the external aspect of the catheter is more rounded . the lumen walls 12 and 13 are comprised of materials conventional to balloon dilatation catheters . suitable materials include polyolefins such as polyethylene , polyethylene terepthalate , urethane , polyester , and various copolymers thereof . pushing wire 5 can be made from any rigid , medically acceptable material suitable for such use , including , but not limited to wires or hypotubes comprised of stainless steel or other rigid materials . the construction according to the invention leads to flexibility in product design . for example , the choice of pushing wire or its absence allows the designer to impart various features to the catheter in the form of various flexibility and pushability combinations . also , a hollow pushing wire would facilitate infusion of fluids , drugs , and / or contrast media through the catheter into the distal vasculature . further , it is within the scope of the invention that catheter 1 may have a third coextensive lumen that would similarly facilitate infusion of liquids , drugs and / or contrast media or even provide an alternative location for pushing wire 5 . in a preferred embodiment of the invention , as shown in fig1 a lubricious coating or a section of thin tubing 14 of lubricious material is sealed into lumen 3 . there are several known materials suitable for this purpose , such as polytetrafluoroethylene ( available as teflon ® from dupont ), polysiloxanes , etc . in this embodiment the tubing section 14 can hold the pushing wire 5 in position . according to a preferred aspect of the invention shown in fig3 a slitting means 20 is removedly mounted proximally on guidewire 9 . then , as the catheter 1 is withdrawn with guidewire 9 remaining in position , for example , with its distal end across a stenotic lesion , lumen 3 engages the slitter means 20 , lumen 3 is slit , and catheter 1 is separated from guidewire 9 . this would eliminate the requirement for the operator to change hands as catheter 1 is removed and would facilitate quick removal of the catheter 1 from the patient . in addition , since the balloon is not slit , it can be reinflated outside the patient to verify the inflated diameter . the catheter 1 may have visual length markings 30 along its shaft that would enable the operator to predict when the catheter 1 would exit the guiding catheter into the vasculature . this would reduce the fluoroscope time . the preferred design would put the markings directly on pushing wire 5 ( heat shrink tubing rings , inks , paints , etc .). since pushing wire 5 is substantially positioned within the guidewire lumen 3 , the markings would not be exposed to the patient ( i . e ., markings would not come off , and materials which could be toxic if exposed may be used ). if a thin tubing 14 is used within lumen 3 , the markings could alternately be placed within or , preferably , around tubing 14 . the preparation of a catheter 1 according to the invention is shown in fig4 , 6 and 7 . double lumen workpiece 21 can be prepared by methods well known to those skilled in the art . in a preferred method workpiece 21 is prepared by sealingly clamping the distal end of double lumen extruded tubing 22 , a cross - section of which is shown in fig4 and applying heat and pressure to blow the extruded tubing 22 to form workpiece 21 . after workpiece 21 is prepared , additional heat and pressure are applied to cause the proximal portion of lumen 2 to shrink , leaving the distal portion of lumen 2 to form the balloon 4 . heat sealing or application of suitable adhesive seals the distal portion of balloon 4 . lubricious tubing 14 is inserted into lumen 3 . heat is applied to cause lumen 3 to shrink such that lubricous tubing 14 is positively engaged within lumen 3 . optionally , pushing wire 5 is inserted into lumen 3 prior to shrinking between tubing 14 and lumen wall 13 . when lumen 3 shrinks , pushing wire 5 and lubricous tubing 14 are fixedly constrained within lumen 3 . in another embodiment of the invention , a removable hub means 24 is in fluid communication with the proximal opening 10 of lumen 3 , as shown in fig8 . such hub means 24 facilitates infusion of fluids or drugs through lumen 3 . optionally , hub means 24 may extend distally into lumen 3 along guidewire 9 . also , if tubing 14 were to extend proximally from opening 10 , hub means 24 may be adjoined to and in fluid communication with tubing 14 . hub means 24 is removedly bonded , joined , or attached to either proximal opening 10 or tubing 14 . therefore , when hub means 24 is to be removed , such as when catheter 1 is to be removed , removal of hub means 24 is accomplished by pulling hub means 24 in the proximal direction over the proximal end of guidewire 9 . an advantage of the design and preparation according to the invention is that the catheter can be of integral design and multiple bonding steps can be avoided . the balloon and both lumens can be formed from a single piece . this design permits improvements in manufacturing yields , quality , and reliability due to simplified construction . guidewire 9 may be a conventional guidewire , preferably a spring guidewire , as is well known . typical guidewires are shown in u . s . pat . nos . 4 , 757 , 827 , 4 , 815 , 478 , 4 , 813 , 434 , 4 , 619 , 274 , 4 , 554 , 929 , 4 , 545 , 390 , 4 , 538 , 622 , 3 , 906 , 938 , 3 , 973 , 556 , and 4 , 719 , 924 , all of which are incorporated herein by reference . in addition , the shaft of guidewire 9 could be solid or hollow , such as a hypotube , with an open distal end , to facilitate drug infusion . operation and use of the angioplasty apparatus shown in fig1 may now be briefly described as follows : a guiding catheter is inserted into the coronary artery in a conventional manner . the guidewire 9 is then introduced into the balloon dilatation catheter 1 by either a back loading technique where the proximal extremity of the guidewire 9 is inserted backwardly through opening 11 of balloon dilatation catheter 1 , or a forward loading technique , where the distal extremity of the guidewire 9 is inserted in proximal opening 10 . the guidewire 9 is advanced proximally until the proximal extremity of the guidewire is near the proximal extremity of the dilatation catheter 1 and so that the distal extremity of the guidewire 9 with its flexible or floppy tip 23 protrudes at least partially from the distal extremity of the balloon dilatation catheter . a guidewire gripping means , or torquer , such as a slitter 20 , is now attached to the guidewire 9 near its proximal extremity , and the guidewire 9 is then advanced ahead of the balloon dilatation catheter 1 until it enters the arterial vessel of the patient . the balloon dilatation catheter 1 is held stable by the fingers of the hand while the guidewire 9 is being advanced . the positioning of the guidewire 9 in the desired arterial vessel can be observed under a fluoroscope by using x - ray or fluoroscopic techniques well known to those skilled in the art . the torquer can be utilized to rotate the guidewire 9 to facilitate positioning of its distal tip in the desired arterial vessel so that the distal extremity of the guidewire can be advanced into the stenosis which it is desired to open or enlarge . as soon as the guidewire 9 is in the desired location , it can be held stationary by two fingers of the hand and then the balloon dilatation catheter 1 is advanced over the guidewire until the deflated balloon 4 is across the desired lesion or stenosis . if any difficulty is encountered by the person conducting the procedure in introducing the balloon dilatation catheter so that the balloon 4 resists crossing the lesions or stenosis , the guidewire 9 can be retracted slightly . the operator then can observe under the fluoroscope to see that the tip of the guidewire 9 is wiggling in the bloodstream indicating that it is free to move in the bloodstream . then the operator can grasp both the guidewire and the dilatation catheter in one hand and advance them as a unit so that they can cross the stenosis as a unit . it has been found by utilizing such a procedure , greater pushability can be obtained in advancing the balloon dilatation catheter across the stenosis . in other words , more force can be applied to the balloon to cause it to cross the stenosis or lesion in case the opening there is very small . when the balloon 4 has crossed the stenosis or lesion , the balloon 4 can be inflated in a conventional manner by introducing a radiopaque contrast liquid through the lumen 2 . after the inflation has occurred and the desired operation has been performed by enlarging the opening in the stenosis , the balloon dilatation catheter 1 can be removed very rapidly by holding the slitting means 20 stationary and pulling back catheter 1 such that the guidewire lumen 3 is slit and the catheter is separated from the guidewire . as soon as the balloon dilatation catheter 1 has been removed from the guiding catheter , another injection of radiographic contrast liquid can be introduced through the guiding catheter to observe whether or not the balloon dilatation procedure which has been performed on the lesion or stenosis to the satisfaction of the person performing the procedure . with the guidewire still in place , access to the lesion is maintained . if it is ascertained by the operator that additional therapy or diagnostics relating to the stenosis is desired , this can be accomplished very rapidly by selecting the desired catheter of a monorail type , preferably of the type described in co - pending u . s . patent application ser . no . 07 / 969 , 887 , filed oct . 30 , 1992 , and advancing it over the guidewire . the procedural steps described above can be repeated as necessary . the preceding specific embodiments are illustrative of the practice of the invention . it is to be understood , however , that other expedients known to those skilled in the art or disclosed herein , may be employed without departing from the spirit of the invention or the scope of the appended claims .

US-8742893-A

often it is necessary to restrain pets while they are groomed , or bathed , or dried after bathing , or examined by a veterinarian , or while being exercised outdoors , etc . many pet restraining devices are uncomfortable for pets and some may injure pets . the double loop auto - adjust pet restraining device applies a uniform pressure around the entire perimeter of the neck when a pet is retained in the neck area . a second loop of the double loop auto - adjust pet restraining device can be utilized to restrain the body or torso of a pet , the device applies a uniform pressure around the entire perimeter of that body area . the double loop auto - adjust pet restraining device uses a design that enables pets to be restrained in a very humane way . the double loop auto - adjust pet restraining device is self adjusting so as to accommodate many different sizes of pets . the double loop auto - adjust pet restraining device can be modified several different ways and be utilized several different ways .

in keeping with the requirements of patent laws there is described herein below the best mode of the invention that is currently known to the applicant . for the purposes of promoting an understanding of the principles of the invention , reference will now be made to the embodiment illustrated in the drawings and specific language will be used to describe the same . it will nevertheless be understood that no limitation of the scope of the invention is thereby intended , such alterations and further modifications in the illustrated device , and such further applications of the principles of the invention as illustrated therein being contemplated as would normally occur to one skilled in the art to which the invention relates . with reference now to the drawings , and in particular , to fig1 - 17 thereof , the preferred embodiment of the new double loop auto - adjust pet restraining device embodying the principles and concepts of the present invention and generally designated by the reference number 5 will be described . in fig1 shown generally at 5 is a top view of the new double loop auto - adjust pet restraining device 12 . the main loop 13 has a first end 14 and a second end 16 . main loop 13 has a first loop 18 that has first side 20 and a second side 22 . main loop 13 has a second loop 26 that has first side 28 and a second side 30 . sliding snugger 34 slides along main first loop 13 and forms first loop 18 and second loop 26 . rope retainer 36 fastens ends of rope and form a top loop 15 . top loop 15 encircles ring 38 and hook loop 39 of hook 40 . hook 40 has end that opens 42 . strap 56 has a first end 58 that has fastening material 60 and ring 62 . strap 56 has second end 64 that has fastening material 66 and ring 68 . a loop 70 is formed that restrains pet between end 16 of main loop 13 and strap 56 . the circle inside loop 70 shows how the neck of a pet would be positioned inside loop 70 . the arrows show how the restraining forces would be evenly distributed around the entire perimeter of the pets neck when loop 70 is tight . second strap 56 a has a first end 58 a that has fastening material 60 a and hook 59 a . hook generally will be connected to ring 62 a when pet is restrained . second strap 56 a has second end 64 a that has fastening material 66 a and ring 68 a . double loop auto - adjust pet restraining devices can be made of a variety of sizes and of a variety of materials and optional designs . double loop auto - adjust pet restraining devices can be made of a variety of sizes such as small , medium , large , and extra large . also an auto - adjust restraining device can be made in a custom size for a special application . double loop auto - adjust pet restraining devices can be made of a variety of material and combinations thereof . for example the flexible loops could be made of nylon , or polypropylene , or other plastic materials , or hemp , or leather , etc . the flexible loops have a round shape , or a flat shape , and could be made of different diameters and widths of nylon , or polypropylene , or other plastic materials , or hemp , or leather , etc . the flexible loops could be made of different colors and / or combination of colors . the rings could be made of brass , or stainless steel , or plastic , or other materials . the rings could be round . oval . square shaped “ d ” shaped or other shapes . instead of a ring , a loop could be made of the same material as a strap . the hook could be made of brass , or stainless steel , or plastic , or other materials . the ends of the flexible loops could be fastened by different methods . fastening material 36 , 60 , 66 , 60 a , 66 a could be sewn , or riveted , or clamped or any combination thereof . additionally , the fastening material could be made of a variety of different materials . different labels could be incorporated onto the device for different customers . in fig2 . shown generally at 80 is a front view of the double loop auto - adjust pet restraining device 12 hanging from a grooming arm 94 . the main loop 13 has a first end 14 and a second end 16 . main loop 13 has a bottom loop 18 that has first side 20 and a second side 22 . sliding snugger 34 slides along main loop 13 and forms bottom loop 18 and top loop 26 . rope retainer 36 fastens ends of rope and form a fastening loop 15 . fastening loop 15 encircles ring 38 and hook loop 39 of hook 40 . strap 56 has a first end ring 62 . double loop auto - adjust pet restraining device 12 has a first strap 56 and a second strap 56 a . surface of grooming table 82 is where a pet would be positioned . grooming arm 84 has a clamping device 86 at the base 88 where the grooming arm 84 is fastened to grooming table 82 . grooming arm 84 has a vertical section 90 a curved section 92 and a horizontal section 94 . grooming arm terminates in end 96 and has bolt 98 that has a loop 100 that hook 40 of the auto - adjust grooming device 13 can be fastened thereto . shown generally at 110 in fig3 is a side view of the double loop auto - adjust pet restraining device 12 hanging from a grooming arm 94 with a dog 114 is being restrained by the auto - adjust restraining device . the main loop 13 has a first end 14 and a second end 16 . main loop 13 has a bottom loop 18 . main loop 13 has a top loop 26 . sliding snugger 34 slides along main first loop 13 and forms bottom loop 18 and top loop 26 . fastening loop 15 encircles ring 38 and hook loop 39 of hook 40 . strap 56 is positioned around neck 112 of dog 114 . first strap 56 has a ring 62 and ring 68 . a loop 70 is formed that restrains pet between end 16 of main loop 13 and strap 56 . strap 56 is positioned around neck 112 of dog 114 . second strap 56 a has a hook 59 a and ring 68 a . second strap 56 a of double loop pet restraining device 12 restrains rear portion of dog 114 . dog 114 is positioned on surface of grooming table 82 . grooming arm 84 has a vertical section 90 a curved section 92 and a horizontal section 94 . grooming arm terminates in end 96 and has bolt 98 that has a loop 100 that hook 40 of the double loop auto - adjust grooming device 13 is hooked thereto . shown generally at 120 in fig4 . is a close up side view of a dog 114 restrained by the double loop auto - adjust restraining device 12 . first strap 56 has a first end 58 ( not seen ) that has ring 62 . first strap 56 has second end 64 that has ring 68 . first strap 56 is positioned around neck 112 of dog 114 . second strap 56 a has a hook 59 a and ring 68 a ( not seen ). second strap 56 a of double loop pet restraining device 12 restrains rear portion of dog 114 . shown generally at 125 in fig5 is a side view of the double loop auto - adjust pet restraining device 12 hanging from a grooming arm 84 with a dog 114 is being restrained by the auto - adjust restraining device . this view is the opposite side of the dog that is shown in fig3 . the main loop 13 has a first end 14 and a second end 16 . main loop 13 has a bottom loop 18 . main loop 13 has a top loop 26 . sliding snugger 34 slides along main first loop 13 and forms bottom loop 18 and top loop 26 . fastening loop 15 encircles ring 38 and hook loop 39 of hook 40 . first strap 56 is positioned around neck 112 of dog 114 . first strap 56 has a ring 62 and ring 68 . a loop 70 is formed that restrains pet between end 16 of main loop 13 and strap 56 . first strap 56 is positioned around neck 112 of dog 114 . second strap 56 a has a hook 59 a and ring 68 a . second strap 56 a of double loop pet restraining device 12 restrains rear portion of dog 114 . dog 114 is positioned on surface of grooming table 82 . grooming arm 84 has a vertical section 90 a curved section 92 and a horizontal section 94 . grooming arm terminates in end 96 and has bolt 98 that has a loop 100 that hook 40 of the double loop auto - adjust grooming device 13 is hooked thereto . shown generally at 130 in fig6 . is a close up side view of a dog 114 restrained by the double loop auto - adjust restraining device 12 . this is the opposite side of the dog from fig4 . first strap 56 has a first end 58 that has ring 62 . first strap 56 has second end 64 that has ring 68 ( not seen ). first strap 56 is positioned around neck 112 of dog 114 . second strap 56 a has a hook 59 a ( not seen ) and ring 68 a . second strap 56 a of double loop pet restraining device 12 restrains rear portion of dog 114 . sliding snugger 34 slides along main first loop . a loop 70 is formed that restrains neck 112 of dog 114 between end 16 of main loop 13 and strap 56 . shown generally at 135 in fig7 . is a close up top view of a dog 114 restrained by the double loop auto - adjust restraining device 12 . this is the opposite side of the dog from fig4 . first strap 56 has a first end 58 that has ring 62 . first strap 56 has second end 64 that has ring 68 ( not seen ). first strap 56 is positioned around neck 112 of dog 114 . second strap 56 a has a hook 59 a ( not seen ) and ring 68 a . second strap 56 a of double loop pet restraining device 12 restrains rear portion of dog 114 . shown generally at 140 in fig8 . is a side view of a dog 114 restrained by the double loop auto - adjust restraining device 12 . this is the same side of the dog as fig6 and 7 . first strap 56 has a first end 58 that has ring 62 . first strap 56 is positioned around neck 112 of dog 114 . second strap 56 a has a hook 59 a ( not seen ) and ring 68 a . second strap 56 a of double loop pet restraining device 12 is positioned around chest 112 a of dog 114 . sliding snugger 34 slides along main first loop . shown generally at 145 in fig9 . is a front view of a dog 114 restrained by the double loop auto - adjust restraining device 12 . this shows an alternate way that the double loop auto - adjust restraining device 12 can be utilized to restrain a pet . first strap 56 is positioned around neck 112 of dog 114 . second strap 56 a has a hook 59 a and ring 68 a . second strap 56 a of double loop pet restraining device 12 is looped around the vertical section 90 of grooming arm 84 . sliding snugger 34 slides along main first loop . shown generally at 150 in fig1 . is a side view of a dog 114 restrained by the double loop auto - adjust restraining device 12 . first strap 56 has a first end 58 that has ring 62 . first strap 56 is positioned around neck 112 of dog 114 . second strap 56 a has a hook 59 a that is fastened to ring 38 . second strap 56 a of double loop pet restraining device 12 is not being utilized to restrain dog 114 in this application . sliding snugger 34 slides along main first loop . shown generally at 155 in fig1 is a close up front view of a dog 114 restrained by the double loop auto - adjust restraining device 12 . this shows how the double loop auto - adjust restraining device 12 can restrain a pet in a different way . the double loop auto - adjust restraining device 12 has the first strap 56 has a first end 58 that has ring 62 . first strap 56 has second end 64 that has ring 68 . first strap 56 is positioned under a first front leg 113 and across chest 115 of dog 114 . second strap 56 a has a hook 59 a and ring 68 a . second strap 56 a of double loop pet restraining device 12 dangles free and is not utilized . shown generally at 160 in fig1 is a front view of a dog 114 restrained by the double loop auto - adjust restraining device 12 . this shows how the double loop auto - adjust restraining device 12 can restrain a pet in a different way . the double loop auto - adjust restraining device 12 has the first strap 56 has a first end 58 that has ring 62 . first strap 56 has second end 64 that has ring 68 ( not seen ). first strap 56 is positioned under a first front leg 113 and across chest 115 of dog 114 . second strap 56 a has a hook 59 a and ring 68 a . second strap 56 a is positioned under a second front leg 113 a and across chest 115 of dog 114 . shown generally at 165 in fig1 is a close up front view of a dog 114 restrained by the double loop auto - adjust restraining device 12 . this shows how the double loop auto - adjust restraining device 12 can restrain a pet in a different way . this close up view to that shown in fig1 . the double loop auto - adjust restraining device 12 has the first strap 56 has a first end 58 that has ring 62 . first strap 56 has second end 64 that has ring 68 not seen ). first strap 56 is positioned under a first front leg 113 and across chest 115 of dog 114 . second strap 56 a has a hook 59 a and ring 68 a . second strap 56 a is positioned under a second front leg 113 a and across chest 115 of dog 114 . in fig1 shown generally at 170 is a top view of an alternate embodiment of the new double loop auto - adjust pet restraining device 12 m . sliding snugger 34 m slides along main first loop 13 m that has hook 40 m . first strap 56 m has a first end that has a ring and second end that has a ring . second strap 56 n has a first end that has a ring and second end that has a ring . second strap 56 n crosses over first strap 56 m . in fig1 shown generally at 175 is a front view of the alternate embodiment of the new double loop auto - adjust pet restraining device 12 m restraining dog 114 . first strap 56 m has a first end that has a ring and second end that has a ring . second strap 56 n has a first end that has a ring and second end that has a ring . second strap 56 n crosses over first strap 56 m across the chest of the dog . this is similar to the way the dog is restrained in fig1 . shown generally at 180 in fig1 is a front view of a dog restrained by the double loop auto - adjust pet restraining device 12 . this shows how the top loop 26 on the double loop auto - adjust restraining device 12 can fit a hand 192 so that the double loop auto - adjust restraining device can be utilized as a leash . auto - adjust pet restraining device 12 is substantially the same auto - adjust pet restraining device 12 discussed in fig1 . in fig1 shown generally at 185 is a top view of an alternate embodiment of the new double loop auto - adjust pet restraining device 12 x . first strap 56 x has a first end that has a “ d ” shaped ring 62 x and second end that has a “ d ” shaped ring 68 x . in fig1 shown generally at 190 is a top view of an alternate embodiment of the new double loop auto - adjust pet restraining device 12 z . first strap 56 z has a first end that has a loop 62 z and second end that has a loop 68 z . in fig1 shown generally at 195 is a tcp view of an alternate method of fastening the hook 59 a to the main loop 13 of the new double loop auto - adjust pet restraining device 12 . hook loop 59 b of hook 56 a is hooked directly over main loop 13 , rather than using a ring . in fig2 is shown generally shown at 200 is a top view of two prior art pet restraining devices . these devices are commonly referred to as grooming loops . the first grooming loop 202 has main loop 204 has a top end 205 and a bottom end 206 . main loop 202 has a bottom loop 212 that has first side 214 and a second side 216 . main loop 204 has a top loop 223 that has first side 224 and a second side 226 . sliding snugger 220 slides along main loop 204 and forms bottom loop 212 and top loop 223 . top end 205 has ring 230 secured thereto and a hook 232 . hook 232 has end that opens . the second grooming loop 240 has a first end 242 that has a fastening loop 243 and a loop end 244 . end 246 has a ring 248 . restraining loop 249 is formed to restrain pets . this generally is referred to a choker style grooming loop . in fig2 is shown generally shown at 225 is a front view a prior art grooming loop 202 hanging from a grooming arm 254 . grooming loop 202 has main loop 204 that has a top end 205 and a bottom end 206 . main loop 204 has a bottom loop 212 that has first side 214 and a second side 216 . main loop 204 has a top loop 223 that has first side 224 and a second side 226 . sliding snugger 220 slides along main loop 204 and forms bottom loop 212 and top loop 223 . top of main loop 205 has ring 230 secured thereto and a hook 232 . hook 232 has end that opens . surface of grooming table 252 is where a pet would be positioned . grooming arm 254 has a vertical section 256 a curved section 258 and a horizontal section 260 . grooming arm terminates in end 262 that has a loop 264 that hook 232 of the prior art grooming loop 202 is fastened thereto . in fig2 is shown generally shown at 250 is a front view a prior art grooming loop 202 hanging from a grooming arm 254 with grooming loop 202 around the neck 272 of dog 274 . grooming loop 202 has main loop 204 has a top end 205 and a bottom end 206 . main loop 202 has a bottom loop 212 that has first side 214 and a second side 216 . main loop 204 has a top loop 223 that has first side 224 and a second side 226 . sliding snugger 220 slides along main loop 204 and forms bottom loop 212 and top loop 223 . top of main loop 205 has ring 230 secured thereto and a hook 232 . hook 232 has end that opens . surface of grooming table 252 is where dog 274 is positioned . grooming arm 254 has a vertical section 256 a curved section 258 and a horizontal section 260 . grooming arm terminates in end 262 that has a loop 264 that hook 232 of the prior art grooming loop is fastened thereto . all of the restraining forces of this prior art grooming device are directed at throat area of the pet when the pet is retained . in fig2 is shown generally shown at 275 is a front view a two prior art grooming loops hanging from a grooming arm 260 . first grooming loop 202 has a bottom loop 212 and a top loop 223 . top of main loop 205 has ring 230 secured thereto and a hook 232 . hook 232 has end that opens and is attached to loop 264 of grooming arm 260 . second rooming loop 202 a has a bottom loop 212 a and a top loop 223 a . sliding snugger 220 a slides and forms bottom loop 212 a and top loop 223 a . top loop of main loop 205 a has ring 230 a secured thereto and a hook 232 a . hook 232 a has end that opens . hook 232 a on second grooming loop 202 a is fastened to loop 230 on first grooming loop 202 . in fig2 is shown generally shown at 300 is a front view a two prior art grooming loops hanging from a grooming arm 260 with a dog 274 being restrained by the prior art grooming loops . first rooming loop 202 has a bottom loop 212 and a top loop 223 . sliding snugger 220 slides and forms bottom loop 212 and top loop 223 . top of main loop 205 has ring 230 secured thereto and a hook 232 . hook 232 is fastened to loop 264 of grooming arm 254 . bottom loop 212 of first grooming loop 202 is positioned around neck 272 of dog 274 . all of the restraining forces of this prior art grooming device are directed at throat area of the pet when the pet is retained . second grooming loop 202 a has a bottom loop 212 a and a top loop 223 a . sliding snugger 220 a slides and forms bottom loop 212 a and top loop 223 a . top loop of main loop 205 a has ring 230 a secured thereto and a hook 232 a . hook 232 a has end that opens . hook 232 a on second grooming loop 202 a is fastened to loop 230 on first grooming loop 202 . bottom loop 212 a of second grooming loop 202 a is positioned around belly 292 of dog 274 . all of the restraining forces of this prior art grooming device are directed at the sensitive under belly area of the pet when the pet is retained . in fig2 is shown generally shown at 325 is a closeup view of two prior art grooming loops hanging from a grooming arm with a dog 274 being restrained by the prior art grooming loops . first rooming loop 202 has a bottom loop 212 . sliding snugger 220 slides and forms bottom loop 212 . bottom loop 212 of first grooming loop 202 is positioned around neck 272 of dog 274 . all of the restraining forces of this prior art grooming device are directed at the sensitive throat area of the pet when the pet is retained . second grooming loop 202 a has a bottom loop 212 a . sliding snugger 220 a slides and forms bottom loop 212 a . bottom loop 212 a of second grooming loop 202 a is positioned around belly 292 of dog 274 . all of the restraining forces of this prior art grooming device are directed at the sensitive under belly area of the pet when the pet is retained . the objects and advantages of the invention will become apparent when the drawings are studied in conjunction with reading the following description and the claims . this invention having been described in its presently contemplated best mode , it is clear that it is susceptible to numerous , variations , modifications , modes and embodiments within the ability of those skilled in the art and without departing from the true spirit and scope of the novel concepts or principles of this invention . also , it is to be understood that the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting . it should be understood that the preferred embodiment has been shown and described and that all changes and modifications that come within the spirit of the invention are desired to be protected . the invention is capable of other embodiments and of being practiced and carried out in various ways . as such , those skilled in the art will appreciate that the conception , upon which this disclosure is based , may readily be utilized as a basis for the designing of other structures , methods and systems for carrying out the several purposes of the present invention . it is important , therefore , that the claims be regarded as including such equivalent constructions insofar as they do not depart from the spirit and scope of the present invention . accordingly , the scope of the invention is defined by the scope of the following claims .

US-23122508-A

a toy set for fishing play mainly includes a casing having an animal contour , inside which there is arranged a driving mechanism and a plurality of toothed rotary trays . the driving mechanism drives various gear sets , which are linked with eyeballs and limbs of the fake animal . as a result , the toy set can imitate a variety of gestures of the animal while fishing play is going on , showing great fun .

as can be seen from fig1 and 2 , a toy set according to the invention includes a casing inside which there are disposed a driving mechanism ( 10 ) and a plurality of toothed rotary trays ( 11 ), ( 12 ), ( 13 ), and ( 14 ). the casing consists of an upper half ( 15 ) and a lower half ( 16 ) which are formed in an animal form . in the illustrative embodiment shown in the accompanying drawings the casing shows a frog in its outer appearance and the periphery of the casing is shaped like a frog &# 39 ; s head and limbs . the frog head portion formed on the upper half ( 15 ) is provided with two eye sockets ( 17 ), behind which an eyeball moving mechanism ( 18 ) and a u - shaped plate ( 19 ) are secured . furthermore , a plurality of movable limb - shaped parts ( 20 ), ( 21 ), ( 22 ), and ( 23 ) are arranged on the frog body portion , each of limb - shaped parts being composed of an outer shell ( 24 ), ( 25 ), ( 26 ), ( 27 ) and a link ( 28 ), ( 29 ), ( 30 ), ( 31 ). each link ( 28 ), ( 29 ), ( 30 ), ( 31 ) is further furnished with a projecting pin ( 32 ), ( 33 ), ( 34 ), ( 35 ) to which a connecting rod ( 36 ), ( 37 ), ( 38 ), ( 39 ) is attached . on the inner surface of the upper half ( 15 ) there are four equidistantly spaced toothed rotary trays ( 11 ), ( 12 ), ( 13 ), and ( 14 ) that are used for fishing play . additionally , a switch ( 40 ) and a battery compartment ( 42 ) with a cover ( 41 ) are respectively formed on two opposed sides of lower half ( 16 ). referring now to fig3 and 4 , these drawings illustrate the operation of the toy set of the invention . a motor ( 43 ) situated on the inner surface of the upper half ( 15 ) is used to drive a worm ( 44 ) of a driving mechanism ( 10 ). the driving mechanism ( 10 ) further drives a first driving gear ( 46 ) of a first gear set ( 45 ), which causes to rotate a first driven gear ( 47 ) that is engaged with the first driving gear ( 46 ). consequently , a first eccentric pin ( 48 ) disposed on the side face of the second driven gear ( 47 ) forces a first connecting rod ( 49 ) to move . the first connecting rod ( 49 ) has one end pivotally attached to the first eccentric pin ( 48 ) and the other end connected to the eyeball moving mechanism ( 18 ) by means of an elongated hole ( 50 ), which is formed on the first connecting rod and fitted over a projecting pin ( 53 ), the projecting pin ( 53 ) being situated at the central point of a crossbar ( 52 ) of the eyeball moving mechanism ( 18 ) and two fake eyeballs being affixed to two opposed ends of the crossbar ( 52 ). with such an arrangement , the motion of eyeballs can be spurred by the first connecting rod ( 49 ). additionally an arcuated recessed portion ( 54 ) is formed on one side edge of the first connecting rod ( 49 ) near the first driving gear ( 46 ) to prevent the connecting rod ( 49 ) from possible interference with the gear when the toy set is in operation . the first driven gear ( 47 ) of the first gear set ( 45 ) further urges the first rotary tray ( 11 ), which in turn motivates a second driving gear ( 56 ) of the second gear set ( 55 ) and a central gear ( 59 ) both of which are in engagement with the first rotary tray . furthermore , along with the rotation of the second driving gear ( 56 ), a second driven gear ( 57 ) impels the first upper limb - shaped part ( 20 ) and the first lower limb - shaped part ( 21 ) to sway by using an eccentric pin ( 58 ), which is arranged on the side face of the second driven gear ( 57 ), to drag the second and the third connecting rod ( 36 ), ( 37 ). at the same time the central gear ( 59 ) concurrently drives the other three toothed rotary trays ( 12 ), ( 13 ), and ( 14 ), of which the second rotary tray ( 12 ) rotates a third driving gear ( 61 ) of a third gear set ( 60 ). the rotation of the third driving gear ( 61 ) causes a third driven gear ( 62 ) to move , which is engaged with the third driving gear ( 61 ). similarly the third driven gear ( 62 ) also uses an eccentric pin ( 63 ), which is arranged on the side face of the third driven gear ( 62 ), to set the fourth and the fifth connecting rod ( 38 ), ( 39 ) in motion , causing the second upper and the second lower limb - shaped part ( 22 ), ( 23 ) to sway . in addition , a press plate ( 64 ) is used to hold the second driving gear ( 56 ), the third driving gear ( 61 ), and the central gear ( 59 ). in this way , the toy set of the invention can be operated by the power delivered through a driving mechanism ( 10 ) to limb - shaped parts and eyeballs . evidently the number of the rotary trays of the toy set of the invention can be one or more depending on the requirement . fig3 illustrates that the movable parts of the toy set such as eyeballs ( 51 ) and four limb - shaped parts ( 20 ), ( 21 ), ( 22 ), and ( 23 ) are urged to sway by means of an arrangement of gears and links . fig4 shows that the eyeballs ( 51 ) are moved upwardly and four limb - shaped parts ( 20 ), ( 21 ), ( 22 ), and ( 23 ) retract inwardly . these movements can be varied by means of many combinations of a variety of angular travels of gears . as described above , the invention has disclosed a novel fishing toy . referring now to fig5 it illustrates an embodiment of the invention , in which fishing rods ( 65 ) and fake fishes ( 66 ) have been placed in position . according to the invention , the toy makes use of a driving mechanism and toothed rotary trays in cooperation with links and gear arrangements to create simulated movements of an animal &# 39 ; s limbs , which , accompanied by interesting fishing play , produce unique attractiveness and superior marketing competitive ability . evidently the invention is of practical value in industry .

US-59936696-A

a sea cucumber preparation and manufacturing method thereof , comprising steps as follows : put the cut and well - cleaned fresh sea cucumber or soaked sea cucumber into an airtight container ; at 70 ˜ 130 ° c ., gelatinate for 1 min ˜ 20 h , freeze - dry till the water content is less than 10 wt %, then sequentially carry out coarse , ultra - micro and nanometer crushing till the fineness reaches 10 ˜ 1000 nm . add water into the sea cucumber nanometer powder to carry out proteinase enzymolysis , after the enzymolysis is finished , inactivate the proteinase , separate and take the supernatant and dry to get nanometer sea cucumber extract . evenly mix the extract with panax pseudo - ginseng saponins extract at the proportion of 99 ˜ 70 %: 1 ˜ 30 %. the content of the sea cucumber polysaccharide in the mixture is 2 . 5 ˜ 8 . 0 wt %, the content of panax pseudo - ginseng saponins is 0 . 3 ˜ 21 . 0 wt %. the compound preparation has complementary and synergistic effects on pharmacological effect . the side effects of single preparation can be eliminated through the compound preparation , the pharmacological functions of the sea cucumber or panax pseudo - ginseng single preparation are greatly enhanced , and can be used for anti - coagulation , diabetes and other various medicinal purposes .

( 1 ) raw material processing : cut the fresh sea stichopus , take out the viscus , sufficiently clean the sea cucumber wall , and put it into an airtight container . ( 2 ) gelatination : heat the container at 70 ˜ 80 ° c . for 20 hours . ( 3 ) vacuum freeze - dry : freeze - dry the gelatinated sea cucumber till the water content is 0 . 1 %. ( 4 ) coarse crush : crush the freeze - dried sea cucumber to get sea cucumber powder with fineness of 10 ˜ 300 mesh . ( 5 ) ultra - micro crush : ultra - micro crush the coarse crushed sea cucumber powder with an airflow crusher , to get ultra - micro sea cucumber powder with fineness of 100 ˜ 3000 mesh . ( 6 ) nanometer crush : nanometer crush , with a high energy ball grinding mill , the ultra - micro sea cucumber powder obtained by the airflow crusher , the nanometer crush time being 4 hours . ( 7 ) enzymolysis : add the nanometer sea cucumber powder with water at ( the weight ) ratio of 1 : 3 and mix up evenly , add bromelain at the ratio of nanometer sea cucumber powder : bromelain equal to 1 g : 10 mg and enzymolysis for 5 hours at 40 ° c . under ph 6 ˜ 7 ; after the enzymolysis reaction is finished , heat the enzymolysis reaction solution for 20 min at 90 ° c . centrifuge and separate the enzymolysis product , take the enzymolysis supernatant , dry directly to get nanometer sea cucumber extract . ( 8 ) mix the nanometer sea cucumber extract with the panax pseudo - ginseng saponins extract at the ratio of nanometer sea cucumber extract : panax pseudo - ginseng saponins extract equal to 99 %: 1 %. the product is a light brown powder , and the main active ingredients are sea cucumber polysaccharide and panax pseudo - ginseng saponins ( calculated by r1 + rb1 + rg1 ingredient total contents ), wherein the content of sea cucumber polysaccharide is 7 . 8 % and the content of panax pseudo - ginseng saponins is 0 . 5 %. the example product is carried out with the efficacy experiment of influence on blood coagulation parameter tt , rt by treating by irrigating stomachs of mice . the results are shown in table 1 . put the product into a capsule , 0 . 3 g for each capsule . ( 1 ) raw material processing : cut the fresh cucumaria frondosa , take out the viscus , sufficiently clean the sea cucumber wall and the viscus respectively , and put them together into an airtight container . ( 2 ) gelatination : heat the container at 80 ˜ 90 ° c . for 15 hours . ( 3 ) vacuum freeze - dry : freeze - dry the gelatinated sea cucumber till the water content is 1 %. ( 4 ) coarse crush : crush the freeze - dried sea cucumber to get sea cucumber powder with fineness of 10 ˜ 300 mesh . ( 5 ) ultra - micro crush : ultra - micro crush the coarse crushed sea cucumber powder with an airflow crusher , to get ultra - micro sea cucumber powder with fineness of 100 ˜ 3000 mesh . ( 6 ) nanometer crush : nanometer crush , with a high energy ball grinding mill , the ultra - micro sea cucumber powder obtained by the airflow crusher , the nanometer crush time being 8 hours . ( 7 ) enzymolysis : add the nanometer sea cucumber powder with water at ( the weight ) ratio of 1 : 4 and mix up evenly , add alkaline proteinase at the ratio of nanometer sea cucumber powder : alkaline proteinase equal to 1 g : 0 . 5 mg and enzymolysis for 2 hours at 65 ° c . under ph 6 ˜ 7 ; after the enzymolysis reaction is finished , heat the enzymolysis reaction solution for 15 min at 95 ° c . centrifuge and separate the enzymolysis product , take the enzymolysis supernatant , dry directly to get nanometer sea cucumber extract . ( 8 ) mix the nanometer sea cucumber extract with the panax pseudo - ginseng saponins extract at the ratio of nanometer sea cucumber extract : panax pseudo - ginseng saponins extract equal to 90 %: 10 %. the product is a light brown powder , and the main active ingredients are sea cucumber polysaccharide and panax pseudo - ginseng saponins ( calculated by r1 + rb1 + rg1 ingredient total contents ), wherein the content of sea cucumber polysaccharide is 4 . 6 % and the content of panax pseudo - ginseng saponins is 6 . 2 %. the influences on tt and rt value by pure sea cucumber nanometer powder and those by the example product after treating mice by different treating ways are shown in table 2 . ( 1 ) raw material processing : soak the dry see stichopus in water , when is softened cut the sea stichopus wall , sufficiently clean the sea cucumber wall , and put it into an airtight container . ( 2 ) gelatination : heat the container at 90 ˜ 100 ° c . for 10 hours . ( 3 ) vacuum freeze - dry : freeze - dry the gelatinated sea cucumber till the water content is 3 %. ( 4 ) coarse crush , ( 5 ) ultra - micro crush , and ( 6 ) nanometer crush are the same as those in example 2 . ( 7 ) enzymolysis : add the nanometer sea cucumber powder with water at ( the weight ) ratio of 1 : 5 and mix up evenly , add trypsase at the ratio of nanometer sea cucumber powder : trypsase equal to 1 g : 10 mg and enzymolysis for 5 hours at 45 ° c . under ph 8 ˜ 9 ; after the enzymolysis reaction is finished , heat the enzymolysis reaction solution for 10 min at 100 ° c . centrifuge and separate the enzymolysis product , take the enzymolysis supernatant , dry directly to get nanometer sea cucumber extract . ( 8 ) mix the nanometer sea cucumber extract with the panax pseudo - ginseng saponins extract at the ratio of nanometer sea cucumber extract : panax pseudo - ginseng saponins extract equal to 80 %: 20 %. the product is a light brown powder , and the main active ingredients are sea cucumber polysaccharide and panax pseudo - ginseng saponins ( calculated by r1 + rb1 + rg1 ingredient total contents ), wherein the content of sea cucumber polysaccharide is 6 . 3 % and the content of panax pseudo - ginseng saponins is 10 . 9 %. experiment is carried out with respect to the influence on fasting plasma glucose effects of experimental diabetic mice caused by alloxan , and the results are shown in table 3 . 1 ) raw material processing : cut the saline dry sea stichopus , desalt it in water , when the saline dry sea stichopus is softened cut the sea stichopus wall , sufficiently clean , and put it into an airtight container . ( 2 ) gelatination : heat the container at 100 ˜ 105 ° c . for 5 hours . ( 3 ) vacuum freeze - dry : freeze - dry the gelatinated sea cucumber till the water content is 5 %. ( 4 ) coarse crush and ( 5 ) ultra - micro crush are the same as those described in example 2 . ( 6 ) nanometer crush : nanometer crush , with a high energy ball grinding mill , the ultra - micro sea cucumber powder obtained by the airflow crusher , the nanometer crush time being 12 hours . ( 7 ) enzymolysis : add the nanometer sea cucumber powder with water at ( the weight ) ratio of 1 : 6 and mix up evenly , add neutral proteinase at the ratio of nanometer sea cucumber powder : neutral proteinase equal to 1 g : 1 mg and enzymolysis for 1 hours at 50 ° c . under ph 6 . 7 ˜ 7 ; after the enzymolysis reaction is finished , heat the enzymolysis reaction solution for 5 min at 100 ° c . centrifuge and separate the enzymolysis product , take the enzymolysis supernatant , dry directly to get nanometer sea cucumber extract . ( 8 ) mix the nanometer sea cucumber extract with the panax pseudo - ginseng saponins extract at the ratio of nanometer sea cucumber extract : panax pseudo - ginseng saponins extract equal to 70 %: 30 %. the product is a light brown powder , and the main active ingredients are sea cucumber polysaccharide and panax pseudo - ginseng saponins ( calculated by r1 + rb1 + rg1 ingredient total contents ), wherein the content of sea cucumber polysaccharide is 5 . 4 % and the content of panax pseudo - ginseng saponins is 15 . 2 %. ( 1 ) raw material processing : sork the saline dry sea stichopus , when it is softened heat the saline sea stichopus in water of 100 ˜ 105 ° c . for 1 hour , cut the saline sea stichopus , sufficiently clean , desalt and at the same time sork the saline sea stichopus wall with pure water , and put the sea stichopus wall into an airtight container . ( 2 ) gelatination : heat the container at 105 ˜ 110 ° c . for 2 hours . ( 3 ) vacuum freeze - dry : freeze - dry the gelatinated sea cucumber till the water content is 7 %. ( 4 ) coarse crush and ( 5 ) ultra - micro crush are the same as those described in example 1 . ( 6 ) nanometer crush : nanometer crush , with a high energy ball grinding mill , the ultra - micro sea cucumber powder obtained by the airflow crusher , the nanometer crush time being 16 hours . ( 7 ) enzymolysis : add the nanometer sea cucumber powder with water at ( the weight ) ratio of 1 : 7 and mix up evenly , add alkaline proteinase at the ratio of nanometer sea cucumber powder : alkaline proteinase equal to 1 g : 0 . 1 mg and enzymolysis for 3 hours at 65 ° c . under ph 7 ˜ 8 ; and then adjust the temperature to 45 ° c ., add trypsase at the ratio of nanometer sea cucumber powder : trypsase to 1 g : 10 mg and enzymolysis for 3 hours under ph 8 ˜ 9 , after the enzymolysis reaction is finished , heat the enzymolysis reaction solution for 10 min at 100 ° c . centrifuge and separate the enzymolysis product , take the enzymolysis supernatant , dry directly to get nanometer sea cucumber extract . ( 8 ) mix the nanometer sea cucumber extract with the panax pseudo - ginseng saponins extract at the ratio of nanometer sea cucumber extract : panax pseudo - ginseng saponins extract equal to 80 %: 20 %. the product is a light brown powder , and the main active ingredients are sea cucumber polysaccharide and panax pseudo - ginseng saponins ( calculated by r1 + rb1 + rg1 ingredient total contents ), wherein the content of sea cucumber polysaccharide is 4 . 4 % and the content of panax pseudo - ginseng saponins is 7 . 9 %. after mixing make tablet at the ratio of raw material : excipients equal to 2 : 1 ( 1 ) raw material processing : soak the dry cucumaria frondosa , when it is softened cut the cucumaria frondosa wall , sufficiently clean , and put into an airtight container . ( 2 ) gelatination : heat the container at 110 ˜ 120 ° c . for 1 hours . ( 3 ) vacuum freeze - dry : freeze - dry the gelatinated sea cucumber till the water content is 9 %. ( 4 ) coarse crush and ( 5 ) ultra - micro crush are the same as those described in example 1 . ( 6 ) nanometer crush : nanometer crush , with a high energy ball grinding mill , the ultra - micro sea cucumber powder obtained by the airflow crusher , the nanometer crush time being 18 hours . ( 7 ) enzymolysis : add the nanometer sea cucumber powder with water at ( the weight ) ratio of 1 : 8 and mix up evenly , add alkaline proteinase at the ratio of nanometer sea cucumber powder : alkaline proteinase equal to 1 g : 0 . 1 mg and enzymolysis for 1 hours at 65 ° c . under ph 7 ˜ 8 ; and then add alkaline proteinase at the ratio of nanometer sea cucumber powder : alkaline proteinase to 1 g : 0 . 1 mg and enzymolysis for 3 hours under ph 7 ˜ 8 at 65 ° c ., after the enzymolysis reaction is finished , heat the enzymolysis reaction solution for 10 min at 100 ° c . centrifuge and separate the enzymolysis product , take the enzymolysis supernatant , dry directly to get nanometer sea cucumber extract . ( 8 ) mix the nanometer sea cucumber extract with the panax pseudo - ginseng saponins extract at the ratio of nanometer sea cucumber extract : panax pseudo - ginseng saponins extract equal to 90 %: 10 %. the product is a light brown powder , and the main active ingredients are sea cucumber polysaccharide and panax pseudo - ginseng saponins ( calculated by r1 + rb1 + rg1 ingredient total contents ), wherein the content of sea cucumber polysaccharide is 2 . 6 and the content of panax pseudo - ginseng saponins is 3 . 2 %. after mixing make granules at the ratio of raw material to excipients equal to 1 : 1 . ( 1 ) raw material processing : cut the fresh sea stichopus , take out the viscus , sufficiently clean the sea cucumber wall , and put it into an airtight container . ( 2 ) gelatination : heat the container at 120 ˜ 130 ° c . for 10 minutes . ( 3 ) vacuum freeze - dry : freeze - dry the gelatinated sea cucumber till the water content is 10 %. ( 4 ) coarse crush and ( 5 ) ultra - micro crush are the same as those described in example 1 . ( 6 ) nanometer crush : nanometer crush , with a high energy ball grinding mill , the ultra - micro sea cucumber powder obtained by the airflow crusher , the nanometer crush time being 20 hours . ( 7 ) enzymolysis : add the nanometer sea cucumber powder with water at ( the weight ) ratio of 1 : 10 and mix up evenly , add neutral proteinase at the ratio of nanometer sea cucumber powder : neutral proteinase equal to 1 g : 0 . 8 mg and enzymolysis for 1 hours at 50 ° c . under ph 6 . 7 ˜ 7 , and add alkali proteinase at the ratio of nanometer sea cucumber powder : alkali proteinase equal to 1 g : 1 mg and enzymolysis for 1 hours at 65 ° c . under ph 7 ˜ 8 , and then adjust the temperature to 45 ° c ., add trypsase at the ratio of nanometer sea cucumber powder : trypsase equal to 1 g : 10 mg and enzymolysis for 1 hours under ph 8 ˜ 9 , after the enzymolysis reaction is finished , heat the enzymolysis reaction solution for 10 min at 100 ° c . centrifuge and separate the enzymolysis product , take the enzymolysis supernatant , dry directly to get nanometer sea cucumber extract . ( 8 ) mix the nanometer sea cucumber extract with the panax pseudo - ginseng saponins extract at the ratio of nanometer sea cucumber extract : panax pseudo - ginseng saponins extract equal to 95 %: 5 %. the product is a light brown powder , and the main active ingredients are sea cucumber polysaccharide and panax pseudo - ginseng saponins ( calculated by r1 + rb1 + rg1 ingredient total contents ), wherein the content of sea cucumber polysaccharide is 7 . 5 % and the content of panax pseudo - ginseng saponins is 3 . 2 %. ( 1 ) raw material processing : cut the fresh sea stichopus , take out the viscus , sufficiently clean the sea cucumber wall , and put it into an airtight container . ( 2 ) gelatination : heat the container at 105 ˜ 110 ° c . for 40 minutes . ( 3 ) vacuum freeze - dry : freeze - dry the gelatinated sea cucumber till the water content is 9 %. ( 4 ) coarse crush , ( 5 ) ultra - micro crush and ( 6 ) nanometer crush are the same as those described in example 7 . ( 7 ) enzymolysis : add the nanometer sea cucumber powder with water at ( the weight ) ratio of 1 : 9 and mix up evenly , add alkali proteinase at the ratio of nanometer sea cucumber powder : alkali proteinase equal to 1 g : 10 mg and enzymolysis for 1 hours at 65 ° c . under ph 7 ˜ 8 , and then adjust the temperature to 45 ° c ., add trypsase at the ratio of nanometer sea cucumber powder : trypsase equal to 1 g : 100 mg and enzymolysis for 1 hours under ph 8 ˜ 9 , after the enzymolysis reaction is finished , heat the enzymolysis reaction solution for 10 min at 100 ° c . centrifuge and separate the enzymolysis product , take the enzymolysis supernatant , dry directly to get nanometer sea cucumber extract . ( 8 ) mix the nanometer sea cucumber extract with the panax pseudo - ginseng saponins extract at the ratio of nanometer sea cucumber extract : panax pseudo - ginseng saponins extract equal to 80 %: 20 %. the product is a light brown powder , and the main active ingredients are sea cucumber polysaccharide and panax pseudo - ginseng saponins ( calculated by r1 + rb1 + rg1 ingredient total contents ), wherein the content of sea cucumber polysaccharide is 3 . 3 % and the content of panax pseudo - ginseng saponins is 6 . 8 %. after mixing make granules at the ratio of raw material to excipients equal to 1 : 1 . ( 1 ) raw material processing : cut the fresh sea cucumber , take out the viscus , sufficiently clean the sea cucumber wall , and put it into an airtight container . ( 2 ) gelatination : heat the container at 100 ˜ 105 ° c . for 120 minutes . ( 3 ) vacuum freeze - dry : freeze - dry the gelatinated sea cucumber till the water content is 3 %. ( 4 ) coarse crush , ( 5 ) ultra - micro crush and ( 6 ) nanometer crush are the same as those described in example 7 . ( 7 ) enzymolysis : add the nanometer sea cucumber powder with water at ( the weight ) ratio of 1 : 6 and mix up evenly , add alkali proteinase at the ratio of nanometer sea cucumber powder : alkali proteinase equal to 1 g : 5 mg and enzymolysis for 1 hours at 65 ° c . under ph 7 ˜ 8 , and then adjust the temperature to 45 ° c ., add trypsase at the ratio of nanometer sea cucumber powder : trypsase equal to 1 g : 1000 mg and enzymolysis for 1 hours under ph 8 ˜ 9 , after the enzymolysis reaction is finished , heat the enzymolysis reaction solution for 10 min at 100 ° c . centrifuge and separate the enzymolysis product , take the enzymolysis supernatant , dry directly to get nanometer sea cucumber extract . ( 8 ) mix the nanometer sea cucumber extract with the panax pseudo - ginseng saponins extract at the ratio of nanometer sea cucumber extract : panax pseudo - ginseng saponins extract equal to 90 %: 10 %. after mixing make tablet at the ratio of raw material : excipients equal to 2 : 1 the product is a light brown powder , and the main active ingredients are sea cucumber polysaccharide and panax pseudo - ginseng saponins ( calculated by r1 + rb1 + rg1 ingredient total contents ), wherein the content of sea cucumber polysaccharide is 4 . 7 % and the content of panax pseudo - ginseng saponins is 4 . 1 %. ii . laboratory efficacy experiment of mixture of nanometer sea cucumber extract and panax pseudo - ginseng saponins extract 1 . influence to blood coagulation time parameter tt , rt by treating by irrigating stomachs of mice : see table 1 2 . influences to tt value and rt value of pure sea cucumber nanometer powder and compound sea cucumber preparation after treating mice through different treat ways : ( 2 ) determination of thrombin time ( tt ): add blood plasma to be determined 50 ul , 1 mol / l ph7 . 4 tris - hcl buffer solution 50 ul and 5 u / ml thrombin solution 50 ul into the determination cup of the blood coagulation analyzer sequentially , and the blood coagulation analyzer records the blood coagulation time automatically while the thrombin solution is added . the time from that the thrombin solution is added to that the blood coagulation is formed is recorded as blood plasma coagulation time , called thrombin time for short . ( 3 ) determination of re - calcification time ( rt ): add blood plasma to be determined 100 μl , then add 0 . 025 mol / l cacl2 solution 100 μl into the determination cup of the blood coagulation analyzer sequentially , and the blood coagulation analyzer records the blood coagulation time ( re - calcification time ) automatically while the cacl2 solution is added . ( i ) treating by injection from caudal vein of the mice : accurately weigh sea cucumber nanometer powder or compound sea cucumber preparation 100 mg , add distilled water 5 ml , mix by rotating at 2800 r / min for 30 seconds , then centrifuge at 3000 r / min for 15 min , take the supernatant that is sea cucumber nanometer powder or compound sea cucumber preparation aqueous extract for reservation . 45 kunming variety mice are divided into 3 groups randomly , those are normal saline group , nanometer sea cucumber powder group and compound sea cucumber preparation group , 15 mice for each group . the normal saline group is injected with normal saline 0 . 1 ml / 10 g weight from the caudal vein , while the sea cucumber nanometer powder group and the compound sea cucumber preparation group are respectively injected with above said sea cucumber aqueous extract 0 . 1 ml / 10 g weight from the caudal vein . 15 min after the injection , collect blood 0 . 45 ml on the eyeballs of the mice , add 0 . 05 ml 3 . 8 % sodium citrate anti - coagulation , then adding 0 . 2 ml normal saline , centrifuge for 10 min at 3000 r / min after being mixed evenly , take the supernatant to determine the tt and rt values . ( ii ) treating by injection from abdomen of the mice : 18 kunming variety mice are divided into 3 groups randomly , those are normal saline group , nanometer sea cucumber powder group and compound sea cucumber preparation group , 6 mice for each group . the normal saline group is injected with normal saline 0 . 2 ml / 10 g weight from the abdomen , while the sea cucumber nanometer powder group and the compound sea cucumber preparation group are respectively injected with 50 mg / ml common sea cucumber powder and nanometer powder suspension 0 . 2 ml / 10 g weight from the abdomen . 30 min after the injection from the abdomen , collect blood 0 . 45 ml on the eyeballs of the mice , add 0 . 05 ml 3 . 8 % sodium citrate anti - coagulation , then adding 0 . 2 ml normal saline , centrifuge for 10 min at 3000 r / min after being mixed evenly , take the supernatant to determine the tt and rt values . ( iii ) treating by irrigating stomachs of the mice : 60 kunming variety mice are divided into 6 groups , those are respectively 2 groups for normal saline group , nanometer sea cucumber powder group and compound sea cucumber preparation group , which are respectively treated by irrigating stomachs for 1 week and 2 weeks , 10 mice for each group . the normal saline group is treated by irrigating stomachs with normal saline 0 . 2 ml / 10 g weight , while the sea cucumber nanometer powder group and the compound sea cucumber preparation group are respectively treated by irrigating stomachs with 50 mg / ml sea cucumber nanometer powder and compound sea cucumber preparation suspension 0 . 2 ml / 10 g weight , ( 1 g / kg weight ), twice for one day . collect blood 0 . 45 ml on the eyeballs of the mice 1 h after the last stomach irrigation , add 0 . 05 ml 3 . 8 % sodium citrate anti - coagulation , then adding 0 . 2 ml normal saline , centrifuge for 10 min at 3000 r / min after being mixed evenly , take the supernatant to determine the tt and rt values . as shown in table 2 , after the mice are treated by the caudal intravenous injection , the abdomen injection and 2 weeks stomach irrigation , compared with ns group , rt values of the sea cucumber nanometer groups are respectively extended for 1259 . 46 %, 236 . 54 % and 284 . 04 %, compared with ns group , rt values of the compound sea cucumber preparation groups are respectively extended for 1895 . 95 %, 698 . 08 % and 717 . 02 %, and all have statistical significances ( p & lt ; 0 . 01 ), and the rt extension of the compound sea cucumber preparation is more significant than rt extension of nanometer powder ; compared with rt values of nanometer powder groups , rt values of compound sea cucumber preparation groups are respectively extended for 46 . 82 %, 137 . 14 % and 112 . 74 %, and the differences between the two groups have statistical significances ( p & lt ; 0 . 01 ). compared with ns group , although the tt values have extension trend after treating by injection and orally taking , but have no statistical significances ( p & gt ; 0 . 05 ). after the mice are treated by irrigating stomachs for 1 week , compared with ns group , rt values of sea cucumber nanometer powder group and compound sea cucumber preparation group are all extended significantly , respectively for 641 . 18 % and 905 . 88 %, and have statistical significances ; although rt of the nanometer powder is extended for 35 . 71 % compared with common powder group , the differences between the two groups have no statistical significances ( p & gt ; 0 . 05 ). the detail summary of the experiment see table 2 : take male , 18 ˜ 22 g kunming variety mice , randomly take 10 mice from them as normal control group . other mice are injected with alloxan 50 mg / kg after fasting ( water is allowed ) for 16 h , determine the fasting plasma glucose ( fpg ) fasting for 5 h after the mice are stable for 15 days , mice with fpg & gt ; 10 mmol / l are high plasma glucose model mice . 10 mice for normal control group . take 40 high plasma glucose mice , randomly divide into high plasma glucose model group , compound sea cucumber preparation high dosage ( 0 . 5 g / kg ) group , compound sea cucumber preparation low dosage ( 0 . 25 g / kg ) group and positive drug metformin 200 mg / kg group . mice of the compound sea cucumber preparation high dosage group and the compound sea cucumber preparation low dosage group are respectively treated with 0 . 025 g / ml and 0 . 0125 g / ml suspension of compound sea cucumber preparation and normal saline 0 . 2 ml / 10 gbw by irrigating stomachs , mice of the metformin 200 mg / kg group are treated with 10 mg / ml metformin normal saline solution 0 . 2 ml / 10 gbw by irrigating stomachs , while mice of the normal control group and high plasma glucose model group are treated with equal volume of normal saline by irrigating stomachs . mice of each group are treated twice each day ( b . i . d ) continuously for 4 weeks . determine the fasting plasma glucose ( fpg ) for mice of each group at 7th day , 14th day and 28th day with germany roche superior iv type glucose meter , and record the weights of mice . b . influences of compound sea cucumber preparation to glucose tolerance of experimental diabetic mice caused by alloxan : building of mice high glucose model , animal grouping and treating ways are the same as above description . after mice of each group are determined fasting plasma glucose ( fpg ) fasting for 5 h with germany roche superior iv type glucose meter at 28th treating day , mice are treated with 2 g / kg glucose by abdomen injection , to determine the glucose value 30 min , 60 min , 120 min and 240 min after glucose load , and calculate the area under the glucose tolerance curve ( auc ) according to trapezoid area method as formula below : auc ⁢ ⁢ ( mmol · h ⁢ / ⁢ l ) = ∑ i = 1 n - 1 ⁢ ⁢ c i + c i + 1 2 · δ ⁢ ⁢ t wherein , c is the plasma glucose value ( mmol / l ), t is the time after glucose load ( h ), i is the glucose value number ; c0 , c1 , c2 , c3 , c4 are respectively plasma glucose value of before glucose load ( 0 min ) and 30 min , 60 min , 120 min and 240 min after glucose load . c . effects of compound sea cucumber preparation to insulin resistance hepg2 cell model : human liver cancer cell line hepg2 provided by dalian medical university is vaccinated in a dmem culture medium which contains 10 % volume fraction of fetal calf serum ( supplementing penicillin , streptomycin 100 u · l − 1 respectively ), and the culture medium is placed in a 5 % co2 cell culture box at 37 ° c . hepg2 cells grow anchorage - dependently , digesting the cells by 0 . 25 % pancreatic enzymes , the cells passage 1 time every 3 days , then taking cells in logarithmic phase for experiment . preparation for sea cucumber n powder solution : dissolve with dmem culture solution , then prepare mother solution with concentration of 1600 mg / l , then dilute the mother solution at equal ratio to required concentration according to specific situation . preparation for metformin solution : dissolve with dmem culture solution , the concentration is 30 mg / l . digest monolayer culture hepg2 cells with 0 . 25 % pancreatin , prepare single cell suspension with dmem culture solution containing 10 % fetal calf serum , adjust the cell concentration to 5 × 10 4 · ml − 1 and total amount 200 ul for each well to vaccinate on 96 - well cell culture plate . incubate for 8 h in culture box in the conditions of 37 ° c . and 5 % co2 to form monolayer anchorage - dependent cells . wash the cells twice with dmem culture solution without fetal calf serum , then incubate the cells for 16 h with 5 × 10 − 7 mol · l − 1 insulin culture solution in culture box in the conditions of 37 ° c . and 5 % co2 . the hepg2 cells incubated for 16 h with insulin culture solution are model cells . count the prepared cell suspension , adjust the cell concentration to 5 × 10 4 · ml − 1 , vaccinate on 96 - well cell culture plate , 8 - well in duplicate for each group , total amount of 200 ul for each well . the experiment is divided into 5 groups : normal control group , insulin resistance model group , compound sea cucumber preparation high and low dosage groups and metformin positive control group . except the normal control group , each other group is incubated for 16 h after adding insulin with ultimate concentration of 5 × 10 − 7 mol · l − 1 into culture solution so as to form insulin resistance model . after model formation , cells are incubated with culture solution without insulin , each treating group is respectively incubated with culture solutions at ultimate concentrations of compound sea cucumber preparation 2 . 5 g · l − 1 , compound sea cucumber preparation 5 . 0 g · l − 1 and metformin 30 mg · l − 1 · 24 h after treating , detect the glucose in the culture solution with glucose oxidase method , minus the glucose average value of blank duplicate wells of unvaccinated cells to calculate the glucose consumptions of each porocyte . determinate the content of glycerin in the culture solution with gpo - pod enzyme method , minus the average glycerin content of blank duplicate wells of unvaccinated cells to calculate the glycerin consumption of each porocyte . c - 5 . determination the influence of drug to cell proliferation with mtt method prepare mtt culture solution with 5 g · l − 1 mtt basic solution and serum free dmem culture solution according to volume ratio of 1 : 9 , after the cell glucose consumption experiment and glycerin consumption experiment are finished and the culture solution to be determined is taken out , add mtt culture solution to each well , culture continuously at 37 ° c ., terminate the culture after 4 h , and carefully draw and abandon the culture supernatant in the well , add 200 μl dimethyl sulfoxide for each well , vibrate 10 min to dissolve the crystals sufficiently , determine the absorbency value of each well in a micro - plate reader , calculate the cell survival proportion to evaluate the influences of drug to cell proliferation . d - 1 influences of compound sea cucumber preparation to fasting plasma glucose of experimental diabetic mice caused by alloxan it can be known from table 5 and table 6 that , compound sea cucumber preparation can increase the glucose consumption of insulin resistance hepg2 cells by 96 . 6 % and 114 . 2 % respectively at the concentrations of 2 . 5 g / l and 5 . 0 g / l ( p & lt ; 0 . 01 ), increase the glycerin consumption respectively by 162 % and 167 % ( p & lt ; 0 . 01 ). at this concentration , the cell proliferation is only 4 %- 6 %, so we can believe that the increases of above said glucose and glycerin consumptions are not caused by cell proliferation , but mainly caused by direct influences of glucose metabolism biochemical process by active ingredients of compound sea cucumber preparation .

US-201113576961-A

an improved sole for use with all types of footwear , including dress , casual , and athletic shoes and sandals , which has an upper layer having a plurality of chambers filled with helium . the upper layer is attached to an outsole having indentations , corresponding to the chambers , and coated with a fluidic polymeric material .

referring first to fig1 the sole of the present invention is constructed of an upper layer 10 molded into substantially the shape as shown . the upper section is comprised of a top surface 11 having a toe end 12 and a heel end 13 . top surface 11 is usually substantially flat . however , it will be understood that top surface 11 may have an upward slope along the perimeter and may have a slope between toe end 12 and heel end 13 to accommodate a raised heel on the outsole 20 . protruding from the bottom surface 14 of upper layer 10 are a plurality of chambers which contain helium gas . in the preferred embodiment , upper layer 10 has a heel chamber 15 , instep chamber 16 , ball chambers 17 , and return chamber 18 . referring now to fig2 heel chamber 15 is connected to the rear portion of central instep chamber 16 . central instep chamber 16 is substantially tubular in shape and extends lengthwise along the instep portion of the sole . central instep chamber 16 is connected to heel chamber 15 by way of a one - way valve which permits helium to flow in only one direction , from the heel chamber 15 into central instep chamber 16 . the forward portion of central instep chamber 16 is connected to the midsection , 17 a , of ball chambers 17 . ball chambers 17 are comprised of a plurality of tubes , 17 b through 17 j , extending crosswise from and connecting with a central lengthwise tube 17 a . each of tubes 17 b through 17 j connects to tube 17 a . central instep chamber 16 is connected to central lengthwise tube 17 a by way of a one - way valve which permits helium to flow only from the central instep chamber 16 into central lengthwise tube 17 a . the arrows in fig2 illustrate the flow of helium through the chambers of upper layer 10 . tubes 17 b through 17 j connect to return chamber 18 by way of one - way valves which permit the helium to flow from tubes 17 b through 17 j into return chamber 18 . return chamber 18 accepts helium flowing from tubes 17 b through 17 j and channels the helium along the outside portions of the instep section of the sole . return chamber 18 connects to heel chamber 15 by way of two one - way valves 18 a and 18 b which permit the helium to flow only from return chamber 18 into heel chamber 15 . each of chambers 15 , 16 , 17 a - 17 j , and 18 protrude downward from about 4 to 7 millimeters from the bottom surface of upper layer 10 . the remaining dimensions of the chambers vary and are determined by the size of the footwear . chambers 15 through 18 are filled by way of valve 35 ( also shown in fig1 ). it will be understood that valve 35 may be any of a variety of currently available valves , such as self - sealing diaphragms . as the heel strikes the ground , the helium in heel chamber 15 will be pushed forward out of heel chamber 15 through instep chamber 16 . as the foot rotates through the stride , the helium is pushed into central tube 17 a and from there into tubes 17 b through 17 j . as the stride rotates to place pressure onto the ball of the foot , the helium is forced into return chamber 18 and back into heel chamber 15 . it will be understood that the heel pressure is greater than that exerted by the ball of the foot . therefore , in the preferred embodiment of the sole of the present invention , instep chamber 16 is larger in diameter than the side portions , 18 c and 18 d , of return chamber 18 . because helium is very light , the helium will flow more rapidly between the chambers than would air or heavier gasses , as are commonly used in athletic footwear . this rapid flow of helium will assist in the natural rotation of the foot stride thereby imparting additional lift and power to the wearer . referring again to fig1 the sole of the present invention is further comprised of an outsole 20 having a heel portion 21 , a toe portion 22 , a top surface 23 and a bottom surface 24 . outsole 20 is molded from an appropriate synthetic material and in the preferred embodiment is made of polyisoprene . molded into the top surface 23 of outsole 20 are a plurality of indentations in substantially the shape of chambers 15 , 16 , 17 a - 17 j , and 18 of upper layer 10 . as shown in fig1 indentation 25 corresponds to chamber 15 , indentation 26 to chambers 16 and portions of chamber 18 , and indentation 27 to portions of chamber 18 and chambers 17 a - 17 j . each of chambers 25 through 27 are approximately 6 to 9 millimeters larger in height and 3 to 6 millimeters larger in width than the corresponding chambers . the sole of the present invention is assembled by adhering or affixing upper layer 10 to outsole 20 . consequently , there is a space between the lower surfaces of the chambers of upper layer 10 and the upper surfaces of the indentations of outsole 20 . in the preferred embodiment of the sole of the present invention , such space is filled with a fluidic polymeric compound . the fluidic polymeric compound is injected by way of valve 36 . it will be understood that valve 36 may be any of a variety of currently available valves , such as self - sealing diaphragms . it will be understood , however , that such space may alternatively be filled with air or other suitable gas . the fluidic polymeric compound is composed of a mixture of a short - chain glycol , such as ethylene or propylene glycol , a short - chain alkoxylated alcohol , such as butoxy ethanol , and a desiccant , preferably in the form of a silicate salt , such as sodium silicate . additional elements of the fluidic polymeric compound may include surfactants and / or fibrous plugging and matting agents . any of a number of currently available surfactants , soluble in the glycol / alcohol / silicate mixture could be used , such as sodium lauryl sulfate . fibrous plugging and matting agents are currently available , including for example , fibrous cellulosic materials . the layer of fluidic polymeric material provides an improvement in the ability of the sole to conform to the shape of the foot during a stride thereby increasing comfort while providing support . the fluidic polymeric material further strengthens the chambers 15 through 18 by providing a counter - pressure to that imposed by the foot . the combination of resiliency and conformability provided by the fluidic polymeric material prevents the helium filled chambers from bursting while yet remaining comfortable for the wearer . referring now to fig2 and 3 , the upper layer and the walls of each of chambers 15 , 16 , 17 a - 17 j and 18 are comprised of three layers of material : ( 1 ) an inner layer of mylar , 30 , of approximately one - half millimeter thickness , which is surrounded by a layer of ; ( 2 ) aluminum foil , 31 , of approximately one - fourth millimeter thickness , which is surrounded by a layer of ; ( 3 ) a short chain alkyl polymer , such as polypropylene , 32 , of approximately one millimeter thickness . this construction of the upper layer 10 and chambers 15 through 18 provide significant improvement in containing the helium within the chambers such that a sufficient helium pressure is achieved over an acceptable and standard service life of the footwear . referring now to fig4 the upper surface , 23 , of outsole 20 is laminated with an approximately one millimeter layer of aluminum foil , 33 . over the layer of aluminum foil 33 is adhered a layer of a short chain alkene polymer , such as polyisobutylene , 34 , of approximately one to two millimeters thickness . the layers of aluminum foil 33 and short chain alkene polymer 34 further improve the containment of helium during the service life of the footwear . while the invention has been described herein by way of specific embodiments , it will be understood that the invention may be embodied in other forms .

US-53468700-A

analysis of a goat serum product with many therapeutic effects is described . the product is identified as containing proopiomelanocortin and corticotropin releasing factor peptides , as well as breakdown products of these peptides . we describe methods of treatment of diseases including cancers , multiple sclerosis , and neural disorders using these peptides and their products , as well as medicaments including such peptides and methods of producing the peptides .

approximately 400 cc of blood is taken from a goat under sterile technique . the animal may typically be re - bled in 10 to 14 days , once the volume of blood is replenished . a pre - bleeding regime may be useful to stimulate production of the active components of the serum . the blood is then centrifuged to separate the serum , and the serum filtered to remove large clots and particulate matter . the serum is then treated with supersaturated ammonium sulphate ( 47 % solution at 4 ° c .) to precipitate antibodies and other material . the resulting solution is centrifuged in a beckman j6m / e centrifuge at 3500 rpm for 45 minutes , after which the supernatant fluid is removed . the precipitated immunoglobulin and other solid material are resuspended in pbs buffer ( phosphate buffered saline ) sufficient to redissolve the precipitate . the solution is then subjected to diafiltration against a pbs buffer with a molecular weight cut - off of 10 , 000 daltons , at 4 ° c . after diafiltration the product is filtered through a 0 . 2 micron filter into a sterile container and adjusted to a protein concentration of 4 mg / ml . the solution is put into vials to give single doses of 1 ml , and stored at − 22 ° c . prior to use . the effects of the serum have been previously described , while determination of the active components has not previously been effected . a sample of the composition was size fractionated on a gel , and a western blot performed using antibodies to β endorphin . a strong signal was detected , indicating the presence of β endorphin , although the apparent molecular weight was approximately 31 kda , far larger than the expected size of β endorphin . this suggested that β endorphin was present in the sample as part of a larger peptide ; the size being consistent with that of pomc . we have also carried out mass spectrometry on the composition , and have detected at least two pomc - derived peptides , β endorphin and corticotrophin - related molecules . crh - bp ( corticotropin releasing hormone binding protein ) has also been identified . pomc peptides and crf - bp have been identified in the product by thermofinnegan lcq mass spectrometry . crf mainly regulates the synthesis and secretion of acth in the anterior pituitary . the administration of pomc and / or its component peptides in addition to crf and crf - bp is thought to initiate a cascade effect thus enhancing the production of systemic and sustained elevated concentrations of pomc peptides . crf - bp has the ability to act as a reservoir for crf . fig1 to 4 show the hits obtained from mass spectrometry analysis of tryptic digests from the product separated from contaminating proteins by sds - page . as mentioned above , some of these molecules are inducers and regulators of the pomc cascade . further investigation using more focused analysis ( e . g . peptide fractionation , immunoprecipitation and concentration ) will reveal more of the peptides present . fig1 indicates the presence of a pomc - derived corticotropin , fig2 that of crf - bp , fig3 that of proenkephalin a , and fig4 that of proenkephalin b . the presence of crf - bp suggests that the product contains some crf , while pomc and related peptides are also clearly present . we have also investigated the effects of treatment with the serum composition on patients &# 39 ; own sera . these effects are described below . fig5 shows mass spectrometry of patients &# 39 ; sera before and after treatment . the spectra from 2 to 10 kd are compared . this molecular weight range is associated with the bioactive peptides of interest . clear differences in the peptide expression in the 2 to 6 kd region can be seen by comparing the profiles in the pre and post treatment sera . for ease of comparison an overlapping view of the profiles is also provided . fig6 shows comparative peptide / protein expression in six treated patients . each patient shows increased levels of induced peptide / protein expression particularly in the 4 kd region . fig7 a shows the mass spectrometry profiles of unprocessed goat serum before vaccination ( pre - immune profile , top panel ), unprocessed serum 53 days post - immunisation , and the processed product . it can be seen that in the lower two panels the profile of the serum is significantly different to that of the pre - immune profile , indicative of the induction of protein expression . the profiles present here represent the active product , and a specific immunisation / bleed protocol has been shown to be useful in the induction of this serum profile . an overlapping view of the profiles is shown ( fig7 b ). fig8 shows comparative levels of acth in the sera of patients before and after receiving treatment . this is also compared with levels of acth in serum from healthy volunteers and in the product administered to patients . sera were diluted 1 : 100 and quantified by an elisa of sera compared with the product . data are the mean of three determinations +/− standard errors . post treatment n = 5 ; pre treatment n = 3 ; normal human sera n = 5 . the data show that treatment increases acth levels . fig9 compares levels of β endorphin in the serum of treated patients with that in the sera of the same patients before treatment . this is compared with levels in the sera of healthy volunteers and in the product . sera were diluted 1 : 100 and quantified by an elisa of sera compared with the product . data are the mean of three determinations +/− standard errors . the data show that treatment increases β endorphin levels . evidence for a switch from a pro - inflammatory th - 1 profile to an anti - inflammatory th - 2 cytokine profile in treated patients fig1 shows the levels of tgf - 3 in the serum of two groups of patients before and after treatment . the two groups of patients ( n = 3 for each group ) show differing responses with respect to the concentrations of tgf - β produced , but all patients showed an increase in serum levels in response to treatment ( pre sera = patients &# 39 ; serum levels before treatment ; post 2 nd and post 5 th = after the 2 nd and 5 th administration ). the data show that treatment induces increased concentration of the anti - inflammatory cytokine tgf - β . fig1 shows the levels of il - 4 in the serum of one group of patients before ( pre - sera ) and after treatment . it can be seen that after treatment ( post 2 nd ), the levels of il - 4 are significantly increased in the patients &# 39 ; sera ( n = 5 ). however , following the 5 th administration , the levels of il - 4 had dropped in all patients , but remained higher than they had been pre - treatment . il - 4 is known to downregulate the production of the pro - inflammatory cytokines from th - 1 cells . it may be that the consistent changes in concentration seen in all patients is consistent with il - 4 &# 39 ; s role in the th - 1 to th - 2 switch . fig1 shows the levels of il - 6 in the serum of one group of patients before and after treatment . it can be seen that after treatment ( post 2 nd and post 5 th ) the levels of il - 6 are reduced in the patients &# 39 ; sera ( n = 4 ). fig1 shows the levels of ifn in the serum of one group of patients before and after treatment . it can be seen that after treatment ( post 2 nd and post 5 th ) the levels of ifn - γ are reduced in the patients &# 39 ; sera . fig1 shows that treatment of human peripheral blood cells ( pbmcs ) induces the production of the anti - inflammatory cytokine il - 10 in the monocyte sub population . t and b lymphocytes and monocytes were separated from pbmcs obtained from human volunteers . all cell types were treated with equivalent doses of product for 16 h , and their supernatants assayed for il - 10 content using elisa . it can be seen that il - 10 levels produced by the t cell population were unaffected by treatment and that only a small increase in il - 10 was induced in the b cells . however , a significant elevation of il - 10 concentration was induced in the monocytes population by the treatment . all determinations were made in triplicate +/− standard deviations . these data are representative of at least three separate experiments . fig1 shows the comparative levels of vasopressin in the product , control patients and patients treated with the product and pre - treatment . the figure shows that there is no significant difference between any of the serum groups , however the product contains significant levels of vasopressin , sufficient to elicit a response in the patients . it is known that vasopressin acts synergistically with crf to release pomc . all determinations were made in triplicate +/− standard deviations . these data are representative of at least 3 separate experiments . patients pre - treatment n = 3 ; treated patients n = 6 . fig1 shows the increased presence of crf in the product compared with the placebo and the increase in the treated patients compared with the non - treated individuals ; the latter is evidence for the induction of crf in the patients in response to treatment . all determinations were made in triplicate +/− standard deviations . these data are representative of at least 3 separate experiments . control individuals n = 4 ; treated patients n = 13 . although preliminary , the evidence to date is therefore consistent with the major active component being crf acting in concert with other components , which is thought to induce pomc production . there is also evidence that pomc itself and pomc - derived peptides may be used as a treatment . this suggests new pharmaceutical compositions and uses for crf and pomc , as well as indicating additional disorders which may be treatable using crf and pomc . we have also provided a convenient method of producing crf and pomc from goats . the data so far suggests that the product not only contains crf , pomc peptides and anti - inflammatory cytokines ( il - 10 and tgf - β ) but also induces the expression and release of crf and hence pomc peptides in the patient , which then transform the patients &# 39 ; immunological profile from a th - 1 pro - inflammatory profile to a predominantly th - 2 anti - inflammatory profile . other observations on the composition effects are consistent with the active component being crf which leads to pomc production . for example , effects on leukocyte adherence may be attributable to beta endorphin . the serum product increases il - 10 production by human pbmc ; alpha msh affects il - 10 production . effects on nerve conduction and neuroprotective effects may be ascribed to acth and vasopressin ; effects on appetite may be due to alpha msh . the product itself also contains significant levels of il - 10 and tgf - β ( data not shown ). alpha msh has potent anti - inflammatory effects in all major forms of inflammation and it antagonises the effects of pro - inflammatory cytokines such as tnfα and il1 - β . cross talk exists between the cytokine systems and the pomc system which has been observed in patients treated with the composition to result in the reduction of pro - inflammatory cytokines and the establishment ( retained over the course of treatment ) of a th - 2 anti - inflammatory cytokine profile including elevated levels of il - 10 and tgf - β . we have also identified increased levels of il1 - β in the serum product . the serum product has previously been shown to be very sensitive to proteolytic degradation ; this is consistent with the theory that the pomc is proteolysed to give individual hormones on administration , but that further degradation destroys activity . in particular , alpha msh is believed to have significantly reduced activity if a terminal tripeptide sequence is removed ; again , this is consistent with the active component including pomc . the product itself is unstable by nature as its active components are short - lived , but exhibit powerful effects . we have also conducted experiments which suggest that the serum modulates nitric oxide production by leukocytes ; this is consistent with effects of beta endorphin . we also believe that the serum inhibits pha - induced pbmc proliferation , suggesting an explanation for the serum &# 39 ; s immunomodulatory effects . we have also seen a reduced response of pbmcs in the presence of the product to lps - induced stimulation and mixed lymphocyte reactions ( data not shown ). the product may also induce tyrosine phosphorylation in human brain microglial cells , and has been shown by western blotting to modulate the nfib pathway ( data not shown ). nfκb is known to regulate the transcription of genes involved in the regulation of pro - inflammatory cytokines , hence the inhibition of nfκb would act to reduce the pro - inflammatory cytokine response in autoimmune disease and reduce inflammatory responses . further experiments to investigate this are underway . receptors ( mcr3 and mcr4 ) for some pomc peptides are found in the retinal ganglion cells that form the optic nerve and may be stimulated by pomc peptides produced after treatment . this may account for some of the rapid improvements in vision experienced by ms patients with optic neuritis which have previously been described . it is known that acth triggers the corticosteroid pathway which can exert effects in as little as 20 to 30 minutes . preliminary data suggests that the concentrations of the peptides in the product may be insufficient to elicit therapeutic responses in patients after dilution in the blood volume of the patient . however , the product could act locally ( as it is injected in a subcutaneous bolus ) to induce a biochemical cascade which triggers the synthesis and release of the bioactive peptides in the treated patients . it is now known that any medical treatments that interfere with the product , for example by competing for receptors or blocking molecules in the hpa should be avoided . in support of this hypothesis mass spectrometry of the product has identified additional molecules some of which are involved in the induction and regulation of the corticotropin system ; namely crh binding protein and leu - enkephalin , corticotropin - lipotropin precursor and pro - enkephalin a precursors ( see fig1 to 4 ), in addition , and perhaps more importantly , we have discovered that two of the major pomc peptides are upregulated significantly in treated patients &# 39 ; sera compared with levels before treatment , and also compared with levels from healthy control volunteers . this finding , together with immunological data , suggests that the treatment induces the expression and release of pomc peptides in the patient , which then transforms the patients &# 39 ; immunological profile from a th - 1 pro - inflammatory profile to a th - 2 anti - inflammatory profile . the further elucidation of the cascade mechanism in the patients is currently under investigation . it should be noted that although the product is anti - inflammatory in nature it does not completely inhibit the inflammatory response . our data suggest that the product induces a shift from the unfavourable th - 1 cytokine profile seen in auto - immune diseases to a more favourable balanced cytokine level . this may appear initially after treatment as a rapid anti - inflammatory th - 2 shift as the th - 1 network is turned off . later on after treatment the th - 1 network operates albeit at a lower level . the reported effects of the serum product on tumours leads us to consider the possibility of anti - angiogenic effects of the serum . in this regard , the proteins thrombospondin - 1 ( tsp - 1 ) and platelet factor 4 ( pf - 4 ) have been identified in the product by mass spectrometry of tryptic digests from sds page gels . computer database searches using biowork browser for peptide identification yielded strong matches across several species including homo sapiens . although precise quantification of the tsp - 1 and pf - 4 protein content of the product has not yet been established , the visible nature of the protein bands on sds page gels indicates that the proteins are present in biologically significant ( upper nanogram ) quantities . a summary of the hypothesised components of the product , and the method of action , is shown in fig1 . the product is thought to contain crf , with some levels of crf - bp , beta endorphin , vasopressin , and enkephalins . crf induces production of further crf in the patient , as do beta endorphin and the enkephalins . endogenous crf causes production of pomc , which gives rise to among others acth , alpha msh , and beta endorphin . this last product acts in a feedback loop , with low levels stimulating further crf release , while high levels inhibit crf release . this whole crf / pomc cascade is thought to induce an immunological switch in the patient , which could explain the surprising beneficial effects seen in a variety of conditions .

US-201213544413-A

an extension mounting apparatus on which a bowel anastomosis ring device may be mounted in prefixed position to facilitate handling , insertion and closure in bowel ends to be anastomosed may be advantageously removably attached to an inserter to provide an applicator which enables insertion in the bowel and manipulation from a point exterior of the area to be anastomosed so as to cause the bowel anastomosis ring device halves to become controllably connected to couple the bowel ends to be joined together in contiguous abutting relationship . a method of performing low colorectal anastomosis using the bowel anastomosis ring device and closing the mating ring halves by manipulating the applicator exteriorly of the anus involves passing the inserter portion of the applicator from the interior of the rectum to the exterior of the anus so that placement is always from the clean area of surgery and anastomosis to the dirty and contaminated end .

referring to fig1 there is shown , in two parts , an anastomosis ring device applicator referred to generally at 2 . the applicator includes a mounting extension 4 and an inserter 6 . the mounting extension 4 is formed of a tubular housing 8 on which are positioned , at spaced - apart locations , respective mating halves , distal half 10 and proximal half 12 , of a bowel anastomosis ring device , seen at 14 in fig3 . the bowel anastomosis ring device 14 is of the type described in u . s . patent application ser . nos . 198 , 448 and 287 , 500 filed oct . 20 , 1980 and july 27 , 1981 , respectively , referred to above . slidably and rotatably positioned coaxially within the tubular housing 8 is a rod - like shaft 16 , the distal end 18 of which is bifurcated and provided with holding tabs 20 the purpose of which will be described below . as used herein , the term &# 34 ; distal &# 34 ; shall refer to that part of the applicator which is furthest away from the surgeon - user and the term &# 34 ; proximal &# 34 ; shall refer to that part of the applicator which is closest to the surgeon - user . the distal end will include the bowel anastomosis ring device while the proximal end will include the manipulation knob . the tubular housing 8 , seen also in fig3 includes a generally cylindrical central portion 22 terminating in a closed end 24 and an open end 26 . proximate to the closed end 24 are two l - shaped openings 28 , circumferentially diametrically opposed to one another , through which can project the tabs 20 of the shaft 16 . proximate the open end 26 the tubular housing 8 is surrounded by a collar 30 having a beveled portion 32 for tight fitting engagement into the opening of the inserter 6 , as described hereinafter . also located on the tubular housing 8 proximate to the collar 30 is a retaining curcumferential projection 32 for retaining the bowel anastomosis ring device half 12 in place on the housing 8 . an l - shaped opening 34 is formed adjacent to the retaining ring 32 to receive the pin 36 on the bifurcated termination 18 of the rod 16 upon closure of the ring halves . the holding tabs 20 of the rod - like shaft 16 extend through the respective openings 28 and engage , by means of the projection 38 , the bowel anastomosis ring device ring half 10 , as seen in fig1 . the tabs 20 can be caused to withdraw from the openings 28 by counterclockwise rotation within the tubular housing 8 by virtue of the cam surfaces 40 which cause the bifurcations of the end 18 and the tabs located thereon to be forced together so that they may be withdrawn from the openings 28 and fitted within the interior of the tubular housing 8 . the cam surfaces 40 are formed and placed in relationship to the wall 42 of the opening 28 so as to be caused to be withdrawn upon counterclockwise revolution of the shaft 16 . the inserter 6 is formed of a tubular outer housing 44 and may be curved as shown in fig1 . the outer housing 44 is open at one end 46 to receive the beveled surface of the collar 32 when the inserter 6 and the mounting extension 4 are joined together . slidably and rotatably positioned within the tubular housing 44 is a rod - like shaft 46 terminating at one end in a bayonet - type connection 50 which can form an interlock with complimentary portions 52 located on the shaft 16 of the mounting extension 4 . the shaft 46 terminates at its other end in a threaded portion 52 and has spaced along its length circumferential spacers 54 to provide it with axial stability within the housing 44 . a rotatable knob 56 is threaded on the end of the shaft portion 52 and is provided with a reduced diameter portion 58 having a circular flange 60 secured to a cylindrical housing 62 which is slidably positioned in the tubular housing 44 . pivotally mounted on the housing 62 is a button 64 biased by a spring 66 so that upon slidable movement the button 64 can be caused to project into the opening 68 cut into the curcumference of the housing 44 . the mechanical functioning of the applicator 2 is described as follows . the ring - like half members of the bowel anastomosis ring device , 10 and 12 respectively , are mounted on the extension 4 which is connected , through insertion of the collar portion 32 into the opening 46 of the inserter 6 . an interlock is made between shafts 16 and 46 by means of members 52 and 50 , respectively . the ring half 10 is held in place on the tubular housing 8 by the tabs 20 and the projections 38 and caused to move toward ring member 12 by linear movemet of the knob 56 such as by grasping and withdrawing it and cylindrical housing 62 from the housing 44 in the proximal direction . as the knob 56 is linearly retracted from the inserter housing 44 , the shaft 46 is caused to move the shaft 16 of the extension mounting 4 . this movement and the fact of the tabs 20 being positioned behind the ring half 10 cause the entire tubular housing 8 to move linearly with respect to the collar 32 and the ring member 12 and to be drawn concentrically into the interior space of the tubular housing 44 . after a predetemined linear movement , based on the anastomosis to be done , has been completed , the button 64 which has moved with the cylindrical housing 62 projects into the opening 68 of the housing 44 indicating that linear movement of the knob 56 is to cease . at this point , the ring halves 10 and 12 are close enough to one another for further approximation to be done by a more closely controlled movement . this is achieved by now rotating the knob 56 which , through the threaded engagement on the portion 52 of the shaft 46 , causes the shaft 46 to move linearly in relationship to the rotational movement of the knob 56 . this in turn causes the shaft 16 and tubular housing 8 to further draw the ring member 10 toward the half 12 until the two are engaged with one another . the tabs 20 can now be removed from their position behind the ring member 10 by a counterclockwise movement of the knob 56 and hence of the rod 46 and rod 16 connected thereto to cause the cam surfaces 40 to strike the surfaces 42 in the openings 28 in the extension housing 8 . this squeezes the bifurcations of the end 18 together for withdrawal through the interior of the housing 8 and 44 . the entire extension mounting 4 and inserter 6 which together form the applicator 2 can then be withdrawn from the bowel anastomosis ring device 14 . an alternative embodiment of the knob is shown in fig1 - 14 . referring thereto , it is seen that the knob 70 is formed of two wing - like halves 72 having living hinges causing them to spring open when the band 74 holding them closed is released . fig1 illustrates an alternative form for causing the controllable closing of the halves 10 and 12 by rotation of the wings 72 . the housing 62 has fixed thereon a cam surface 76 along which travels the cam follower 78 , a cylindrical projection on the rod shaft 46 , in order to translate rotational movement of the rod 46 into linear movement and close the two halves 10 and 12 of the bowel anastomosis ring device . instead of the button 64 indicating when the linear movement has resulted in the desired gross adjustment , a visual indicator resulting from a mark or color band on the shaft 46 can appear in the window 80 . fig6 a and 8 through 11 illustrate the use of the applicator device of fig1 and the method of bowel anastomosis according to this invention . fig7 b illustrates the applicator device of fig1 in a method of tubular anastomosis according to this invention . although not critical to the practice of the method of tubular anastomosis , it is preferred that the incision 128 ( i . e ., not the incision 126 ) be the closest incision to the heart muscle , as this provides the maximum amount of arterial blood for healing . it is also to be understood that the use of the applicator for bowel anastomosis shown in fig8 through 11 describe identically the use of the application for tubular anastomosis except that the applicator is removed through the incision 128 instead of the rectum 110 and anus 112 . as described in the copending applications referred to above , the bowel anastomosis ring device consists of two identical halves of mushroom cap configuration which are caused to snap together , as shown at 14 in fig3 thereby clamping sections of the bowel there between . according to this invention , the device can be used without the inserter 6 . for example , the ring halves can be mounted on the extension mounting 4 in prefixed position and inserted between ends of the bowel to be anastomosed through a colostomy . of course , the bowel anastomosis ring device can be used , as described in the copending applications referred to above , without either an extension mounting or inserter for anastomosis not requiring colostomy or transanal application . however , as illustrated in fig6 a and 8 through 11 , the present invention makes possible a method for low anterior anastomosis utilizing transanal insertion proceeding from the clean surgical site to the dirty end to avoid contamination . referring generally to fig6 and 7a , there is schematically illustrated the applicator 2 and an abdomen 100 with an incision 102 therein providing access to the bowel 104 of which a diseased portion has been removed leaving lower bowel portion 106 and upper bowel portion 108 . the lower bowel portion 106 communicates through the rectum 110 to the exterior of the body through the anus 112 . fig7 a shows the applicator being placed in the opening of the lower bowel half 106 . fig7 b schematically illustrates the applicator 2 in place with a phantom illustration showing the placement of the applicator . the applicator is placed through an incision 126 which provides access to a tubular vessel 120 of which a diseased portion has been removed . this leaves a first tubular vessel portion 124 and a second portion 122 . the first portion 124 communicates through the incision 128 to the exterior of the body . fig8 shows the applicator 2 in place with the bowel halves 106 and 108 having been secured to the halves 12 and 10 of the bowel anastomosis ring device such as by purse string sutures . fig9 shows the knob 56 being linearly withdrawn , in the proximal direction , away from the inserter housing 6 and the body to cause the shaft 46 to move linearly to cause the tubular housing 8 of the extension mounting 4 to be withdrawn moving bowel anastomosis ring half 10 towards the other half 12 , as described above . this is a gross adjustment . fig1 illustrates the closure rod having been withdrawn to its fullest extension so that the two ring halves are brought into close approximation just prior to locking . the button or other indicator signals this position . at this point , the surgeon checks the proposed anastomosis and makes modifications as necessary . the bowel anastomosis ring device halves can be separated by merely reversing the linear direction of the closure rod so as to open the halves up . if satisfactory , the applicator can now be activated for final closure of the two halves for engagement in place . this is achieved by rotating the knob 56 , in the direction shown in fig1 , to translate the rotational movement , as previously described , into linear movement and controllably bring the two halves together for engagement . the applicator is then removed from the closed bowel anastomosis ring device by counterclockwise motion which disengages the tabs from the ring device and withdrawn from the body through the rectum and anus as shown in fig1 . this is done without obstruction or trauma to the anastomosis or distal colonic tissue . it will be understood that the mounting extension 4 and inserter 6 can be made integral as one unit for certain situations of anastomosis of tubular body organs . however , an advantage of the embodiment shown is that the mounting extension 4 can be provided in a variety of sizes with the rings 10 and 12 prefixed thereon in different positions depending on the anastomosis to be achieved . the inserter 6 can be packaged separately to be useful with a variety of the mounting extensions 4 . although a particular advantageous utility of the invention is in bowel anastomosis and with clamping ring devices used for such anastomosis , the device and method according to this invention may find utility in other types of anastomosis of tubular body members with appropriate adaptation for size and location involved . in addition , the method of this invention providing the new procedure of anastomosis by proceeding from the clean surgical site toward the dirty end when there is to be transanal insertion and manipulation outside of the body , can also find advantageous utility in anastomosis that utilize means other than clamping ring devices , such as stapling means which clamp the tubular members to be joined there between , and the like .

US-58827684-A

a catheter assembly is provided having an inner member and an outer member extending along a longitudinal axis , the inner member and the outer member having a coaxial configuration and dimensioned for relative axial movement . the outer member has a wall defining a longitudinal slot ; a leaf spring is connected to the inner member , the leaf spring being adapted to engage with the longitudinal slot so as to maintain rotational alignment between inner member and outer member .

the present invention relates to a rapid exchange delivery catheter system in which a stent is delivered intraluminally into a human patient &# 39 ; s body lumen , such as a coronary artery , carotid artery , renal artery , peripheral artery and veins , and the like . the invention provides for a stent delivery catheter assembly , a method of assembly , and a method of use in which a stent is implanted in a patient . there are numerous prior art stent delivery systems which may be used in conjunction with the present invention . the stent delivery systems suitable for use with the present invention are “ rapid exchange ” delivery systems which have an outer sheath adapted to slide over an inner sheath so as to cover a stent . the invention described in detail herein is described in the context of an elastically self - expanding stent delivery system . however , the invention is not limited to such use , and may equally be used with a delivery system for a balloon expanded stent or heat expanded stent . in one embodiment of the invention , as exemplified in fig1 a rapid exchange catheter assembly 20 is provided to deliver and implant a stent . rapid - exchange catheters are known in the art and details of the construction and examples of use are set forth in u . s . pat . nos . 5 , 458 , 613 ; 5 , 346 , 505 ; and 5 , 300 , 085 . rapid exchange catheter assembly 20 incorporates an inner member 22 and an outer member 24 arranged in coaxial alignment . inner member 22 is slidably positioned within outer member 24 and relative axial movement between the two members is provided by inner member control handle 26 and outer member control handle 28 . the control handles 26 , 28 can take numerous forms , but are depicted schematically for ease of illustration . as an example , however , control handles 26 , 28 can take the form of a thumb - switch arrangement , a rotating - screw - type arrangement , or a ratcheting arrangement . such control handle means are well known in prior art catheter - delivery systems . inner member 22 has a proximal end 30 and a distal end 32 . inner member comprises a catheter 34 which has proximal end 36 and distal end 38 . the catheter 34 may be surrounded by a firstjacket 35 , adapted to lend lubricity to the inner member . inner member further comprises a guide wire lumen 40 , having proximal end 42 and distal end 44 . as exemplified in fig1 guide wire lumen 40 is configured to extend distally , from its proximal end 42 which is positioned adjacent to catheter 34 and just proximal of the distal end 38 thereof , to its distal end 44 which is located at the distal end 32 of the inner member . the profile of the guide wire lumen 40 extends distally along and adjacent the catheter 34 , and then deflects from being adjacent to the catheter so as to extend coaxially therewith . inner member 22 further includes a helical coil 46 having a proximal end 48 and a distal end 50 . the helical coil may be positioned surrounding the guide wire lumen 40 at a location on the guide wire lumen where it extends coaxially with the catheter 34 . as exemplified in fig3 the helical coil 46 may be connected to the catheter 34 by means of flexible arms 52 which extend from the coil to a ring 54 surrounding the catheter 34 and crimped onto the catheter . preferably , the helical coil , arms , and rings may be laser cut from a single tubular metallic structure . the arms are adapted to transfer axial force from the catheter 34 to the helical coil 46 . it will be appreciated that the helical coil 46 provides a degree of stiffness to the inner member at a position where there is no catheter , while at the same time providing adequate flexibility . with continued reference to fig1 inner member 22 further comprises a distal tip 56 which surrounds the guide wire lumen 40 at the distal end 32 of the inner member , and is shaped to provide a low profile a traumatic end so as to facilitate movement of the delivery system through the patient &# 39 ; s vasculature . a flexible protective layer 58 may cover the distal tip . a self expanding stent 60 in compressed state may be positioned about the distal tip 52 , held in place by outer member 24 . a blocking element 62 adapted to prevent proximal movement of the stent 60 relative to inner member 22 may be positioned between the distal tip 56 and the helical coil 46 , and may also be adapted to act as a radio - opaque marker . in an alternative embodiment , the helical coil may extend all the way to the distal end 32 of the inner member , with the distal tip 56 adapted to accommodate the coil . a second protective jacket 63 may surround the coil 46 , the guide wire lumen 40 , and portion of the catheter 34 , as exemplified in fig1 . the outer member 24 is configured to surround the inner member 22 , and may have a diameter at its distal end larger than at its proximal end in order to accommodate all the elements of the inner member . the self - expanding stent 60 in its compressed state is positioned around the distal tip 56 of the inner member 22 and is held in compressed state by the outer member 24 . as exemplified in fig4 - 6 , when the outer member is withdrawn proximally relative to the inner member , the stent 60 is permitted to assume its expanded state so as to support the body lumen within which it is implanted . a further component of the inner member 22 is a leaf spring 64 . in one embodiment the leaf - spring may be attached to the catheter 34 via a cylindrical sleeve 66 adapted to fit onto the catheter at a position proximal of the proximal end 42 of the guide wire lumen 40 . for purposes of assembly , the leaf - spring may be first attached to the cylindrical sleeve 66 by inserting the ends of the leaf - spring through the wall of the sleeve so that the central portion of the leaf - spring is positioned on the outside of the sleeve lumen while the ends of the leaf - spring are positioned within the sleeve lumen , as exemplified in fig1 a . the resulting combination may then be slid longitudinally over the catheter 34 to the desired position , as exemplified in fig1 . the sleeve may be fixed to the inner member either by adhesive , by heat welding , or by laser welding . alternatively , the sleeve may be heated prior to sliding it over the inner member , so that , when cooled , a friction fit to the inner member is achieved . once the leaf - spring 64 is fixed to the inner member , it is adapted to protrude into a slot 68 formed in the wall of the outer member 24 . in a further aspect , the leaf spring may also protrude beyond the slot so that a substantial portion of the leaf spring is positioned outside the outer member . it will be appreciated that when the leaf - spring protrudes into the slot it provides rotational alignment between the outer member and the inner member . by maintaining such rotational alignment , the ease with which a guide wire may be threaded through the delivery system 20 is greatly enhanced , as is explained more fully below . in one particular embodiment , the leaf - spring may be made of a material having highly elastic properties such as a nickel - titanium alloy including nitinol , or a chromium - cobalt - nickel alloy including elgiloy ™ ( manufactured and sold by elgiloy of elgin , ill . ), which will not readily lose its shape through plastic deformation should it be subjected to large strain . this quality is useful in that it has been found that , during assembly or storage of the delivery catheter 20 , the leaf - spring 64 may be accidentally subjected to strains which might plastically deform or fracture a leaf - spring of similar proportions made of stainless steel . in one embodiment , outer member 24 may be modified in that the perimeter of the slot 68 in the outer member may be reinforced by adding thereto a collar 69 formed of the same material as the outer member , so that the thickness of the outer member along the longitudinal edges of the slot is greater than the overall average thickness of the outer member . the collar may be connected to the outer member by adhesive or known heat or laser welding techniques . it will be appreciated that the ability of the outside catheter to resist bending is reduced in the vicinity of the slot , and thus accidental excessive bending at the location of the slot may cause the outer member to plastically deform and form a permanent kink along a longitudinal edge of the slot , which may render the delivery assembly unusable . thus , reinforcement of the outer member in the vicinity of the slot as described above may reduce accidental damage of such kind . the slot itself may be cut into the outer member and the collar with a sharp edge , or , alternatively , by known means using laser . with reference to fig4 - 6 , preparation for deploying a stent within a patient ( not shown ) using the delivery assembly of the present invention may commence using procedures which are well - known in the art , with the positioning of a guide wire 70 in the vasculature of the patient , after which the proximal tip ( not shown ) of the guide wire is left protruding from the patient . the proximal tip is then inserted in the distal end 44 of the guide wire lumen 40 and threaded through the guide wire lumen until the proximal tip emerges from the proximal end 42 of the lumen . when the proximal tip of the guide wire is further advanced proximally from the proximal end 42 of the guide wire lumen , it may first contact the leaf - spring 64 and then deflect outwardly to emerge from the slot 68 in the outer member 24 . while the short cross section of the leaf - spring may be generally rectangular ( fig2 a ), in order to facilitate outward deflection of the guide wire the short cross sectional profile of the leaf - spring may depart from a rectangular shape , and may either have a generally “ u ” shape or a generally “ v ” shape as exemplified in fig2 b and 2 c . the leaf - spring may be adapted to remain engaged within the slot after the guide wire is advanced through the slot , as exemplified in fig4 but to disengage at a later stage , as set forth below . the delivery system 20 is then advanced over the guide wire and its distal portion is inserted into the patient as required . in order to implant the self - expanding stent 60 , the guide wire 70 is positioned in a patient &# 39 ; s body lumen , at vessel wall 72 , and typically guide wire 70 extends past a stenosed region 74 . the catheter 20 is advanced along the guide wire until the stent 60 is positioned within stenosed region 74 . as exemplified in fig5 and 6 , self - expanding stent 60 is implanted in stenosed region 74 by moving outer member 24 in a proximal direction , either while simultaneously moving inner member 22 in a distal direction or while holding it stationary relative to the patient . the leaf - spring 64 may be adapted to disengage from the slot when the outer member is moved proximally over the inner member , in that the outer member may depress the leaf - spring and , also , the outer member itself may slightly deform so as to pass over the leaf - spring . as portions of self - expanding stent 60 are no longer contained by outer member 24 , the stent will expand radially outwardly into contact with the vessel wall 72 in the area of stenosed region 74 . when fully deployed and implanted , as shown in fig6 the stent 60 will support and hold open the stenosed region 74 so that blood flow is not restricted . it will be appreciated that , after the leaf - spring is disengaged from the slot and during proximal movement of the outer member 24 relative to inner member 22 , the leaf - spring 64 represents no appreciable resistance to the movement of the outer member 24 , as the leaf - spring is no longer engaged in the slot 68 of the outer member but may slide against the inner wall of the outer member . after stent 60 is implanted and contacts stenosed region 74 , the catheter 20 and guide wire 70 are withdrawn from the patient &# 39 ; s vascular system . the stent as described herein can be formed from any number of materials , including metals , metal alloys and polymeric materials . preferably , the stent may be formed from metal alloys such as stainless steel , tantalum , or the so - called heat sensitive metal alloys such as nickel titanium ( niti ). stents formed from stainless steel or similar alloys typically are designed , such as in a helical coil or the like , so that they are spring biased outwardly . with respect to all of the embodiments disclosed above , inner member 22 and outer member 24 can be formed from polymeric materials including polyurethanes , polyethylenes , polyethylterpthalate , and nylons . similarly , sleeve 66 can be formed from polyurethane , elastomeric polyesters and the like . generally speaking , the more proximal portions of inner member 22 and outer member 24 will be formed of a polymeric material that is stiffer than the distal section so that the proximal section has sufficient pushability to advance through the patient &# 39 ; s vascular system . on the other hand , the more distal portion of inner member 22 and outer member 24 can be formed of a more flexible material so that the distal portion of the catheter will remain flexible and track more easily over the guide wire . other modifications and improvements may be made without departing from the scope of the invention . for example , the leaf spring is not limited to the shape exemplified in the drawings , but may be any expanding member and may assume any shape which expands to protrude through an opening or slot in the outer member . accordingly , it is not intended that the invention be limited , except as by the appended claims .

US-91949001-A

a training device used by a golfer to visually analyze their body position during their golf swing . the device generally includes a base with a first indicator , and a front plate with a second indicator . in use , the device is positioned in front of the golfer with the first and second indicators being visually aligned . the golfer visually watches the relative positions of the indicators during the course of the swing . by observing the degree of sway in real time , the golfer can limit sway in the back swing and control it on the downswing enabling the golfer to stay behind the ball thus making proper impact possible . some sway during the golf swing is inevitable . the device enables the golfer to have awareness of the degree and direction of sway and the dynamic timing of sway position at impact .

the present application is directed to a training device for use by a golfer to maintain their body in a proper position during their golf swing . the device basically includes a base and a plate that the golfer can visually observer during their golf swing . each of the base and plate include indicators that are visually aligned relative to each other prior to the golf swing . the golfer observes the device during the course of the swing . the indicators remain visually aligned when the golfer maintains their body sway relative to a line perpendicular to the ball flight line . the indicators become visually misaligned when the golfer moves their body during the golf swing . the device provides a straight - forward mechanism for a golfer to visually determine the position of their body and therefore the resultant body position during their golf swing . fig1 illustrates an embodiment of the device 10 used for the golfer to visually analyze their body position during their golf swing . the device 10 generally includes a base 20 with a first indicator 21 , and a front plate 30 with a second indicator 31 . in use , the device 10 is positioned in front of the golfer with the first and second indicators 21 , 31 being visually aligned . the golfer visually watches the relative positions of the indicators 21 , 31 during the course of the swing . the golfer maintains the proper body position when the indicators 21 , 31 remain aligned during the course of the swing . the golfer has improper position when the indicators 21 , 31 become misaligned during the course of the swing . the base 20 includes a top side 22 that faces upwards when in use , and an opposing bottom side 23 . the base 20 further includes a first end 24 that faces towards the golfer when the device 10 is in use , and an opposing second end 25 . the base 20 may include various shapes and sizes depending upon the context of use . in one embodiment as illustrated in fig1 , the base 20 includes a generally rectangular shape . the first indicator 21 is positioned along the top side 22 for visual alignment by the golfer . the indicator 21 extends from the first end 24 towards the second end 25 . the indicator 21 may extend the entire length of the base 20 between the first and second ends 24 , 25 as illustrated in fig1 , or may extend just a limited portion of the length . the indicator 21 may be evenly positioned along the width of the base 20 ( i . e ., equi - distant from each lateral side ) as illustrated in fig1 , or may be positioned in closer proximity to one of the lateral sides . the indicator 21 is positioned along the top side 22 forming a first section 27 on a first lateral side and a second section 28 on a second lateral side . the first and second sections 27 , 28 include visually different appearances . the different visual appearances may be caused by but are not limited to different colors , patterns , textures , and combinations thereof . in one specific embodiment , the first section 27 includes a first color , and the second section 28 includes a different second color . the indicator 21 may include a variety of different aspects . in one embodiment as illustrated in fig1 , the indicator 21 is formed by the boundary of the two sections 27 , 28 . in another embodiment as illustrated in fig2 , the indicator 21 is a line that is visually distinct from either of the two sections 27 , 28 . in one embodiment , the line includes a first color ( e . g ., black ), and the two sections 27 , 28 are each different colors . the indicator 21 may also have different shapes . in one embodiment as illustrated in fig1 and 2 , the indicator 21 is straight . in another embodiment , the indicator 21 includes a non - linear shape . fig3 includes the indicator 21 with a series of straight segments connected at various angles . other embodiments may include a curved shape or segments , or various combinations of segments with different shapes . further , additional embodiments may include two or more separate indicators 21 . in one specific embodiment , each of the separate indicators 21 includes a common shape . in the various embodiments , the width of the indicators may be constant along the length , or may vary . the indicators 21 may include lines that extend along a portion or entirety of the base 20 . the indicators 21 may also include various other shapes , such as a circle , rectangle , design , picture , etc . the plate 30 is positioned in front of the base 20 when viewed by the golfer . the plate 30 may include a first end 33 and an opposing second end 34 . the plate 30 is operatively connected to the base 20 with the first end 33 in proximity to the first end 24 of the base 20 . the plate 30 may include a variety of different shapes and sizes . in one embodiment , the size and shape of the plate 30 are substantially the same as the base 20 . the plate 30 includes a transparent section 32 that allows the user to visually see the base 20 through the plate 30 . the transparent section 32 may include the entirety of the plate 30 , or a limited section . fig1 includes the entire plate 30 forming the transparent section 32 . the transparent section 32 may be constructed from various materials , including but not limited to glass , plexi - glass , and lucite . in another embodiment as illustrated in fig4 , the plate 30 includes a transparent section 32 and an opaque section 35 . in one embodiment , a coating is applied to a surface of the transparent section 32 to form the opaque section 35 . an indicator 31 extends across a portion or an entirety of the transparent section 32 of the plate 30 . the indicator 31 extends in a lengthwise direction of the plate 30 between the first and second ends 33 , 34 . the indicator 31 may extend across an entirety of the length , or along just a limited section of the length . fig1 includes an embodiment with the indicator 31 extend across the entire length . the indicator 31 may include various shapes and sizes . in one embodiment as illustrated in fig1 , the indicator 31 is a substantially straight line with a constant thickness . other embodiments include the indicator 31 with a non - linear shape , such as a series of straight segments connected at various angles , an overall curved shape or curved segments , and various combinations of segments with different shapes . further , additional embodiments may include two or more separate indicators 31 . in one specific embodiment , each of the separate indicators 31 includes a common shape . in the various embodiments , the width of the indicators may be constant along the length , or may vary . the indicators 31 may include lines that extend along a portion or entirety of the plate 30 . the indicators 31 may also include various other shapes , such as a circle , rectangle , design , picture , etc . the indicators 31 may be the same or different than the indicators 21 . a hinge 40 may connect the base 20 with the plate 30 . the hinge 40 may include a first section 41 that is connected to the base 20 and a second section 42 that is connected to the plate 30 . the hinge 40 provides for adjusting an angular position α of the plate 30 relative to the base 20 . the hinge 40 provides for selectively positioning the device 10 between a closed orientation and an open orientation . the close orientation occurs when the device 10 is not in use and is in a folded arrangement that occupies a minimum of space . in one embodiment , the plate 30 and base 20 are in an overlapping arrangement with the plate 30 being substantially parallel with the base 20 . the open orientation positions the plate 30 relative to the base for the golfer to visually align the indicators 26 , 31 . this may include the plate 30 positioned at an angle α within a range of between about 10 - 90 degrees relative to the base 20 . this angle may vary depending upon a variety of variables , such as but not limited to the height of the golfer , the distance the golfer stands from the device 10 , the topography of the surface that the golfer is using . in some embodiments , the plate 30 is positioned at an angle greater than 90 relative to the base 20 when in use . the hinge 40 provides for relative movement between the base 20 and plate 30 . in one embodiment , the indicators 21 , 31 of the base 20 and plate 30 remain within a common plane at the various angular positions . in use , the device 10 is placed in an open position with the base 20 and plate 30 positioned at the desired angular position for the golfer to visually observe the indicators 21 , 31 . the device 10 is positioned in front of the golfer . in one embodiment , the device 10 is positioned with the indicators 21 , 31 positioned perpendicular to the swing of the golfer . the device 10 is positioned with the indicators 21 , 31 being aligned when the golfer is at their set position with the club aligned with the golf ball and prior to starting their golf swing . fig6 illustrates the view of the device 10 from the golfer in this set position . the device 10 is aligned with the indicators 21 , 31 aligned and in a visually overlapping arrangement . in this embodiment , the indicator 31 is a straight line that is positioned over the indicator 21 formed at the boundary of the sections 27 , 28 of the base 20 . the golfer watches the device 10 during the course of their golf swing . as the golfer &# 39 ; s body sways away from the ball during the back swing , the golfer observes that the indicators 21 , 31 become misaligned . the degree of misalignment is directly proportional to the amount of sway occurring in the swing . allowing the golfer to minimize sway away from the ball during the back swing causes a tighter , rounder coil of the body . the indicators also enable the golfer to know how far forward their body has moved during the downswing . when the golfer moves their body during the golf swing , the indicators 21 , 31 will become visually misaligned . fig7 illustrates the golfer &# 39 ; s view of the device 10 when the golfer moves their body backwards during the golf swing . the movement results in the golfer observing the device 10 from an angle with the indicator 31 moving forward relative to the indicator 21 and into the first section 27 . this visually confirms to the golfer that their body has moved backwards during the golf swing . similarly , fig8 illustrates the golfer &# 39 ; s view of the device 10 when the golfer &# 39 ; s body moves forward during the golf swing . the movement causes the golfer to observe the device 10 at an angle with the indicator 31 visually moving behind the indicator 21 . this visually confirms that the golfer has moved forward during the golf swing . the device 10 provides for real - time feedback to the golfer while they are making their golf swing . the golfer is then able to focus on working on keeping their body aligned during their golf swing . spatially relative terms such as “ under ”, “ below ”, “ lower ”, “ over ”, “ upper ”, and the like , are used for ease of description to explain the positioning of one element relative to a second element . these terms are intended to encompass different orientations of the device in addition to different orientations than those depicted in the figures . further , terms such as “ first ”, “ second ”, and the like , are also used to describe various elements , regions , sections , etc and are also not intended to be limiting . like terms refer to like elements throughout the description . as used herein , the terms “ having ”, “ containing ”, “ including ”, “ comprising ” and the like are open ended terms that indicate the presence of stated elements or features , but do not preclude additional elements or features . the articles “ a ”, “ an ” and “ the ” are intended to include the plural as well as the singular , unless the context clearly indicates otherwise . the present invention may be carried out in other specific ways than those herein set forth without departing from the scope and essential characteristics of the invention . the present embodiments are , therefore , to be considered in all respects as illustrative and not restrictive , and all changes coming within the meaning and equivalency range of the appended claims are intended to be embraced therein .

US-201213490227-A

methods and devices are disclosed for the delivery of a neurotransmitter from an implanted , neurotransmitter - secreting cell culture to a target region in a subject . the cell culture is maintained within a biocompatible , semipermeable membrane which permits the diffusion of the neurotransmitter therethrough while excluding viruses , antibodies , and other detrimental agents present in the external environment from gaining access . implantable cell culture devices are disclosed , some of which may be retrieved from the subject , replaced or recharged with new , neurotransmitter - secreting cell cultures , and reimplanted .

a method for the constitutive delivery of neurotransmitter to a localized target region of a subject suffering from a neurological deficiency , and a device for practicing this method has been devised . the method includes encapsulating neurotransmitter - secreting cells within a protective , selectively permeable membrane or cell culture device , and implanting the device in a target region of a subject . the target region may be any part of the subject &# 39 ; s anatomy which responds to and requires neurotransmitter for normal function . this region may be any part of the nervous system , but will most often be the brain , as it is the source of numerous neurological dysfunctions . the cells to be encapsulated and implanted may be any which secrete the desired neurotransmitter . they may be allografts , or cells from another of the same species as the subject in which they are to be implanted , or they may be xenografts , or those from another of a different species . more particularly , they may be a component of a body organ which normally secretes a particular neurotransmitter in vivo . preferable cells include those dopamine - secreting cells from the embryonic ventral mesencephalon , from neuroblastoid cell lines or from the adrenal medulla . more generally , any cell which secretes a neurotransmitter or a precursor , analog , derivative , agonist or fragment of a desired neurotransmitter having similar neurotransmitter activity can be used , including , for example , cells which elicit l - dopa , a precursor of dopamine and bromocriptine , a dopamine agonist . further , any cells which have been genetically engineered to express a neurotransmitter or its agonist , precursor , derivative , analog , or fragment thereof which has similar neurotransmitter activity are also useful in practicing this invention . thus , in such an approach , the gene which encodes the neurotransmitter , or its analog or precursor is either isolated from a cell line or constructed by dna manipulation . the gene can then be incorporated into a plasmid , which , in turn , is transfected into a set of cells for suppression . the cells which express the neurotransmitter can be grown in vitro until a suitable density is achieved . a portion of the culture is then used to seed the implantable device . ( see , e . g ., maniatis et al ., molecular cloning ( 1982 ), herein incorporated by reference for further discussion of cloning vehicles and gene manipulation procedures .) regardless of the source , the neurotransmitter - secreting cells as tissue fragments or culture aggregates are placed into an implantable , selectively permeable membrane which protects them from deleterious encounters with viruses and elements of the immune system . such protection is particularly important for preserving allografts or xenografts which are eventually considered foreign even in the &# 34 ; immuno - priviledged &# 34 ; brain . therefore , the membrane should bar viruses , macrophages , complement , lymphocytes , and antibodies from entry while allowing the passage of nutrients , gases , metabolic breakdown products , other solutes , and the neurotransmitter to pass therethrough . accordingly , any biocompatible and nonresorpable materials having pores enabling the diffusion of molecules having a molecular weight of up to about 50 , 000 daltons are useful for practicing the present invention , with acrylic copolymers , polyvinylidene fluoride , polyurethane isocyanates polyalginate , cellulose acetate , polysulfone , polyvinyl alcohols , polyacrylonitrile , derivatives , and mixtures thereof being the most preferable . the cell culture device may take any shape which will accommodate the cells to be encapsulated , and which will not cause undue trauma upon surgical implantation . a preferable implantable cell culture device 10 shown in fig1 is a tubular , selectively permeable membrane 22 having ends 12 and 14 through which neurotransmitter - secreting cells 25 are loaded into cell compartment 16 . ends 12 and 14 may then be permanently occluded with caps 17 and 19 or , alternatively , with an epoxy glue or sutures of a biocompatible and nonresorpable material like polypropylene . the device 20 as shown in fig1 can be surgically implanted into the brain of a subject such that membrane 22 is in immediate contact with brain tissues . the method of the present invention may include an additional step whereby the initially encapsulated and implanted cells are removed from the subject in the event that they cease to produce neurotransmitter , expire , or are no longer needed to correct the neurological dysfunction . as illustrated in fig2 retrieval of implanted cell culture device 20 is preferably accomplished by means of guide wire 18 which is permanently attached to end cap 17 or 19 . this wire may be constructed of any nonresorpable , biocompatible material with enough tensile strength to support the cell culture device . the cellular contents of the device may be replaced in the event that it is desirable to reimplant the device after its retrieval . a exemplary cell culture device useful in practicing this method is shown in fig3 . device 30 is tubular , having ends 12 and 14 reversibly covered with removable , friction - fitted caps 22 and 24 , respectively , to enable the extraction and replacement of cells 25 in cell compartment 16 with new cells . the device 30 as shown in fig3 can be surgically implanted into the brain of a subject such that guide wire 18 is located directly under the epithelial tissues of the head , and membrane 22 is in immediate contact with brain tissue . the following examples more fully illustrate preferred features of the invention . xm - 50 tubes ( amicon corp ., lexington , mass .) consisting of polyvinyl chloride acrylic copolymer and having an internal diameter ( id ) of 600μ and a wall thickness of 100μ were obtained . each tube was composed of a selectively permeable inner membrane supported by a trabecular network which was covered by an open polymer film . the inner membrane had a nominal molecular weight cut - off of 50 , 000 daltons . the polymer tubes were cleaned and sterilized , cut into sections approximately 3 - 4 mm in length , and capped at each end with an epoxy polymer glue . young male albino cd - 1 rats ( 250 - 300 g ) were anesthetized with an intraperitoneal injection of sodium thiopental ( 25 mg / kg ), and placed in a stereotaxic apparatus . the parietal cortex was exposed through a small craniotomy . the polymer tubes were implanted by gently pushing them into the parietal cortex parenchyma . skin closure was achieved with 6 . 0 polypropylene sutures . aseptic surgical technique was maintained through the procedure . cohorts of 3 animals received 3 - 4 mm length xm - 50 tubes for 1 , 2 , 4 , and 12 weeks . at retrieval time , deeply anesthetized animas were perfused transcardially with 200 ml of a heparinized tris buffer solution followed by 200 ml of 4 % paraformaldehyde and 0 . 1 % glutaraldehyde in tris buffer . samples of the striatum were excised and post - fixed overnight by immersion , and subsequently were transferred into 15 % and then 30 % buffered sucrose . once equilibrated , the samples were quick - frozen in dry ice . thick sections 20 - 25 mm were cut on a frozen sliding microtome . sections chosen for immunostaining were then incubated , free - floating , in primary antiserum for 3 days at 4 ° c . in 0 . 1 % triton x - 100 , 0 . 1m tris buffer , ph 7 . 4 with blanking serum . primary antiserol used were to glial fibrillary acidic protein ( gfap ) ( a gift from dr . larry eng , stanford university , palo alto , calif .) and to neuron - specific enolase ( nse ) ( dakopatts , denmark ). section were rinsed briefly in tris buffer prior to incubation in a secondary swine anti - rabbit antiserum ( 1 : 225 ) in tris buffer at room temperature . after rinsing , sections were incubated in a soluble complex of rabbit peroxidase - antiperoxidase ( pap ) ( dakopatts , denmark ) ( 1 : 100 ), and the reaction visualized with a solution of diaminobenzidine and hydrogen peroxide . sections were mounted , counterstained with cresyl violet , dehydrated , and coverslipped . reaction to the hollow tubes was analyzed with a zeiss im 35 microscope ( oberkochen , fed . rep . west germany ) interfaced with a video monitor . for ultrastructural examination , anesthetized animals were transcardially perfused with a modified karnovsky &# 39 ; s fixative . samples were post - fixed in 0 . 75 % osmium tetroxide , dehydrated , an then embedded in spurr &# 39 ; s low viscosity resin . semi - thin sections for light microscopy were cut and stained with toluidine blue and basic fuchsin . ultra - thin sections of selected specimens were stained with reynold &# 39 ; s lead citrate and uranyl acetate . electron microscopic analysis was performed with a phillips 410 . no neurological deficit was observed in any of the implanted animals . a necrotic zone was not detected around the polymer tubes for any time period as assessed by the nissl stain . nse immunolabeling showed the preservation of the typical columnar orientation of the cortical neurons neurons with typical apical dendrites were observed in close apposition to the polymer capsule membrane . reactive astrocytes as determined by gfap immunolabeling were observed up to 400 μm from the polymer capsule during the first 2 weeks post - implantation . the area in which the reactive astrocytes were detected diminished with time such that at 12 weeks , immunoreactive astrocytes were seen only in close apposition to the polymer membrane material . transmission electron microscopy ( tem ) showed minimal collagen deposition around the polymer capsule . normal synapses were seen within 3 - 5μ of the brain - implant interface . foreign body giant cells were not detected surrounding the polymer tube . microglia identified by their bipolar appearance and rod - like nucleus were observed in the wall trabeculae of the tubes . no cells entered the internal tubular space , demonstrating the selectively permeable nature of the polymer membrane . embryonic ( e14 - 16 ) mouse ventral mesencephalon were dissected into 1 mm 3 pieces , put in rpmi 1640 ( gibco laboratory , grand island , n . y .) and then cut into 8 - 10 smaller pieces . these pieces were mechanically placed into the polymer tube . the tube ends were then capped with an epoxy polymer glue . loaded capsules were implanted in the parietal brain cortex of rats as described above . implants were allowed to remain for 1 , 2 , 4 and 8 weeks before retrieval . animals with implants were sacrificed and examined as described in example i above . mouse embryonic mesencephalic tissue retrieved from polymer tubes implanted in the rat brain consisted of intact tissue interspersed with some necrotic tissue at the various implantation times . the tissue was usually centrally located in the tube . tem demonstrated the presence of well preserved neuronal cell bodies , axons , synapses , and glial cells . the presence of intact cells in the polymer capsule after several weeks of implantation suggests that free diffusion of nutrients occurs through the permselective membrane , and that the tissue is immunoprotected by the polymer membrane . the minimal tissue reaction to the polymer material by the host brain constitutes a favorable factor for free diffusion through the polymer membrane experimental parkinsonism can be induced in rats by unilateral destruction of the mesostriatal dopamine system using the neurotoxin 6 - hydroxydopamine ( 6 - ohda ). the drug - induced unilateral lesions initiate a rotational or circling response that can be easily quantitated by pharmacological methods . under the influence of the dopamine agonist metamphetamine , rotational behavior , i . e ., the number of rotations per time interval correlates to the extent of the lesion . metamphetamine induces the animal to rotate ipsilaterally ( i . e ., towards the side of the lesion ). lesions were induced with 12 μg 6 - ohda - hcl disolved in 8μl 0 . 2 mg ascorbic acid / ml 0 . 9 % nacl . this solution was injected stereotaxically over a 5 minute period . the animals were tested for unilateral lesions 7 - 10 days after injection . 5 mg metamphetamine per kg rat was injected . rotational behavior was then recorded 30 minutes after injection . rotations were recorded over 6 one min . intervals with at least a 2 min . rest period between recordings . to stimulate the animals a high frequency ultrasonic device was used during the one minute recording intervals . animals that rotate consistently at least 8 turns / min . were used for the transplantation test . embryonic ( e14 - 16 ) mouse mesencephalic tissue was isolated , placed in tissue culture medium , and cut into tiny pieces . these tissue fragments , or alternatively cells from the la - n - 5 human neuroblastoma cell line ( a gift of j . de ybenes , columbia univ ., n . y .) were aspirated or mechanically inserted into the lumen of 3 - 4 mm long polymer capsules which were then capped with a polymer glue . 5 young male albino cd - 1 sprague - dawley rats ( 250 - 300 g ) ( charles river labs ) having base - line rotational values in the range of 11 - 12 turns / min . pre - transplantation received mesencephalic xenografts . the filled capsules each containing approximately 10 6 cells per capsule were transplanted , one capsule per animal , in the caudate / putamen portion of the brain with the hope that part of the capsule would be bathed in the ventricular system . no significant changes in behavior were observed within the first 2 weeks post - transplantation . by 3 weeks a reduction in rotational behavior became evident . after 4 - 5 weeks , the animals were rotating about 2 - 3 turns / min .

US-8550493-A

an improved children &# 39 ; s marionette theatre for self - propelled puppet - like objects utilizing a housing formed from collapsible sides , back and ceiling members that may be readily collapsed into a relatively flat compact structure for ease of transport and storage . the housing defines a stage on which puppet - like objects are displayed and includes an upper ceiling member disposed over the stage . the upper ceiling member has path - like guide means formed by a track suspended from the under surface of the ceiling member and on which self - propelled puppet transport vehicles are supported . means are provided for securing puppet - like objects to the self - propelled vehicles for display and movement across the stage . the puppet - like objects may comprise facsimiles of the sun , earth , moon and other planets as well as the inclusion of lighting effects to simulate stars , galaxies and constellations .

fig1 is a front perspective view of a housing ( 11 ) having a front central opening through which a viewer observes the stage area ( 12 ) of the children &# 39 ; s animated marionette theatre formed in part by the housing ( 11 ). for a more detailed description of suitable material and methods for forming the housing ( 11 ), reference is made to co - pending u . s . pat . no . 3 , 812 , 611 , the disclosure of which is hereby incorporated by reference in its entirety . briefly , however , it can be said that the housing ( 11 ) may be formed from any suitable , inexpensive material such as paper board , cardboard , plastic or the like and generally has side , top , and at least partial back walls which may be hinged together to form a collapsible box . the front of the housing may be closed by suitable curtain material shown generally at ( 13 ) and ( 14 ), that is drawn open at the commencement of a play in the usual manner . the curtain material preferably does not draw away from the top portion of the front of the housing ( 11 ) in order that the top portion of the curtain material hides the mechanical details of the theatre from a viewer as will be described hereinafter . however , for convenience , in fig1 the top portion of the curtain has been shown broken away to enable the viewer to see , at least in part , some of the mechanisms to be described hereinafter . the animated children &# 39 ; s marionette theatre shown in fig1 differs from the theatre disclosed in co - pending u . s . pat . no . 3 , 812 , 611 primarily in the design and construction of the upper ceiling member ( 15 ). as best seen in fig2 of the drawings , the upper ceiling member ( 15 ) of the current invention comprises an essentially solid , flat member supported on the side walls of housing ( 11 ). as shown in dotted outline form at ( 16 ) in fig1 the upper ceiling member ( 15 ) has secured to its under surface a guide means ( 16 ) that is formed by a track in which at least one self - propelled puppet transport vehicle ( 17 ) is supported . the track ( 16 ) may be comprised by two opposing essentially z - shaped track members ( 18 ) and ( 19 ) that are secured to the under surface of the upper ceiling member ( 15 ) by screws ( 21 ). the track members ( 18 ) and ( 19 ) include inwardly projecting edges or lips that are spaced apart and define a central opening throughout the extent of the guide track ( 16 ) formed by the track members ( 18 ) and ( 19 ). as disclosed in the above - referenced co - pending u . s . pat . no . 3 , 812 , 611 , the self - propelled puppet transport vehicle ( 17 ) may comprise a mechanical spring wound toy tractor , an electric battery driven toy tractor , or other similar self - propelled vehicle having wheels ( 23 ) that ride along the upper surfaces of the inwardly extending lips ( 22 ) of track members ( 18 ) and ( 19 ). the self - propelled puppet transport vehicle ( 17 ) has a lower rotatable shaft ( 24 ) projecting from its under surface and includes a spring wound , electric drive or other suitable motor mechanism ( not shown ) for rotating the shaft ( 24 ) at some predetermined rotational speed . this mechanism for rotating shaft ( 24 ) is in addition to the drive mechanism for causing the wheels ( 23 ) to move the transport vehicle ( 17 ) along the guide path formed by the track members ( 18 ) and ( 19 ). secured to the lower end of the rotatable shaft ( 24 ) is a flat , circular rotatable member ( 25 ) of the lazy susan - type . the member ( 25 ) is secured to shaft ( 24 ) so that it rotates in synchronization with shaft ( 24 ). as a result of this arrangement , the lazy susan member ( 25 ) will be slowly rotated as the puppet transport vehicle ( 17 ) is caused to move along the extent of the guide path ( 16 ) defined by the track members ( 18 ) and ( 19 ). to facilitate loading and unloading the entire arrangement of the transport vehicle ( 17 ) and attached rotatable lazy susan member ( 25 ) onto the track members ( 18 ) and ( 19 ), it is desirable that the elongated track ( 16 ) defined by the track members ( 18 ) and ( 19 ) extend from one open - ended point ( 16a ) at the edge of the ceiling member ( 15 ) ( preferably the back edge ) over a predetermined path and terminate at a second open - ended point ( 16b ) on an edge of the ceiling member . as a result of such construction , the self - propelled puppet transport vehicles readily may be loaded and unloaded on the track along the open accessible back edge of the ceiling member . in the embodiment of the invention shown in fig1 and 2 , the particular puppet - like objects which are depicted are intended to represent the sun shown at ( 31 ), the earth shown at ( 32 ) and moon ( 33 ) together with other planets of the universe including mercury ( 34 ), venus ( 35 ), mars ( 36 ), jupiter ( 37 ) and saturn ( 38 ). the sun ( 31 ) is represented by a rather large lightbulb located at the center of rotation of the lazy susan member ( 25 ). the planet mercury is located closest to the sun is mounted on a short rotating arm ( 39 ) which in turn is driven by a self - rotating mechanism ( 41 ) of conventional construction for causing the arm ( 39 ) and lightbulb ( 34 ) representing the planet mercury to be rotated around the shaft ( 24 ) at a rate of rotation faster than that of shaft ( 24 ). similarly , the lightbulb representing the earth ( 32 ) has a small rotating arm ( 42 ) and self - rotating mechanism ( 43 ) attached thereto for causing the smaller lightbulb ( 33 ) representative of the moon to be rotated about the earth . the two outermost planets , saturn ( 38 ) and jupiter ( 37 ), likewise are mounted on respective elongated rotating lever arms ( 44 ) and ( 45 ) which , in turn , are rotated relative to the shaft ( 24 ) and rotating lazy susan member ( 25 ) by self - rotating mechanisms ( 46 ) and ( 47 ), respectively . other puppet - like objects could be used in place of the sun , earth and other planets depicted , should it be desired . for example , it would be entirely possible to suspend an array of horses from the lazy susan member ( 25 ) in the manner of the merry - go - round . further , in place of the rotating shaft ( 24 ) and lazy susan member ( 25 ) it would be entirely possible to suspend individual puppet - like characters from a general purpose puppet transport vehicle ( 17 ) in a manner similar to that described in the above - referenced co - pending u . s . pat . no . 3 , 812 , 611 . fig5 is a schematic illustration of a suitable , mechanically wound spring type of general purpose , self - propelled puppet transport vehicle usable with the invention . the general purpose puppet transport vehicle shown in fig5 corresponds identically to that illustrated and described in fig4 and 4a of u . s . pat . no . 3 , 812 , 611 with the exception that the letter a has been appended to each of the reference numerals employed in connection with fig5 . for a more detailed description of the general purpose puppet transport vehicle shown in fig5 reference is made to the appropriate portions of co - pending u . s . pat . no . 3 , 812 , 611 . for the purpose of the present disclosure , it is believed sufficient to point out that the general purpose puppet transport vehicle 17 shown in fig5 includes a pair of hooks 48a and 50a on which puppet - like objects readily can be attached to the puppet transport vehicle by a child playing with the marionette theatre . other forms of readily manipulated attaching means could be employed in place of the hooks 48a and 50a as would be obvious to one skilled in the art . the general purpose puppet transport vehicle 17 shown in fig5 comprises a mechanical , spring wound toy tractor having wheels 31a supported from a body member 32a that contains a coil spring 33a capable of being wound around a shaft 34a by a key 35a . shaft 34a has a drive gear 36a keyed to it which meshes with and drives a speed increasing gear 37a that in turn drives a pinion 38a and worm gear 39a secured to the axle that drives wheels 31a . other drive configurations are possible and for that matter a small battery operated , electric motor drive could be employed for driving the general purpose , self - propelled puppet transport vehicles 25 . the term &# 34 ; general purpose &# 34 ; is derived from the fact that the puppet transport vehicle shown in fig5 can be employed to move any desired puppet - like character or object across the stage of the marionette theatre in accordance with the wishes of a child operating the marionette theatre . in this manner , considerable diversity in the nature of the puppet plays which can be presented with the theatre can be achieved . because of the ease in changing puppet - like objects to be suspended from the general purpose transport vehicle , presentation of a puppet play by a child is facilitated . in addition to the above described members and objects , it would be desirable for completeness and authenticity to include a background screen in the area to the rear of the marionette theatre housing ( 11 ) upon which pictures of stars , constellations , galaxies and perhaps clouds can be displayed from a suitable light projector such as those indicated at ( 51 ) and ( 52 ). with such a background , it will be appreciated that a considerable educational effect can be made on young minds with a playhouse constructed in accordance with the present invention by using the rotating lazy susan member ( 25 ) with the sun ( 31 ) as its center and the various planets of the universe rotating about it , coupled with an appropriate description of the makeup of the universe . by changing the backdrop and lighting effects to show the earth , and utilizing only the sun ( 31 ), demonstrations can be made of how the sun comes out and rises to the east and sets in the west with an appropriate description tied to the movement of the puppet transport vehicle as it causes the sun ( 31 ) to rise by moving out and across the front of the stage and then set as it moves toward ( 16b ) in its path of movement from ( 16a ) to ( 16b ). other plots and arrangements will be suggested to those skilled in the art in the light of these teachings . fig3 is a partially broken away perspective view of a second embodiment of an animated children &# 39 ; s marionette theatre according to the present invention . in the embodiment of the invention shown in fig3 the upper ceiling member ( 15 ) itself is provided with a central opening and a circular , rotatable ceiling portion ( 15a ) is provided which acts as a lazy susan member . the peripheral edge of rotatable ceiling portion ( 15a ) may be provided with an overriding lip portion which is supported by and rides on suitable ball bearing , roller bearing , or other anti - friction members ( not shown ). a notched gear tooth rack is formed around the peripheral edge of rotatable ceiling portion ( 15a ) as indicated at ( 61 ) in fig4 and coacts with a pinion gear drive indicated generally in dotted outline form at ( 62 ) in fig1 for causing the rotatable ceiling portion ( 15a ) to be slowly rotated . suspended from the hub of the central rotatable ceiling portion ( 15a ) is a fixed shaft ( 24 ) which supports a plurality of rotating arms ( 44 ), ( 45 ), ( 63 ), ( 64 ), ( 65 ), and ( 39 ), for supporting the various planets represented by the lightbulbs ( 32 ) and ( 34 - 38 ), and the enlarged lightbulb ( 31 ), secured to the end of shaft ( 24 ) representing the sun . a plurality of rotatable self - driven mechanisms ( 41 ), ( 66 - 68 ) of conventional known construction coact with the central shaft ( 24 ) to cause the rotating arms ( 44 ), ( 45 ), ( 63 - 65 ), and ( 39 ), to be rotated relative to the central shaft ( 24 ). the speeds of rotation of each of the drive mechanisms may be different to allow for relative rotation between the sun and the various planets . here again , the planet earth represented by the lightbulb ( 32 ) is provided with an additional lever arm ( 42 ) and self - rotating mechanism ( 43 ) for causing the smaller bulb ( 33 ) representative of the moon to be rotated about the earth . with this arrangement , the universal arrangement of the planets , the sun and the moon are not caused to be moved over the ceiling portion of the marionette theatre but remain relatively fixed in the center of the stage , although rotated relative to each other . on the under surface of the central rotating ceiling member portion ( 15a ), a guide means ( 16 ) is provided which is formed by essentially z - shaped track members ( 18 ) and ( 19 ) mounted by set screws or other suitable means to the under surface of ( 15a ) to form a circular track , as indicated by ( 16 ) in fig1 around the periphery of the rotatable ceiling member . a puppet transport vehicle ( 17 ) is mounted in and supported by the track members ( 18 ) and ( 19 ) on the under surface of rotatable seiling member ( 15a ). puppet transport vehicle ( 17 ) has suspended from it a puppet - like object which may be in the form of a space ship as shown at ( 71 ). with this arrangement , the lazy susan ceiling member ( 15a ) is caused to rotate together with the self - rotating drive mechanisms ( 41 ) and ( 66 - 68 ) for causing relative rotation of the various planets , the earth and the moon with respect to the sun . concurrently with this action , the space ship ( 71 ) is caused to move through space over the guide means ( 16 ) provided by the track members ( 18 ) and ( 19 ). if desired , suitable switching accommodations can be provided at the back of the ceiling member ( 15 ) that connect with the track ( 16 ) in the rotatable ceiling member portion ( 15a ) in a manner similar to track switches of a railroad track , to facilitate loading and unloading of the puppet transport vehicles onto track members ( 18 ) and ( 19 ). further , parallel track arrangements may be included as indicated by the second dotted line set of track ( 72 ) shown in fig3 of the drawings . also , suitable light projectors such as shown at ( 51 ) may be provided along with a backdrop for projecting light images of stars , galaxies , constellations , clouds or other images needed to provide a realistic effect for the viewer of the marionette theatre . from the foregoing description , it will be appreciated that the present invention provides a new and improved animated children &# 39 ; s marionette theatre . the new and improved animated children &# 39 ; s theatre includes an improved construction for the suspended track on which a puppet transport vehicle moves together with an improved lazy susan - type of suspension for the various puppet - like objects being displayed on the stage of the theatre . having described several embodiments of a new and improved animated children &# 39 ; s marionette theatre according to the invention , it is believed obvious that other modifications and variations of the invention will be suggested to those skilled in the art in the light of the above teachings . it is , therefore , to be understood that changes may be made in the particular embodiments of the invention described which are within the full intended scope of the invention as defined by the appended claims .

US-68648676-A

apparatus which can be embodied in an electronic wristwatch monitors the integrity of a wrist strap ground . an input terminal to which a known ground is coupled is provided . an oscillator produces a fixed frequency which is mixed with a signal from the input terminal to provide a composite signal . the composite signal is coupled to one input of an exclusive or - gate . the other input of the exclusive or - gate is coupled directly to the output of the oscillator . the output of the or - gate is processed to produce an output signal indicative of the phase relationship between the oscillator output and the composite signal . when the input terminal is grounded , the phase relationship between the oscillator output and the composite signal changes , resulting in a change in the output signal which can be used to trigger an indicator to indicate to a user whether he or she is properly grounded .

fig1 illustrates in block diagram form a ground monitoring circuit in accordance with the present invention . a shielded ground cable 12 is coupled at a first end thereof to a source of electrical ground when in use , which ground is illustrated in fig1 as a conductive mass 10 . the other end of ground cable 12 is coupled to an input terminal 80 of the circuitry . input terminal 80 is connected to the center or &# 34 ; main &# 34 ; conductor of shielded cable 12 through a current limiting resistor 14 on the order of 1 megohm . resistor 14 protects the user of the device against electric shock should there be an internal short in the detector circuitry . resistor 14 is also used as part of a ground cable fault detection circuit described below . an additional current limiting resistor 16 on the order of 100 k - ohms is coupled between the conductive shield of ground cable 12 and the monitor circuit ground ( which is isolated from the earth ground represented by conductive mass 10 ). resistor 16 will protect a user from shock should the shield of ground cable 12 become exposed and connected to a hazardous voltage source . an additional cable fault test resistor 13 ( on the order of megohm ) is coupled between the main conductor and shield of cable 12 at the first end thereof . resistor 13 serves as the predominant input impedance path to the ground monitoring circuit . the combination of resistors 13 , 14 and 16 form a ground cable impedance that can be monitored to determine whether the ground cable is in proper working order or is open or shorted . the cable impedance forms part of a voltage divider with resistor 15 that is connected to voltage source vcc . the voltage divided between resistor 15 and the cable impedance is monitored at input terminal 80 by a comparator 19 which compares the voltage at input terminal 80 with a reference voltage v ref1 input to the comparator at terminal 23 . if the cable impedance is proper , the voltage at input terminal 80 will be within a predetermined range and the output of comparator 19 on line 21 will indicate that the cable is in good working order . on the other hand , for example , if cable 12 is shorted internally , resistor 13 will also be shorted and the cable impedance will consequently drop . this will cause the voltage at input terminal 80 to drop and comparator 19 will output a signal on line 21 to indicate a cable fault condition . a cable fault condition will also be output should the cable 12 become open or disconnected from input terminal 80 . input terminal 80 and hence , the electrical ground source 10 is coupled to a body portion ( e . g ., wrist ) of a user through a conductive metal electrode 50 ( fig5 ) which is placed into skin contact with the user &# 39 ; s body . thus , a user of the present apparatus will be grounded when ground cable 12 is coupled to a proper electrical ground . a signal applied to input terminal 80 will pass to a filter 18 which may be a high - pass filter or a band - pass filter . the purpose of filter 18 is to suppress any a . c . hum ( e . g ., 60 hz ) which may be present at input terminal 80 . in normal operation , input terminal 80 would be connected to ground via ground cable 12 . however , if a proper ground connection is not made , some other signal will be present at input terminal 80 and detected by the remainder of the circuitry of fig1 . the signal from input terminal 80 passes through filter 18 and is mixed at mixer 22 with a stable oscillator signal from oscillator 20 . variable resistance 26 is provided to adjust the sensitivity of the ground monitoring circuit . resistor 26 will also introduce a delay into the oscillator signal as it travels to mixer 22 . mixer 22 in effect beats the filtered signal from input terminal 80 with the stable periodic signal from oscillator 20 . the resultant &# 34 ; composite signal &# 34 ; is amplified by amplifier 24 and input to one input of an exclusive or - gate 30 . in balanced condition , amplifier 24 has enough gain to square up the signal and guarantee digital signal levels to drive exclusive or - gate 30 . the other input of exclusive or - gate 30 is coupled to the output of oscillator 20 via a delay circuit 25 . the function of the delay circuit 25 is to match the delay inherent in mixer 22 , resistor 26 , and amplifier 24 so that absent any other influences ( e . g ., ground at input terminal 80 ), the two signals input to exclusive or - gate 30 will be in phase and balancing will have been achieved . in operation , if input terminal 80 is properly grounded , then the condition of the balanced circuit comprising mixer 22 , amplifier 24 , delay 25 , and resistor 26 will be disrupted . the resultant imbalance will cause the digital waveform from amplifier 24 to no longer match the stable waveform output from delay circuit 25 . the failure of the two signals input to exclusive or - gate 30 to match ( i . e ., remain in phase ) will cause the or - gate output to go high in proportion to the imbalance . a detector 32 is coupled to receive the output of exclusive or - gate 30 and integrates the or - gate output to produce a corresponding d . c . logic level . comparator means 34 coupled to the output of detector 32 and to a reference voltage v ref2 at terminal 36 determines whether the d . c . logic level is above or below a predetermined threshold value . the threshold value ( established by v ref2 ) is set so that a d . c . logic level above the threshold is indicative of a proper ground condition at terminal 80 . likewise , a d . c . level below the threshold value indicates that input terminal 80 is not properly grounded . thus , the output of comparator 34 on line 35 can be used to drive a visual display ( e . g ., light emitting diode or liquid crystal display ) and / or an aural alarm to indicate to a user whether a proper ground is present at input terminal 80 . those skilled in the art will appreciate that the combination of oscillator 20 , exclusive or - gate 30 , and detector 32 form a frequency discrimination phase - lock - loop known in the art for other purposes such as radio frequency signal tuning . it will also be appreciated that the circuitry of the ground monitor will require a stable voltage supply ( e . g ., using conventional regulators ) in order to assure balanced operation . this is particularly important when the circuit is battery powered , to maintain proper operation as the battery wears down . the output of comparator 34 on line 35 can be used to drive a display 42 and / or optionally an alarm 43 as shown in fig2 . in such instance , display interface and decoder circuitry 40 will decode a signal from comparator 34 to display an appropriate signal ( e . g ., &# 34 ; gnd &# 34 ; as shown at 66 in fig4 ) or inhibit an audible alarm when a proper ground is present at input terminal 80 . integrated circuits which include decoder 40 and appropriate drivers for display 42 and / or alarm 43 are well known in the art . the display interface circuitry and decoder 40 can be incorporated in an integrated circuit that also includes the electronics for a wristwatch , and the ground monitor can share the display used to display the time . the ground monitoring circuitry of fig1 is intended to be incorporated in integrated circuit form in combination with a wrist strap . in a preferred embodiment , the wrist strap is packaged together with an electronic watch as best illustrated in fig4 . in such an embodiment , it is desirable to ensure that the wristwatch / wrist strap / ground monitor 60 is properly worn on the wrist of a user . in order to achieve such assurance , an additional terminal or contact 48 can be provided on the back of the wristwatch / wrist strap / ground monitor 60 as shown in fig5 . in use , the case 62 of the apparatus is secured against the wrist of a user by a strap 70 in a conventional manner . contacts 48 and 50 ( which are interleaved for reliable skin contact over a large surface area ) will be in intimate contact with the user &# 39 ; s wrist . contact 50 is connected to input terminal 80 of the circuitry shown in fig1 so that when ground cable 12 is properly grounded , the user will also be properly grounded through his or her wrist . the circuit of fig3 will ensure that the wristwatch / wrist strap / ground monitor 60 is properly worn by the user by inhibiting a body contact signal on output line 49 of gate 44 , which is normally used to drive a display or inhibit an alarm signal to the user , unless both contacts 48 and 50 are in intimate contact with the user &# 39 ; s skin . as already stated , contact 50 is normally connected to ground . contact 48 is coupled to the input of a gate and to a power source vcc through voltage divider resistor 46 . if proper skin conductivity is present across contacts 48 and 50 , gate 44 will turn on and provide a body contact signal on output line 49 . this signal is input to the display logic via decoder 40 to provide a display to the user that proper body contact has been achieved . two embodiments of a combination wristwatch / wrist strap / ground monitor are illustrated in the drawings . in fig4 the ground monitor shares the display used by the wristwatch , so that when the ground monitoring circuit is not in operation , the wristwatch will display the current time , as indicated in phantom at 68 . alternatively , as shown in fig6 a unitary case 82 can hold a wristwatch display 84 together with a separate ground monitor display 86 . display 84 will always show the current time . display 86 can be , for example , a liquid crystal display that has minimum power requirements and includes three bars 90 , 92 and 94 together with the legend &# 34 ; gnd &# 34 ;. bar 90 is displayed to indicate that the ground cable 12 is in proper working order and is triggered by the output signal from comparator 19 on line 21 . bar 92 is displayed to indicate that the wristwatch / wrist strap / ground monitor 60 is properly worn by the user and is triggered by the output signal from gate 44 on line 49 . bar 94 is displayed to indicate that input terminal 80 is connected to a proper electrical ground and is triggered by the output signal from comparator 34 on line 35 . when all three conditions are met and each of bars 90 , 92 and 94 is displayed , the legend &# 34 ; gnd &# 34 ; will also be shown in display 86 to inform a user that the ground monitor is operating properly and a proper ground has been effected . if the &# 34 ; gnd &# 34 ; legend is not displayed , at least one of bars 90 , 92 , or 94 will also be off , thereby signalling to the user which of the three conditions has not been met . the ground monitor display is driven by decoder logic 40 which receives signals designating the state of each of the three conditions on lines 21 , 35 , and 49 . alarm 43 can optionally be provided to give an audible signal when all three conditions are not met . miniature piezoelectric alarms for wristwatches are well known in the art , and a similar device can be used for alarm 43 . the wristwatch / wrist strap / ground monitor 60 shown in fig4 and 6 can be removably coupled to a proper ground source via ground cable 12 which is terminated at one end thereof with a jack 72 that plugs into terminal 80 , and at the other end thereof with a banana plug 76 which plugs into a known ground source . banana plug 76 can include a built - in resistor ( resistor 13 shown in fig1 ) to provide shock protection to a user . similarly , jack 72 can incorporate a protective resistor ( resistor 14 shown in fig1 ). in such case , banana plug 76 and jack 72 are preferably molded in one piece together with their respective protective resistors to prevent tampering with the protective feature of the assembly . it will now be appreciated that the present invention provides apparatus for tethering personnel to an electrical ground and monitoring the integrity of the ground . the apparatus can be combined with a conventional electronic wristwatch for the convenience of a user thereof . although this invention has been described in considerable detail , such description is intended as being illustrative rather than limiting , since the invention may be variously embodied without departing from the spirit thereof as set forth in the following claims .

US-78405385-A

a turkey call device and assembly for simulating multiple calls of a wild turkey hen . the turkey call device and assembly comprises a housing with a plurality of striker plates and at least one striker member . in one embodiment , the housing comprises two striker plates on the top thereof and a third striker plate on the bottom thereof . the bottom striker plate is capable of producing a locator call . the locator call has a hearing range of up to one half of a mile so as to eliminate the need for a user to travel long distances for the device to be heard from afar . each striker plate and striker member can be formed from different materials . in this way , the turkey call device and assembly enables a user to reproduce multiple sounds , such as yelps , cuts , cackles , kee kees , runs , purrs , clucks , and other turkey hen sounds .

before explaining at least one embodiment of the inventive concepts disclosed herein in detail , it is to be understood that the inventive concepts are not limited in their application to the details of construction and the arrangements of the components or steps or methodologies set forth in the following description or illustrated in the drawings . the inventive concepts disclosed herein are capable of other embodiments or of being practiced or carried out in various ways . also , it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting the inventive concepts claimed herein in any way . in the following detailed description of embodiments of the inventive concepts , numerous specific details are set forth in order to provide a more thorough understanding of the inventive concepts . however , it will be apparent to one of ordinary skill in the art that the inventive concepts within the disclosure may be practiced without these specific details . in other instances , well - known features have not been described in detail to avoid unnecessarily complicating the instant disclosure . as used herein , the terms “ comprises ,” “ comprising ,” “ includes ,” “ including ,” “ has ,” “ having ,” or any other variation thereof , are intended to cover a non - exclusive inclusion . for example , a process , method , article , or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed . if used herein the notation “ a - n ” appended to a reference numeral is intended as merely convenient shorthand to reference one , or more than one , and up to infinity , of the element or feature identified by the respective reference numeral ( e . g ., 100 a - n ). similarly , a letter following a reference numeral is intended to reference an embodiment of the feature or element that may be similar , but not necessarily identical , to a previously described element or feature bearing the same reference numeral ( e . g ., 110 , 110 a , 110 b , etc .). such shorthand notations are used for purposes of clarity and convenience only , and should not be construed to limit the instant inventive concept ( s ) in any way , unless expressly stated to the contrary . further , unless expressly stated to the contrary , “ or ” refers to an inclusive or and not to an exclusive or . for example , a condition a or b is satisfied by anyone of the following : a is true ( or present ) and b is false ( or not present ), a is false ( or not present ) and b is true ( or present ), and both a and b are true ( or present ). in addition , use of the “ a ” or “ an ” are employed to describe elements and components of the embodiments herein . this is done merely for convenience and to give a general sense of the inventive concepts . this description should be read to include one or at least one and the singular also includes the plural unless it is obvious that it is meant otherwise . finally , as used herein any reference to “ one embodiment ” or “ an embodiment ” means that a particular element , feature , structure , or characteristic described in connection with the embodiment is included in at least one embodiment . the appearances of the phrase “ in one embodiment ” in various places in the specification are not necessarily all referring to the same embodiment . the inventive concepts disclosed herein are generally directed to a turkey call device comprising a housing having an open front , open back , a top , bottom , and first and second sides extending therebetween . the turkey call device includes an acoustic chamber positioned within the housing that extends between the open front and open back of the housing . the housing includes a plurality of recessed grooves located on the top and bottom of the housing . in some embodiments , the housing may include one recessed groove positioned on the top of the housing and one recessed groove positioned on the bottom of the housing . in some embodiments , the housing may include one recessed groove positioned on the bottom of the housing and two or more recessed grooves positioned on the top of the housing . the recessed grooves extend between the open front and open back of the housing . each recessed groove is configured to hold a striker plate therein . each striker plate may be formed from a slate of aluminum , acrylic , or stone , for example , so as to be capable of producing different turkey call sounds . referring now to fig1 - 3 , shown therein is an exemplary embodiment of a turkey call device 100 . the turkey call device 100 includes a housing 105 having an open front 110 , an open back 115 , a top 120 , a bottom 125 , and first and second sides ( 130 and 135 ) extending there between . the turkey call device 100 includes an acoustic chamber 140 positioned within the housing 105 that extends vertically between the open front 110 and open back 115 of the housing 105 . the turkey call device 100 further includes a first recessed groove 145 located on the top 120 of the housing 105 and configured to hold a first striker plate 150 therein . the first recessed groove 145 extends vertically between the open front 110 and open back 115 of the housing 105 . the turkey call device 100 further includes a second recessed groove 165 located on the bottom 125 of the housing 105 . the second recessed groove 165 is configured to hold a second striker plate 170 therein . the second recessed groove 165 extends vertically between the open front 110 and open back 115 of the housing 105 . in some embodiments , the turkey call device 100 further includes a third recessed groove 155 located on the top 120 of the housing 105 and configured to hold a third striker plate 160 therein . the third recessed groove 155 extends vertically between the open front 110 and open back 115 of the housing 105 and is positioned parallel to the first recessed groove 145 . similarly , in some embodiments , the turkey call device 100 may also include a fourth recessed groove located on the top of the housing and a fourth striker plate positioned within the fourth recessed groove . the fourth recessed groove extending vertically between the open front and open back of the housing and positioned parallel to the first and second recessed groove . the housing 105 includes an open front 110 , an open back 115 , a top 120 , a bottom 125 , and first and second sides ( 130 and 135 ) extending therebetween . the housing 105 may be constructed of any desired material , including but not limited to , wood , maple wood , acrylic , plastics , metals , alloys , non - metals , steel , titanium , carbon fiber , polymers , resins , ceramics , composite materials , or combinations thereof . in some embodiments the housing 105 may be elongated and generally rectangular in shape , while in some embodiments the housing 105 may be substantially square or may have any other desired shape , as will be appreciated by persons of ordinary skill in the art having the benefit of the instant disclosure . further , embodiments of the housing 105 may include reinforcing or bracing structures , such as ribs , struts , braces , rods , or any other suitable reinforcing structure , or combinations thereof . in some embodiments , the housing 105 of the turkey call device 100 is tapered . for example , the open front 110 and open back 115 of the housing 105 may be tapered from the top 120 of the housing 105 to the bottom 125 of the housing 105 , so that the top 120 of the housing 105 is more narrow than the bottom 125 of the housing 105 . in this way , the housing 105 may be more easily held and used by a person . the turkey call device 100 further includes an acoustic chamber 140 positioned within the housing 105 and extending vertically between the open front 110 and open back 115 of the housing 105 . the acoustic chamber 140 is a hollow open ended resonance chamber formed within the housing 105 that allows the resonant oscillation of sound waves . the dimensions and position of the acoustic chamber 140 amplify the sound produced by the turkey call device 100 when in use . for example , when a striker member is rubbed across a striker plate of the turkey call device 100 , the resulting vibration produces a unique sound , similar to that of a turkey , which is amplified by the acoustic chamber 140 . the turkey call device 100 further includes a first recessed groove 145 located on the top 120 of the housing 105 that is configured to hold a first striker plate 150 therein . the first recessed groove 145 extends vertically between the open front 110 and open back 115 of the housing 105 . the first recessed groove 145 is formed within the housing 105 to hold a first striker plate 150 . the depth of the first recessed groove 145 is greater than the depth of the first striker plate 150 so that the first striker plate is recessed within the first recessed groove 145 . the first recessed groove 145 is generally rectangular in shape . however , it is to be understood that the first recessed groove 145 may have any desired shape configured to matingly receive a first striker plate 150 therein such that the first striker plate 150 is substantially below or flush with the housing 105 . in some embodiments , the first recessed groove 145 may be generally rectangular in shape . while in some embodiments the first recessed groove 145 may be substantially square , circular , or triangular , in shape . the first striker plate 150 is held by and attached to the first recessed groove 145 . the first striker plate 150 is generally rectangular in shape . however , it is to be understood that the first striker plate 150 may have any desired shape configured to matingly rest or attach to the first recessed groove 145 therein such that the first striker plate 150 is substantially below or substantially flush with the housing 105 . in some embodiments , the first striker plate 150 may be generally rectangular in shape . while in some embodiments the first striker plate 150 may be substantially square , circular , or triangular in shape so as to attach and fit within the shape of the first recessed groove 145 . further , the first striker plate 150 may have any desired thickness sufficient to create the desired turkey call sound . variations in thickness of the first striker plate 150 result in the first striker plate 150 producing different turkey call sounds , as will be appreciated by persons of ordinary skill in the art having the benefit of the instant disclosure . the first striker plate 150 may be attached to or rest within the first recessed groove 145 using fasteners , adhesives , velcro , glues , combinations thereof , and the like . in some embodiments , the first striker plate 150 and the first recessed groove 145 may be formed as a unitary body , such as via casting , machining , molding , or any other desired method or technique . the first striker plate 150 is configured to produce a turkey call sound by rubbing a striker member across the first striker plate 150 . in this way , the vibration between the first striker plate and the striker member create sound , which mimics the sound of a turkey call , and which is amplified by the acoustic chamber 140 of the turkey call device 100 . the first striker plate 150 is preferably formed from aluminum slate , but may be formed from any suitable material sufficient to produce a turkey call sound upon rubbing the first striker plate 150 with a striker member . for example , the first striker plate 150 may be formed from stone , aluminum slate , aluminum , slate , acrylic , wood , plastic , composites , combinations thereof and the like . further , in some embodiments , if the first striker plate 150 becomes worn , a user may remove and replace the first striker plate 150 with a new first striker plate 150 , either formed from the same material or from a different material . in this way , the turkey call device 100 can create many different turkey calls . for example , a user may change the first striker plate 150 and replace it with another first striker plate 150 formed from a different material , in the event the first striker plate 150 becomes worn or in the event the user desires to create a different turkey call sound . the turkey call device 100 further includes a second recessed groove 165 located on the bottom 125 of the housing 105 and configured to hold a second striker plate 170 therein . the second recessed groove 165 extends vertically along the bottom 125 of the housing 105 between the open front 110 and open back 115 of the housing 105 . the second recessed groove 165 and the second striker plate 170 operate similarly to the first recessed groove 145 and first striker plate 150 . however , the second recessed groove 165 and second striker plate 170 are centrally located along the bottom of housing 105 . the second striker plate 170 is configured to produce turkey call sounds and in particular a locator call . the locator call has a hearing range of up to one half of a mile so as to eliminate the need for the user to travel long distances for the device to be heard from afar . the second recessed groove 165 and second striker plate 170 are used in combination with the first recessed groove 145 and first striker plate 150 to produce different turkey call sounds . in some embodiments , the first recessed groove 145 and second recessed groove 165 are of different dimensions . in this way , the turkey call device 100 is able to produce multiple turkey call sounds . while the second recessed groove 165 is preferably positioned centrally on the bottom 125 of the housing 105 , it should be understood that the position of the second recessed groove 165 may vary , depending upon the desired shape and configuration of the turkey call device 100 , as will be appreciated by persons of ordinary skill in the art having the benefit of the instant disclosure . the second recessed groove 165 is formed within the housing 105 to hold a second striker plate 170 . the second recessed groove 165 is generally rectangular in shape . however , it is to be understood that the second recessed groove 165 may have any desired shape configured to matingly receive a second striker plate 170 therein such that the second striker plate 170 is substantially below or flush with the bottom 125 of the housing 105 . in some embodiments , the second recessed groove 165 spans the height of the housing 105 . in some embodiments , the second recessed groove 165 may be generally rectangular in shape . while in some embodiments the second recessed groove 165 may be substantially square , circular , or triangular , in shape . the second striker plate 170 is held by and attached to the second recessed groove 165 . the depth of the second recessed groove 165 is greater than the depth of the second striker plate 170 so that the second striker plate 170 is recessed within the second recessed groove 165 . the second striker plate 170 is generally rectangular in shape . it is to be understood that the second striker plate 170 may have any desired shape configured to matingly rest or attach to the second recessed groove 165 therein such that the second striker plate 170 is substantially below or substantially flush with the bottom 125 of the housing 105 . in some embodiments , the second striker plate 170 may be generally rectangular in shape . while in some embodiments the second striker plate 170 may be substantially square , circular , or triangular in shape so as to attach and fit within the shape of the second recessed groove 165 . additionally , in some embodiments , each of the first recessed groove 145 and second recessed groove 165 , comprise a rectangular cross section . in this way , the first striker plate 150 and second striker plate 170 , rest flush against the first recessed groove 145 and second recessed groove 165 , respectively . the second striker plate 170 may have any desired thickness sufficient to create the desired turkey call sound . variations in thickness between the first striker plate 150 and second striker plate 170 allow the turkey call device 100 to produce different turkey call sounds , as will be appreciated by persons of ordinary skill in the art having the benefit of the instant disclosure . in some embodiments , for example , the first striker plate 150 is greater in width than the second striker plate 170 , thereby allowing the third second plate 170 to produce different sounds than the first striker plate 150 . the second striker plate 170 may be attached to or rest within the second recessed groove 165 using fasteners , adhesives , velcro , glues , combinations thereof , and the like . in some embodiments , the second striker plate 170 and the second recessed groove 165 may be formed as a unitary body , such as via casting , machining , molding , or any other desired method or technique . the second striker plate 170 is configured to produce a turkey call sound upon rubbing a striker member across the second striker plate 170 . in this way , the vibration created between the second striker plate 170 and the striker member create sound , which mimics the sound of a turkey call , and which is amplified by the acoustic chamber 140 of the turkey call device 100 . the second striker plate 170 is preferably formed from aluminum slate , but may be formed from any suitable material sufficient to produce a turkey call sound upon rubbing the second striker plate 170 with a striker . for example , the second striker plate 170 may be formed from stone , aluminum slate , aluminum , slate , acrylic , wood , plastic , composites , combinations thereof and the like . further , in some embodiments , the second striker plate 170 may be selectively removed and replaced with a new second striker plate 170 , either formed form the same or from a different material . in this way , the turkey call device 100 can create many different turkey calls , by varying or replacing the second striker plate 170 . for example , a user may remove and replace the second striker plate 170 with another second striker plate 170 if the second striker plate 170 becomes worn or if the user desires to the turkey call device 100 to produce a different turkey call sound . in some embodiments , the turkey call device 100 further includes a third recessed groove 155 located on the top 120 of the housing 105 and configured to hold a third striker plate 160 therein . the third recessed groove 155 and the third striker plate 160 operate similarly to the first recessed groove 145 and first striker plate 150 . the third recessed groove 155 extends vertically between the open front 110 and open back 115 of the housing 105 and is positioned parallel or in a side by side orientation to the first recessed groove 145 such that the first recessed groove 145 and third recessed groove 155 are separated by a portion of the housing 105 . in some embodiments , the first striker plate 150 and third striker plate 160 span the height of the housing 105 . further , in some embodiments , the third striker plate 160 is greater in width than the first striker plate 150 , thereby allowing the first striker plate 150 to produce different sounds from the third striker plate 160 . while the third recessed groove 155 is preferably positioned parallel to the first recessed groove 145 , it should be understood that the position of the third recessed groove 155 may vary , depending upon the desired shape and configuration of the turkey call device 100 , as will be appreciated by persons of ordinary skill in the art having the benefit of the instant disclosure . the third recessed groove 155 is formed within the housing 105 to hold a third striker plate 160 . the depth of the third recessed groove 155 is greater than the depth of the third striker plate 160 so that the third striker plate 160 is recessed within the third recessed groove 155 . the third recessed groove 155 is generally rectangular in shape . however , it is to be understood that the third recessed groove 155 may have any desired shape configured to matingly receive a third striker plate 160 therein such that the third striker plate 160 is substantially below or flush with the housing 105 . in some embodiments , the third recessed groove 155 may be generally rectangular in shape . while in some embodiments the third recessed groove 155 may be substantially square , circular , or triangular , in shape . the third striker plate 160 is held by and attached to the third recessed groove 155 . the third striker plate 160 is generally rectangular in shape . however , it is to be understood that the third striker plate 160 may have any desired shape configured to matingly rest or attach to the third recessed groove 155 therein such that the third striker plate 160 is substantially below or substantially flush with the housing 105 . in some embodiments , the third striker plate 160 may be generally rectangular in shape . while in some embodiments the third striker plate 160 may be substantially square , circular , or triangular in shape so as to attach and fit within the shape of the third recessed groove 155 . further , the third striker plate 160 may have any desired thickness sufficient to create the desired turkey call sound . variations in thickness of the third striker plate 160 with the first striker plate 150 result in the turkey call device 100 producing different turkey call sounds , as will be appreciated by persons of ordinary skill in the art having the benefit of the instant disclosure . the third striker plate 160 may be attached to or rest within the third recessed groove 155 using fasteners , adhesives , velcro , glues , combinations thereof , and the like . in some embodiments , the third striker plate 160 and the third recessed groove 155 may be formed as a unitary body , such as via casting , machining , molding , or any other desired method or technique . the third striker plate 160 is configured to produce a turkey call sound upon rubbing a striker member across the third striker plate 160 . in this way , the resulting vibrations produce sound , which mimic the sound of a turkey call , and which are amplified by the acoustic chamber 140 of the turkey call device 100 . the third striker plate 160 is preferably formed from acrylic , but may be formed from any suitable material sufficient to produce a turkey call sound upon rubbing the second striker plate 160 with a striker member . for example , the third striker plate 160 may be formed from stone , acrylic , aluminum slate , acrylic slate , aluminum , slate , wood , plastic , composites , combinations thereof and the like . further , in some embodiments , the third striker plate 160 may be selectively removed and replaced with a new third striker plate 160 , either formed form the same or from a different material . in this way , the turkey call device 100 can create many different turkey calls , by varying or replacing the material of the third striker plate 160 . for example , a user may change and replace the third striker plate 160 with another third striker plate 160 formed from a different material if the third striker plate 160 becomes worn or if the user desires to create a different turkey call sound . in operation , the housing 105 of the turkey call device 100 is held in a user &# 39 ; s non - dominant hand , while a striker member 275 ( as shown in fig5 ) is held in the user &# 39 ; s dominant hand , so that the striker member 275 is held similarly to a writing utensil . the striker member 275 can then be drawn towards or rubbed across the first striker plate 150 , third striker plate 160 , or second striker plate 170 . for example , a striker member 275 formed cherry wood can be used with each of the first striker plate 150 , third striker plate 160 , or second striker plate 170 , to produce sounds that mimic turkey sounds , and more specifically , turkey hen sounds . while , a striker member 275 formed from walnut wood can also be used with each of the first striker plate 150 , third striker plate 160 , or second striker plate 170 , to produce sounds that mimic turkey sounds , and more specifically , turkey hen sounds . in this way , the turkey call device 100 can produce at least six different types of hen sounds . referring now to fig4 - 5 , shown therein a turkey call assembly 200 . the turkey call assembly 200 is implemented similarly to the turkey call device 100 and further includes a striker member 275 as shown in fig5 . in some embodiments , the turkey call assembly 200 may include a first recessed groove and first striker plate located on the top of the housing and a second recessed groove and second striker plate located on the bottom of the housing . while in some embodiments , the turkey call assembly 200 may also include a third recessed groove and third striker plate located on the top of the housing and a fourth recessed groove and fourth striker plate also located on the top of the housing . in some embodiments , the first recessed groove , third recessed groove , and fourth recessed groove may be positioned in a side by side or parallel orientation along the top of the housing . as shown in fig4 - 5 , the turkey call assembly 200 includes a housing 205 having an open front 210 , an open back 215 , a top 220 , a bottom 225 , and first and second sides ( 230 and 235 ) extending therebetween . the turkey call assembly 200 includes an acoustic chamber 240 positioned within the housing 205 that extends vertically between the open front 210 and open back 215 of the housing 205 . the turkey call assembly 200 includes a first recessed groove 245 located on the top 220 of the housing 205 and that extends vertically between the open front 210 and open back 215 of the housing 205 and an aluminum slate first striker plate 250 positioned within the first recessed groove 245 . the turkey call assembly 200 further includes a second recessed groove 265 located on the bottom 225 of the housing 205 . the second recessed groove 265 extends vertically between the open front 210 and open back 215 of the housing 205 . the turkey call assembly further includes an aluminum slate second striker plate 270 positioned within the second recessed groove 265 . the turkey call assembly 200 also includes a third recessed groove 255 located on the top 220 of the housing 205 . the third recessed groove 255 extends vertically between the open front 210 and open back 215 of the housing 205 and is positioned parallel to or in a side by side orientation with the first recessed groove 245 . the turkey call assembly 200 includes an acrylic slate third striker plate 260 positioned within the third recessed groove 255 . as shown in fig5 , the turkey call assembly 200 also includes a striker member 275 having a first section 280 having a proximal end 285 and a distal end 290 . the striker member 275 also includes a second section 295 having an upper end 300 and a lower end 305 . the proximal end 285 of the first section 280 is attached to the upper end 300 of the second section 295 . wherein the distal end 290 of the striker member 275 is rubbed across the aluminum slate first striker plate 250 , the aluminum slate second striker plate 270 , and the acrylic slate third striker plate 260 , so as to produce at least three different turkey call sounds . the striker member 275 is preferably constructed from wood , such as cherry wood or walnut wood . however it should be understood that the striker member 275 may be constructed of any desired material , including but not limited to , stone , wood , cherry wood , walnut wood , acrylic , plastics , metals , alloys , non - metals , steel , titanium , carbon fiber , polymers , resins , ceramics composite materials , or combinations thereof . in some embodiments the striker member 275 may be generally elongated and rectangular in shape , while in some embodiments the striker member 275 may be substantially square or may have any other desired shape , as will be appreciated by persons of ordinary skill in the art having the benefit of the instant disclosure . further , embodiments of the striker member 275 may include reinforcing or bracing structures , such as ribs , struts , braces , rods , or any other suitable reinforcing structure , or combinations thereof . in some embodiments , the second section 295 of the striker member 275 is tapered . for example , the upper end 300 may be tapered from the lower end 305 , so that the upper end 300 is more narrow than the lower end 305 . in this way , the second section 295 may be more easily held and used by a person . the striker member 275 may have any desired thickness sufficient to strike or rub the aluminum slate first striker plate 250 , the aluminum slate second striker plate 270 , and the acrylic slate third striker plate 260 so as to produce three different turkey call sounds . variations in thickness of the striker member 275 and variations in the material used for the striker member 275 result in the turkey call assembly 200 producing different turkey call sounds . for example , the striker member 275 may be formed from walnut wood , cherry wood , or other suitable materials as will be appreciated by one of ordinary skill in the art having the benefit of the instant disclosure . in some embodiments , the turkey call assembly 200 includes a pair of striker members 275 . each of the striker members 275 is composed of different types of hardwood , such as walnut and cherry wood , so as to produce a different sound when engaging the aluminum slate first striker plate 250 , acrylic slate third striker plate 260 , or aluminum slate second striker plate 270 . in operation , the housing 205 of the turkey call assembly 200 is held in a user &# 39 ; s non - dominant hand , while a striker member 275 is held in the user &# 39 ; s dominant hand , so that the striker member 275 is held similarly to a writing utensil . the striker member 275 can then be drawn towards or rubbed across the aluminum slate first striker plate 250 , acrylic slate third striker plate 260 , or aluminum slate second striker plate 270 . for example , a striker member 275 formed cherry wood can be used with each of the aluminum slate first striker plate 250 , aluminum slate second striker plate 270 , or acrylic slate third striker plate 260 , to produce sounds that mimic turkey sounds , and more specifically , turkey hen sounds . while , a striker member 275 formed from walnut wood can also be used with each of the aluminum slate first striker plate 250 , aluminum slate second striker plate 270 , or acrylic slate third striker plate 260 , to produce different sounds that mimic turkey sounds , and more specifically , turkey hen sounds . in this way , the turkey call device 200 can produce at least six different types of hen sounds . it is to be appreciated that embodiments of the turkey call device 100 or turkey call assembly 200 may be shipped with the housing 105 and housing 205 fully or partially assembled , or with the turkey call device 100 or turkey call assembly 200 fully or partially disassembled in the form of a kit , as will be readily appreciated by persons of ordinary skill in the art having the benefit of the instant disclosure . from the above description , it is clear that the inventive concepts disclosed herein are adapted to carry out the objects and to attain the advantages mentioned herein as well as those inherent in the inventive concepts disclosed herein . while exemplary embodiments of the inventive concepts disclosed herein have been described for purposes of this disclosure , it will be understood that numerous changes may be made which will readily suggest themselves to those skilled in the art and which are accomplished within the broad scope of the inventive concepts disclosed herein and defined by the appended claims .

US-201615226563-A

in order to solve such problem that heating a mark such as a one - chip microprocessor which is easily damaged thermally in case of curing a heat - curing resin enclosing such one - chip microprocessor could have not been essentially made in event of embedding sealably such mark in the resin section of a denture , the present invention is characterized by that a groove - shaped recess for inserting the mark has previously been defined in a wax pattern indispensable for fabrication of the denture . for defining such recess , the implement for making a recess for embedding sealably the mark which is provided with a head shaped so as to have substantially the same dimension as that of the mark is used . more specifically , the head of the implement which has been heated by hot water is pressed upon a surface of the wax pattern to define such a groove - shaped recess as a result of melting a portion of the wax thus heated . then , a heat - curing resin is poured into the recess defined in the wax pattern , whereby a cured resin section containing the recess is shaped . thereafter the mark is inserted into the groove - shaped recess , and then a gap defined around the mark and an exposed portion of the mark is covered with a resin used for direct restoration which cures instantly at ordinary temperatures , or a photo - polymerizing resin to sealably embed the gap and the exposed part of the mark . when a one - chip microprocessor transmitting identification number us utilized as a mark and is embedded in the resin section of such denture , the resulting denture can be identified simply and positively . as a result , management for dentures becomes very easy un dentist &# 39 ; s or dental mechanic &# 39 ; s office .

referring to fig1 and 2 each illustrating an embodiment of the denture 1 capable of identifying its owner according to the present invention wherein a groove - shaped recess has been previously defined on a resin layer of an artificial gingival section 3 thereof as a groove 5 for holding a mark 6 such as a one - chip microprocessor to sealably embed the same therein . more specifically , a recess is defined in the case when a wax pattern is fabricated in a dental mechanic &# 39 ; s office on the basis of a patient &# 39 ; s tooth form acquired in a dental office as the groove 5 for holding such mark on the wax pattern at a site where the resin layer of the artificial gingival section 3 in the vicinity of an artificial molar tooth 4 becomes thicker . in case of defining the above described groove 5 for holding a mark , it is convenient to employ an exclusive implement 7 for making a recess used for embedding sealably a mark shown in fig3 . referring to fig3 the implement 7 for making a recess used for embedding sealably a mark composed of a head 8 shaped so as to have substantially the same dimension as that of the mark 6 of one - chip microprocessor or the like to be sealably embedded , and a grip 9 to the extreme end of which is attached the aforesaid head 8 is shown . first , the head 8 of the implement 7 for making a recess used for embedding sealably a mark is immersed in water warmed at about 40 ° c ., and the head thus warmed is forcibly pressed on a wax pattern . as a result , the paraffin wax solidified compactedly is softened locally , whereby a recess having slightly larger size than that of the mark can be defined without damaging the wax pattern . in this case , however , there is a fear of deforming the wax pattern , if the head is warmed excessively , then the wax melts easily . therefore , temperature of warmed water should be carefully adjusted . alternatively , a groove - shaped recess may be defined on a wax pattern by scraping off the wax into a contour corresponding roughly to a required recess by the use of denturist &# 39 ; s knife . then , the head 8 of the above described implement 7 for making recess used for embedding sealably a mark is forcibly inserted into the contour of the above described tentative recess , so that a finished groove 5 for holding mark into which such a target mark is contained tightly can easily be defined . in any case , it is very easy working for dental mechanic to define such groove 5 for holding a mark by the use of the implement 7 for making recess used for embedding sealably a mark . a time required for such working is slight and not so much labor is required therefor . the head 8 may be prepared from any material such as metal , synthetic resin , ceramics , wood , bamboo and the like . after defining a recess on a wax pattern as a groove for holding a mark , a heat - curing resin is poured into , a gap of the wax pattern and heated . in the artificial gingival section 3 of the resin cured by heating , the groove 5 for holding a mark may be formed at a desired site . the optimal site at which the groove 5 for holding a mark is to be defined resides in the artificial gingival section 3 in the vicinity of the artificial molar tooth 4 on a cheek side where the resin layer is the thickest from the viewpoints of workability , and possible damage of the denture due to occlusal force or external force . in this respect , however , any site , i . e ., anywhere in the resin layer of a plate 2 of denture or the like section may be selected for defining the groove 5 for holding a mark so far as the site selected has a sufficient thickness for embedding sealably the mark such as a one - chip microprocessor . accordingly , a site for defining the groove 5 for holding a mark is not particularly limited . furthermore , it is desirable that a depth of the groove 5 for holding a mark is kept at such a degree where the mark 6 does neither project nor retracts from a level of the resin layer surface in case of embedding sealably the mark 6 . according to such arrangement as described above , there is neither fear of inflicting pain on its user as a result of pressing the mucous membrane in the user &# 39 ; s cheek with a section where the mark 6 has been embedded and sealed , nor there is malaise even if the section is touched with the user &# 39 ; s tongue . it is also easy to define the above - mentioned groove 5 for holding a mark on a denture which has already been employed by a patient . in this case , a groove - shaped recess is cut on an artificial gingival section having a thicker thickness by means of a cutter for dental use , and a mark such as a one - chip microprocessor contained in the recess may be sealably embedded with the use of a resin used for direct restoration or the like resin . although preferable is one - chip microprocessor as the mark used in the present invention , a metallic plate on which user &# 39 ; s name has been punched , an alphabetically shaped synthetic resin plate , a star - or an animal - shaped ceramic plate , or any suitable storage means which will be widely used in the future may be sealably embedded in a recess . while a commercially available one - chip microprocessor for animal use having a size of around 2 mm diameter and 11 mm length may be applied to the present invention , such size is considered to be relatively too large for use in the present invention . accordingly , it is desirable to develop a novel one - chip microprocessor used exclusively for dental field in case of practicing the present invention . as a matter of course , the smaller size of such one - chip microprocessor results in the better result in the invention . in this respect , storage capacity of information may be adjusted for miniaturization of one - chip microprocessor to be 15 - digit or less according to iso standard . when it is arranged in such that owner &# 39 ; s name , e . g ., hisashi kishigami or his initials , e . g ., h . k . of a denture can be read together with number of several digit by a reader , management for dentures , identifying work of dentures after having been washed , or the like working in dental office become much more accelerated . in case of fabricating a denture according to the present invention , it is preferable for embedding sealably a mark to use a resin for direct restoration comprising methyl methacrylate as the major component such as &# 34 ; repairsin &# 34 ; ( trade name ) manufactured by k . k . g . c . dental products . a mixture of liquid ( monomer ) and powder ( polymer ) of &# 34 ; repairsin &# 34 ; is applied to a one - chip microprocessor contained in a groove - shaped recess 5 in accordance with a conventional brush - on technique . as a result , the mixture sets at ordinary temperatures after lapse of 7 to 8 minutes , so that the one - chip microprocessor can be positively embedded and sealed in a resin layer of an artificial gingival section or the like . since the resin for direct restoration used adheres perfectly to a heat - curing resin used for molding the artificial gingival section , there is no fear of slipping the mark embedded and sealed from the recess . alternatively , a photo - polymerizing resin such as &# 34 ; unifast &# 34 ; ( trade name ) manufactured by k . k . g . c . dental products which is cured with visible rays may be employed for embedding sealably a mark . in this case , a one - chip microprocessor contained in a groove - shaped recess is covered with an admixture of powder and liquid of &# 34 ; unifast &# 34 ;, and then , when visible rays are projected on the groove - shaped recess thus covered by the use of a device for irradiating light rays , the photo - polymerizing resin sets at ordinary temperatures after lapse of several minutes without accompanying any thermal treatment . it is preferred to prepare a transparent portion for embedding and sealing a mark , or the portion having a different color from that of an artificial gingival section . as a result of such modification , the portion where a mark has been embedded and sealed can be recognized at a glance , whereby an operator can allow quickly a reader to come near the mark of one - chip microprocessor to read a number registered . thus , such reading work for identification becomes easier , and it results in a shorter period of time for working required for identifying dentures . the present invention may not only be applied to denture , but also any oral artificial product comprising a resin layer such as orthodontic appliance . a manner of practice according to the present invention will be described hereinafter in conjunction with the accompanying drawings . in fig1 and 2 , a groove - shaped recess 5 for holding a mark 6 such as a one - chip microprocessor to sealably embed the same therein is defined on an artificial gingival section 3 supported by a plate 2 of a denture 1 on either side of patient &# 39 ; s cheek . in usual denture 1 , since a resin layer in the vicinity of an artificial molar tooth implanted in the artificial gingival section 3 is the thickest , so that the mark 6 can be positively embedded sealably in the resin layer with a sufficient room , even if the mark is a commercially available one - chip microprocessor for animal use . in case of embedding sealably the mark 6 , liquid ( monomer ) of a direct resin for restoration is first applied into the groove - shaped recess 5 for holding mark , thereafter , the mark 6 is forcibly inserted in the groove - shaped recess 5 as shown by the arrow a in fig2 and then , the surface of the mark 6 is also coated with the monomer liquid . then , the tip of a brush is moistened with the monomer liquid , and the tip of the brush thus moistened is allowed to be in contact with a powdered polymer , and a gap defined between the artificial gingival section 3 and the mark 6 is filled with the powder deposited on the tip of the brush , and at the same time , the surface of the mark 6 is also covered with the powder in accordance with a conventional brush - on procedure . within a period - of several minutes , the liquid begins to polymerize together with the powder , so that such deposition of a mixture of the liquid and the powder is repeated further several times according to the brush - on technique . finally , the mixture is deposited at a degree wherein the level thereof is slightly higher than the surface of the artificial gingival section 3 , and is covered with cellophane , silver foil and the like to allow the same to stand until the resin is set . the curing reaction is completed at ordinary temperatures after the elapse of about seven minutes . after curing , the resulting product is immersed in warm water of about 70 ° c . for around 20 minutes , and then , the portion under which the mark has been embedded and sealed is smoothed with a grinder , whereby troubles in feeling of tongue in a denture &# 39 ; s user may be avoided . the one - chip microprocessor used for experiments in the course of the development for the invention is &# 34 ; lifechip &# 34 ; ( trade name ) imported from the destron - fearing corporation in the u . s . a . and sold by dai - nippon seiyaku k . k . in japan , and the one - chip microprocessor has a cylindrical shape of 2 mm diameter and 11 mm length . the one - chip microprocessor is covered by a plastic cap for avoiding intracorporeal movement , so that it is served for experiments after removing the cap . as a result of experiments , such one - chip microprocessor embedded and sealed in a denture functioned normally , so that when a hand - held reader was allowed to come near the portion under which the one - chip microprocessor had been embedded and sealed within a distance of 5 cm or shorter therefrom and emitted inquiry signal , response signal responded instantly from the one - chip microprocessor , whereby a number of 15 - digit was displayed on a display of the reader . thus , such registered number belonging to a denture of its owner can be positively read irrespective of a position of the portion under which a one - chip microprocessor has been embedded and sealed , even when it is any site in the artificial gingival section of the denture . in this case , however , since it is troublesome to frequently turn on such hand - held reader , every dentures may be allowed to come near the antenna of a stationary reader one by one in the case where a number of dentures must be identified continuously . fig3 is an embodiment of an implement 7 for making recess used for sealably embedding a mark required for fabricating a denture according to the present invention . in the beginning of experiments , the present inventor picked up a one - chip microprocessor , and was allowed to be forcibly in direct contact with a wax pattern thereby defining a recess thereon . however , this procedure is somewhat troublesome , and it was difficult to make a recess having a suitable contour thereof . before long , an implement to make a recess for holding one - chip microprocessor is prepared by the inventor himself . after repeating experiments , a head 8 was utilized in place of one - chip microprocessor . finally , the head 8 is fixed on grip 9 , and further it has been found by the inventor that a contour of the head 8 having a trapezoidal section is most desirable . more specifically , a head 8 having such trapezoidal section is employed to define a recess upon a wax pattern by forcibly pressing the head thereon , and then , when the head 8 is removed from the wax pattern , edges of the recess of the wax pattern are not damaged , but a clear contour of a groove - shaped recess 5 for holding a mark can be defined on the wax pattern because of the trapezoidal section . in the implement 7 for making a recess used for sealably embedding a mark shown in fig3 the head 8 has such dimensions that a longer side and a shorter side are 12 mm and 2 mm in the top surface of the trapezoidal section which correspond substantially to those of the above described one - chip microprocessor , respectively , as well as a longer side and a shorter side are 12 mm and 3 mm in the bottom surface thereof , and a height thereof is about 3 mm . a grip 9 is secured to the bottom surface of the head 8 at the central portion thereof . any contour of the grip 9 may be applied , and a size of which may be the one being sufficient for holding the same with a hand . a prototype of the head 8 was made from hard box - wood material . as a result , it was very convenient to make a recess for holding a mark , because the head 8 of box - wood is not excessively heated in case of warming the same in hot water , so that there is no fear of excessively melting a wax pattern . however , box - wood is expensive and much labor is required for working box - wood material . accordingly , the head 8 may be made from a synthetic resin material coated with teflon in such that wax does not stick to the head 8 . the present invention which has been practiced in the manner as described above exhibits the following advantages . namely , a mark has been embedded and sealed after defining a recess for holding the same on an artificial tooth implanted in a denture according to a conventional technique , while a mark is embedded and sealed in the resin layer having a thicker thickness of artificial gingival section in a denture capable of identifying its owner according to the present invention . thus , there is no fear of deteriorating strength of artificial tooth , so that a denture according to the present invention can be applied for positively confirming identities of old people in practical use . furthermore , since a one - chip microprocessor is employed as a mark to be sealably embedded and a registered number of the one - chip microprocessor is read by a reader , an owner of a dentures according to the present invention can be identified easily and positively . accordingly , when an alzheimer &# 39 ; s patient with poriomania is kept from harm in another place , or when an old man who is in indistinct consciousness as a result of a traffic accident , his ( or her ) identity can be immediately specified so far as the old man puts on a denture with a one - chip microprocessor according to the invention . moreover , in a dental office where a number of dentures must be managed , when a registered number of a one - chip microprocessor embedded and sealed in each denture is checked against records contained in clinical recording or computer , a date on which each denture was fabricated and the like information can be instantly specified . in senior citizens &# 39 ; home where a number of dentures must be collectively washed in every meals , each denture after having been washed can be returned to its owner without accompanying any mistake by reading successively a registered number of each denture by means of a reader . thus , the staff for washing dentures can perform quickly and easily their working for treating such dentures after finishing every meals as a result or being released from conventional troublesome reading of carved characters . since a direct resin for restoration is used as a resin for embedding sealably a mark in case of fabricating a denture capable of identifying its owner according to the present invention , a one - chip microprocessor can be embedded sealably in a resin layer of the denture without heating the one - chip microprocessor having no heat - resisting properties . furthermore , when an implement for making a recess for sealably embedding a mark is employed , a groove - shaped recess having the substantially same dimension as that of a one - chip microprocessor can be very easily and positively defined on a wax pattern without damaging the same . thus , a one - chip microprocessor may be tightly held in the groove - shaped recess defined on the resin layer of a denture , and it can be embedded sealably with the use of a direct resin for restoration or the like . it will be appreciated by those of ordinary skill in the art that the present invention can be embodied in other specific forms without departing from the spirit or essential characteristics thereof . the presently disclosed embodiments are therefore considered in all respects to be illustrative and not restrictive . the scope of the invention is indicated by the appended claims rather than the foregoing description , and all changes that come within the meaning and range of equivalents thereof are intended to be embraced therein .

US-18321698-A

an adjustable work chair comprising a frame , a seat support structure , and a versatile seat combination . the adjustable work chair has a seat support structure which allows alterations to the seat &# 39 ; s height and orientation . furthermore , the adjustable work chair may be mobile through alternative embodiments using hinged castors , may provide knee support through alternative embodiments including knee pads , or may have a tray for holding instruments , parts , tools , or other equipment . the adjustable work chair provides a comfortable platform that allows the operator to efficiently perform tasks over a prolonged time frame . additionally , embodiments of the adjustable work chair provides a platform which allows the operator to alter the seat &# 39 ; s height , location , or orientation to provide a wide range of positions ranging from a seating position to a creeper position .

in accordance with the present invention , an adjustable work chair is provided which comprises a base , a support structure , and a seat structure . fig . i depicts the present invention with a two piece seat ( 50 ). a t - shaped base ( 10 ) provides a stable foundation . the t - shaped base consists of a first length ( 11 ) comprising the long axis and a second length ( 12 ) attached to an end of the first length ( 11 ) and oriented along the transverse axis of the t - shaped base ( 10 ). a first arm ( 21 ) is attached at the intersection between the first length ( 11 ) and the second length ( 12 ) of the t - shaped base ( 10 ). the first arm ( 21 ) is cantilevered and telescopes ( 22 ) to extend down the long axis of the base at an acute angle to the first length ( 11 ) of the t - shaped base ( 10 ). an end of the first arm ( 20 ) is attached to an attaching means ( 40 ) for coupling the first arm ( 20 ) to a seat ( 50 ) and a second arm ( 30 ). a second arm ( 30 ) is variably attached ( 31 ) to the first length ( 11 ) of the t - shaped base ( 10 ) such that it may be fixed to the first length ( 10 ) a any one of a number of positions ( 32 ). the first arm ( 20 ) and the second arm ( 30 ) are used in conjunction to orient the seat ( 50 ). the seat ( 50 ) comprises two pieces . the first piece is a pad ( 51 ) attached at an angle to the attachment means ( 40 ) by a stem ( 53 ). the second piece which is a pad ( 52 ) attached to the attachment means ( 40 ) by a second stem ( 54 ). the seat ( 50 ) is attached to the attachment means such that the seat ( 50 ) having pieces ( 51 , 52 ) may be independently adjusted . the invention may also comprise a single - piece , pivoting seat ( 60 ). as shown in fig2 the seat ( 60 ) comprises one piece member which slides along its own length . fig2 shows such an adjustable seat where one pad ( 60 ) is attached to the attaching means ( 40 ) such that a detent , screw or similar means of sliding the pad ( not shown ) may be released or loosened to allow the user to adjust the work chair . the seat ( 60 ) rotates about the transverse axis of the work chair in relation to the long axis of the t - shaped base ( a ). in the preferred embodiment , the seat ( 60 ) banana - like in shape and slides along an arc to a variety of positions relative to the attaching means 40 . the embodiment shown in fig2 comprises the first arm ( 20 ) and the second arm ( 30 ) which are similarly attached to the attachment means ( 40 ). however , other embodiments of the present invention may similarly utilize the one - piece seat ( 60 ). in another embodiment of the invention shown in fig3 the second arm ( 30 ) is replaced by a positively pressured gas shock ( 70 ). the gas shock ( 70 ) is attached at a point along the long axis of the t - shaped base ( 71 ). additionally , the gas shock ( 70 ) is cantilevered and oriented up the long axis of the t - shaped base ( 10 ) such that is extends up at an acute angle from the base , intersecting the attaching means ( 40 ). the gas shock ( 70 ) provides an adjustment means ( 72 ) whereby the user may extend or compress the seat with only a release of the adjustment means ( 72 ) and either a slight increase or decrease in weight applied onto the seat ( 50 ) by the user . therefore , the gas shock ( 70 ) allows the user to adjust the seat ( 50 ) without standing up . the gas shock ( 70 ) may be utilized with both the one piece ( 60 ) and the two piece seats ( 50 ). in still another embodiment of the invention shown in fig4 a knee pad ( 80 ) may be added to the invention to permit a user to assume a hybrid sitting - kneeling position . while two knee pads ( 80 ) are depicted in fig4 one of ordinary skill in the art would see that there are other embodiments which include one or more knee pads ( 80 ) on an upper surface ( 13 ) of the transverse portion ( 12 ) of the t - shaped base ( 10 ). furthermore , fig5 shows an embodiment of the invention with an adjustable knee pad ( 90 ). the adjustable knee pad ( 90 ) comprises at least one arm ( 91 ) which is attached to the long portion ( 11 ) of the t - shaped base ( 10 ). the at least one arm ( 91 ) extends upward toward the transverse portion ( 12 ) of the t - shaped base ( 10 ). a transverse portion ( 92 ) is attached to the at least one arm ( 91 ) at an end of the at least one arm ( 91 ). the transverse portion ( 92 ) of the at least one arm ( 91 ) is parallel to the transverse portion ( 12 ) of the t - shaped base ( 10 ), and the transverse portion ( 92 ) of the at least one arm ( 91 ) has at least one pad ( not shown ) on an upper surface ( 13 ) of the transverse portion ( 92 ) of the at least one arm ( 91 ). the at least one arm ( 91 ) is adjustable such that the transverse portion ( 92 ) of the at least one arm ( 91 ) may be elevated above the t - shaped base ( 10 ). a second arm ( 93 ) is shown in this symmetrical embodiment ( fig5 ), though one of ordinary skill of the art could other obvious alternative arrangements . additionally , the two - piece seat ( 50 ) or the second arm ( 50 ) could be used in conjunction with the adjustable knee pad ( 90 ) as well . the base ( 10 ) may further include swiveled castors ( 100 ) to provide mobility as depicted in fig6 . in the present embodiment , the castors ( 100 ) are located at the corners of the t - shaped base , but one of ordinary skill in the art may find other obvious configurations . each castor is located on a lower surface of the base ( not shown ) to allow directional movement of the adjustable work chair . it should also be understood that the castors ( 100 ) may be design for use on a variety of terrains and surfaces . such castors ( 100 ) may be used in any of the embodiments of the invention . furthermore , the castors ( 100 ) may be offset ( 110 ), lowering the base ( 10 ) closer to the ground in fig7 than the original castors ( 100 ) in fig6 . the offset ( 110 ) is accomplished by using a t - shaped base ( 10 ) having elbows ( 111 ) at each corner of the base ( 10 ), so the swiveled castors may be placed so that a large portion of the castor ( 112 ) is oriented above the t - shaped base ( 10 ) along the plane ( c ) formed by the lower surface ( not shown ) of the base ( 10 ). only a nominal portion of the castor ( 110 ) extends below the frame ( 113 ), so the base ( 10 ) is lower to the ground . the offset ( 110 ) may also be used with any of the embodiments of the invention . fig8 and 9 depict a further preferred embodiment of this invention . the embodiment of fig8 and 9 provides enhanced versatility which enables the user to adjust the work chair between three positions ; the creeper position wherein the user lays flat in relation to the ground , the kneeling position , and the seated position . the design of fig8 and 9 increases the number of useful positions to enable the user to perform a task in the most comfortable and safe position . the following description will focus on the elements of this embodiment that differ from the previous embodiments . the distinguishing feature of the embodiment of fig8 and 9 centers around the design of the seating / creeping member which unfolds of expands from an upright seating to a flat creeper platform . in the flat creeper position , the work chair assumes a relatively flat position and has all of the utility and benefits of a conventional creeper . a t - shaped base is once again utilized to provide a stable foundation . the t - shaped base consists of a first length ( 111 ) comprising the long axis and a second length ( 112 ) attached to an end of the first length ( 111 ) and oriented along the transverse axis of the t - shaped base . it should be noted that the first length ( 111 ) of this embodiment may require increased support strength , for example , two parallel lengths may be used to form the first length ( 111 ) as illustrated in fig9 . moreover , more than one castor may be provided at the end of the first length ( 111 ) for improved support and stability . a kneeling cushion ( 160 ) may be suitable provide adjacent the second length ( 112 ) as described in the foregoing embodiments . a first arm ( 121 ) is attached at the intersection between the first length ( 111 ) and the second length ( 112 ) of the t - shaped base . the first arm ( 121 ) is cantilevered and comprises telescoping member ( 122 ) to extend down the long axis of the base at an acute angle to the first length ( 111 ) of the t - shaped base . an end of the first arm ( 121 ) is attached to an attaching means ( 140 ) for coupling the first arm ( 121 ) to a seat member ( 150 ) and a second arm ( 130 ). the second arm ( 130 ) is variably attached to the first length ( 111 ) of the t - shaped base such that it may be either fixed to the first length ( 111 ) a any one of a number of positions as described with respect to fig1 or may comprises a piston - cylinder arrangement as described with respect to fig3 . the first arm ( 121 ) and the second arm ( 130 ) are used in conjunction to orient the seat ( 150 ). the seat ( 150 ) comprises a first main cushion member ( 152 ) and a second main cushion member ( 154 ). the first and second main cushion members ( 152 , 154 ) may assume different positions relative to one another depending , for example , on the orientation of the first arm ( 111 ) and second arm ( 130 ). significantly , the second main cushion member ( 154 ) further comprises auxiliary pads ( 153a , 153b , 155 ). the auxiliary pads ( 153a , 153b , 155 ) are pivotally connected to the second main cushion member ( 154 ) and are adapted to unfold to form a creeper surface as illustrated by fig9 . it should be understood that the auxiliary pads may be designed in any suitable manner to expand into this creeper surface . for example , the auxiliary pads may slide relative to the second main cushion member ( 154 ) or may be formed as telescoping members which telescope out of the second main cushion member ( 154 ). in any event , the embodiment of fig8 and 9 provides a novel work chair having multiple positions ranging from an upright seating position to a flat creeper position . while the foregoing invention has been shown and described with reference to several preferred embodiments , it will be understood by those possessing skill in the art that various changes in form and detail may be made without departing from the spirit and scope of this invention .

US-66173596-A

a method and system for baking a dual - component bakery product includes providing an uncooked product comprising an envelope , at least substantially made of dough , and a filling . the filling is heated by electromagnetic waves so as to initiate a cooking state . subsequent to the heating of the filling , the envelope is baked in a heat transfer oven . rising of the dough is advantageously also effected by means of the electromagnetic waves , preferably simultaneously with the heating of the filling for cooking the latter . the invention further includes a dual - component bakery product obtained by such methodology .

fig1 shows a microwave oven used in the invention in cross - section . the oven comprises a resonance cavity 20 provided with a coupling device 22 for supplying the energy of the microwaves used . the generator of these waves is not shown for simplicity &# 39 ; s sake . the tests described below were carried out with a conventional magnetron and a conventional oven for household use . such a device will normally be of a heavier design for industrial applications , with a longer operational life as desired for continuous operation . this then relates to , for example , cooling of the outer wall , a larger volume , a stronger wave source , and possibly a different frequency used for the wave source , as applicable . the microwave oven may be used in the “ batch ” mode , i . e . the products are loaded into the microwave oven , the latter is energized for a short period ( see below ), and the bakery products are unloaded for further treatment . preferably , however , a more continuous process is used wherein the bakery products 24 are supplied on a conveyor belt 26 , as shown . the step of depositing the products on the belt 26 is not shown for simplicity &# 39 ; s sake . furthermore , the physical aspects of the baking process will not be discussed . it suffices to note that the water content of the filling ensures that a temperature of 100 ° c . will not be readily exceeded , that the microwave energy also has an effect on the appearance and composition of the envelope , and that the baking process in general is very complicated . the products to be baked are fed into the microwave oven , for example , in the raw state . they have a filling ( shown hatched ) consisting of a minced meat product such as sausage or the like and an envelope that is shown in white . the shape of the product is a usual one such that in the case of a meat pastry the length may be , for example , 12 cm , the width 6 cm , and the thickness 2 . 5 cm ; the filling extending over substantially the entire length of the product and having a width of 2 . 5 cm and a thickness of 1 cm . these dimensions , however , are by no means limitative , indeed mini meat pastries are well known . furthermore , the advantages of the invention may lead to the use of dimensions , compositions , shapes , colors , etc . that were hitherto not usual . similar values apply to sausage rolls ; however , these are not discussed separately . it was surprisingly found that the rising of the dough of the dual - component bakery product 24 can also take place in the microwave oven . a long rising process at 28 ° c . may thus be omitted . the microwave oven is energized once the products have arrived in the oven . this energizing may take place continuously while at the same time the conveyor belt also moves continuously ; alternatively , the oven and / or the conveyor belt may be energized intermittently . the latter takes place preferably ( at least partly ) if the process starts with deep - frozen ingredients . defrosting thereof may take place at room temperature , but this takes ( much ) longer . as will be explained below , a heating time of 30 seconds up to a few minutes , for example at most 3 minutes , is a good choice , but longer or shorter times are equally possible , in dependence also on the microwave power and the average speed of the conveyor belt in relation to the oven size and the product to be prepared . the atmosphere surrounding the dual - component bakery products 21 is preferably given an increased moisture level during the treatment of the bakery products 24 in the microwave oven . the microwave oven 24 is for this purpose preferably provided with means for keeping the moisture content in the resonance cavity high . said means may comprise , for example , a steam moistening installation ( not shown in the drawing ). the device as drawn is designed for continuous operation , the inlet opening 28 and the delivery opening being permanently open . suitable measures are then to be taken so as to ensure that only a negligibly small microwave power can escape at said openings . measures that are appropriate per se are formed , for example , in that said openings are shaped as microwave pipes with special arrangements comprising stubs acting as reflectors for the wavelength used for the centimeter or decimeter microwaves . such arrangements are not unusual in microwave technology . besides , the wave intensity becomes quickly less in such openings ( tubes ) as the distance increases owing to absorption by the wall , especially if the latter is coated with a radiation - absorbing material , and / or by the bakery products present in the inlet and delivery openings . these opening may then be constructed as tubes , for example , and be only slightly wider / higher than the bakery products being processed . as long as there are no bakery products present in the openings or the oven , furthermore , the microwave energy may be switched off by a blocking device that is present ( not shown ). fig2 shows a detail of a microwave oven used in the invention . the oven is discontinuously operated here , after the microwave resonance cavity has been closed off with a cover exactly in - between two bakery products 24 . the closing mechanism comprises , for example , a transmission rod 34 that is driven in the direction of the arrow by an electromagnetic coil 36 . a similar arrangement is present at the inlet opening in this case . alternative closing arrangements are equally conceivable . fig3 shows a baking arrangement used in the invention with a series / parallel converter . the oven of fig1 is shown in plan view here , the resonance cavity 20 , the bakery products 24 , the conveyor belt 26 , and the inlet and delivery openings 28 , 30 being visible . the conveyor belt 26 moves to the right and enters the oven 40 . here the products are taken over by a wide conveyor belt 42 , for example in that they are pushed in lateral direction off the conveyor belt 26 by a mechanical pushing device ( not shown ). the conveyor belt 26 runs outside the plane of drawing underneath the ovens 20 , 40 back to the inlet 28 . the conveyor belt 42 moves in downward direction in the figure and leaves the oven 40 at the delivery end 44 after completion of the baking time . the products are now ready for further treatment such as cooling down , packaging , delivering , or deep - freezing . these conventional operations are not described in any detail here . the oven 40 may operate on the basis of various technologies , such as radiation or convection . whatever this technology , the heat is always supplied to the bakery products through transmission via the outside thereof . the conveyor belt 42 runs outside the plane of drawing back to the inlet of the oven 40 . good results are obtained at oven temperatures between 200 and 250 °. thus excellent results are obtained at approximately 250 ° and a baking time of , for example , approximately 5 minutes for ( flaky ) meat pastries and approximately 8 minutes for sausage rolls . the arrangement of fig3 shows two fully separated ovens interconnected by a transport device that drives the conveyor belt 26 , while also a series / parallel rearrangement is effected . it is possible that this separation is less discrete , for example in that the spatial heating zones partly overlap and the heat transfer starts as early as at the delivery opening 30 . the table below lists the results of a number of baking experiments . microwave oven hot - air oven power time temperature time ( w ) ( s ) result (° c .) ( m ′ s ″) result 400 30 sausage 200 10 ′ 00 ″ done done ( 65 ° c .) 400 30 sausage 210 8 ′ 15 ″ done ; well done browned ( 65 ° c .) 400 30 sausage 250 5 ′ 30 ″ done done ( 65 ° c .) the three columns on the left relate to the cooking of the filling ; this is the same for all three cases with a microwave power of 400 w , a cooking time of 30 seconds , and a result of good quality . the three columns on the right relate to the baking in the hot - air oven , for which three different temperatures were used and an optimum baking time was empirically determined each time . a good - quality result was obtained in all three cases , the second line yielding the best product appearance . it should be noted that the test arrangement used was for only a single sausage roll . the respective power settings and oven volumes are to be adapted in upward direction in an industrial application . if the cooking time in the microwave oven is 30 seconds , and the baking time 8 minutes , the oven 40 must have a width of approximately 5 times the length of one sausage roll , i . e . 5 × 12 cm plus various interspacings , which is in a range of 70 to 100 cm . the length of the oven 40 must then be 8 ÷ ½ = 16 times the width of a sausage roll ( being c . 6 cm ) plus various interspacings , that is in a range of 1 10 to 150 cm . alternative configurations are obviously possible . it is clear that the total processing time can be approximately halved . a similar improvement is achievable for a different oven technology . the present invention was described above with reference to preferred embodiments thereof . those skilled in the art will realize that numerous modifications may be applied therein without departing from the scope of the appended claims . the description should accordingly be regarded as illustrative rather than limitative , and no restrictions should be derived therefrom other than those mentioned in the claims . for example , although the invention is particularly suitable for dual - component bakery products with meat fillings , especially because stringent requirements are to be imposed here as regards sterility , the invention is in principle equally applicable to bakery products with a filling of vegetables or fruit , such as spring rolls or fruit pies . the invention is also applicable to dual - component bakery products whose envelope is realized by a bread dough , a flaky pastry , a winded risen dough ( which is a mixture having properties somewhere in - between those of flaky pastry and bread dough ), or other dough .

US-57415404-A

a pyrotechnic release mechanism is actuated by an electrical signal from a remote telemetry actuator such as a radio transmitter to cause two normally connected parts to separate . when used as shown with an animal collar mounted data acquisition system , the two parts can be separated to release the collar . if desired , a separate data storage device can be released to permit stored data to be recovered . the device comprises two parts with interfitting members normally held in position with a coupling pin . a pyrotechnic device is positioned behind the pin , and upon firing , the pin is moved sufficiently to clear one of the members at least , so that the two members will then separate . the device can be used to permit remotely controlled recovery of a part that is normally mounted together and which are to be separated . the movement of the separating pin after actuation can also be used for energizing a transmitter or signaling circuit that will send out a locator signal to simplify retrieval of the parts to be recovered . the linear actuation of the separating pin ensures simplicity of operation and reliability .

a release mechanism or separation device made according to the present invention indicated generally at 10 is shown mounted onto a collar assembly 11 that is made for fitting onto the neck of an animal ( not shown ). the collar assembly is made up of several strap sections including upper strap sections 12 and 13 , and lower strap sections 14 and 15 which are connected to the strap sections 12 and 13 with suitable fasteners 16 . the interior of the collar 11 can be lined with suitable soft foam rubber shown at 20 , and as can be seen the collar assembly 11 can be irregularly shaped , but generally forms an enclosure that will fit over the neck of an animal . the strap sections that are joined together also could be part of a harness used for mounting equipment on an animal . the strap sections 14 and 15 are used for mounting a data acquisition module and power pack housing indicated generally at 25 which has ears 26 that are supported on the strap sections 14 and 15 through suitable fasteners 27 . the interior of the housing 25 contains components indicated at 28 which can include power sources such as batteries , and telemetering equipment comprising a transmitter , a receiver , and other sensors and digital memory for data acquisition and storage . the components 28 can include a digital memory 30 , for example , that would provide input data from an animal activity sensor of some type so that it can measure the distance that the animal may have traveled . a magnet based activity sensor shown generally at 31 may be used . such activity sensor is more completely described in our copending application ser . no . 897127 , filed on even date herewith and entitled magnet based animal activity sensor . telemetry devices which may be mounted on the collar are shown in the copending u . s . patent application of l . david mech et al ., ser . no . 623 , 389 , filed june 22 , 1984 , for drug injection animal capture collar . the collar disclosed in that u . s . patent application included injection darts that could be remotely actuated to plunge needles in the neck muscles of animals to tranquilize them for recapture . the release mechanism shown of the present invention can provide a back - up device for recovering the collar if the drugs from the darts were ineffective . when the data acquisition device or collar is to be recovered , for example with data in the memory indicated at 30 , the separation device 10 of the present invention can be actuated by remote signals that can be transmitted by a remote transmitter to a radio signal receiver 28a comprising one of the components 28 in the housing 25 . the receiver 28a may be connected to provide an electrical firing signal to the separation device through suitable leads running along the collar straps . a first form of the release mechanism or separation device is shown in more detail in fig2 and 4 . the separation device 10 includes first and second portions , 35 and 36 , respectively . the first portion 35 is mounted with suitable fasteners 37 to the collar strap 12 , and as shown is positioned on top of the collar strap . the second portion 36 is mounted with suitable fasteners 38 to the collar strap 13 . the first portion 35 has a pair of spaced apart , aligned lugs 40a and 40b at opposite ends thereof . the lugs 40a and 40b are integral with and at one edge of a fastening plate 41 through which the fasteners 37 pass . the spacing of the lugs 40a and 40b leaves a space 43 between them , and the second fastener member 36 as shown has a single lug 45 which interfits between the lugs 40a , 40b in the space 43 . the lug 45 is carried on a mounting plate 46 of the second portion which is connected to the collar strap 13 with fasteners 38 . the first lug 40a has a bore 47 therein , see fig4 the bore 47 aligns with a blind bore 50 that is formed in the lug 45 coupled to the second fastener member 36 . the bore 50 is made so that when the lugs 45 and 40a and 40b are interfitting , the bore 50 will align with the bore 47 , and a pin 52 is inserted through both bores to hold the two lugs 40a and 45 in a fixed position relative to each other . the lugs 40a and 45 will be permitted to hinge about the axis of the pin 52 . as can be seen , the pin 52 has suitable o rings 53 and 54 thereon . the o ring 53 seals in the bore 47 , and the o ring 54 seals within the bore 50 . a squib indicated generally at 60 is provided in the closed end portion of bore 50 and a filling of suitable pyrotechnic powder is also provided . the squib has suitable leads 61 extending therefrom . an electrical signal along leads 61 will cause an ignition of the squib and burning of the pyrotechnic powder generates a gas pressure which will propel the pin 52 outwardly from the bore 50 with sufficient force to clear the bore 50 . once the pin clears the bore 50 , it is then no longer connected to the lug 45 and the lugs 45 , and 40a and 40b will separate . this will permit the collar straps sections 12 and 13 to separate . the data acquisition equipment in the housing 25 will drop off an animal wearing the collar 11 so that it can be retrieved . the pack 25 can have a locator beacon signal transmitted from it , so that people having receivers turned to a set frequency can find the dropped package . the collars are used for providing signals for locating animals , and following animals , so a transmitter in the pack 25 is usual for tracking an animal wearing the collar . fig5 and 7 illustrate a modified form of the invention wherein a collar or harness strap 70 can be fastened onto an animal in any desired way , or the strap 70 could be an attachment strap coupled to other objects or equipment . in this form of the invention , a separation device indicated at 71 has a base member 72 with a plate 73 thereon , and in this form of the invention , the plate 73 is fastened to the collar strap 70 with suitable fasteners 74 . a separating portion 75 , in this form of the invention is fastened to the base portion 72 and not to any fixed object . an object or part that is to be retrieved may be attached to portion 72 , however . the first or base portion 72 has a pair of lugs 76a and 76b which are spaced apart , and the separating portion 75 has a lug 77 that fits between the lug portions 76a and 76b . in this form of the invention , the lug 76a has a bore shown at 79 , and an aligning bore 81 is provided in the lug 77 . a pin 82 has suitable o rings at its opposite ends , as can be seen , and these o rings seal in their respective bores 79 and 81 . a squib shown generally in dotted lines at 84 is provided to provide ignition of a pyrotechnic powder also in the package with the squib to propel the pin 82 outwardly and to permit the separable portion 75 to fall off the collar strap 70 ( or other support ), as it is released from the base member 72 . as can be seen in fig7 separable portion 75 can be made to have an interior chamber 85 , and can be made in cover and bottom sections 86 and 87 that can be fastened together in a suitable manner . the chamber 85 may house a memory chip with a small power source , so that the memory can be used to store data collected by sensors and when it is desired to analyze the data , the separable part 75 can be released from the base 72 by actuating the squib 84 to ignite the pyrotechnic powder and forcing the pin 82 out . the separating part 75 can also have a small transmitter in it to provide a signal so that it can be found , or can be provided with other identifying indicia . in this way an entirely self contained separable member can be separated from a data acquisition collar of an animal or other object . fig8 shows a further modified form of the invention which permits the reusing of the release pin , and as shown , the separating device indicated at 90 has a first portion 91 that can have a fastener plate for fastening the portion to a strap of a collar or harness as shown in the previous forms of the invention . the first portion of the separating device has a lug 92 thereon . a second portion 94 of the separating device has a pair of spaced lugs 94a and 94b that extend from the base . the lug 94b is part of a removable member 96 that is held onto the rest of separable portion 94 with suitable cap screws 97 . as can be seen , the removable member 96 is needed so that the parts can be assembled . a bore 97 is provided in the lug 94a and is a two step bore , having a small diameter portion 97a and a large diameter portion 97b that is at the end adjacent lug 92 . a pin 100 is slidably mounted in the bore portion 97b , and has a small diameter neck portion 101 that slides in the bore 97a . a suitable o ring 102 is provided on the pin portion within the bore 97b . the outer end of pin 100 opposite from neck 101 fits within a bore 104 in the lug 92 , and has an ring 105 that is sealed on the interior of the bore 104 . a suitable squib detonator and pyrotechnic powder package indicated at 106 is provided in a small inner end portion of the bore 104 . in this form of the invention , when the pin 100 is propelled outwardly by pyrotechnic action , the pin portion 101 moves through bore portion 97a and a shoulder 110 engages the inner shoulder between bore portions 97a and 97b . shoulder 110 is formed where the larger pin portion 100 meets the smaller pin neck portion 101 . the engaging shoulders act as a stop and prevent the pin 100 from being expelled from the bore . however , the pin 100 is selected in length so that the end that is initially in the bore 104 will be completely clear of the lug 92 after actuation , and the separable member 91 is then free to permit one of the parts to drop away from another . because the pin 100 is captured , it will remain in place in the lug 94a and can be reused merely by pushing the small diameter neck 101 back into bore 104 of lug 92 on a new separable portion when the parts are put back together . of course , the squib and pyrotechnic powder 106 would have to be reloaded for new operation . fig9 , and 11 show another modified form of the invention which permits reusing of the release pin . as shown a separating device indicated at 120 has a first base portion 122 that may have a fastener plate 124 for fastening the base portion 122 to a strap of a collar or harness ( shown in previous forms of the invention ). the base portion 122 of the separating device 120 has housing lugs 128 and 130 thereon . a second separate housing portion or leg 132 fits on the base 122 between lugs 128 and 130 ( see fig1 ). lug 130 of the base 122 has a through bore 138 . the through bore 138 has an open side forming a release opening 139 as shown in fig1 . the side surfaces defining the opening 139 taper and narrow from the bore 138 to the exterior as seen in fig1 . the second housing portion 132 has a two - step bore 142 defined therein . the pin 144 has a first large diameter piston portion 144a slidably mounted in the large diameter portion 142a of the two - step bore 142 and a second large diameter retainer portion 144c mounted in the through bore 138 of lug 130 . the large diameter portions 144a and 144c are connected by a small diameter shank 144b . the pin 144 has suitable o ring seals 160 , 162 and 164 on the large diameter pin portions , as in other forms of the invention . the shank 144b of the pin is mounted to pass through the small diameter portion 142b of the two - step bore 142 . the lug 128 has a bore 140 defined therein one end of which axially aligns with and opens to the bore portion 142a in housing portion 132 when the lug 132 and housing portion 132 are mounted on the base . the large diameter piston portion 144a will slidably fit into bore 140 and is of length to be positioned partially within bore 140 and partially within bore portion 142a . a pyrotechnic device 156 having leads extending therefrom for receiving a remote detonating signal is located in a small end portion 158 of the bore 140 . the remote end of bore portion 158 is closed . the device 120 is assembled with the lugs 128 and 130 on the base 122 and the squib 156 is placed in the small diameter portion of bore 140 . the pin 144 is placed in bore 142 . the second large diameter retainer portion 144c will slide through bore portion 142b . the large diameter piston portion 144a is seated completely within bore portion 142a . the second housing portion or lug 132 then can be moved into position between the lugs 128 and 130 to align the bores 138 , 140 and 142 . the shank 142a will slip through opening 139 to permit the second housing portion to fully seat . the pin 144 is then pushed so the large diameter piston portion 144a is partially in bore 140 and partially in bore portion 142a , and second large diameter portion 144c of pin 144 is in bore 138 to lock the second housing portion 132 in the assembly . in this form of the invention , when the squib is detonated the pin 144 is propelled outwardly by the pyrotechnic action until the first large diameter portion 144a of the pin 144 strikes the shoulder 166 formed between the large diameter bore portion 142a and the small diameter bore portion 142b of the bore 142 . the first large diameter piston portion 144a of the pin is then moved out and clears the bore 140 of lug 128 . the second large diameter portion 144c of the pin is moved out to clear the through bore 138 of the lug 130 so that the small diameter neck portion 144b of the pin is aligned with the opening 139 of the through bore 138 . the small diameter neck portion 144b of the pin 144 may then pass out the opening 139 of the through bore 138 and the first base portion 122 and the second housing portion or lug 132 may separate . the pin 144 is retained in the two - step bore 142 and may be used again to attach to another collar assembly or mounting plate . the &# 34 ; squibs &# 34 ; are known devices that are available commercially , and serve to detonate pyrotechnic powder using a suitable electrical signal . pyrotechnic powders are also commercially available and boron potassium nitrate ( bkno 3 ) has been found to be suitable . the separation devices shown are easily manufactured , relatively low cost , and substantially fool proof in operation . they can be made of any of a number of types of material including metal or plastics . the release mechanism is driven by microcomputer electronics and programming from components in housing 25a or separate controls . triggering is accomplished by a radio signal or , if desired , automatically after a pre - programmed interval , or following some critical event such as premature loss of battery voltage . the release mechanism is useful in a number of situations . in the case of recapture collars such as those disclosed in the mech et al . u . s . pat . no . 4 , 652 , 261 , the release mechanism is useful for recovery of the collar if the recapture is unsuccessful . it also will permit removing recapture dart needles in the animal &# 39 ; s neck muscles when the collar falls free . the recapture collar controls may be programmed to trigger the release mechanism 1 - 6 hours after the recapture attempt using the drug darts as a back - up for recapturing the data . in the case of data acquisition in the collar ( i . e ., storage of acquired data in semiconductor ram or eeprom , etc . memories or cassette tape , attached to or part of the collar or harness ) the collar can be automatically released after a specific time interval , in response to a specific event , or upon receipt of a triggering radio signal . the collar or harness can then be retrieved and the data read out of the memories by appropriate techniques . in the case of data acquisition or specialized sensing , one or several data - acquisition packages made as shown in fig5 - 7 , for example , can be attached to a collar or harness and released serially over time from the collar or harness . upon release from the collar or harness , each data - acquisition package may be programmed to begin triggering its own radio - transmitter location beeper or beacon for ease of retrieval . in the case of data - acquisition packages , each package would have its own controlling electronics , and each package could be independently triggerable by radio - signal , or in response to events critical to its own integrity . although the present invention has been described with reference to preferred embodiments , workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention .

US-8077187-A

the invention concerns new pharmaceutical agents comprising the known medicinal celecoxib for oral administration and adapted to release the celecoxib in a controlled manner over an extended period , typically for a period of up 10 - 12 hours or more . the invention also includes a method for the production of the new pharmaceutical agents and a method for their use to achieve the desirable therapeutic effects of celecoxib , for example in the management of pain .

according to the invention , typical pharmaceutically acceptable excipients which may be present in the core include , for example , ethylcellulose and similar water - insoluble cellulose derivatives , and polymethacrylates , such as the eudragit ™ ne , eudragit ™ rs and eudragit ™ rl types which are commercially available from rohm polymers , darmstadt , germany , and long - chain fatty acid derivatives such as magnesium stearate , sodium stearyl fumarate , glyceryl tristearate , glyceryl behenate and glyceryl palmitostearate . one or more additional pharmaceutical excipients such as diluents , carriers , lubricants or compression aids , for example , lactose , microcrystalline cellulose , colloidal silicon dioxide , talc , hydrogenated vegetable oil ( for example that commercially available as lubritab ™) or magnesium stearate or the like , may be present in the core or another part of the overall compositions of the invention . typical pharmaceutically acceptable solubilisers in the coating include , for example , anionic surfactants such as sodium lauryl sulphate . other constituents which may be present in the coating include , for example , hypromellose and polysorbatum , but other well know coating constituents may also be included . in particular , the coating may also contain one or more conventional pharmaceutically acceptable pigments such as titanium dioxide or iron oxide and a sweetener or taste masking agent may also optionally be present . the compositions of the invention may be in single unit dosage form such as tablets or capsules , of which tablets are preferred . alternatively they may be in multiple unit dosage form , in the form of granules , pellets or mini - tablets . the term “ pharmaceutically acceptable ” refers to a constituent of a pharmaceutical composition that is generally known to be suitable for pharmaceutical use and safe for administration to humans and animals . without wishing to be bound by any theory , it is believed that the largely water - insoluble core forms a matrix that controls diffusion of water into the composition . this water dissolves the celecoxib within a certain time enabling release of dissolved material in a sustained manner . for preparing the core , the celecoxib active ingredient may either be granulated with the water - insoluble material or else homogenised into an intimate mixture that can be further used in the manufacture of the oral dosage forms . inclusion of celecoxib and a solubiliser such as an anionic surfactant like sodium lauryl sulphate into the coating is believed to result in the initial fast release of the celecoxib to achieve the required biological effects within a short time . the compositions according to the invention may be manufactured by standard pharmaceutical processes well known in the art , for example as illustrated in the accompanying examples . it will be understood that the order of adding particular constituents and excipients in the manufacture of compositions of the invention may be varied according to standard practice . however , in general it is preferred to mix the celecoxib active ingredient with one or more of the lipid pharmaceutically acceptable ingredients , for example , with the eudragit ™ polymer when present . the particular amount of celecoxib in the core and in the coating of a composition according to the invention may typically be in the general range 5 - 75 % by weight . however , preferred compositions include those in which the core contains , for example about 70 - 85 %, and the coating about 15 - 30 %, by weight of celecoxib active ingredient . especially preferred compositions include those in which the core contains , for example , about 80 % and the coating about 20 % by weight of celecoxib active ingredient . the overall amount of celecoxib per unit pharmaceutical composition ( for example per tablet ) is about 100 - 700 mg , and preferably about 100 - 300 mg . compositions according to the invention provide at least 20 % ( and preferably 30 % release ) of celecoxib within 1 hour with extended release of celecoxib over a further 15 hours , making compositions of the invention suitable for single daily dosing . the release of celecoxib may be measured using standard techniques well known in the pharmaceutical arts such as those provided for checking dissolution of active ingredients in pharmacopoeias such as the us pharmacopoeia . the invention also provides a novel extended release pharmaceutical composition comprising celecoxib in the amount of 50 - 700 mg per unit dosage form ( and preferably 50 - 250 mg per unit dosage form ), dispersed between a largely water - insoluble core and a hydrophilic coating . it may also be desirable for the core to include a further component which comprises a largely water insoluble , largely water impermeable substance , such as magnesium stearate , sodium stearyl fumarate , glyceryl tristearate , glyceryl behenate or glyceryl palmitostearate , itself mixed with celecoxib and such a pharmaceutical composition is provided as a further feature of the invention . typically in such a composition the celecoxib in the further component of the core constitutes about 10 - 30 % of the overall weight of celecoxib in the composition . the invention also provides a process for the manufacture of a new extended release pharmaceutical composition of celecoxib as defined above which comprises the steps of preparing the core by mixing celecoxib with one or more additional pharmaceutically acceptable excipients and then applying the hydrophilic coating in a conventional manner . the invention also provides a method for delivering a cox - 2 inhibitory amount of celecoxib over an extended period to an animal requiring such treatment for example in the management of pain which comprises administering to such animal an effective amount of a novel extended release composition of the invention as defined above . the celecoxib used as active ingredient may be in any convenient physical form which remains stable during and following formulation . the celecoxib is generally used as a powder with particle size with d 90 of about 50 - 200 μm and preferably of about 50 - 80 μm . a particularly suitable form of celecoxib for use in the compositions of the invention is that referred to as celecoxib form n . this form n is essentially free of amorphous and other polymorphic forms and has characteristic x - ray diffraction pattern peaks , expressed in d values , at about 16 . 0 å , 15 . 3 å , 12 . 3 å , 10 . 6 å , 8 . 0 å , 6 . 5 å , and 5 . 4 å . celecoxib form n may be obtained by heating a stirred suspension of the known , thermodynamically most stable celecoxib form iii in n decane or n - tetradecane at about 165 ° c . to give an emulsion . this is then cooled with stirring to about 145 ° c ., reheated to about 165 ° c . and then cooled to about 110 ° c . the crystalline solid obtained is separated from the resultant suspension and dried under vacuum at 100 ° c . to give celecoxib form n . the invention provides as a still further and preferred feature an extended release coated pharmaceutical composition as defined above which is characterised in that the celecoxib active ingredient is celecoxib form n . the invention will now be illustrated by the following non - limiting examples : component core coating celecoxib (%) 80 20 composition of the tablets ( mg ) celecoxib * 100 . 00 microcrystalline cellulose 169 . 20 lactose 160 . 00 eudragit ™ rs 20 . 00 glyceryl tristearate 11 . 00 lubritab ™ 11 . 00 calcium hydrogen phosphate 10 . 00 colloidal silicon dioxide 3 . 80 magnesium stearate 5 . 00 talc 2 . 08 hypromellose 3 . 30 polysorbatum 80 1 . 50 sodium lauryl sulphate 0 . 08 titanium dioxide 2 . 90 iron oxide , red 0 . 08 iron oxide , yellow 0 . 06 * d 90 = 62 μm , d 50 = 17 μm ( mixture of various batches ) celecoxib was intermixed with lactose and parts of microcrystalline cellulose and colloidal silicon dioxide and granulated with an aqueous dispersion of eudragit ™ rs . wet granules were dried in a fluid - bed dryer , and then milled through a 20 mesh ( 0 . 8 mm ) screen to obtain appropriate size distribution of the granules suitable for compression . glyceryl tristearate , lubritab ™, calcium hydrogen phosphate and the remaining parts of microcrystalline cellulose and colloidal silicon dioxide , were blended 20 min prior to sieving through a 30 mesh ( 0 . 6 mm ) sieve . magnesium stearate , screened through a 30 mesh ( 0 . 6 mm ) sieve was added to the core component above . the final blend was homogenised for another 5 minutes and then compressed into tablets . the remaining part of celecoxib was dispersed in an aqueous suspension of talc , hypromellose , polysorbatum , sodium lauryl sulphate , titanium dioxide and iron oxides , and used for tablet coating . components core coating celecoxib (%) 80 20 composition of the tablets ( mg ) celecoxib ( d 90 = 68 μm , d50 = 13 μm ) 100 . 00 microcrystalline cellulose 169 . 20 lactose 160 . 00 eudragit ™ rs 20 . 00 glyceryl tristearate 5 . 00 lubritab ™ 5 . 00 calcium hydrogen phosphate 10 . 00 colloidal silicon dioxide 3 . 80 magnesium stearate 5 . 00 talc 2 . 08 hypromellose 3 . 30 polysorbatum 80 1 . 50 sodium lauryl sulphate 0 . 08 titanium dioxide 2 . 90 iron oxide , red 0 . 08 iron oxide , yellow 0 . 06 celecoxib was intermixed with lactose and parts of microcrystalline cellulose and colloidal silicon dioxide and granulated with an aqueous dispersion of eudragit ™ rs . wet granules were dried in a fluid - bed dryer , and then milled through a 20 mesh ( 0 . 8 mm ) screen to obtain appropriate size distribution of the granules suitable for compression . glyceryl tristearate , lubritab ™, calcium hydrogenphosphate and the remaining parts of microcrystalline cellulose and colloidal silicon dioxide , were blended for 20 min prior to sieving through a 30 mesh ( 0 . 6 mm ) sieve . magnesium stearate , screened through a 30 mesh ( 0 . 6 mm ) sieve was added to the core component above . the final blend was homogenised for another 5 minutes and then compressed into tablets . the remaining part of celecoxib was dispersed in an aqueous suspension of talc , hypromellose , polysorbatum , sodium lauryl sulphate , titanium dioxide and iron oxides , and used for tablet coating . components core coating celecoxib (%) 80 20 composition of the tablets ( mg ) celecoxib ( d 90 = 68 μm , d50 = 13 μm ) 100 . 00 microcrystalline cellulose 169 . 20 lactose 160 . 00 eudragit ™ rs 20 . 00 glyceryl tristearate 1 . 00 lubritab ™ 1 . 00 calcium hydrogen phosphate 10 . 00 colloidal silicon dioxide 3 . 80 magnesium stearate 5 . 00 talc 2 . 08 hypromellose 3 . 30 polysorbatum 80 1 . 50 sodium lauryl sulphate 0 . 08 titanium dioxide 2 . 90 iron oxide , red 0 . 08 iron oxide , yellow 0 . 06 celecoxib was intermixed with lactose and part of the microcrystalline cellulose and colloidal silicon dioxide and granulated with an aqueous dispersion of eudragit ™ rs . wet granules were dried in a fluid - bed dryer , and then milled through a 20 mesh ( 0 . 8 mm ) screen to obtain appropriate size distribution of the granules suitable for compression . glyceryl tristearate , lubritab ™, calcium hydrogen phosphate and the remaining parts of the microcrystalline cellulose and colloidal silicon dioxide were blended 20 min prior to sieving through a 30 mesh ( 0 . 6 mm ) sieve . magnesium stearate , screened through a 30 mesh ( 0 . 6 mm ) sieve was added to the core component . the final blend was homogenised for another 5 minutes and then compressed into tablets . the remaining part of celecoxib was dispersed in an aqueous suspension of talc , hypromellose , polysorbatum , sodium lauryl sulphate , titanium dioxide and iron oxides , and used for tablet coating . [ this example describes release studies on the illustrative coated mono - component formulations of the invention described in examples 1 - 3 above .] samples of formulation were placed in 900 ml of 37 ° c . phosphate buffer ph 6 . 8 containing 0 . 5 % sodium lauryl sulphate (“ nals ”) using the procedure described for method ii in the us pharmacopoeia ( 100 rpm ). the release of celecoxib was determined by uv spectroscopy ( λ = 255 nm ). the results obtained are shown in table 1 below and in fig1 . this example describes the preparation of an alternative composition of the invention : in which the core contains an additional water insoluble , water impermeable substance component which has itself been blended with celecoxib . composition of the tablets ( mg ) celecoxib 100 . 00 microcrystalline cellulose 200 . 00 lactose 200 . 00 eudragit ™ rs 40 . 00 glyceryl tristearate 60 . 00 talc 5 . 00 magnesium stearate 3 . 00 hypromellose 10 . 00 polysorbatum 80 1 . 90 sodium lauryl sulphate 0 . 10 celecoxib ( 70 parts by weight ) was intermixed with microcrystalline cellulose and lactose and granulated with an aqueous dispersion of eudragit ™ rs . wet granules were dried in a fluid - bed dryer , and then milled through a 20 mesh ( 0 . 8 mm ) screen to obtain appropriate size distribution of the granules suitable for compression . celecoxib ( 10 parts by weight ) was mixed with glyceryl tristearate , blended 15 minutes and sieved through a 30 mesh ( 0 . 6 mm ) sieve . components a and b above and talc were homogenised for 15 minutes . magnesium stearate , screened through a 30 mesh ( 0 . 6 mm ) sieve was added to the final blend and homogenised for another 5 minutes . the final blend was compressed into tablets . the remaining celecoxib ( 20 parts by weight ) was dispersed in an aqueous suspension of hypromellose , polysorbatum and sodium lauryl sulphate and used for tablet coating . if desired , various pigments , such as titanium dioxide or iron oxides , may be added to the hydrophilic coating . note : the celecoxib used in examples 1 - 3 and 5 may conveniently be celecoxib form n which may be prepared as follows : celecoxib form iii ( 2 . 5 g ) is suspended in 50 ml of n - tetradecane and then heated to about 165 ° c . while stirring . the emulsion obtained is stirred at the same temperature for about 15 min and then cooled to about 145 ° c . it is then reheated to about 165 ° c . and then cooled to about 110 ° c . the resultant suspension is separated by filtration and the crystals obtained are dried at 100 ° c . under the vacuo for 12 hours to yield celecoxib form n . fig2 shows an x - ray powder diffraction ( xrpd ) pattern for a representative sample of celecoxib form n measured using cukα radiation on a powder sample collected using a panalytical x &# 39 ; pertpro powder diffractometer . the pattern has characteristic peak position ( expressed in d values ) at 16 . 0 ± 0 . 2 å , 15 . 3 ± 0 . 2 å , 12 . 3 ± 0 . 2 å and 10 . 6 ± 0 . 2 å , and further characteristic peaks at 8 . 0 ± 0 . 2 å , 6 . 5 ± 0 . 1 å , and 5 . 4 ± 0 . 1 å . the starting celecoxib form iii may itself be produced , for example , as described in us patent application publication no . 2004 / 0087640a starting from celecoxib produced by any known process , for example that described in example 1 of u . s . pat . no . 5 , 910 , 597 . [ this example describes release studies on a typical composition of the invention made according to example 5 .] a sample of the tablets from example 5 was placed in 900 ml of 37 ° c . phosphate buffer ph6 . 8 containing 0 . 5 % sodium lauryl sulphate using the procedure described for method i in the us pharmacopoeia . the release of celecoxib was determined by uv spectroscopy at λ = 255 nm as shown in the attached fig3 . the results show the immediate release of & gt ; 20 % of celecoxib in the first 15 minutes followed by extended release over the next 10 hours with & gt ; 30 % of celecoxib remaining .

US-79112205-A

medical devices and methods for delivering therapeutic fluids transcutaneously to a body of a patient via a fluid delivery device and an adapter is provided . a luer slip connector is provided at a first connecting end of the adapter . a therapeutic fluid container is connected with the second connecting end such that the container &# 39 ; s neck is received in the second connecting end and a hollow penetrating member provided in the adapter punctures the septum of the container to admit the therapeutic fluid into a needle - less syringe from the container . after , fluid emerges from the tip of the penetrating member , the second connecting end of the adapter is attached to the fluid delivery device , thereby filling the reservoir with the fluid and pushing the syringe plunger forward to inject fluid into reservoir .

the foregoing and other features , aspects , and advantages of the present invention will be more apparent from the following detailed description , which illustrates exemplary embodiments of the present invention . referring now to fig1 , there is illustration of an exemplary embodiment of a fluid delivery device 100 constructed in accordance with some of the embodiments of the present invention , also referred to as a patch unit , which may be adherable to a patient &# 39 ; s body , and a remote control unit ( not shown ), which communicates with the patch unit 100 . the patch unit may comprise a disposable portion 10 , which is detachably connectable to a reusable portion 12 . the configuration of the fluid delivery device comprising such a patch unit is disclosed in applicants israel patent application no . 171813 as well as in u . s . patent application ser . no . 11 / 397 , 115 , both disclosures herein incorporated by reference in their entireties . one of the advantageous of such a fluid delivery device 100 configuration is that the relatively expensive components may be deployed within the reusable portion 12 while less expensive components might be accommodated within the disposable portion 10 . by virtue of this provision , the use of the device is significantly more economical for the patient . reusable portion 12 of a fluid delivery device 100 may be removably coupled to a disposable portion 10 in operative association , as shown in fig1 . in fig2 , only the disposable portion 10 of the fluid delivery device is shown . the disposable portion 10 may include a u - shaped housing defined by lateral walls lw 1 and lw 2 , by bridging section bs and by butt ends be 1 and be 2 . one of ordinary skill in the art would recognize that the u - shaped housing may vary in shape in perspective to a non - formal u - shape . additional components of the disposable portion 10 may include a reservoir 14 situated between lateral walls and butt end be 2 . the reservoir 14 preferably includes a therapeutic fluid , e . g . insulin . the reservoir 14 is in fluid communication with a delivery tube 16 , terminating by an outlet port 18 . through this port the fluid can be delivered to a cannula ( not shown ), which is subcutaneously inserted in a patient . the reservoir 14 can be filled with the therapeutic fluid through an inlet port 20 , which may be made in butt end be 2 . the butt end be 2 may include a rectangular configuration terminating by a face 22 . a sealing cover 24 preferably seals the inlet port 20 . in accordance with the design of the patch fluid delivery device unit 100 , a portion of the delivery tube 16 , which extends along the bridging section bs may be placed between a stator plate and wheels of a peristaltic pump of the reusable portion 12 ( not shown ). when these wheels rotate , they depress the tube 16 to the plate and squeeze it . accordingly , the fluid is periodically pumped from the reservoir 14 to exit port 18 and further to the cannula . with reference to fig3 - 5 adapter 26 of the invention is generally illustrated , which may be suitable for connecting the reservoir 14 with a syringe filled with a therapeutic fluid . preferably , the adapter 26 is configured as an elongated tubular structure made of a plastic suitable for medical use , which in a preferred embodiment is of inexpensive material . the adapter 26 may include a first connecting end 28 , and may also include an opposite second connecting end 30 , with an intermediate body portion 32 . the first connecting end 28 may be attachable to a needle - less syringe 50 , as seen in fig8 . the second connecting end 30 may be releasably attachable either to a circular neck of container for therapeutic fluid or to an end ( e . g ., rectangular butt end be 2 ) of a housing of a fluid delivery device ( e . g ., that of the patch unit 100 ). the second connecting end 30 may be provided also with an abutment wing 34 , which may be used to rest on lateral wall lw 2 of the housing when the second connecting end 30 is connected to the butt end be 2 of the housing . referring to fig4 and 5 , it is seen that the second connecting end 30 may be provided with a border wall 36 delimiting a depression . the contour of the border wall 36 comprises a circular portion 38 and a non - circular portion 40 . the non - circular portion 40 may be a rectangular shape or any other shape which would be understood by one of ordinary skill in the art . the circular portion 38 of the border wall 36 may define a circular region d 1 of the depression . this region d 1 is preferably intended for receiving the circular neck of the fluid container . the non - circular portion 40 of the border wall may define a non - circular region d 2 of the depression . this region d 2 can be used for receiving butt end be 2 of the housing . the circular 38 and non - circular 40 regions may be configured and dimensioned to allow a tight fit with the received items irrespective whether it is circular neck of the fluid container or butt end of the housing . circular portion of the border wall is provided with gaps g 1 , g 2 , g 3 , to provide a discontinuous arrangement , which preferably provides a degree of elasticity . it is understood by one of ordinary skill in the art that the number of gaps g 1 - g 3 may vary accordingly between alternative embodiments . seen in the center of the region d 1 is a sharpened end 42 of a penetrating member , which is secured at the first connecting end of the adaptor 26 . the sharpened end is preferably fully concealed within depression delimited by the border wall 36 and therefore is preferably not accessible . by virtue of this provision inadvertent puncture may be prevented . as shown in fig6 , the first connecting end 28 may be provided with a core 44 , in which a cavity 46 may be provided . the shape of the core and of the cavity may be selected to constitute a female half of luer slip connector . a hollow penetrating member 48 is secured within the core such that sharp end 42 of the penetrating member protrudes inside region d 1 of the depression made in the second connecting end 30 of the adapter 26 . by virtue of this provision , fluid communication is provided between cavity 46 and the depression in the second connecting end 30 . as a suitable penetrating member , one can use a hollow needle or a cannula , according to one embodiment . instead of dedicated core with cavity 46 , one can use ready - to - use female half of luer connector , which would be suitably embedded in the first connecting end 28 . referring to fig7 and 8 it is shown how a needle - less syringe 50 is connected to the first connecting end 28 of the adapter 26 . it is seen that male half 52 of luer slip connector provided at the syringe 50 is inserted within female half 46 of the luer connector associated with the first connecting end 28 . referring to fig9 a and 9b it is shown how the second connecting end 30 may be attached to a fluid container 54 . it is seen in fig9 b , that when a neck 56 of the container is fully received within circular depression region d 1 of the second connecting end 30 , the penetrating member 48 pierces a cover 58 of the container and protrudes inside the container . one of skill in the art can readily appreciate that since there is provided fluid communication between the first 28 and second 30 connecting ends , the therapeutic fluid could be withdrawn from the container through the penetrating member into the syringe 50 . referring now to fig1 a and 10 b it is shown the second connecting end 30 of the adapter 26 being attached to rectangular butt end be 2 of the housing , while first connecting end 28 is attached to syringe 50 such that reservoir 14 can be filled or replenished by the therapeutic fluid from the syringe 50 . it is seen that the butt end be 2 is received within depression in the second connecting end 30 such that it is embraced by non - circular portion 38 of the border wall and by abutment wing 34 juxtaposed with lateral wall lw 2 of the housing . in this position piercing member 48 pierces sealing cover 24 of the reservoir 14 such that therapeutic fluid can be delivered through inlet port 20 to the reservoir from syringe 50 . below is an exemplary method , according to some embodiments of the present invention , of how a reservoir of a fluid infusion device can be filled with the aim of adapter of the invention . when filling the reservoir of the fluid infusion device , the first connecting end of the adapter may be attached to the male half of luer connector of a needle - less regular syringe as illustrated in fig7 . typically , such syringes are supplied with separate therapeutic fluid containers in a pharmacy store . the second connecting end of the adapter may then be firmly attached to the fluid container until circular portion of the border wall engages the orbicular neck of the fluid container and piercing member pierces sealing cover of the container . in one embodiment , in order to eliminate entering of air into syringe , the syringe connected to adapter is held in a vertical position whereas the second connecting end is on top , as illustrated in fig8 a . by pulling the syringe &# 39 ; s plunger backward , fluid from the container can be withdrawn through the piercing member into the syringe . when the syringe is filled with the desired dose , the fluid container is detached from the second connecting end . it is worth noting that entrapment of air bubbles during the withdrawing process should preferably be prevented . for this purpose , according to an embodiment of the invention , air is primed from the syringe before withdrawal of the medicament fluid . during the priming , the syringe is preferably held in a vertical position whereas the second connecting end is on top . then , the plunger of the syringe may be slightly pushed inwardly until a first drop ( s ) of the fluid appears at the tip of the penetrating member . after the syringe is filled with the fluid , the second connecting end of the adapter may be separated from the container and then attached to the housing of the disposable portion of the fluid infusion device as illustrated in fig1 a and fig1 b . the therapeutic fluid can be now transferred from the syringe to the reservoir of the fluid infusion device . it is worth noting that during attachment and filling of the reservoir , the adapter and the housing are preferably held in a vertical position such that the outlet port of the housing is on top . then , the plunger may be slowly pushed inwardly until first drop ( s ) of fluid appears at the outlet port , indicating that reservoir is full and that air in delivery tube was primed . the adapter can then be detached from the housing and the fluid infusion device is ready to operate . although particular embodiments have been disclosed herein in detail , this has been done by way of example for purposes of illustration only , and is not intended to be limiting with respect to the scope of the appended claims , which follow . in particular , it is contemplated that various substitutions , alterations , and modifications may be made without departing from the spirit and scope of the invention as defined by the claims . other aspects , advantages , and modifications are considered to be within the scope of the following claims . the claims presented are representative of the inventions disclosed herein . other , unclaimed inventions are also contemplated . the applicant reserves the right to pursue such inventions in later claims .

US-98968007-A

this invention is a self spotting safety bench press composed of an adjustable bench and uprights located on either side of the bench adjacent the lifters upper body . lifting arms extend from the uprights into the barbells pathway and have the ability to slide up and down to contact the barbell and decrease the weight exerted on the exerciser . hydraulic cylinders provide force to each lifting arm , which is depressed below the barbells path before use . when assistance is needed , the exerciser releases a hydraulic restrictor valve causing the arms to ascend removing a user - determined amount of weight from the barbell while permitting the user to continue performing repetitions . a second restrictor valve can allow only upward movement should the exerciser fail . a third flow restrictor valve adjusts the rate of arm travel . an air charged hydraulic accumulator provides the hydraulic pressure to the cylinders .

in the following description , terms such as horizontal , upright , vertical , above , below , beneath , and the like , are used solely for the purpose of clarity in illustrating the invention , and should not be taken as words of limitation . the drawings are for the purpose of illustrating the invention and are not intended to be to scale . [ 0057 ] fig1 shows a composite drawing of the device . there are 2 uprights ( 1 a , 1 b ) parallel to each other and tilted slightly away from the longer side of the seat ( 4 ). two adjustable weight rests and seat supports ( 12 a , 12 b ) are located on the inner side of each upright . protruding from the front of each upright ( 1 a , 1 b ) is a lifting arm ( 8 a , 8 b ) that extends perpendicular to gravity , and in the direction of the seat ( 4 ). each upright ( 1 a , 1 b ) has a support ( 2 a shown only ) and is connected to the other via a cross bar ( 3 ). mounted on the cross bar is an accumulator ( 15 ). the accumulator is attached to a pump ( 16 ) via an air supply line ( 17 ). the other end of the accumulator is connected to hydraulic cylinders ( 11 a , 11 b ) via a fluid supply line ( 18 ). the hydraulic cylinders ( 11 a , 11 b ) are mounted at one end to the bottom of an upright ( 1 a , 1 b ) on the hydraulic cylinder upright attachment ( 10 ), and the other end to the hydraulic cylinder slide attachment ( 9 a , 9 b ) that protrudes from the outer side of each upright ( 1 a , 1 b ). above the center of the cross bar ( 3 ) is an adjustable seat support bar ( 32 ) that supports one end of the seat ( 4 ). the other end of the seat is supported by an adjustable vertical seat support ( 5 ). attached to the vertical seat support , close to the floor is an actuator . actuator cables ( 22 ) extend from the actuator to hydraulic fluid valves ( see fig8 ). [ 0058 ] fig2 focuses on upright ( 1 b ). the inner side and front side of upright ( 1 b ) contains weight rest support holes ( 23 ) extending partially down the upright . the front of upright ( 1 b ) to the right of the holes contains a lifting arm slot ( 24 ). [ 0059 ] fig3 shows the outer side of the upright ( 1 b ) containing a hydraulic cylinder slide attachment slot ( 24 ) and a hydraulic cylinder upright attachment ( 10 ). contained within the upright are centering holes for holding the slide bar ( 6 b ) that can be seen in fig4 . [ 0060 ] fig4 shows the parts an upright ( 1 b ) contains without the upright itself included . the slide bar ( 6 b ) nearly extends the full length of the upright ( 1 b ). mounted on the slide bar ( 6 b ) is the slide ( 7 b ), which has been fastened with the hydraulic cylinder slide attachment ( 9 b ). in addition , the slide has lift arm support holes ( 26 ) and slide bearings ( 14 ) at either end . the lifting arm ( 8 b ) is able to be mounted on the slide ( 7 b ) in various positions . [ 0061 ] fig5 shows lifting arm ( 8 ). the slide contact of the lifting arm ( 8 ) contains two semi circles ( 27 a , 27 b ). the first is directly behind the arm extension ( 27 a ) to contact the front of the slide . this semicircle contains a pin at its center that coincides with the lift arm support holes ( 26 ). the second semi circle ( 27 b ) contacts the back of the slide . this contact point is higher on the slide ( 7 b ) ( fig4 ) than the first semicircle . this semicircle arrangement causes the lift arm pin ( 28 ) to slide out of the lift arm support hole ( 26 ) ( fig4 ) when the tip of the arm is raised ( the pivot pint roughly being between the upper and lower semicircles ). this action also causes the semi circles to no longer tightly contact the slide ( 7 b ), permitting movement of the lifting arm up and down the slide ( 7 b ) enabling adjustment . [ 0062 ] fig6 and 7 show the adjustable seat and weight rest ( 12 b ). this piece is “ u ” shaped to partially wrap around an upright ( 1 b ). it contains two mounting pins . the first pin is located on the backside of the front plate containing the barbell support extension . the second pin is located on the side plate to extend into the inner weight rest support holes ( 23 ). pin location coincides with the weight rest support holes ( 23 ). pin location allows the front pin to slide into the rest support hole ( 23 ) when the adjustable seat and weight rest ( 12 b ) is rotated clockwise 90 degrees . with the first pin seated in the support hole , rotation of the adjustable weight rest ( 12 b ) 90 degrees counter clock wise ( with the front pin within the support hole ( 23 ) being the axis of rotation ) seats the inner pin in the inner rest support hole ( 23 ). this part also has a semicircle attachment mounted on its inner most face . this semicircle is of suitable size and shape to support the seat support bar ( 32 ) when attached to an upright . [ 0063 ] fig8 shows the hydraulic and pneumatic system that powers the self - spotting bench . the accumulator ( 15 ) is connected at one end to an air pump ( 16 ) via an air line ( 17 ). a hydraulic line ( 18 ) exits the accumulator ( 15 ) from the other end and leads to three valves ; one - way valve to cylinder ( 20 ), one - way valve to accumulator ( 21 ), and the flow rate valve ( 19 ). the hydraulic line then splits and leads to each hydraulic cylinder ( 11 a , 11 b ). turning now to fig1 , another embodiment for an accumulator ( 34 ) has no moving parts and no internal partition . accumulator ( 34 ) has a pressure vessel casing ( 35 ) that encloses an upper internal region ( 36 ) and a lower internal region ( 37 ). lower internal region ( 37 ) is filled with a hydraulic fluid ( 38 ). upper internal region ( 36 ) is filled with a compressible medium ( 39 ) such as air . hydraulic lines 40 serve as fluid conduits between the hydraulic cylinders of fig1 and lower internal region ( 37 ). hydraulic lines ( 40 ) are connected to a three - way hydraulic valve 41 that controls and directs the flow of hydraulic fluid between accumulator ( 34 ) and the hydraulic cylinders of fig1 . three - way hydraulic valve ( 41 ) has a first position ( 42 ) that only allows hydraulic fluid ( 38 ) to flow to the hydraulic cylinders , a second position ( 43 ) that only allows hydraulic fluid ( 38 ) to flow into accumulator ( 34 ) and a third position ( 44 ) that allows hydraulic fluid ( 38 ) to flow in either direction . three - way valve ( 41 ) is connected to a port ( 45 ) that passes through pressure vessel casing ( 35 ) into lower internal region ( 37 ). also , a flow dispersion device such as a baffle ( 46 ) is connected to port ( 45 ) to prevent excess air bubbles from forming in hydraulic fluid ( 38 ). a manual pressure release valve ( 47 ) allows an operator to decrease the lifting force supplied from accumulator ( 34 ) by venting a significant portion of compressible medium 39 to the atmosphere . moreover , a compressible medium pump ( 38 ) is included to recharge accumulator ( 34 ) with compressible medium ( 39 ) whenever the operator desires to increase the lifting force providing by accumulator ( 34 ). preferably , compressible medium pump ( 38 ) is a foot - operated air pump connected to the accumulator by way of an air line 49 in communication with upper internal region ( 36 ). a desiccant 50 is included within air line 49 to prevent moisture build - up inside accumulator 34 . a pressure indication gauge ( 51 ) is in communication with upper internal region ( 39 ) to indicate the potential lift force that can be provided by accumulator 34 . furthermore , a safety pressure release valve ( 52 ) is in communication with upper internal region ( 39 ) and will vent compressible medium ( 39 ) to the atmosphere in the event the pressure inside accumulator ( 34 ) begins to approach a predetermined safe pressure limit . a turbulence - reducing medium ( 53 ) is also enclosed by pressure vessel casing ( 35 ) to prevent hydraulic fluid ( 38 ) from being sprayed out of safety pressure release valve ( 52 ). fig1 depicts turbulence - reducing medium ( 53 ) as a rigid mesh . however , turbulence medium ( 53 ) can also be a set of fins or a set of baffle plates or practically any other type of fluid damping medium . [ 0069 ] fig1 shows another alternate accumulator ( 54 ) made up of a pressure vessel casing ( 55 ) having a first compartment ( 56 ) and a second compartment ( 57 ). compartments ( 56 ) and ( 57 ) are separated by a partition ( 58 ) made from a continuous flexible membrane that prevents a compressible medium ( 59 ) in first compartment ( 56 ) from coming into contact with a hydraulic fluid ( 60 ) in second compartment ( 57 ). at least one hydraulic fluid line ( 61 ) is in communication with second compartment ( 57 ) to direct hydraulic fluid to and from hydraulic cylinders . similar to accumulator ( 15 ) shown in fig1 alternate accumulator ( 54 ) can be positioned horizontally underneath seat 4 . [ 0071 ] fig9 shows the barbell ( 33 ) free weight starting point held on the adjustable weight rest and seat bar support ( 12 ). the distance from the seat ( 4 ) ( and therefore the lifter ) can be adjusted by rotating each adjustable weight rest 90 degrees away from the upright ( 1 a , 1 b ) using the front pin as a pivot point . after being rotated , the adjustable weight rest and seat bar support ( 12 ) can be separated from the upright ( 1 ) by moving it perpendicular to the upright in the direction the lifting arm ( 8 ) extends . the adjustable weight rest and seat bar support ( 12 ) can be reattached in other locations performing the reverse of these instructions in any other weight rest support hole ( 23 ). the lifting arm range location can be adjusted upward and downward to the lifters preference . this is done by tilting the tip of the lifting arm ( 8 a , 8 b ) upward , causing the semicircles ( 27 ) to separate from the slide ( 7 ) and the support pin ( 28 ) to slide out of the lift arm support hole ( 26 ). in this position , the lifting arm can be slid up and down the slide ( 7 ) then relocated in another position . with the barbell held on the adjustable weight rest ( 12 a , 12 b ) the lifter can now set the one - way flow valve to accumulator ( 21 ) to be active . this will allow the lifting arms ( 8 a , 8 b ) to only move downward . the lifter has two options as to how to depress the lifting arms ( 8 a , 8 b ). the first option is to get in the exercising position , remove the barbell ( 33 ) from the adjustable weight rest ( 12 a , 12 b ) allowing the weight to lower and depress the lifting arms ( 8 a , 8 b ), and then start repetitions from the lowest point the bar traveled . the second option is to depress each lifting arm ( 8 a , 8 b ) by hand to a point where it will not interfere with the exercise until released . if the lifter desires an increased or decreased assisting force exerted on the barbell by the lifting arms , an air adjustment can be made to the accumulator by either pumping ( 16 ) more air in or releasing air . if the rate at which the lifting arm ascends is too slow or fast , the adjustable hydraulic fluid flow valve ( 19 ) can also be manipulated to suit user preference . with the lifting arms depressed and equipment adjusted to suit lifter preferences , the repetitions are started . when the lifter needs a “ spot ” the one way flow valve ( to accumulator ) is released . the compressed air in the accumulator ( 15 ) acts as a spring and forces hydraulic fluid through the hydraulic cylinder fluid supply line ( 17 ) and into the hydraulic cylinder ( 11 a , 11 b ). the cylinder shaft then raises the slide ( 7 ) causing the attached lifting arm to also rise . the lifting arms contact the barbell and assist ( spot ) the lifter . the opposite of this action occurs when the lifting arms are being depressed ( i . e . the hydraulic fluid in the hydraulic cylinders ( 11 a , 11 b ) is forced back into the accumulator where potential energy is stored in the form of compressed air . with the one - way flow valve ( to accumulator ) ( 21 ) released , the lifting arms ( 8 ) will be permitted to move up and down while still asserting an assisting force on the barbell ( 33 ). this allows the lifter to continue by performing assisted repetitions when he / she could no longer lift the original weight unassisted . should the upward force desired by the lifter exceed the weight of the barbell the entire weight will be lifted by the machine , not permitting assisted repetitions . when the lifter is no longer able to perform the assisted repetitions ( or whenever else the lifter desires ) the one way flow valve ( to cylinder ) ( 20 ) can be engaged . this will only allow hydraulic fluid to flow toward the cylinders ( 11 a , 11 b ), thus allowing the lifting arms to raise but not be lowered . this will allow the lifter to lift the barbell with assistance , and then prevent the barbell ( 33 ) from falling on the lifter when failure occurs . the manipulation of the one - way flow valves ( 21 , 22 ) mentioned above is accomplished by use of an actuator ( 13 ) the exerciser manipulates with his / her lower leg or foot . the actuator ( 13 ) is connected to the hydraulic valves via actuator cables ( 22 ) and pulley transmission system . when the actuator ( 13 ) is kicked once in the direction of the accumulator ( 15 ) the one - way valve to the accumulator ( 21 ) will be released . when kicked a second time the one - way valve to the cylinder ( 20 ) will be engaged . the system can then be reset by either kicking the actuator ( 13 ) a third time or manually resetting the one way flow valves ( 21 , 22 ). due to the stress the exerciser is experiencing during failure , the exercisers leg or foot is likely to contact the actuator with significant force . the actuator therefore has a limited range of motion and does not transfer all of this energy to the valves . for the same reason , the actuator is constructed with suitable smooth surface area as to not injure the exerciser when kicked . the design of the actuator ( 13 ) shown in fig1 is not intended to limit the scope of this invention . a lanyard that attaches to the exercisers leg or foot is also feasible . thus the reader will see that the self - spotting safety bench press of this invention provides a dependable spotting machine that increases user safety . the spotting speed and force exerted is fully adjustable to suit user preferences , as is the spotting arm range location , weight rest position , and seat position . this machine has two spotting modes . the first mode allows the lifter to continue repetitions ( up and down ) assisted by the machine . the second mode only allows upward movement , preventing the weight from falling on the lifter . furthermore , this machine requires no electrical power and is of a weight and size similar to traditional non - spotting bench presses . these attributes make this machine more likely to be used in homes and other private residences . while the above description contains much specificity , these should not be construed as limitations on the scope of the invention , but rather as an exemplification of one preferred embodiment thereof . many other variations are possible . for example , the uprights described above do not have to be tilted away from the seat extension of the bench . still , another example is that the spotting device used with this machine is not to be limited to use with only one type of seat . a seat adjustable to various incline , decline and flat positions and seats in fixed positions are all types that can be used with this device . accordingly , the scope of the invention should be determined not by the embodiments illustrated , but by the appended claims and their legal equivalents .

US-69508703-A

a non - pharmaceutical apparatus , system and process for treating and / or detecting biological targets , such as infectious diseases , are provided in various implementations . in one implementation , a medical device , system and / or process targets biologic targets such as microorganisms , fungi , bacteria and viruses resident in an infected environment . further various method of detecting the biological targets are also provided .

fig1 shows an environment 100 in which biological targets 102 ( e . g ., fungi , bacteria , viruses or other microorganisms ) are present . the biologic targets 102 for example , may be present within a biofilm or other configuration within the environment 100 . the environment 100 may further comprise one or more substrates . in one particular implementation , the biological targets 102 , for example , may be present as colloidal particles in a “ suspension ” of physiological fluids 104 ( e . g ., a viscoelastic fluidic suspension such as an interstitial fluid that flows between tissue cells 106 of humans and other animals ). the biological targets may comprise charged or uncharged colloidal particles . a charged biological target 102 , for example , may be positively charged or negatively charged . bacteria , for example , are typically negatively charged particles . fungi and viruses , for example , also have various charges . fig2 shows an example implementation in which an environment 200 comprises a plurality of colloidal particles 202 each having a positive charge or a negative charge . the plurality of colloidal particles 202 , for example , may have invaded a tissue viscoelastic fluidic suspension 204 . the suspension , for example , may be present in a physiological system , such as in a matrix of an infected nail , an infected wound , acne , or the like . in the implementation shown in fig2 , a pair of electrodes 208 and 210 is provided adjacent to the environment 200 for electrically coupling with the environment 200 . although various implementations , such as this one , show a pair of electrodes configured for coupling with the environment antennas are also shown herein that comprise a monopole electrode configuration that may also be used in place of the dipole arrangement showed in this and other implementations . in one implementation , for example , a low frequency electromagnetic signal is applied across the pair of electrodes 208 and 210 . in another implementation , an electromagnetic signal including a relative low frequency component ( e . g ., a modulation signal ) and a relative high frequency component ( e . g ., like a carrier signal ). although a pair of electrodes are shown in this particular implementation , any number of electrodes may be used , including a single monopole electrode design as shown in some of the antennas discussed below . the electromagnetic signal , for example , may comprise an electromagnetic signal of less than about 500 khz . in one particular implementation , for example , the electromagnetic signal may be in the range from about 5 khz to about 200 khz , although other frequencies are also possible . in the implementation of a dual ( or more component ) electromagnetic signal a relative high frequency component ( having a relative small wavelength ) and the relative low frequency component ( having a relative large wavelength ), various frequency components of the electromagnetic signal may be selected for desired interactions with the environment and / or the biological targets in the environment . the relative low frequency component , for example , may be selected to achieve one or more specific functionality such as described throughout this document . functionalities , for example , may include generating ions and / or electrical double layers within , at or adjacent to the environment , controlling , moving or otherwise affecting one or more ion , particle , biological target , solution or other component , altering an environmental condition ( e . g ., ph ), or the like . similarly , the relative high frequency component may be selected to direct the relative low frequency component ( and its effects ) within a discrete environment or target region , such as near the biological targets . specifically , the relatively smaller wavelength of the relative high frequency component allows a more specific targeting of a region than the relatively longer wavelength of the relative low frequency component . in addition , one or both frequency components of the electromagnetic signal may be selected for a particular interaction with the environment and / or the biological target . in one particular implementation , for example , a relative high frequency component of the electromagnetic signal may be selected for its interaction with a particular substrate in the environment ( e . g ., a tissue ) that may effectively demodulate the relative low frequency component ( e . g ., a modulation signal ) from the selected relative high frequency component ( e . g ., carrier wave signal ) within the target environment . the electromagnetic signal generates ions 212 in the environment 200 . the ions 212 are free to migrate within the environment 200 . in addition to the generated ions 212 , intracellular and extracellular liquids contain ions 212 that are also free to migrate within the environment 200 ( e . g ., within an electric field generated by the electromagnetic signal applied to the electrodes 208 and 210 ). where the electrode ( s ) 208 and 210 are in direct contact with a fluid 204 of the environment 200 , ions may be introduced at a transition between the electrode ( s ) and the fluid 204 adjacent to the electrode ( s ) 208 and 210 . where the electrode ( s ) 208 and 210 are not in direct contact with the fluid 204 , however , the ions can be introduced by an inductive — capacitive resonant charging process . the electromagnetic field introduced by the electrodes 208 and 210 creates a “ double layer ” formed by the ions . where the electrode ( s ) 208 and 210 are in direct contact with a fluid 204 of the environment ( e . g ., through a porous barrier such as a nail ), the double layer is created at the transition between the electrode ( s ) 208 and 210 . in the double layer , a surface charge of the electrode ( s ) 208 and 210 is mirrored by a parallel layer of ions within the fluid 204 . the ions in the fluid form a diffuse layer of free ions under the influence of electric attraction and thermal motion . where the electrodes are not in contact with a fluid of the environment 200 , however , the double layer may be created at a transition in which different layers or objects have different material or electrical properties . a double layer may similarly form at various tissue transitional surfaces ( e . g ., a nail , a nail matrix or other tissue transition ). thus , a layer of ions within a fluid 204 may mirror a parallel surface charge on a tissue within the environment 200 . ions generated in the environment 200 are also attracted to and surround the charged colloidal particles 202 . the ions , for example , may alter a ph of the environment 200 and / or alter a charge of individual colloidal particles 202 within the environment 200 . many biological targets are sensitive to ph and , thus , by creating ions ( e . g ., hydrogen or hydroxide ions ) in the environment the ph within the environment ( or within a closely controlled region of the environment ) may be controlled to create an environment inhospitable to a particular type of target particle . depending upon the target , ph can be controlled in situ to provide an inhospitable environment for the target . thus , a ph of an environment may be controlled to be more acidic or basic depending on a particular target . in addition , a charge of the colloidal particles 202 ( e . g ., proteins , bacteria , and fungus ) within a suspension provides for reciprocal repulsion of the particles that keeps those particles in suspension . a loss of charge , however , can reduce the repulsive forces of the colloidal particles 202 ( e . g ., biological targets ) which , in turn , can lead to clotting and precipitation of the particles within the physiological fluid . charged particles ( e . g ., charged colloidal or other charged target particles ) within the environment can also be detected , controlled ( e . g ., oriented or displaced ), and / or treated through an electrical coupling ( e . g ., capacitive or inductive coupling ) and / or electroacoustics via the electrodes 208 and 210 ( or another set of electrodes or antennas ). a signal applied to the pair of electrodes 208 and 210 , for example , can be used to couple the electrodes 208 and 210 to environment 200 to provide an electrostatic or electromagnetic charge in the environment 200 in which the targets such as the charged colloidal particles 202 reside . in one particular implementation in which a double layer is formed within the environment 200 , for example , the double layer can be used to localize the targets such as charged colloidal particles 202 in a particular region of the environment . the particles 202 localized within region , for example , may be easier to treat by virtue of the region in which they are localized . nail fungus targets , for example , may be able to be localized within a nail bed under a nail and away from a root of the nail so that they may be more easily treated ( e . g ., via a laser or microwave bulk heating approach ). in addition , the localized particles 202 , may also be more effectively treated simply by their proximity to each other ( e . g ., a given treatment may be more effective since the particles 202 are localized together for treatment and a higher percentage of the targets 202 may be treated with the same treatment technique ). coagulated target particles , for example , can be targeted for treatment , such as with energy to heat the targeted particles ( e . g ., bulk heating ), a modulated signal ( e . g ., an amplitude modulated radio frequency signal superimposed on a “ charging ” direct current signal ), electroacoustic energy , or any other targeted treatment methodology . as described above , for example , a ph of the environment 200 can controlled creating ions within the environment ( e . g ., within a specific region of the environment ). in addition , positive ions of a target particle may be “ pulled off ” the target particle so that the particle will not spread and can be destroyed . once damaged and / or isolated , a target particle may be destroyed through bulk heating , ph manipulation , electroacoustic energy , optoelectric treatment such as broadband light or effective components of broadband light ( e . g ., uva and / or uvb ) and / or through other methodologies . in one implementation , for example , electrostatic , electroacoustic , and / or electrokinetic forces may be used to compromise a cellular wall of a target particle . in another implementation , the environment 200 is charged using electrostatic energy and / or the modulated signal described above , and a specific ultrasound frequency signal is also applied to the environment 200 . the ultrasound frequency signal may be applied to the environment 200 via the pair of electrodes 208 and 210 or via another source . the ultrasound frequency causes motion of a complex “ target - external ion ” ( e . g ., a super - ion ) and electrical current is generated in the environment 200 due to mechanical motion of the target - external ion . the generated electrical current , in turn , can provide a local voltage breakdown between the target - external ions other close target - external ions to create mechanical destruction of the target particles ( e . g ., destruction of a target fungus stem at a location where the fungus is tethered , comprising a cellular wall of a target particle , or the like ). in this particular implementation , heating caused by the electroacoustic generated current can further affect free particles within the environment 100 ( e . g ., free fungus spores that have broken off the target fungus stems ). electrically “ presoaked ” tissue with immobilized colloidal particles ( biological targets ) can be further treated with non - focused or partially focused ( non - point hifu ) energy ultrasound energy . in one implementation transducer frequency delivered depends on a depth and target treatment location . in a nail treatment implementation , for example , application of ultrasound energy may be delivered at a frequency between 7 and 14 mhz or for other skin application between 2 . 2 mhz and 14 mhz . one skilled in the art , based on this disclosure , however , would readily appreciate that these are merely example implementations recognize that other frequency ranges may be used for these particular or many other applications . in one implementation , ultrasound introduces acoustic energy that titrates a colloidal particle - charge system and moving charge in an acoustic field created local eddy currents that locally create cell wall heating and thermal breakdown locally . also , a colloidal particle - charge system may be vibrated at an ultrasound frequency to bring colloidal particles beyond an elastic cell wall barrier to mechanically compromise a biologic target to damage or destroy microorganisms . a secondary effect of ultrasound excitation is a cavitation effect caused by strong shear fields . for example , microorganism in some cases are sufficiently long ( e . g ., fungus ) that they could break under a strain induced in an ultrasound field . ultrasound effects can also be carefully tuned via a transducer frequency design to have a minimal thermal component and / or a non - dominant thermal component of a treatment ( i . e ., thermal energy does not comprise a dominant modality of treating a biological target ), rather although thermal energy may be created , other modalities described herein comprise the dominant manner of treatment . in one particular implementation , for example , an ultrasound effect may be increased or maximized by connecting a firing sequence of an ultrasound transducer to a firing sequence of a modulated electromagnetic energy source ( e . g ., antenna ) due to the formation of an electric double layer and a parasitic discharge . although several ultrasound transducers and electromagnetic antenna designs are described herein , many other designs may also be useful in one or more of the treatments or devices described herein as well . electroacoustic phenomena arise when ultrasound radiation propagates through a fluid containing ions . the phenomena moves the ions , and the motion generates electrical signals because the ions have an electric charge . the coupling between ultrasound and an electric field is referred to as electroacoustic phenomena . fluid , for example , may comprise a simple newtonian liquid , or a complex heterogeneous dispersion , emulsion or even a porous body . examples of electroacoustic effects , depending on the nature of the fluid , include the following : ( i ) ion vibration current / potential ( ivi ) in which an electrical signal arises when an acoustic wave propagates through a homogenous fluid ; ( ii ) streaming vibration current / potential ( svi ) in which an electric signal arises when an acoustic wave propagates through a porous body in which the pores are filled with fluid ; ( iii ) collowid vibration current / potential ( cvi ) in which an electric signal arises when ultrasound propagates through a heterogeneous fluid , such as a dispersion or emulsion ; and ( iv ) electric sonic amplitude ( esa ), an inverse of a cvi effect , in which an acoustic field arises when an electric field propoagates through a heterogeneous fluid . the movement of ions ( including free ions and / or colloidal particles ) through a fluid , such as in an environment comprising biological targets , creates a current . a collaborative action between electrostatically or an amplitude modulated antenna induced electric double layer and acoustic waves introduced by an ultrasound source provides a treatment ( e . g ., destruction , reduction , damage , injuring , or other treatment ) for biological targets within an environment . in one implementation , for example , an electric double layer can be regarded as behaving like a parallel plate capacitor with a compressible dielectric filling . compressing the dielectric filling of a specific kind ( e . g ., size , dynamics , etc .) could be used as an identification of the colloidal particles / biologic target organisms ( e . g ., biologic target microorganisms ). in this implementation , electrical noise detection can also be used to detect a presence of a certain size target , activity , kill rate and the like . use of an acoustic wave source to create a streaming vibration current representing an electrical signal that arises when an acoustic wave propagates through a porous body of the environment ( e . g ., a nail plate or other porous body ) in which the pores are filled with a fluid that couples as a mediator between the porous body and an ultrasound electrode . the same effect could also be enhanced by an electrostatic approach as described above , a galvanic electrolysis and / or an ac modulation approach . in yet another implementation , target particles 202 may be exposed to broadband light or to one or more components of broadband light , such as uva and / or uvb to destroy or otherwise harm the target particles 202 . where the target particles 202 have been localized , for example , broadband light may be directed onto the localized target particles 202 . similarly , where motion of the target particles 202 is controlled , broadband light may be directed into a path through which the target particles 202 will move to destroy or otherwise harm the target particles 202 . in addition , where target particles 202 are free floating in the environment 200 ( e . g ., spores broken off stems of fungus ), the free floating particles 202 may be exposed to broadband light within the environment to destroy or otherwise harm the target particles 202 . where a fungus spore has broken off of stems of the fungus , for example , exposure of the spores to broadband light may prevent the spore from starting another stem root at the other location as well where the light could affect any superficial fungus , such as a surface of a nail plate or a mission nail plate location . fig3 shows an example implementation in which an electrical double layer is formed within an environment 300 via an application of an electromagnetic signal to a pair of electrodes 308 and 310 coupled to the environment . in this implementation , the electrical double layer is created proximal to a transitional surface in or adjacent to the environment 300 . a transitional tissue within the environment 300 , for example , is electrically charged and ions within the environment surround one or more target particles within the environment to electrically charge the particles to an isoelectric point . at an isoelectric point , a colloidal system is least stable from a zeta potential standpoint . the isoelectric point is related to a specific ph value for which the zeta potential is equal to 0 mv . clustering groups of combined particles ( e . g ., target particles and surrounding ions ) to larger groups of particles creates gradients of materials with a more substantial electrical capacitive difference relative to a surrounding tissue ( i . e ., colloidal islands ). the colloidal islands can then be exposed to higher frequencies ( e . g ., between 1 mhz to 2 . 4 ghz or similar frequencies ) where maxwell - wagner conditions are dominant by selectively heating the colloidal islands alone . in addition , the colloidal islands can have ph values modified locally for a short time period to a ph value ( s ) that provide unfavorable living conditions for a particular living target particle . at the same time , the colloidal islands can be exposed to electrical force based vibration where the particle walls are compromised to destroy or damage the target particles within the colloidal islands . fig4 shows an example of a system for targeting nail fungus in a toe . the system comprises a pair of electrodes that forms a double layer under a toenail . in the implementation shown in fig4 , a target particle comprises a negatively charged fungus particle , although any other target particle having a positive or negative charge may be used . where a positive charged target particle is used , for example , the polarization of the electrodes may be reversed to reverse the charge of the double layer within the toenail environment . the double layer , for example , may be formed by an electrostatic charge and / or by an alternating current ( ac ) charge . the alternating current charge , for example , may comprise an amplitude modulated radio frequency superimposed on an intermittent charging direct current signal . in this particular implementation , the double layer comprises positively charged ions that are attracted to and interact with the negatively charged fungus target particles . as shown in fig4 , the fungus target particles are each surrounded by a plurality of positively charged ions generated by the electrostatic charge and / or alternating current charge . as described above with respect to fig1 , the double layer field may be used to move , align , or locate the fungus target particles to aid treatment of the target particles . further , the positive ions increase the ionization of the environment in which the toe is exposed . the increased ionization may be used to alter a ph of the toenail environment to increase the hostility of the toenail environment to the targeted fungus particles or to otherwise increase an effectiveness of the treatment of the targeted fungus . as described above , the increased ionization of the environment can decrease a charge of target particles within a suspension to reduce repulsion between the particles and encourage clotting and precipitation of the target particles . once the target particles are coagulated within the sterile or germinal matrix of the toe , the target particles may be treated in any number of ways , such as by breaking down the targeted particles ( e . g ., with electrostatic or ac energy ), exposure to electromagnetic vibration to compromise a cellular structure of the targeted particles , electroacoustic current generation created by motion of ionic targets in suspension ( e . g ., a physiological fluid such as a interstitial fluid ), a current induced cellular wall breakdown , application of broadband light , bulk heating , and / or the like . fig5 ( labeled “ contact approach ”) shows an example implementation of a contact approach of a particle targeting device in which a pair of electrodes are arranged around a toe . in this particular implementation , a first electrode is positioned directly adjacent to a nail plate of a patients toenail . the second electrode is electronically coupled to the first electrode and is arranged to provide an electrical field within a patient , such as a sterile matrix and / or a germinal matrix of a nail bed of a toenail . in fig5 , the nail plate is shown having a void where the toenail had fallen off due to a fungus infection of the toenail . fig6 ( labeled “ non - contact approach ”) shows an example implementation of a non - contact approach of a particle targeting device in which a pair of electrodes are arranged around a toe . in this particular implementation , a first electrode is separated from the nail plate of the patient by a layer of air , gel , or other separator . the second electrode is electronically coupled to the first electrode and is arranged to provide an electrical field within a patient , such as a sterile matrix and / or a germinal matrix of a nail bed of a toenail , through the layer of air , gel , or other separator material . in fig6 , the nail plate is shown having a void where the toenail had fallen off due to a fungus infection of the toenail . in this particular implementation , the conductive gel or other separator may extend into the void to make a better connection with the sterile and / or germinal matrix of the toenail . fig7 illustrates an example schematic circuit diagram of an ultrasound pulser programmable logic device that may be used to provide an ultrasound signal for coupling with an environment comprising biological targets . fig8 shows an example of a sleeve antenna configured to slide over the distal end of a digit , such as the toe shown or a finger , for treating and / or detecting a biological target . in this particular implementation , for example , the sleeve antenna comprises a root electrode for introducing an electromagnetic field to the underlying foot of the nail and also a light transmission device ( e . g ., fiber optics , optical waveguide or the like ). in addition to applying an electrostatic field through the root electrode , light transmission of broadband light ( or one or more component thereof ) can be applied to the environment ( in this case a nail bed of the underlying toe ). in this manner , both an electrostatic and an opto - electrical mechanism of action are provided by providing light through the light transmission element . fig9 shows an ear in which biological targets can be treated and / or detected as described herein . an ear infection behind an ear drum , for example may include colloidal particles in solution behind the ear drum . fig1 shows an example of a biological target microorganism in an electromagnetic field in which a plurality of generated ions surround the microorganism . the ions , in this implementation , form an electrical double layer around the biological target and also provide a local ph change in situ . the double layer formation around the target as well as the change in ph can decrease the motility of the microorganism . fig1 shows an example of a biological target microorganism disposed in an ultrasound field in which the ultrasonic field is used to control and / or move the microorganism . for example , the ultrasound field may be used to provide motion and moving the microorganism with it . in addition , the motion , in various implementations , may be used to break down a cellular wall beyond an elastic bather of the target microorganism . fig1 a and 12b show an example of an ultrasound transducer crystal that can be used to generate an ultrasound field within an environment comprising biological targets . in this particular implementation , the transducer comprises an ultrasound transducer and an rf antenna . the ultrasound transducer further comprises an ultrasound backing layer and a an ultrasound reflector as well as a matching layer . the matching layer in this implementation comprises a fixed matching component and a replaceable , disposable matching component that can protect the transducer from coming into direct contact with the environment , fluids within the environment and / or targets within that environment . in this particular implementation , for example , the transducer is shown generating an electromagnetic signal that includes a first relatively low frequency component of about 200 khz and a second relatively high frequency component of about 500 mhz and further generating an ultrasound signal having a frequency range of about 1 to about 14 mhz . in this implementation the transducer provides a fully integrated ultrasound transducer and an rf antenna element . in some implementations , for example , the ultrasound transducer may comprise a transducer crystal disposed in a back of a reflector . the reflector may include any number of materials , such as a ceramic material . the transducer shown in fig1 a and 12b further include a backing and matching layer that can be made from standard or specially designed materials . further the waveforms shown represent an interleaved rf and ultrasound delivery . in this implementation , the interleaved timing may can be closely controlled depending upon desired treatment conditions . in an interleaved implementation , for example , the interleaved timing can be used to determine a strategy of thermal or non - thermal discrimination . this enables accurate targeting with a minimal fringe of the rf and ultrasound field , thus enabling laser accuracy targeting but with minimal heating optimization . fig1 shows an example transducer including a combination rf antenna and hifu ultrasound transducer . the ultrasound transducer includes a waveguide and an hifu reflector for directing the ultrasound energy to the environment . the transducer further comprises a dual matching layer for efficiently transferring energy with the environment . the dual matching layer includes a permanent matching layer and a disposable matching layer than can be removed and discarded after use . in this particular implementation , the rf antenna comprises an external inductive rf coil antenna in which the coil is wound around an exterior of a bell ceramic ultrasound reflector instead of a deposited - sputtered antenna . in this implementation , the coils are represented by dots shown around the exterior of the bell reflector . the transducer is configured to provide an rf field normal to a surface of the environment ( e . g ., skin ) and enable deeper tissue penetration . an ultrasound crystal can be disposed in the back of the bell . in this implementation , the transducer further includes a matching layer designed as a good dielectric as well as a good acoustic matching layer at the same time . the transduce reflector further provides focus for depth of treatment . fig1 shows another example transducer for providing electromagnetic and ultrasound excitation to an environment including biological targets . in this particular implementation , the transducer comprises an rf antenna and hifu ultrasound transducer combination . in this implementation , the antenna has a flat antenna capacitive coupling mesh printed on a flat ultrasound transducer crystal . a ceramic bell reflector also serves a dual purpose as an ultrasound transducer reflector and an rf waveguide . the transducer further comprises disposable matching layers that may be used with an antenna , such as the ones shown in fig1 and 13 , for coupling to the environment while reducing the likelihood that the antenna is contaminated by the biological targets . fig1 shows an example of a matching layer or waveguide dielectric comprising an rf inductive antenna coil and an ultrasound transducer that may be used for coupling an electromagnetic field and / or an ultrasound field with an environment comprising biological targets . fig1 shows an example of an antenna configured for inductively and capacitively coupling an electromagnetic radio frequency ( rf ) field and a transducer for coupling an ultrasound field with an environment comprising biological targets . in this implementation , the transducer comprises a hifu ultrasound transducer including an hifu reflector , an active backing layer and a permanent matching layer and a disposable matching layer . the transducer further comprises an rf monopole antenna . the transducer , in this implementation are terminated by the distant matching network to increase or maximize efficiency and for the transducer to be seen by an electronic system as a particular load ( e . g ., a 50 ohm load ). at a system side , there is a proximal matching network to compensate for a transmission line or handpiece cable . in several of these implementations , such as shown in fig1 , the matching layer comprises a unique two part design in which a permanent matching layer ( e . g ., molded within a dome of a combinational transducer and terminated with a flash surface ). the permanent matching layer further includes a connection ( e . g ., snap or threaded connection ) configured to connect with a disposable matching layer . fig1 shows another example of a focused multi - element antenna device for coupling an electromagnetic field and / or ultrasound field with an environment comprising biological targets . in this implementation , two different disposable matching layers are shown for use in an application where the disposable matching layer comes into contact with the environment ( e . g ., a tissue ). in the first implementation , a cylindrical matching layer design provides a shaped structure for matching a first anatomical structure . the second implementation shows a conical design for smaller and more precise areas such as a nail specific area and a larger area designed for a larger surface area treatment such as dermatitis or trauma wounds . fig1 shows a block diagram of example treatment and detection methodologies that may be used to treat and / or detect biological targets within an environment . fig1 shows an example graph of a zeta potential plotted with respect to a ph level that may be used in various implementations for detecting biological targets within an environment . in various implementations , one or more techniques of detecting biological targets within an environment can be used to determine the presence , quantity and / or type of biological targets disposed within an environment of interest . the detection of one or more biological target may be performed before treatment to determine whether treatment is warranted , during treatment ( e . g ., feedback ) to determine whether the treatment is working and / or after treatment to determine if the treatment was successful ( e . g ., determine whether more treatment is warranted or if a different type of treatment is warranted ). since a pressure wave gradient in an ultrasonic wave moves particles relative to a fluid in which it is located , the motion and the motion of biologic target particles / organisms disturb an electric double layer that exists at a particle - target organism ( e . g ., a negatively charge ion ) interface . the disturbance could come from a motion of live particles / biologic targets as well . particles carry a surface charge . ions of a diffuse layer are located in the fluid and can also move with the fluid . fluid motion relative to the particles can drag these diffuse ions in the direction of one or the other particle &# 39 ; s poles . as a result , an excess of negative ions in the vicinity of a left hand pole and an excess of positive surface charge at the right hand pole . this charge excess creates a particle dipole moment . the dipole moments generate an electric field that would generate an electric current . in one implementation , for example , a current is measured , such as via one or more electrodes ( e . g ., lateral electrodes ). in addition , this data can be used ( e . g ., indirectly ) to calculate a zeta potential in concentrated colloids of the environment . this parameter , in one implementation , is used to measure a degree of repulsion between adjacent particles ( e . g ., live particles ), the activity or degree of infection and / or an efficacy of a treatment ( e . g ., efficacy of killing and possibly a kill rate ). from a theoretical viewpoint , for example , zeta potential is an electric potential in an interfacial double layer ( dl ) at a location of the slipping plane versus a point in the bulk fluid away from the interface . in other words , zeta potential is the potential difference between a dispersion medium and a stationary layer of fluid attached to a dispersed particle . in one implementation , a flocculation ( grouping particles ) is created as described above by keeping a zeta potential in real - time in a range from about 0 to about 5 mv . ( a typical zeta potential is in mv : ( i ) from 0 to + 5 mv — rapid coagulation or flocculation , ( ii ) from +/− 10 to 30 mv — incipient stability , ( iii ) +/− 30 to 40 mv 000 moderate stability , ( iv ) from +/− 40 to 60 — good stability , and ( iv ) above 61 mv — excellent stability . by electrically charging a treatment zone , a zeta potential may be steered towards flocculation of target particles and thus reduce or even eliminate colonies of biological target particles . detection using an electric sonic amplitude is a reverse to colloidal vibration current . under an influence of an electric field described above with respect to an oscillating electric field , the particles move relative to a liquid which generates ultrasound . in one implementation , an ultrasound echo could be used as a control mechanism . thus , electroacoustic sensing , treatment and detection may be interrelated . in addition , a link between ph of the environment and the zeta potential may be used so that zeta potential is used to measure ph and a change in ph . see e . g ., fig1 . in one implementation , for example , micro - motion detection of particles ( e . g ., biological targets ) using in - phase and quadrature voltage increase as a result of cell surface coverage is performed via one or more electrodes ( e . g ., lateral electrodes ). in one implementation , particle motion and / or growth or reduction in colonies is observed . motion sensitivity can be in the nanometer ( nm ) range . it is further possible to observe effects of high burst shock into an area as well as it could be used for control for electrode contact . in addition , mechanical constriction of a treatment area and observation of a change in blood perfusion may also be used . in one implementation , for example , a reduction of perfusion and an increase in oxygen intake may also provide an opportunity to kill or otherwise treat colonies via contact with oxygen - enriched fluid . in another implementation , a layered structure of tow - finger comprise a layered structure of tissue materials and can be used to detect a location of target particles and dynamic impedance changes due to the presence of particles . in one design based on impedance motion sensing a lock - in amplifier is used for treatment where one electrode used is gold plated and a counter electrode is a second electrode . changes in electrical resistance reflect attachment and motion of cells and target particles . in yet another implementation , brownian noise is used to detect an efficacy of a treatment as well as an extent of bacteria and other biological target presence at a given location . in one implementation , brownian noise ( also referred to as “ red noise ” refers to a power density that decreases 6 db per octave with increasing frequency ( density proportional to 1 / f 2 ) over a frequency range that does not include dc ( and in a general sense does not include a constant component , or value at zero frequency ). in other implementations , brownian or “ red ” noise may refer to any system where power density decreases with increasing frequency . in the firs implementation , brownian noise can be determined by an algorithm that simulates brownian motion or by integrating white noise . brownian noise is not named for a power spectrum that suggests the color brown ; rather , the name is related to brownian motion . “ red noise ” describes the shape of the power spectrum , with pink being between red and white . also known as “ random walk ” or “ drunkard &# 39 ; s walk ” noise , red noise can be used to detect an efficacy of the treatment as well as the extent of bacteria ( or other biological targets ) presence at a given location . in another implementation , dynamic impedance may be used to detect the treatment efficacy and control of the treatment delivery ( e . g ., as feedback ) for any of the aforementioned modalities . a zeta potential ( as described above ) and / or sulfur detection ( e . g ., as an indication of a fungus presence ) can be used to detect an efficacy of treatment . ( see e . g ., fig1 .) the embodiments of the invention described herein are implemented as logical steps in one or more computer systems . the logical operations of the present invention are implemented ( 1 ) as a sequence of processor - implemented steps executing in one or more computer systems and ( 2 ) as interconnected machine or circuit modules within one or more computer systems . the implementation is a matter of choice , dependent on the performance requirements of the computer system implementing the invention . accordingly , the logical operations making up the embodiments of the invention described herein are referred to variously as operations , steps , objects , or modules . furthermore , it should be understood that logical operations may be performed in any order , unless explicitly claimed otherwise or a specific order is inherently necessitated by the claim language . although embodiments of this invention have been described above with a certain degree of particularity , those skilled in the art could make numerous alterations to the disclosed embodiments without departing from the spirit or scope of this invention . for example , although examples of specific biological targets such as fungus , nail fungus , bacteria , and the like are disclosed in specific examples , one of ordinary skill in the art would recognize from the teaching herein that the apparatuses , systems and methods for treating and / or detecting those biological targets may be altered to treat and / or detect any other number of biological targets in many other types of environments . all directional references ( e . g ., upper , lower , upward , downward , left , right , leftward , rightward , top , bottom , above , below , vertical , horizontal , clockwise , and counterclockwise ) are only used for identification purposes to aid the reader &# 39 ; s understanding of the present invention , and do not create limitations , particularly as to the position , orientation , or use of the invention . joinder references ( e . g ., attached , coupled , connected , and the like ) are to be construed broadly and may include intermediate members between a connection of elements and relative movement between elements . as such , joinder references do not necessarily infer that two elements are directly connected and in fixed relation to each other . it is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative only and not limiting . changes in detail or structure may be made without departing from the spirit of the invention as defined in the appended claims . the above specification , examples , and data provide a complete description of the structure and use of exemplary embodiments of the invention . since many embodiments of the invention can be made without departing from the spirit and scope of the invention , the invention resides in the claims hereinafter appended . furthermore , structural features of the different embodiments may be combined in yet another embodiment without departing from the recited claims .

US-201414776623-A

a bipolar electrosurgical instrument that is configured for use in mis and other electrosurgical procedures . the instrument is constructed as a bipolar electrode comprising a bare wire as the active electrode spaced from a window below which is the return electrode . the bare wire electrode preferably is configured as a straight wire projecting laterally from the distal end or with straight or curved sections that extend rearwardly toward the window . when energized , a bipolar discharge is generated between the active and return electrodes .

the reader is directed to the referenced prior applications for a more detailed description of the prior applications which will assist in understanding the improvements offered by the present application . in the present application , fig1 is a schematic view of one form of electrosurgical instrument 10 in accordance with the invention . it comprises a rigid handle 12 with a conventional front end adapted to receive and hold rigidly the shank end ( not shown ) of an elongated support member 14 whose working end 16 is shown at the left . the support member 14 terminates in a distal end section 22 of reduced diameter . the handle 12 is electrically - insulating or if conductive covered with an electrically - insulating coating . similarly , the shaft of the elongated support member 14 is also coated with an electrically - insulating coating , leaving bare the active electrode 20 at the working end 16 ( see fig2 and 3 ). the support member 14 is long enough ( see reference numeral 18 ) to extend through a conventional trocar or channel so that its working end 16 is exposed inside the patient . at the right end of the handle 12 is shown a cable 6 which contains two insulated wires for receiving bipolar electrosurgical currents from a conventional electrosurgical apparatus 8 . the active parts of the bipolar electrode comprise a metal wire electrode 20 and a return or ground electrode 26 which is accessible via a window 24 in the insulated support member 14 . as illustrated in fig3 the cable 6 which extends through most of the handle and support member electrode comprises a first conductor 32 which is connected internally to the return electrode 26 , and a second conductor 30 which is connected internally to the wire 20 via a channel shown schematically at 21 . in this first embodiment , the active wire electrode 20 extends laterally of the longitudinal or long axis of the support member 14 . specifically , and preferably , it extends at an angle of 90 ° to the long axis . in the structure shown , all exposed surfaces are electrically - insulating , except for the active wire 20 and the return 26 which is accessible via the window 24 . the end section 22 is made of electrically - insulating material . the support member body 14 , from the dividing line 36 is coated with an electrically - insulating coating 38 . as a result , part of the conductive ground 26 underlying the electrically - insulating coating 38 is not exposed to the outside , but , if a conductive or semi - conductive fluid is present , it will be able to access at least some of the conductive return underlying the coating 38 . the two wires 30 , 32 are not only insulated from each other so that bipolar electrosurgical voltages can be applied between them , but they are also insulated from the support member 14 . in this description , by “ axial ” is meant parallel to the long axis of the support member 14 ( horizontal in fig3 ). by “ lateral ” is meant transverse to the long axis of the support member 14 ( vertical in fig3 ). “ lateral ” is intended to include 90 ° for the embodiments of fig1 - 3 , as well as an acute angle , such as 45 °, for the embodiment of fig5 . once the surgeon has positioned the working end 16 of the instrument with respect to the tissue to be operated on , he or she then activates the electrosurgical apparatus 8 causing a discharge of bipolar currents between the active wire electrode 20 and the return electrode 26 capable of causing excision of or ablation of or shrinkage of tissue or cauterization of a blood vessel in the usual way . the active wire is best used as a needle electrode or with its front side passing over the tissue . as with the embodiments of the prior application , the insulating coating on the support member 14 will prevent accidental touching of patient tissue by the electrode sides , so that the bipolar discharge is locallized to the spacing between the bare parts 20 , 26 . the operation can take place in a wet field with a conductive or semi - conductive fluid completing the current path , or in a dry field where the electrosurgical currents from the active wire 20 seek out the closest return or ground which will be the electrode 26 . the surgeon positions the electrode 20 so as to touch or pass lightly over the tissue to be modulated as needed for the procedure being followed . for example , a suitable metal for the electrodes is brass , tungsten or stainless steel . the spacing 34 between the two electrodes can vary between 0 . 35 - 0 . 55 inches , preferably about 0 . 47 inches . the spacing 34 also happens to be the distance between the wire electrode 20 and the nearer edge of the window 24 . the height 36 of the wire electrode 20 can vary between 0 . 06 - 0 . 1 inches , preferably about 0 . 08 inches . the width 38 of the insulated end can vary between 0 . 08 - 0 . 1 inches , preferably about 0 . 1 inches . the dimensions of the window 24 can vary between about 0 . 3 - 0 . 5 × 0 . 6 - 0 . 9 inches , preferably about 0 . 38 × 0 . 6 inches . the underlying conductive ground 26 will have about the same width dimension as the window , and extend in the length direction about 2 - 3 times longer than the window length . the depth of the conductive return or ground below the window surface is preferably about 0 . 023 inches . the overall length of the support member 14 typically will be about 3 - 8 inches . fig1 - 3 illustrate a preferred embodiment of the invention in which the active wire electrode 20 is configured as a straight wire extending at right angles to the long axis of the support member 14 . both the point , as well as the side of the wire , can be used by the surgeon . fig4 and 5 show two other preferred embodiments of the invention involving an active wire in which only sides of the wire can be used to modulate the tissue . the rest of the electrode remains the same , except that some of the spacings and dimensions change . in fig4 the active wire electrode 46 is configured as a leading first section that extends at right angles to the long axis of the support member 14 , a second mid - section that extends parallel to the long axis , and a trailing third section that also extends at right angles to the long axis of the support member 14 . the corresponding preferred dimensions are : the first section has a height 52 of 0 . 03 - 0 . 07 inches , preferably about 0 . 05 inches ; the second section has a length 44 of 0 . 2 - 0 . 3 inches , preferably about 0 . 24 inches ; the third section has a height the same as that of the first section and is spaced 45 from the window edge of 0 . 15 - 0 . 25 inches , preferably about 0 . 2 inches . in this case , the front side of the first and the top side of the second section can be used for tissue modulation . in fig5 the active wire electrode 46 is configured as a leading curved first section that extends out at right angles from a sloped end surface of the end section 22 and bends rearward to form a second straight mid - section that extends roughly parallel to the sloped end surface of the end section 22 and then bends rearward to form a trailing curved third section followed by a short straight section before it ends embedded in the end section 22 . the corresponding preferred dimensions are : the end surface slopes to form an acute angle 72 of about 20 - 40 °, preferably about 30 °; the first section has a radius of curvature 76 of about 0 . 04 - 0 . 06 inches , preferably about 0 . 05 inches ; the second section has a length 64 of 0 . 14 - 0 . 17 inches , preferably about 0 . 16 inches ; the third section has a radius of curvature 74 approximately the same as that of the first section ; and the fourth section has a length 66 of 0 . 03 - 0 . 07 inches , preferably about 0 . 05 inches . in this case , the front curved side of the first section , the outer straight side of the second section , the rear curved side of the third section , or the rearwardly - facing straight side of the fourth section can be used for tissue modulation . for example , the curved sections can serve to cut or shave or smooth tissue , the straight sections to shave or smooth tissue , the third curved section for point coagulation of bleeders , and the fourth straight section for cutting . thus , this electrode configuration offers the most flexibility to the surgeon in his or her choice of modulating surfaces . where the end of the fourth section embeds in the holder can be spaced about the same distance from the window edge as 45 of fig2 . other usable mechanical or electrical structures following the teachings of the prior applications when combined with that of the present application will be appreciated by those skilled in this art . the electrosurgical apparatus 8 preferably is an ultra high frequency ( rf ) radiosurgical energy source , which operates in the range of about 1 . 5 - 4 mhz . studies have shown that the 1 . 5 - 4 mhz frequency range is the preferred rf energy to incise and coagulate tissue , generally modulate tissue , because tissue thermal necrosis is minimal and , when interfaced with the electrosurgical electrode of the invention , provides excellent cutting , smoothing and hemostasis especially for joint orthopedic procedures . an example of suitable electrosurgical apparatus is the model surgitron dual - frequency electrosurgical unit manufactured by and available from ellman international , inc . of hewlett , n . y . while the invention has been described in connection with preferred embodiments , it will be understood that modifications thereof within the principles outlined above will be evident to those skilled in the art and thus the invention is not limited to the preferred embodiments but is intended to encompass such modifications .

US-75097701-A

spinal surgery systems are provided . in one embodiment , a system includes threaded caps and screw assemblies . each assembly includes a cannulated and threaded screw having upper and lower ends , a polyaxial head permanently fixed to the screw upper end in a ball - and - socket engagement , and an extension portion fixed to the head wherein extension portion movement causes the head to move in concert . each head has a receiving area for engaging a rod and a threaded area for receiving one of the caps after the rod is engaged in the receiving area . each extension portion has : two arms spaced apart such that the arms are on opposite sides of the polyaxial head receiving area ; and at least one point of weakness such that forcing the arms away from one another causes the extension portion to divide at the point of weakness and separate the extension portion from the head .

the equipment and methods set forth herein may allow spine surgeons to perform posterior lumbar decompressions ( e . g ., laminectomies , microdiscectomies , facetectomies , and lumbar interbody fusions ) in addition to posterior pedicle screw instrumentation through a small , single incision . notably , the disclosed equipment and methods may allow spine surgeons to perform a decompressive laminectomy from a posterior approach through smaller incisions than possible with prior art systems . a minimally invasive fusion procedure ( and equipment used ) according to one embodiment is shown and described with reference to fig1 through 46 of the accompanying drawings . as set forth above , fig1 and 2 show generic vertebrae 100 . fig3 similarly shows generic vertebrae 100 . in fig4 , with the aid of fluoroscopy , a port 200 has been placed percutaneously through the patient &# 39 ; s skin at a facet joint 118 . the incision location is shown in fig1 at line 152 . the port 200 is shown in detail in fig5 a through 5 c . unlike prior art ports , which are tubular and have upper and lower ends that are generally perpendicular to the sidewall , the port 200 has a lower end 202 that is not perpendicular to sidewall 204 . though various angles may be appropriate , an angle between twenty and forty degrees to the horizon , and preferably an angle of approximately thirty degrees , may be most desirable . this angled configuration may allow the lower end 202 of the port 200 to be simultaneously positioned along the facet 118 and adjacent lamina 108 of the vertebrae 100 . this distinguishes the port 200 from prior art by allowing the surgeon to perform a facetectomy / microdiscectomy concomitant to performing a laminectomy through the same approach for spinal decompression . in addition , the port 200 includes a lip ( sometimes referred to herein as “ rim ”) 208 at an upper end 206 . the rim 208 provides an advantage over the prior art in that a nerve root retractor 180 ( shown in fig6 holding nerve roots 182 out of the way ) and / or other equipment may be attached to the rim 208 , allowing hands - free operation of the attached equipment . and , as shown in fig5 a through 5 c , an engagable portion 209 may extend upwardly from the lip 208 . though not shown in the drawings , an arm may attach to the engagable portion 209 and secure the port 200 to the bed to stabilize the port 200 . it should be understood that other engagable configurations may additionally , or alternately , be used . while various materials and configurations would be appropriate for the port 200 , in one currently preferred embodiment , the port 200 is constructed of titanium , the sidewall 204 has a wall thickness of about one millimeter , and the rim 208 has an outer diameter that is about four millimeters greater than the inner diameter . the inner diameter of the port 200 may vary in increments ( e . g ., two millimeter increments , from 16 to 26 millimeters inner diameter ), allowing for use in different patients with different pathology . accordingly , multiple ports 200 may be present to allow the appropriately - sized port 200 to be selected for a given procedure . in some embodiments , the port 200 may contain a radiopaque ring at the tip for visualization by intraoperative fluoroscopy , while the port itself is radiolucent ; the surgeon may thus determine exactly where the port 200 is docked in the patient by imaging this radiopaque ring . returning now to fig4 , after the port 200 is secured in place , the facet joint 118 and lamina 108 may be resected using conventional tools and a microscope . once the lamina 108 is removed , the contra lateral lamina may be removed as well by under - cutting the spinous process . removal of the lamina 108 allows the spinal cord to be decompressed centrally , and removal of the facet 118 and intervertebral disc 154 allows the nerve root to be decompressed . after the necessary portions are removed , adjacent vertebrae 100 are fused together by a spinal fusion device 190 ( fig7 ), which is well known in the art , and may include such devices as a bony implant , a peek ( polyether keytone ) implant , bone morphogenic protein , a titanium cage , et cetera . the fusion device 190 is attached to an insertion tool 192 placed in the port 200 and wedged into the disc space using fluoroscopy . once the fusion device 190 is appropriately positioned , hemostasis is obtained and the port 200 is removed . as time passes , bone growth will result in spinal fusion as the spinal fusion device 190 is incorporated into the end plates of the bodies 102 of adjacent vertebrae 100 , fusing both vertebrae 100 into a single bony unit . stabilization , which in this case involves placement of pedicle screw instrumentation , significantly improves arthrodesis rates and provides stability in patients with instability , such as may result from fractures or spondylolisthesis . pedicle screw instrumentation begins with placement of standard jamshidi needles ( not shown ) into adjacent pedicles 104 ( or pedicles 106 ) with use of intraoperative fluoroscopy . this is done through the patient &# 39 ; s skin , as the port 200 has been removed . bone penetrating , stainless steel , “ k - wires ” 193 ( fig8 ) are then passed through the jamshidi needles into the pedicles 104 ( or the pedicles 106 ) of each vertebra 100 and are advanced into the vertebral bodies 102 of the vertebrae 100 above and below the interbody fusion device 190 . though the patient &# 39 ; s skin is not shown in the accompanying drawings , it should be understood that the k - wires 193 stick out through the skin percutaneously . next , a pedicle screw assembly 400 is inserted over each k - wire 193 and advanced into the pedicle 104 ( or the pedicle 106 ) and into the vertebral body 102 . fig9 shows one screw assembly 400 in place , and the screw assembly 400 is shown in detail in fig1 through 18 . a screwdriver 500 for use in placing the screw assembly 400 is shown in fig1 a through 19 c and described below . the screw assembly 400 includes a pedicle screw 410 , a screw head 420 , and an extension portion 430 . the pedicle screw 410 ( fig1 ) has an upper end 412 , a lower end 414 , and a cannulated core 416 that extends between the ends 412 , 414 and allows the screw 410 to be inserted over ( and guided by ) the k - wire 193 . the upper end 412 is configured to be driven by the screwdriver 500 , and may take a variety of shapes ( e . g ., hexagonal cavity 413 , an octagonal cavity , etc .). the screw head 420 ( which may also be referred to herein as a “ polyaxial head ”) is specifically shown in fig1 and 14 and is permanently fixed to the upper end 412 of the screw 410 through a ball - and - socket joint ( see fig1 , 16 , and 37 , though the structure that prevents the screw 410 from separating from the screw head 420 is not shown in the drawings ). the ball - and - socket joint allows 360 degree rotation along the axis of the screw 410 and additionally allows the screw head 420 to pivot relative to the screw 410 . the screw head 420 defines a receiving area 421 and may include structure 424 for coupling the screw head 420 to the extension portion 430 . the extension portion 430 is attached to the screw head 420 and includes at least two arms 432 to allow percutaenous placement of the screw 410 over the k - wire 193 and to allow percutaneous manipulation of the polyaxial head 420 while inserting a rod 700 and a cap screw 900 , which are discussed below . an important development over the prior art concerns the extension portion 430 and the manner in which the extension portion 430 is coupled to the pedicle screw 410 . as detailed in fig1 , the extension portion 430 may have at least one point of weakness or “ defect ” 433 , allowing the extension portion 430 to be broken apart and separated from the head 420 when no longer needed . as best shown in fig3 , a catch 439 may interact with a cavity 425 in the head 420 ( also shown in fig1 and 14 ) and a passage 435 ( also shown in fig1 ) in the extension portion 430 to temporarily couple the extension portion 430 to the screw head 420 ( i . e ., before the extension portion 430 is broken at the defect 433 ). while other means for fastening the screw head 420 to the extension portion 430 may also be used ( e . g ., a protrusion extending from the head 420 or the extension portion 430 interacting with a cavity in the extension portion 430 or the head 420 , etc . ), the catch 439 may allow the screw head 420 to be coupled to the extension portion 430 without further weakening the defect 433 . attention is now directed to the screwdriver 500 , shown in fig1 a through 19 c . the screwdriver 500 includes a shaft 510 having an end 512 complementary to the upper end 412 of the screw 410 for driving the screw 410 , and the shaft 510 is hollow to allow the k - wire 193 to pass therethrough . in addition , a guide 520 is fixedly coupled to the shaft 510 ( e . g ., through welding , a set screw , or any other appropriate method / device ) such that the guide 520 and shaft 510 rotate together . the guide 520 has passageways 522 configured to allow the arms 432 to pass through , temporarily securing the screwdriver 500 to the screw assembly 400 . by securing the screwdriver 500 to the screw assembly 400 ( i . e ., to the arms 432 ), the screwdriver / percutaneous pedicle screw complex is more rigid , which may be desirable . to increase rigidity and prevent migration of the guide 520 along the arms 432 , a set screw , complementary latching structure , and / or other fastening devices may be included to temporarily lock the guide 520 to the screw assembly 400 . though not shown , a handle may be coupled to the shaft 510 above the guide 520 . once the screws 410 are in place in the pedicles 104 ( or the pedicles 106 ), the screwdriver 500 and the k - wires 193 may be removed ( fig2 ). at this point in the procedure , the only devices extending through the patient &# 39 ; s skin may be the extension arms 432 for each screw assembly 400 . because of their attachment to the screw heads 420 , movement of the extension arms 432 may rotate the screw heads 420 three hundred and sixty degrees and also tilt the screw heads 420 . the desired rod 700 length is then selected . the rod length may be selected in various ways , such as by inspecting intraoperative fluoroscopic images or using a measurement device 600 ( fig2 ), for example . the measurement device 600 has two arms 610 operatively coupled together ( e . g ., by a pivot 612 , a sliding mechanism , etc . ), and a calibrated scale 614 is attached to one arm 610 such that the other arm 610 lines up with markings along the scale 614 . the arms 610 of the measurement device 600 are passed through the skin of the patient along the extension portions 430 such that each arm 610 contacts one of the heads 420 of the two screw assemblies 400 . a desired rod length is determined using the calibrated scale 614 , and the appropriate length rod 700 is selected . the rod 700 is typically curved to allow reconstruction of the normal curvature of the lumbar spine ; this curvature is known as lordosis . however , in some cases , the surgeon may select a straight rod 700 . the scale 614 may add a predetermined distance ( e . g ., 10 mm ) to the measured distance , and the ends of the arms 610 may be configured like ends of the rod 700 ; for example , each arm end may extend 5 mm ( or another appropriate distance ) outward from a respective screw head 420 . after the appropriate length rod 700 is selected , it is positioned using a percutaneous rod insertion tool 800 such that it is received in the receiving area 421 of the two screw heads 420 . the rod insertion tool 800 is shown in detail in fig2 through 33 . fig2 shows the rod insertion tool 800 secured to the rod 700 . as shown , the rod insertion tool 800 includes an elongate housing 810 having upper and lower ends 812 a , 812 b . the lower end 812 b is shown having a smaller diameter than the upper end 812 a ; this allows the lower end 812 b to function inside the patient &# 39 ; s body as needed , and also allows the surgeon to easily maneuver the upper end 812 a . the rod insertion tool 800 also includes a rotating end 820 , a control system for the rotating end 820 , an attachment device 840 , and a control system for the attachment device 840 . the rotating end 820 and the control system for the rotating end 820 are shown in fig2 through 27 . the rotating end 820 is shown in detail in fig2 and includes an attachment side 822 which rotates from a first position facing generally the same direction as the central axis of the housing 810 ( fig2 ) to a second position facing generally perpendicular to a central axis of the housing 810 ( fig2 ). when the rod 700 is coupled to the attachment device 840 , the rod 700 extends generally parallel to the housing axis when the rotating end 820 is at the first position , and extends generally perpendicular to the housing axis when the rotating end 820 is at the second position ( fig2 through 24 ). the rotating end 820 is pivotably coupled to the housing 810 at pivot point 824 . the control system for the rotating end 820 includes a thumbwheel 832 ( fig2 through 25 ) and an internal plunger 834 ( fig2 through 26 ). the thumbwheel 832 and the internal plunger 834 are configured with complementary structure such that rotation of the thumbwheel 832 causes the internal plunger 834 to become higher or lower relative to the housing 810 . while various structures may be acceptably used to achieve this motion , one example is complementary threads , such that the thumbwheel 832 acts as a stationary nut and the plunger 834 acts as a linearly - moving screw . in such a configuration , only a portion of the plunger 834 needs to be threaded ( i . e ., the portion interacting with the thumbwheel 832 as the attachment side 822 moves between the first and second positions ). to keep the plunger 834 from rotating ( instead of moving linearly ), the plunger 834 may interact with the housing 810 away from the threaded portion . for example , protrusions 836 ( fig2 ) on the plunger 834 may interact with rails or slots ( not shown ) in the housing 810 . as shown in the drawings , the plunger 834 may include an internal channel 835 . to translate the linear movement of the plunger 834 into rotational movement of the rotating end 820 , a link 838 may be pivotably coupled to the plunger 834 and the rotating end 820 , as shown in fig2 and 27 . when the plunger 834 is raised , the attachment side 822 may rotate about the pivot point 824 to the first position ( fig2 ), and when the plunger 834 is lowered , the attachment side 822 may rotate about the pivot point 824 to the second position ( fig2 ). turning now to the attachment device 840 and the control system for the attachment device 840 , attention is directed specifically to fig2 and 28 through 33 . the attachment device 840 includes a protrusion 842 ( fig2 ) for aligning the rod 700 , a deformable crown 844 ( fig2 through 31 ), and an actuator 852 ( fig2 , 32 , and 33 ). the deformable crown 844 is naturally at a cylindrical configuration , as shown in fig2 through 31 , and includes a plurality of expansion channels 846 . while various materials and configurations may of course be acceptable , an exemplary crown 844 is constructed of a resilient material such as titanium , has an outer diameter 844 a of approximately 0 . 12 inches , an inner diameter 844 b of approximately 0 . 10 inches , a height 844 c of approximately 0 . 216 inches , a channel depth 844 d of approximately 0 . 16 inches , and a channel width 844 e of approximately 0 . 02 inches . the actuator 852 ( fig2 , 32 , and 33 ) has a first portion 854 that is generally cylindrical and a second portion 856 that is generally conical , and the actuator 852 sits inside the crown 844 ( fig2 ). the actuator 852 may be configured such that the cylindrical portion 854 does not deform the crown 844 , and the conical portion 856 causes the crown 844 to expand . while various materials and configurations may of course be acceptable , an exemplary actuator 852 is constructed of the same material as the crown 844 , has an outer diameter 852 a for the cylindrical portion 854 of approximately 0 . 09 inches , has a maximum diameter 852 b for the conical portion 856 of approximately 0 . 11 inches , has an overall length 852 c of approximately 0 . 2 inches , and has a length 852 d for the conical portion 856 of approximately 0 . 12 inches . the control system for the attachment device 840 includes a screw 862 ( fig2 ) and an internal cable ( not shown ). the internal cable extends from the screw 862 ( which alternately may be a thumbwheel similar to thumbwheel 832 , or may be any other device for causing linear movement of the internal cable ) to the actuator 852 ( e . g ., to cavity 853 ) and passes through the internal channel 835 of the plunger 834 . when the screw 862 is utilized to increase tension on the internal cable , the internal cable pulls the actuator 852 inward , causing the crown 844 to expand ; when the screw 862 is utilized to reduce tension ( or impart a pushing force upon ) the internal cable , the internal cable pushes ( or allows the actuator 852 to move ) outward , allowing the crown 844 to contract ( fig2 ). the internal cable may be any appropriate structure capable of providing sufficient pulling and pushing forces , as described above and understood by one of skill in the art . an exemplary internal cable is constructed of 7 × 49 stainless steel with an outer diameter of approximately 0 . 044 inches . in use , then , the rod 700 is selected , and is aligned such that the protrusion 842 mates with cavity 712 at one end 710 of the rod 700 ( fig3 and 35 ), and the crown 844 and actuator 852 are inserted in cavity 714 of the rod 700 ( fig3 ) such that the crown 844 is generally cylindrical . the screw 862 is then used to increase tension on the internal cable , causing the actuator conical portion 856 to deform the crown 844 . with the crown 844 deformed , the crown 844 exerts force on the rod 700 , in effect locking the rod 700 to the attachment device 840 . using the rod insertion tool 800 , the rod 700 is inserted through the patient &# 39 ; s skin ( i . e ., inside an extension portion 430 ) such that the rod 700 is generally aligned with the center axis of the shell 820 . once the rod 700 is inserted , the thumbwheel 832 is rotated , causing the internal plunger 834 to lower and the rotating end 820 ( and the attached rod 700 ) to rotate . after the rod 700 is received in the receiving areas 421 of the two screw heads 420 , the screw 862 is used to provide a pushing force ( or release tension ) on the internal cable , allowing the actuator conical portion 856 to exit the crown 844 and the crown 844 to return to the cylindrical configuration . with the crown 844 at the cylindrical configuration , the attachment device 840 may be separated from the rod 700 and the rod insertion tool 800 may be removed . turning to fig3 through 38 , once the rod 700 is in place in the receiving areas 421 of the two screw heads 420 , a cap 900 is fixed to a threaded portion of each of the screw heads 420 . the caps 900 may be placed using the screwdriver 500 or another tool ( e . g ., a simple screwdriver having an appropriate driving mechanism ), and the caps 900 lock the rod 700 in place by exerting force on the rod 700 . if compression is desired , one of the caps 900 is set in place and tightened , and the other cap 900 is set in place but not yet tightened . before the second cap 900 is tightened , a compressor device 1000 is fitted onto the arms 432 of each extension portion 430 ( fig3 ). pressure is then applied from the compressor device 1000 to the arms 432 to provide compressive stress across the instrumentation construct to improve interbody fusion device surface area contact with the adjacent vertebral body endplates , thus increasing the probability of successful fusion of the vertebrae during healing and minimizing post - operative interbody graft migration . while compressive forces are applied , the second cap 900 is tightened , securing the rod 700 in a compressed position . the extension portions 430 of adjacent screw assemblies 400 may overlap slightly during compression ; this is possible because the extension portions 430 of adjacent screw assemblies 400 are thin and low profile , which allows more effective compression . the compressor device 1000 is shown in detail in fig4 through 42 and has a pivot 1002 , two arms 1004 , and a notched indicator 1006 attached to one arm 1004 . each arm 1004 has an attachment portion 1005 ( fig4 and 42 ) configured for attachment to the extension portions 430 of the screw assemblies 400 . a tooth 1008 coupled to the second arm 1004 can be advanced along the notched indicator 1006 in the manner of a ratchet to set and maintain a desired level of compression . more particularly , the notched indicator 1006 has a toothed side that engages the tooth 1008 on the second arm 1004 to maintain a compressed state . compression is maintained until the tooth 1008 is released from the indicator 1006 to permit removal of the compressor device 1000 from the extension portions 430 after the second cap 900 is tightened . after the rod 700 is in place and both caps 900 are tightened , the extension portions 430 may be removed from the pedicle screws 410 and the screw heads 420 by simply pulling the arms 432 away from one another , causing the extension portions 430 to fail at the defects 433 , which are best shown in fig1 . in an exemplary embodiment , approximately a 30 ° angle between the arms 432 is required to separate the extension portions 430 from the pedicle screws 410 and the screw heads 420 ; this of course can be altered ( e . g ., by altering the design of the defects 433 ), however . once the extension portions 430 are removed , the fascia and skin may be closed , and the procedure may be concluded . in prior art percutaneous pedicle screw systems , early release of the percutaneous screw extensions is a significant problem . this typically requires complete removal of the pedicle screw , and a larger diameter pedicle screw / extension complex is then assembled and re - inserted into the pedicle over a new k - wire . this requires extensive operative time , and can be a major source of patient morbidity . salvage tool 1500 ( shown in fig4 a through 46 ) effectively reconstructs the extension portion 430 in the event that the extension portion 430 is released prematurely ; this avoids the need for pedicle screw removal and replacement . to be clear , salvage tool 1500 is currently not intended to be used in every surgery , or even routinely , but is instead a device which may be used if necessary . the salvage tool 1500 contains two extensions 1510 that are manufactured to the same dimensions and configurations as the original extension portion 430 . salvage tool 1500 also contains a trigger 1522 along a handle 1520 . by pulling the trigger 1522 , the two extension arms 1510 are brought from an open alignment ( fig4 a ) into a closed ( parallel ) alignment ( fig4 b and 45 ). this may be accomplished , for example , through linkage coupled to at least one of the extensions 1510 and operable by the trigger 1522 to rotate the extension 1510 to the closed alignment when the trigger 1522 is pressed . various other mechanical systems may alternately be used to rotate at least one of the extensions 1510 upon pressing the trigger 1522 , as will be clear to one skilled in the art . the extension ( s ) 1510 may be biased to the open alignment ( e . g ., by one or more spring ), and a lock 1530 may be employed to maintain the extension ( s ) 1510 at the closed alignment for a period of time . the lock 1530 shown in fig4 and 45 is simply a catch that is rotatable about the handle 1520 to maintain the trigger 1522 at the pressed configuration until released . again , various other mechanical devices may alternately be used to lock the extension ( s ) 1510 at the closed alignment , as will be clear to one skilled in the art . to use the salvage tool 1500 ( e . g ., in the event of premature separation of extension portions 430 from pedicle screw 410 ), the extensions 1510 are inserted adjacent the screw head 420 . the trigger 1522 is then pulled , bringing the extensions 1510 to the closed alignment along the screw head 420 , and the lock 1530 may be employed . as shown in fig4 , a ledge ( or “ wall ”) 1511 may be located at the distal end 1510 a of each extension 1510 to extend along the lower side of the screw head 420 when the extensions 1510 are in place . the extension portions 430 are thus reconstructed , allowing the operation to continue ( e . g ., the rod 700 may be positioned and / or secured ) without having to convert to an open procedure or remove and replace the pedicle screw 410 . while the procedure set forth above includes only two screw assemblies 400 , multilevel procedures may also be performed using the equipment and techniques set forth above . as an example , a two level minimally invasive procedure according to one embodiment is shown and described with reference to the above description and fig1 through 46 of the accompanying drawings , and additionally with reference to fig4 through 56 of the accompanying drawings . for a two level procedure , the steps set forth above to fuse vertebrae 100 ( i . e ., the steps utilizing the port 200 ) are repeated on an additional adjacent vertebra 100 such that the additional vertebra 100 is similarly fused . this situation is shown schematically in fig4 . for a multilevel fusion , screw assemblies 400 are first fixed to the upper and lower vertebrae 100 a , 100 b ( fig4 ) in the same manner as described above ( i . e ., starting with placement of jamshidi needles and ending with removal of the screwdriver 500 and the k - wires 193 after the screws 410 are in place in the pedicles 104 or 106 ). next , an alignment tool 1600 is attached to the extension portion 430 of the fixed screw assemblies 400 . the alignment tool 1600 is shown in fig4 through 56 and includes opposed rails 1610 ( identified individually as 1610 a and 1610 b ) and a plurality of receiving members 1620 . in some embodiments , at least one of the receiving members 1620 is permanently coupled to at least one of the rails 1610 such that it may or may not be movable along the rail 1610 but cannot be separated from the rail 1610 . in other embodiments , all of the receiving members 1620 are removably coupled to the rails 1610 . each receiving member 1620 is configured to receive a respective extension portion 430 . in some embodiments , as shown in fig4 through 56 , the receiving members 1620 for use at the ends 1600 a of the alignment tool 1600 each have first and second holes 1622 a , 1622 b configured to receive the arms 432 of respective extension portions 430 ( these receiving members 1620 are identified individually as 1620 a ), while receiving members 1620 for use in a middle region 1600 b of the alignment tool 1600 each have a single hole 1624 for receiving the arms 432 of respective extension portions 430 ( these receiving members 1620 are identified individually as 1620 b ). the holes 1624 may be rectangular , as shown in fig4 and 49 , or may be circular , as shown in fig5 a through 56 , or may be any other appropriate shape . a circular shape may be desirable for allowing easier rotation of the extension portion 430 inside the hole 1624 . while only one receiving member 1620 b is shown in the drawings , it should be appreciated that additional receiving members 1620 b may be required for procedures requiring placement of four or more pedicle screws 410 . if a receiving member 1620 is movable along the rails 1610 , a locking device is preferably included to restrict the receiving member 1620 from moving from a desired location along the rail 1610 a . for example a set screw 1632 ( fig5 a and 50 b ) operable by the user may extend through hole 1634 in the receiving device 1620 to interact with the rail 1610 a passing through hole 1636 in the receiving device 1620 , effectively locking the receiving member 1620 to the rail 1610 a . while a specific embodiment of a locking device is shown in the accompanying drawings , one skilled in the art will appreciate that other locking devices and configurations may alternately , or additionally , be used . additionally , a locking device is preferably included to restrict the receiving member 1620 from moving from a desired location along the arms 432 of a respective extension portion 430 . for example , a set screw 1642 ( fig5 a and 50 b ) operable by the user may extend through hole 1644 in the receiving device 1620 to interact with the rail 1610 b passing through hole 1646 in the receiving device 1620 . because pressure on the rail 1610 b from set screw 1640 causes the rail 1610 b to exert pressure on the arm 432 ( which passes through hole 1622 b for receiving members 1620 a , and which passes through hole 1624 for receiving members 1620 b ), this effectively locks the receiving member 1620 to both the rail 1610 b and the arm 432 . while a specific embodiment of a locking device is shown in the accompanying drawings , one skilled in the art will appreciate that other locking devices and configurations may alternately , or additionally , be used . in use , then , the extension portions 430 of the upper and lower screw assemblies 400 are coupled to respective receiving members 1620 ( e . g ., receiving members 1620 a ), which may require adjusting the receiving members 1620 along the rails 1610 , as set forth above . once in place , the locking devices are used to fix the receiving members 1620 to the rails 1610 and also to fix the receiving members 1620 to the extension portions 430 . at this point , intraoperative fluoroscopy may be utilized . the unlocked receiving member 1620 ( e . g ., receiving member 1620 b ), and specifically the hole 1624 , is aligned with the pedicle 106 ( or the pedicle 108 ) and fixed to the rails 1610 , as set forth above . next , the remaining screw assembly 400 is fixed to the remaining vertebra 100 in the same manner as described above and used for the prior two screw assemblies 400 ( i . e ., starting with placement of a jamshidi needle and ending with removal of the screwdriver 500 and the k - wire 193 after the screw 410 is in place in the pedicle 104 or 106 ), though the jamshidi needle , the k - wire 193 , and the screw assembly 400 are all inserted through the hole 1624 . by using the alignment tool 1600 ( e . g ., by working through the hole 1624 ), all of the screw heads 420 will be aligned to receive the rod 700 . this is generally shown in fig5 , though it should be appreciated that the rod 700 would never be in place before all of the screw assemblies 400 are in place , and that the caps 900 would not be set in place until after the rod 700 is positioned in all three receiving areas 421 . the rod 700 is selected as set forth above . next , using the rod insertion tool 800 , the rod 700 is positioned through the extension portion 430 of the upper screw assembly 400 or the lower screw assembly 400 , and rotated , as set forth above , such that the rod 700 is positioned in all three receiving areas 421 of the screw heads 420 . caps 900 are then set in place as described above , and only one cap 900 ( e . g ., the cap 900 in the middle ) is tightened . once the caps 900 are set in place , the alignment tool 1600 may be released from the extension portions 430 and set aside . if compression is desired , the compressor device 1000 may be used generally as set forth above . the upper or lower screw assembly 400 is first compressed with the central screw assembly 400 and locked into place by tightening the appropriate cap 900 , and then the other screw assembly 400 is compressed with the central screw assembly 400 and locked into place by tightening the remaining cap 900 . to conclude the procedure , the extension portions 430 may be removed from the pedicle screws 410 and the screw heads 420 as set forth above , and the fascia and skin may be closed . a summary of the procedures described above is illustrated in the flowchart of fig5 . procedure 2000 begins with an incision 2002 for a posterior approach to the patient &# 39 ; s spine . the port 200 is then inserted through the skin incision until it is flush with the facet 118 . the decompression is then performed at step 2004 through the port 200 , which includes a facetectomy and microdiscectomy . if a laminectomy is needed ( see step 2005 ), it is performed at step 2006 through the port 200 , and then the procedure 2000 continues to step 2008 ; if a laminectomy is not needed , the procedure 2000 continues from step 2004 to step 2008 . at step 2008 , the nerve root is gently retracted medially with a nerve root retractor 180 that may be attached to the port 200 . the discectomy is then completed at step 2010 , and the interbody fusion device 190 is inserted through the port 200 into the intervertebral space between the vertebral bodies 102 to elicit arthrodesis . the port 200 is then removed , and the procedure 2000 continues to step 2012 . at step 2012 , k - wires 193 are inserted into the pedicles 104 ( or 106 ) of the vertebrae using jamshidi needles , and cannulated pedicle screws 410 ( of screw assemblies 400 ) are inserted percutaneously over the k - wires 193 into the upper and lower vertebrae 100 of the spinal segment to be stabilized . if a multilevel fusion is performed ( see step 2014 ), the alignment tool 1600 is placed over the percutaneous extensions 430 of the screw assemblies 400 and then the intervening pedicle screw ( s ) 410 is / are inserted through the alignment tool 1600 at step 2016 . this guarantees alignment of the middle pedicle screw ( s ) 410 within the construct , thereby facilitating rod placement , and the procedure 2000 continues to step 2018 . if more than two vertebrae are not involved , the procedure 2000 moves from step 2012 to step 2018 . if an extension portion 430 of a screw assembly 400 is accidentally released prematurely ( see step 2018 ), the salvage tool 1500 is used at step 2020 to grip the screw head 420 , allowing completion of the procedure 2000 without replacing the pedicle screw assembly 400 ; the procedure 2000 then continues to step 2022 . if the extension portion 430 is not released prematurely , the procedure 2000 moves from step 2018 to step 2022 . at step 2022 , the appropriate rod length is measured ( e . g ., from intraoperative fluoroscopic images or using the measurement device 600 ), and the procedure 2000 continues to step 2024 . at step 2024 , the rod 700 having the appropriate length is selected and inserted into the rod insertion tool 800 . the rod insertion tool 800 is then used to insert the rod 700 between the percutaneous screw extensions 430 of the most caudad or cephalad pedicle screw assembly 400 within the construct . next , the rod 700 is rotated into position within the receiving areas 421 of the polyaxial heads 420 , and the caps 900 are set in place . one cap 900 is tightened , securing the rod 700 in place . the procedure 2000 then moves to step 2026 , where different paths are taken depending on whether compression is desired . if so , the procedure 2000 continues to step 2028 ; if not , the procedure 2000 continues to step 2030 . at step 2028 , the compressor device 1000 is fitted onto the extension portions 430 and adjusted to provide the amount of compression that is desired . the untightened caps 900 are tightened while compression is applied to maintain the instrumentation construct in the compressed position , and the compressor device 1000 is set aside . the procedure 2000 then moves to step 2032 . at step 2030 , the untightened caps 900 are fully tightened to finish securing the rod 700 in place , and the procedure 2000 continues to step 2032 . at step 2032 , the extension portions 430 are removed , and the incision is closed at step 2034 to end the procedure 2000 . it should be understood that the matter contained in the above description and / or shown in the accompanying drawings should be interpreted as illustrative and not in a limiting sense . those skilled in the art appreciate that variations from the specified embodiments disclosed above are contemplated herein . certain features and subcombinations are of utility and may be employed without reference to other features and subcombinations and are contemplated within the scope of the claims . further , various steps set forth herein may be carried out in orders that differ from those set forth herein without departing from the scope of the present methods . the description should not be restricted to the above embodiments , but should be measured by the following claims .

US-60975209-A

a dispensing container for dispensing tissues one at a time from a web of perforated tissue material such as a web of premoistened , perforated towels . a cap is removably secured to the container body and a dispensing outlet is formed in the cap , with the outlet comprising a generally enlarged portion through which the tip of the leading tissue of the web can be passed , a groove portion extending from one end of said enlarged portion , and a generally circular portion at the opposite end of said groove . the generally circular portion of said outlet functions to apply tension to the web when the web is pulled from the container , the tension causing the leading tissue to separate at the perforation from the next tissue and leave exposed the tip of the next tissue to facilitate the next dispensing operation .

referring now in more detail to the application drawing , wherein like parts are indicated by like reference numerals , the dispensing container constructed in accordance with the present invention is generally indicated at 10 and comprises a body 12 and a cap 14 . the body 12 is formed with a reduced diameter neck portion 16 the outer periphery of which is formed with an annular recess 20 adapted to receive the bead 18 when the cap is snapped down over the neck 16 . a frictional fitting is thereby provided between the cap and the body , whereby the cap may be easily manually removed for supplying additional webs to the container . although a snap fit has been illustrated for the cap and the body , it will be understood that the cap and body may be provided with screw threads or other suitable securing means for removably retaining the cap on the body . it will also be understood that the body and cap , although shown circular in the application drawings , can be square , oval , or any desired shape and is of sufficient height and volume to receive the web of tissues therein . referring to fig4 and 5 , the web of tissues is indicated in dash lines at w and in the form shown the individual tissues are dispensed from the inside of the roll rather than the outside , although either arrangement is satisfactory . the web of tissues is preferably premoistened prior to placement in the container 10 , although it will be understood that a moisturizing liquid can be contained within the body 12 for contact with the web w . the present invention relates to the dispensing outlet formed in the cap 14 , and reference is made to fig3 - 6 . the cap is formed with a recess 22 in the upper surface thereof , and a dispensing outlet generally indicated at 26 is formed in the recess through the remaining thickness of the cap . the dispensing outlet 26 includes an enlarged portion 28 , triangular as shown , a slot or groove portion 30 , and a generally circular end portion 32 . a lid 34 is integral with and hinged to the cap at the end of the recess 24 , preferably by means of a &# 34 ; living hinge ,&# 34 ; with the thickness of the lid 34 coinciding with the depth of the recess 22 whereby the lid , when closed , is flush with the top surface of the cap 14 , with the lid in such position covering the dispensing outlet 26 . as shown in fig2 the lid 34 preferably extends slightly beyond the periphery of the cap 14 , as shown at 36 , to provide a tab by means of which the lid can be raised to expose the dispensing outlet . the entire construction of the cap 14 and the body 12 can be molded from a suitable plastic material , with neither the material nor the molding techniques forming a part of the present invention . the cap 14 can be molded as one piece and no part - molding operations or assembly is required , whereby manufacturing costs are minimized . as noted , the web w is provided in roll form , with the roll varying in width , for example , from 5 to 12 inches depending upon the size of the container , with the web being perforated at spaced increments along the length of the roll . the spacing between perforations will vary depending upon the width of the roll , with perforations every 6 to 9 inches being typical . the tissue is preferably comprised of non - woven fabric or paper material having the necessary web strength characteristics to satisfactorily absorb the tension applied to the web during the dispensing operation in which the leading tissue is separated along the perforations from the succeeding tissue . again , the present invention is not directed to the particular material used , and in this regard it should be noted that the dispensing outlet of the present invention works equally well with wet or dry tissues . a non - woven fabric can be used and special papers are also commercially available , with paper having a substantial cost advantage over non - woven fabric . the manner in which the tissues are dispensed from the web w through the dispensing outlet 26 is as follows . the container is normally supplied to the retailer with the lid 34 in a closed position covering the recess 22 and the dispensing outlet , and the innermost , leading tissue of the web , assuming the tissues are dispensed from the inside of the roll rather than the outside , is positioned just below the dispensing outlet 26 . when it is desired to dispense a tissue from the container , the consumer moves the lid 34 to an open position as shown in fig4 - 5 , and grasps and pulls the tip of the leading tissue through the enlarged portion 28 of the dispensing outlet , with such enlarged portion being sufficient in area to enhance grasping of the tissue without difficulty , a problem encountered in certain prior art dispensing containers . the cap 14 can be temporarily removed and the tip of the tissue threaded through the enlarged portion 28 in the event the tissue cannot be grasped from the exterior of the cap . after pulling or threading the lead end of the tissue through the enlarged portion 28 of the dispensing outlet , the tissue is pulled upwardly and outwardly so that the tissue passes through the slot 30 toward and into the circular portion 32 of the outlet . at this point , the tissue is located entirely within the circular portion 32 and the adjacent end of the slot 30 of the dispensing outlet , and when the leading tissue is completely exterior of the container , as can be visually seen from the presence of the perforations which separate the tissues , the leading tissue is pulled radially outwardly of the container as shown in fig5 whereby the leading tissue is separated at the perforations from the next tissue . the leading end of the next tissue remains exposed exteriorly of the dispensing outlet whereby the dispensing of the next tissues can be effected simply by pulling the next tissue upwardly and outwardly as described . between dispensing operations , the lid 34 is preferably closed to prevent evaporation from the moist tissues , with the length of tissue extending through the dispensing outlet not being sufficient in quantity to interfere with the closing of the lid . the recess 22 and lid 34 are preferably dimensioned so as to provide a fairly tight fit when the lid is closed , with the tab 36 at the forward end of the lid facilitating lifting of the same prior to the next dispensing operation . if desired , the recess 22 and lid 34 may be constructed so as to provide a more positive interfitting so as to move positively maintain the lid in its closed position . highly satisfactory dispensing is achieved by virtue of the dispensing outlet in accordance with the present invention . due to the shape of the dispensing outlet , particularly the enlarged circular opening and the slot adjacent thereto , it is possible to repeatedly feed and tear off the leading tissue by applying uniform tension to the tissue through the dispensing outlet . as previously noted , too little tension or frictional resistance at the dispensing outlet results in &# 34 ; roping &# 34 ; of the web so that more than one tissue is dispensed at one time . on the other hand , if the tension or frictional resistance is excessive , the tension in the tissue results in premature tearing of the lead tissue either above the line of perforations or when the perforations have not yet reached the dispensing outlet . the result in either event is undesirable and adversely effects the proper dispensing of the next tissue . an important factor in accordance with the improved results achieved by the present invention is the relationship between the size of the circular portion 32 of the dispensing outlet and the perforations in the web w . the spacing and size of the perforations directly effect the amount of tension required to be applied to the leading tissue to achieve separation of the same from the succeeding tissue , as do the area of the circular portion 32 of the dispensing outlet and the quantity of tissue material pulled therethrough . the quantity of material depends upon the width of the web w , and the diameter of the circular portion 32 of the outlet should be generally proportional to the width of the web w . this can be easily effected during manufacturing by providing a cap having a dispensing outlet specifically adapted to dispense tissues from a web having a particular width to fit the container . however , a significant advantage of the present invention resides in the ability of the dispensing outlet to properly tension the web despite variations in web width and bulk . excess material not contained in the circular portion 32 of the outlet 26 is allowed to spill over into the slot or groove 30 , with the tension in the web during the tearing or separation , however , being controlled principally by the material in the portion 32 . once the tearing along the perforations is initiated response to the pulling of the tissue upwardly and outwardly , the tearing will continue along the perforations of the material located in the groove . as will be readily understood by those skilled in the art , with webs of greater width or bulk , the amount of material spilling over into the groove will be greater , without , however , adversely affecting the substantially uniform pressure needed to effect separation of the tissues . also significant is the dimensional relationship of the slot 30 to the circular portion 32 of the outlet . where the web width is 5 - 8 inches , a circular opening of 1 / 8 inch provides excellent dispensing , and the width of the slot 30 is preferably one - half the diameter of the circular opening , or 1 / 16 inch . this relationship serves to direct the tissue into the circular opening and to permit any excess material to remain in the slot . after substantial experimentation , the arrangement of the slot and circular opening was found to permit repeated dispensing of the tissues with uniform levels of tension applied to the leading tissue . at least 50 % and preferably up to 75 % of the tissue should be positioned in the circular opening 32 during dispensing , and lesser amounts are indicative of the need to use a larger opening and slot for the particular material dispensed . this can be readily accommodated by changing the cap to one in which the dispensing outlet has a larger slot and circular opening . it will thus be seen that the objectives of the invention have been achieved . by virtue of the novel shape of the dispensing outlet , if is possible to repeatedly dispense individual tissues from a web of tissues by applying a constant tension on the leading tissue as it is pulled upwardly through the dispensing outlet . the tissue is pulled both upwardly and radially outwardly and the leading tissue is separated at the perforation line , leaving an exposed portion of the next tissue to facilitate the next dispensing operation . between dispensing operations , the lid can be moved to a closed position thereby covering the exposed tissue and preventing evaporation of the tissues in the container .

US-62774775-A

organophosphate nerve agents and pesticides are potent inhibitors of acetylcholinesterase . though oxime nucleophiles can reactivate an ache - phosphyl adduct , the adduct can undergo a reaction called aging , leading to an aged - ache adduct . the invention provides compounds and methods that can be used to reactivate an aged - ache adduct . such compounds and methods are useful to counteract organophosphorus poisoning .

the following definitions are used , unless otherwise described : halo is fluoro , chloro , bromo , or iodo . alkyl denotes both straight and branched groups ; but reference to an individual radical such as propyl embraces only the straight chain radical , a branched chain isomer such as isopropyl being specifically referred to . aryl denotes a phenyl radical or an ortho - fused bicyclic carbocyclic radical having about nine to ten ring atoms in which at least one ring is aromatic . heteroaryl encompasses a radical of a monocyclic aromatic ring containing five or six ring atoms consisting of carbon and one to four heteroatoms each selected from the group consisting of non - peroxide oxygen , sulfur , and n ( r x ) wherein r x is absent or is h , o , ( c 1 - c 4 ) alkyl , phenyl or benzyl , as well as a radical of an ortho - fused bicyclic heterocycle of about eight to ten ring atoms comprising one to four heteroatoms each selected from the group consisting of non - peroxide oxygen , sulfur , and n ( r x ). the term ache - op includes adducts formed when an organophosphorous ( op ) agent binds to a residue ( e . g . a serine residue ) in the catalytic triad of the active site of ache . the term aged - ache adduct includes adducts formed when an ache - op adduct experiences a solvolytic loss of an alkyl group . the term reactivation ( or resurrection ) describes the process whereby an aged - adduct is converted to a corresponding ache - op adduct ( e . g . using a compound or method of the invention ). when x is a counter ion it is understood x can be any suitable counterion . even if it lacks significant ache resurrecting activity , a salt of formula i can be useful as an intermediate for the preparation or purification of other salts of formula i that have ache resurrecting activity . accordingly in the compounds of formula ( i ), x can be any counterion . for example , in an embodiment of the invention x can be − bf 4 , cf 3 so 3 − , f − , cl − , br − , f − , monobasic sulfate , dibasic sulfate , monobasic phosphate , dibasic phosphate , or tribasic phosphate , no 3 − , pf 6 − , no 2 − , carboxylate , c e f f so 3 − , ( where e = 2 - 10 and f = 2e + 1 ), or arylsulfonyl , wherein aryl is optionally substituted with one or more groups independently selected from halo , cyano , nitro , carboxy , hydroxy , ( c 1 - c 3 ) alkyl , ( c 1 - c 3 ) alkoxy , ( c 1 - c 3 ) alkanoyl , ( c 1 - c 3 ) alkoxycarbonyl , ( c 2 - c 3 ) alkanoyloxy , and ( c 1 - c 3 ) alkylthio , wherein any ( c 1 - c 3 ) alkyl , ( c 1 - c 3 ) alkoxy , ( c 1 - c 3 ) alkanoyl , ( c 1 - c 3 ) alkoxycarbonyl , ( c 2 - c 3 ) alkanoyloxy , and ( c 1 - c 3 ) alkylthio can optionally be substituted with one or more halo . an aged - ache adduct includes enzyme bound phosphonates as described herein that have experienced a solvolytic loss of an alkyl group ( for example , see fig1 : r = isopropyl for sarin , pinacoyl for soman ). the aged adduct can be a phosphonate ester monoanion , which is intrinsically less reactive as an electrophile that the erstwhile neutral phosphonate ester of the initial phosphonyl - ache adduct . specific values listed below for radicals , substituents , and ranges , are for illustration only ; they do not exclude other defined values or other values within defined ranges for the radicals and substituents . specifically , ( c 1 - c 3 ) alkyl can be methyl , ethyl , propyl , or isopropyl ; ( c 1 - c 3 ) alkoxy can be methoxy , ethoxy , propoxy , or isopropoxy ; ( c 1 - c 3 ) alkanoyl can be formyl , acetyl , or propanoyl ; ( c 1 - c 3 ) alkoxycarbonyl can be methoxycarbonyl , ethoxycarbonyl , propoxycarbonyl , or isopropoxycarbonyl ; ( c 1 - c 3 ) alkylthio can be methylthio , ethylthio , propylthio , or isopropylthio ; ( c 2 - c 3 ) alkanoyloxy can be acetoxy or propanoyloxy ; aryl can be phenyl , indenyl , or naphthyl ; and heteroaryl can be furyl , imidazolyl , triazolyl , triazinyl , oxazoyl , isoxazoyl , thiazolyl , isothiazoyl , pyrazolyl , pyrrolyl , pyrazinyl , tetrazolyl , pyridyl , ( or its n - oxide ), thienyl , pyrimidinyl ( or its n - oxide ), indolyl , isoquinolyl ( or its n - oxide ) or quinolyl ( or its n - oxide ). the compounds of formula i can be formulated as pharmaceutical compositions and administered to a mammalian host , such as a human patient in a variety of forms adapted to the chosen route of administration , e . g ., orally or parenterally , by intravenous , intramuscular , topical or subcutaneous routes . thus , the present compounds may be systemically administered , e . g ., orally , in combination with a pharmaceutically acceptable vehicle such as an inert diluent or an assimilable edible carrier . they may be enclosed in hard or soft shell gelatin capsules , may be compressed into tablets , or may be incorporated directly with the food of the patient &# 39 ; s diet . for oral therapeutic administration , the active compound may be combined with one or more excipients and used in the form of ingestible tablets , buccal tablets , troches , capsules , elixirs , suspensions , syrups , wafers , and the like . such compositions and preparations should contain at least 0 . 1 % of active compound . the percentage of the compositions and preparations may , of course , be varied and may conveniently be between about 2 to about 60 % of the weight of a given unit dosage form . the amount of active compound in such therapeutically useful compositions is such that an effective dosage level will be obtained . the tablets , troches , pills , capsules , and the like may also contain the following : binders such as gum tragacanth , acacia , corn starch or gelatin ; excipients such as dicalcium phosphate ; a disintegrating agent such as corn starch , potato starch , alginic acid and the like ; a lubricant such as magnesium stearate ; and a sweetening agent such as sucrose , fructose , lactose or aspartame or a flavoring agent such as peppermint , oil of wintergreen , or cherry flavoring may be added . when the unit dosage form is a capsule , it may contain , in addition to materials of the above type , a liquid carrier , such as a vegetable oil or a polyethylene glycol . various other materials may be present as coatings or to otherwise modify the physical form of the solid unit dosage form . for instance , tablets , pills , or capsules may be coated with gelatin , wax , shellac or sugar and the like . a syrup or elixir may contain the active compound , sucrose or fructose as a sweetening agent , methyl and propylparabens as preservatives , a dye and flavoring such as cherry or orange flavor . of course , any material used in preparing any unit dosage form should be pharmaceutically acceptable and substantially non - toxic in the amounts employed . in addition , the active compound may be incorporated into sustained - release preparations and devices . the active compound may also be administered intravenously or intraperitoneally by infusion or injection . solutions of the active compound or its salts can be prepared in water , optionally mixed with a nontoxic surfactant . dispersions can also be prepared in glycerol , liquid polyethylene glycols , triacetin , and mixtures thereof and in oils . under ordinary conditions of storage and use , these preparations may contain a preservative to prevent the growth of microorganisms . the pharmaceutical dosage forms suitable for injection or infusion can include sterile aqueous solutions or dispersions or sterile powders comprising the active ingredient which are adapted for the extemporaneous preparation of sterile injectable or infusible solutions or dispersions , optionally encapsulated in liposomes . in all cases , the ultimate dosage form should typically be sterile , fluid and stable under the conditions of manufacture and storage . the liquid carrier or vehicle can be a solvent or liquid dispersion medium comprising , for example , water , ethanol , a polyol ( for example , glycerol , propylene glycol , liquid polyethylene glycols , and the like ), vegetable oils , nontoxic glyceryl esters , and suitable mixtures thereof . the proper fluidity can be maintained , for example , by the formation of liposomes , by the maintenance of the required particle size in the case of dispersions or by the use of surfactants . the prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents , for example , parabens , chlorobutanol , phenol , sorbic acid , thimerosal , and the like . in many cases , it will be preferable to include isotonic agents , for example , sugars , buffers or sodium chloride . prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption , for example , aluminum monostearate and gelatin . sterile injectable solutions can be prepared by incorporating the active compound in the required amount in the appropriate solvent with various other ingredients enumerated above , as required , followed by filter sterilization . in the case of sterile powders for the preparation of sterile injectable solutions , suitable methods of preparation include vacuum drying and the freeze drying techniques , which yield a powder of the active ingredient plus any additional desired ingredient present in the previously sterile - filtered solutions . for topical administration , the present compounds may be applied in pure form , e . g ., when they are liquids . however , it will generally be desirable to administer them to the skin as compositions or formulations , in combination with a dermatologically acceptable carrier , which may be a solid or a liquid . useful solid carriers include finely divided solids such as talc , clay , microcrystalline cellulose , silica , alumina and the like . useful liquid carriers include water , alcohols or glycols or water - alcohol / glycol blends , in which the present compounds can be dissolved or dispersed at effective levels , optionally with the aid of non - toxic surfactants . adjuvants such as fragrances and additional antimicrobial agents can be added to optimize the properties for a given use . the resultant liquid compositions can be applied from absorbent pads , used to impregnate bandages and other dressings , or sprayed onto the affected area using pump - type or aerosol sprayers . thickeners such as synthetic polymers , fatty acids , fatty acid salts and esters , fatty alcohols , modified celluloses or modified mineral materials can also be employed with liquid carriers to form spreadable pastes , gels , ointments , soaps , and the like , for application directly to the skin of the user . examples of useful dermatological compositions which can be used to deliver the compounds of formula i to the skin are known to the art ; for example , see jacquet et al . ( u . s . pat . no . 4 , 608 , 392 ), geria ( u . s . pat . no . 4 , 992 , 478 ), smith et al . ( u . s . pat . no . 4 , 559 , 157 ) and wortzman ( u . s . pat . no . 4 , 820 , 508 ). useful dosages of the compounds of formula i can be determined by comparing their in vitro activity , and in vivo activity in animal models . methods for the extrapolation of effective dosages in mice , and other animals , to humans are known to the art ; for example , see u . s . pat . no . 4 , 938 , 949 . the amount of the compound , or an active salt or derivative thereof , required for use in treatment will vary not only with the particular salt selected but also with the route of administration , the nature of the condition being treated and the age and condition of the patient and will be ultimately at the discretion of the attendant physician or clinician . the desired dose may conveniently be presented in a single dose or as divided doses administered at appropriate intervals , for example , as two , three , four or more sub - doses per day . the sub - dose itself may be further divided , e . g ., into a number of discrete loosely spaced administrations ; such as multiple inhalations from an insufflator or by application of a plurality of drops into the eye . compounds of the invention can also be administered in combination with other therapeutic agents , for example , other agents that are useful for the treatment of organophosphorous poisoning . when the compounds of the invention are administered to counteract organophosphorous poisoning , for example in a chemical warfare situation , they may be self - administered , for example , by means of a syringe or a spring - loaded syringe . when the compounds of the invention are administered as a combination with other agents ( e . g . 2 - pam , atropine , and / or diazepam ), the combination may also be administered by a single injection device such as , for example , a syringe or a spring - loaded syringe capable of simultaneously administering the one or more of the agents . the synthesis of the n - methyl - methoxypyridinium compounds can be conducted by exposure of starting pyridines to trialkoxonium ( e . g . trimethoxonium ) tetrafluoroborate or another alkylating agent ( e . g . meotf ) in a suitable solvent ( e . g . methylene chloride or toluene ) before or after oxime formation as illustrated in scheme 1 . the invention will now be illustrated by the following non - limiting examples . a 3 ml glass vial was equipped with a rubber septum and magnetic stir bar . the vial was brought into a glove box and charged with trimethyloxonium tetrafluoroborate ( 198 mg , 1 . 33 mmol ). the vial was sealed and removed from the glove box . a separate 3 ml vial was charged with 2 - methoxy - 6 - pyridinecarboxaldehyde ( aldrich # 662933 , 184 mg , 1 . 34 mmol ) and was dissolved in ch 2 cl 2 ( 1 . 5 ml ). the solution of pyridine was added via syringe onto the solid trimethoxonium tetrafluoroborate at room temperature . the vial which contained the pyridine was rinsed with ch 2 cl 2 ( 1 ml ) and the rinse solution was injected into the reaction vial . the reaction vial was kept at room temperature and stirring was maintained at ca . 400 - 600 rpm . over the course of the reaction ( 17 h ), the solid trimethoxonium tetrafluoroborate gradually dissolved , the solution clarified , and an oil gradually formed . at the end of the reaction , hexanes ( 2 ml ) were added after which stirring was stopped . any solid or oil was allowed to settle and the solvent was removed by glass pipette . the solid or oil was then rinsed with several portions of hexanes followed by diethyl ether . residual solvent was then removed in vacuo to provide the compound n - methyl - 6 - methoxy - 2 - pyridinecarboxaldehyde tetrafluoroborate . this oil was used for oxime formation without further purification . a flask was charged with naoch 3 ( 18 . 5 mg , 0 . 34 mmol ) and hydroxylamine hydrochloride ( 31 mg , 0 . 44 mmol ) and the solids were taken up in meoh ( 2 ml ) and left at room temperature for 5 min . the preceding aldehyde ( 80 mg , 0 . 34 mmol ) was dissolved in meoh ( 3 ml ) and was injected into the solution of hydroxylamine . after 18 hr at room temperature , the reaction was diluted with ethyl ether , filtered through sand , and concentrated in vacuo . the residue was taken up in acetonitrile and filtered through celite and concentrated in vacuo . the residue was taken up in acetone and slow diffusion of hexanes into the solution provided compound 100 ( 37 mg , 43 %) as a crystalline salt . a 3 ml glass vial was equipped with a rubber septum and magnetic stir bar . the vial was brought into a glove box and charged with meotf ( 116 μl , 1 . 06 mmol ) by micropipette . the vial was sealed and removed from the glove box . a separate 3 ml vial was charged with 4 - methoxy - 2 - pyridinecarboxaldehyde ( astatech c10253 , 145 mg , 106 mmol ) and was dissolved in phme ( 1 ml ). the solution of pyridine was added via syringe onto the meotf at room temperature . the vial which contained the pyridine was rinsed with phme ( 0 . 5 ml ) and the rinse solution was injected into the reaction vial . the reaction vial was kept at room temperature and stirring was maintained at ca . 400 - 600 rpm . after 20 h , hexanes ( 2 ml ) were added after which stirring was stopped . any solid or oil was allowed to settle and the solvent was removed by glass pipette . the solid or oil was then rinsed with several portions of hexanes followed by diethyl ether . residual solvent was then removed in vacuo to provide the compound n - methyl - 4 - methoxy - 2 - pyridinecarboxaldehyde triflate ( 300 mg , 94 %). this oil was used for oxime formation without further purification . a flask was charged with naoch 3 ( 18 mg , 0 . 34 mmol ) and hydroxylamine hydrochloride ( 27 mg , 0 . 39 mmol ) and the solids were taken up in meoh ( 1 ml ) and left at room temperature for 5 min . the preceding aldehyde ( 79 mg , 0 . 26 mmol ) was dissolved in meoh ( 2 ml ) and was injected into the solution of hydroxylamine . after 18 hr at room temperature , the reaction was diluted with ethyl ether , filtered through sand , and concentrated in vacuo . the residue was purified by c - 18 reverse phase chromatography ( water / acetonitrile , 0 - 100 %) and concentrated under a stream of air , which afforded compound 101 ( 18 mg , 22 %) as a crystalline salt . recombinant human acetylcholinesterase ( hache ) was irreversibly inhibited by exposure to an organophosphonate ( op ) analog of sarin , 7 -( isopropyl methylphosphonyl )- 4 - methylumbelliferone ( timperley , c . m ., et al ., j . fluor . chem ., 2006 , 127 , 1554 - 1563 ). the fully inhibited hache - op adduct was separated on a sephadex g - 50 quick spin column to remove excess nerve agent , and it was “ aged ” for 48 hours at 27 ° c . uninhibited hache was prepared following the same procedure by substituting acetonitrile in place of the op inhibitor , and it served as the control throughout the resurrection assay procedure . hydrolysis of acetylthiocholine ( atch ) by hache was measured spectrophotometrically following the ellman et al . assay method ( ellman , g . l ., et al ., biochem . pharmacol ., 1961 , 7 , 88 - 95 ) at t = 0 and 48 hours . op inhibited hache was assayed after treatment with 2 - pralidoxime ( 2 - pam ) to determine the percentage of “ aged ” hache (% ache aged ), or residual hache , activity as defined by equation ( 1 ). this % ache aged is the ratio of the initial rates for op inhibited hache ( ache inhibited ) and uninhibited hache ( ache free ) catalyzed hydrolysis of atch . fig2 depicts the procedural steps for a resurrection assay that can be used to determine the activity of a test compound ( e . g . compound 100 ). resurrection assays were performed by preparing a 100 μl incubation solution of 0 . 024 μg of “ aged ” hache in 0 . 1 % ( w / v ) bsa , 50 mm phosphate buffer ( ph 7 . 3 ), and 885 μm compound 100 . “ aged ” hache was incubated for 1 hour , 4 hour , and 24 hour periods at 27 ° c . following each incubation period , a 10 μl aliquot of the “ aged ” hache incubation solution was assayed in 50 mm phosphate buffer ( ph 7 . 3 ), 0 . 3 mm atch and 0 . 45 mm dtnb following a 30 minute incubation with 100 μm 2 - pam and a total volume of 300 μl . the percent of “ aged ” hache reactivated ( ache react ) by 2 - pam was calculated using equation ( 2 ), which is the ratio of the initial rates of “ aged ” hache ( ache aged ) and ache free catalyzed hydrolysis of atch assayed following each incubation with compound 100 . from equation ( 3 ), the percent of resurrected hache was determined . resurrection assay data is shown in the following table for 1 . 77 mm compound 100 , where v i is the initial rates for ache aged and ache free catalyzed hydrolysis of atch . background rates were measured in the absence of hache . all experiments were done in duplicate . all publications ( including topczewski et al ., organic letters , 15 , 1084 - 1087 ( 2013 ), patents , and patent documents are incorporated by reference herein , as though individually incorporated by reference . the invention has been described with reference to various specific and preferred embodiments and techniques . however , it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention .

US-201414163859-A

disclosed is a patch which is a formulation including deposited clonidine crystals and provides stable transdermal absorbability even after storage at varying temperatures . the patch disclosed includes a backing and a medicated layer integrally superposed on one surface of the backing . the medicated layer contains : 5 to 30 % by weight of clonidine including clonidine in a crystallized state ; 25 to 90 % by weight of a macromolecular base having a viscosity - average molecular weight of 800 , 000 or larger ; and 5 to 60 % by weight of a liquid additive capable of dissolving the clonidine . the weight ratio of the liquid additive to the macromolecular base ] is 0 . 1 to 2 . 0 .

the present invention will next be described more specifically by way of examples , but the invention is not limited thereto . thirty nine parts by weight of a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd . ), 13 parts by weight of clonidine , 8 parts by weight of light silicic acid anhydride ( product name : aerosil 200 , manufactured by nippon aerosil co ., ltd . ), and 560 parts by weight of toluene were stirred until uniform to obtain a mixed solution . then 28 parts by weight of a macromolecular base ( a ) having a viscosity - average molecular weight of 800 , 000 or larger ( high - molecular weight polyisobutylene , viscosity - average molecular weight : 1 , 100 , 000 , product name : oppanol b100 , manufactured by basf ) and 12 parts by weight of a macromolecular base ( b ) having a viscosity - average molecular weight of 10 , 000 or larger and less than 800 , 000 ( low - molecular weight polyisobutylene , viscosity - average molecular weight : 36 , 000 , product name : oppanol b10sfn , manufactured by basf ) were added to the mixed solution . the mixture was mixed uniformly to prepare a medicated layer - forming solution . the obtained medicated layer - forming solution was applied to 38 μm - thick release liner made of polyethylene terephthalate ( pet ) and having a silicon - treated surface to a dry thickness of 50 and dried in an oven at 80 ° c . for 60 minutes to obtain a medicated layer ( thickness : 50 μm ). then a 25 μm - thick pet film was prepared as a backing . the pet film was superposed on the surface of the medicated layer and pressed thereagainst to integrally superpose the backing on the surface of the medicated layer , and a patch in example 1 was thereby obtained . thirty eight parts by weight of a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd . ), 3 parts by weight of clonidine , 9 parts by weight of light silicic acid anhydride ( product name : aerosil 200 , manufactured by nippon aerosil co ., ltd . ), and 560 parts by weight of toluene were mixed and stirred until uniform to obtain a mixed solution . then 35 parts by weight of a macromolecular base ( a ) having a viscosity - average molecular weight of 800 , 000 or larger ( high - molecular weight polyisobutylene , viscosity - average molecular weight : 1 , 100 , 000 , product name : oppanol b100 , manufactured by basf ) and 15 parts by weight of a macromolecular base ( b ) having a viscosity - average molecular weight of 10 , 000 or larger and less than 800 , 000 ( low - molecular weight polyisobutylene , viscosity - average molecular weight : 36 , 000 , product name : oppanol b10sfn , manufactured by basf ) were added to the mixed solution . the mixture was mixed uniformly to prepare an adhesive layer - forming solution . the obtained adhesive layer - forming solution was applied to pet release liner having a silicon - treated surface to a dry thickness of 50 μm and dried in an oven at 80 ° c . for 60 minutes to obtain an adhesive layer ( thickness : 50 μm ). a 25 μm - thick porous polypropylene film ( product name : celgard # 2400 , manufactured by celgard , llc ) pre - impregnated with a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd .) in an amount of 9 g / m 2 was integrally superposed on the surface of the adhesive layer . then the medicated layer of example 1 with the pet release liner removed was integrally superposed on the porous polypropylene film to obtain a patch in example 2 . the porous polypropylene film had a large number of through holes extending between the opposite surfaces thereof . forty seven parts by weight of a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd . ), 13 parts by weight of clonidine , 8 parts by weight of light silicic acid anhydride ( product name : aerosil 200 , manufactured by nippon aerosil co ., ltd . ), and 560 parts by weight of toluene were mixed and stirred until uniform to obtain a mixed solution . then 29 parts by weight of a macromolecular base ( a ) having a viscosity - average molecular weight of 800 , 000 or larger ( high - molecular weight polyisobutylene , viscosity - average molecular weight : 1 , 100 , 000 , product name : oppanol b100 , manufactured by basf ) and 3 parts by weight of a macromolecular base ( b ) having a viscosity - average molecular weight of 10 , 000 or larger and less than 800 , 000 ( low - molecular weight polyisobutylene , viscosity - average molecular weight : 36 , 000 , product name : oppanol b10sfn , manufactured by basf ) were added to the mixed solution . the mixture was mixed uniformly to prepare a medicated layer - forming solution . the obtained medicated layer - forming solution was applied to polyethylene terephthalate - made release liner having a silicon - treated surface to a dry thickness of 50 μm and dried in an oven at 80 ° c . for 60 minutes to obtain a medicated layer ( thickness : 50 μm ). then a 25 μm - thick pet film was prepared as a backing . the pet film was superposed on the surface of the medicated layer and pressed thereagainst to integrally superpose the backing on the surface of the medicated layer . separately , 47 parts by weight of a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd . ), 3 parts by weight of clonidine , 8 parts by weight of light silicic acid anhydride ( product name : aerosil 200 , manufactured by nippon aerosil co ., ltd . ), and 560 parts by weight of toluene were mixed and stirred until uniform to obtain a mixed solution . then 39 parts by weight of macromolecular base ( a ) having a viscosity - average molecular weight of 800 , 000 or larger ( high - molecular weight polyisobutylene , viscosity - average molecular weight : 1 , 100 , 000 , product name : oppanol b100 , manufactured by basf ) and 3 parts by weight of a macromolecular base ( b ) having a viscosity - average molecular weight of 10 , 000 or larger and less than 800 , 000 ( low - molecular weight polyisobutylene , viscosity - average molecular weight : 36 , 000 , product name : oppanol b10sfn , manufactured by basf ) were added to the mixed solution . the mixture was stirred uniformly to prepare an adhesive layer - forming solution . the obtained adhesive layer - forming solution was applied to pet release liner having a silicon - treated surface to a dry thickness of 50 μm and dried in an oven at 80 ° c . for 60 minutes to obtain an adhesive layer ( thickness : 50 μm ). a 25 μm - thick porous polypropylene film ( product name : celgard # 2400 , manufactured by celgard , llc ) pre - impregnated with a liquid additive ( liquid paraffin , product name : hicall . m72 , manufactured by kaneda co ., ltd .) in an amount of 9 g / m 2 was integrally superposed on the surface of the adhesive layer . then the medicated layer of example 3 with the pet release liner removed was integrally superposed on the porous polypropylene film to obtain a patch in example 3 . the porous polypropylene film had a large number of through holes extending between the opposite surfaces thereof . thirty nine parts by weight of a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd . ), 1 part by weight of clonidine , 9 parts by weight of light silicic acid anhydride ( product name : aerosil 200 , manufactured by nippon aerosil co ., ltd . ), and 560 parts by weight of toluene were mixed and stirred until uniform to obtain a mixed solution . then 36 parts by weight of a macromolecular base ( a ) having a viscosity - average molecular weight of 800 , 000 or larger ( high - molecular weight polyisobutylene , viscosity - average molecular weight : 1 , 100 , 000 , product name : oppanol b100 , manufactured by basf ) and 15 parts by weight of a macromolecular base ( b ) having a viscosity - average molecular weight of 10 , 000 or larger and less than 800 , 000 ( low - molecular weight polyisobutylene , viscosity - average molecular weight : 36 , 000 , product name : oppanol b10sfn , manufactured by basf ) were added to the mixed solution . the mixture was mixed uniformly to prepare an adhesive layer - forming solution . a patch of example 4 was obtained by repeating the same procedure as in example 2 except that the above adhesive layer - forming solution was used . twenty eight parts by weight of a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd . ), 13 parts by weight of clonidine , 8 parts by weight of light silicic acid anhydride ( product name : aerosil 200 , manufactured by nippon aerosil co ., ltd . ), and 560 parts by weight of toluene were mixed and stirred until uniform to obtain a mixed solution . then 40 parts by weight of a macromolecular base ( a ) having a viscosity - average molecular weight of 800 , 000 or larger ( high - molecular weight polyisobutylene , viscosity - average molecular weight : 1 , 100 , 000 , product name : oppanol b100 , manufactured by basf ) and 11 parts by weight of a macromolecular base ( b ) having a viscosity - average molecular weight of 10 , 000 or larger and less than 800 , 000 ( low - molecular weight polyisobutylene , viscosity - average molecular weight : 36 , 000 , product name : oppanol b10sfn , manufactured by basf ) were added to the mixed solution . the mixture was uniformly mixed to prepare a medicated layer - forming solution . the obtained medicated layer - forming solution was applied to polyethylene terephthalate - made release liner ( thickness : 38 μm ) having a silicon - treated surface to a dry thickness of 50 μm and dried in an oven at 80 ° c . for 90 minutes to obtain a medicated layer ( thickness : 50 μm ). then a 25 μm - thick pet film was prepared as a backing . the pet film was superposed on the surface of the medicated layer and pressed thereagainst to integrally superpose the backing on the surface of the medicated layer . separately , 39 parts by weight of a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd . ), 1 part by weight of clonidine , 9 parts by weight of light silicic acid anhydride ( product name : aerosil 200 , manufactured by nippon aerosil co ., ltd . ), and 560 parts by weight of toluene were mixed and stirred until uniform to obtain a mixed solution . then 36 parts by weight of a macromolecular base ( a ) having a viscosity - average molecular weight of 800 , 000 or larger ( high - molecular weight polyisobutylene , viscosity - average molecular weight : 1 , 100 , 000 , product name : oppanol b100 , manufactured by basf ) and 15 parts by weight of a macromolecular base ( b ) having a viscosity - average molecular weight of 10 , 000 or larger and less than 800 , 000 ( low - molecular weight polyisobutylene , viscosity - average molecular weight : 36 , 000 , product name : oppanol b10sfn , manufactured by basf ) were added to the mixed solution . the mixture was stirred uniformly to prepare an adhesive layer - forming solution . the obtained adhesive layer - forming solution was applied to pet release liner having a silicon - treated surface to a dry thickness of 50 μm and dried in an oven at 80 ° c . for 60 minutes to obtain an adhesive layer ( thickness : 50 μm ). a 25 μm - thick porous polypropylene film ( product name : celgard # 2400 , manufactured by celgard , llc ) pre - impregnated with a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd .) in an amount of 9 g / m 2 was integrally superposed on the surface of the adhesive layer . then the medicated layer of example 5 with the pet release liner removed was integrally superposed on the porous polypropylene film to obtain a patch of example 5 . the porous polypropylene film had a large number of through holes extending between the opposite surfaces thereof . patches were produced as in example 5 except that the amounts of clonidine , the macromolecular base ( a ), the macromolecular base ( b ), the liquid additive , and light silicic acid anhydride in the medicated layer and the adhesive layer and the thickness of the adhesive layer were changed as described in tables 4 and 5 . forty seven parts by weight of a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd . ), 1 part by weight of clonidine , 8 parts by weight of light silicic acid anhydride ( product name : aerosil 200 , manufactured by nippon aerosil co ., ltd . ), and 560 parts by weight of toluene were mixed and stirred until uniform to obtain a mixed solution . then 30 parts by weight of a macromolecular base ( a ) having a viscosity - average molecular weight of 800 , 000 or larger ( high - molecular weight polyisobutylene , viscosity - average molecular weight : 1 , 100 , 000 , product name : oppanol b100 , manufactured by basf ) and 14 parts by weight of a macromolecular base ( b ) having a viscosity - average molecular weight of 10 , 000 or larger and less than 800 , 000 ( low - molecular weight polyisobutylene , viscosity - average molecular weight : 36 , 000 , product name : oppanol b10sfn , manufactured by basf ) were added to the mixed solution . the mixture was uniformly mixed to prepare an adhesive layer - forming solution . the obtained adhesive layer - forming solution was applied to polyethylene terephthalate - made release liner ( thickness : 38 μm ) having a silicon - treated surface to a dry thickness of 50 μm and dried in an oven at 80 ° c . for 90 minutes to obtain an adhesive layer ( i ) ( thickness : 50 μm ). next , an adhesive layer - forming solution was prepared in the same manner as described above . the obtained adhesive layer - forming solution was applied to polyethylene terephthalate - made release liner ( thickness : 38 μm ) having a silicon - treated surface to a dry thickness of 30 μm and dried in an oven at 80 ° c . for 90 minutes to obtain an adhesive layer ( ii ) ( thickness : 30 μm ). by repeating the above procedure , two adhesive layers ( ii ) were produced . the two adhesive layers ( ii ) with the pet - made release liner removed therefrom were superposed on the surface of the adhesive layer ( i ) formed on the pet - made release liner to thereby obtain an adhesive layer ( thickness : 110 μm ). a 25 μm - thick porous polypropylene film ( product name : celgard # 2400 , manufactured by celgard , llc ) pre - impregnated with a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd .) in an amount of 9 g / m 2 was integrally superposed on the surface of the adhesive layer . then the medicated layer in example 9 with the pet release liner removed was integrally superposed on the porous polypropylene film to obtain a patch in example 11 . the porous polypropylene film had a large number of through holes extending between the opposite surfaces thereof . forty seven parts by weight of a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd . ), 1 part by weight of clonidine , 8 parts by weight of light silicic acid anhydride ( product name : aerosil 200 , manufactured by nippon aerosil co ., ltd . ), and 560 parts by weight of toluene were mixed and stirred until uniform to obtain a mixed solution . then 30 parts by weight of a macromolecular base ( a ) having a viscosity - average molecular weight of 800 , 000 or larger ( high - molecular weight polyisobutylene , viscosity - average molecular weight : 1 , 100 , 000 , product name : oppanol b100 , manufactured by basf ) and 14 parts by weight of a macromolecular base ( b ) having a viscosity - average molecular weight of 10 , 000 or larger and less than 800 , 000 ( low - molecular weight polyisobutylene , viscosity - average molecular weight : 36 , 000 , product name : oppanol b10sfn , manufactured by basf ) were added to the mixed solution . the mixture was mixed uniformly to prepare an adhesive layer - forming solution . the obtained adhesive layer - forming solution was applied to polyethylene terephthalate - made release liner ( thickness : 38 μm ) having a silicon - treated surface to a dry thickness of 50 μm and dried in an oven at 80 ° c . for 90 minutes to obtain an adhesive layer ( i ) ( thickness . : 50 μm ). by repeating the above procedure , three adhesive layers ( i ) were produced . the pet release liner was removed from two of the three adhesive layers ( i ), and the two adhesive layers ( i ) with the pet release liner removed were integrally superposed on the surface of the remaining adhesive layer ( i ) formed on the pet release liner to thereby obtain an adhesive layer ( thickness : 150 μm ). a patch of example 12 was obtained by repeating the same procedure as in example 11 except that the above - produced adhesive layer was used . forty seven parts by weight of a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd . ), 1 part by weight of clonidine , 8 parts by weight of light silicic acid anhydride ( product name : aerosil 200 , manufactured by nippon aerosil co ., ltd . ), and 560 parts by weight of toluene were mixed and stirred until uniform to obtain a mixed solution . then 30 parts by weight of a macromolecular base ( a ) having a viscosity - average molecular weight of 800 , 000 or larger ( high - molecular weight polyisobutylene , viscosity - average molecular weight : 1 , 100 , 000 , product name : oppanol b100 , manufactured by basf ) and 14 parts by weight of a macromolecular base ( b ) having a viscosity - average molecular weight of 10 , 000 or larger and less than 800 , 000 ( low - molecular weight polyisobutylene , viscosity - average molecular weight : 36 , 000 , product name : oppanol b10sfn , manufactured by basf ) were added to the mixed solution . the mixture was uniformly mixed to prepare an adhesive layer - forming solution . the obtained adhesive layer - forming solution was applied to polyethylene terephthalate - made release liner ( thickness : 38 μm ) having a silicon - treated surface to a dry thickness of 50 μm and dried in an oven at 80 ° c . for 90 minutes to obtain an adhesive layer ( i ) ( thickness : 50 μm ). by repeating the above procedure , four adhesive layers ( i ) were produced . the pet release liner was removed from three of the four adhesive layers ( i ). the three adhesive layers ( i ) with the pet release liner removed were integrally superposed on the surface of the remaining adhesive layer ( i ) formed on the pet release liner to thereby obtain an adhesive layer ( thickness : 200 μm ). a patch of example 13 was obtained by repeating the same procedure as in example 11 except that the above - produced adhesive layer was used . forty seven parts by weight of a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd . ), 13 parts by weight of clonidine , 8 parts by weight of light silicic acid anhydride ( product name : aerosil 200 , manufactured by nippon aerosil co ., ltd . ), and 560 parts of toluene were stirred until uniform to obtain a mixed solution . then 20 parts by weight of a macromolecular base ( a ) having a viscosity - average molecular weight of 800 , 000 or larger ( high - molecular weight polyisobutylene , viscosity - average molecular weight : 1 , 100 , 000 , product name : oppanol b100 , manufactured by basf ) and 12 parts by weight of a macromolecular base ( b ) having a viscosity - average molecular weight of 10 , 000 or larger and less than 800 , 000 ( low - molecular weight polyisobutylene , viscosity - average molecular weight : 36 , 000 , product name : oppanol b10sfn , manufactured by basf ) were added to the mixed solution . the mixture was mixed uniformly to prepare a medicated layer - forming solution . a patch of comparative example 1 was obtained by repeating the same procedure as in example 1 except that the above medicated layer - forming solution was used . forty seven parts by weight of a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd . ), 3 parts by weight of clonidine , 9 parts by weight of light silicic acid anhydride ( product name : aerosil 200 , manufactured by nippon aerosil co ., ltd . ), and 560 parts by weight or toluene were mixed and stirred until uniform to obtain a mixed solution . then 29 parts by weight of a macromolecular base ( a ) having a viscosity - average molecular weight of 800 , 000 or larger ( high - molecular weight polyisobutylene , viscosity - average molecular weight : 1 , 100 , 000 , product name : oppanol b100 , manufactured by basf ) and 12 parts by weight of a macromolecular base ( b ) having a viscosity - average molecular weight of 10 , 000 or larger and less than 800 , 000 ( low - molecular weight polyisobutylene , viscosity - average molecular weight : 36 , 000 , product name : oppanol b10sfn , manufactured by basf ) were added to the mixed solution . the mixture was uniformly mixed to prepare an adhesive layer - forming solution . the obtained adhesive layer - forming solution was applied to 38 μm pet release liner having a silicon - treated surface to a dry thickness of 50 μm and dried in an oven at 80 ° c . for 60 minutes to obtain an adhesive layer ( thickness : 50 μm ). a 25 μm - thick porous polypropylene film impregnated with a liquid additive ( liquid paraffin , product name : hicall m72 , manufactured by kaneda co ., ltd .) in an amount of 9 g / m 2 was integrally superposed on the surface of the adhesive layer . then the medicated layer of comparative example 1 with the release liner removed was integrally superposed on the porous polypropylene film to obtain a patch in comparative example 2 . the porous polypropylene film had a large number of through holes extending between the opposite surfaces thereof . each of the medicated layers that had been formed on the release liner in the examples and comparative examples but had not been integrally superposed on the pet films was removed from the release liner immediately after production . then the medicated layer was cut into a square shape of side 2 cm to obtain an observation sample . next , the observation sample was observed under a polarizing microscope at a magnification of 100 ×, and a photograph was taken . the obtained photograph was observed to determine the presence or absence of clonidine in a crystallized state . when crystals having a crystal diameter of 1 μm or larger were observed , it was determined that clonidine in a crystallized state was deposited . the crystal diameter means the diameter of the minimum perfect circle that can surround a crystal on the photograph . clonidine deposited in a crystallized state was confirmed in all the medicated layers produced in the examples and comparative examples . 2 . observation of crystals under polarizing microscope ( storage at 25 ° c ., 40 ° c ., and 60 ° c .) each of the medicated layers that had been formed on the release liner in examples 1 and 3 and comparative example 1 but had not been integrally superposed on the pet films was removed from the release liner immediately after production . then the medicated layer was cut into three square sheets of side 2 cm to obtain observation samples . next , the observation samples were observed under a polarizing microscope at a magnification of 100 ×, and photographs were taken . the observation samples were wrapped and sealed with aluminum wrapping materials and stored in temperature atmospheres of 25 ° c ., 40 ° c ., and 60 ° c . after one month , each observation sample was removed , and the same observation area as that observed immediately after production was immediately observed and photographed , and the crystallized states of clonidine were compared . the results are shown in table 1 . the crystalline forms of clonidine in the medicated layers in examples 1 and 3 immediately after production were different from that in comparative example 1 . in examples 1 and 3 , only a very small amount of clonidine crystals disappeared even after storage at 60 ° c . for one month . however , in comparative example 1 , the disappearance of clonidine crystals was obvious . in examples 1 and 3 , the differences in changes in the crystallized state of clonidine due to the differences in storage temperature were very small . however , in comparative example 1 , the changes in the crystallized state of clonidine were significantly different at different storage temperatures . therefore , it was confirmed that , in the medicated layer included in each patch of the present invention , the change in the crystallized state of clonidine due to temperature change during storage was small . after each of the patches in examples 2 , 3 , and 4 and comparative example 2 was stored at 25 ° c . for one month or at 60 ° c . for one month , a rounded square test piece of side 1 . 8 cm ( application area : 3 cm 2 ) was cut from the patch . dorsal skin removed from a hairless mouse ( male , 8 weeks old ) was fixed on a franz diffusion cell maintained at 37 ° c ., and the test piece with the release liner removed was applied to the upper end of the skin through the adhesive layer of the test piece . a physiological saline solution with its ph adjusted to 7 . 2 was used as a receptor solution , and the lower end of the skin was immersed in the receptor solution . the receptor solution on the lower side of the skin was collected 3 , 6 , 24 , 30 , and 48 hours after the test piece was applied to the skin , and the concentration of clonidine was measured by hplc . then the permeation amount of clonidine per unit area of the test piece [ q ( mg / cm 2 )] determined from the clonidine concentration [ n ( mg / ml )] and the amount of the receptor solution [ w ( ml )] was computed at each time point using the formula : q ( mg / cm 2 )= n ( mg / ml )× w ( ml )/ 3 ( cm 2 ), and the determined value was used as a cumulative skin permeation amount . when the permeation amounts of clonidine were computed , since the receptor solution had been collected before the computation , the permeation amounts were corrected on the basis of the amount of the receptor solution collected . the results for examples 2 and 4 are shown in fig1 , the results for example 3 are shown in fig2 , and the results for comparative example 2 are shown in fig3 . in examples 2 , 4 , and 3 , no or a very small change in the clonidine permeation amount due to storage temperature change was found . however , in comparative example 2 , a significant change in the clonidine permeation amount due to storage temperature change was found . therefore , it was confirmed that , in the medicated layer included in each patch of the present invention , the stability of the absorption performance against temperature change during storage was improved . after each of the patches in examples 5 to 8 and comparative example 3 was stored at 25 ° c . for two weeks or at 60 ° c . for two weeks , a rounded square test piece of side 1 . 8 cm ( application area : 3 cm 2 ) was cut from the patch . dorsal skin removed from a hairless mouse ( male , 8 weeks old ) was fixed on a franz diffusion cell maintained at 37 ° c ., and the test piece with the release liner removed was applied to the upper end of the skin through the adhesive layer of the test piece . a physiological saline solution with its ph adjusted to 7 . 2 was used as a receptor solution , and the lower end of the skin was immersed in the receptor solution . the receptor solution on the lower side of the skin was collected 20 , 40 , and 60 hours after the test piece was applied to the skin , and the concentration of clonidine was measured by hplc . then the permeation amount of clonidine per unit area of the test piece [ q ( mg / cm 2 )] determined from the clonidine concentration [ n ( mg / ml )] and the amount of the receptor solution [ w ( ml )] was computed at each time point using the formula : q ( mg / cm 2 )= n ( mg / ml )× w ( ml )/ 3 ( cm 2 ), and the determined value was used as a cumulative skin permeation amount . when the permeation amounts of clonidine were computed , since the receptor solution had been collected before the computation , the permeation amounts were corrected on the basis of the amount of the receptor solution collected . the results for example 5 and comparative example 3 are shown in fig4 , the results for examples 6 and 7 are shown in fig5 , and the results for example 8 are shown in fig6 . after each of the patches in examples 9 to 13 was stored at 25 ° c . for two weeks , a rounded square test piece of side 1 . 8 cm ( application area : 3 cm 2 ) was cut from the patch . dorsal skin removed from a hairless mouse ( male , 8 weeks old ) was fixed on a franz diffusion cell maintained at 37 ° c ., and the test piece with the release liner removed was applied to the upper end of the skin through the adhesive layer of the test piece . a physiological saline solution with its ph adjusted to 7 . 2 was used as a receptor solution , and the lower end of the skin was immersed in the receptor solution . the receptor solution on the lower side of the skin was collected 20 , 40 , and 60 hours after the test piece was applied to the skin , and the concentration of clonidine was measured by hplc . then the permeation amount of clonidine per unit area of the test piece [ q ( mg / cm 2 )] determined from the clonidine concentration [ n ( mg / ml )] and the amount of the receptor solution [ w ( ml )] was computed at each time point using the formula : q ( mg / cm 2 )= n ( mg / ml )× w ( ml )/ 3 ( cm 2 ), and the determined value was used as a cumulative skin permeation amount . when the permeation amounts of clonidine were computed , since the receptor solution had been collected before the computation , the permeation amounts were corrected on the basis of the amount of the receptor solution collected . the results for examples 9 to 13 are shown in fig7 . for each of examples 2 and 3 and comparative example 2 , a flat rectangular test piece of 2 . 5 cm length × 5 . 0 cm width was cut from the adhesive layer before superposition . one lateral edge of the test piece with the release liner removed was applied to a stainless steel test plate ( application surface : 2 . 5 × 2 . 5 cm ). a 2 kg rubber roller was moved back and forth one time on the test piece at a speed of 5 mm / second to compression - bond the test piece on the test plate , and the resultant test piece was left to stand at 40 ° c . for 20 minutes . a 300 g weight was attached to the other lateral edge of the test piece , and the test plate and the test piece were vertically erected while the weight was supported so that no load was applied to the test piece . then the support of the weight was released to apply the load of the weight to the test piece . the time from the release of the support of the weight until the test piece fell off the test plate was measured . when the test piece did not fall off even after 60 minutes , the distance ( mm ) of the displacement of the test piece was measured . the results are shown in table 2 . in each of the test pieces in examples 2 and 3 , the falling of the weight was not observed even after 60 minutes , and the weight was displaced only slightly . however , in the test piece in comparative example 2 , the weight fell off in a short time . therefore , it was confirmed that , in each patch of the present invention , the cohesion of the plaster was high and the adhesion of the patch was good . for each of examples 2 and 3 and comparative example 2 , a rectangular test piece of 3 cm length × 4 cm width was cut from the adhesive layer before superposition , and the release liner was removed from the test piece . then the test piece was secured to a 30 ° inclined surface of a ball tack tester such that only the lateral middle section ( 3 cm width × 3 cm length ) of the adhesive layer was exposed . a steel ball conforming to jis z0237 was rolled from a position upwardly spaced 10 cm apart from the upper edge of the exposed adhesive layer of the test piece along the inclined surface , and whether or not the steel ball stopped on the test piece was observed . when the steel ball did not stop on the test piece and passed through the test piece , a smaller steel ball was rolled in the manner described above . the above procedure was repeated to measure the size of the smallest one of the steel balls that stopped on the test piece . the results are shown in table 3 . the larger the number of the steel ball , the larger the steel ball . the sizes of the steel balls that stopped on the test pieces in examples 2 and 3 were smaller than that for the test piece in comparative example 2 . however , the test pieces in examples 2 and 3 were found to have sufficient tackiness . therefore , it was confirmed that the adhesion of each patch of the present invention bore comparison with that of the patch in comparative example 2 . according to the present invention , a patch in which the behavior of dissolution - deposition of clonidine present in a crystallized state in the medicated layer due to temperature change during storage is stabilized can be provided . the temperature ( quality ) control of such a patch during distribution and storage can be facilitated .

US-201113882565-A

a method and apparatus for suppressing a fire utilizing non - azide solid gas propellant generation to produce and transport a suitable gas for suppressing a fire in a normally occupied area . the nitrogen gas produced by the solid propellant gas generation is optionally treated to remove undesirable elements such as water and / or carbon dioxide from the product gas prior to the delivery of the product gas to the protected hazard area .

according to the present invention , a pre - packed solid gas generator is used for generating a gas mixture that is suitable for suppressing a fire from a solid non - azide chemical . preferably , the solid chemical ( not shown ) used in the solid gas generator ( s ) may be similar to those used as gas generators for automobile air bags . the solid chemical does not contain azides . azide compositions can be regarded as harmful to human health , and furthermore , often generate less gas by weight relative to non - azide compositions . newer generation automotive air bags for cars utilize such non - azide systems and any of these may be used in solid gas generators . in operation , solid gas generators produce an inert or near inert gas such as nitrogen , which reduces the concentration of oxygen in a room below the level that will sustain combustion . however , the oxygen concentration is maintained at a sufficient level to meet the requirements of the national fire prevention association &# 39 ; s 2001 standard for clean agent halon 1301 alternatives in normally occupied areas . as shown in fig1 a and 1b , a gas generator fire suppression tower 1 is provided containing a pre - packed non - azide solid propellant canister 3 and a discharge diffuser 5 for discharging generated gases . the tower 1 is secured in position by floor mounting bolts 7 passing through a mounting flange 10 , or any other suitable means . the diffuser 5 is likewise secured to the tower 1 using flange bolts with nuts 6 . a pyrotechnic device 9 ( i . e . a squib ) is attached to the pre - packed canister 3 by way of a connector 11 , and to a fire detection and release control panel discussed in greater detail with reference to fig2 a and 3 . the squib is used to initiate the inert gas generation in response to electrical activation . a propellant retainer 12 is provided along with various optional filters and / or screens 13 , as discussed in greater detail below . turning to fig2 a in combination with fig3 the discharge diffuser 5 is shown having a perforated cap 15 . a raceway ceiling mounting foot 17 is provided for securing a conduit / wiring raceway 19 ( e . g . steel pipe ) between the fire detection and release panel 21 ( fig3 ) and a conduit connection 23 on a bracket 25 . the conduit continues downwardly to the squib 9 , as shown at 27 . fig2 b - 2 d show alternative embodiments of discharge diffusers 5 , for different installations of the tower 1 , which may serve either as replacements for the perforated cap diffuser or be placed thereover . more particularly , fig2 b depicts a 180 ° directional diffuser cap 5 a useful for installations wherein the tower is disposed along a wall . fig2 c depicts a 360 ° directional diffuser cap 5 b useful for installations wherein the tower is centrally disposed . fig2 d depicts a 90 ° directional diffuser cap 5 c useful for installations wherein the tower is disposed in a corner . with reference to fig3 a system is shown according to the present invention for suppressing fires in an enclosed space using a plurality of towers 1 as set forth in fig1 and 2 . in operation , a sensor 31 , upon detecting a fire , issues a signal to the control panel 21 which , in response , activates an alarm signaling device 33 ( e . g . audible and / or visual alarm ). alternatively , an alarm may be initiated by activating a manual pull station 35 . in response , the control panel 21 initiates a solid gas generator by igniting the pyrotechnic device 9 , which in turn ignites the chemicals in the pre - packed canister 3 that produce the fire suppressing gas . the fire suppressing gas mixture preferably comprises nitrogen gas and may contain water vapor and / or carbon dioxide . however , as discussed above , the chemicals used in the solid gas generator do not contain azides . as indicated above , the fire suppressing gas mixture may contain carbon dioxide and water vapor , which are optionally filtered using filters 13 ( fig1 ), resulting in the production of a filtered fire suppressing gas mixture . more particularly , the fire suppressing gas mixture may be filtered so that the gas introduced into the room ( fig3 ) contains from about zero to about five wt % carbon dioxide and preferably , from about zero to about three wt % carbon dioxide . more preferably , substantially all of the carbon dioxide in the mixture is filtered out of the mixture . the fire suppression gas mixture may also be filtered so that the gas introduced into the room will not form any substantial amount of liquid water when introduced into the environment of the fire . preferably , the concentration of water vapor in the environment of the fire is maintained so that the water vapor is maintained above its dew point . moreover , screens may be used to reduce the temperature of the fire suppressing gas generated as a result of igniting the pre - packed canister 3 . although the filters and screen ( s ) 13 are shown as being separate from the pre - packed canister 3 , it is contemplated that at least the screen ( s ) may be incorporated as part of the canister structure . since there is no requirement to use compressed gas cylinders , discharge piping and discharge nozzles for the supply or transport of an extinguishing gas mixture , the system of fig3 enjoys several advantages over the known prior art . firstly , the use of only non - azide solid gas generators allows large amounts of gases to be generated with relatively low storage requirements . this reduces the cost of the system , making it more attractive to retrofit existing halon 1301 systems with environmentally acceptable alternatives ( i . e . inert or near - inert gasses are characterized as being zero ozone depleting and have zero or near - zero global warming potential ). secondly , the system benefits from simplified installation and control since all of the solid gas generators need not be provided at one central location . instead , one or more solid gas generators or towers 1 are preferably positioned at the location where the fire will have to be suppressed . in this way , the generation of fire suppressing gases within the hazard area , substantially simplifies the delivery of the gases without the need of a piping system extending throughout a building or perhaps through one or two walls . thirdly , the provision of independently positioned towers 1 results in the gas being generated and delivered to the hazard area almost instantaneously as it is released . this increases the response time of the fire suppressing system and it &# 39 ; s ability to inert the hazard area and suppress the fire in a normally occupied area . each solid gas generator 1 is preferably designed to generate a quantity of gas needed to extinguish a fire in room , should the need arise . the filtered fire suppressing gas mixture is delivered into the room ( fig3 ) containing a fire . the volume of filtered fire suppressing gas to be delivered into the room depends on the size of the room . preferably , enough of the filtered fire suppressing gas mixture is delivered into the room to suppress any fire in the room , yet still permit the room to be habitable by human life for a predetermined time . more preferably , a volume of filtered fire suppressing gas mixture is delivered into the room that permits the room to be habitable by human life for approximately one to five minutes , and more preferably from three to five minutes , as per the requirements of the national fire prevention association &# 39 ; s 2001 standard for halon 1301 clean agent alternatives in normally occupied areas . the many features and advantages of the invention are apparent from the detailed specification and , thus , it is intended by the appended claims to cover all such features and advantages of the invention that fall within the true spirit and scope of the invention . further , since numerous modifications and changes will readily occur to those skilled in the art , it is not desired to limit the invention to the exact construction and operation illustrated and described , and accordingly all suitable modifications and equivalents may be resorted to , falling within the scope of the invention .

US-28659002-A

a method for treatment of epilepsy and cerebral concussion in mammals by administration of a vasodilator in an effective amount , the vasodilator being bamethan , derivatives thereof , bamethan sulfate , derivatives thereof , 1 - epinephrine derivatives having a terminal alkyl substitutent attached to nitrogen and containing at least three carbon atoms , and mixtures thereof . the frequency of epileptic seizures in mammalian patients is substantially reduced by this treatment .

the generic structural formula of the vasodilator used in the method of the invention is as follows : ## str1 ## derivatives of 1 - epinephrine ( adrenalin ) wherein the terminal alkyl group ( r ) attached to nitrogen contains from 3 to 8 carbon atoms , and wherein x is hydrogen or hydroxyl , are effective in the present method . the 1 - epinephrine native compound has a terminal methyl group attached to nitrogen , and this is believed to account for the alpha - adrenergic effect , so that 1 - epinephrine acts as a vasoconstrictor . however , when the methyl group on epinephrine is substituted by an alkyl group containing from 3 to 8 , preferably 4 , carbon atoms , the adrenergic effect is weakened , and the affinity to the beta receptors increases . the effect then becomes one of vasodilation and anticonvulsive action . the upper limit on the number of carbon atoms is not critical and may exceed 8 if desired , but the lower limit of 3 carbon atoms should be observed . bamethan is a preferred compound in the practice of the method of the invention and has the following structural formula : ## str2 ## bamethan has a terminal butyl group attached to nitrogen . this compound , or the sulfate salt thereof , is produced by a number of companies under product names such as vasculate , vaskulit , vaskunicol , rotesar , butedrin , bupatol and garmian . bamethan is also known as butyl - nor - sympatol . the hypothetical cause of epilepsy of vascular origin has been set forth above . a form of epilepsy known as status epilepticus is a state in which attacks occur in rapid succession without recovery of consciousness . this may be of vascular origin . this form can also be treated in accordance with the present method . cerebral concussion of a severity which may have lasting effect is also believed to respond to the present treatment . experimental studies conducted on numerous patients in a foreign country ( hungary ) have verified the effectiveness of the method of the invention . reference is made to fig1 from which it is apparent that nearly 50 % of patients treated with bamethan sulfate had a decreased frequency in seizures , a very small percentage became free of seizures , and about 12 % to 13 % were unchanged . fig2 is a graphic representation of correlation between seizure frequency with conventional antiepileptic drugs and decrease in seizure frequency over a six week period of time , when treated with bamethan or bamethan sulfate . the basic seizure frequency at zero time on the graph of fig2 was that existing with a conventional antiepileptic drug prescribed by a clinic and taken regularly , such as phenobarbital , hydantoin derivatives , primidone , tridione , etc . treatment with bamethan sulfate was begun at zero time , and for the first three weeks the conventional antiepileptic drugs were also continued . after three weeks the conventional antiepileptic drugs were gradually tapered off or discontinued altogether , with bamethan sulfate treatment extended out to six weeks . in practice , such treatment would be continued for a minimum of two years , with the reduced seizure frequency shown at the six week stage in the graph of fig2 in a stabilized state . it is apparent from fig2 that patients initially having a high number of seizures per week were greatly benefitted , and after six weeks displayed lower frequency of seizures than patients initially having much lower seizure frequencies . in all instances , however , improvement was significant . fig3 is a representation of portions of eeg charts comparing patterns before and after intramuscular injection of bamethan sulfate . it will be apparent that some localization resulted from treatment . an analysis of more than 60 cases on the basis of the region of lesion is set forth in the following table . this is in accordance with the gibbs classification . it is apparent that improvement on average was about 50 %. table______________________________________ slightly noregion : improved improved change total rate______________________________________focalfrontal -- -- 5 5 7 . 2 % temporal 18 4 -- 22 31 . 8 % anteriormid - -- 3 1 4 7 . 2 % temporaldiencephal 3 2 -- 5 7 . 2 % all 21 9 30 53 . 4 % improve - mentsdiffusepure 9 3 -- 12 17 . 3 % petit malmixed 6 1 -- 7 10 . 1 % petit malmyoclonic -- 4 -- 4 5 . 7 % pure 3 5 -- 8 11 . 6 % grand malhyp - -- 1 1 2 2 . 8 % sarrhythmiaall 18 14 32 47 . 5 % improve - ments______________________________________ regular treatment is administered orally by tablets containing 0 . 015 g bamethan sulfate , five times daily , for a person of average weight . dosage ranges from 0 . 0003 to 0 . 0013 g per kilogram of body weight . treatment for status epilepticus is effected by intramuscular injection , the dosage level being 1 to 2 ml of 1 % solution twice in two hours .

US-5545687-A

a method and system for capturing expert behavior that the expert is not even necessarily conscious of , such as gaze patterns , that are tied to positive outcomes , and to create a catalog of these behaviors . the system compares the current behavior of a person , for example a novice , against this catalog of expert behaviors . if the current behavior is significantly different , the system would adapt various aspects of the interface to bring the current behavior closer in line to that of the expert .

the present invention is directed to a system and computer - implemented method for controlling skill acquisition interfaces via a user interface . one embodiment is described herein is in the context of eye pattern gazing recognition technology . however , the present invention is adapted for use with many other recognition technologies including , but not limited to : handwriting recognition , speech recognition and gesture recognition . fig1 illustrates a gaze tracking device 101 attached to a computer display device 103 . as illustrated , the gaze tracking device 101 is mounted below the computer display 103 and in one embodiment , comprises a video lens 105 for real - time video capture , with an infrared led 107 mounted on the center of the lens 105 . one skilled in the art will understand that one of many different types of gaze tracking devices can be used and mounted in various positions according to the invention . the computer display device 103 has a display area 109 that the computer can access to display information . the computer generally creates a plurality of windows 111 and 113 for this informational display . the expert user gazes images that are formed on the display . as the expert user looks at the display area 109 , the gaze tracking device determines behavioral attributes , e . g ., the user &# 39 ; s gaze position when viewing the image , represented as one or more gaze “ coordinates ” relating to the displayed user interface . the gaze coordinate is an ordered pair of values providing the immediate two - dimensional coordinates of where the user &# 39 ; s gaze is positioned on the screen display . a number of gaze coordinates can be used to develop a gaze position that is a two dimensional coordinate of a time weighted average of the gaze coordinates . the invention need not have precise gaze coordinates , however , the gaze coordinates tolerance must be accurate to at least approximately a ¼ inch . one skilled in the art will understand that the gaze position could be displayed via the user interface as a rectangle , polygon , circle or other shape representing an area of interest . further one skilled in the art will understand that the gaze tracking device 101 may be configured to provide the gaze position only when the expert user has shown interest in a displayed area for a sufficient time , or that application or system program logic may be utilized to detect when the user has shown an interest by monitoring the gaze coordinates over some period of time . the gaze position is developed when the system detects that the user has become interested in a particular area of the display . the system detects this condition by recognizing that the expert user &# 39 ; s gaze has been limited to a particular region of the displayable area 109 for a period of time . these particular gaze patterns will be transferred from expert to novice , as will be explained below . fig2 illustrates aspects of a gaze position determined from gaze coordinates returned from a gaze tracking device 101 of fig1 . the dashed rectangle labeled as 201 indicates the boundaries of a displayed image ( not shown ). because the gaze tracking device has an inherent tolerance and because the user &# 39 ; s gaze constantly moves ( because of involuntary eye movements ) even when focused on an area of interest , this embodiment of the invention provides the gaze position as an area 205 where the user &# 39 ; s gaze is fixed . the provided area 205 indicates that the user &# 39 ; s gaze did not leave the specified area for a given time , e . g ., a half second . the application program that uses the returned circular area 205 is able to determine that the user &# 39 ; s gaze is well within the image 201 because the provided circle is completely contained within the area of the image . if the user has interest in the entire image , the gaze would be more diffused resulting in a larger circle . for example , in comparing the image labeled 201 with an image 211 , the user viewing the image 201 has focused in on a particular aspect of the image as indicated by the circle labeled as 205 . the user viewing the image 211 has indicated more interest in the totality of the image as compared to a particular aspect of the image as indicated by the circle labeled as 209 . one skilled in the art will understand that a rectangle or other area indication can be used as well as a circle . again , these particular gaze patterns will be transferred from expert to novice , as will be explained below . in another embodiment of the invention , the gaze tracker device 101 of fig1 returns the gaze position as a point . for example , a dashed rectangle labeled as 203 in fig2 indicates the boundaries of a different displayed image ( again this image is not shown ). in this embodiment , the gaze tracker , after processing gaze movements over some period of time , simply returns a point that is a time weighted average of the position of the gaze . this point is indicated by the arrow labeled as 207 in fig2 . fig3 illustrates the process used to develop a gaze position from a plurality of gaze coordinates provided via a computer device &# 39 ; s user interface . the process starts at a terminal 301 . next at a step 303 , the process performs any necessary setup or initialization steps . this includes initializing timer program logic to periodically gather instantaneous gaze coordinate data from the gaze tracker apparatus , acquiring user preference data and other one - time initializations . next at a step 305 , the process receives a plurality of gaze coordinates . these gaze coordinates indicate the position of the user &# 39 ; s gaze over a given time . after a sufficient number of gaze coordinates are gathered , the process examines the gaze coordinates for a focus pattern at a branch point 307 . a focus pattern occurs when the gaze coordinates are all within some boundary without gaze coordinates being statistically far from the others . if the gaze coordinates do not show a focused gaze , the gathering of instantaneous gaze coordinates continues as shown by an arrow 306 . if , at the branch point 307 a focus pattern is found , then a step 309 determines an area of focus that contains the statistically significant gaze coordinate ( s ). finally , in a step 311 the gaze position is made available to the program logic for use . finally , the process repeats as shown by an arrow 312 by returning to step 305 for receiving new gaze position coordinates . in the case where the gaze position is presented as an area instead of a simple coordinate pair , the receiving program logic determines which view is overlapped by the gaze position . there are various well known methods in the art to present the gaze position to program logic such as an application program . these include but are not limited to : providing an exception to an application , and sending an interprogram message containing the gaze position to the application . fig4 illustrates a computer system referenced to by the general reference character 402 , configured to support the invention . the system 402 includes a processor 433 having an input / output (“ i / o ”) or user interface section 435 , a central processing unit (“ cpu ”) 437 and a memory section 439 . the i / o or user interface section 435 is connected to a keyboard 441 , a disk storage unit 443 , a network interface 445 to provide access to a network 417 , a display unit 447 , a pointing device 448 , a gaze - tracker device 455 , a speaker 457 and a cd - rom drive unit 449 . the cd - rom unit 449 can read a cd - rom medium 451 that typically contains a plurality of programs 453 and data . the cd - rom 449 and the disk storage unit 443 comprise a file storage mechanism . one skilled in the art will understand that the file storage mechanism may comprise read only memory , ram or other storage technology that allows a computer to access data . such a computer system is capable of executing programmed logic that embodies the invention . an important characteristic of modern computing systems is the interface between the human user and the computer . modern computer systems use a graphical user interface ( gui ) to simplify the interaction between a user and a computer . a gui equipped computer communicates with a user by displaying graphics , including text and icons , on a display screen and the user communicates with the machine both by typing in textual information in response to dialogs and by manipulating the displayed icons with a pointing device , such as a mouse . one characteristic of a gui between the human user and the computer found , for example , on a modern computing system , is that the gui is only responsive to a user &# 39 ; s explicit manipulation of the pointing device or keyboard . in the case of a mouse , the user physically moves the mouse device and a cursor on the display moves accordingly . some pointing devices actually track the user &# 39 ; s gaze and move the cursor to where the user “ looks ” on the display screen . however , even with the gaze tracking ( eye tracking ) devices , the gui only responds to the user &# 39 ; s explicit commands whether that command be a button press , a blink , or a shift of view . the computer remains a tool that the user operates by issuing explicit commands . according to the invention , in the embodiment of gaze pattern recognition technologies as depicted herein for non - limiting , exemplary purposes , the gaze patterns of expert behavior are first captured when that expert is viewing an image or performing a task via a gui . subsequent , as part of the invention , the gaze patterns of a novice performing the identical task via the gui , are compared to the prior captured and stored gaze patterns of the expert via the gui when viewing the same image . the differences between both gaze patterns are determined by well - known machine learning algorithms which differences are associated with significant outcomes ( positive or negative outcomes ) in real time . in one embodiment , machine learning implements hidden markov model and state - duration hidden markov modeling techniques . in these techniques , “ sequential ” patterns of eye gaze location and eye gaze duration are tracked . a hidden markov model is built for experts and one is built for novices to capture the different behaviors . then , a naive bayes - like classifier may be trained to predict the labels ( experts or novices ) for a new eye - gaze sequence . detailed description of hidden markov model and state - duration hidden markov models and selected applications in speech recognition can be found in rabiner , l . r . proceedings of the ieee . any differences that are detected between the gaze patterns as determined by well - known machine learning algorithms are also compiled into a database of differences that is stored in disk storage unit 443 in fig4 . the database , which is maintained for associated images or tasks , is a catalog of all the differences in behavior between the expert and the novice . the two primary aspects that would be watched for comparative purposes , in one example embodiment , are the differences in location ( where the gaze is fixated ) and duration ( how long a given area gets attention ), although the tracking of the gaze path may also be performed . more particularly , the detection of differences in gaze patterns , in accordance with an example embodiment , is implemented by machine learning technologies that implementing techniques ( machine learning methods , e . g ., supervised or unsupervised learning ) to extract rules and patterns out of data sets ( e . g ., prior experts &# 39 ; gaze pattern training data ) and associate these patterns and rules with significant ( i . e ., positive or negative outcomes ). this prior - implemented machine learning step tracks each one or more expert &# 39 ; s behavior for a given task , e . g ., viewing images , and ties the expert &# 39 ; s behavior with either a successful ( positive ) or negative outcome which are maintained by the system . then , subsequently , for a new novice n viewing the same image type or performing similar behavior , the novice behavior patterns are tracked , e . g ., by gaze tracking devices in the example implementation ; and , in real - time , an analysis is performed against the machine learned trained data sets to detect for any difference in the novice behavior patterns . for example , it is determined whether the detected gaze location / duration differences are tied to one or more positive or negative outcomes of the machine learned trained data sets ( e . g ., one or more experts &# 39 ; recorded gaze pattern training data ). finally , the display is modified , in real - time , accordingly in order to correct , if necessary , the novice &# 39 ; s behavior ( e . g ., if behavior is detected as tied to negative outcomes ). thus , in the example described provided , the display will indicate to user if that novice &# 39 ; s behavior needs to change ( e . g ., novice &# 39 ; s gaze pattern needs to be re - redirected , tracked along another path , alter duration of an area upon which a gaze is to be fixated )). as mentioned , the correction of differences is performed via a user interface , in accordance with a preferred embodiment . the goal is to train the novice so that they learn to “ look ” at things the way an expert does . therefore , if it is detected by gaze tracking device that there is a given area of the object being displayed on the screen ( e . g . medical radiographic film , airport x - ray image , seismographic image ) that gets significant attention from an expert and is not being viewed in a similar way by the novice , the system generates a display to draw the gaze pattern of the novice closer to that of the expert . this could be done in the following ways : by movement of the image , by effecting color change of the displayed image or by effecting intensity change in the displayed image . it is understood that additional ways for aligning a novice &# 39 ; s gaze pattern to that of the expert &# 39 ; s are contemplated ( e . g ., play back of an audio instruction / command ). fig5 illustrates a flowchart describing the process for comparing the gaze patterns of an expert and the gaze patterns of a novice , in accordance with the example embodiment of the invention employing eye ( gaze pattern ) tracking technology for skills acquisition . in a first step 500 , there is performed the gaze tracking of an expert performing a task , for example a radiologist examining a displayed image , that may be video , audio or text . the gaze patterns of the expert are tracked , using eye - tracking technology at step 510 . this step includes the implementation of machine learning wherein the behavior patterns , i . e ., experts recorded gaze patterns for the same image ( e . g ., with respect to gaze location / duration of the viewed image and / or other attributes ) are tied to significant outcomes . then , subsequently , after the expert &# 39 ; s gaze patterns are captured , a novice performs the same task 520 ( e . g ., gazes at the same image ) and , in real - time , the novice &# 39 ; s gaze patterns are tracked for that same image at step 530 . the two sets of gaze patterns are further compared at step 540 and at step 545 , the detected differences are analyzed for behavior that are tied to significant outcomes via the machine learning algorithms employed . then , at step 550 , differences between the two sets are determined and a database of these differences may then be created . the system thus tracks a novice &# 39 ; s gaze pattern of that particular image while working and compares the novice &# 39 ; s tracked gaze pattern to the database of captured and stored expert gaze patterns . when a deviation occurs , i . e ., a gaze pattern is not fixated at an area that needs attention , or the gaze pattern indicates viewing along an incorrect path , e . g ., a “ negative ” outcome , it is corrected through the user interface at step 560 . the correction of differences may be implemented via the gui by creating movement of the image , color change of the image or intensity change in the image , individually , or in combination , to help facilitate the promotion of novice behavior to expert level of behavior . as will be readily apparent to those skilled in the art , the present invention can be realized in hardware , software , or a combination of hardware and software . any kind of computer / server system ( s )— or other apparatus adapted for carrying out the methods described herein — is suited . a typical combination of hardware and software could be a general purpose computer system with a computer program that , when loaded and executed , carries out the respective methods described herein . alternatively , a specific use computer , containing specialized hardware for carrying out one or more of the functional tasks of the invention , could be utilized . the present invention , or aspects of the invention , can also be embodied in a computer program product , which comprises all the respective features enabling the implementation of the methods described herein , and which — when loaded in a computer system — is able to carry out these methods . computer program , software program , program , or software , in the present context mean any expression , in any language , code or notation , of a set of instructions intended to cause a system having an information processing capability to perform a particular function either directly or after either or both of the following : ( a ) conversion to another language , code or notation ; and / or ( b ) reproduction in a different material form . while it is apparent that the invention herein disclosed is well calculated to fulfill the objects stated above , it will be appreciated that numerous modifications and embodiments may be devised by those skilled in the art , and it is intended that the appended claims cover all such modifications and embodiments as fall within the true spirit and scope of the present invention .

US-61417509-A

an inspection instrument having a generally elongated flexible shaft extending between a control head at a proximal end and an objective assembly at a distal end . a bending section adjacent the objective assembly enables movement of the objective assembly between a neutral position and angularly disposed positions . a control member on the control head causes deflection of the objective assembly by means of a pair of operating cables which are operatively connected at their opposite ends to the control member and to the objective assembly . a compensating mechanism engages the cables intermediate their ends and is effective to guard the cable against excessive loads and also to readily accommodate variations in the working length of the cables as occurs when the cables are permanently stretched .

turn now to the drawings and initially to fig1 which illustrates an endoscope 20 or other similar elongated flexible inspection instrument . as generally illustrated , the endoscope 20 has a control head 22 , an elongated flexible shaft 24 terminating at an objective assembly 26 which is preceded by a suitable controlled bending section 28 . typically , the shaft 24 houses a fiber optical system which extends between the objective assembly 26 at a distal end of the endoscope 20 and an eyepiece 30 mounted on the control head 22 . however , it will be understood that the shaft 24 could alternately contain a conventional lens system should that be desirable . it is through the eyepiece 30 that the operator observes the object being examined . a control member 32 is pivotally mounted on the control head 22 in a manner which will be more completely described below and is effective to move the objective assembly 26 between a position which is generally axially aligned with a central axis of the body 24 and at least one of the positions angularly disposed relative thereto as illustrated by dotted lines in fig1 . as previously noted , the invention is intended for use in endoscopes and the like with a deflecting tip or objective assembly where the objective assembly is actuated by a control cable . the invention has a two fold function . first , it limits the amount of load that can be applied to the control cable ; and second , it provides a simple method of taking up the free working length of the same cable . fig2 is representative of a typical prior art construction . as shown in fig2 such a conventional endoscope 34 is seen to comprise a control head 36 and an elongated flexible body 38 terminating at a objective assembly 40 . through an appropriate control mechanism 42 located within the control head 36 , a control handle 44 operate control cables 48 and 50 , respectively , to thereby deflect the objective assembly 40 in one direction or another , as desired . however , it will be appreciated that in the construction of the conventional endoscope 34 , there is a direct movement relationship between the control handle 44 and the objective assembly 40 . that is , any movement by the control handle 44 is imparted to the objective assembly 40 , and vice versa . similarly , if one of these elements is constrained while the other is moved , the movement will impart to the cables 48 , 50 stresses which are substantially greater than normal . in turn , this condition can cause cable stretch , cable failure , or even damage to another part of the system . such a situation can occur , for example , when a stiff accessory is used , or when the objective assembly 40 bears against an object to be viewed , and the operator moves the control handle 44 in an attempt to dislodge the object or move the objective assembly 40 past the object . in times past , the remedy for such an occurrence required major servicing of the endoscope . users of endoscopes do not customarily have the equipment or personnel to repair these sophisticated instruments , so they must be returned to a qualified service facility thereby causing loss to the user by reason of the unavailability of the instrument , possibly for an extended period of time . thereupon , even at an equipped facility , the endoscope would have to be disassembled , cables or other damaged parts replaced , then reassembled . in the event the only problem with an instrument was that one or both of the cables 48 , 50 had been stretched , then it would be necessary to take up the slack in the cables by means of turnbuckles 52 which were integrally attached to the cables for this purpose . this is a time consuming and costly process and takes the instrument out of commission until it is repaired . the present invention serves to eliminate the undesirable operational aspects of the prior art as just described . fig3 is a diagramatic illustration of a construction embodying the invention which serves as such an improvement . as shown in fig3 the control member 32 can be pivoted to and fro about an axis 54 and generally in the directions indicated by a double arrow head 56 . the arcuate movement of the control lever 32 is imparted , by a control mechanism 58 , to a pair of control cables 60 and 62 , respectfully , which terminate distal to the objective assembly 26 . however , the control cables 60 , 62 are intercepted as they proceed from the control mechanism 58 to the objective assembly by respective compensating mechanisms 64 . each compensating mechanism comprises first and second spaced apart cable guides in the form of pulleys 66 and 68 around which the control cables 60 and 62 are collectively wound . that is , as seen in fig3 each of the cables 60 and 62 is wound around its respective pair of pulleys 66 , 68 two and a half times before it continues on toward the distal end of the endoscope 20 . it will be appreciated that the number of loops formed by the cables 60 , 62 is not critical for the purposes of the invention but are determined by design requirements . in the course of the operation of the invention , as excessive stress is applied to the cables 60 and 62 , the pulleys 66 are caused to move against the bias of first pre - loaded compression springs 70 ( see fig4 , and 6 ) and in the direction of the second pulleys 68 . the spring rate of each spring 70 and the number of loops formed by the cables determines the maximum load on the cables 60 and 62 . that is , when that magnitude of load is reached , then the compensating mechanism 64 makes available an additional length of cable at the maximum value of tensile load being experienced by the cables . a specific construction which permits this movement will be described below in greater detail . additionally , in the event the endoscope 20 experiences slack in the cables 60 and 62 , the pulleys 68 can be moved in a direction away from the pulleys 66 to thereby take up such slack . furthermore , this operation can be readily accomplished by the user without the necessity of returning the instrument to a repair facility . again , a construction enabling this operation will be described below . continue now with reference again especially to fig4 , and 6 . the control head 22 includes a generally cylindrical control housing 72 which encompasses the control mechanism 58 and the compensating mechanism 64 . a chassis block 74 is suitably attached , as by fasteners 76 to a distal end of the control housing 72 so as to be operatively integral therewith . a guide block 78 is supported by the control housing 72 intermediate the chassis block 74 and the control mechanism 58 . a pair of parallel , spaced apart rods 80 and 82 associated with each of the cables 60 and 62 are fixed at spaced locations , to the chassis block 74 and to the guide block 78 . for example , ends of the rods 80 and 82 may be threadedly engaged with tapped bores 84 in the chassis block 74 ( fig6 ). additionally , the rods 80 and 82 can be fittingly received within smooth bores 86 in the guide block 78 such that they extend through and beyond the guide block in the direction of the control head 22 . by reason of this construction , the guide block 78 is held firmly in position against an annular shoulder 88 . also , it will be appreciated that the cables 60 and 62 extend freely through axially directed passages 89 in the guide block 78 and through similar passages not shown in the chassis block 74 . as seen especially in fig6 and 8 , the rods 80 are tubular and receive therethrough fiber optic bundles 89a as they pass through the control head 22 . a pair of first carriage members 90 positioned in side by side relationship and associated with each of the control cables 60 and 62 are slideably received on the rods 80 and 82 as is particularly well seen in fig6 . the first carriage members 90 are positioned between chassis block 74 and the guide block 78 and are engaged by and biased pre - loaded onto the chassis block by means of the springs 70 which encircle and are supported by the rods 80 . as seen in fig7 each of the carriage members 90 is provided with an integral stub shaft 92 which extends transversely through a recessed region 94 . a first compensator pulley 66 ( equivalent to the pulleys 66 illustrated in fig3 ) is rotatably mounted on the stub shaft 92 and held rotatably in position thereon by means of a suitable retainer lug 98 . in a similar fashion , a pair of second carriage members 100 are slideably mounted on the rods 80 between the guide block 78 and the control mechanism 58 . second compensator pulleys 68 ( equivalent to the pulleys 68 illustrated in fig3 ) are rotatably mounted on their associated carriage members 100 just as the pulleys 66 are rotatably mounted on their associated carriage members 90 . it will be appreciated that in each instance , the axis of rotation for the pulleys 66 and 68 extends in a direction generally transverse of the control cables 60 and 62 . as previously explained , each of the cables 60 and 62 is looped at least once around each of its associated pulleys 66 and 68 , collectively , as it extends between the control mechanism 58 and the objective assembly 40 . the compensating mechanism 64 which has just been described insures that the control cables 60 and 62 will not be subjected to a tensile load in excess of a predetermined magnitude , as determined by the spring rate of the springs 70 . the springs , of course , can be replaced by others having different spring rates and therefore , allow a different tensile load to occur in the control cables 60 and 62 should that be desired . in any event , during the operation of the endoscope 20 , should the tensile load in a cable exceed a predetermined value , which would occur , for example , if the objective assembly 40 was prevented from moving while the control lever 32 continued to be moved by the operator . in that event , the carriage 90 associated with a particular one of the control cables would move along the rods 80 and against the bias of the springs 70 to thereby shorten the distance between the pulleys 66 and 68 . by so doing , the working length of the control cable is extended to accommodate the continued motion of the control lever while avoiding damage to the control cable or to any other component of the endoscope . a construction operable to prevent the occurrence of slack in the cables 60 and 62 will now be described with particular reference to fig8 and continuing reference to fig5 and 6 . a generally cylindrical internal or spring housing 104 associated with each of the cables 60 and 62 is suitably mounted on the guide block 78 and extends generally parallel to and spaced from the rods 80 and 82 in the direction of the chassis block 74 . the mounted end of the housing 104 may be threadly engaged with a tapped bore 106 in the guide block 78 . within the guide block 78 , the tapped bore 106 communicates with a smooth bore 108 which slideably receives therein a plunger 110 . a free end of the housing 104 is provided with a shoulder 112 ( fig5 ) which supports one end of a compression spring 114 . the other end of the compression spring engages an internal end of the plunger 110 and biases the plunger to the right as seen in fig5 , and 8 . a free end of the plunger 110 has a broadened abutment face 116 thereon which serves to engage an associated carriage member 100 . it will be appreciated that even when the cables 60 and 62 are in their relaxed condition , their tension is such as to draw the carriage members 100 to the left ( viewing fig4 , and 6 ) toward the guide block 78 and into engagement with abutment face 116 . simultaneously , the spring 114 which is designed to have a spring rate less than that of the springs 70 urges the plunger 110 to the right ( viewing fig4 , 6 , and 8 ) such that the abutment face 116 engages the carriage member 100 . during initial fabrication of the endoscope 20 , when an equilibrium position between the plunger 110 and its associated carriage member 100 is achieved , the plunger 110 is selectively held against further movement relative to the guide block 78 . this is achieved by means of a screw 118 which is threadly engaged with a radial tapped bore 120 formed in the guide block 78 and communicating with a flattened surface or region 122 formed on the plunger 110 and generally facing the tapped hole . subsequently , should the cable 60 or 62 become stretched such that the pulleys 66 and 68 no longer properly engage the cable , the operator can readily correct the situation and immediately thereafter put the endoscope to its intended use . specifically , this can be achieved by removing a cap 124 , or other suitable cover , on the housing 72 ( see fig9 ) aligned with the set screw 118 . the operator then releases the set screw 118 from engagement with the flattened region 122 allowing the spring 114 to move the plunger 110 which pushes the carriage 100 so that the pulley 68 once again engages its associated control cable . this operation , in turn , draws all strands looped around the pulleys 66 and 68 , collectively , into the normal taut condition . when this is accomplished , set screw 118 is again tightened into engagement with the flattened region 122 , and the cap 124 is replaced on the housing 72 . in fig4 the carriage members 90 and 100 nearest the reader and their respective pulleys 66 and 68 associated with the control cable 62 are illustrated at their extreme or hard left positions . that is , the carriage member 90 is hard against the chassis block 74 and the carriage member 100 is hard against the abutment face 116 which , in turn , is at its extreme left hand position against the guide block 78 . at the same time , in fig4 the carriage members 90 and 100 farthest from the reader and their respective pulleys 66 and 68 associated with the control cable 60 are illustrated at their typical working positions . that is , the carriage member 100 is shown positioned to the right a distance d 1 which presumably is necessary for its associated pulley 68 to engage the cable 60 and is held in that position by the plunger 110 . the carriage member 90 is shown positioned to the right a distance d 2 which results from the tension in the cable 60 which imparts compression to the spring 70 . turn now to fig1 , 11 , and 12 for a detailed description of the control mechanism 58 . the heart of the control mechanism 58 is a pair of control pulleys 126 and 128 associated with the control cables 60 and 62 , respectively . by way of an integral stub shaft 130 , journal bearing 132 and pulley housing 134 associated with each pulley , the pulleys 126 and 128 are rotatably mounted on the control head 22 about a common transverse axis extending generally parallel to the axes of the compensator pulleys 66 and 68 . as best illustrated in fig3 and 10 , the control cable 62 is attached at its end to the control pulley 128 and extends around the control pulley in a counter - clockwise direction as it extends toward its associated one of the compensator pulleys 68 . in a similar fashion , the control cable 60 is suitably attached at its end to control pulley 126 and extends around that pulley in a clockwise direction toward its associated one of the compensator pulleys 68 . the control lever 32 is bifurcated so as to have a pair of parallel depending legs 135 which terminate at enlarged ends 136 formed with key slots 138 . the key slots 138 fittingly receive keys 140 formed at the extremity of each of the stub shafts 130 on the pulleys 126 and 128 . in turn , large screws 142 are threadly received in tapped bores 146 within the stub shafts 130 to hold the entire assembly together . a pair of pins 144 are fittingly received in smooth bores 146 to assure that the pulleys 126 and 128 will rotate as a unit upon operation of the lever 32 . cylindrical shaped lever stops 148 are threadly received in appropriately located tapped bores 150 in each pulley housing to thereby define the limits of arcuate travel of the lever 32 . the entire control mechanism 58 is mounted to the control housing 72 by means of assembly screws 152 . while a preferred embodiment of the invention has been disclosed in detail , it should be understood by those skilled in the art that various other modifications may be made to the illustrated embodiment without departing from the scope as described in the specification and defined in the appended claims .

US-85667786-A

a pet toy makes a sound when bitten or squeezed by an animal . the toy contains a resilient shell that substantially surrounds the sound - producing material . the toy also contains a core constructed of an elastic material located beneath the sound - producing material . the sound - producing material is a plastic material such as polyethylene terephthalate , which deforms when external pressure is applied to it , creating sound and vibration . in an embodiment of the invention , air permeates the sound - producing material , the core is hollow , and acoustic ports are located at each end of the toy , all to enhance its sound generating characteristics . in another embodiment , a strand is attached to or passes through the core of the pet toy . in another embodiment , an elastic outer sleeve is attached to the sound - producing material at various locations between their surfaces , to reposition the sound - producing material to its original orientation after an external pressure of force is released .

while this invention is capable of embodiment in many different forms , there is shown and described in the drawings and associated text , specific embodiments , with the understanding that the present disclosure is to be considered an exemplification of the principles of the invention and is not intended to limit the invention to the embodiments illustrated . the following description and drawings are illustrative and are not to be construed as limiting . numerous specific details are described herein to provide a thorough understanding of the disclosure . however , in certain instances , well - known or conventional details may not be described in order to avoid obscuring the description . references to one , or an , embodiment in the present disclosure can be , but not necessarily are , references to the same embodiment ; and , such references mean at least one of the embodiments . reference in this specification to “ one embodiment ” or “ an embodiment ” means that a particular feature , structure , or characteristic described in connection with the embodiment is included in at least one embodiment of the disclosure . the appearances of the phrase “ in one embodiment ” in various places in the specification are not necessarily all referring to the same embodiment , nor are separate or alternative embodiments mutually exclusive of other embodiments . moreover , various features are described which may be exhibited by some embodiments and not by others . similarly , various requirements are described which may be requirements for some embodiments , but not for other embodiments . the terms used in this specification generally have their ordinary meanings in the art , within the context of the disclosure , and in the specific context where each term is used . certain terms that are used to describe the disclosure are discussed below , or elsewhere in the specification , to provide additional guidance to the practitioner regarding the description of the disclosure . it will be appreciated that same thing can be said in more than one way . consequently , alternative language and synonyms may be used for any one or more of the terms discussed herein , nor is any special significance to be placed upon whether or not a term is elaborated or discussed herein . synonyms for certain terms are provided . a recital of one or more synonyms does not exclude the use of other synonyms . the use of examples anywhere in this specification , including examples of any terms discussed herein , is illustrative only , and in no way limits the scope and meaning of the disclosure or of any exemplified term . likewise , the disclosure is not limited to various embodiments given in this specification . for purposes of this detailed description , it is envisioned that in one example of use of the invention , a dog will be holding the pet toy in its mouth , and press down on the shell layer of the toy with its teeth . during this process , the dog would bite down on the pet toy , which would then produce a crackling noise in addition to a vibration felt by the dog , to provide both audible and / or tactile feedback to the dog . this description is not meant to limit the scope of the claims , but rather to describe one embodiment of the invention . pet toy 20 , as shown in fig1 - 5 , comprises core 22 , crackling member or layer 24 and shell 26 . pet toy 20 may take the form of many different shapes . the embodiment shown in fig1 - 5 is in the shape of a bone . in a preferred embodiment as shown in fig4 , core 22 has a generally cylindrical , hollow tube shape between first end 40 and second end 42 , defining generally cylindrical outside surface 44 and generally cylindrical inside surface 46 . in some embodiments , outside surface 44 and inside surface 46 are substantially continuous . it should be understood that , according to the principles of the present disclosure , core 22 can have a variety of configurations . while core 22 is shown as hollow in fig4 , in one particular embodiment , core 22 need not be hollow . core 22 is constructed of a durable material that may also be resilient such as thermoplastic elastomer , silicone , fluorosilicone , polyethylene or a similar elastic material , and may be molded in one or more parts . core 22 may also be constructed of materials having varying degrees of deformability . crackling member or layer 24 comprises one or more substantially flat sheets of plastic material that are rolled , or otherwise situated , about outside surface 44 of core 22 . in should be understood that the cross - sectional view of crackling layer 24 shown in fig4 , and the similar view of crackling layer 24 ″ in the alternative embodiment illustrated in fig1 , are each illustrated with the crackling layer having a single , relatively thick layer , to exemplify the structure and configuration of the respective embodiments of the pet toy according to the principles of the present disclosure , and that these exemplary illustrations of these crackling layers are examples of the variety of configurations of crackling layers according to the principles of the present disclosure , which variety also includes the layered configuration illustrated in fig5 . alternatively , in other embodiments , such as shown in fig7 , crackling layer 24 ′ can be formed of textured , ridged , or undulating sound - emitting plastic material . crackling layer 24 is constructed of one or more layers of a sound - producing material that exhibits plasticity , such that the material will deform when external pressure is applied . one example of such material is polyethylene terephthalate ( pet ). pet is commonly used as a material for disposable plastic soda bottles . among its other properties , pet is “ plastic ,” meaning it will deform when external pressure is applied . when pet is deformed , a crackling sound is made , and a vibration is generated that can be sensed by the animal applying the force that caused the deformation . the pet or other suitable material may be deformed repeatedly , each time generating the desired sound and vibration . crackling layer 24 may contain one or more layers of pet or other suitable material , that may be wrapped around core 22 . in another preferred embodiment of the invention as shown in fig5 , the area of the sheet of plastic material used in crackling layer 24 exceeds that of outside surface 44 , such that crackling layer 24 may wrap around itself , outside surface 44 , more than one time . crackling layer 24 comprises inside surface 50 that may come into contact with outside surface 44 of core 22 , and outside surface 52 that may come into contact with inside surface 64 of shell 26 . shell 26 substantially encases crackling layer 24 , and is shown in fig1 - 5 . it should be understood that a pet toy according to the principles of the present invention may include additional layers within shell 26 . for example , a toy according to the principles of the present disclosure with the construction illustrated in fig1 - 4 could include additional crackling layers , and other intermediate layers therebetween , to provide a larger toy as well as varying or enhanced sounds and vibrations . shell 26 , as shown in fig4 , comprises a first end 60 , second end 62 , an inside surface 64 and an outside surface 66 . inside surface 64 is shaped in a generally cylindrical manner , mirroring the tube shape of outside surface 44 of core 22 , although with a larger diameter and length , to enable crackling layer 24 and core 22 to substantially fit inside shell 26 . as shown in the preferred embodiment of fig1 , shell 26 may also comprise additional texture elements , such as ring 27 , located along outside surface 44 . other rings or ridges 70 , 71 and 72 , and protrusions 73 , 74 and 75 can be utilized to stimulate the dog &# 39 ; s gums . shell 26 may further comprise one or more bone - shaped extremities 68 located at first end 60 and / or second end 62 . extremities 68 may be arranged in an offset configuration , as illustrated in fig1 - 5 , and may act to keep the remainder of shell 26 from touching the ground , and to inhibit fluids such as dog drool from entering acoustic port 28 , located at first end 60 and / or second end 62 . it should be understood that , a pet toy according to the principles of the present disclosure can have a variety of configurations , including multiple bone - shaped ( or otherwise shaped ) extremities being aligned or in a coplanar arrangement . suitable materials of construction for shell 26 include thermoplastic elastomer , silicone , fluorosilicone , polyethylene , or a similar durable and elastically deformable material , that may be molded into one or more parts . core 22 may be constructed of the same material as shell 26 . when paired with a core component comprising an elastic material , suitable materials of construction of shell 26 also include rope material , woven fabrics , or other durable materials . indeed , as illustrated in the alternative embodiment of fig1 , pet toy 20 ′″, shell 26 ′″ comprises a different , relatively thinner material than core 22 ′″— such as a woven fabric . referring again to fig1 - 5 , when external force or pressure , such as that which is expected from a dog &# 39 ; s bite , is applied to pet toy 20 in its initial or first unbitten orientation or configuration while under no force , this bite force comes into contact with outside surface 66 of shell 26 . resilient shell 26 then dissipates and transfers the force of a piercing bite , such that the bite will not puncture shell 26 or crackling layer 24 . the force of the bite will cause pet toy 20 to have a second orientation or configuration in which inside surface 64 of shell 26 to presses down on outside surface 52 of crackling layer 24 , which in turn causes inside surface 50 of crackling layer 24 to press down on outside surface 44 of core 22 . the force on outside surface 44 of core 22 is , at least in part , returned to inside surface 50 of crackling layer 24 , thus focusing the force from the dog &# 39 ; s bite on crackling layer 24 . the force of the dog &# 39 ; s bite acts to deform a portion of crackling layer 24 , and creates the desired crackling sound and vibration . shell 26 and core 22 are sufficiently durable to withstand the pressure of a dog &# 39 ; s bite and will transfer at least a portion of the force of the dog &# 39 ; s bite to the crackling layer 24 , rather than absorb all such force . furthermore , shell 26 acts to prevent a dog &# 39 ; s bite from directly contacting crackling layer 24 , which may cause one or more layers of pet in crackling layer 24 to break , or leech pet chemicals to the dog &# 39 ; s teeth , gums or tongue . finally , when the bite force is released , as at least one of core 22 and shell 26 is constructed of an elastic material , the memory return functionality of the one or more elastic components operates to return pet toy 20 to the first orientation or configuration . in the return action , the crackling layer 24 again deforms as it returns to the majority of its original orientation to produce yet additional crackling sound and / or vibration . in the preferred embodiment of the invention as shown in fig4 and 5 , there is air in between core 22 and shell 26 . it is believed that air assists in transmitting the sound generated by crackling layer 24 . for this reason , additional space between core 22 and shell 26 is provided , to allow air to permeate crackling layer 24 . it should be understood that , in alternative embodiments of a pet toy according to the principles of the present disclosure , the core and shell components may be coupled to each other so as to prevent or inhibit the passage of air therebetween , and that pet toy may be configured without air between those components . in a preferred embodiment of the invention as shown in fig4 and 5 , core 22 has inside surface 46 , and is thus substantially hollow . it is believed that a substantially hollow core 22 also assists in transmitting the noise generated by the deformations in crackling layer 24 . in addition , when core 22 is substantially hollow , shell 26 may further comprise one or more acoustic ports 28 . acoustic port 28 comprises at least one hole in shell 26 and / or core 22 , that also allows sound to travel from crackling layer 24 where it is generated , to the outside where it may be heard , and is shown in particular in fig3 and 4 . while acoustic port 28 is shown in combination with a substantially hollow core 22 , it may also be utilized with a solid core 22 in another embodiment of the invention . it is believed that acoustic port 28 enhances the sound produced by crackling layer 24 , such that it generates even more sound and vibration . while acoustic ports 28 may be located anywhere on shell 26 and core 22 , in a preferred embodiment acoustic ports 28 are located at either end of shell 26 . fig6 , shell 26 ′ is in the shape of a small barbell with varying thicknesses along the length of shell 26 ′. in this embodiment , extremities 68 ′ are in the shape of small barbell ends , and , as set forth above with regard to extremities 68 , similarly act to prevent most of shell 26 ′ from touching the ground , and inhibit the flow of any dog drool from entering acoustic port 28 ′. in an embodiment of the invention as shown in particular in fig7 , the one or more layers of sound - producing pet material of the crackling member or layer 24 ′ are textured , such that when force is applied to deform the sound - producing material , the material may deform in multiple locations among the material , enhancing the noise and vibrations made in the deformation , and enhancing the life of the sound - producing material by allowing for additional places for new deformations in the material , with repeated use . in addition , the textured portions of the sound - producing material of crackling member or layer 24 ′ are less likely to lie flat against one another , as the textured portions space apart the layers of material , and thus assist in enabling air to permeate within crackling layer 24 ′. in an embodiment , as shown in fig8 , core 22 ′ may be constructed to include a portion of shell 26 ′ in one piece . it should be understood that , in this and other alternative embodiments of a pet toy according to the principles of the present disclosure , the core and shell components may be sealed to one another so as to prevent or inhibit the passage of air therebetween . furthermore , the pet toy may include strand 30 ′, located at least partially inside core 22 ′. in an embodiment of the invention as shown in particular in fig8 and 9 , strand 30 ′ comprises a length of flexible material , which could include one or more filaments of pet or other sound - producing material 32 ′, which passes through and / or attaches to inside surface 46 ′ of core 22 ′. strand 30 ′ may be used by a person or a dog to pick up , carry or throw a pet toy according to the principles of the present disclosure without touching shell 26 ′, and may also be visually attractive . suitable materials for strand 30 ′ include , among others , ribbon , cord , rope , or canvas . in another alternative embodiment as shown in fig1 , a pet toy 20 ″ includes an elastic shell 26 ″ and plastic crackling member 24 ″, with or without a core member 22 ″, illustrated in phantom in fig1 . crackling member 24 ″ is fixed relative to elastic shell 26 ″ at attachment points 80 ″, or attachment regions 82 ″, 83 ″ and 84 ″— which can be comprised of one of variety of conventional adhesive attachment points or welds , that may be tacked or tack welded . alternatively , the pet can be laminated by adhesive or welded to elastic shell 26 ″, by extending attachment regions 82 ″, 83 ″ and / or 84 ″ over a larger region of the surfaces between shell 26 ″ and crackling member 24 ″. according to the principles of the present invention , when elastic shell 26 ″ deforms from a first configuration , under no force — to a second , deformed configuration upon biting , crackling member 24 ″ deforms to produce a sound and / or a vibration . when elastic shell 26 ″ substantially returns to the first configuration after the biting force is removed , elastic shell 26 ″ prompts the shape of crackling member 24 ″ to substantially its original shape as a result of the affixation of crackling member 24 ″ to elastic shell 26 ″. at that time , yet additional crackling sound and / or vibration may be generated . in another embodiment of the invention , a resilient and / or elastic core member can likewise be positioned within the layer of crackling material to enhance the return of the crackling material back to its pre - bite position — while generating yet further sound and / or tactile vibration . the foregoing description and drawings merely explain and illustrate the invention , and the invention is not limited thereto , except as those skilled in the art who have the present disclosure before them will be able to make modifications and variations therein without departing from the scope of the invention .

US-201314050507-A

a method for localizing ischemia in segments of a heart in a patient under test includes attaching a plurality of electrodes to the patient to form a plurality of leads , capturing electric signals at each of the leads , determining a normalized vector magnitude for each lead as is inherent in a normal heart , calculating an output for each cardiac segment as a percentage of the left ventricle by adding up the contributions for all of the leads in the direction of each segment at the j point based on the normalized vector magnitudes and a correct calibration factor for conversion to the percent of lv and taking a dot product of each lead vector and each segment vector to identify a normalized response for each lead at each segment center and using the dot products to multiply the st j - point signal for each lead .

the following is a detailed description of example embodiments of the invention depicted in the accompanying drawings . the example embodiments are presented in such detail as to clearly communicate the invention and are designed to make such embodiments obvious to a person of ordinary skill in the art . however , the amount of detail offered is not intended to limit the anticipated variations of embodiments ; on the contrary , the intention is to cover all modifications , equivalents , and alternatives falling within the spirit and scope of the present invention , as defined by the appended claims . in fig2 the physical location of the precordial leads are shown as normally used in a 12 lead ecg , at the frank torso measurement points . in fig3 , each of the precordial leads — v 1 to v 6 — are shown from their respective points on the torso to the wilson central terminal . image surface from the horizontal cross - sections as mentioned in frank and pictured in mcfarlane , who added lead vectors v 1 - v 6 . the starting points on the torso for leads v 1 , v 2 and v 3 are interpolated between the levels / slices 5 and 6 ( as seen in fig2 ). the remainder of leads , v 4 , v 5 and v 6 , start at the level / slice 6 . the length and direction of each of these leads gives dimensions in the coordinates “ x ” and “ z .” by adding a frontal plane diagram , a “ y ” dimension is added to each of the leads . the limb leads are longest in the frontal plane because the points of attachment to the body are located on the arms and the legs . the “ i ” lead is measured between the left and right arm with the plus terminal the left . the “ ii ” lead is measured between the left arm and the left leg and the “ iii ” lead between the right arm and the left leg . it was initially thought that the orientation of these leads formed an equilateral triangle with the top leg between the arms and the other two legs , from these points to the middle of the body near the bottom of the torso . the true orientation of this triangle is shown in fig4 and used in the system and method disclosed herein along with the derived leads ( as shown in fig3 ). the invention uses these leads , i . e ., the signal and direction to derive responsiveness of the lead . in fig4 , the same electrical measurement contours for each of the horizontal levels is shown in the frontal plane . these contours / data allows the plotting of the lead vector response of the limb leads as well as the precordial leads . the limb leads form what is called the burger triangle showing the lead vector response of leads i , ii and iii . for this triangle , the response of the leads avl , avr and avf also may be derived and are shown in this figure . the ecg vectors measured from the frank diagrams are in 3 dimensions — x , y , and z . as used herein , the term “ vector ” means the magnitude and direction of an ecg signal captured by an ecg machine in either analog or sampled form . these vectors are distributed at about 30 degree increments in the frontal and horizontal planes . with the ability to measure both plus and minus voltages on each of the leads , there is 360 degree coverage by these leads in the 2 planes . the inventive system and method finds the average vector magnitude of all the leads . then to accomplish the normalization , the average magnitude is divided by each of the individual magnitudes . this deemphasizes strong leads and emphasizes weak leads , thus , no matter the direction of the vector to be measured , the same response would be found at the output of the sum of these normalized vectors . the direction and magnitude of these normalized lead vectors in the frontal and horizontal planes is shown in fig5 and 6 , respectively . each of the lead vectors is defined in 3 dimensions , although the magnitude of the response in the orthogonal axis for the vectors shown is minimal . a model of the heart previously developed by the inventor herein and disclosed in olson , et al . is used in a simulation program in which vector directions were established at 1 mm spacing . a realistic model of the heart was also defined at 1 mm spacing . in fig7 a and 7b , cross sections of the heart model are presented . at the centroid of each quadrant , a vector pointing perpendicular to the endocardial surface of the left ventricle is depicted . this vector direction is obtained by taking the cross product of orthogonal vectors in the plane of the surface at each point ( on a frank torso as shown in fig2 ). the centroid is obtained by bisecting the vertical spread of the vertical opening and the angular spread of the horizontal opening for each segment . the vertical opening is 28 mm and the horizontal opening is 90 degrees . centroids of segments are shown in fig7 a where fig7 b depicts centroids of quadrants . also shown are the location of the vectors at the centroid of each segment which is determined geometrically as the central point for each dimension on the endocardium . the vector direction is found by taking the cross product of surface vectors at their point of origin . thus , by selecting a location that is at the centroid of each of the segments on the endocardium , a vector direction is known and can be used as a good representation of the vector that would occur in the event the segment was ischemic . it is known that the potential on the endocardium is high since these muscle cells are well profused by the blood in the inside of the left ventricle . as the ischemia develops , the cells in the middle and on the epicardium suffer loss in action potential due to loss of profusion . the resultant vector points away from the endocardium and towards the epicardium when the ischemia extends across the thickness of the cross section ( transmural ischemia ). the direction vector , as described above , is used to represent the average for each of the 12 segments . examples of these for the 12 segments of the lv are shown in fig7 c . that is , fig7 c shows the unit vectors for each segment representing the direction of the ischemic vectors . the unit vectors representing anteroseptal are black from 1 to 3 with 1 apical ; the anterosuperior are green from 4 - 6 with 4 apical ; the posterolateral are blue from 10 to 12 with 10 apical ; and the inferior are purple from 7 to 9 with 7 apical . these vector directions represent the case of transmural ischemia . in the case of semi transmural ischemia ( such as in a stress test ), only the inner part of the myocardium is ischemic . as a result the reference vector for each segment points in the opposite direction ( 180 degree difference in phase ). semi transmural ischemia , blood flow is limited in the arteries on the inner surface of the heart and cells in the middle of the epicardium have a longer action potential than what is present on the endocardium . this results in a higher potential in the middle of the cross section after the j point and thus a vector at this time pointing towards the endocardium or the reverse of the direction depicted in fig7 a , 7 b and 7 c . the output ( i . e ., amount of ischemia ) for each segment is found by adding up the contributions for all the leads in the direction of each of the segment vectors . in the case of an ischemic event , the best measure of the effect on the lead signal is at the j point . this is the point where the normal activation of the myocardial cells that are not ischemic stops . each lead shows its response to the sum of the ischemic activity at this point in time ( j - point ). each lead has a vector direction and each segment has a vector direction . by taking the dot product of these 2 vectors , a normalized response for each lead at each segment center is found . the contribution of each lead to a segment is the component of that lead in the direction of the segment vector ( the dot product of the 2 ). since these products are scalars , they each can be multiplied by their respective st j - point signal for each lead to get their net total contribution to the ischemic level at each unit vector location . if the sign of the dot product and the sign of the st signal are the same , their product is used because they indicate transmural ischemia . if the dot product and sign of the st segment are opposite in sign , a separate sum is calculated indicating semi - transmural ischemia . examples of the plotting of these outputs for each patient of groups separated by their coronary artery affected by the ischemia are shown in fig8 , 9 and 10 . fig8 shows lad patients with near 100 percent correlation with the maximum deflection in segments 1 to 6 . fig9 shows lcx patients where 14 out of 15 are found to be correctly classified . in the rca group in fig1 , 14 correct and 10 rca or lcx , 1 rca or lad and 2 lcx are found . please note that in these plots , the order of segments 7 , 8 , 9 and 10 , 11 , 12 were changed , since the physical order is 10 , 11 , 12 and 7 , 8 , 9 , as shown in the mercator projection diagram of fig1 . location of the infarction output on the mercator and the 17 segment circle diagram the mercator projection diagram of the left ventricle can be translated to a bulls eye representation , as shown in fig1 . this shows the location of the coronary arteries in the bulls eye diagram by a point by point transformation of the mercator coronary layout . quadrants are shown for the mercator segments and their orientation in the 17 segment circle diagram in fig1 . the horizontal lines that are shown in the fig1 mercator projection diagram ( 12 segments ) are translated over their active extent to circles in the bulls eye diagram of fig1 . the outer circle represents the top line in the mercator diagram and bottom or the tip of the apex of the heart is the center of the bull &# 39 ; s eye . this translation is shown for each quadrant and the coronary arteries are arranged in relationship to their geometric translation . the more preferred numbering of the bulls eye segments and their arrangement is shown in fig1 , the 17 segment model . in the event of the infarction of the left ventricle , sylvester , et al ., have shown that the amount of infarction in each segment can be estimated from the 12 lead ecg characteristics . these segments are normally adjacent to each other and arranged in accordance with the type of infarction . lad infarction is found to exist in one or more of the segments 1 to 6 , 7 , and 10 . rca infarction is found to exist in segments 7 to 9 and lcx is found to exist in segments 10 to 12 ( according to sylvester ). the inventive system and method create a new elliptical area ( in the mercator that represents the area at risk in percent of the left ventricle . for each type of infarction , an ellipse or indicia to visually represent the percent of the lv that is infarcted , according to the rules of sylvester , is located in the related segments with a center location that is weighted by the infarction , as described for the ischemic case below . the results of the processing by the inventive system and method are illustrated in fig1 and 14 . that is , fig1 and 14 respectively show how an infarcted area ( shaded in black ) would appear in a mercator projection diagram and in a bulls eye diagram . a visual cue identifying a percent of lv that is affected enables clinicians , for example , emergency room personnel , to accurately estimate the degree of damage the patient has suffered and what treatment should be provided immediately , if any . the location and the size of the ischemic area are very important for determining the degree of risk to the patient . it has been found that the ischemic area is related to the magnitude of the st vector at the j point . this has been reported in the journals and has been compared to the aldrich score with good correlation . this relationship for real patient data is shown in fig1 b , and a least square fit of the st vector magnitude to the % lv determined from the aldrich score can then be used to convert st magnitude data to % lv . this method has more resolution than the aldrich score which only uses a binary measure of a lead output . in addition , the st magnitude evaluates both positive and negative st deviation so that all leads contribute to the total measurement . in the invention as claimed , the magnitude of the st vector in each of the leads is determined and then translated to each of the segments . the sum of the magnitude of the dot products of the segment vectors also is a measure of the ischemic area and if the results of tests of these quantities on patients is made equivalent , the amount of ischemia assigned to each segment is readily found . it has been found that the magnitude determined by the st magnitude determined from the dower transform of the 12 lead ecg to the x , y , and z total vector is highly correlated with the magnitude determine from the segment vectors . this would be suspected since dower used the frank lead vectors in the derivation of his formula . the amount of ischemia associated with each segment in the display communicates to the clinician the magnitude of the ischemia and where it is located . the maximum area for a segment is approximately 8 percent of the total area of the heart . if a few segments are less than 8 percent , but they are adjacent , it is logical to join these areas into a combined area that looks like a typical single photon emission computed tomography ( spect ) drawing . this is highlighted in fig1 and 14 , wherein the black ( shaded ) area is the infarcted area in both the mercator and the bulls eye circle diagram . to accomplish the location process , the segment signal levels are used to find a weighted location for the center of an ellipse . in the case where the highest levels are in the segments 1 to 6 , which has been shown to be lad , these segments are used to find a horizontal weighted center by comparing segments 1 + 2 + 3 to segments 4 + 5 + 6 . in a similar manner , a vertical weighted center is found by using segments ( 1 + 4 ), segments ( 2 + 5 ) and segments ( 3 + 6 ). once the center is found , an ellipse is drawn ( automatically ) with an axis ratio of 3 : 2 for height to width and an area equal to the percent lv ischemic . this is done in the mercator projection dimensions and then translated to the circle diagram . fig1 a and 15b shows a diagram of an lad infarction and an lad ischemia together . the infarction is shown inside of the ischemia and they are both elliptical in shape . the infarct is computed as 6 % of the lv and the ischemia as 23 %. the combine area at risk is 29 %. a similar method is used for the rca case where the segments used are 7 to 12 . an illustration of an rca case for ischemia and an lad case f or infarction is shown in fig1 a and 16b . the center of the ellipse for their segments were quite different since they represented entirely different areas of the heart if the segments are large in segments 4 , 5 , 6 along with a larger value for 7 , 8 , 9 and a smaller value for segments 10 , 11 , 12 such as in lcx . then the horizontal weighting would include 3 groups . this is an entirely new presentation to the cardiologist and should prove to be an extremely valuable tool . that is , the inventive system and method provide the cardiologist with an ability to see the location of the ischemia and the infarction in 2 views of the heart : 1 . a mercator drawing showing all the coronary arteries and 4 quadrants with 3 segments each and 2 a bulls eye drawing with the same information but arranged in a circular format with 17 segments . the size of the infarction and the ischemia are made in proportion to the size of the damaged area as a % of the lv in a linear relation to the areas on the surface of the mercator projection . these are then translated to the bulls eye diagram which is slightly distorted in the outside rings which cover more area than the inside . showing both the location and the size of the damaged area for the infarct which is not recoverable and the ischemic which is recoverable should be an invaluable aid to making decisions on patient treatment . fig1 a is a simplified block diagram of an exemplary system 300 for monitoring a patient under test according to the inventive principles . st - segment resolution according to one embodiment . the system 300 includes a plurality of leads 310 electrically connected to a front end or receiver component 312 that is in communication with a processor 313 , a memory device 314 , a display device 316 , an audio component 318 , and an interface component 320 . the leads 310 include wires and electrodes configured to attach to a patient ( not shown ) to detect ecg signals . the receiver 312 may include , for example , an amplification component 322 to amplify the ecg signals detected by the leads 310 , a filtering component 324 to eliminate undesirable noise from the ecg signals , and an analog - to - digital ( nd ) converter 326 to provide converted ecg signals through a system bus 328 to the processor 313 . the processor 313 may include a special purpose processor configured to perform the processes described herein . in another embodiment , the processor 313 is a general purpose processor configured to execute computer executable instructions ( e . g ., stored in the memory device 314 ) to perform the processes described herein . in addition , or in other embodiments , the processor 313 may be connected to a host computer 330 having a display device 332 . the host computer 330 may include computer executable instructions for performing the processes described herein . the host computer 330 may be used in certain embodiments . thus , these aspects of the present invention is directed to a programmed product , comprising a non - transitory signal - bearing storage media tangibly embodying a program of machine - readable instructions executable by a digital data processor incorporating the cpu 112 and hardware above , to perform the method of the invention . this signal - bearing storage media may include , for example , a ram contained within the processor 313 or 330 , as represented by the fast - access storage for example . alternatively , the instructions may be contained in another signal - bearing storage media , for example , a magnetic data storage diskette 350 ( fig1 b ), directly or indirectly accessible by the cpu 112 . whether contained in the diskette 350 , or some other computer readable medium , the processor / server 110 comprising cpu 112 , or elsewhere , the instructions may be stored on a variety of machine - readable data storage media , such as dasd storage ( e . g ., a conventional “ hard drive ” or a raid array ), magnetic tape , electronic read - only memory ( e . g ., rom , eprom , or eeprom ), an optical storage device ( e . g . cd - rom , worm , dvd , digital optical tape ). other suitable signal - bearing media include memory devices in transmission media and instructions stored in formats such as digital and analog and memory devices in communication links and wireless . in an illustrative embodiment of the invention , the machine - readable instructions may comprise software object code . it should also be obvious to one of ordinary skill in the art that the technique of the present invention could be implemented on a network in a variety of configurations . hence , the invention includes a computer program product including a processor and a set of processor readable instructions that when executed by the processor execute method for localizing ischemia in a patient under test and presenting a visual representation of the identified ischemia and / or infarction in a mercator or bulls eye diagram . as will be evident to persons skilled in the art , the foregoing detailed description and figures are presented as examples of the invention , and that variations are contemplated that do not depart from the fair scope of the teachings and descriptions set forth in this disclosure . the foregoing is not intended to limit what has been invented , except to the extent that the following claims so limit that .

US-201213684429-A

a rotary cutting deck for a mower includes a cutting deck supported by wheels at three of the four corners of the deck . the other corner of the cutting deck , namely a corner of the deck that is close to the mower , is supported by a corner suspension that lifts upwardly with a biasing force sufficient to elevate that corner of the deck above the ground . this corner suspension takes the place of the caster wheel that would normally support this corner of the deck , and thus permits the deck to be moved closer to the side of the mower , thus reducing overall mower width without decreasing the width of the cutting swath .

one embodiment of a rotary cutting deck according to this invention is shown in fig1 - 5 with the rotary cutting deck being generally illustrated as 2 . cutting deck 2 is of the type that is intended to be attached to a traction frame 4 of a mower 6 so that cutting deck 2 is propelled over the ground as mower 6 travels over the ground . one cutting deck 2 or multiple cutting decks 2 may be attached to mower 6 . only a portion of mower 6 is shown in fig1 namely a portion of traction frame 4 and one of the front drive wheels 8 of mower 6 . cutting deck 2 houses or carries one or more rotary cutting elements ( not shown ), such as rigid blades , that rotate in substantially horizontal cutting planes about substantially vertical axes . a hydraulic motor 10 may be mounted on top of cutting deck 2 for providing power for rotating the cutting elements carried within a cutting chamber on the underside of cutting deck 2 . other power sources for rotating the cutting elements can be used . cutting deck 2 is shown as a wing deck attached to one side of traction frame 4 of mower 6 . as is well known in the art , a lift arm 12 attaches cutting deck 2 to traction frame 4 . an outer end 14 of lift arm 12 is pivotally coupled to an attachment 18 at the approximate center of cutting deck 2 by various pivot joints 16 a , 16 b , and 16 c that permit pitching , rolling , and yawing of cutting deck 2 about the three x , y and z axes of an xyz coordinate system . instead of the separate pivot joints 16 a - 16 c shown , a single ball joint could be used to provide the same motion for cutting deck 2 . an inner end 20 of lift arm 12 is connected to traction frame 4 by a pivot shaft 22 . a hydraulic cylinder 24 is provided on traction frame 4 for selective operation by the operator of mower 6 . this cylinder is connected between traction frame 4 and inner end 20 of lift arm 12 to pivot lift arm 12 upwardly and downwardly about pivot shaft 22 . this will raise and lower cutting deck 2 between its substantially horizontal cutting position ( shown in fig1 ) and a raised generally upright transport position ( not shown ) in which cutting deck 2 has been folded up along the side of traction frame 4 . thus , lift arm 12 is used for moving traction frame 4 between its operating and its transport positions . lift arm 12 also serves to propel cutting deck 2 as traction frame 4 of mower 6 is driven over the ground . in addition to lift arm 12 , a second support arm 26 extends between traction frame 4 and a rear portion of cutting deck 2 . this second support arm comprises a shock absorber for bi - directionally absorbing impact shocks and resisting the yawing action of cutting deck 2 about the vertical pivot axis . the details of the shock absorber comprising the second support arm 26 are , inter alia , the subject of another patent application assigned to the assignee of this invention , namely u . s . ser . no . 09 / 507 , 313 , which is copending herewith . referring to fig1 cutting deck 2 has three support wheels adjacent three corners of cutting deck 2 . there is an inner front support wheel 28 adjacent the inner front corner of cutting deck 2 , and outer front support wheel 30 adjacent the outer front corner of cutting deck 2 , and an outer rear support wheel 32 adjacent the outer rear corner of cutting deck 2 . the two front support wheels 28 and 30 are not caster wheels but are rotatable support wheels that rotate about pivot shafts that do not themselves rotate about vertical axes . the outer rear support wheel 32 comprises a caster wheel that is capable of rotating about a substantially vertical pivot axis 34 . each of the support wheels 28 , 30 and 32 can be adjusted relative to cutting deck 2 to change the height of cut . this is done in generally conventional ways known in the art . for example , the front support wheels 28 and 30 can be adjusted up and down by virtue of various support pins received in one of a plurality of adjustment holes 34 provided on the height of cut mechanism . the rear caster wheel is provided with a rotatable adjustment knob 36 which , when rotated , raises and lowers the yoke 38 that supports the rear caster wheel . the precise type of height adjustment mechanism used in conjunction with the support wheels can be varied . a corner suspension is provided for the remaining corner of cutting deck 2 to keep this corner elevated above the ground during operation of cutting deck 2 without having to use a support wheel at that corner . the corner suspension is indicated generally as 40 in fig1 - 3 . corner suspension 40 acts on the inner rear corner of cutting deck 2 . as shown in fig1 - 3 , corner suspension 40 acts between cutting deck 2 and a portion of second support arm 26 that overlies cutting deck 2 . since second support arm 26 is pivotally connected at either end to cutting deck 2 and traction frame 4 , second support arm 26 will move up and down with cutting deck 2 as cutting deck 2 floats and follows the ground contours . by locating corner suspension 40 on that portion of second support arm 26 overlying cutting deck 2 , the location and placement of corner suspension 40 is simplified with corner suspension 40 also moving generally in concert with cutting deck 2 . corner suspension 40 comprises a bellcrank 42 that is pivotally mounted on a pivot rod 44 that is carried on second support arm 26 . a generally vertical connecting link 46 extends between one arm of bellcrank 42 and the inner rear corner of cutting deck 2 . the lower end 47 of connecting link 46 is connected to the inner rear corner of cutting deck 2 through a height adjustment mechanism 48 . namely , lower end 47 of connecting link 46 can be pinned in one of a plurality of vertically spaced adjustment holes 50 provided on height adjustment brackets 52 carried on the inner rear corner of cutting deck 2 . in addition , the upper end 49 of connecting link 46 can be connected to one of a plurality of vertically spaced holes 54 provided on the first arm of bellcrank 42 , to further increase the number of height adjustment settings that are possible . height adjustment mechanism 48 between the inner rear corner of cutting deck 2 and connecting link 46 can obviously be varied . for example , the use of plural adjustment holes 54 on the first arm of bellcrank 42 can be deleted with the upper end 49 of connecting link 46 simply pinned to the first arm of bellcrank 42 in only one location . secondly , connecting link 46 has its lower end 47 shown located between two height adjustment brackets 52 with its lower end 47 being pinned to both brackets . however , only one height adjustment bracket 52 could be used in place of the two brackets 52 that are shown . in addition , other height adjustment mechanisms for connecting lower end 47 of connecting link 46 to cutting deck 2 could be used . the second arm of bellcrank 42 is connected to a spring 60 that extends between the second arm of bellcrank 42 and an anchor 62 that is located on second support arm 26 . spring 60 imposes a force tending to rotate bellcrank 42 in the direction of the arrow a . see fig2 . this force is thus arranged to pull up on connecting link 46 , and thus to pull up on the inner rear corner of cutting deck 2 , as shown by the arrow b adjacent connecting link 46 . again see fig2 . spring 60 provides a biasing force which is chosen to be sufficient to keep the inner rear corner of cutting deck 2 elevated above the ground during normal cutting operation of cutting deck 2 . this force also helps keep the three support wheels 28 , 30 and 32 in contact with the ground . using a resilient spring force to impose a load on the inner rear corner of cutting deck 2 elevates that corner of cutting deck 2 without having to use any support wheel on that corner . thus , the caster wheel that would normally be found on that corner of cutting deck 2 can simply be deleted . this is advantageous since there is one less caster wheel that sees wear and would eventually have to be replaced . it also allows cutting deck 2 to be spaced more closely to frame 4 with no interference occurring between the caster wheel and the side of traction frame 4 when cutting deck 2 is folded up into its transport position . accordingly , the transverse width of mower 6 can be minimized when the cutting decks 2 are raised and mower 6 is in its transport mode . the applicants have found that the above - described corner suspension 40 effectively supports the inner rear corner of cutting deck 2 without the need for any support wheel . this corner suspension 40 , in concert with the other three support wheels 28 , 30 and 32 , allows cutting deck 2 to float and adjust to ground contours and provides an even and consistent height of cut over that swath of grass being cut by cutting deck 2 . since all of the support wheels 28 , 30 and 32 are desirably equipped with height of cut adjustment mechanisms , it is necessary for corner suspension 40 to also have this ability , which has been implemented by having lower end 47 of connecting link 46 connect to cutting deck 2 through a height of cut adjustment mechanism 48 . in some operational conditions , it has been found that the inner rear corner of cutting deck 2 bounces up and down during operation . in order to minimize this undesired bouncing , an oil filled damper 70 is used between the second arm of bellcrank 42 and another anchor 72 on second support arm 26 . this damper 70 tends to smooth out and eliminate undesirable bouncing of cutting deck 2 . however , damper 70 could be eliminated if so desired and corner suspension 40 including spring 60 would still be useful for elevating the inner rear corner of cutting deck 2 without using a support wheel . various modifications of this invention will be apparent to those skilled in the art . while corner suspension 40 has been shown as being applied to only the inner rear corner of cutting deck 2 , a similar corner suspension could also be used on the inner front corner of cutting deck 2 in place of inner front support wheel 28 . thus , the scope of this invention is to be limited only by the appended claims .

US-78272601-A

the invention relates to mascara compositions comprising a plant extract , especially , an apple extract component dispersed in a silicone oil . these mascaras can also contain a fiber component unrelated to the fiber content of the fruit extract . the fiber component , when it is charged , is capable of aligning itself with the natural direction of the eyelashes when an antistatic component is also present . the mascaras contain a natural ingredient of apple extract and are not tacky .

mascara compositions of the present invention are similar to presently known mascaras in that they incorporate the basic formulation elements of a mascara . however , a mascara composition is not presently known to comprise a plant extract component in which the plant extract is dispersed in a silicone oil . it has been surprisingly discovered that a mascara composition containing the plant extract as a natural ingredient is easy to apply to the lashes and adheres to the lashes without being too sticky or tacky . the mascara compositions of the present invention also leave the lashes looking longer , fuller , and natural ( i . e ., the lashes are not clumped together , and do not looked spiked or pointed ). the plant extract component can be derived from a fruit or a vegetable or any other similar type of plant , especially fruits or vegetables that are tacky or sticky . the plant extract , as used in the present specification , is prepared using the whole fruit or vegetable that is , for example , ground , liquefied , pressed or processed using similar methods such that the whole processed plant is dispersible in a silicone oil . except for the seeds , no part of the plant is removed or separated from the extract ( i . e ., the constituents of the fruit or vegetable are not filtered ). the whole pulp and skin of the fruit or vegetable are used . a separation procedure is typically employed when making a plant extract to remove constituents of the plant that are tacky or sticky . it has been discovered , however , that the present invention achieves a non - tacky mascara using an unfiltered plant extract dispersed in silicone oil . this has not been previously disclosed . examples of fruits , include but are not limited to , apples , pears , peaches , nectarines , mangoes , papayas , apricots , or any other type of fruit that can be made into an extract ; and examples of vegetables , include but are not limited to , yams , potatoes , peas , beans , peppers , squashes , carrots , or any other type of vegetable that can be made into an extract . it is within the scope of the present invention to include combinations of fruits , combinations of vegetables , and combinations of fruits and vegetables . preferably the plant extract is an apple extract . the extract is dispersed in any cosmetically or pharmaceutically acceptable silicone oil . however , preferably a suitable volatile silicone oil is used . suitable volatile silicone oils for use in the composition include , but are not limited to , both cyclic and linear silicones . thus , cyclomethicones , such as for example , hexamethylcyclotrisiloxane , octamethylcyclotetrasiloxane , decamethylcyclopentasiloxane ; and volatile linear dimethylpolysiloxane can be used . non - volatile polymeric silicones such as dimethicone ; alkylated derivatives of polymeric silicones such as cetyl dimethicone , phenyl trimethicone , or lauryl trimethicone ; hydroxylated derivatives of polymeric silicones such as dimethiconol , or mixtures thereof can also be used . preferably , the volatile silicone oil is cyclomethicone . the extract dispersed in silicone oil is present in an amount of from about 0 . 05 to about 0 . 50 percent by weight of the composition , and preferably about 0 . 1 to about 0 . 4 percent by weight of the total composition . the plant extract can be dispersed in the silicone oil and then added as the extract component to the mascara composition , or alternatively , the plant extract component can be obtained premade with the extract already dispersed in the silicone oil . a predispersed apple extract in cyclomethicone , for example , is available commercially from collaborative laboratories , inc . of east setauket , n . y . the mascara compositions of the invention are easily used by the consumer . they are simply applied to the upper and / or the lower lashes and allowed to dry for about a minute or two . the resulting coat of mascara is smooth and non - tacky . the eyelashes are lengthened , separated , and have a natural appearance . the plant extract also contributes natural plant derived fibers to the mascara as such fibers can be naturally present in the extract . these fibers include water soluble and insoluble fibers . in addition , the mascara can also comprise in combination with the plant derived fibers a non - plant fiber component which enhances the thickness of the eyelashes . non - plant fibers include synthetic fibers and naturally occurring fibers from non - plant sources such as , for example , chitin . the addition of synthetic fibers to mascara is known in the art and is disclosed in , for example , jp 7179323 , incorporated herein by reference . it is also known to include fibers , especially synthetic fibers , in cosmetic compositions in general , as disclosed in , for example , u . s . pat . no . 4 , 820 , 510 , also incorporated herein by reference . however , it is not disclosed in these references to make a mascara using plant derived fibers contained in a plant extract dispersed in a silicone oil . accordingly , examples of synthetic fibers which can be combined with the plant fibers include , but are not limited to , nylon , polyester , polypropylene , polyethylene , acrylic , aramid , rayon , cotton , wool , silk , and blends thereof . in a preferred embodiment , an antistatic component is present to align the fibers , both natural and synthetic , with the eyelashes and separate the eyelashes to render fuller , longer , and more natural - looking eyelashes . the antistatic component can be any kind that manipulates the fibers such that they align parallel with the direction of the natural eyelashes , and that is cosmetically or pharmaceutically acceptable for use around the eye . examples of suitable antistatic agents include but are not limited to , surfactants such as nonionic , anionic , cationic , or amphoteric surfactants , in particular surfactants with quatemium groups . preferably , mild surfactants are used such as lipo - peg - 2dl or disodium cocoamphodiacetate ( miranol ), or mixtures thereof . other antistatic agents include polysaccharides such as chitin , and derivatives , such as , for example , etherified chitin , like carboxymethylated chitin and hydroxyethylated chitin , and esterified chitin , like acetylated chitin and sulfonated chitin , chitosan , quaternary chitosan , and derivatives such as , for example , carboxy methyl chitosan , sulfoethyl chitosan , and other derivatives thereof as disclosed in u . s . pat . no . 4 , 822 , 598 , incorporated herein by reference . preferably the antistatic component is a polysaccharide , more preferably the antistatic component is chitin . the antistatic component is present in an amount of from about 0 . 01 percent to about 10 . 00 percent by weight of the composition . chitin , in its natural state , exists in small flakes or short fibrous material derived from the carapace or tendons of crustaceans . in addition , it is known in the art to prepare or regenerate fibers of chitin having tensile strength close to that of natural chitin , as disclosed in u . s . pat . no . 4 , 029 , 727 , incorporated herein by reference . the presence of chitin in the form of fibers , either natural or synthetic contributes to the fiber content of the compositions of the present invention . chitin is also known to possess antimicrobial properties and may provide antimicrobial activity to the compositions of the present invention . in addition , some types of chitin such as that derived from squid , have a tendency to gel , in which case , the amount of chitin must not interfere with the smoothness and non - tackiness of the present invention achieved with the plant extract dispersed in silicone oil . another component of the mascara is a film - forming agent . the use of a film - former improves the wear of the mascara , and can confer transfer - resistance to the mascara . the film - forming agent may be any which is cosmetically acceptable for use around the eye . examples of useful film - forming agents include natural waxes , polymers such as acrylic acid copolymers , polyethylene polymers , and copolymers of polyvinylpyrrolidone ( pvp ), ethylene vinyl acetate , dimethicone gum , and resins , such as shellac , polyterpenes , and various silicone resins , e . g ., trimethylsiloxysilicate . preferably , the film former is pvp and acrylic acid copolymer which produces a smooth , non - tacky film on the lashes . the film - former is used in an amount of from about 0 . 1 to about 50 . 0 percent , preferably from about 0 . 5 to about 20 . 0 percent by weight of the composition , more preferably 1 . 0 to 10 . 0 percent the mascara compositions of the invention may also comprise additional , optional components . for example , it may be desirable to add one or more preservatives or antioxidants to the formulation . appropriate preservatives may include propyl paraben , butyl paraben , mixtures thereof , or isoforms thereof , as well as bha or bht . the composition contains one or more pigments . any pigment appropriate for use in the eye area may be used . examples of useful pigments are metallic oxides , such as titanium or iron oxides , bismuth oxychloride , carmine , chromium oxide or chromium hydroxide greens , ultramarines , ferric ferrocyanide , ferric ammonium ferrocyanide , mica , fd & amp ; c blue no . 1 , fd & amp ; c red no . 40 , fd & amp ; c yellow no . 5 , and fd & amp ; c green no . 5 . pigment will typically be used in an amount of up to about 20 percent , preferably at about 1 to about 10 percent by weight of the composition as a whole . other additional components are viscosifying agents such as waxes and other gellants , in an amount of from about 1 to about 30 percent by weight of the composition , preferably up to about 20 percent . the waxes may be any synthetic or natural waxes which are suitable for use in the eye area ; preferably , the wax is plant - derived , for example , carnauba wax , candelilla wax , beeswax , synthetic wax , shellac wax , spermaceti , lanolin wax , ozokerite , bran wax , ceresin wax , bayberry wax , paraffin , rice wax and jojoba wax . preferably the wax is beeswax . the gellant may be , for example , bentone , triglycerides , aluminum stearate , c 18 - c 36 acid glycol esters , glyceryl stearate , glyceryl tribehenate and the like . other viscosifying agents include alginates , carbomers , celluloses , gums , carageenans , starches or silicates . the quantities of gellants and viscosifying agents , like the presence of some forms of chitin , must not alter the smoothness and non - tackiness of the plant extract dispersed in the silicone oil . fillers can also optionally be added , in an amount of about 1 to about 20 percent by weight of the composition , preferably from about 1 to about 10 percent ; these may be , for example , silica , pmma , nylon , alumina , barium sulfate , talc or any other filler typically used in such compositions . [ 0026 ] ingredient % amount phase i purified water 40 . 80 simethicone 0 . 15 pvp 3 . 00 methylparaben 0 . 60 phase ii talc 5 . 00 iron oxides 10 . 00 phase iii nylon fiber 1 . 25 phase iv beeswax 10 . 00 ozokerite 10 . 00 glyceryl stearate 8 . 00 butylparaben 0 . 20 propylparaben 0 . 20 triclosan 0 . 10 phase v silicone oil based apple 0 . 10 extract acrylates copolymer 10 . 00 phase vii phenoxyethanol 0 . 50 phase viii chitin 0 . 10 add phase i ingredients together and mix in a vessel until uniform at a temperature of 50 ° c . add phase ii ingredients and phase iii ingredients and mix after addition of each . combine phase iv ingredients in a separate vessel and mix at a temperature of 80 ° c . when mixture is completely dissolved and clear , transfer mixture to vessel containing phase i through iii ingredients . separately add the remaining phase v , vi , vii and viii ingredients in sequence and mix after adding each . let cool to room temperature . a mascara composition containing apple extract , substantially described in example 1 , is prepared and tested . a study is conducted in cool and warm climates for a period of 27 days . in the cool climate , 51 panelists are selected from new jersey , and in the warm climate , 47 panelists are selected from florida . thus , a total of 98 panelists , women ages 18 to 65 years old , are chosen . the panelists wear conventional mascara at least 5 days per week and desire lashes that appear longer . the panelists are instructed to use the mascara of the present invention at least once a day . they are permitted to apply the mascara as often as they deem it to be necessary and / or desirable . however , they are to apply the mascara as they would apply their normal mascara . to remove the mascara the panelists are to use soap and water or their normal eye makeup remover . at the conclusion of the study , panelists complete a self - administered questionnaire . results of the study indicate that 74 % of panelists rate the mascara excellent / very good for being comfortable on the lashes and 87 % find the mascara to be the same as or better than the mascara they use most often . with respect to a natural appearance , 41 % of panelists rate the mascara excellent / very good and 90 % find the appearance to be as natural as the brand they use most often . from the results of the study , 67 % of the panelists also indicate that they find the mascara to be excellent / very good at not causing lashes to look spiked / pointed and 91 % find it to be the same as or better than the mascara they use most often ; 65 % find that the mascara does not cause their lashes to clump together and 84 % find that it does this the same as or better than the mascara they use most often ; 62 % find that the mascara lengthens the lashes and 70 % find that it lengthens the same as or better than the brand they use most often , and 60 % find that the mascara causes a separation of the lashes and 80 % find that it performs better than the mascara they use most often . therefore , this study demonstrates the ability of the mascara compositions containing a plant extract to be non - tacky and to produce longer , fuller , natural looking lashes the same as or better than that of conventional mascaras .

US-32418299-A

the present invention provides purified blood plasma products from fraction ii + iii containing proteins at concentrations useful for the treatment of various diseases and infections including hepatitis b virus . methods of manufacture and treatment are also provided . the purified blood plasma products regulate levels of immune cells and their proteins in the organs and peripheral blood of treated subjects . examples of immune cells and associated proteins regulated by the purified blood plasma products include cd62l levels on t cells , cd4 +, cd8 +, cd28 +, and foxp3 + t cells , b cells , as well as granulocytes and macrophages .

characterization of lymphoid tissues and peripheral blood in hbv infected balb / c mice treated with raas 105 investigation was made into the effects of raas 105 on multiple cell lineages in lymphoid tissues and peripheral blood in hbv infected balb / c mice . hbv infection and raas 105 treatment were performed by id unit at wuxi . at the termination , blood samples and lymphoid tissues were provided to us for analysis of various cell lineages by facs . two independent experiments were performed . one experiment was to test therapeutic effects of raas 105 and the other experiment was to test prophylactic effects of raas 105 . compared with the vehicle group , the differences observed in the animals treated with raas 105 therapeutically include : 1 ) percentages of t cells and b cells in peripheral blood , spleen and lymph nodes were decreased significantly ; 2 ) cd62l was greatly downregulated on both cd4 + and cd8 + t cells in the spleen and lymph nodes ; 3 ) granulocytes and monocytes / macrophages in peripheral blood and lymph nodes increased significantly ; 4 ) the percentages of regulatory t cells ( cd4 + cd25 + foxp3 + ) in the spleen and lymph nodes were increased significantly . however , prophylactic treatment with raas 105 led to somewhat different results . in the group treated with raas 105 , t - and b - lymphocytes were also decreased . the percentages of monocytes and macrophages were increased albeit to a less degree . these results suggested that administration of raas 105 had significant effects on the frequencies of immune cell lineages . peripheral blood was collected through cardiac puncture . after removing red blood cells with lysis buffer followed by two rounds of washing using 1 × pbs , mononuclear cells ( monocytes , macrophages , dendritic cells , and lymphocytes ) and granulocytes were obtained . spleen and lymph nodes cell suspension were obtained after filtering through 70 μm cell strainer . cell viability and number were analyzed by vi - cell cell viability analyzer followed by cell surface staining . cells were centrifuged and resuspended in staining buffer ( 0 . 08 % nan 3 / pbs + 1 % fbs ) containing appropriate fluorescent - conjugated antibodies . after 30 min incubation at 4 ° c . in the dark , cells were washed twice with 0 . 08 % nan 3 / pbs ( 200 μl per sample ), and resuspended with 400 μl 0 . 08 % nan 3 / pbs in bd falcon tubes ( 12 × 75 mm , 5 ml ) followed by facs analysis . to investigate the therapeutic and prophylactic effect of raas 105 on the immune system in mice infected with hbv , the study had divided into two parts . the purpose of this study was to investigate the effect of raas 105 on cellular composition in lymphoid tissues and peripheral blood of hbv infected mice treated with raas 105 . total 10 female balb / c mice including 2 naïve mice at the same age were transferred from infectious disease ( id ) group of wuxiapptec . the group and the regimen information were shown by table 1 . total t cells and b cells were characterized by cd3 and cd19 , respectively . hbv infection did not change the percentages of cd3 + t cells compared with naïve mice . therapeutic treatment of raas 105 reduced the percentages of both cd3 + t cells and cd1913 cells significantly ( fig1 ). the representative facs profiles from each group were illustrated in fig2 . fig1 . percentages of t and b lymphocytes in peripheral blood . total lymphocytes were gated . after therapeutic treated by raas 105 , percentages of tb cells significantly decreased in peripheral blood . ( by test ) fig2 . percent of t cells and b cells in peripheral blood . total lymphocytes were gated . further analysis of the percentages of cd4 + and cd8 + ( non - cd4 + ) t cell lineages were performed gating on total cd3 + t cells . the results showed there were no differences in the percentages of cd4 + and cd8 + t cells among all the groups ( fig3 ). the representative facs profiles from each group were illustrated in fig4 . fig3 . percentages of cd4 and cd8 t cells in peripheral blood . total cd3 t cells were gated and further analyzed for cd4 / cd8 percentages . fig4 . percentages of cd4 and cd8 t cells in peripheral blood . total cd3 t cells were gated . percentages of total cd11c + dendritic cells ( dc ) and gr - 1 + granulocytes in peripheral blood were investigated . hbv infection reduced the percentages of cd11c + dcs , a phenomenon which also be observed in human patients , whereas the percentages of gr - 1 + granulocytes were not affected . therapeutic treatment of raas 105 did not show any effect on cd11c + dcs , but increased the percentages of gr - 1 + granulocytes significantly ( fig5 ). the representative facs profiles from each group were illustrated in fig6 . fig5 . percents of dendritic cells and granulocytes in peripheral blood . total live cells were gated . after therapeutic treatment , percents of granulocytes increased in peripheral blood ( by t test ) fig6 . percents of granulocytes / dendritic cells in peripheral blood . total live cells were gated . percentages of monocytes were examined using surface marker cd11b . it increased significantly as same as gr1 + granulocytes compared with the vehicle group ( fig7 ). the representative facs profiles from each group were illustrated in fig8 . fig7 . percentages of monocytes in peripheral blood . total live cells were gated . after treatment , percentages of monocytes in peripheral blood significantly increased ( t test ) fig8 . percentages of monocytes in peripheral blood . total live cells were gated . cell lineages in spleen including t cell lineages ( cd4 + / cd8 + t cells , naïve t cells , memory t cells and regulatory t cells ), b cells , mdcs , pdcs , granulocytes and macrophages were characterized by cell surface and intracellular markers . percentages of total t cells and b cells in spleen were investigated . therapeutic treatment of raas 105 reduced the percentages of both cd3 + t cells and cd19 + b cells significantly ( fig9 ). the representative facs profiles from each group were illustrated in fig1 . fig9 . percentages of t and b lymphocytes in spleen . total lymphocytes were gated . after therapeutic treatment by raas 105 , percents of t cells and b cells significantly decreased in spleen . fig1 . percents of t cells and b cells in spleen . total lymphocytes were gated . further analysis of the percentages of cd4 + ( non - cd8 + ) and cd8 + t cell lineages were performed gating on total cd3 + t cells . there were no differences in the percentages of cd4 + and cd8 + t cells among all the groups ( fig1 ). the representative facs profiles from each group were illustrated in fig1 . fig1 . percentages of cd4 and cd8 t cells in spleen . total cd3 t cells were gated and further analyzed for cd4 / cd8 percentages . fig1 . percentages of cd4 and cd8 t cells in spleen . total cd3 t cells were gated . three t cell lineages , naïve t cells ( cd44 low cd62l high ), central memory t cells ( t cm s , cd44 high cd62l high ) and effector memory t cells ( t em s , cd44 high cd62l low ), were characterized by surface markers cd44 and cd62l . percentages of these t cell lineages in cd4 + or cd8 + t cells were analyzed respectively . both in cd4 + and cd8 + t cells , percentages of naïve t cells and t cm s decreased and t em s increased after the therapeutic treatment of raas 105 , suggesting the compound may have effect to promote the transformation of t cells from naïve t cells to memory t cells in spleen ( fig1 and 15 ). the representative facs profiles from each group were illustrated in fig1 and 16 . fig1 . t cell subsets percentages in spleen . total cd4 t cells were gated and t cell subsets were determined . fig1 . cd4 t cell subsets percentages in spleen . total cd4 t cells were gated and t cell subsets were determined . fig1 . t cell subsets percentages in spleen . total cd8 t cells were gated and t cell subsets were determined . fig1 . cd8 t cell subsets percentages in spleen . total cd8 t cells were gated and t cell subsets were determined . regulatory t cells ( tregs ) were analyzed by cell surface staining of anti - cd4 and anti - cd25 antibodies followed by intracellular staining of anti - foxp3 antibody . percents of tregs in spleen increased compared with the vehicle group ( fig1 ). the representative facs profiles from each group were illustrated in fig1 . fig1 . percentages of foxp3 regulatory t cells in spleen . foxp3 regulatory t cells were analyzed by intracellular staining . after treatment , the percentage of t regulate cells is increased . fig1 . percentages of regulatory t cells in spleen . total cd4 t cells were gated . dendritic cells , including myeloid dendritic cells ( mdc , b220 − cd11c + ) and plasmacytoid dendritic cells ( pdc , b220 + cd11c + ) in spleen were analyzed . no significant differences of mdcs and pdcs were observed among all groups ( fig1 ). the representative facs profiles from each group were illustrated in fig2 . fig1 . percentages of pdcs and mdcs in spleen . total live cells were gated . there were no significant differences after compound treatment . ( by t test ) fig2 . percentages of mdc and pdcs in spleen . total live cells were gated . cd11b + macrophages and gr - 1 + granulocytes in spleen were analyzed . there were no significant alterations among all groups in the percentages of these cell lineages in spleen , as shown in fig2 . the representative facs profiles from each group were illustrated in fig2 . fig2 . percentages of macrophages and granulocytes in spleen . total live cells were gated . there were no significant differences after compound treatment . ( by t test ) fig2 . percentages of macrophages / granulocytes in spleen . total live cells were gated . cell lineages in draining lymph nodes including t cell lineages ( cd4 + / cd8 + t cells , naïve t cells , memory t cells and regulatory t cells ), dcs , granulocytes and macrophages were characterized by cell surface and intracellular markers . percentages of total t cells in lymph nodes were analyzed . hbv infection did not affect the percentages of cd3 + t cells but therapeutic treatment of raas 105 reduced it significantly compared with vehicle group ( fig2 ). the representative facs profiles from each group were illustrated in fig2 . fig2 . percentages of t cells in lymph nodes . total lymphocytes were gated . after the treatment , the percentage of t cells in the lymph nodes were significantly decreased ( t test ) fig2 . percentages of cd3 t cells in lymph nodes . total lymphocytes were gated . further analysis of the percentages of cd4 + and cd8 + t cell lineages were performed gating on total cd3 + t cells . percentages of cd4 + t cells tended to decrease while cd8 + t cells tended to increase , suggesting that therapeutic treatment of raas 105 may have effect on the ratio of cd4 + / cd8 + t cells in lymph nodes ( fig2 ). the representative facs profiles from each group were illustrated in fig2 . fig2 . percentages of cd4 and cd8 t cells in lymph nodes . total cd3 t cells were gated and further analyzed for cd4 / cd8 percentages . after therapeutic treatment , the percentage of cd4 t cells decreased . ( by t test ) fig2 . percentages of cd4 and cd8 t cells in lymph nodes . total cd3 t cells were gated and further analyzed for cd4 / cd8 percentages . three t cell lineages , naïve t cells , t cm s and t em s were characterized by surface markers cd44 and cd62l . percentages of these t cell lineages in cd4 + or cd8 + t cells were analyzed respectively . the results in lymph nodes were comparable to those in spleen . both in cd4 + and cd8 + t cells , percentages of naïve t cells and t cm s decreased and t em s increased after the therapeutic treatment of raas 105 , suggesting the compound also have effect to promote the transformation of t cells from naïve t cells to memory t cells in lymph nodes ( fig2 and 29 ). the representative facs profiles from each group were illustrated in fig2 and 30 . fig2 . cd4 t cell subsets percentages in lymph nodes . total cd4 t cells were gated and t cell subsets were determined . no significant differences were found in all the groups compared to vehicle group . fig2 . cd4 t cell subset percentages in lymph nodes . total cd4 t cells were gated and t cell subsets were determined . fig2 . cd8 t cell subsets percentages in lymph nodes . total cd8 t cells were gated and t cell subsets were determined . fig3 . cd8 t cell subsets percentages in lymph nodes . total cd8 t cells were gated and t cell subsets were determined . regulatory t cells ( tregs ) were analyzed . percentages of tregs in lymph node slightly increased without significant differences ( fig3 ). the representative facs profiles from each group were illustrated in fig3 . fig3 . percentages of foxp3 regulatory t cells in lymph nodes . there were no significant alterations after compound treatment fig3 . percentages of regulatory t cells in lymph nodes . total cd4 t cells were gated . one representative profile from each group is shown . total dendritic cells in lymph nodes were analyzed . therapeutic treatment of raas 105 may reverse the reduction of dcs induced by hbv infection ( fig3 ). the representative facs profiles from each group were illustrated in fig3 . fig3 . percentages of dcs in lymph nodes . total live cells were gated . after treatment , percents of dcs increased significantly ( by t test ) fig3 . percentages of dcs in lymph nodes . total live cells were gated . cd11b + macrophages and gr - 1 + granulocytes in lymph nodes were analyzed . both percentages of cd11b + macrophages and gr - 1 + granulocytes increased significantly ( fig3 ). the representative facs profiles from each group were illustrated in fig3 . fig3 . percentages of macrophages and granulocytes in lymph nodes . total live cells were gated . percentages of macrophages and granulocytes significantly increased in lymph node . ( by t test ) fig3 . percentages of macrophages / granulocytes in lymph nodes . total live cells were gated . total 14 female balb / c mice including 2 naïve mice at the same age were transferred from infectious disease ( id ) group of wuxi apptec . the group and the regimen information were shown by table 2 . total t cells and b cells were characterized . unlike therapeutic treatment , prophylactic treatment of raas 105 had no effect on percentages of cd3 + t cells but reduced the percentages of cd19 + b cells although the statistical significance was not found ( fig3 ). the representative facs profiles from each group were illustrated in fig3 . fig3 . percents of t and b lymphocytes in peripheral blood . total lymphocytes were gated . fig3 . percents of t cells and b cells in peripheral blood . total lymphocytes were gated . further analysis of the percentages of cd4 + and cd8 + ( non - cd4 + ) t cell lineages were performed gating on total cd3 + t cells . unlike therapeutic treatment , prophylactic treatment reduced percentages of cd4 + t cells and increased percentage of cd8 + t cells , suggesting the potential effect of raas 105 to reduce the ratio of cd4 + / cd8 + t cells in peripheral blood ( fig3 ). the representative facs profiles from each group were illustrated in fig4 . fig3 . percentages of cd4 and cd8 t cells in peripheral blood . total cd3 t cells were gated and further analyzed for cd4 / cd8 percentages . after prophylactic treated by raas 105 , percentages of cd4 t cells decreased while cd8 t cells increased ( by t test ) fig4 . percentages of cd4 and cd8 t cells in peripheral blood . total cd3 t cells were gated . results of total cd11c + dendritic cells ( dc ) and gr - 1 + granulocytes in peripheral blood were also different from those in therapeutic treatment . prophylactic treatment of raas 105 reversed the reduction of dcs induced by hbv infection , but had no significant effect on granulocytes in peripheral blood ( fig4 ). the representative facs profiles from each group were illustrated in fig4 . fig4 . percentages of dendritic cells and granulocytes in peripheral blood . total live cells were gated . after prophylactic treated , percents of dendritic cells increased in [ eripheral blood . fig4 . percentages of granulocytes / dendritic cells in peripheral blood . total live cells were gated . percentages of monocytes were examined . there were no significant differences among all groups ( fig4 ). the representative facs profiles from each group were illustrated in fig4 . fig4 . percentages of monocytes in peripheral blood . total live cells were gated . fig4 . percentages of monocytes in peripheral blood . total live cells were gated . cell lineages in spleen including t cell lineages ( cd4 + / cd8 + t cells , naïve t cells , memory t cells and regulatory t cells ), b cells , mdcs , pdcs , granulocytes and macrophages were characterized by cell surface and intracellular markers . percentages of total t cells and b cells in spleen were investigated . unlike therapeutic treatment , prophylactic treatment did not show effects on percentages of cd3 + t cells and cd19 + b cells ( fig4 ). the representative facs profiles from each group were illustrated in fig4 . fig4 . percentages of t and b lymphocytes in spleen . total lymphocytes were gated . fig4 . percentages of t and b cells in spleen . total lymphocytes were gated . further analysis of the percentages of cd4 + ( non - cd8 + ) and cd8 + t cell lineages were performed gating on total cd3 + t cells . percentages of cd4 + t cells slightly decreased and cd8 + t cells slightly increased in spleen ( fig4 ). the representative facs profiles from each group were illustrated in fig4 . fig4 . percentages of cd4 and cd8 t cells in spleen . total cd3 t cells were gated and further analyzed for cd4 / cd8 percentages . after prophylactic treated by raas 105 , the percentage of cd4 t cells slightly decreased while cd8 t cells slightly increased ( by t test ) fig4 . percentages of cd4 and cd8 t cells in spleen . total cd3 t cells were gated and further analyzed for cd4 / cd8 percentages . naïve t cells , central memory t cells and effector memory t cells were investigated . percentages of these t cell lineages in cd4 + or cd8 + t cells in spleen were analyzed respectively . both in cd4 + and cd8 + t cells , percentages of naïve t cells decreased and t em s increased significantly after the prophylactic treatment of raas 105 ( fig4 and 51 ). the representative facs profiles from each group were illustrated in fig5 and 52 . fig4 . t cell subset percentages in spleen . total cd4 t cells were gated and t cell subsets were determined . fig5 . t cell subsets percentages in spleen . total cd4 t cells were gated and t cell subsets were determined . fig5 . t cell subsets percentages in spleen . total cd8 t cells were gated and t cell subsets were determined . fig5 . t cell subsets percentages in spleen . total cd8 t cells were gated and t cell subsets were determined . results of regulatory t cells ( tregs ) were comparable with those in therapeutic treatment . percentages of tregs in spleen increased compared with the vehicle group by prophylactic treatment of raas 105 ( fig5 ). the representative facs profiles from each group were illustrated in fig5 . fig5 . percentages of foxp3 regulatory t cells in spleen . foxp3 regulatory t cells were analyzed by intracellular staining . fig5 . percentages of regulatory t cells in spleen . total cd4 t cells were gated . dendritic cells , including mdcs and pdcs in spleen were analyzed . no significant differences of mdcs and pdcs were observed among all groups after prophylactic treatment ( fig5 ). the representative facs profiles from each group were illustrated in fig5 . fig5 . percentages of pdcs and mdc in spleen . total live cells were gated . there were no significant differences after compound treatment ( by t test ) fig5 . percentages of mdcs and pdcs in spleen . total live cells were gated . cd11b + macrophages and gr - 1 + granulocytes in spleen were analyzed . percentages of macrophages and granulocytes increased , but no statistical differences were observed , as shown in fig5 . the representative facs profiles from each group were illustrated in fig5 . fig5 . percentages of macrophages and granulocytes in spleen . total live cells were gated . there were no significant differences after compound treatment . ( by t test ) fig5 . percentages of macrophages / granulocytes in spleen . total live cells were gated . cell lineages in draining lymph nodes including t cell lineages ( cd4 + / cd8 + t cells , naïve t cells , memory t cells and regulatory t cells ), dcs , granulocytes and macrophages were characterized by cell surface and intracellular markers . percentages of total t cells in lymph nodes were analyzed . similar with therapeutic treatment , hbv infection did not affect the percentages of cd3 + t cells but prophylactic treatment of raas 105 reduced it significantly compared with vehicle group ( fig5 ). the representative facs profiles from each group were illustrated in fig6 . fig5 . percentages of t cells in lymph nodes . total lymphocytes were gated . after the treatment , percents of t cells in the lymph nodes were significantly decreased . ( t test ) fig6 . percentages of cd3 t cells in lymph nodes . total lymphocytes were gated . further analysis of the percentages of cd4 + and cd8 + t cell lineages were performed gating on total cd3 + t cells . percentages of cd4 + t cells tended to decrease while cd8 + t cells tended to increase after prophylactic treatment , as was seen in therapeutic treatment ( fig6 ). the representative facs profiles from each group were illustrated in fig6 . fig6 . percentages of cd4 and cd8 t cells in lymph nodes . total cd3 t cells were gated and further analyzed for cd4 / cd8 percentages . after prophylactic treatment , percents of cd4 t cells decreased ( by t test ) fig6 . percentages of cd4 and cd8 t cells in lymph nodes . total cd3 t cells were gated and further analyzed for cd4 / cd8 percentages . results of naïve t cells , central memory t cells and effector memory t cells were totally difference with those in therapeutic treatment . prophylactic treatment did not show significant effects on naïve t cells and t cm s , but increased percentages of t em s ( fig6 and 65 ). the representative facs profiles from each group were illustrated in fig6 and 66 . fig6 . t cell subsets percentages in lymph nodes . total cd4 cells were gated and t cell subsets were determined . no significant differences were found except effector memory t cells compared to vehicle group . fig6 . t cell subsets percentages in lymph nodes . total cd4 t cells were gated and t cell subsets were determined . fig6 . t cell subsets percentages in lymph nodes . total cd8 t cells were gated and t cell subsets were determined . no significant differences were found in all the groups compared to vehicle group . fig6 . t cell subsets percentages in lymph nodes . total cd8 t cells were gated and t cell subsets were determined . regulatory t cells were analyzed . there were no significant differences among all groups ( fig6 ). the representative facs profiles from each group were illustrated in fig6 . fig6 . percentages of foxp3 regulatory t cells in lymph nodes . foxp3 regulatory t cells were analyzed by intracellular staining . there were no significant alterations after compound treatment . ( by t test ) fig6 . percentages of regulatory t cells in lymph nodes . total cd4 t cells were gated . results of total dendritic cells in lymph nodes were similar with those in therapeutic treatment . prophylactic treatment of raas 105 also increased the percentages of dcs significantly compared with vehicle group ( fig6 ). the representative facs profiles from each group were illustrated in fig7 . fig6 . percentages of dcs in lymph nodes . total live cells were gated . after the treatment , percentages of the dcs increased significantly ( by t test ) fig7 . percentages of dcs in lymph nodes . total live cells were gated . cd11b + macrophages and gr - 1 + granulocytes in lymph nodes were analyzed . both macrophages and granulocytes increased significantly ( fig7 ). the representative facs profiles from each group were illustrated in fig7 . fig7 . percentages of macrophages and granulocytes in lymph nodes . total live cells were gated . after therapeutic treated by raas 105 , percents of macrophages and granulocytes significantly increased . ( by t test ) fig7 . percentages of macrophages / granulocytes in lymph nodes . total live cells were gated . the effects of raas 105 on different cell lineages in lymphoid tissues and peripheral blood in hbv infected mice were investigated by facs analysis . t cell lineages ( including cd4 + / cd8 + t cells , naïve t cells , memory t cells and regulatory t cells ), b cells , dendritic cells ( including mdcs , pdcs ), granulocytes and monocytes / macrophages were analyzed . raas 105 was administered in two different time schedules for therapeutic and prophylactic treatment . therapeutic treatment revealed some interesting findings . the animals treated with raas 105 exhibited alterations in multiple immune cells and various lineages compared with that in the vehicle group , including reduction of lymphocytes and increase of granulocytes and monocytes . prophylactic treatment led to less dramatic alterations in the immune cells .

US-201515355304-A

this invention encompasses methods for the treatment or prevention of a physiological disorder associated with an excess of tachykinins , said disorder being an allergy which method comprises administering to a mammal in need of said treatment an effective amount of a compound of formula i ## str1 ## wherein r 1 and r 3 are independently hydrogen , -- ch 3 , ## str2 ## wherein ar is optionally substituted phenyl ; r 2 is selected from the group consisting of pyrrolidine , hexamthylenemino , and piperidino ; or a pharmaceutically acceptable salt of solvate thereof .

the current invention concerns the discovery that a select group of benzothiophenes , those of formula i , are useful as tachykinin receptor antagonists . the invention encompasses uses practiced by administering to a mammal or human in need thereof a dose of a compound of formula 1 or a pharmaceutically acceptable salt or solvate thereof effective to inhibit a physiological disorder associated with an excess of tachykinins . the term inhibit includes its generally accepted meaning which includes prophylactic administration to a mammal or human subject to incurring a disorder described herein , and holding in check and / or treating existing disorders . as such , the methods include both therapeutic and prophylactic administration . generally , the compound is formulated with common excipients , diluents or carriers , and compressed into tablets , or formulated as elixirs or solutions for convenient oral administration , or administered by the intramuscular or intravenous routes . the compounds can be administered transdermally , and may be formulated as sustained release dosage forms and the like . the compounds used in the methods of the current invention can be made according to established and analogous procedures , such as those detailed in u . s . pat . nos . 4 , 133 , 814 , 4 , 418 , 068 , and 4 , 380 , 635 all of which are incorporated by reference herein . in general , the process starts with a benzo [ b ] thiophene having a 6 - hydroxyl group and a 2 -( 4 - hydroxyphenyl ) group . the starting compound is protected , alkylated , and deprotected to form the formula i compounds . examples of the preparation of such compounds are provided in the u . s . patents discussed above , and in the examples in this application . optionally substituted phenyl includes phenyl and phenyl substituted once or twice with c 1 - c 6 alkyl , c 1 - c 4 alkoxy , hydroxy , nitro , chloro , fluoro , or tri ( chloro or fluoro ) methyl . the compounds used in the methods of this invention form pharmaceutically acceptable acid and base addition salts with a wide variety of organic and inorganic acids and bases and include the physiologically acceptable salts which are often used in pharmaceutical chemistry . such salts are also part of this invention . typical inorganic acids used to form such salts include hydrochloric , hydrobromic , hydroiodic , nitric , sulfuric , phosphoric , hypophosphoric and the like . salts derived from organic acids , such as aliphatic mono and dicarboxylic acids , phenyl substituted alkanoic acids , hydroxyalkanoic and hydroxyalkandioic acids , aromatic acids , aliphatic and aromatic sulfonic acids , may also be used . such pharmaceutically acceptable salts thus include acetate , phenylacetate , trifluoroacetate , acrylate , ascorbate , benzoate , chlorobenzoate , dinitrobenzoate , hydroxybenzoate , methoxybenzoate , methylbenzoate , o - acetoxybenzoate , naphthalene - 2 - benzoate , bromide , isobutyrate , phenylbutyrate , β - hydroxybutyrate , butyne - 1 , 4 - dioate , hexyne - 1 , 4 - dioate , caprate , caprylate , chloride , cinnamate , citrate , formate , fumarate , glycollate , heptanoate , hippurate , lactate , malate , maleate , hydroxymaleate , malonate , mandelate , mesylate , nicotinate , isonicotinate , nitrate , oxalate , phthalate , teraphthalate , phosphate , monohydrogenphosphate , dihydrogenphosphate , metaphosphate , pyrophosphate , propiolate , propionate , phenylpropionate , salicylate , sebacate , succinate , suberate , sulfate , bisulfate , pyrosulfate , sulfite , bisulfite , sulfonate , benzene - sulfonate , p - bromophenylsulfonate , chlorobenzenesulfonate , ethanesulfonate , 2 - hydroxyethanesulfonate , methanesulfonate , naphthalene - 1 - sulfonate , naphthalene - 2 - sulfonate , p - toluenesulfonate , xylenesulfonate , tartarate , and the like . a preferable salt is the hydrochloride salt . the pharmaceutically acceptable acid addition salts are typically formed by reacting a compound of formula i with an equimolar or excess amount of acid . the reactants are generally combined in a mutual solvent such as diethyl ether or benzene . the salt normally precipitates out of solution within about one hour to 10 days and can be isolated by filtration or the solvent can be stripped off by conventional means . bases commonly used for formation of salts include ammonium hydroxide and alkali and alkaline earth metal hydroxides and carbonates , as well as aliphatic and aromatic amines , aliphatic diamines and hydroxy alkylamines . bases especially useful in the preparation of addition salts include ammonium hydroxide , potassium carbonate , sodium bicarbonate , calcium hydroxide , methylamine , diethylamine , ethylene diamine , cyclohexylamine and ethanolamine . the pharmaceutically acceptable salts generally have enhanced solubility characteristics compared to the compound from which they are derived , and thus are often more amenable to formulation as liquids or emulsions . pharmaceutical formulations can be prepared by procedures know in the art . for example , the compounds can be formulated with common excipients , diluents , or carriers , and formed into tablets , capsules , suspensions , powders , and the like . examples of excipients , diluents , and carriers that are suitable for such formulations include the following : fillers and extenders such as starch , sugars , mannitol , and silicic derivatives ; binding agents such as carboxymethyl cellulose and other cellulose derivatives , alginates , gelatin , and polyvinyl pyrrolidone ; moisturizing agents such as glycerol ; disintegrating agents such as agaragar , calcium carbonate , and sodium bicarbonate ; agents for retarding dissolution such as paraffin ; resorption accelerators such as quaternary ammonium compounds ; surface active agents such as cetyl alcohol , glycerol monostearate ; adsorptive carriers such as kaolin and bentonire ; and lubricants such as talc , calcium and magnesium stearate , and solid polyethyl glycols . the compounds can also be formulated as elixirs or solutions for convenient oral administration or as solutions appropriate for parenteral administration , for instance by intramuscular , subcutaneous or intravenous routes . additionally , the compounds are well suited to formulation as sustained release dosage forms and the like . the formulations can be so constituted that they release the active ingredient only or preferably in a particular part of the intestinal tract , possibly over a period of time . the coatings , envelopes , and protective matrices may be made , for example , from polymeric substances or waxes . the particular dosage of a compound of formula i according to this invention will depend upon the severity of the condition , the route of administration , and related factors that will be decided by the attending physician . generally , accepted and effective daily doses will be from about 0 . 1 to about 1000 mg / day , and more typically from about 50 to about 200 mg / day . such dosages will be administered to a subject in need of treatment from once to about three times each day , or more often as needed . it is usually preferred to administer a compound of formula i in the form of an acid addition salt , as is customary in the administration of pharmaceuticals bearing a basic group , such as the piperidino ring . for such purposes the following dosage forms are available . in the formulations which follow , &# 34 ; active ingredient &# 34 ; means a compound of formula i . ______________________________________formulation 1 : gelatin capsuleshard gelatin capsules are prepared using the following : ingredient quantity ( mg / capsule ) ______________________________________active ingredient 0 . 1 - 1000starch , nf 0 - 650starch flowable powder 0 - 650silicone fluid 350 centistokes 0 - 15______________________________________ the ingredients are blended , passed through a no . 45 mesh u . s . sieve , and filled into hard gelatin capsules . examples of specific capsule formulations of the compound raloxifene that have been made include those shown below : ______________________________________ingredient quantity ( mg / capsule ) ______________________________________formulation 2 : raloxifene capsuleraloxifene 1starch , nf 112starch flowable powder 225 . 3silicone fluid 350 centistokes 1 . 7formulation 3 : raloxifene capsuleraloxifene 5starch , nf 108starch flowable powder 225 . 3silicone fluid 350 centistokes 1 . 7formulation 4 : raloxifene capsuleraloxifene 10starch , nf 103starch flowable powder 225 . 3silicone fluid 350 centistokes 1 . 7formulation 5 : raloxifene capsuleraloxifene 50starch , nf 150starch flowable powder 397silicone fluid 350 centistokes 3 . 0______________________________________ the specific formulations above may be changed in compliance with the reasonable variations provided . ______________________________________formulation 6 : tabletsingredient quantity ( mg / tablet ) ______________________________________active ingredient 0 . 1 - 1000cellulose , microcrystalline 0 - 650silicon dioxide , fumed 0 - 650stearate acid 0 - 15______________________________________ alternatively , tablets each containing 0 . 1 - 1000 mg of active ingredient are made up as follows : ______________________________________formulation 7 : tabletsingredient quantity ( mg / tablet ) ______________________________________active ingredient 0 . 1 - 1000starch 45cellulose , microcrystalline 35polyvinylpyrrolidone 4 ( as 10 % solution in water ) sodium carboxymethyl cellulose 4 . 5magnesium stearate 0 . 5talc 1______________________________________ the active ingredient , starch , and cellulose are passed through a no . 45 mesh u . s . sieve and mixed thoroughly . the solution of polyvinylpyrrolidone is mixed with the resultant powders which are then passed through a no . 14 mesh u . s . sieve . the granules so produced are dried at 50 °- 60 ° c . and passed through a no . 18 mesh u . s . sieve . the sodium carboxymethyl starch , magnesium stearate , and talc , previously passed through a no . 60 u . s . sieve , are then added to the granules which , after mixing , are compressed on a tablet machine to yield tablets . suspensions each containing 0 . 1 - 1000 mg of medicament per 5 ml dose are made as follows : ______________________________________formulation 8 : suspensionsingredient quantity ( mg / tablet ) ______________________________________active ingredient 0 . 1 - 1000 mgsodium carboxymethyl cellulose 50 mgsyrup 1 . 25 mgbenzoic acid solution 0 . 10 mlflavor q . v . color q . v . purified water to 5 ml______________________________________ the medicament is passed through a no . 45 mesh u . s . sieve and mixed with the sodium carboxymethyl cellulose and syrup to form a smooth paste . the benzoic acid solution , flavor , and color are diluted with some of the water and added , with stirring . sufficient water is then added to produce the required volume . the biological activity of the compounds of the present invention are evaluated employing an initial screening assay which rapidly and accurately measures the binding of the tested compound to known nk - 1 receptor sites . assays useful for evaluating tachykinin receptor antagonists are well known in the art . see , e . g ., j . jukic , et al ., life sciences , 49 : 1463 - 1469 ( 1991 ); n . kucharczyk , et al ., journal of medicinal chemistry , 36 : 1654 - 1661 ( 1993 ); n . rouissi , et al ., biochemical and biophysical research communications , 17 6 : 894 - 901 ( 1991 ). radioreceptor binding assays are performed using a derivative of a previously published protocol . d . g . payan , et al ., journal of immunology , 133 : 3260 - 3265 ( 1984 ). in this assay an aliquot of im9 cells ( 1 × 10 6 cells / tube in rpmi 1640 medium supplemented with 10 % fetal calf serum ) is incubated with 20 pm 125 i - labeled substance p in the presence of increasing competitor concentrations for 45 minutes at 4 ° c . the im9 cell line is a well - characterized and readily available human cell line . see , e . g ., annals of the new york academy of science , 190 : 221 - 234 ( 1972 ); nature ( london ), 251 : 443 - 444 ( 1974 ); proceedings of the national academy of sciences ( usa ), 71 : 84 - 88 ( 1974 ). these cells are routinely cultured in rpmi 1640 supplemented with 50 μg / ml gentamicin sulfate and 10 % fetal calf serum . the reaction is terminated by filtration through a glass fiber filter harvesting system using filters previously soaked for 20 minutes in 0 . 1 % polyethylenimine . specific binding of labeled substance p is determined in the presence of 20 nm unlabeled ligand . the cho - hnk - 2r cells , a cho - derived cell line transformed with the human nk - 2 receptor , expressing about 400 , 000 such receptors per cell , are grown in 75 cm 2 flasks or roller bottles in minimal essential medium ( alpha modification ) with 10 % fetal bovine serum . the gene sequence of the human nk - 2 receptor is given in n . p . gerard , et al ., journal of biological chemistry , 265 : 20455 - 20462 ( 1990 ). for preparation of membranes , 30 confluent roller bottle cultures are dissociated by washing each roller bottle with 10 ml of dulbecco &# 39 ; s phosphate buffered saline ( pbs ) without calcium and magnesium , followed by addition of 10 ml of enzyme - free cell dissociation solution ( pbs - based , from specialty media , inc .). after an additional 15 minutes , the dissociated cells are pooled and centrifuged at 1 , 000 rpm for 10 minutes in a clinical centrifuge . membranes are prepared by homogenization of the cell pellets in 300 ml 50 mm tris buffer , ph 7 . 4 with a tekmar ® homogenizer for 10 - 15 seconds , followed by centrifugation at 12 , 000 rpm ( 20 , 000 × g ) for 30 minutes using a beckman ja - 14 ® rotor . the pellets are washed once using the above procedure . and the final pellets are resuspended in 100 - 120 ml 50 mm tris buffer , ph 7 . 4 , and 4 ml aliquots stored frozen at - 70 ° c . the protein concentration of this preparation is 2 mg / ml . for the receptor binding assay , one 4 - ml aliquot of the cho - hnk - 2r membrane preparation is suspended in 40 ml of assay buffer containing 50 mm tris , ph 7 . 4 , 3 mm manganese chloride , 0 . 02 % bovine serum albumin ( bsa ) and 4 μg / ml chymostatin . a 200 μl volume of the homogenate ( 40 μg protein ) is used per sample . the radioactive ligand is [ 125 i ] iodohistidyl - neurokinin a ( new england nuclear , nex - 252 ), 2200 ci / mmol . the ligand is prepared in assay buffer at 20 nci per 100 μl ; the final concentration in the assay is 20 pm . non - specific binding is determined using 1 μm eledoisin . ten concentrations of eledoisin from 0 . 1 to 1000 nm are used for a standard concentration - response curve . all samples and standards are added to the incubation in 10 μl dimethylsulfoxide ( dmso ) for screening ( single dose ) or in 5 μl dmso for ic 50 determinations . the order of additions for incubation is 190 or 195 μl assay buffer , 200 μl homogenate , 10 or 5 μl sample in dmso , 100 μl radioactive ligand . the samples are incubated 1 hr at room temperature and then filtered on a 48 well brandel cell harvester through gf / b filters which have been presoaked for two hours in 50 mm tris buffer , ph 7 . 7 , containing 0 . 5 % bsa . the filter is washed 3 times with approximately 3 ml of cold 50 mm tris buffer , dh 7 . 7 . the filter circles are then punched into 12 × 75 mm polystyrene tubes and counted in a gamma counter . utility of the compounds described herein is illustrated by activity in at least one of the above assays . since the compounds of formula i are effective tachykinin receptor antagonists , these compounds are of value in the treatment of a wide variety of clinical conditions which can be due to an excess of tachykinin . thus , the invention provides methods for the treatment or prevention of a physiological disorder associated with an excess of tachykinins , which method comprises administering to a mammal in need of said treatment an effective amount of a compound of formula i or a pharmaceutically acceptable salt , solvate or prodrug thereof . the term &# 34 ; physiological disorder associated with an excess of tachykinins &# 34 ; encompasses those disorders associated with an inappropriate stimulation of tachykinin receptors , regardless of the actual amount of tachykinin present in the locale . these physiological disorders may include disorders of the central nervous system such as anxiety , depression , psychosis , and schizophrenia ; neurodegenerative disorders such as dementia , including senile dementia of the alzheimer &# 39 ; s type , alzheimer &# 39 ; s disease , aids - associated dementia , and down &# 39 ; s syndrome ; demyelinating diseases such as multiple sclerosis and amyotrophic lateral sclerosis and other neuropathological disorders such as peripheral neuropathy , such as diabetic and chemotherapy - induced neuropathy , and post - herpetic and other neuralgias ; acute and chronic obstructive airway diseases such as adult respiratory distress syndrome , bronchopneumonia , bronchospasm , chronic bronchitis , drivercough , and asthma ; inflammatory diseases such as inflammatory bowel disease ; allergies such as eczema and rhinitis ; hypersensitivity disorders such as poison ivy ; ophthalmic diseases such as conjunctivitis , vernal conjunctivitis , and the like ; cutaneous diseases such as psoriasis , contact dermatitis , atopic dermatitis , urticaria , and other eczematoid dermatites ; addiction disorders such as alcoholism ; stress - related somatic disorders ; reflex sympathetic dystrophy such as shoulder / hand syndrome ; dysthymic disorders ; adverse immunological reactions such as rejection of transplanted tissues , gastrointestinal disorders or diseases associated with the neuronal control of viscera such as ulcerative colitis , crohn &# 39 ; s disease and irritable bowel syndrome ; disorders of bladder function such as bladder detrusor hyper - reflexia and incontinence ; disorders of blood flow caused by vasodilation and vasospastic diseases such as angina , migraine , and reynaud &# 39 ; s disease ; and pain or nociception , for example , that attributable to or associated with any of the foregoing conditions , especially the transmission of pain in migraine . for example the confounds of formula i may suitably be used in the treatment of disorders of the central nervous system such as anxiety , psychosis , and schizophrenia ; neurodegenerative disorders such as alzheimer &# 39 ; s disease and down &# 39 ; s syndrome ; respiratory diseases such as bronchospasm and asthma ; inflammatory diseases such as artritis , inflammatory bowel disease ; adverse immunological disorders such as rejection of transplanted tissues ; gastrointestinal disorders and diseases such as disorders associated with the neuronal control of viscera such as ulcerative colitis , crohn &# 39 ; s disease and irritable bowel syndrome ; incontinence ; disorders of blood flow caused by vasodilation ; and pain or nociception , for example , that attributable to or associated with any of the foregoing conditions or the transmission of pain in migraine . for example , nk - 1 antagonists are most especially preferred in the treatment of pain , especially chronic pain , such as neuropathic pain , post - operative pain , and migraines , pain associated with arthritis , cancer - associated pain , chronic lower back pain , cluster headaches , herpes neuralgia , phantom limb pain , central pain , dental pain , neuropathic pain , opiod - resistant pain , visceral pain , surgical pain , bone injury pain , pain during labor and delivery , pain resulting from burns , post partum pain , angina pain , and genitourinary tract - related pain including cystitis . in addition to pain , nk - 1 antagonists are especially preferred in the treatment and prevention of urinary incontinence ; motility disorders of the gastrointestinal tract , such as irritable bowel syndrome ; acute and chronic obstructive airway diseases , such as bronchospasm , bronchopneumonia , asthma , and adult respiratory distress syndrome ; inflammatory conditions , such as arthritis inflammatory bowel disease , ulcerative colitis , crohn &# 39 ; s disease , neurogenic inflammation , allergies , rhinitis , cough , urticaria , conjunctivitis , irritation - induced miosis ; tissue transplant rejection ; plasma extravasation resulting from cytokine chemotherapy and the like ; spinal cord trauma ; stroke ; cerebral stroke ( ischemia ); alzheimer &# 39 ; s disease ; parkinson &# 39 ; s disease ; multiple sclerosis ; amyotrophic lateral sclerosis ; schizophrenia ; anxiety ; and depression . nk - 2 antagonists are especially preferred in the treatment of urinary incontinence , bronchospasm , asthma , adult respiratory distress syndrome , motility disorders of the gastrointestinal tract , such as irritable bowel syndrome , and pain . __________________________________________________________________________sequence listing ( 1 ) general information :( iii ) number of sequences : 4 ( 2 ) information for seq id no : 1 :( i ) sequence characteristics :( a ) length : 5 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : peptide ( xi ) sequence description : seq id no : 1 : phexaaglyleumet15 ( 2 ) information for seq id no : 2 :( i ) sequence characteristics :( a ) length : 11 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : peptide ( xi ) sequence description : seq id no : 2 : argprolyspr oglnglnphepheglyleumet1510 ( 2 ) information for seq id no : 3 :( i ) sequence characteristics :( a ) length : 10 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : peptide ( xi ) sequence description : seq id no : 3 : hislysthraspserphevalglyleumet1510 ( 2 ) information for seq id no : 4 :( i ) sequence characteristics :( a ) length : 10 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : peptide ( xi ) sequence description : seq id no : 4 : aspmethisaspphephevalglyleumet1510

US-16848493-A

the invention relates to a manual - opened and auto - closed umbrella , which utilizes two springs provided around a shaft and therein accompanying with a runner and a frame to control the umbrella being opened manually and closed automatically . the umbrella is to be opened manually that compresses the springs at the same time , and by a touch to automatically close the umbrella . the manual - opened and auto - closed umbrella therefore obtains a certain utilization and improvement .

referring to fig1 to 5 , the present invention relates to an improved umbrella , which can be manually opened and automatically closed , which includes a shaft ( 1 ) being consisted by several tubes . in this embodiment for explanation , the shaft ( 1 ) includes an outer tube ( 11 ), a middle tube ( 12 ), and an inner tube ( 13 ). a handle ( 15 ) with a button ( 151 ) is connected with lower end of the shaft ( 1 ) and an upper joint ( 14 ) is connected with top end of the shaft ( 1 ). a runner ( 2 ) provided around the shaft ( 1 ). a double - ears receiver ( 3 ) is provided around the shaft ( 1 ) above the runner ( 2 ). a control - closing spring ( 30 ) is also provided around the shaft ( 1 ) between the upper joint ( 14 ) and the receiver ( 3 ). the umbrella frame ( 4 ) has its inner ends pivoted with the upper joint ( 14 ) and the runner ( 2 ). by use of movement of the runner , the frame ( 4 ) is expended to open the umbrella or is concentrated to close the umbrella . as shown in fig2 , an upper controller ( 5 ) and a middle fixer ( 6 ) with an inner spring ( 51 ) therebetween are provided in the shaft ( 1 ). a bow ( 52 ) received in the upper controller ( 5 ) has its lower hook end ( 521 ) extend outward from a slot ( 61 ) of the middle fixer ( 6 ). a lower fixer ( 7 ) placed below middle fixer ( 6 ) has a rod ( 71 ) for winding inner ends of two ropes ( 31 ), both of which have their outer end extend upward to pass around a related wheel ( 16 ) under the upper joint ( 14 ), then downward to pass around another wheel ( 32 ) on the receiver ( 3 ), and at last upward to connect with the upper joint ( 14 ), meanwhile the ropes ( 31 ) are kept in tension always . the lower fixer ( 7 ) has a bottom v - shaped elastic slice ( 72 ). an inner controller ( 8 ) received in a lower inside position of the shaft ( 1 ) connects with the lowest end of an inner wire ( 81 ) having its top end connect with the upper controller ( 5 ). the inner controller ( 8 ) is provided with a side projection ( 82 ) facing the button ( 151 ) of the handle ( 15 ). a loop ( 9 ) placed in the handle ( 15 ) has a convex ( 91 ) opposite to the button ( 151 ) and face the projection ( 82 ) of the inner controller ( 8 ). please refer to fig3 , the upper controller ( 5 ) has its lower side an inclined plane ( 53 ) and the bow ( 52 ) has a top inner hook ( 522 ) and a lower hook end ( 521 ), wherein a small spring ( 523 ) is placed inside the lower hook end ( 521 ) to provide a stable elastic force for push the lower end outward . as in fig4 and 5 , when the umbrella is in closed state , the projection ( 82 ) is stopped in a slot ( 131 ) of the inner tube ( 13 ). at this time , the control - closing spring ( 30 ) and the inner spring ( 51 ) are prolonged , and the inner wire ( 81 ) is released . the frame ( 4 ) is closed beside the shaft ( 1 ) and the receiver ( 3 ) contacts with the runner ( 2 ) far away from the upper joint ( 14 ) that the umbrella is closed stably . in use , the umbrella is to be opened manually by pushing the runner ( 2 ) upward that the shaft ( 1 ) is prolonged and the frame ( 4 ) is expanded to open the umbrella as shown in fig6 and 7 . at the moment , the control - closing spring ( 30 ) and the inner spring ( 51 ) are compressed and positioned . to close the umbrella , referring to fig8 to 11 , when the user pushes the button ( 151 ), the projection ( 82 ) will be pushed and released from the inner tube ( 13 ). both upper controller ( 5 ) and inner controller ( 8 ) are capable of moving upward , meanwhile the lower inclined plane ( 53 ) will push the top inner hook ( 522 ) of the bow ( 52 ) to force the lower hook end ( 521 ) to move inward and release the engagement between the middle tube ( 12 ) and the outer tube ( 11 ). so , the middle tube ( 12 ) moves upward to be received in the outer tube ( 11 ) and then the outer tube ( 11 ) moves downward to press the v - shaped slice ( 72 ) to release the engagement between the middle tube ( 12 ) and the inner tube ( 13 ). at this time , the inner fixer ( 7 ) moves upward since the ropes ( 31 ) are not limited anymore . therefore , the control - closing spring ( 30 ) can rapidly extended to force the receiver ( 3 ) and the runner ( 2 ) downward that pulls the frame ( 4 ) concentrated to the shaft ( 1 ) and closes the umbrella automatically . if a user wants to use the umbrella again , he just needs to repeat the above operation , i . e . to push the runner for opening the umbrella , and a force on button of the handle to automatically close the umbrella . thus , we can find that the operation of the present invention is totally different from the prior art and is useful for people to apply the umbrella as normal . moreover , it can be understood that the above - mentioned embodiments including a frame with three folded ribs are only exemplary of the present invention . any modification , such as a frame with four or more ribs and a shaft with four or more tubes , having the same or similar merit is still claimed in this application .

US-36287406-A

an intramedullary fixation device having a distal section ; a proximal section ; a connecting member for adjustably securing the distal and proximal sections end to end along a longitudinal axis ; means for securing the proximal section to a first bone ; and means for securing the distal section to a least one different bone . the connecting member is rotated to provide compression across a bone arthrodesis site to be stabilized and fused . also described is a method of utilizing the intramedullary fixation device with an outrigger assembly .

the following detailed description is of the best mode or modes of the invention presently contemplated . such description is not intended to be understood in a limiting sense , but to be an example of the invention presented solely for illustration thereof , and by reference to which in connection with the following description and the accompanying drawings one skilled in the art may be advised of the advantages and construction of the invention . the invention is intended to cover alternatives , modifications , and equivalents , which may be included within the spirit and scope of the invention as defined by the appended claims . fig1 - 11 illustrate the intramedullary fixation device of the present invention , fig1 - 14 and 17 illustrate the combination intramedullary fixation device and outrigger assembly , and fig1 - 16 illustrate the outrigger assembly alone . referring to fig1 , there is shown an embodiment of the intramedullary fixation device 12 of the present invention for stabilizing the position of and fusing together the tibia t ( shin bone ) relative to the talus a ( adjoining ankle ) and calcaneus c ( heel ) bones , and which is to be inserted through the bottom of the foot into the medullary canal of the tibia . intramedullary nail 12 is comprised of two main sections , referred to generally herein as proximal section 14 and distal section 16 . in addition , compression bolt 18 ( see fig7 ) is used to join proximal section 14 to distal section 16 , and in addition to provide the required tension or compression of the ankle joint once installed , as will also be described in detail below . in addition , alignment outrigger device 20 ( fig1 ) is provided , which is used to precisely position nail 12 in the tibia t and fixed to the talus a and calcaneus c bones . also shown in fig1 is driving device 24 which is used to adjust compression bolt 18 . proximal 14 and distal 16 sections of intramedullary nail 12 generally have a rounded or circular shape , and are preferably made of surgical stainless steel or surgical stainless titanium , and correspond generally to the - shape of the tibia medullary canal . referring more particularly now to fig5 , proximal section 14 of nail 12 has a forward end 25 and a rearward end 26 , and is slightly tapered along its longitudinal axis 23 from rearward end 26 to forward end 25 , the outer surface of which end is preferably smooth and rounded . through - holes 28 extending perpendicular to longitudinal axis 23 are spaced apart in the shaft of proximal section 14 near forward end 25 , through which holes 28 support screws 30 ( see fig1 ) are passed to secure proximal section 14 of nail 12 to the tibia bone in position in the tibia medullary canal . it will be understood that screws 30 may have different lengths and sizes as required and known to those skilled in the art . a bore 32 extends inwardly from the rearward end 26 of proximal section 14 along longitudinal axis 23 , forming non - threaded sleeve area 34 adjacent rearward end 26 , a short non - threaded section 35 adjacent sleeve area 34 and having a smaller diameter than sleeve area 34 , with inwardly extending circumferential bearing surface 37 formed between areas 34 and 35 , and extending inwardly from short section 35 an internal screwthreaded area 36 for receiving compression bolt 18 . see also fig1 and 9 . in addition , at least one alignment notch 38 is provided in sleeve area 34 adjacent rearward end 26 , for receiving corresponding tab in distal section 16 and for properly aligning the sections of nail 12 in the manner described below . as shown in fig6 a , distal section 16 of nail 12 has an upper end 40 and a lower end 41 , and is preferably slightly tapered from lower end 41 to upper end 40 along its longitudinal axis 42 . a plurality of holes 44 are situated in distal section 16 near lower end 41 extending perpendicular to longitudinal axis 42 and spaced apart a predetermined distance , for receiving screws 30 passed through the talus and calcaneus bones . situated on the upper end 40 of distal section 16 is arm 46 having a reduced outer diameter and being sized to be slidingly received in sleeve 34 of bore 32 in proximal section 14 , while as best shown in fig1 and 9 a bore 48 extends through distal section 16 from upper end 40 to lower end 41 , which bore 48 has a smaller diameter section 49 adjacent upper end 40 and arm 46 , and a larger diameter section 50 , with inwardly extending bearing surface or end wall 51 between such sections . threads 52 are provided in the inner walls of larger diameter section 50 of bore 48 adjacent lower end 41 , while a plurality of spaced apart rectangular notches 54 are formed in lower end 41 . bore 48 is sized to receive compression bolt 18 , best shown in fig7 , which bolt has a reduced diameter section 60 and a larger diameter head section 62 , forming outwardly extending bearing surface 63 between sections 60 and 62 . reduced diameter section 60 includes a threaded section 64 , a non - threaded shaft section 66 , a shallow notch 67 situated between such sections , and head section 68 . a socket 70 is provided in the end surface of enlarged diameter section 62 to facilitate rotating bolt 18 in either a clockwise or counterclockwise direction using driving device 24 as described in more detail below . as shown in fig1 and 9 , head section 62 of compression bolt 18 is sized to be received in bore 50 of distal section 16 of nail 12 , while at the same time reduced diameter section 60 of bolt 18 is passed through bore sections 50 , with threaded section 64 extending outwardly through forward end 40 while shaft section 66 remains in bore 49 in arm 46 . when arm 46 is inserted in sleeve 34 , male threaded section 64 is received on the female threads in bore section 36 , and when rotated on the threads arm 46 is pulled towards sleeve 34 until bearing surface 63 of head section 62 engages against bearing surface 51 in bore 50 . compression bolt 18 is adjustably secured to proximal section 14 by clip 72 , shown in fig8 , which clip is secured around the outer surface of bolt 18 in slot 67 , to prevent threaded section 64 from being moved outwardly out of bore 32 past sleeve section 34 . the present inventor &# 39 ; s system also includes an improved outrigger assembly 20 , shown alone in fig1 - 16 and with nail 12 attached in fig1 - 14 and 17 , which assembly 20 is used to properly position and align intramedullary fixation device 12 while it is being inserted and secured in the patient &# 39 ; s tibia medullary canal and then while a compressive for is applied across the arthrodesis site . outrigger assembly 20 includes an alignment beam 80 that is detachably and adjustably secured to handle 82 in a slot 83 along one side edge of handle 82 so that the beam extends outwardly from the handle , while a nail engaging shaft 84 is secured to handle 82 in an aperture 85 along the opposite side edge of the handle , so that nail 12 when engaged with shaft 84 is spaced apart and in parallel with beam 80 . outrigger assembly 20 is preferably made of carbon fiber which is radiolucent and thus does not appear in x - rays , although other materials such as surgical stainless steel may be used . beam 80 is secured in slot 83 by two different locking mechanisms on opposite sides of the slot . the first of these is a threaded pin 86 which is threadably secured in an aperture 87 in handle 82 , which aperture 87 extends laterally between the outer side surface of handle 82 and slot 83 . thus , when pin 86 is inserted in aperture 87 with beam 80 in slot 83 and tightened , its forward end extends through aperture 87 and presses against the side surface of beam 80 , preferably in one of several notches 88 ( see fig1 ) in the corresponding side surface of beam 80 , to hold it in place in slot 83 . pin stop 89 also engages with beam 80 . the second locking mechanism is provided on the opposite side of slot 83 in handle 82 . as shown in the cross sectional view in fig1 , an angled aperture 90 is provided in handle 82 having a larger diameter end section 92 , a reduced diameter center section 94 , and second reduced diameter section 96 terminating at slot 83 . in addition , a transverse slot 98 is cut out in handle 82 extending through reduced diameter center section 94 . aperture 90 receives a lock shaft 100 having a head section 102 , a non - threaded shaft section 104 , a threaded shaft section 106 , and a forward non - threaded pin section 108 . head section 102 is sized to be received in end section 92 of aperture 90 , shaft sections 104 and 106 are sized to be received in center section 94 of aperture 90 , and pin section 108 is sized to be received in section 96 of aperture 90 . lock spring 110 is placed around non - threaded shaft section 104 , while adjustor knob 112 is secured over threaded shaft section 106 in transverse slot 98 , such that turning knob 112 causes lock shaft 100 to move either forwardly or rearwardly in aperture 90 , with the forward end of pin section 108 extending into one of several similarly angle apertures 114 in beam 80 , thereby locking beam 80 in place . notches 116 aligned with apertures 114 are also provided in beam 80 , which when aligned properly with handle 82 engage teeth 117 on the inner surface of slot 83 adjacent second reduced diameter section 96 of aperture 90 . thus , the tension on beam 80 can be adjusted on one side by rotating knob 112 , and on the other side using threaded pin 86 to ensure that such tension is generally equal and further than beam 80 is locked in place . intramedullary fixation device mounting shaft 84 has a bottom section 118 that is generally square or rectangular and fits in aperture 85 in handle 82 , a slide lock receiving section 120 adjacent bottom section 118 , a short conical section 122 adjacent slide lock receiving section 120 , a second short enlarged diameter section 124 adjacent conical section 122 , and a shaft section 126 for engaging with nail 12 . cavity 128 extends through nail mounting shaft 84 , and alignment tabs 130 that engage with notches 54 in the outer end 41 of distal section 16 of nail 12 as well as notches 154 on compression disc 150 , shown in fig4 , are provided on the outer end of shaft section 126 . another slot 134 and associated notch 135 ( see fig1 ) are provided in the side surface of handle 82 adjacent aperture 85 , in which slide lock device 136 is inserted . slide lock device 136 has a head or button section 138 , a rectangular shaft section 140 having a lateral through hole 142 , and a pin section 144 extending forwardly from shaft section 140 , around which pin 144 coil spring 146 is secured . when bottom section 118 of nail mounting shaft 84 is inserted in aperture 85 , first slide lock device 136 is inserted in aperture 134 until lateral hole 142 is aligned with aperture 85 , and bottom section 118 is passed through lateral hole 142 , and slide lock receiving section 120 , which section has a width that is slightly greater than the width of shaft section 140 , is aligned in hole 142 . slide lock device 136 serves as a position stop locking device , as spring 146 causes shaft section 140 to press against the side surface of slide lock receiving section 120 , thereby locking nail receiving shaft 84 in place secured to handle 82 . when button 138 on slide lock device 136 is pressed inwardly , shaft 84 is released and outrigger assembly 20 can be swiveled or rotated with respect to shaft 84 and nail 12 in a three hundred sixty degree range around shaft 84 and nail 12 , and can be stopped and locked at ninety degree intervals . such unique feature enables the outrigger assembly to be rotated to different positions or angles around a patient &# 39 ; s legs as desired , with the nail 12 remaining stationary or fixed to the patient &# 39 ; s tibia . this may be desired in some cases where the outrigger assembly is in the surgeon &# 39 ; s way while another step or task is being performed , and allows the assembly to be moved out of the way and then back again after a task has been completed , or where the outrigger assembly must be moved in order to complete the operation . nail 12 is secured to outrigger assembly 20 as follows . the notches 54 in the lower end 41 of distal section 16 of intramedullary fixation device or nail assembly 12 are aligned in the desired position with tabs 130 on the outer end of shaft section 126 of nail mounting shaft 84 . in addition , compression disc 150 , shown in fig4 a , is positioned between lower end 41 of nail 12 and tabs 130 so that it will be held between the lower end of the nail and forward end of shaft section 126 . as shown in fig4 a , disc 150 has an aperture 152 through its center area , to accommodate shaft section 126 passing through such aperture . the purpose of disc 150 is to prevent the lower end of nail 12 from pulling upwardly into the calcaneus or heel bone when the bolt 18 is rotated to bring the distal section 16 of nail 12 upwardly to proximal section 14 . rather , with compression disc 150 abutting against the bottom surface of the patient &# 39 ; s heel , the upward movement of distal section 16 will cause the spaces between the lower end of the tibia and top surface of the talus , as well as between the bottom surface of the talus and top surface of the calcaneus , to shrink and eventually be eliminated , as shown in fig2 and 3 , and resulting in a desirably compressed ankle joint . in a preferred embodiment , the compression disc 150 is placed against the heel bone internal to the body . in an alternate embodiment , the compression disc 150 is placed against the heel bone external to the body . once alignment tabs 130 on the outer end of shaft 84 have been engaged with notches 54 on the lower end 41 of nail 12 , with compression disc 150 inserted in - between , then nail attachment device 160 is used to secure nail 12 to shaft 84 . as is best illustrated in fig1 , device 160 is comprised essentially of a knob 162 attached to one end of an elongated shaft 164 having male threads 166 on its opposite end . shaft 164 is sized to be slidably received in cavity 128 in nail mounting shaft 84 , and in addition a cavity 168 extends through shaft 164 from end to end . male threads 166 are engaged with female threads 52 on the lower end of distal section 16 of fixation device 12 , and causing nail 12 to be tightly secured to mounting shaft 84 . note also that compression bolt 18 is already positioned in nails sections 14 and 16 , and that nail 12 is in an uncompressed state . after a hole has been is drilled upwardly through the bottom of the calcaneal bone c , talus a ( if not so eroded or degraded that it no longer separates the tibia from the calcaneal bone ) and into the medullary canal the tibea t and cleaned out appropriately using techniques known to those skilled in the art , the forward end 25 of proximal section 14 of nail 12 is inserted upwardly into such hole into the tibia , also in the known manner . screw holes 170 are provided in the distal end of beam 80 , which during use of outrigger assembly 20 are aligned with holes 28 in proximal section 14 of nail 12 . similarly , similarly screw holes 172 in beam 80 will be aligned with holes 44 in distal section 16 of nail 12 , to ensure that screws 30 are properly positioned and aligned with inserted through the tibia , talus , and calcaneus . using outrigger assembly 20 , holes are then drilled into the tibia , which holes are aligned with holes 28 in nail 12 , and then screws 30 are inserted in such holes to secure proximal section 14 of nail 12 in position in the tibia . then , compression driver 24 is used rotate bolt 18 , which movement causes distal section 16 to move upwardly towards proximal section 14 . as shown in fig1 , compression driver 24 has a handle section 180 , a shaft or blade section 182 and a tip 184 which is designed to match and be received in socket 70 in the end of bolt 18 . blade section 182 is sized to slidingly fit through cavity 168 in nail attachment device 160 , and is long enough so that tip 184 can be engaged with socket 70 in bolt 18 . bolt 18 is turned so that threaded shaft section 64 is moved upwardly into threaded section 36 if proximal section 14 of nail 12 , causing distal section 16 to slowly move upwardly toward distal section 18 . as indicated above and as is best illustrated in fig3 and 4 , such movement causes the calcaneus and talus bones to also be forced to moved upwardly toward the lower end of the tibia . eventually , by continuing to rotate driver 24 to turn bolt 18 , an adequate amount of compression of the ankle joint will be accomplished , after which driver 24 may be removed from cavity 168 in mounting shaft 84 . then , the surgeon must secure the talus and calcaneus bones in such a compressed position against the lower end of the tibia , and this is accomplished by drilling the appropriate holes in the talus and calcaneus through orifices 172 in beam 80 of outrigger assembly 20 , and the inserting screws through such holes and into holes 44 in distal section 16 of nail 12 . once properly secured , nail attachment device 160 can be removed from the lower end 41 of nail 12 , and compression plate 150 will also be coincidingly removed . preferably a suitable screw threaded cap will be placed over the lower end of nail 12 on threads 52 . fig2 - 3 are exemplary embodiments of uses for the intramedullary fixation device for use in ankle arthrodesis . fig2 is a side view of the nail 12 in a non - compressed state in position within the tibia ( t ), talus ( a ) and calcaneus ( c ) bones . fig3 is the nail 12 of fig2 in a compressed state . fig4 b is the nail of fig2 in a non - compressed state along with the compression disc 150 being placed against the heel bone . fig2 and 4b also show the direction of compression . fig1 - 20 are exemplary alternate embodiments of uses for the intramedullary fixation device . fig1 is a side view of the intramedullary fixation device of the present invention as applied to an fifth metatarsal fracture in an uncompressed configuration . the proximal portion 14 of nail 12 is secured to a first portion of a metatarsal bone and the distal portion 16 of nail 12 is secured to a second portion of the metatarsal bone . the direction of compression is also shown . a compression disc 150 would also be used and placed to provide a compressive force on the bones during compression of the nail 12 but prior to the distal portion 16 being affixed to the second portion of the metatarsal bone . the compression disc 150 may be placed internal or external to the body . fig1 is a side view of the intramedullary fixation device of the present invention as applied to a long bone fracture in an uncompressed configuration . the proximal portion 14 of nail 12 is secured to a first portion of a long bone and the distal portion 16 of nail 12 is secured to a second portion of the long bone . the direction of compression is also shown . the long bone may be any bone having a fracture which would benefit from the compressive forces of nail 12 being applied thereupon . examples of a long bone include the tibia and femur . a compression disc 150 would also be used and placed to provide a compressive force on the bones during compression of the nail 12 but prior to the distal portion 16 being affixed to the second portion of the long bone . the compression disc 150 may be placed internal or external to the body . fig2 is a side view of the intramedullary fixation device of the present invention as applied to subtalar joint fusion in an uncompressed configuration . the proximal portion 14 of nail 12 is secured to the talus ( a ) and the distal portion 16 of nail 12 is secured to the calcaneus ( c ) bones . the direction of compression is also shown . a compression disc 150 would also be used and placed to provide a compressive force on the bones during compression of the nail 12 but prior to the distal portion 16 being affixed to the second portion of the calcaneus bone . the compression disc 150 may be placed internal or external to the body . while the present invention has been described at some length and with some particularity with respect to the several described embodiments , it is not intended that it should be limited to any such particulars or embodiments or any particular embodiment , but it is to be construed with references to the appended claims so as to provide the broadest possible interpretation of such claims in view of the prior art and , therefore , to effectively encompass the intended scope of the invention .

US-50047309-A

an apparatus for trapping pests is disclosed including a housing defining an internal chamber with a floor in which an entrapped pest remains until being released from the chamber , an inclined , tubular passageway spaced above the floor of said chamber that is closed at a first end and open at a second end , a space for receiving bait placed underneath the passageway , an aperture formed in the wall of the passageway and in communication with the internal chamber , and an occluding element that is insertable and displaceable within the passageway . the occluding element is upwardly displaceable upon ingress of a pest within the passageway by pressure exerted by the pest and downwardly displaceable by gravity upon passage of the pest through the aperture formed in the wall of the passageway , so that the pest is trapped within the chamber following displacement of the element below the aperture .

the present invention is a novel trap that has no moving parts for confining pests in a housing within which they are free to move about , without causing pain or suffering to the pests , whereupon they may released into a natural habitat , such as a forest , transferred to a zoo , or be destroyed . a pest is trapped by means of a gravity - actuated occluding element that is freely displaced within an inclined passageway upon passage therethrough of the pest . referring now to fig1 , one preferred embodiment of the inventive trap , generally designated as 10 , is shown . trap 10 comprises housing 5 , a plurality of inclined passageways 15 and a gravity - actuated occluding element 25 insertable into a corresponding passageway 15 . housing 5 , which is stabilized by support members 2 and 3 , is provided with a pair of sidewalls 7 having a flat bottom 8 and sides 9 and a multi - curved upper edge 11 , front wall 12 extending between , and parallel to , the two opposing sidewalls 7 , curved covering 14 , the shape of which is compatible with the contour of upper edge 11 , and removable rear portion 16 , which is configured to close , and prevent escape from , opening 17 , all of which define an internal chamber in which an entrapped pest is free to move about until being released therefrom . rear portion 16 is slidable within suitably shaped grooves 13 . covering 14 is formed with apertures 19 , to allow for the circulation of air within the chamber . housing 5 is preferably produced from injected molding to allow for cost - effective manufacturing , and may be made from transparent plastic , so that an entrapped pest may be readily visible , or alternatively , from an opaque material for those users having a weak constitution . handle 21 connected to covering 14 facilitates transportation of the housing . each passageway 15 is tubular , and is formed with a closed end 26 and an open end 27 ( fig2 a ). open end 27 of each passageway 15 is connected to front wall 12 in such a way that the passageway is inclined with respect to bottom 8 of housing 5 , with the open end being spaced above bottom 8 and the closed end being higher than the open end . aperture 22 is formed in the upper surface of each passageway , at an intermediate location between closed end 26 and open end 27 , and preferably relatively close to closed end 26 , as will be explained hereinafter , and is in communication with the internal chamber . spherical occluding element 25 is insertable within each passageway 15 , and the outer diameter of each element is substantially equal to , and less than , the inner diameter of a corresponding passageway . as a result , a pest entering a passageway cannot squeeze between element 25 and wall 34 of the passageway . after element 25 is inserted within a passageway , abutment 29 ( fig2 a ) is affixed to the inner surface of wall 34 , to thereby limit the downward displacement of element 25 and to prevent the discharge thereof from the passageway . abutment 29 is positioned on a suitable location along wall 34 , in order to ensure that at least one scent permeating hole 28 formed in the bottom of the passageway inner surface will not be covered by element 25 . occluding element 25 may be made from any suitable material having a relatively low coefficient of friction , and is preferably made from polypropylene , or any other suitable polymer that is rigid and smooth . element 25 may be solid or hollow . an exemplary occluding element is a ping - pong ball . bait for attracting a pest is placed within wedge - shaped receptacle 33 having a perforated cover 35 and a slidable rear portion 38 . the width of receptacle 33 is slightly less than rear opening 17 , to allow the receptacle to be removable from the housing so that the bait may be replaced . bait may remain within receptacle 33 for an extended period of time since the bait is inaccessible to pests confined within housing 5 . the spacing between rear portion 38 of the receptacle and cover 35 is significantly less than the body width of a pest confined within the housing . the interior of receptacle 33 is accessible to a user by upwardly sliding rear portion 38 within suitably shaped grooves . receptacle 33 is structured such that the inclination of cover 35 is substantially equal to the inclination of passageways 15 , so that perforations 37 of cover 35 will be in close proximity to scent permeating holes 28 of the passageway . a pest entering a passageway 15 will therefore smell the scent permeating through holes 28 and will upwardly push element 25 while searching for the source of the scent . receptacle 33 may be integrally formed with a tray 39 , in order to facilitate release of a confined pest , or insertion and removal of the receptacle . furthermore , pest droppings are collected on tray 39 , and cleaning of housing 5 is simplified by use of tray 39 . it will be appreciated that bait need not be placed in a receptacle , but rather may be placed in an open space underneath at least one of the passageways , as illustrated in fig2 - 4 . the following description relates to the confinement of mice , but this should be considered as a non - limitative example , since the trap is suitable for the confinement of other types of pests as well , such as rodents , snakes and insects . the efficacy of the present invention in terms of trapping mice is illustrated in fig2 a - g . mouse 31 approaches open end 27 of passageway 15 in fig2 a after smelling the scent of bait 37 through scent permeating holes 28 and jumps into the passageway in fig2 b . in fig2 c , mouse 31 searches for bait 37 and begins to push occluding element 25 upwards . element 25 is further pushed by the mouse in fig2 d and approached aperture 22 . as element 25 is additionally pushed in fig2 e , mouse 31 sees aperture 22 and thinks that bait 37 can be found by traversing the aperture . mouse 31 traverses aperture 22 in fig2 f and jumps into the chamber in fig2 g , while element 25 rolls downwards until contacting abutment 29 , thereby trapping the mouse and confining it to the internal chamber . as shown in fig3 , more than one mouse 31 may be trapped by housing 5 at a given time and confined within internal chamber 42 . each mouse may enter chamber 42 simultaneously via different passageways or successively via the same passageway , or via multiple passageways . the mice may live in coexistence within the chamber , due to the relatively large area enclosed by the housing , within which the mice can walk around and eat . after a period of time , mice 31 are released from the housing via closable opening 17 and chamber 42 may be cleaned . when being confined within chamber 42 , mice 31 seek different ways of escape therefrom , as shown in fig4 . since opening 17 is closed , rearward escape is precluded . similarly , escape through passageway 15 is also precluded , due to the presence of occluding element 25 . the trapped mice are not capable of drawing occluding element 25 towards closed end 26 of the passageway , due to the smoothness of element 25 . studies conducted by the applicant indicated that mice indeed attempted to draw the occluding element upwards , but were unsuccessful to do so . the studies further revealed that the mice were not intelligent enough to collaborate , that is a mouse standing on top of passageway 15 did not jump into the passageway during that instance that element 25 was displaced upwardly of aperture 22 , as shown in fig2 f , which would have afforded that mouse freedom . by forming aperture 22 at a position proximate to closed end 26 , the chances of escape are further reduced , since occluding element 25 downwardly rolls within a split second , before a mouse realizes that escape is possible . it was found that the illustrated configuration of the trap was successful in confining a variety of pests , including cats , snakes and cockroaches . the dimensions of the passageways and chamber were changed , relative to the size of the pest which was intended to be captured . the trapped pests were not harmed in any way , and were able to be released to their natural habitat . fig5 illustrates another embodiment of the invention wherein each passageway 47 is made from wire netting . some smaller pests such as ants may slip on a smooth passageway and therefore may not have the needed stability to displace the occluding element . the wire netting applies a reactive force to the legs of a pest that has entered a passageway . the required force applied by the pest in order to upwardly displace the occluding element is therefore reduced , resulting in a greater number of pests that can upwardly displace the element and be trapped after entering the chamber via aperture 49 . in order to provide optimal stability to pests entering a passageway , the mesh count , or the number of metal wires per linear inch , is predetermined , depending on the size of the intended pest to be confined . by employing wire netting , dirt and sand clinging to the body of a pest may fall through the open space between parallel wires to the floor of the internal chamber . without use of wire netting , the dirt and sand is liable to accumulate within a passageway and prevent the occluding element from rolling downwards , after being upwardly displaced , due the sand and / or dirt which would be interspersed between the occluding element and the wall of the passageway and cause an increase in the frictional force applied to the element . while some embodiments of the invention have been described by way of illustration , it will be apparent that the invention can be carried into practice with many modifications , variations and adaptations , and with the use of numerous equivalents or alternative solutions that are within the scope of persons skilled in the art , without departing from the spirit of the invention or exceeding the scope of the claims .

US-29711005-A

an appliance and methods are described that include embodiments of a mandibular advancement or positioning device which can use elastic bands to pull the jaw forward . the appliance has an upper plastic tray conforming to the patient &# 39 ; s upper teeth and including a set of retention hooks coupled to the upper plastic tray via being encased in plastic , one on the right and one on the left anterior buccal portion of an upper plastic base . the appliance also has a lower plastic tray conforming to the patient &# 39 ; s lower teeth and has a set of bite pads integrated with a second set of plastic retention hooks encased in plastic extending outwardly from the tooth . the appliance includes the upper and lower plastic trays and specially formed elastic bands of a plurality of lengths and strengths replaceably attached to the retention hooks on both sides of the trays to pull the mandible forward for treatment .

embodiments herein relate to methods and systems for manufacturing an oral appliance that requires only a single office visit . during the office visit , a patient can be fitted for an oral appliance by first obtaining an upper ( maxillary ) and lower ( mandibular ) impression of the teeth and supporting soft tissue including the upper hard palate . this impression must be extremely accurate to avoid tooth soreness , and / or movement when the appliance is placed in the patient &# 39 ; s mouth . the impression is taken by : ( 1 ) having the patient rinse with a pre - impression mouth wash to eliminate any saliva distortion ; and ( 2 ) pouring the impressions immediately to avoid distortion using a hard lab stone . referring now to fig1 , the impressions are used to make a mode of the patient &# 39 ; s teeth 110 and 112 . the model 110 and 112 are then altered by temporarily attaching a first set of retention hooks to the mode of the patient &# 39 ; s upper teeth . the attachment can be by dental wax , glue , such as a polymer glue or super glue . the retention hooks are placed between the cuspid and first bicuspid on the upper model . next , with the upper models held in centric occlusion with the lower model , a measuring device can be placed over the upper retention hook and with a fine point “ sharpie ”™ pen to scribe a mark on the lower model 23 , 25 , 27 mm , depending on the size of the patient &# 39 ; s dental arch . referring to fig1 , marks 120 and 130 illustrate possible locations for marking models 110 and 112 . in one embodiment , a kit including an appropriate measuring device can be included to enable proper placement of the marks . referring to fig2 , in one embodiment , lower bite pads 220 are temporarily attached . the lower bite pads 220 can be integrated with a second set of retention hooks 230 . a scribed line on the lower model in one embodiment can be under the center of the second set of retention hooks and the top portion of the bite pad and should be level with the bite pad on the opposite side of an arch . in one embodiment , the displacement between the corresponding retention hook of the second set of retention hooks and the corresponding retention hook of the first set of retention hooks can be 23 , 25 , or 27 millimeters displaced as measured from center to center . referring to fig3 , a view 300 of the appliance , including both upper and lower trays , illustrates line 320 , as a measurement between retention hooks on one side of the trays . next , in a machine typically seen in a dentist &# 39 ; s office , such as a thermo - plastic machine 400 shown in fig4 . the dentist can place sheets of plastic 410 in the machine so that upon heating and applying a vacuum , the sheets are pulled down over the model 420 of the patient &# 39 ; s upper and lower teeth , one at a time , with the temporarily attached first set of retention hooks and the set of bite pads integrated with the second set of retention hooks . the machine can operate on the upper and lower teeth models separately , as will be appreciated by those skilled in the art . the heated plastic 410 encases , via vacuum sealing , each of the upper and lower teeth models and the retention hooks and bite pads to form upper and lower plastic trays adapted to fit over the teeth of the patient with the retention hooks and bite pads encased by the plastic . in one embodiment , the bite pads can be placed to create an 8 mm anterior vertical opening between the upper and lower teeth to assist with treating sleep apnea . information can be obtained from the patient as to any pressures on the teeth or gingiva . also , in an embodiment , the appliance , including both upper and lower trays , can be checked for comfort and evenness of opening from side to side with the patient . if pressures are felt by the patient on any tooth or any area of the gingiva , then these areas can be carefully relieved . some reasons for pressure on the teeth or gums include the following : ( 1 ) an inaccurate impression ; and / or ( 2 ) a warped model . advantageously , in a single office visit , there is generally no concern of intervening tooth movement or dental work since the impression can be obtained and the appliance manufactured on a same visit . the machine 400 can be a thermo plastic machine , a vacuum - forming machine or the like . for example , the machine 400 can be configured to heat the sheets of plastic and vacuum seal the models of the upper and lower teeth to encase the temporarily attached first set of retention hooks , both right and left , and the set of bite pads integrated with the second set of retention hooks , both right and left as shown in fig1 . after the plastic is vacuum sealed over the models , bite pads and retention hooks , the trays formed by the plastic are removed from the models . removal can be accomplished by cutting with scissors , a dental burr , or a knife or other sharp implement . in an embodiment , the removal of the trays from the models causes the temporarily attached retention hook and bite pads to be released from the models and become integrated with the plastic trays created by the vacuum sealing process . referring to fig5 , to insure proper release from the models , in one embodiment , the retention hooks are formed such that each retention hook includes an edge 510 that enables the plastic 520 to seal around each retention hook to prevent the retention hooks from remaining attached to the respective model . in an embodiment , edge 510 can include a groove or other shape that enables the retention hooks to become secured by the plastic around the circumference of each retention hook to insure detaching of each retention hook from each model . likewise , referring to fig6 , retention hook includes an edge 610 to enable plastic 620 to encase the hook and bite pad combination to prevent the retention hook and bite pad combination from remaining attached to a model . edge 610 can be a groove or other shape that insures detachment from the model . likewise , each bite pad can be configured with a groove or the like to assist removing of the bite pad from the model . referring to fig7 , shown is an embodiment of the final appliance 700 including encased first set of retention hooks 720 and set of bite pads 730 integrated with the second set of retention hooks from the models to form a dental appliance 700 including both upper and lower trays . fig7 illustrates an embodiment including elastic bands 750 that couple the first tray and the second tray to enable the appliance 700 to treat sleep apnea . the vacuum forming over the retention hooks encases the retention hooks and the bite pads such that upon cooling , the appliance includes the retention hooks such that elastic bands 750 can be securely placed over the retention hooks during treatment . the appliance 700 created with plastic covering the retention hooks and bite pads enables attachment of a pair of elastic bands 750 to be removably placed over the first and second sets of encased retention hooks to create a sleep apnea appliance , as shown in fig7 . in one embodiment , the bite pads can be configured with one or more grooves and / or edges such that the plastic covering the retention hooks and bite pads does not prevent “ snap on ” bite pad extensions from being placed on each of bite pads . thus , as shown in fig7 , bite pads 730 can include bite pad extensions that enable the bite pads to increase the vertical displacement between the upper and lower trays . in one embodiment , at least three different snap on bite pad extensions of various thicknesses can be configured to snap over the encased bite pads on the bottom tray to increase the amount of vertical displacement of the lower jaw when the appliance is worn . thus , if successful treatment for sleep apnea is not obtained with the vertical displacement rendered by the plastic - encased bite pads of the lower jaw , adequate vertical displacement can be obtained by temporarily snapping one of a plurality of thicknesses of “ snap on bite extensions ” over the encased bite pads . in one embodiment , the choice of size of bite pad extension can be in accordance with a determined patient comfort including much air flow and efficacy . in one embodiment , a bite pad extension can be permanently secured via a thin mix of orthodontic acrylic or a thin mix of light cure material . to permanently secure the bite pad extension , a prepared mix can be placed inside a dry “ snap on bite pad extension ”. after firmly securing the extension over a dry encased bite pads right & amp ; left , mix material can escape through two holes in the bit pad extension to enable proper sealing . the lower appliance with extensions on the bite pads can be cured as is known for acrylic material or cured with a light can . after bite pad extensions , if necessary , are attached over the encased bite pads to add vertical opening , a patient using the appliance can be fitted with a different appliance with known advancement and vertical opening for successful treatment via a permanent appliance . while particular aspects of the present subject matter described herein have been shown and described , it will be apparent to those skilled in the art that , based upon the teachings herein , changes and modifications may be made without departing from this subject matter described herein and its broader aspects and , therefore , the appended claims are to encompass within their scope all such changes and modifications as are within the true spirit and scope of this subject matter described herein . furthermore , it is to be understood that the invention is solely defined by the appended claims . it will be understood by those within the art that , in general , terms used herein , and especially in the appended claims ( e . g ., bodies of the appended claims ) are generally intended as “ open ” terms ( e . g ., the term “ including ” should be interpreted as “ including but not limited to ,” the term “ having ” should be interpreted as “ having at least ,” the term “ includes ” should be interpreted as “ includes but is not limited to ,” etc .). it will be further understood by those within the art that if a specific number of an introduced claim recitation is intended , such an intent will be explicitly recited in the claim , and in the absence of such recitation no such intent is present . for example , as an aid to understanding , the following appended claims may contain usage of the introductory phrases “ at least one ” and “ one or more ” to introduce claim recitations . however , the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “ a ” or “ an ” limits any particular claim containing such introduced claim recitation to inventions containing only one such recitation , even when the same claim includes the introductory phrases “ one or more ” or “ at least one ” and indefinite articles such as “ a ” or “ an ” ( e . g ., “ a ” and / or “ an ” should typically be interpreted to mean “ at least one ” or “ one or more ”): the same holds true for the use of definite articles used to introduce claim recitations . in addition , even if a specific number of an introduced claim recitation is explicitly recited , those skilled in the art will recognize that such recitation should typically be interpreted to mean at least the recited number ( e . g ., the bare recitation of “ two recitations ,” without other modifiers , typically means at least two recitations , or two or more recitations ). furthermore , in those instances where a convention analogous to “ at least one of a , b , and c , etc ,” is used , in general such a construction is intended in the sense one having skill in the art would understand the convention ( e . g ., “ a system having at least one of a , b , and c ” would include but not be limited to systems that have a alone , b alone , c alone , a and b together , a and c together , b and c together , and / or a , b , and c together , etc .). in those instances where a convention analogous to “ at least one of a , b , or c , etc .” is used , in general such a construction is intended in the sense one having skill in the art would understand the convention ( e . g ., “ a system having at least one of a , b , or c ” would include but not be limited to systems that have a alone , b alone , c alone , a and b together , a and c together , b and c together , and / or a , b , and c together , etc .). it will be further understood by those within the art that any disjunctive word and / or phrase presenting two or more alternative terms , whether in the description , claims , or drawings , should be understood to contemplate the possibilities of including one of the terms , either of the terms , or both terms . for example , the phrase “ a or b ” will be understood to include the possibilities of “ a ” or “ b ” or “ a and b .” the herein described aspects depict different components contained within , or connected with , different other components . it is to be understood that such depicted architectures are merely exemplary , and that in fact many other architectures can be implemented which achieve the same functionality . in a conceptual sense , any arrangement of components to achieve the same functionality is effectively “ associated ” such that the desired functionality is achieved . hence , any two components herein combined to achieve a particular functionality can be seen as “ associated with ” each other such that the desired functionality is achieved , irrespective of architectures or intermedical components . likewise , any two components so associated can also be viewed as being “ operably connected ” or “ operably coupled ,” to each other to achieve the desired functionality . any two components capable of being so associated can also be viewed as being “ operably couplable ” to each other to achieve the desired functionality . specific examples of operably couplable include but are not limited to physically mateable and / or physically interacting components and / or wirelessly interactable and / or wirelessly interacting components and / or logically interactable and / or logically interacting components . while certain features of the described implementations have been illustrated as disclosed herein , many modifications , substitutions , changes and equivalents will now occur to those skilled in the art . it is , therefore , to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the embodiments of the invention .

US-201113520520-A

an intravascular implant and methods of using the implant within the vasculature of the body , for example near a vascular aneurysm , are disclosed . a method of treating an aneurysm includes positioning a vascular graft comprising a tubular channel having a first end and a second end in a blood vessel , securing the vascular graft in place with an expandable anchoring member , and filling a seal cuff on the vascular graft , wherein the seal cuff extends radially outward beyond an exterior surface of the vascular graft , wherein the seal cuff comprises a first seal portion and a second seal portion and wherein the first seal portion is separated from the second seal portion by a first gap and a second gap along a circumference of the seal cuff .

fig1 illustrates an embodiment of an intravascular implant 2 . the implant 2 can have a connector 4 having a first end 6 and a second end 8 . the first end 6 can be attached to an anchor 10 . the anchor 10 can have a central tip 12 . the central tip 12 can be attached to the first end 6 . the anchor 10 can also have multiple tines or arms 14 extending radially from the central tip 12 , such as in an uncovered umbrella structure . the central tip 12 can be rotatably or flexibly attached to the arms 14 . leaves 16 can be attached at two ends to adjacent anus 14 . a flow - through area 18 can be an open port defined by any leaf 16 and the arms 14 to which that leaf 16 attaches . the second end 8 can be attached to a seal 20 . the second end 8 can attach to the seal 20 through an attachment device 22 , for example struts . the attachment device 22 can be integral with the second end 8 , integral with the seal 20 , or an independent part . attachment devices 22 can also be used to attach the connector 4 to the anchor 10 . the seal 20 can have a first proximal end 24 and a first distal end 26 . a second implant 28 can be attached to the seal 20 , for example at the distal end 26 , or the second implant 28 can be an integral part of the seal 20 . fig2 illustrates a single gasket embodiment of the seal 20 . the seal 20 can have a first seal ring 30 at the proximal end 24 . the seal 20 can also have a second seal ring 32 at the distal end 26 . the seal rings 30 and 32 can have radially extending spring force elements or tissue mainstays 33 . the tissue mainstays 33 can be , for example a barb , spike , hook , peg , a coil , pigtail or leaf spring , or any combination thereof . the seal rings 30 and 32 can be made from nickel - titanium alloy ( e . g ., nitinol ), titanium , stainless steel , cobalt - chrome alloy ( e . g ., elgiloy ® from elgin specialty metals , elgin , ill . ; conichrome ® from carpenter metals corp ., wyomissing , pa . ), polymers such as polyester ( e . g ., dacron ® from e . i . du pont de nemours and company , wilmington , del . ), polypropylene , polytetrafluoroethylene ( ptfe ), expanded ptfe ( eptfe ), polyether ether ketone ( peek ), nylon , extruded collagen , silicone , radiopaque materials , or any combination thereof . examples of radiopaque materials are barium , sulfate , titanium , stainless steel , nickel - titanium alloys and gold . the seal 20 can have a first seal cover 34 attached at the proximal end 24 to the first seal ring 30 and at the distal end 26 to the second seal ring 32 . the seal cover 34 can be made from polymers such as polyester ( e . g ., dacron ® from e . i . du pont de nemours and company , wilmington , del . ), polypropylene , ptfe , eptfe , peek , nylon , polylactic acid ( pla ), poly ( lactic - co - glycolic acid ) ( plga ), polyglycolic acid ( pga ), polyurethane , polyethylene , vascular , valvular or pericardial tissue , extruded collagen , silicone , metal mesh , radiopaque materials , or any combination thereof . a seal flow port 36 can be the hole defined by the inner radii of the seal rings 30 and 32 and the seal cover 34 . the seal 20 can have a seal diameter 38 that can depend on the diameter of the vessel in a given patient . the seal diameter 38 can be from about 5 mm ( 0 . 2 in .) to about 50 mm ( 2 . 0 in . ), for example about 30 mm ( 1 . 2 in .). the seal 20 can have a seal height 40 from about 1 mm ( 0 . 04 in .) to about 6 cm ( 2 . 4 in .). fig3 illustrates an embodiment of the seal 20 that can have a first gasket 42 and a second gasket 44 . such a design can incrementally decrease the pressure across a given length so no one gasket 42 or 44 endures the entire pressure . the first gasket 42 can be similar to a single gasket seal embodiment illustrated in fig2 , except that the first seal cover 34 can be attached to the second seal ring 32 at a first gasket distal end 46 . the second gasket 44 can have a second seal cover 48 . the second seal cover 48 can be attached at a second gasket proximal end 50 to the second seal ring 32 and / or the second seal cover 48 can be integral with the first seal cover 34 . the second seal cover 48 can also attach at the distal end 26 to a third seal ring 52 . fig4 illustrates an embodiment of the seal rings 30 , 32 and 52 ( shown as 30 ). the seal ring 30 can have diametrically opposed thin sections 54 and diametrically opposed thick sections 56 . the seal ring 20 can have a seal ring thickness 58 that can vary from a minimum in the thin sections 54 to a maximum in the thick sections 56 . the seal ring 30 can also have a constant thickness along the entire circumference of the seal ring 30 . the seal ring 30 can also have a gap in the circumference of the seal ring 30 , forming a “ c ”- ring ( not shown ) as known to one having ordinary skill in the art . fig5 illustrates an embodiment of the seal 20 that can have a seal volume 60 . the seal volume 60 can be a bladder or collar filled by a fluid , for example saline , plasma , helium , oxygen , radiopaque materials ( including small pieces of solids ), blood , epoxy , glue , or any combination thereof . the bladder can be inflated in vivo by a method known to those having ordinary skill in the art . the seal volume 60 can also be a solid , for example polymers such as polyester ( e . g ., dacron ® from e . i . du pont de nemours and company , wilmington , del . ), polypropylene , ptfe , eptfe , peek , nylon , polylactic acid ( pla ), poly ( lactic - co - glycolic acid ) ( plga ), polyglycolic acid ( pga ), polyurethane , polyethylene , vascular , valvular or pericardial tissue , extruded collagen , silicone , radiopaque materials , or any combination thereof . a first and / or second seal flow ports 62 and 64 , respectively , can be defined , for example as cylinders , within the seal volume 60 . once deployed , multiple seal flow ports 62 and 64 can attach to multiple second implants 28 , or multiple legs of the second implant 28 that can extend distal of the seal into the iliac arteries . a connector port 66 can also be defined , for example as a cylinder , within the seal volume 60 . the second end 8 of the connector 4 can be placed into the connector port 66 . the seal volume 60 can be inflated after the second end 8 is placed into the connector port 66 to constrict and pressure fit the connector port 66 around the second end 8 , thereby fixedly attaching the seal 20 to the connector 4 . fig6 illustrates an embodiment of the seal 20 that can have a helical seal coil 68 having a first end 70 and a second end 72 . the ends 70 and 72 can be dulled , for example by attaching small balls as shown . the seal coil 68 can have a number of turns 74 , for example from about 1 . 25 turns 74 to about 50 turns 74 , for example about 5 turns 74 . fig7 illustrates an embodiment of the seal 20 that can have a structure similar to the anchor illustrated in fig1 but with a vertically inverted orientation . fig8 illustrates an embodiment of the seal 20 that can have a first seal ring 30 and a second seal ring 32 that are mechanically insulated from each other . this structure enables the seal rings 30 and 32 to fit to more easily fit and seal an irregularly shaped vessel . a first hub 76 can be fixedly attached or rotatably attached to first seal struts 78 and a center beam 80 . the first seal struts 78 can slidably connect on the outside or inside of the first seal ring 30 at free points 82 . the first seal struts 78 can be fixedly or rotatably attached to the second seal ring 32 at fixation points 84 . the first seal struts 78 can be fixedly attached or rotatably attached to a first collar 86 . the first collar 86 can be slidably attached to the center beam 80 . a second hub 88 can be fixedly attached or rotatably attached to second seal struts 90 and the center beam 80 . the second seal struts 90 can slidably connect on the outside or inside of the second seal ring 32 at the free points 82 . the second seal struts 90 can be fixedly or rotatably attached to the first seal ring 30 at the fixation points 84 . the second seal struts 90 can be fixedly attached or rotatably attached to a second collar 92 . the second collar 86 can be slidably attached to the center beam 80 . the seal struts 78 and 90 , the hubs 76 and 88 , and the collars 86 and 92 can be from the same materials as the seal rings 30 , 32 and 52 . the seal rings 30 and 32 can be wave - shaped . fig9 illustrates a top view of one embodiment of the wave - shaped seal ring 30 , showing a circular shape from above . fig1 illustrates a side view of the wave - shaped seal ring 30 illustrated in fig8 and 9 , showing two periods of smooth oscillation in a seal ring height 94 . fig1 illustrates an embodiment of the seal ring 30 that can have sharp oscillations in the seal ring height 94 . angled seal ring struts 96 can form the seal ring 30 into a zigzag . fig1 illustrates a seal ring 30 that can have a combination of alternating lock zones 98 and angled seal ring struts 96 . the lock zones 98 can be substantially parallel to the circumference of the seal ring 30 . fig1 illustrates an embodiment of cross - section a - a ( shown in fig1 ) of the intravascular implant 2 without the seal 20 . the anchor 10 can have connectors 4 attached to the arms 14 . the second end 8 of each connector 4 can have an integral attachment device 22 . the attachment device 22 can be made of a slide 100 and an interference piece 102 defining a catch 104 there between . the slide 100 can have a slide angle 106 from about 90 ° to about 180 °. the slide 100 can also have a slide height 108 from about 0 . 38 mm ( 0 . 015 in .) to about 6 . 35 mm ( 0 . 250 in . ), for example about 3 . 18 mm ( 0 . 125 in .). the interference piece 102 can have an interference piece depth 110 from about 0 . 38 mm ( 0 . 015 in .) to about 4 . 95 mm ( 0 . 195 in .). the slide 100 and interference piece 102 can be from the same materials as the seal rings 30 , 32 and 52 or seal covers 34 and 48 . fig1 illustrates an embodiment of the intravascular implant 2 . the anchor 10 can have a solid ring , and can be fixedly or rotatably attached to about two or more connectors 4 . the seal ring 30 can be vertically surrounded by the slides 100 and the interference pieces 102 . the seal ring 30 can , therefore , be engaged in the catch 104 and fixedly attached to the connectors 4 . fig1 illustrates an embodiment of the attachment device 22 . the attachment device 22 can have first and second slides 100 a and 100 b , first and second interference pieces 102 a and 102 b , a catch 104 defined by the slides 100 a and 100 b and the interference pieces 102 a and 102 b . the attachment device 22 can also have a rod slot 112 defined between the first slide 100 a and second slide 100 b , and between the first interference piece 102 a and the second interference piece 102 b . fig1 illustrates an embodiment of cross - section b - b ( shown in fig6 ) of the seal 20 . the two turns of the coil 68 can define the catch 104 . the coil 68 can have a coil wire diameter 114 from about 0 . 03 mm ( 0 . 001 in .) to about 1 . 3 mm ( 0 . 050 in . ), for example about 0 . 64 mm ( 0 . 025 in .). fig1 illustrates an embodiment of the connector 4 that can be attached to the attachment devices 22 , that can be , in turn , attached to the seal 20 . the connector 4 can be a flexible wire , coil , rod or combinations thereof and can be hollowed . the connector 4 can also be threaded to rotatably fit the anchor 10 and seal 20 or attachment device 22 . the connector can be made from any material listed for the anchor 10 . the attachment devices 22 can be wires , coils , rods or combinations thereof . the connector 4 can also be directly attached to the seal 20 . the connector 4 can be attached to the attachment devices 22 at a connector interface 116 . the connector interface 116 can have a hub , slider , or collar . the connector interface 116 can be a direct attachment . the connector 4 and attachment device 22 can also be an integral part . the seal 20 and attachment device 22 can also be an integral part . fig1 illustrates an embodiment of the connector 4 that can be made from a helical connector coil 118 . the connector coil 118 can be made from a wire , for example a guidewire , having a diameter from about 0 . 46 mm ( 0 . 018 in .) to about 2 . 54 mm ( 0 . 100 in .). fig1 illustrates an embodiment of the connector 4 that can be made from the connector coil 118 and a connector wire or rod 120 . the connector wire or rod 120 can also be made from a wire , for example a guidewire , having a diameter from about 0 . 46 mm ( 0 . 018 in .) to about 2 . 54 mm ( 0 . 100 in .). fig2 illustrates an embodiment of the connector 4 that can have sharp oscillations in connector width . angled connector struts 124 can form the connector 4 into a zigzag . fig2 illustrates an embodiment of the intravascular implant 2 that can a longitudinal axis 126 . the attachment device 22 can attach the connector 4 to the anchor 10 such that the first end 6 can be substantially on the longitudinal axis 126 . the second end 8 can attach to the seal 20 substantially along a radial perimeter of the seal 20 . fig2 illustrates an embodiment of the intravascular implant 2 that can have the attachment device 22 attach the connector 4 to the seal 20 such that the second end 8 can be substantially on the longitudinal axis 126 . the first end 6 can attach to the anchor 10 substantially along a radial perimeter of the anchor 10 . fig2 illustrates an embodiment of the intravascular implant 2 that can have multiple connectors 4 . the connectors 4 can rotatably or fixedly attach to each other near their centers at joint points 128 . joined pairs of connectors 4 can form x - beams 128 . the x - beams 128 can define transverse flow ports 132 . fig2 illustrates an embodiment of the anchor 10 shaped as a helical anchor coil 134 having a first end 136 and a second end 138 . the ends 136 and 138 can be dulled , for example by attaching small balls as shown . the seal coil 134 can have from about 1 turn 140 to about 10 turns 140 , for example about 4 turns 140 . the anchor 10 can also have an anchor width 142 from about 5 mm ( 0 . 2 in .) to about 50 mm ( 2 in .). the anchor 10 can also have an anchor height 144 . fig2 illustrates an embodiment of the anchor 10 . the anchor 10 can have the central tip 12 , the arms 14 , and the leaves 16 as shown and described in fig1 . the arms 14 can also extend radially beyond each attachment point 146 of each arm 14 and each leaf 16 to form a diminishing spring force element or tissue mainstay 148 . the spring force elements or tissue mainstays 148 on the anchor 10 can be the same material and design as the tissue mainstays 33 on the seal 20 , and vice versa . anchor collar 150 can be slidably mounted to the connector 4 to radially extend or contract the arms 14 and to adjust the height between the anchor 10 and the seal 20 to better place the implant 2 with regard to the transverse vessels , for example the renal arteries , and vascular wall abnormalities . the anchor collar 150 can be fixedly or rotatably attached to arm supports 152 . the arm supports 152 can be fixedly or rotatably attached to the arms 14 at support points 154 . the arm supports 152 can also be an integral part of the anchor collar 150 and / or the arms 14 . the central tip 12 , arms 14 , leafs 16 , mainstays 148 , and arm supports 152 can be made from the same materials listed for the seal rings 30 , 32 and 52 . fig2 illustrates a top view of an embodiment of anchor 10 . each leaf 16 can have a first leaf end 156 and a second leaf end 158 . the first leaf end 156 of one leaf 16 can merge with the second leaf end 158 of the neighboring leaf 16 and the intermediate arm 14 into a cover 160 . the cover 160 can be a cylinder with two open ends . the leaf 16 , first leaf end 156 , second leaf end 158 and cover 160 can be fixedly or rotatably attached . the first leaf end 156 and the second leaf end 158 can terminate within the cover 160 . when deployed , the leaf 16 can press against the vascular wall to maintain a substantially circular cross - section of the vessel . fig2 illustrates an embodiment of the intravascular implant 2 having the arms 14 supported at support points 154 by the connectors 4 . the seal 20 can also be radially collapsible and expandable . fig2 and 29 illustrate embodiments of the intravascular implant 2 that can have a first anchor 10 and a second anchor 162 . the second anchor can be fixedly or rotatably attached to connectors 4 at support points 154 . the second anchor 162 can also be vertically inverted with respect to the first anchor , as shown in fig2 . the tissue mainstays 33 , shown in fig2 , can be directly attached to the seal rings 30 , 32 or 52 by , for example , melting , screwing , gluing , welding or use of an interference fit or pressure fit such as crimping , or combining methods thereof , to join the connector 4 to the seal 20 . the tissue mainstays 33 and the seal rings 30 , 32 or 52 can be integrated , for example , by die cutting , laser cutting , electrical discharge machining ( edm ) or stamping from a single piece or material . the connector interface 116 , shown in fig1 , can also directly attach to the connector 4 and the seal 20 or be integrated thereto by any method listed for the tissue mainstays 33 and the seal rings 30 , 32 or 52 . the arm supports 152 , shown in fig2 , can also be integrated with the anchor collar 150 and / or the arms 14 by any method listed for the tissue mainstays 33 and the seal rings 30 , 32 or 52 . as shown in fig2 , the leaf 16 , first leaf end 156 , second leaf end 158 and cover 160 can be fixedly or rotatably attached or integrally formed by any by any method listed for the tissue mainstays 33 and the seal rings 30 , 32 or 52 . as shown in fig1 , the connector coil 118 and connector rod 120 can be attached at the first connector end 6 and the second connector end by methods known to one having ordinary skill in the art . integrated parts can be made from pre - formed resilient materials , for example resilient alloys ( e . g ., nitinol , elgiloy ®) that are preformed and biased into the post - deployment shape and then compressed into the deployment shape . any elongated parts used in the intravascular implant 2 and the second implant 28 , for example the tip 12 , the arms 14 , the leafs 16 , the attachment devices 22 , the seal rings 30 , 32 and 52 , the seal coil 68 , the connector coil 118 , the connector rod 120 , the connector strut 124 , the anchor coil 134 and the arm supports 152 , can be ovalized , or have an oval cross section where necessary , to ease crimping with other parts . the intravascular implant 2 can be collapsed or compressed into a deployment configuration to enable minimally invasive implantation into the vasculature of a patient . fig3 illustrates one embodiment of compressing the seal ring 30 , as shown in fig4 , by applying outward radial forces , as shown by arrows 164 , to the thin sections 54 and / or by applying an inward radial force , as shown by arrows 166 , to the thick sections 56 . other embodiments can be compressed by applying inward radial forces spread around the circumference of the implant and / or other methods known to those having ordinary skill in the art . the intravascular implant 2 can be loaded into a delivery catheter 168 by methods known to those having ordinary skill in the art . because the design of the intravascular implant 2 can separate the anchor 10 from the seal 20 , a low profile catheter can be used to deliver the intravascular implant 2 . as illustrated in fig3 , the delivery catheter 168 can be positioned , as shown by the arrow , at a vascular site 170 using a guidewire ( not shown ) and an “ over - the - wire ” delivery method , known to those having ordinary skill in the art . a control line 172 can also extend distally from the implant 2 . the control line 172 can include controls used to manipulate any part of the intravascular implant 2 such as rotating the seal 20 , expanding or contracting the arms 14 , or separating delivery devices from the implant 2 , and / or to deliver a substance such as a medication or radiopaque material , and / or to receive signals such as optical or electrical signals . the vascular site 170 can be adjacent to a vascular aneurysm 174 , for example an abdominal aortic aneurysm , having a proximal neck 176 and transverse vessels 180 , for example renal arteries , proximal to the vascular aneurysm 174 . fig3 illustrates that the catheter 168 can be partially distally retracted , as shown by arrows 182 , thereby exposing the arms 14 while retaining the seal 20 . once exposed , the arms 14 can expand radially , as shown by arrows 184 . expansion of the arms 14 can occur due to resilient material expansion or mechanical manipulation . the tissue mainstays 148 can seat in the wall of the vascular site 170 proximal to the transverse vessels 180 , preventing the anchor 14 from moving distally . multiple , independent arms 14 can adjust to the surrounding vasculature geometry to fit as needed for secure attachment to the vascular wall . the distance between the central tip 12 and the seal 20 can be an effective connector length 186 . the effective connector length 186 can be adjusted after the tissue mainstays 148 have been seated in the wall of the vascular site 170 . the effective connector length 186 can be adjusted by rotating the seal 20 , as shown by arrows 188 , along a threaded connector 4 . fig3 illustrates that the arms 14 can be contracted , as shown by arrows 190 . the anchor 10 can then be easily repositioned , as shown by arrows 192 . the intravascular implant 2 can be made from or combined with radiopaque materials and markers to aid the placement , adjustments and repositioning of the intravascular implant 2 and associated parts with the use of an angiogram . fig3 illustrates an embodiment of the connector 4 and the anchor 10 that can have a contraction line 193 releasably connected to the anchor collar 150 . contraction line 193 can be formed of coaxial hypotubes . contraction line 193 can also be part of control line 172 . the arms 14 can be biased to radially expand or radially contract . fig3 illustrates that the contraction line 193 can be pulled , as shown by arrow 194 , which can result in a distal movement of the anchor collar 150 , as shown by arrow 196 . the distal movement of the anchor collar 150 can cause the arm supports 154 and , in turn , the arms 14 to rotate inward and radially contract , as shown by arrows 198 . the above process can be reversed and the arms 14 can be radially expanded . the contraction line can be separated from the anchor collar 150 when placement of the anchor 10 is finalized . fig3 illustrates an embodiment of the connector 4 and the anchor 10 that can have a fixed hub 200 that is fixedly held in space , for example by the seal 20 , the delivery catheter 168 and / or the control line 172 , distal to the anchor collar 150 . the fixed hub 200 can also be slidably connected to the connector 4 . fig3 illustrates that the connector 4 can be pulled distally , as shown by arrow 202 , which can cause the anchor collar 150 to butt against the fixed hub 200 and be forced proximally with respect to the connector 4 , as shown by arrow 204 . the proximal movement of the anchor collar 150 can cause outward rotation and radial expansion of the arm supports 154 and , in turn , the arms 14 , as shown by arrows 206 . the above process can be reversed and the arms 14 can be radially contracted . the arms 14 can be locked into place by methods known to those having ordinary skill in the art . fig3 illustrates that the catheter 168 can be retracted distally of the seal 20 , as shown by arrows 208 . retracting the catheter 168 can expose the seal 20 , allowing the seal 20 to radially expand , as shown by arrows 210 . the seal 20 can be placed to seat in the proximal neck 176 . when fully deployed , the intravascular implant 2 can have an open - walled structure , and can therefore be placed adjacent to the transverse vessels 180 without interfering with the flow through the transverse vessels 180 . fig3 illustrates the intravascular implant 2 that can be implanted in the vascular site 170 . the distal end 26 can be attached to a second implant 28 , for example a vascular graft such as an abdominal aortic aneurysm graft , for example a gel weave aortic graft . the second implant 28 can have two branching legs 212 . fig4 illustrates a cross - section of an embodiment of the attachment device 22 and second end 8 of the seal 4 . the seal ring 30 can be proximal to the slides 100 . the seal cover 34 or the second implant 28 can extend from the seal ring 30 . fig4 illustrates pulling the seal ring 30 along the slides 100 , as shown by arrows 214 . movement of the seal ring 30 along the slides 100 can cause the seal ring to radially contract , as shown by arrows 216 . once the seal ring 30 is distally clear of the slides 100 , the seal ring 30 can radially expand , as shown by arrows 218 , and seat into the catch 104 . once in the catch 104 , the seal ring 30 can be held vertically in place by the distal side of the slide 100 and the proximal side of the interference piece 102 . as illustrated in fig4 , the second implant 28 can be attached to the seal ring 30 at the proximal end of the second implant 28 . the seal ring 30 can be releasably attached to deployment rods 220 . as illustrated in fig4 , the deployment rods 220 can be used to position the seal ring 30 proximal to the attachment device 22 and so that the deployment rods 220 align into the rod slots 112 . ( the second implant 28 is not shown in fig4 for clarity ). the deployment rods 220 can be pulled distally , as shown by arrow 222 , thereby moving the seal ring 30 distally . as illustrated in fig4 , the seal ring 30 can then seat into the catch 104 . the deployment rods 220 can be detached from the seal ring 30 and removed from the vascular site 170 . the control line 172 can be removed from the vascular site 170 whenever removal is deemed appropriate during the implantation procedure . fig4 illustrates an embodiment of the intravascular implant 2 deployed at a vascular site 170 . the vascular site 170 can have a severely tortuous region over which the implant 2 is placed . the flexibility of the connector 4 compensates for the contortion in the vascular site , enabling the arms 14 to intersect the wall of the vascular site 170 at a substantially perpendicular angle , and enabling the seal 20 to seat into the proximal neck 176 to open into the at a substantially parallel angle to the body of the second implant 28 . stress and fractures in the intravascular implant 2 and in the tissue at the vascular site 170 can be minimized due to the anchor 10 being mechanically insulated from the seal 20 by use of the connector 4 . additionally , stresses can be reduced because the tissue in the vascular site 170 adjacent to the anchor 10 does not need to seal , and the tissue in the vascular site 170 adjacent to the seal 20 does not need to anchor . additional intravascular implants 2 , as shown , can be deployed at the distal ends 224 of the second implant 2 , for example in the iliac arteries , to additionally secure the second implant 2 . the arms 14 and / or the seal 20 can apply chronic stress to the adjacent tissue in the vascular site 170 causing a controlled migration of the arms 14 and / or seal 20 into the wall of the vascular site 170 to a specified depth predetermined by the tissue mainstays 33 and / or 148 . the predetermined depth can be the length of the tissue mainstay 33 and / or 148 , or a force exerted by the tissue mainstay 33 and / or 148 . the controlled migration is then halted by either a distribution of force along the greater surface area between the tissue mainstay 33 and / or 148 and the wall of the vascular site or the diminishing force on the same surface area once the radially central end ( with respect to the anchor 10 ) of the tissue mainstay 33 and / or 148 has reached the wall of the vascular site 170 , or a combination of both . tissue can then ingrow around the tissue mainstay 33 and / or 148 providing a biologic seal or anchor so that the integrity of the seal or anchor is not purely mechanical . it is apparent to one having ordinary skill in the art that various changes and modifications can be made to this disclosure , and equivalents employed , without departing from the spirit and scope of the invention . elements shown with any embodiment are exemplary for the specific embodiment and can be used on other embodiments within this disclosure .

US-201715670797-A

a method of reducing the concentration of a chemical or drug substance in the blood plasma that targets the same or similar receptors as the normal neurotransmitters in the central or peripheral nervous system includes titrating an initial peak concentration of the chemical or drug substance in the blood for a predefined dosing period , titrating a lowest concentration level of the chemical or drug substance in the blood immediately before the end of the dosing period , and providing a plurality of subsequent dosing periods where each subsequent dosing period requires administration of a dosing amount of the chemical or drug substance and titrating of the peak concentration and the lowest concentration level to ensure that the lowest concentration level of the chemical or drug substance in the blood plasma for the subsequent dosing period is decreased by not more than five percent of the lowest concentration level of the previous dosing period and where the plurality of dosing periods added together extends the method for seventy days or more .

dependence on psychoactive substances such as opioid drugs has been a major health issue across the globe for many years . among users , there is an increase in the transmission of hiv and hepatitis c , which , in effect , increases health care costs for the user but also for the community they effect . a person can become dependent on psychoactive substances with regular drug use in two manners , physically and psychologically . physically , the brain becomes used to or adapts to the presence of the drug in order to function “ normally ”. psychoactive drugs affect the central nervous system and alter what the brain considers normal function . at the beginning of drug use , the user may experience a euphoria because the drug affects the nucleus accumbens , or the brain &# 39 ; s “ pleasure center ”. neurons in the nucleus accumbens use the same neurotransmitter as dopamine , although each drug affects this area differently , drugs either stimulate dopamine release or enhance its activity , directly or indirectly . initially the body only needs a minimal amount of a substance to function normally and attain the state of euphoria , however , over time and with chronic use , the body builds a tolerance for the drug and therefore needs more of the drug to function normally . additionally , chronic drug use results in less and less stimulation of the nucleus accumbens until eventually it produces no state of euphoria . this physical dependence is a combination of an increased tolerance to a drug and a physical need for the drug to function . the method and regimen for blood level reduction described herein lead to gradual normalization of these changes over an extended period of time . the brain that had adapted to chronic chemical or drug use , now readapts to a chemical or drug - free state . withdrawal refers to the signs and symptoms that appear when an individual becomes physically dependent on a drug and drug use is suddenly discontinued or decreased in dosage . the appearance of withdrawal symptoms can be within a few hours or after several days of discontinuation . the time depends on the drug &# 39 ; s elimination half - life . the discontinuation of drug use may produce a state of dysphoria , because the neurotransmitter levels within neural regions such as nucleus accumbens declines below normal levels . these subnormal levels may be characterized by depression , anxiety , and craving . other common signs of withdrawal are increased heart rate and / or blood pressure , tremors , nausea , hallucinations , body aches , and excessive sweating , diarrhea , night terrors , restless leg syndrome , vomiting , dehydration , formications ( crawling skin ), as well as vivid or disturbing dreams of drug use . some of the withdrawal symptoms themselves require hospitalization , such as hallucinations and seizures . other possible serious risks include an increased danger to self and / or others . the preferred embodiment of the present invention incorporates the use of a long term , controlled drug tapering regimen coupled with blood titration to determine blood levels of the drug substance in order to achieve the cessation of chemical or drug use . unlike prior art approaches to treatment , the present invention achieves cessation of chemical or drug use by using a regimen that very gradually lowers blood levels for an extended period of time . a key aspect of the method and regimen of the present invention requires that the decrease in the lowest blood level from the previous lowest blood level of the chemical or drug substance cannot be more than five percent ( 5 %). this specific multidose strategy is also useful to inhibit withdrawal symptoms associated with abrupt cessation medications as noted in section 2 . development of the variable multidose treatment protocol to reduce physical symptoms of withdrawal after several years of clinical experience in the use of buprenorphine , it became clear that a single dose in mg of buprenorphine given over a short period of time would not lead to a drug - free status . buprenorphine taken sublingually has a mean half - life of 12 - 37 hrs . if the dose is reduced rapidly , the patient reacts with both physical and emotional symptoms of withdrawal . by reducing the dose slowly , the patients experience a period where there is little or no decline in biologically available narcotic and thus feel more secure as they are not experiencing even minor withdrawal symptoms . accordingly , the drug rehabilitation protocol was altered to resemble the current protocol that will provide gradual reduced doses and blood levels , replacing the use of higher fixed doses . commercially available buprenorphine ( suboxone ® & amp ; subutex ®) is available in strengths of 8 . 0 mg as well as 2 . 0 mg . however , that these medications would not suffice for a successful program , because the 2 . 0 mg dose was too large and too steep cut - off . a 2 . 0 mg dose reduction of buprenorphine caused significant withdrawal symptoms in an experienced or chronic user of narcotic type medications . as a result , reduction in dosage was be tapered below 1 . 0 mg as well as using two doses of buprenorphine daily for those patients who had very heavy daily narcotic use patterns ( i . e . over 240 . 0 mg of oxycontin ® daily ). during inception of development of multidose treatment that led to the current invention , and using the then current state of art , buprenorphine troches for the treatment ( not maintenance ) of opiate dependence was used on a patient that was a 21 years old male who was using i . v . 5 - 8 bags of heroin daily . he was started on 3 mg of buprenorphine and remained on this dose for three days . after a two day period without opiates , an attempt was made to administer the opiate blocker naltrexone which was intended to assure that a person is indeed drug free and remained so . however , this treatment did not succeed as severe withdrawal symptoms precipitated by this treatment resulted in his to return to drug use . many alterations in treatment protocols to prevent withdrawal were made . the alterations included a greater variety of doses ranging from 8 . 0 to 4 . 0 mg administered in a deceasing amount over time . at first the dose strengths varied from 8 . 0 mg administered once daily with a daily reduction of 2 . 0 mg until to 4 . 0 mg , and then to 2 . 0 mg . however during the earliest use of buprenorphine , it was understood that to go from administering 3 . 0 mg or even 2 . 0 mg to sobriety was too steep a cut - off point ( i . e . patient would experience challenging withdrawal symptoms ) and that fixed doses do not serve the patients well . a 6 . 0 mg dose was then added to the protocol . this lengthened the withdrawal period from three days to seven . this change was occasioned by the observation that the drop from 8 . 0 mg to 4 . 0 mg was all too frequently accompanied by a significant return of withdrawal symptoms and , at times , a return to use . despite these alterations in the treatment protocol the results were still not what were expected . the observation was made that a cut - off of 2 . 0 mg would cause a return of withdrawal symptoms within 24 hrs and thus the likelihood of a return to drug use before naltrexone could be started . the data indicated that the downward transition or incremental decrease needed to be smoother . as a result , a 1 . 0 mg lozenges were administered a fractional buprenorphine dose was administered to reduce the severity of withdrawal symptoms . this strategy was in response to ongoing withdrawal symptoms following the “ conclusion ” of withdrawal or a “ final ” 3 . 0 mg dose of buprenorphine . to mitigate the withdrawal symptoms , a dose of 1 . 5 mg of buprenorphine was given to the patient . this particular treatment was unsuccessful as the ongoing withdrawal symptoms were too difficult for the patient who relapsed as a result . stepwise increments were amended to proceed in the sub 1 . 0 mg dose range . the taper at this time was 1 . 0 mg , 0 . 75 mg , 0 . 5 mg , to 0 . 25 mg then a four day period of blank troches followed by an upward taper of troches with naltrexone going from 0 . 5 mg of naltrexone to 10 . 0 mg of naltrexone . with serial doses of 0 . 25 mg of buprenorphine many patients continued to report perceptible and , in some cases , intolerable withdrawal symptoms . as a result of the ongoing objective patient observations and patient &# 39 ; s subjective complaints of withdrawal symptoms , a 0 . 1 mg dose was introduced . additionally , a dose of 1 . 5 mg as well as a dose of 0 . 75 mg was added to the dose progression series . although withdrawal complaints were limited , they were still present , and generally in the late phases of treatment . the data indicated that in order to reduce the complaints of withdrawal symptoms , the dose increments had to be further reduced in the sub 2 . 0 mg taper range . a strategy of 0 . 1 mg decreases in dose was implemented when the patients reached the 4 . 0 mg dose range ( i . e ., 2 . 0 mg twice a day ) and 0 . 01 mg deceases in the below 1 . 0 mg range . the effect of this change also to extended the withdrawal period to about six to eight weeks from four weeks . the extended treatment time , allowed for concentrating the treatment on the psychological side of the dependency after the physical dependency subsided . this extension of service allowed for greater focus on the emergence of cravings as the patients approached the 2 . 0 mg barrier . to further reduce the physical and psychological symptoms of withdrawal , the rate of taper or stepwise decrease in buprenorphine dose was reduced to 1 . 0 mg every other day and doses were given twice a day . although successful for the most part in eliminating withdrawal symptoms , there continued to be a group of patients who were large users of longer acting narcotics such as methadone and oxycontin ® that found that they continued to have significant withdrawal symptoms . an induction phase of treatment is expanded from 3 - 5 days to 5 - 10 days before the withdrawal process is started . in an effort to eliminate the last vestiges of withdrawal symptoms , the taper was altered to reduce the dose to 5 . 0 mg every other day . additionally , the number of sub 0 . 1 mg doses administered was increased resulting in a transition of almost 100 % of our patients safely and in a symptomless manner from the opiate buprenorphine to the blocker naltrexone . the change further lengthened the treatment course from two months to three or more months . the length of treatment was dependent upon the daily dose of narcotics taken prior to entering treatment . as a result , all of the treatments ended when an individual was successfully started on naltrexone , i . e ., the individual was entirely off of narcotics . the protocol no longer stopped when buprenorphine content of the lozenges was discontinued . instead , the patients returned daily and were given ‘ blank ’ lozenges . after a sufficient period to allow for a total washout of residual buprenorphine , the patients were transitioned to naltrexone 0 . 5 mg in lozenge form . this concentration then was gradually increased to 10 . 0 mg . when a patient reached 10 . 0 mg naltrexone in lozenge form , they were moved to naltrexone po . the methods described herein have been successful in individuals who were using massive amounts of pain killer type narcotics , such as doses of fentanyl as actiq in excess of 1200 mcgm # 10 daily , as well as methadone and illegal forms of opiates ( heroin 4 + gm iv daily ). patients to be treated include those with the following exemplary drug use profiles : percocet ® 500 / 10 mg , 5 - 30 tabs per day ; vicodin ® 500 / 10 mg , 5 - 30 tabs per day ; oxycontin ® 10 - 80 mg , 1 - 25 tabs per day ; methadone 10 - 400 mg per day ; mscontin ® 100 - 400 mg per day ; fentanyl 75 1200 mcgm per day ; ultram ® 50 - 100 mg 10 - 50 tabs per day ; diluadid ® 4 - 76 mg per day ; demerol ® 50 - 1500 mg per day ; heroin intranasally or intravenously 1 “ bag ” to 4 g per day ; and suboxone ® 2 - 32 mg per day . since naltrexone is administered following the cessation of narcotic , there can be no residual narcotic in a patient &# 39 ; s system , otherwise the naltrexone will push the patient into withdrawal . therefore , the patient must wait about a week before to start naltrexone , even with extremely low doses , doses that may be considered to be homeopathic but are high enough to cause withdrawal symptoms if the narcotic is not fully washed out . as necessitated by the recognition that naltrexone , even administered at 12 . 5 mg , causes a return of withdrawal symptoms for up to five days after the end of buprenorphine treatment . the patient has to wait at least five days , remaining opiate free , before naltrexone could start . another change in the protocol dealt with the growing awareness of the psychology of opiate dependence , or the psychological withdrawal symptoms . initially , all patients were informed daily of the dose that they were to receive in the office and the proposed dose schedule for their complete detoxification . this clearly caused distress with the patients who would become panicky or anxious upon learning that they would receive a smaller dose today than yesterday and that their treatment would likely end in four days time . the patients were exhibiting the psychological withdrawal symptoms associated with reducing the amount of opioid in their body . understanding psychological withdrawal symptoms , and seeing how it complicated the withdrawal process , the protocol was changed to : a ) make all of the lozenges look and taste the same and b ) absence of discussions regarding dose with patients as it lead to unnecessary anxiety . instead , the discussion is focused on withdrawal symptoms and craving type symptoms . a craving is a dysphoric affective state that occurs in the process of withdrawal from a drug of dependence in the absence of nvd but may include physical symptoms of pain , malaise , insomnia , headache , anergia , anorexia , or vivid and disturbing dreams of drug use . further observations indicated that to end the treatment with a buprenorphine troche and then ask the patient to wait five to seven days before starting on naltrexone would likely lead to relapse . therefore , naltrexone was compounded into fractional doses starting at 1 . 0 mg . by so doing , the time with no medication is shortened and the risk of any withdrawal symptoms is reduced by creating the blocking of opiate residue by naltrexone . most medications that have the potential for dependence are dosed so that they will be effective , i . e ., they will resolve the target symptom be it pain , anxiety , seizures , depression etc . in contrast , the target symptom of the multidose approach is the withdrawal symptom ( s ); a therapeutic dose is one that does not cause withdrawal symptoms . any medication that causes withdrawal symptoms upon abrupt cessation , when withdrawn slowly according to the multidosing schedule confers clinical benefit by reducing or eliminating physiological and / or psychological withdrawal symptoms . certain families of medications such as the benzodiazepines ( librium ®, valium ®, xanax ®, klonopin ®, ativan ®, etc ) have well known pathways that lead to their withdrawal states . benzodiazepines that are abruptly stopped cause severe seizures as well as panic attacks . in addition , over time some individuals develop a psychological dependence on this type of medication as well as a physical one . for these individuals , a micro dose approach to cessation is the most clinically sound way to get a person off the drug . this approach especially applicable for those subjects , who have become dependent on this class of medication and who also have a concomitant alcohol dependence since the benzodiazepines and alcohol are seen as similar by the body . abrupt cessation of a benzodiazepine in an active drinker can cause that person to increase their alcohol consumption . for example , the effects of xanax ® withdrawal ( as an example ) are described below . what has become clinically apparent with xanax ® which appears to be somewhat different than the other benzodiazepines is that the patient &# 39 ; s ability to self - detox ( longer acting benzodiazepines such as klonopin ®/ valium ®) or be able to be gradually tapered off of the medication is markedly more difficult . thus once the physiologic dependence has occurred with xanax ®, the ability of the patient to discontinue use successfully on their own is quite low , and medical assistance becomes of significant necessity in the majority of cases . the withdrawal syndrome from xanax ® and other benzodiazepines are quite similar , with the exception that xanax ® has a much higher incidence of panic attack and a bereavement type of emotional lability that is singularly more severe . since the symptoms are almost all internal , with a few physical or objective manifestations , the diagnosis of it can be very difficult . patients have a difficult time verbally describing what is occurring , and much of the descriptions often take on a quality or character reminiscent of the emotional or psychiatric problem for which they originally began taking xanax ®, rather than a withdrawal symptom . the withdrawal syndrome is diagnosed based on the following description of symptoms . in the early stage of withdrawal , there is a presentation of a sense of anxiety and apprehension associated with increasing subjective sense of tremor and mild bifrontal headache . this rapidly progresses to feelings of panic - like anxiety with tachycardia and palpitations , as well as a rapidly progressing feeling of de - realization , which is an altered sense of reality . symptoms may also be associated with marked startle response and a general amplification of most sensory input . as the withdrawal syndrome progresses , there is a marked disturbance of proprioception , with difficulty in ambulation relative to feeling “ dizzy ” and “ unsteady ,” needing to use reference and physical objects to steady oneself . with the proprioceptive problem increasing in severity simple acts such as swallowing , signing one &# 39 ; s name , talking or even buttoning a shirt can become extremely difficult . many patients at this stage describe hot / cold sensations and generalized myalgia . there is also a progression of extreme emotional lability with sudden outbursts of crying or near panic levels of anxiety and fearfulness which will have sudden onset without clear connection to external events . associated with this are frequent hypochodriacal fears of morbid consequence from the sensations they are feeling , such as fear of heart attack or stroke . patients experience a type of emotional dysphoria which is very difficult for them to verbalize , but which come very close by cumulative description to a bereavement type of feeling that is very painful emotionally . additionally , the amplification of almost all sensory information coming into the brain , other than that of taste , can produce many bizarre misinterpretation of sensory stimulation ranging from feeling one &# 39 ; s teeth rotating in their sockets to parts of their bodies disassociating or “ falling off ”. as the withdrawal symptoms progress , illusionary and hallucinatory phenomena , predominately of a visual nature , begin to manifest themselves , initially with patterns and geometric shapes , and then into full - formed complex visual hallucinations . these symptoms also often become associated with delusions of bodily dysfunction or discorporation . it is frequent and common for the patient to conclude that he is having a nervous breakdown , or “ going crazy ” as an attempt to try to understand the process at hand , not understanding it as withdrawal phenomena . with further progression , disorientation to person and place occurs with full delirium , and eventually withdrawal will finalize with tonic - clonic major motor seizure activity , generally singular in nature , although several cases of status have been reported . the last triad of symptoms , hallucinosis , delirium and seizure , are classified as major symptoms of xanax ® withdrawal and other symptoms of drugs in this category . the withdrawal syndrome can take from months , e . g ., 2 - 6 months , up to two years to fully resolve . another class of medication that is favorably withdrawn using the multidose regimen of the present invention is ssri antidepressants , e . g ., paxil ® and zoloft ®, as well as the non ssri antidepressant wellbutrin ®. the methods are useful to safely and effectively reduce and then cease dependence on antidepressants such as those that inhibit neuronal uptake of serotonin , norepinephrine , and / or dopamine . the listed withdrawal symptoms for paxil ® are noted in the below chart and are representative of other ssri type antidepressants . complaints of insomnia and “ body shock ” are terrifying to a person wishing to get off of this medication but finding that they subject to highly unpleasant and disruptive consequences of sudden cessation such as : intense insomnia ; extraordinarily vivid dreams ; extreme confusion during waking hours ; intense fear of losing sanity ; steady feeling of existing outside of reality ( depersonalization at times ); memory and concentration problems ; panic attacks ; severe mood swings ( heightened irritability / anger ); suicidal thoughts ; dizziness / vertigo ; feeling of shocks ( similar to mild electric one , running the length of your body ); unsteady gait ; slurred speech ; headaches ; profuse sweating , e . g ., at night ; muscle cramps ; blurred vision ; breaking out in tears ; hypersensitivity to motion , sounds , smells ; decreased appetite ; nausea ; abdominal cramping , diarrhea ; loss of appetite ; and / or chills / hot flashes . effexor ® is another antidepressant with a withdrawal syndrome that is reduced or eliminated using a tapering multidose strategy . prior to the invention , individuals seeking to cease medication struggled for years , e . g ., two years . the schedule involved months skipping one day in between dose , nine months later two days in between , and as of three months ago , 3 days in between , followed by 4 days in between . withdrawal symptoms included a sensation of buzzing ( electrical impulses ) upon eye or head movement , nausea , difficulty concentrating , forgetfulness , numbness in feet , twitching in the leg , disruptive sleep , night sweats , blurred vision , hallucinations , and difficulty with daily activities including work and driving . tapered multidosing as described herein obviates the need to take off a week of work and allows the individual being treated to function without marked distress . often such symptoms are rarely or not reported to physicians , and physicians currently have no strategy for dealing with the problem . tapered multidosing gives the clinician the ability to rapidly and safely get their patients off of medications that pose a risk of substantial discomfort if they are not discontinued at a slow , steady and gradual pace . the strategy is also applicable to other antidepressants , e . g ., the monoamine oxidase ( mao ) inhibitor class of drugs such as nardil ®, parnate ®, and marplan ®, which may be associated with seizures if withdrawn rapidly . anti - seizure medication also poses a withdrawal risk , e . g ., seizures , if abruptly terminated . however , tapered multidose reduction schedules for such drugs , e . g ., barbiturates such as phenobarbitols , dilantin ®, depacote ®, reduce or eliminate the risk of adverse effects of cessation of the drug . this patient began treatment with being administered a dosage of 6 . 0 mg of buprenorphine daily , via four lozenges . from there , the dosage of buprenorphine decreased daily by 0 . 5 mg , until the dosage was 2 . 0 mg . from there the patient &# 39 ; s dosage was decreased 0 . 2 mg a day until the dosage was 1 . 0 mg . at that point , the dosage was reduced by 0 . 1 mg a day and the dosage of 0 . 2 mg was given for two days . when the patient reached a dosage of 0 . 1 mg , the dosage was then dropped to 0 . 05 mg , however , due to the patient suffering from withdrawal symptoms , the dosage was increased to 0 . 1 mg , which was administered for three days . at which point the dosage was again decreased to 0 . 05 mg a day for two days . the dosage was then decreased to 0 . 03 mg , then to 0 . 01 mg of the last day of treatment with buprenorphine . the patient was then given a 1 . 0 mg dosage of quinine . on the last day the patient was given a 100 mg dosage of seroquel ®. a summary of the dosage can be seen in table 1 below : this patient began treatment with being administered a dosage of 6 . 0 mg of buprenorphine daily , via nine lozenges . from there the dosage of buprenorphine decreased daily by 0 . 25 mg , until the dosage was 2 . 0 mg . from there , the patient &# 39 ; s dosage was decreased 0 . 2 mg a day until the dosage was 1 . 0 mg . at that point , the dosage was reduced by 0 . 1 mg a day . when the patient reached a dosage of 0 . 1 mg , the dosage was then dropped to 0 . 05 mg , the dosage was then 0 . 03 mg , and finally 0 . 01 mg on the final day of treatment with of buprenorphine . the patient was then given a 1 . 0 mg dosage of quinine for two days . on the last day the patient was given a 0 . 5 mg dosage of naltrexone . a summary of the dosage can be seen in table 2 below : this patient began treatment with being administered a dosage of 7 . 5 mg of buprenorphine daily , via four lozenges . from there the dosage of buprenorphine decreased daily by 0 . 5 mg , until the dosage was 2 . 0 mg . from there , the patient &# 39 ; s dosage was decreased 0 . 2 mg a day until the dosage was 1 . 0 mg . at that point , the dosage was reduced by 0 . 1 mg a day . when the patient reached a dosage of 0 . 1 mg , the dosage was then dropped by 0 . 02 mg each day until finally the dosage was mg on the final day of treatment with of buprenorphine . the patient was then given a 1 . 0 mg dosage of quinine for four days . on the last day the patient was given a 0 . 5 mg dosage of naltrexone . a summary of the dosage can be seen in table 3 below : this patient began treatment having buprenorphine being administered a dosage of 4 . 0 mg of buprenorphine . typically , a patient is given two doses of medication , at the same amount of buprenorphine , daily spaced approximately 12 hours apart and each dose is given for about two days . from there the each new dosage of buprenorphine decreased overtime by 10 %, until dosage 16 , at which point , the patient &# 39 ; s dosage was decreased 15 % for three dosages . at that point , the dosage was reduced by 20 % for each dosage over the course of two dosages . the next two dosages were reduced 25 %. the dosages from dosage 23 to dosage 30 were reduced by another 30 % per dosage . a summary of the dosage can be seen in table 4 below : this patient began treatment having buprenorphine being administered a dosage of 8 . 0 mg of buprenorphine , twice a day . typically , a patient is given two doses of medication , at the same amount of buprenorphine , daily spaced approximately 12 hours apart and each dose is given for about two days . each two - day period is defined as a dosing period . the decrease in the dosing amount per dosing period was 0 . 5 mg until 6 mg was reached and then each dosing amount per dosing period was decreased by 0 . 25 mg . at 4 mg , the dosing amount per period was decreased by 0 . 2 mg until 2 mg was reached and then each dosing amount per dosing period was decreased by 0 . 02 mg . at 0 . 08 mg , the dosing amount per period was then decreased by 0 . 01 mg until 0 . 0 mg was reached . the total days of the decreasing regimen was 71 days . a placebo was given for 4 - 5 days before naltrexone administration began . fig1 shows a graphical representation of the rate of decline of the amount of buprenorphine administered and a summary of the dosage can be seen in table 5 below : it was further discovered that there were additional problems that appeared during the 71 day regimen as it relates to the concentration levels of the drug in the blood stream . these problems with dosing and withdrawal issues occurred around the fiftieth day of the regimen . consequently , the data of table 6 was then plotted on a semi log . fig2 shows a graphical representation of the dosing regimen plotted as a log scale . it appears that the curve is closely linear over the first fifty days but then declines more rapidly . a review of the dosing data indicated that the decrease in dosing and the linearity of the log curve was closely tied to the relative difference of the dosing amount in a subsequent dosing period to the dosing amount in the previous dosing period . the problem was determined to be the lowest level of the drug substance present in the blood plasma before the next dosing amount in the next dosing period . from data based on high success rates ( 90 % or greater ) in achieving freedom from physical dependence to opioids and related substances using specific gradually decreasing but measured doses , and projected blood levels based on the pharmacokinetic profile of the replacement narcotic buprenorphine hydrochloride that has an opioid agonist effect , it was concluded that blood level reductions of no greater than five percent ( 5 %) per day from the previous day can lead to successful cessation of use . the data included the treatment of patients on agents that included buprenorphine , codeine , fentanyl , heroin ( diacetylmorphine ), hydrocodone , hydromorphone , methadone , morphine , oxycodone , proposyphene , tramadol , other opiates , and non - opiates such as pentazocine . the results indicated that the highest success rate in drug cessation was achieved beyond 90 days . the final results by treatment days using a replacement narcotic compound buprenorphine hydrochloride that achieved calculated blood levels of no greater than five percent ( 5 %) reduction from the previous period are illustrated in table 6 to confirm these findings , numerical tabulations for multidosing involving buprenorphine for ninety ( 90 ) and one hundred twenty ( 120 ) days confirm the gradual blood level changes required for successful cessation . the original data contains data at different dosing levels of 8 mg , 12 mg , 16 mg , and 24 mg . some of the data ( the first 15 days of data of the 90 days ) for the 8 mg and 24 mg is shown in table 7 for the 90 - day regimen while fig3 shows a graphical illustration of all of the data showing the peak and lowest level concentrations for the 90 - day regimen . because peak concentration of a drug substance in the blood typically occurs about 1 hour after taking , blood concentration levels were calculated from empirical data 1 hour after a dose is administered and immediately before the next dose is administered to obtain peak concentration and lowest level concentration . the tapering is performed in a gradual decreasing format based on a log curve similar to the log curve of the actual data of the first 40 - 50 days of table 5 . some of the data ( the first 20 days of data of the 120 days ) for the 8 mg and 24 mg is shown in table 8 for the 120 - day regimen while fig4 shows a graphical illustration of all of the data showing the peak and lowest level concentrations for the 120 - day regimen . although the preferred embodiments of the present invention have been described herein , the above description is merely illustrative . further modification of the invention herein disclosed will occur to those skilled in the respective arts and all such modifications are deemed to be within the scope of the invention as defined by the appended claims .

US-19514308-A

a water bag of the present invention includes a soft bag with an intake , a lid detachably covering the intake of the bag , a hose having an end connected to the bag and a mouthpiece connected to a free end of the hose . the hose has a water inlet to inject water into the soft bag and a cap detachably covering the water inlet . therefore , water may be injected through the water inlet directly without having to take the soft bag out of the backpack .

as shown in fig1 , a water bag of the preferred embodiment of the present invention includes : a lid 12 covers the intake 11 to close or open the intake 11 . a hose 15 has an end connected to the bag 10 . the bag 10 has three rings 13 on a side for the hose 15 passing through . a mouthpiece 20 is connected to a free end of the hose 15 . a three - way valve 30 has a first end connected to the hose 15 , a second end connected to the mouthpiece 20 and a third end forming a water inlet 31 . on an interior wall of the water inlet 31 of the connector three - way 30 , a threaded section 32 is provided . the water inlet 31 may be engaged with a common mineral water bottle , as shown in fig7 . a cap 35 has a threaded section 36 to be screwed to a threaded section 32 of the water inlet 31 . the cap 35 is provided with a strip 37 and a ring 38 on an end of the strip 37 . the ring 38 is fitted to an annular slot 33 on the three - way valve 30 adjacent to the water inlet 31 , such that the cover will not loose when the cap 35 is opened . a leakage - proof ring 34 is provided in the cap 35 to press the three - way valve 30 when the cap 35 is screwed onto the three - way valve 30 for leakage - proof . when water in the bag 10 is out , user may open the cap 35 and engage an opening 91 of a common water bottle 90 with the water inlet 31 , as shown in fig7 , to inject water into the bag 10 through the hose 15 . after filling , user only needs to close the cap 35 that is a very convenient operation . in addition , to for convenience of operation , a plastic deformation tube 40 , which may be bent and fixed in a predetermined shape , is mounted between the three - way valve 30 and the mouthpiece 20 . the plastic deformation tube 40 includes a main tube 41 , a sub - tube 42 attached on a circumference of the main tube 41 , and a metal bar 43 in the sub - tube 42 . the metal bar 43 may be bent and fixed at that shape . with the plastic deformation tube 40 , user may adjust the mouthpiece 20 at desired positions , such that user may drink water without having to hold the mouthpiece 20 . the water bag of the present invention is further provided with a switch 50 between the plastic deformation tube 40 . the switch 50 includes two members 51 , 55 , in which the first member 51 is connected to the plastic deformation tube 40 and the second member is connected to the mouthpiece 20 . the members 51 , 55 are connected together and may be rotated relative to each other . the second member 55 as a tunnel 56 , and the first member 51 has a plug 52 . when the members 51 , 55 are turned , the first member 51 may be moved away from the second member 55 , as shown in fig4 , in which water may flow through the switch 50 . the members 51 , 55 also may be turned in opposite direction to have the first member 51 moved toward the second member 55 , as shown in fig5 , in which plug 52 seals the tunnel 56 to cut off water . the mouthpiece 20 includes a flexible body , in which a tunnel 21 is provided , with a closed end . on the closed end of the tunnel 21 , an elongated crack 22 is provided , as shown in fig8 . the crack 22 is closed in a normal condition , such that water will not flow out , and it is opened when the flexible body is compressed along an elongated direction of the crack 22 , such that water may flow out . a cap 25 covers the closed end of the mouthpiece 20 with a strip 26 and a ring 27 . the ring 27 is fitted to a slot 23 on a circumference of the mouthpiece 20 , such that the cap 25 will not loose . the main purpose of the cap 25 is dustproof , except that the cap 25 compresses the mouthpiece 20 to seal the crack 22 for leakage proof when the cap 25 is covered on the mouthpiece 20 . the ring 27 may restrict the flexible body to ensure the crack 22 closed . as shown in fig9 , the tunnel 21 has a quadrilateral section 24 , such as rhombus , square or rectangle , adjacent to the closed end . the crack 22 extends along a diagonal line of the quadrilateral section 24 . the present embodiment shows the crack 22 extends along a short diagonal line of the rhomboidal section 24 that benefits the crack 22 to keep closed . as shown in fig1 , the present invention further provides a lock device 60 , which is an elongated plate with a c - shaped clip 61 on a center thereof and two connectors 62 on opposite sides of the clip 61 . the clip 61 may hold the plastic deformation tube 40 or the hose 15 . the connectors 62 may connect an o - ring 63 ( or elastic band ). the o - ring 63 is wound on a back of a belt of a backpack and engages opposite ends thereof with the connectors 62 to mount the lock device 60 on the backpack , such that the plastic deformation tube 40 may be fixed on the lock device 60 . user may adjust the plastic deformation tube 40 to have the mouthpiece at a suitable position for drinking . the description above is a few preferred embodiments of the present invention and the equivalence of the present invention is still in the scope of the claim of the present invention .

US-49031506-A

the invention relates to an adjustable helmet comprising a first and second shell portion adjustably connected together . each shell features a smooth interference - free sliding surface on which the two shells fit together in an overlapping relationship . the two shells are locked together by a manually operable locking device adapted to engage corresponding anchoring holes . the smooth interference - free sliding surfaces allows easy adjustment of the helmet size .

shown in fig1 and 2 is an adjustable hockey helmet 20 according to the present invention . adjustable helmet 20 is made up of a front shell 22 and a back shell 24 interconnected together and adapted to move in relation to each other , and two locking devices 26 located on each side of helmet 20 just above the wearer &# 39 ; s ears . front shell 22 and back shell 24 are preferably made of a relatively rigid material , such as a polycarbonate material , a rigid thermoplastic , or a thermosetting resin in order to provide a strong helmet that will protect a wearer &# 39 ; s head . in a preferred embodiment , shown in fig1 and 2 , front shell . 22 includes a plurality of ventilation apertures 50 located at various positions . although fig1 and 2 show only ventilation apertures 50 in front shell 22 , it should be expressly understood that back shell 24 may also comprise ventilation apertures . while ventilation apertures 50 are not essential to the present invention , they do provide the added comfort of allowing air to circulate around the wearer &# 39 ; s head , thus permitting perspiration to evaporate . also in a preferred embodiment , and as can be seen in fig1 the inside of helmet 20 is lined with padding 27 . padding 27 is mounted to the inside surfaces of front shell 22 and back shell 24 in order to make helmet 20 more comfortable for the wearer . it is within the scope of the present invention for helmet 20 to have as little , or as much , padding as is necessary for the comfort of the wearer , so long it the padding does not interfere with the movement of front shell 22 and back shell 24 . also shown in fig1 and 2 , are two downwardly extending sides 37 that extend along the sides of the wearer &# 39 ; s face in front of the wearer &# 39 ; s ears . sides 37 provide additional protection to the sides of the wearer &# 39 ; s head , and further provide a useful location for connecting straps 31 . at the base of sides 37 are apertures 33 ( only the right hand side shows aperture 33 ) through which a strap 31 is looped . the other end of strap 31 is looped into a second aperture 35 located on the base of back shell 24 . helmet 20 is designed so that the wearer &# 39 ; s ear fits into the area bounded by back shell 24 , sides 37 and straps 31 . although not shown in the drawings a chin strap is adapted to be attached to each of straps 31 , so that when it is secured beneath the wearer &# 39 ; s chin , helmet 20 is securely fastened onto the wearer &# 39 ; s head . front shell 22 is further equipped with holes 39 , and two screws 29 , both of which can be seen in fig1 . holes 39 are located on downwardly extending sides 37 , and screws 29 are positioned in the center of the portion of front shell 22 that covers the wearer &# 39 ; s forehead . although not shown in the drawings , both screws 29 , and holes 39 , are adapted to facilitate the attachment of a protective visor to helmet 20 . screws 29 are adapted to screw into the frame of a sports visor , and holes 39 are adapted to receive securing tabs located on the sides of the visor . preferably , the visor is of the type wherein the transparent viewing window is hingedly connected to the frame that is screwed into helmet 20 . therefore , the visor can be moved between an upwards and downwards position . when the visor is in the down position the tabs located on the side of the visor fit inside holes 39 to keep the visor in place . and , when the wearer needs to move the visor out of his or her face , he or she must simply push the visor upwards to release the tabs from holes 39 and push the visor into the upward position . as can be seen in fig1 front shell 22 and back shell 24 are designed to be symmetric along the axis dividing the left side of helmet 20 from the right side of helmet 20 . therefore , in order to avoid repetition , only the right hand side of helmet 20 will be described for the remainder of this description . it should be understood that for all intensive purposes the left side of helmet 20 is identical to the right side of helmet 20 , and therefore anything described below can be found on both sides of helmet 20 . as can be seen in fig3 and 4 , front shell 22 is divided into top section 28 and wing sections 30 . top section 28 covers the front and top of the wearer &# 39 ; s head , and wing sections 30 extend along the sides of the wearer &# 39 ; s head , overlapping the sides of back shell 24 . wing sections 30 are divided from top section 28 by slots 32 . in a preferred embodiment , back shell 24 slides into slots 32 of front shell 22 so that wings 30 wrap around the exterior sides of back shell 24 , and the top part 28 of front shell 22 lies underneath the top of back shell 24 . both front shell 22 and back shell 24 have smooth , interference - free sliding surfaces that are adapted to be in contact with each other when helmet 20 is secured in a selected position . the interference - free sliding surfaces of the helmet still experience minor unavoidable friction , but can be moved in relation to each other without substantial interference and in a smooth movement . the sliding surfaces for front shell 22 are located on the exterior surface of the top 28 of front shell 22 and on the interior surfaces of wings 30 , while for back shell 24 , the sliding surfaces are located on the interior of the top of back shell 24 and on the exterior of the sides of back shell 24 . in this way the sliding surfaces of front shell 22 are in contact with the sliding surfaces of back shell 24 when helmet 20 is secured in a chosen size . front shell 22 and back shell 24 are slidably connected to each other by a slot and peg assembly . as can be seen in fig5 back shell 24 has two long slots 34 and 36 , located at a position slightly above the wearer &# 39 ; s ear . front shell 22 has two holes 38 and 40 that align with slots 34 and 36 when front shell 22 and back shell 24 are interconnected . pegs 42 and 44 , which are both made up of two parts 42 a , 42 b and 44 a and 44 b , shown in fig5 and 8 , extend through slots 34 and 36 and further extend through holes 38 and 40 for assembling front shell 22 and back shell 24 . slots 34 and 36 , and holes 38 and 40 have a width that is slightly greater than that of the diameter of pegs 42 and 44 so that pegs 42 and 44 can slide easily within slots 34 and 36 . pegs 42 and 44 are pieced together to assemble front shell 22 and back shell 24 , and are adjusted to leave a very small gap between front and back shell 22 and 24 such that the two may slide relative to one another with minimum friction . the slot and peg assembly allows front shell 22 and back shell 24 to slide backwards and forwards and guides their relative movement . in this embodiment , back shell 24 has long slots 34 and 36 for pegs 42 and 44 to slide within and front shell 22 has holes 38 and 40 . it should be expressly understood that in an alternate embodiment , both front shell 22 and back shell 24 could comprise long slots for pegs 42 and 44 to slide along . or alternately , back shell 24 could have the two holes for pegs 42 and 44 to fit through and front shell 22 could have the long slots . slots 34 and 36 determine the path of movement of front shell 22 and back shell 24 with respect to each other . as can be seen in fig3 and 6 , in a preferred embodiment , slots 34 and 36 are oriented in a slightly downward sloping direction from the back to the front of helmet 20 . alternatively , slots 34 and 36 may be positioned at any angle depending on how front shell 22 and back shell 24 are designed to move in relation to each other . as long as slots 34 and 36 guide front shell 22 and back shell 24 into positions that provide a number of comfortable helmet sizes , they can be in almost any orientation . once a wearer has selected a desired helmet size , front shell 22 and back shell 24 must be securely locked in place so that they are unable to move in relation to each other . for this purpose , adjustable helmet 20 comprises a locking device 26 . as can be seen in fig6 locking device 26 comprises two teeth 76 , and is pivotally attached to wing 30 of front shell 22 . locking device 26 is movable between a release position and a locked position . in the locked position , as can be seen in fig9 b , locking device 26 is closed so that teeth 76 engage both sets of anchoring holes 52 and 54 thereby blocking all movement between front shell 22 and back shell 24 . in the release position , as shown in fig6 locking device 26 is opened so that teeth 76 do not engage anchoring holes 54 and 52 , and front shell 22 and back shell 24 , can move in relation to each other so that the helmet size can be adjusted . the construction and operation of locking device 26 will now be described in more detail . referring back to fig1 and 2 , it can be seen that locking device 26 is located at the tip of wing 30 . the assembly of locking device 26 is best illustrated by fig5 which shows that locking device 26 fits inside indented groove 56 of front shell 22 . a hinge element 58 is located underneath the raised portion 64 of wing section 30 ( also shown in fig6 ) and has two attachment members 60 and 62 that extend through wing 30 into indented groove 56 . attachment members 60 and 62 attach locking device 26 to helmet 20 and act as the pivot points on which locking device 26 rotates . as can be seen in fig1 through 6 , in a preferred embodiment , locking device 26 is in the aesthetically pleasing shape of a rounded scalene triangle . locking device 26 has three unequal sides . as seen in fig5 the longest side 67 of the triangle is the side that is pivotally connected to hinges 62 and 64 . the shortest side 66 is the side that is shielded by the outer surface of wing 30 when locking device 26 is in the locked position . and finally , the third middle - length side 68 is the side that can be held by the wearer to move locking device 26 between its locked position and its release position . as illustrated in fig6 and 7 , locking device 26 comprises four main components , namely cam surfaces 78 and 80 , clevis members 72 , a handle 74 and anchoring teeth 76 . closed cam surface 78 and open cam surface 80 can be seen in fig9 b , which shows locking device 26 in its locked position . when in the locked position , closed cam surface 78 rests against the raised surface 64 of wing 30 . and as can be seen in fig9 when locking device 26 is in its release position , open cam surface 80 rests against the raised surface 64 of wing 30 . in the release position cam surface 80 ensures that locking device 26 does not fall back into the locked position inadvertently . the four clevis members 72 that fit around hinge members 60 and 62 can be seen clearly in fig6 . each clevis member 72 comprises a hole 82 that lines up with holes 84 in hinge members 60 and 62 . once clevis members 72 are positioned around hinge members 60 and 62 so that holes 82 and 84 line up , a pin - like device 86 is slid through the holes , thereby attaching locking device 26 to helmet 20 . in a preferred embodiment , as can be seen in fig1 , pin - like member 86 is in the form of a coiled spring clip that is in its rest position when it is inserted inside holes 82 and 84 . this ensures that pin 86 will not fall out accidentally , since it would need to be manually compressed in order to be removed . in an alternate embodiment , shown in fig1 , the pin is a wire clip 87 in the shape of a dovetail . as can be seen in fig1 , teeth 76 of locking device 26 are located towards the short side 66 of the scalene triangle . in a preferred embodiment of the invention there are two teeth 76 that in the locked position engage with the series of anchoring holes 52 and 54 . teeth 76 ensure that front shell 22 and back shell 24 are securely locked together when locking device 26 is in the locked position . it should be expressly understood that locking device 26 may include as many or as few teeth as is necessary to adequately secure front shell 22 and back shell 24 together . the final section of locking device 26 is handle 74 that can be seen clearly in fig7 through 9 b . handle 74 extends from side 67 to the surfaces of both the short side 66 and the middle - length side 68 . handle 74 is held by the wearer at middle length side 68 in order to move locking device 26 between its locked position and its release position . as described above , both front shell 22 and back shell 24 each comprise anchoring holes 54 and 52 that are adapted to lie on top of each other . when helmet 20 is positioned in its largest size , the two forward - most anchoring holes 53 , which are shown in fig5 will be in alignment with the two holes 54 of front shell 22 . similarly , when helmet 20 is positioned in its smallest size , the rear - most holes 51 of back shell 24 will be in alignment with the two holes 54 of front shell 22 . in the locked position shown in fig8 and 9 b , teeth 76 engage holes 54 of front shell 22 and any two consecutive holes of the series of holes 52 . in the release position shown in fig9 and 10 , teeth 76 of locking device 26 are not inserted within the two holes 54 of front shell 22 , nor any of the series of holes 52 of back shell 24 . therefore , in the release position the wearer is able to easily slide front shell 22 and back shell 24 with respect to each other in order to establish a desired helmet size . it is clear from fig9 and 10 that when locking device 26 is in the release position , there is nothing to interfere with the sliding movement of the two shells . as can be seen in fig1 , which shows the locking device of the prior art , the prior art helmet has extruding ridges and teeth that rub against each other , causing undue friction and limiting the movement of the two shells when the wearer wishes to adjust the helmet size . it should also be noted that slots 34 and 36 , that receive pins 42 and 44 are in a wavy shape that creates enlarged areas and contracted areas . this shape facilitates the movement of pegs 42 and 44 within slots 34 and 36 so that when pegs 42 and 44 are guided into the enlarged portions of slots 34 and 36 , the anchoring holes 54 of front shell 22 are aligned with the anchoring holes 52 of back shell 24 . in operation , a wearer who puts on helmet 20 and realizes that it is too large or too small , does not need to remove helmet 20 . the wearer must simply reach up and grasp handle 74 and pull upwards so that locking device 26 moves into the release position . once locking device 26 is in the release position , the wearer can expand or contract the size of helmet 20 by pushing or pulling shells 24 and 22 in relation to each other . as the two shells move , pegs 42 and 44 move from enlarged portion to enlarged portion within wavy slots 34 and 36 . pegs 42 and 44 will naturally jump from one enlarged portion to another within wavy slots 34 and 36 which correspond to the positions at which teeth 76 naturally align with holes 52 and 54 . therefore , the wearer will be able to align teeth 76 with holes 52 and 54 by feel , since when the wearer is not pulling or pushing , pegs 42 and 44 will naturally be in a position that aligns teeth 76 with holes 52 and 54 . the above description of preferred embodiments should not be interpreted in a limiting manner since other variations , modifications and refinements are possible within the spirit and scope of the present invention . the scope of the invention is defined in the appended claims and their equivalents .

US-31179002-A

the measuring head enables the production of measuring signals relating to electrical activity and measuring signals relating to an ionic or physico - chemical activity , notably ph , and is designed to be located on or in parts of a living body , notably on the head of an unborn infant . it comprises an insulating body bearing fastening claws . at the moment of positioning , the insulating body introduces actively an electrode sensitive to the electrical activity and at least one electrode sensitive to an ionic or physical activity . these electrodes are constructed in needle form , body body having also a reference electrode associated with the electrode sensitive to the ionic or physical activity .

in the embodiment illustrated in fig1 the measuring head includes a single or double claw 1a , of semi - circular shape , movable around a horizontal axle 2a , parallel to the body surface where the measuring head is applied , which can emerge from or penetrate into the casing 3 forming the body of the measuring head , by a rotary movement and enabling the pick - up , when it is driven into the body part , of a signal derived from the electrical activity of the latter . the measuring head includes on the other hand , a selective electrode 4 , sensitive to the hydrogen ion activity , formed by a fine stainless steel tube 5 with a beveled end , containing and protecting the selective electrode 4 proper and allowing the slight protrusion , on the side of the beveled end , of the sensitive diaphragm 6 which can be of glass . this electrode 4 , rectilinear in shape , is given a linear translation movement , along an inclined axis coinciding with the axis of the hollow cylindrical sheath 7 , itself coming into abutment with the casing 3 and extending between the two preceding claws 1a , at the level of the corporeal part . the selective electrode 4 is advantageously a ph detection electrode of the usual commercially sold type . it is seen that the direction of penetration of this electrode is opposite the direction of penetration of the claws 1a , which ensures firm fastening of the measuring head . a movable mechanical element 8a , coupling the selective electrode 4 to the double claw 1a , enables the translation movement of the first to be converted into a rotary movement of the second . this operation is done so that when the selective electrode 4 is pushed downwards into the corporeal part along a linear movement , the double claw 1a is also driven into this same corporeal part in a rotary movement , so that the claw 1a resists the disengagement of the selective electrode 4 . the selective electrode 4 is guided in its translation movement , on the side of the corporeal part , by the base 9 of the measuring head and , at its other end by the flexible sheath 7 which can be formed by means of a spiral steel wire , with contiguous turns . this flexible sheath 7 , sufficiently rigid to protect the elements that it contains , surrounds the electrical cable 10 of the selective electrode 4 , and surrounds the extension 11 of the container of the kcl reference electrode 12 , which can be constituted by a fine polyethylene tube 13 terminating in a porous material 14 , designed to limit the amount of kcl flowing from the reference electrode , and having a sufficient cross - section so that particles or bodies of biological origin do not come to obstruct it . the position of this orifice , as well as its cross section , are selected so as to ensure the best possible electrical contact between the corporeal part and the kcl reference electrode . the flexible sheath 7 also surrounds the electrical lead 20 connected to the double claw 1a , as well as the mechanical element 15a , which can be a sufficiently rigid and flexible steel wire , fastened inside the casing 3 through a collar 16a which can be removable and gripped around the selective electrode 4 , at the level of a groove 17 formed in the insulating ring 18 whose purpose is , moreover , to improve the quality of the junction formed between the rigid part 5 of the selective electrode 4 and its flexible extension which can be a polyethylene tube 19 . the movable fastening axle 21a holds the gripping collar 16a , the movable mechanical element 8a and the movable mechanical element 15a , assembled together . the part in dotted lines , representing the movable mechanical element 8a , corresponds to a position wherein the two types of electrodes are placed in retracted position , inside the casing . in this position , neither the semi - circular claw 1a , nor the needle electrode 4 , can come into contact with the corporeal part . fig2 shows the details of a possible embodiment of a coordinating mechanism for the movements between the semi - circular claw shaped electrode 1b and the selective electrode 4 , endowed with a linear translation movement . it comprises the movable mechanical element 8b , connected on the one hand to the movable fastening axle 21b , fast to the selective electrode 4 sensitive to the ionic activity , and on the other hand to the movable fastening axle 22b , fast to the claw 1b . the fixed fastening axle 2b is fast to the body of the measuring head . it can be surrounded by several turns 22 , integral parts of the double claw 1b , which can play the part of a return spring , contributing , either to the introduction of the electrodes into the corporeal part , or to their retraction within the casing . the movement of the assembly is controlled by the element 15b through the collar 16b and the movable axle 21b . fig3 shows a possible arrangement of the adjusting means , placed at the other end of the flexible sheath 27 , marked as 7 in fig1 . this adjusting means can be constituted by a body 28 , of insulating material , also receiving an abutment the other end of the sheath 27 . it contains a cylindrical cavity 34 intended to guide the other end 25 of the flexible rod , denoted as 15a , in fig1 . the latter is extended , inside , by a handle 33 and includes , in the cylinder 34 , a return spring 32 as well as a ring 31 which is fast to it . this spring , abutting against the ring 31 and against the body of the casing 28 permits , by the pressure that it exerts on the cable 25 , the holding of the two electrodes , denoted as 1a and 4 in fig1 in penetrated position , and , consequently , to hold the measuring head fastened to the corporeal part to which it is applied . it is possible , without departing from the scope of the invention , to contemplate any other adjusting means for the position of the electrodes . the casing 28 holds moreover the two electrical leads 29 and 30 supplying the signal relating to the electrical activity of the corporeal part . the lead 30 is connected to the semi - circular double claw . the lead 29 is shown here electrically connected to the metal sheath 27 . it could be formed otherwise , the essential thing being that it is connected to the reference electrode associated with the one or more claws enabling the signal to be obtained relating to the electrical activity of the corporeal part . the casing also holds the electrical leads 24 and 26 . the lead 26 is the extension of the internal lead from the sensitive selective electrode . the lead 24 is the extension of the inner lead of the kcl reference electrode associated with the selective electrode . it is to be noted that this lead can replace the lead 29 and serve , for the signal relating to the electrical activity , as reference electrical lead . the reference electrode 35 is terminated , within the casing 28 , by a double branch , one containing the electrical lead 24 , the other the filling orifice 23 . this orifice may be most simply constituted by the extension of the polyethylene tube , constituting the extension of the body of this same kcl reference electrode , or by any other device enabling the filling of the latter with kcl , continuously or not , during the measurement or not , without departing from the scope of the invention . in the description given in the fig1 and 3 , the whole of the measuring head is used by placing in one hand , the casing containing the fastening electrodes , the index being placed on the latter , in a hollow provided for this purpose , so as to direct the latter by &# 34 ; touch &# 34 ; within the corporeal part . the other end of the measuring head 28 is held in the other hand taking care , during positioning , to maintain the handle 33 of fig5 pulled and , consequently , to keep retracted , within their casing , the fastening electrodes in order not to injure the corporeal part during positioning . the position of the measuring head on the corporeal part having been selected , it suffices , whilst holding it in position , to release the handle 33 connected to the cable 25 which , under the reaction of the spring 32 which was in compressed position pushing the ring 31 fixed to the cable 25 , has the effect of advancing the selective electrode 4 of fig1 into the corporeal part , as well as the claws 1a shown in the same figure . to withdraw the electrode from the corporeal part , the reverse operation must be followed . reference will now be made to fig4 to 12 in which homologous elements bear the same reference numerals . the base 9 of the head receives , removably , a cap or cover 36 . the form of the base is seen in fig7 to 9 . it includes a rectilinear part 37 with an enlarged rear end 38 having substantially the width of the cap 36 and the base is traversed by an orifice slightly inclined with respect to its inner surface 39 , being enlarged in zone 38 to enable the insertion and fixing by locking of the end of the flexible sheath 7 . in front of the widened part 38 , the base 9 has an upper recess 40 communicating with the orifice 39 and whose edges approach one another slightly to permit the fastening by clipping of the cover 36 having for this purpose a suitable relief 41 . the base 9 still has towards its front part a transverse 42 for the passage of the axle 2a . a cap or cover 36 has the shape shown in fig1 to 12 , this substantially semi - ovoid shape having , at the front end , a groove 43 . when the head of the device is applied to the skin of the unborn infant , the skin has a tendency to project all around the head and this relief tends to penetrate into the notch 43 . this is thus favorable to the penetration of the end of the electrode - needle 4 into the skin . it is also possible , if desired , to create notches laterally to facilitate the penetration of the claws 1a . the reference electrode may advantageously be replaced , by providing in the cover 36 two vertical blind orifices 44 opening at the lower surface . it is seen , in fig1 and 12 , that the shape of these orifices is elongated parallel to the axis of the head . these orifices may be closed at their lower surface by a porous film 45 , for example of paper . the orifice 44 is replaced by a kcl paste or the like , for example based on agar - agar . the bottom of the orifice is lined with a conductive film of silver and silver chloride 46 connected by a lead 47 to a small strip contact 48 situated on the inner surface of the inner wall of the orifice 44 . the lead 47 passes through this wall . the contact strips 48 are applicable against corresponding metal strips 49 housed in lateral recesses of the part 37 of the base 9 to ensure electrical contact . the two contacts 49 are connected to a lead 10 ( shown only in fig1 ). the contacts 48 , 49 may be situated at other places of the base or of the cover shielded from amniotic liquid . in a modified embodiment , it is possible to envisage a discardable cover similar to cover 36 , but without the presence of the orifices 44 . it would suffice to provide , at the places occupied by the two films 45 housings capable of receiving removably reference electrode forming tablets and containing , from below to above , a porous film 49 of paper , a layer of potassium chloride paste 50 , a conducting tablet 51 of silver / silver chloride , said silver tablet coming into contact with a metal contact part 52 present at the bottom of the recess and connected at 53 . such an embodiment can be seen in fig1 . the connection between the needle - electrode 4 and the flexible control element 15 , for example a steel wire , is effected preferably as is seen in fig4 to 6 , by winding the element 15 around the needle 4 so as to form , between two successive turns , a strand separated laterally 15a enabling the hooking of the element 8b . the claws 1a themselves are formed from a single spring steel wire whose two ends are curved back into the form of claws 1a , said claws being extended by a certain number of turns 22 arranged around the axle 2a , said groups of turns being connected by a central strand 1c . it is seen that this central strand passes into a dihedral angle 55 situated at the front part of the base 9 . in order to enable easy replacement of the part constituted by the claws 1a , the windings providing spring function 22 and the central strand 1c , it is possible to provide , in this dihedral angle , a metal pincer ( not shown ) into which the strand 1c becomes removably engaged to be gripped by this pincer . the pincer is connected to the electrical lead 20 to transmit the electrical signals detected by the claws 1a . referring to fig1 , there is seen a control device provided at the outer end of the sheath 7 and playing a similar role to the device shown in fig3 . this device provides a control handle 56 against which the index finger of the operator can be placed . this handle is extended by a rectilinear part 57 provided with a central slot in which a sliding knob 58 capable of being moved by the thumb is slideably guided . on this knob 58 is fastened the end of the flexible element 15 . it is seen that the upper surface of the extension 57 has a rear shoulder 59 forming a stop . normally , the claws 1a are in the position shown in fig6 and , under these conditions , the part 8b is in its rear position , the electrode 4 not emerging from the lower base of the measuring head . the finger 58 is then in a rear position , in which position it is held in abutment , in the position shown in dashed lines , against the stop 59 . from this position the operator , having introduced the measuring head into the neck of the uterus and applied the base of said head against the cranial skin of the still unborn child , lifts the knob 58 which is thus disengaged from the stop 59 . the turns 22 then push back the claws 1a into active position shown in fig4 and , in this movement , the part 8b transmits a traction force to the element 15 which causes the driving of the electrode 4 into its position shown in fig4 and also the forward movement of the knob 58 . the knob has then reached the forward position shown in fig1 . to retract the claws and the electrode 4 , the user pushes back the knob 58 with the thumb rearwards to bring it back into the position shown in dashed lines . if necessary , if the force of the turns 22 is insufficient , the user may , by thrusting against the knob 58 to push it back forwards , aid in the perforation of the cutaneous wall by the claws 1a . in another modification the claws 1a may not serve as electrodes and it is then the metal tube 5 of the electrode 4 which , connected to a lead , for example the flexible rod 15 , detects the electrocardiographic signals . in all cases it is possible to provide a counter electrode ecg on the sheath , coming into contact with a maternal corporeal part . another possible embodiment of the measuring head according to the invention , only including a part of the advantages of the above description , is shown in fig1 as well as in fig1 . fig1 takes up the double spiral electrode embodiment . each claw is electrically insulated from the other and is formed by means of a spiral shaped steel tube of which one end , positioned in the corporeal part , is cut into a bevel . the hollow claw 60a contains and protects the selective electrode whose diaphragm , sensitive to ionic activity , appears at 61a . the second hollow claw 62 contains the extension of the kcl electrode , extended outwards by a member which can be constituted by a flexible polyethylene tube 63a and having the same advantages as those described in the preceding embodiment . the sets of electrical leads 65a and 64a for claw 62 and 66a and 67a for the other claw 60a are insulated from one another , and can pick up the electrical signal relating to the electrical activity of the corporeal part . the electrical leads 64a and 65a enable the pick - up of the measuring signal relating to ionic activity . fig1 shows a modification of the embodiment of fig1 , in the sense where the kcl reference electrode is no longer introduced into the corporeal part by means of the hollow claw 68 , but becomes exposed under the base of the insulating material of the measuring head , creating an electrical contact 69 at the level of the corporeal surface and having an electrical lead 64b . these two latter versions no longer include electrode retraction means . claw 68 , with tip 61b , includes electrical lead 65b , while the other claw 60b includes electrical leads 66b and 67b .

US-2177979-A

this invention relates to alpha - alkyl - alpha -- 1h - 1 , 2 , 4 - triazole - 1 - propanenitriles , their enantiomorphs , acid addition salts and metal salt complexes . these compounds , enantiomorphs , salts and complexes are highly active broad spectrum systemic fungicides effective in controlling phytopathogenicfungi such as barley spot blotch , grape , wheat and bean powdery mildews , grape downy mildew , rice blast , tomato and potato late blights and wheat stem rust .

in accordance with the present invention , there is provided a new class of triazole propanenitriles which are 2 - alkyl - 2 -( 4 - halophenyl )- 1h - 1 , 2 , 4 - triazole - 1 - propanenitriles of the formula ( i ): ## str1 ## wherein x is a fluoro , chloro or bromo atom ; r is ( c 3 - c 8 )- alkyl ; and the agronomically acceptable enantiomorphs , acid addition salts and metal complexes thereof . the term &# 34 ; alkyl &# 34 ; is meant to include both branched and straight chained alkyl groups of from 3 - 8 carbon atoms . typical alkyl groups which are encompassed by the use of this term are propyl , iso - propyl , n - butyl , sec - butyl , iso - butyl , tert - butyl , pentyl , neo - pentyl , iso - pentyl , hexyl , heptyl , iso - octyl and the like . however , straight chained alkyl groups are preferred and if the alkyl group is branched , it is preferred that the branching does not occur at the alpha carbon of the r substituent . the acids which can be utilized in making the acid addition salts of the present invention include , for example , hydrochloric , hydrobromic , nitric , sulfuric , phosphoric , hydroiodic , hdyrofluoric , perchloric , p - toluenesulfonic , methanesulfonic , acetic , citric , tartaric , malic , maleic , oxalic , fumaric and phthalic acids . another embodiment of this invention is the metal salt complexes of the formula ( ii ): ## str2 ## wherein x and r are as defined in formula ( i ) above and m is a cation selected from group iia , ib , iib , vib , viib and viii of the periodic table and x is an anion selected so that the sum of the valence charges of the cation m and anion x equal zero . typical cations encompassed by this invention are magnesium , manganese , copper , nickel , zinc , iron , cobalt , calcium , tin , cadmium , mercury , chromium , lead , barium and the like . typical anions encompassed by this invention are chloride , bromide , iodide , fluoride , sulfate , bisulfate , perchlorate , nitrate , nitrate , phosphate , carbonate , bicarbonate , acetate , citrate , oxalate , tartrate , malate , maleate , fumarate , p - toluenesulfonate , methanesulfonate , mono - or di -( c 1 - c 4 ) alkyldithiocarbamate , ( c 1 - c 4 ) alkylenebisdithiocarbamate and the like . a preferred embodiment of this invention is the compounds , agronomically acceptable enantiomorphs , salts and complexes of formulas ( i ) and ( ii ) wherein x is fluoro or chloro atom and r is ( c 3 - c 6 ) alkyl group with the proviso that if it is a branched alkyl , the branching does not occur at the alpha carbon of the r substituent . a more preferred embodiment of this invention is where x is a fluoro or a chloro atom and r is a propyl , n - butyl , iso - butyl or n - pentyl group and a most preferred embodiment is where x is a chloro atom and r is an n - or iso - butyl group . and the agronomically acceptable enantiomorphs , acid addition salts and metal salt complexes thereof . the compounds of the present invention possess curative , residual and preventive antifungal properties against a broad spectrum of phytopathogenic fungi . they additionally may act as systemic and / or contact fungicides . examples of such fungi include wheat and barley powdery mildew ( erysiphe graminis ), rice blast ( piricularia oryzae ), peanut early leaf spot ( cercospora arachidicola ), banana sigatoka ( mycosphaerella fijiensis ), wheat leaf rust ( puccinia recondita ), wheat stem rust ( puccinia graminis ), septoriosis of wheat ( septoria spp . ), barley net blotch ( helminthosporium teres ), grape powdery mildew ( uncinula necator ), grape black rot ( guignardia bidwellii ), apple scab ( venturia inequalis ), apple powdery mildew ( podosphaera lencotricha ), cucumber powdery mildew ( sphaerotheca fuliginea ), brown rot of stone fruits ( monilinia fructicola ) and rice sheath blight ( rhizoctonia solani ). the triazoles of the present invention can be prepared by conventional synthesis routes . for example , the triazoles may be prepared by nucleophilic displacement of the alkylated phenylacetonitrile bromide ( v ) by a salt , preferably an alkali metal salt , of the triazole , generally about 1 to about 3 equivalents . this reaction can be run either neat or , preferably , in an appropriate solvent such as dimethylsulfoxide ( dmso ), n - dimethylformamide , toluene or xylene at a temperature from about 0 ° c . to about 150 ° c ., preferably from about 25 ° to about 100 ° c . the bromide ( v ) is prepared by bromomethylation of the alkylated phenylacetonitrile ( iv ) by methylenebromide ( generally about 1 . 1 to about 2 equivalents ) under basic conditions , e . g ., sodium or potassium hydroxide , sodium or potassium hydride , potassium methoxide and potassium - t - butoxide ( generally about 1 . 1 to about 2 equivalents ) preferably with the use of a solvent such as dmso , at a temperature from about 0 ° to about 150 ° c ., preferably from about 25 ° to about 100 ° c . the alkylated phenylacetonitriles ( iv ) can be prepared by phase transfer alkylation of the appropriately substituted benzylcyanides ( iii ) with generally about 1 to about 2 equivalents of an alkyl halide ( rx wherein r is as defined above and x is , for example , cl , br , i , tosylate or mesylate ) in the presence of a strong base , e . g ., 50 % ( w / w ) sodium hydroxide or another metal alkoxide , and a catalyst , e . g ., tetrabutylammonium bromide . both the benzylcyanides and the alkyl halides can be readily prepared by techniques known from the literature . this synthesis scheme is shown below : ## str3 ## the acid addition salts of the triazoles of this invention can be prepared by standard techniques well - known in the art . for example , the triazole of formula ( i ) can be dissolved in an appropriate solvent such as diethyl ether , tetrahydrofuran , ethanol , methanol and the like or combinations thereof and treated with an equivalent or excess amount of a mineral or organic acid which may or may not be dissolved in an appropriate solvent , the mixture is then either cooled or evaporated to give the salt which can either be used as such or recrystallized from an appropriate solvent or combination of appropriate solvents . the metal salt complexes of the above triazoles of this invention can be prepared by adding dropwise , with stirring , a stoichiometric amount of a metal salt dissolved in an appropriate solvent or combination of solvents to a solution of the triazole of formula ( i ) dissolved in a similarly appropriate solvent or combination of solvents . the reaction mixture is briefly stirred and the solvent is removed under reduced pressure to give the metal salt complex of the respective triazoles of formula ( ii ). the metal salt complexes can also be prepared by mixing stoichiometric or excess amounts of the metal salt and a triazole of formula ( i ) in the desired amount of solvent containing the appropriate adjuvants just prior to spraying the plants . adjuvants that may be included in this &# 34 ; in situ &# 34 ; preparation may be detergents , emulsifiers , wetting agents , spreading agents , dispersing agents , stickers , adhesives , and the like which are used in agricultural applications . solvents that can be utilized in these procedures include any polar solvent , e . g ., water , methanol , ethanol , isopropanol or ethylene glycol and any aprotic dipolar solvent , e . g ., dimethylsulfoxide , acetonitrile , dimethylformamide , nitromethane or acetone . the metal salt cations that can be used in these procedures can be selected from the group consisting of calcium , magnesium , manganese , copper , nickel , zinc , iron , cobalt , tin , cadmium , mercury , chromium , lead , barium and the like . any appropriate anion , e . g ., chloride , bromide , iodide , sulfate , bisulfate , phosphate , nitrate , perchlorate , carbonate , bicarbonate , hydrosulfide , hydroxide , acetate , oxalate , malate , citrate and the like may be utilized as the counterion in the metal salt . the compounds of this invention possess an asymmetric carbon atom and thus exist as racemic mixtures . the d and 1 enantiomorphs in these racemic mixtures can be separated via standard techniques such as fractional crystallization with d - tartaric acid , 1 - tartaric acid , 1 - quinic acid and the like followed by basification and extraction of the d or 1 enantiomorph free base . the enantiomorphs , acid addition salts and metal salt complexes of the present invention are useful as agricultural fungicides and as such can be applied to various loci such as the seed , the soil or the foliage . for such purposes these compounds can be used in the technical or pure form as prepared , as solutions or as formulations . the compounds are usually taken up in a carrier or are formulated so as to render them suitable for subsequent dissemination as fungicides . for example , these chemical agents can be formulated as wettable powders , emulsifiable concentrates , dusts , granular formulations , aerosols , or flowable emulsion concentrates . in such formulations , the compounds are extended with a liquid or solid carrier and , when desired , suitable surfactants are incorporated . it is usually desirable , particularly in the case of foliar spray formulations , to include adjuvants , such as wetting agents , spreading agents , dispersing agents , stickers , adhesives and the like in accordance with agricultural practices . such adjuvants commonly used in the art can be found in the john w . mccutcheon , inc . publication &# 34 ; detergents and emulsifiers , annual .&# 34 ; in general , the compounds of this invention can be dissolved in certain solvents such as acetone , methanol , ethanol , dimethylformamide or dimethyl sulfoxide and such solutions can be extended with water . the concentrations of the solution can vary from about 1 % to about 90 % with a preferred range being from about 5 % to about 50 %. for the preparation of emulsifiable concentrates , the compound can be dissolved in suitable organic solvents , or a mixture of solvents , together with an emulsifying agent which permits dispersion of the fungicide in water . the concentration of the active ingredient in emulsifiable concentrates is usually from about 10 % to about 90 % and in flowable emulsion concentrates , this can be as high as about 75 %. wettable powders suitable for spraying , can be prepared by admixing the compound with a finely divided solid , such as clays , inorganic silicates and carbonates , and silicas and incorporating wetting agents , sticking agents , and / or dispersing agents in such mixtures . the concentration of active ingredients in such formulations is usually in the range of from about 20 % to about 98 %, preferably from about 40 % to about 75 %. a typical wettable powder is made by blending 50 parts of alpha -( 4 - chlorophenyl )- alpha - butyl - 1h - 1 , 2 , 4 - triazole - 1 - propanenitrile , 45 parts of a syntheic precipitated hydrated silicon dioxide sold under the trademark hi - sil ®, and 5 parts of sodium lignosulfonate . in another preparation a kaolin type ( barden ) clay is used in place of the hi - sil in the above wettable powder , and in another such preparation 25 % of the hi - sil is replaced with a synthetic sodium silico aluminate sold under the trademark zeolex ® 7 . dusts are prepared by mixing the triazoles , enantiomorphs , salts and complexes thereof with finely divided inert solids which can be organic or inorganic in nature . materials useful for this purpose include botanical flours , silicas , silicates , carbonates and clays . one convenient method of preparing a dust is to dilute a wettable powder with a finely divided carrier . dust concentrates containing from about 20 % to about 80 % of the active ingredient are commonly made and are subsequently diluted to from about 1 % to about 10 % use concentration . the enantiomorphs , salts and complexes thereof can be applied as fungicidal sprays by methods commonly employed , such as conventional high - gallonage hydraulic sprays , low - gallonage sprays , air - blast spray , aerial sprays and dusts . the dilution and rate of application can be readily determined by one in the art depending upon the type of equipment used , the desired method , timing and frequency of applications , plants to be treated and disease to be controlled . generally , however , the fungicidal compounds of the present invention will be applied in an amount of from about 0 . 01 to about 20 pounds of active ingredient per acre when applied foliarly or to the soil . as a seed protectant , the amount of the compound coated on the seeds is usually from about 0 . 05 to about 4 ounces of active ingredient per hundred pounds of seed and preferably from 0 . 1 to about 1 ounce per hundred pounds of seed . as a soil fungicide the compounds can be incorporated in the soil or applied to its surface usually at a rate of from about 0 . 05 to about 20 pounds , preferably from about 0 . 02 to about 10 pounds and more preferably from about 0 . 01 to about 3 pounds of active ingredient per acre . as a foliar fungicide , the compounds are usually applied to growing plants at a rate of from about 0 . 01 to about 10 pounds , preferably from about 0 . 02 to about 5 and more preferably from about 0 . 03 to about 1 pound of active ingredient per acre . fungicides which can be combined with the fungicides of this invention include : ( a ) dithiocarbamate and derivatives such as : ferric dimethyldithiocarbamate ( ferbam ), zinc dimethyldithiocarbamate ( ziram ), manganese ethylenebisdithiocarbamate ( maneb ) and its coordination product with zinc ion ( mancozeb ), zinc ethylenebisdithiocarbamate ( zineb ), zinc propylenebisdithiocarbamate ( propineb ), sodium methyldithiocarbamate ( metham ), tetramethylthiuram disulfide ( thiram ), the complex of zineb and polyethylene thiuram disulfide , 3 , 5 - dimethyl - 1 , 3 , 5 - 2 - h - tetrahydrothiadiazine - 2 - thione ( dazomet ); and mixtures of these and mixtures with copper salts ; ( b ) nitrophenol derivatives such as : dinitro -( 1 - methylheptyl ) phenyl crotonate ( dinocap ), 2 - sec - butyl - 4 , 6 - dinitrophenyl 3 , 3 - dimethylacrylate ( binapacryl ), and 2 - sec - butyl - 4 , 6 - dinitrophenyl isopropyl carbonate ; ( c ) heterocyclic structures such as : n - trichloromethylthiotetrahydrophthalimide ( captan ), n - trichloromethylthiophthalimide ( folpet ), 2 - heptadecyl - 2 - imidazole acetate ( glyodine ), 2 - octylisothiazol - 3 - one , 2 , 4 - dichloro - 6 -( o - chloroanilino )- s - triazine , diethyl phthalimidophosphorothioate , 4 - butyl - 1 , 2 , 4 - triazole , 5 - amino - 1 [ bis ( dimethylamino )- phosphinyl ]- 3 - phenyl - 1 , 2 , 4 - triazole , 5 - ethoxy - 3 - trichloromethyl - 1 , 2 , 4 - thiadiazole , 2 , 3 - dicyano - 1 , 4 - dithiaanthraquinone ( dithianon ), 2 - thio - 1 , 3 - dithio -[ 4 , 5 - b ] quinoxaline ( thioquinox ) methyl 1 -( butylcarbamoyl )- 2 - benzimidazole carbamate -( benomyl ), 2 -( 4 &# 39 ;- thiazolyl ) benzimidazole -( thiabendazole ), 4 -( 2 - chlorophenylhydrazono )- 3 - methyl - 5 - isoxazolone , pyridine - 2 - thiol - 1 - oxide , 8 - hydroxyquinoline sulfate and metal salts thereof ; 2 , 3 - dihydro - 5 - carboxanilido - 6 - methyl - 1 , 4 - oxathiin - 4 , 4 - dioxide , 2 , 3 - dihydro - 5 - carboxanilido - 6 - methyl - 1 , 4 - oxathiin , alpha -( phenyl )- alpha -( 2 , 4 - dichlorophenyl )- 5 - pyrimidinyl - melthanol ( triarimol ), cis - n -[( 1 , 1 , 2 , 2 - tetrachloroethyl ) thio ]- 4 - cyclohexene - 1 , 2 - dicarboxyimide , 3 -[ 2 -( 3 , 5 - dimethyl - 2 - oxycyclohexyl )- 2 - hydroxy ]- glutarimide ( cycloheximide ), dehydroacetic acid , n -( 1 , 1 , 2 , 2 - tetrachloroethylthio )- 3a , 4 , 7 , 7a - tetrahydrophthalimide ( captafol ), 5 - butyl - 2 - ethylamino - 4 - hydroxy - 6 - methylpyrimidine ( ethirimol ), acetate of 4 - cyclododecyl - 2 , 6 - dimethylmorpholine ( dodemorph ), and 6 - methyl - 2 - oxo - 1 , 3 - dithiolo -[ 4 , 5 - b ] quinoxaline ( quinomethionate ). ( d ) miscellaneous halogenated fungicides such as : tetrachloro - p - benzoquinone ( chloranil ), 2 , 3 - dichloro - 1 , 4 - naphthoquinone ( dichlone ), 1 , 4 - dichloro - 2 , 5 - dimethoxybenzene ( chloroneb ), 3 , 5 , 6 - trichloro - o - anisic acid ( tricamba ), 2 , 4 , 5 , 6 - tetrachloroisophthalonitrile ( tcpn ), 2 , 6 - dichloro - 4 - nitroaniline ( dichloran ), 2 - chloro - 1 - nitropropane , polychloronitrobenzenes such as : pentachloronitrobenzene ( pcnb ) and tetrafluorodichloroacetone ; ( f ) copper - based fungicides such as : cuprous oxide , basic cupric chloride , basic copper carbonate , copper naphthenate , and bordeaux mixture ; and ( g ) miscellaneous fungicides such as : diphenyl , dodecylguanidine acetate ( dodine ), phenylmercuric acetatic , n - ethylmercuri - 1 , 2 , 3 , 6 - tetrahydro - 3 , 6 - endomethano - 3 , 4 , 5 , 6 , 7 , 7 - hexachlorophthalimide , phenylmercuric monoethanol ammonium lactate , p - dimethylaminobenzenediazo sodium sulfonate , methyl isothiocyanate , 1 - thiocyano - 2 , 4 - dinitrobenzene , 1 - phenylthiosemicarbazide , nickel - containing compounds , calcium cyanamide , lime sulfur , sulfur , and 1 , 2 - bis ( 3 - methoxycarbonyl )- 2 - thioureido ) benzene ( thiophanatemethyl ). the enantiomorphs , acid addition salts and metal salt complexes of this invention can be advantageously employed in various ways . since these compounds possess broad spectrum fungicidal activity , they can be employed as fungicides in turf , fruit orchards , vegetable crops , cereal crops , golf course applications and the storage of cereal grain . other applications of this invention will suggest themselves to those skilled in the art of agriculture and horticulture . in a 300 ml three neck flask fitted with a mechanical stirrer , thermometer and addition funnel was added 20 . 8 gm ( 0 . 1 mol ) of ( p - chlorophenyl ) hexanenitrile , 34 . 8 gm ( 0 . 2 mol ) of methylene bromide and 50 ml of dmso . to the reaction flask was added 24 ml of 50 % ( w / w ) sodium hydroxide , dropwise over a 35 minute period . upon completion of the reaction , it was quenched by adding 500 ml of water . the aqueous mixture was extracted three times with ether , then the combined ether extracts were washed three times with water and once with brine . the organic phase was dried over sodium sulfate , filtered and the solvent removed by rotary evaporation yielding 22 . 6 gm of a yellow oil . nmr : 60 mhz 0 . 8 - 2 . 0 δ ( m , 9h ), 4 . 0 δ ( br , s , 2h ) and 7 . 4 δ ( s , 2h ). in a single neck 500 ml flask fitted with a magnetic stirrer and drying tube was added 26 . 6 gm ( 0 . 09 mol ) of 1 - bromo - 2 - cyano - 2 -( 4 - chlorophenyl ) hexane , followed by 19 . 0 gm of potassium triazole ( 0 . 18 mol ) and 100 ml of dmso . the reaction was stirred for about 48 hours at room temperature and then stirred for about 24 hours at 70 ° c . the reaction was quenched by pouring it into 1500 ml of water . the aqueous mixture was extracted four times with ether and the combined either extracts were washed twice with water and once with brine . the organic phase was dried over sodium sulfate , concentrated and redissolved in a minimum amount of ether . hexane was added until the solution was cloudy , and then flask was placed in the freezer . the crystals which formed were filtered off and dried . the filtrate was concentrated to obtain additional less pure material for a total of 13 . 0 gm . elemental analysis -- theoretical ( found ): c : 62 . 36 ( 62 . 55 , 62 . 38 ); h : 5 . 94 ( 6 . 07 , 6 . 00 ); n : 19 . 41 ( 19 . 22 , 19 . 35 ); cl : 12 . 28 ( 11 . 00 , 11 . 90 ). in a four neck one liter flask fitted with a reflux condenser , mechanical stirrer and addition funnel was placed 227 . 4 gm ( 1 . 5 mol ) of 4 - chlorophenylacetonitrile , 235 . 6 gm ( 3 . 0 mol ) of 1 - chloropropane and 4 . 8 gm ( 0 . 15 mol ) of tetrabutylammonium bromide . 300 gm ( 3 . 75 mol ) of 50 % ( w / w ) naoh was added dropwise over 30 minutes . the reaction mixture quickly exothermed to 50 ° c . and the reaction flask was placed in a cold water bath until the reaction mixture cooled to 35 ° c . thereafter , the reaction mixture was heated for an additional 4 hours at 50 ° c ., then the reaction was quenched by adding 1500 ml of water . the mixture was extracted twice with ether and the organic phase was washed with water and then with 200 ml of 10 % ( w / w ) hydrochloric acid . the ether was dried , filtered , concentrated and distilled . the distillate was collected , at 105 ° c . at 0 . 5 mm , and two main fractions of 156 . 3 gm ( 88 % purity ) and 88 gm ( 60 % purity ) were obtained . the higher purity material was used in the bromomethylation of step b . nmr : 60 mhz ( d - chcl 3 ): 1 . 0 - 2 . 0 δ ( m , 7h ), 3 . 8 - 3 . 9 δ ( t , 1h ) and 7 . 5 δ ( s , 4h ). in a 2000 ml four neck flask fitted with a reflux condensor , mechanical stirrer , thermometer and addition funnel was placed 305 . 0 mg ( 1 . 57 mol ) of 2 -( 4 - chlorophenyl ) pentanenitrile , 409 . 4 gm ( 2 . 36 mol ) of dibromomethane and 400 ml of dmso . 50 % ( w / w ) sodium hydroxide ( 251 . 2 gm , 3 . 00 mol ) was added dropwise over 2 hours with the reaction temperature rising to 50 ° c . a water bath was used to maintain the reaction at about 40 ° c . and after about 4 hours , the reaction was quenched by adding 100 ml of water . after sitting at room temperature for about 16 hours , the mixture was diluted with 1000 ml of ice water , extracted with ether , the combined ether extracts were washed twice with water and then with 10 % ( w / w ) hydrochloric acid and dried over sodium sulfate . the ether was removed by rotary evaporation and the remaining dmso removed under high vacuum to yield 361 . 2 gm of the bromide derivative . nmr : 60 mhz ( d - chcl 3 ) 1 . 0 - 2 . 2 δ ( m , 7h ), 4 . 0 δ ( br s , 2h ) and 7 . 5 δ ( s , 4h ). in a single neck one liter flask was placed 361 . 2 gm ( 1 . 26 mol ) of 1 - bromo - 2 - cyano - 2 -( 4 - chlorophenyl ) pentane and 300 ml of dmso . the potassium salt of triazole ( 270 . 0 gm , 2 . 52 mol ) was added and the flask was placed on a rotary evaporator for 1 hour at 75 ° c . to dissolve the triazole salt . the flask was then heated at 90 ° c . for 4 hours , followed by stirring at room temperature overnight ( about 16 hours ). the reaction was found to be incomplete and reheated to 120 ° c . for about 12 hours followed by stirring it at 90 ° c . for about 36 hours . upon completion of the reaction , the reaction mixture was cooled to room temperature and diluted with 1500 ml of ice water . the water was extracted with 250 ml of ether ; however , since the product crystallized in the ether layer , this layer was then diluted with 1500 ml of ethyl acetate and extracted . the water layer was additionally extracted twice with ethyl acetate and the combined organic extracts were separated into two batches . each was extracted with water ( 6 × 150 ml ) and once with brine . the dark brown organic phase was dried over sodium sulfate and then filtered . the solution was treated then with activated charcoal and filtered and stripped to give a crystalline cake which was recrystallized from ethyl acetate : ether . the product was kept in the freezer for 16 hours and then filtered and washed with hexane . the filtrate was concentrated , hexane added and then triturated to yield an additional solid which was combined with the first crop to give 166 . 8 gm of product . elemental analysis -- theoretical ( found ): c : 61 . 20 ( 61 . 16 ); h : 5 . 50 ( 5 . 56 ); n : 20 . 39 ( 20 . 26 ); cl : 12 . 91 ( 12 . 66 ). the phase transfer procedure was employed as with 2 -( 4 - chlorophenyl ) pentanenitrile , with 400 gm ( 2 . 96 mol ) of p - fluorophenylacetonitrile , 548 gm ( 5 . 92 mol ) of 1 - chlorobutane , 592 gm ( 7 . 4 mol ) of 50 % ( w / w ) sodium hydroxide and 9 . 07 gm ( 0 . 3 mol ) of tetrabutylammonium bromide . the base was added over 2 . 5 hours with the reaction temperature rising to 35 ° c . the reaction was then stirred for about 12 hours at 45 ° c . upon completion , the reaction was quenched with water and the mixture was extracted and washed as in example 1 and then distilled to yield 358 . 8 gm of 91 % pure product . nmr data : 60 mhz ( d - chcl 3 ): 0 . 8 - 2 . 0 δ ( m , 9h ), 3 . 7 - 3 . 8 δ ( t , 1h ) and 7 . 4 - 7 . 5 δ ( br s , 4h ). the bromomethylation procedure of example 1 was employed using 358 . 1 gm ( 1 . 875 mol ) of 50 % ( w / w ) sodium hydroxide , 488 . 9 gm ( 2 . 81 mol ) of dibromomethane and 400 ml of dmso , sodium hydroxide ( 50 %, w / w ) was added dropwise over about 2 hours with the reaction exotherming to 90 ° c . the reaction mixture was cooled to 50 ° c . and the mixture was stirred for 11 hours until the reaction was about 90 % complete . the reaction was quenched and worked up in the manner described in example 1a to yield 379 . 5 gm of a 88 % pure product . the product was used directly to prepare the triazole adduct . nmr : 0 . 8 - 2 . 0 δ ( m , 9h ), 4 . 0 δ ( br s , 2h ), and 7 . 4 δ ( s , 4h ). in a 2 liter four neck flask was placed 379 . 5 gm ( 1 . 33 mol ) of 1 - bromo - 2 - cyano - 2 -( 4 - fluorophenyl )- hexane and 300 ml of dmso to which 156 gm ( 1 . 46 mol ) of potassium triazole was added . the reaction mixture was stirred overnight at 90 ° c . the product was worked up in the manner described in example 1b to yield 340 . 5 gm of a semisolid , 83 % pure . nmr data : 60 mhz ( d - chcl 3 ): 1 . 0 - 2 . 2 δ ( m , 9h ), 4 . 8 δ ( s , 2h ), 7 . 0 - 7 . 8 δ ( m , 4h ), 8 . 05 δ ( s , 1h ) and 8 . 10 δ ( s , 1h ). to 50 . 0 gm ( 0 . 37 mol ) of 4 - fluorophenylacetonitrile , 0 . 6 gm of tetraethyl ammonium bromide , 50 gm ( 0 . 407 mol ) of 1 - bromopropane and 50 ml of dmso was added 35 . 5 gm ( 0 . 44 mol ) of 50 % ( w / w ) sodium hydroxide at room temperature . after the addition was complete , the reaction was stirred at 50 °- 60 ° c . for 3 hours . the reaction mixture was extracted with ether , the organic phase washed with water and then 10 % ( w / w ) hydrochloric acid . the ether was dried , filtered and distilled to give 23 grams of the product ( b . p . 105 °- 110 ° c . at 5 mm ). nmr : 60 mhz ( d - chcl 3 ) 0 . 9 - 2 . 2 δ ( m , 7h ), 3 . 8 - 4 . 0 δ ( t , 1h ), 7 . 0 - 7 . 6 δ ( m , 4h ). the bromomethylation of the previous examples was employed using 23 . 0 gm ( 0 . 129 mol ) of 2 -( 4 - fluorophenyl ) pentanenitrile and 22 . 5 gm ( 0 . 129 mol ) of dibromoethane in 50 ml of dmso . to the reaction mixture was added 11 . 95 gm ( 0 . 15 mol ) of 50 % ( w / w ) sodium hydroxide while stirring at room temperature . the reaction was heated to 60 ° c . for 3 hours , cooled to room temperature and worked up in the manner described in the previous examples , e . g ., 3b . there was obtained 20 . 5 gm of the bromide derivative which was used directly below in step c . nmr : 0 . 7 - 2 . 2 δ ( m , 7h ), 3 . 9 δ ( q , 2h ), and 7 . 0 - 7 . 8 δ ( m , 4h ). to a solution of 8 . 1 gm ( 0 . 76 mol ) of potassium triazole and 30 ml of dmso was added with 15 gm ( 0 . 58 mol ) of 1 - bromo - 2 - cyano - 2 -( 4 - fluorophenyl ) pentane while maintaining the temperature at 50 ° c . while stirring , the reaction mixture was heated further to 80 ° c . for 1 hour and then heated at 100 ° c . for 24 hours . the product was worked up as described in example 3c and after concentration and trituration , 1 . 3 gm of a white solid , m . p . 75 °- 76 ° c ., was obtained . elemental analysis -- theoretical ( found ): c : 65 . 09 ( 64 . 80 ); h : 5 . 86 ( 5 . 95 ); n : 21 . 69 ( 20 . 77 ); f : 7 . 36 ( 7 . 02 ). nmr : 90 mhz ( d - chcl 3 ) 0 . 9 - 1 . 0 δ ( t , 3h ), 1 . 2 - 1 . 8 δ ( m , 2h ), 1 . 9 - 2 . 2 δ ( t , 2h ), 3 . 7 - 3 . 9 δ ( q , 2h ), 7 . 0 - 7 . 5 δ ( m , 4h ) and 7 . 9 δ ( br s , 2h ). the compounds of examples 1 - 4 were tested for their antifungal activity against wheat leaf rust ( wlr ), wheat powdery mildew ( wpm ) and barley spot blotch ( bsb ). the test procedures were as follows : pennoll wheat seedlings about 7 days old were sprayed to runoff with a solution of the test compound comprising 75 parts per million of the test compound suspended in a 2 : 1 : 1 mixture of water , acetone and methanol . after drying , the plants were inoculated with a uredial suspension of p . recondita ( 20 , 000 uredial / ml ). the plants were incubated at 22 ° c . in a mist for 24 hours . after seven days of futher incubation on a greenhouse bench , the percent disease control was determined by counting uredial pustules and comparing it to the number of pustules on control plants . pennoll wheat seedlings ( 7 - 14 days old ) were trimmed to provide a uniform plant height and to facilitate unifrom inoculation . twenty - four hours after their trimming , they were sprayed to runoff with a test compound comprising 5 parts per million of the test compound suspended in a 2 : 1 : 1 mixture of water , acetone and methanol . then mildew spores of wheat powdery mildew cultured on wheat seedlings in a controlled temperature room were shaken from the cultured plants onto the pennoll wheat seedlings . the inoculated seedlings were kept in the controlled temperature room and subirrigated . the percent disease control was rated 8 - 10 days after inoculation . pennrad barley seedlings about 7 days old were sprayed to runoff with a test compound comprising 10 parts per million of the test compound suspended in a 2 : 1 : 1 mixture of water , acetone and methanol . after drying , the plants were inoculated with a conidial suspension of h . sativum ( 20 , 000 conidia / ml ). the plants were incubated at 22 ° c . in a mist for 24 hours . after five days of further incubation on a greenhouse bench , the percent disease control was measured by counting lesions and comparing it to the number of lesions on the control plants . the results of the tests are presented below in table 1 . the disease control ratings utilized in table 1 are as follows : a = 97 - 100 % disease control , b = 90 - 96 % disease control , c = 70 - 89 % disease control , d = 50 - 69 % disease control and e = 49 % or less disease control . table 1______________________________________ disease control ratingcompound wlr wpm bsb______________________________________1 a a b2 a a a3 a b b4 a a c______________________________________

US-21195788-A