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Impaired washout--embolism and ischemic stroke: further examples and proof of concept. We previously posited that impaired washout of emboli was an important mechanism of brain infarction in patients with cerebral hypoperfusion. Hyperviscosity and hypoperfusion enhance thrombus formation promoting embolization of fresh thrombi. Hypoperfusion also reduces dissolution of emboli due to reduced flow velocity leading to classic hemodynamic patterns of stroke. To prove this concept further, we identified patients with severe hemodynamic compromise of either arterial or venous origin, or both, and natural or iatrogenic mechanisms of embolism. Three conditions were investigated in a stroke MRI protocol: 5 patients who had conventional cerebral angiography for the diagnosis of moyamoya disease, 1 patient with atrial fibrillation and thrombosis of the left transverse dural sinus and 1 patient with a patent foramen ovale with atrial septum aneurysm presenting with thrombosis of cortical cerebral veins. In all patients, subcortical arterial embolization within an atypical borderzone of hypoperfusion was observed.

[The effect of heart rate on the time constant of isovolumic relaxation of the left ventricle]. A time constant (T) of the left ventricular isovolumic relaxation, which expresses the relaxation rate of the left ventricle, may be affected by change of the heart rate. There are few clinical reports concerning the relationship between T and heart rate. We studied the relationship between T and heart rate in 10 patients with normal coronary arteries and left ventricular function. Left ventricular pressure was measured using a catheter-tip manometer during right atrial pacing, which was performed at the rate of 10, 20, 40 beats/min in addition to the baseline rate, and finished at 140 or 150 beats/min. Two measurements were made for T.1) Tw from the slope of In (pressure) against time, and 2) Tb by exponential analysis which also estimated the asymptote. As the heart rate increased, both Tw and Tb gradually shortened (Tw: from 38.5 +/- 4.9 msec at the control heart rate to 28.9 +/- 5.6 msec at 140 or 150 beats/min; Tb: from 54.7 +/- 11.4 msec at the control heart rate to 34.9 +/- 5.7 msec at 140 or 150 beats/min). These findings suggest that left ventricular isovolumic relaxation is strongly affected by change of the heart rate in man.

[Truth after death]. Diagnosis is central to medicine. In spite of tremendous diagnostic technological advances, no infallible test exists and in the complex diagnostic process the physician may well get lost. The ultimate feedback on the accuracy of diagnosis is the autopsy. Five patients illustrate that the autopsy may disclose unexpected results. The first patient was a 9-year-old girl who suffered from daily abdominal spasmodic pain but each time recovered. She died suddenly; autopsy revealed intestinal intussusception. A 46-year-old man who was treated for hypertension developed pain in the chest and the lower back, but there were no other signs of myocardial infarction. He died suddenly; autopsy revealed a dissecting aortic aneurysm with rupture in the left pleural cavity. A 21-year-old woman, an excellent swimmer, drowned during a swim in the sea. Autopsy revealed severe widespread coronary disease with multiple myocardial infarction. A 32-year-old Surinam woman developed acute coma and died from cardiorespiratory arrest. At autopsy she had massive pulmonary embolism and generalized lymphadenopathy due to sarcoidosis. The last patient, a 32-year-old woman suffered from fatigue after her fourth child was born. She was admitted with severe dyspnoea and her chest X-ray showed interstitial fibrosis. She died presently and autopsy revealed metastatic colon carcinoma with pulmonary lymphangitis carcinomatosa. Systematic reviews of the results of autopsies show no decline in the percentage of false diagnoses and/or unexpected findings in spite of the enormous growth of the diagnostic armamentarium. Although we may radiologically 'slice' the body in incredible detail or investigate human cells at the molecular level, the autopsy has by no means become obsolete and is an invaluable tool for quality control and teaching.

Simultaneous binding of a cyclophane and classical intercalators to DNA: observation of FRET-mediated white light emission. DNA-assisted Förster resonance energy transfer (FRET) between an anthracene-based cyclophane (CP) and mono- and bis-intercalators such as propidium iodide (PI) and ethidium homodimer-1 (EHD), respectively, has been studied using various photophysical and biophysical techniques. The cyclophane and PI exhibited simultaneous binding to DNA at all concentrations studied and showed DNA-assisted FRET from the excimer of cyclophane with a FRET efficiency of ca. 71%. On the other hand, the bis-intercalator EHD, only at lower concentrations (<3 μM), can act as an acceptor for the energy transfer process with a lower efficiency of ca. 44%. At higher concentrations (>15 μM), EHD, on account of its higher binding affinity, displaces cyclophane from the DNA scaffold. Employing the ternary system comprising of the cyclophane, DNA and PI and fine-tuning the concentrations of the components in a molar ratio of 1 : 0.75 : 0.05 (CP : DNA : PI) we have demonstrated white light emission with CIE coordinates (0.35, 0.37).

Structural defects in chronic peritoneal dialysis catheters contributing to peritonitis. Recurrent peritonitis remains a critical problem in patients treated with continuous ambulatory peritoneal dialysis. 3 case histories are presented documenting an association between catheter defects and peritonitis. Illustrative defects are shown. Improved awareness of the hazard and better catheter design may reduce the risks of peritonitis.

Improvement of treatment outcomes after implementation of comprehensive pharmaceutical care in breast cancer patients receiving everolimus and exemestane. Combination therapy with everolimus and an aromatase inhibitor such as exemestane is an effective treatment option for advanced or recurrent breast cancer. However, the therapy is often limited because of the occurrence of severe adverse events (AEs), including oral mucositis, interstitial lung disease, diarrhea, and rash. Therefore, early management of AEs is extremely important to obtain maximum treatment outcome. We investigated here the effects of comprehensive pharmaceutical care for prevention of severe AEs on patient's quality-of-life (QOL) and continuation of therapy. QOL was assessed every month based on the five-level version of EuroQol-5-Dimension (EQ-5D-5L). AEs were graded according to the Common Terminology Criteria for Adverse Events (ver 4.0). Implementation of comprehensive pharmaceutical care remarkably reduced the incidence of severe oral mucositis as compared with those without such interventions. EQ-5D-5L health states were almost constant during 6 months after intervention, ranging from 0.850 to 0.889. Median time to treatment failure (TTF) was significantly longer after intervention than before [224.0 days, 95% confidence interval (CI): 117-331 days versus 34 days, 21-47 days, hazard ratio (HR): 0.027, 95% CI: 0.005 - 0.154, p<0.001]. These findings suggest that our comprehensive pharmaceutical care is highly effective for enhancing treatment outcome by maintaining patient's QOL.

Vasculitis and thrombotic thrombocytopenic purpura in a patient with limited scleroderma. Inflammatory vasculopathy and thrombotic thrombocytopenic purpura (TTP) are rare complications of scleroderma. We report a 54-year-old woman with limited cutaneous scleroderma who developed medium size and small vessel vasculitis. Inflammatory changes of medium size muscular arteries presented as ovarian vasculitis and mononeuritis multiplex, while arteriolar involvement presented as TTP with associated central nervous system involvement. In addition, possible noninflammatory involvement of small muscular arteries was expressed as Raynaud's phenomenon.

Rat ovarian insulin-like growth factor I (IGF-I) gene expression is granulosa cell-selective: 5'-untranslated mRNA variant representation and hormonal regulation. We, and others, have recently reported that the ovary is a site of insulin-like growth factor (IGF)I gene expression. It was the objective of the present studies to assess the relative ovarian abundance of IGF-I transcripts with alternative 5'-untranslated (UT) regions, their cellular localization, and hormonal regulation. To this end, a solution hybridization/RNase protection assay was employed wherein total rat ovarian RNA was hybridized with a 404-base 32P-labelled rat IGF-I riboprobe corresponding to the Class A 5'UT variant. As in liver, three protected bands [322 (Class A), 297 (Class B), and 242 (Class C) bases long] were noted, in keeping with established alternative 5' UT transcripts. The ovarian (as the hepatic) Class C variant proved the most abundant. The ovarian Class B variant was barely detectable. Cellular localization studies revealed these ovarian IGF-I transcripts to be primarily, if not exclusively, of granulosa but not theca-interstitial cell origin. Treatment of immature (21-23 days old) hypophysectomized rats with a diethylstilbestrol (DES)-containing subcutaneous silastic implant for a total of 5 days resulted in a 2-fold increase in the (densitometrically quantified) abundance of ovarian IGF-I transcripts, a diametrically-opposed effect (2.6-fold decrease) being noted at the level of the liver. Whereas treatment of hypophysectomized rats with oGH by itself (150 micrograms, qd, sc x5 days) resulted in a 5-fold increase in hepatic IGF-I gene expression, a limited, albeit distinct inhibitory effect was observed on the steady-state levels of ovarian IGF-I mRNA. In contrast, combined treatment with oGH and DES yielded a 3-fold increase in the abundance of ovarian IGF-I transcripts, there being no net alteration in hepatic IGF-I gene expression. Taken together, these findings reveal ovarian expression of the 3 known 5'-UT IGF-I mRNA variants, document the granulosa cell as the main somatic ovarian cell of IGF-I mRNA generation, and indicate that hepatic and ovarian IGF-I gene expression are differentially regulated in diametrically opposed directions.

A study on the mechanisms by which minocycline protects against MDMA ('ecstasy')-induced neurotoxicity of 5-HT cortical neurons. 3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is a selective 5-HT neurotoxin in rat brain which has been shown to produce acute neuroinflammation characterized by activation of microglia and release of interleukin-1beta (IL-1beta). We aimed to determine whether or not minocycline, a semi-synthetic tetracycline antibiotic capable of inhibiting microglial activation, could prevent the inflammatory response and reduce the toxicity induced by MDMA. Adult male Dark Agouti rats were given minocycline twice a day for 2 days (45 mg/kg on the first day and 90 mg/kg on the second day; 12-h apart, i.p.). MDMA (12.5 mg/kg; i.p.) was given after the third minocycline injection and animals were killed either 1 h later for the determination of NFkappaB binding activity, 3 h later for the determination of IL-1beta, 24 h later for the determination of microglial activation or 7 days later for the determination of [(3)H]-paroxetine binding as a measure of 5-HT neurotoxicity. MDMA increased NFkappaB activation, IL-1beta release and microglial activation both in the frontal cortex and in the hypothalamus and 7 days later produced a reduction in the density of 5-HT uptake sites in both these brain areas. Minocycline prevented the MDMA-induced increase in NFkappaB activation, IL-1beta release and microglial activation in the frontal cortex and prevented the 5-HT neurotoxicity 7 days later. However, in the hypothalamus, in spite of preventing MDMA-induced microglial activation, minocycline failed to prevent MDMA-induced NFkappaB activation, IL-1beta release and neurotoxicity. This suggests that the protective mechanism of minocycline against MDMA-induced neurotoxicity in frontal cortex involves inhibition of MDMA-induced NFkappaB activation possibly through a reduction in IL-1beta signalling.

[Myasthenia gravis in patients over 50 years of age]. A study was made in the Clinical Provincial Hospital for Surgical Teaching Saturnino Lora in Santiago de Cuba. A group of 23 patients over 50 years of age attended this centre and were treated for the onset of myasthenia gravis between January 1983 and December 1997. To determine some of the clinical and evolutive characteristics of the disease such as: sex, age of onset, initial symptoms of the illness, clinical forms and also the different types of treatment used, evolution and mortality. There was a clear predominance of men, the commonest age of onset was from sixty to seventy, the predominant clinical forms were generalized (mild or moderate), and the initial symptoms were ocular. The most commonly used treatment was by anticholinesterases and steroids. There is significant variability in the evolution of these patients. The larger group improved. However, there was high mortality, mainly in older men.

Determining the effectiveness of conventional and alternative coagulants through effective characterization schemes. Polymeric forms of metal coagulants in water treatment have become increasingly used due to their wider availability and reduction in cost. These specialized coagulant forms and products are claimed by manufacturers to be superior to conventional coagulants in particulate and/or organic removal with inherent advantages of lower alkalinity consumption and lesser sludge production. However, due to their proprietary nature, little is known about their chemical composition. To determine and understand the effectiveness of these alternative coagulants, a comprehensive study was undertaken to characterize metal coagulants, and to comparatively evaluate them on a well-characterized source water. The objective of this study was to provide a scheme for utilities that could be employed as a screening process and a method of selecting an appropriate coagulant based on raw water characteristics and insight into the coagulatability of the source water. Characterizations of coagulants included: (i) active metal content, (ii) anion content, (iii) acidity, (iv) alkalinity consumption, (v) charge reversal by colloidal titration, and (vi) molecular weight determination. A total of five poly-aluminum chlorides (PACl), along with a conventional coagulant (aluminum sulfate or alum) were evaluated. Results show that through the characterization scheme, an effective coagulant (conventional versus alternative) and coagulant type (among various PACl) can be chosen before undertaking time-consuming bench or pilot-scale evaluation.

Efficacy study of two novel hyaluronic acid-based formulations for viscosupplementation therapy in an early osteoarthrosic rabbit model. Viscosupplementation (VS) is a therapy for osteoarthrosis (OA) consisting of repetitive intra-articular injections of hyaluronic acid (HA). It is known to be clinically effective in relieving pain and increasing joint mobility by restoring joint homeostasis. In this study, the effects of two novel HA-based VS hydrogel formulations were assessed and challenged against a pure HA commercial formulation for the first time and this in a rabbit model of early OA induced by anterior cruciate ligament transection (ACLT). The first formulation tested was a hybrid hydrogel composed of HA and reacetylated chitosan, a biopolymer considered to be chondroprotective, assembled thanks to an ionic shielding. The second formulation consisted of a novel HA polymer grafted with antioxidant molecules (HA-4AR) aiming at decreasing OA oxidative stress and increasing HA retention time in the articulation. ACLT was performed on rabbits in order to cause structural changes comparable to traumatic osteoarthrosis. The protective effects of the different formulations were observed on the early phase of the pathology in a full randomized and blinded manner. The cartilage, synovial membrane, and subchondral bone were evaluated by complementary investigation techniques such as gross morphological scoring, scanning electron microscopy, histological scoring, and micro-computed tomography were used. In this study, ACLT was proven to successfully reproduce early OA articular characteristics found in humans. HA and HA-4AR hydrogels were found to be moderately protective for cartilage as highlighted by μCT. The HA-4AR was the only formulation able to decrease synovial membrane hypertrophy occurring in OA. Finally, the hybrid HA-reacetylated chitosan hydrogel surprisingly led to increased subchondral bone remodeling and cartilage defect formation. This study shows significant effects of two innovative HA modification strategies in an OA rabbit model, which warrant further studies toward more effective viscosupplementation formulations.

Nipah viral encephalitis or Japanese encephalitis? MR findings in a new zoonotic disease. An epidemic of suspected Japanese encephalitis occurred in Malaysia in 1998-1999 among pig farmers. In neighboring Singapore, an outbreak occurred among pig slaughterhouse workers. It was subsequently established that the causative agent in the outbreak was not the Japanese encephalitis virus but a previously unknown Hendra-like paramyxovirus named Nipah virus. The brain MR images of eight patients with Nipah virus infection were reviewed. All patients tested negative for acute Japanese encephalitis virus. Seven patients had contrast-enhanced studies and six had diffusion-weighted examinations. All patients had multiple small bilateral foci of T2 prolongation within the subcortical and deep white matter. The periventricular region and corpus callosum were also involved. In addition to white matter disease, five patients had cortical lesions, three had brain stem involvement, and a single thalamic lesion was detected in one patient. All lesions were less than 1 cm in maximum diameter. In five patients, diffusion-weighted images showed increased signal. Four patients had leptomeningeal enhancement and four had enhancement of parenchymal lesions. The brain MR findings in patients infected with the newly discovered Nipah paramyxovirus are different from those of patients with Japanese encephalitis. In a zoonotic epidemic, this striking difference in the appearance and distribution of lesions is useful in differentiating these diseases. Diffusion-weighted imaging was advantageous in increasing lesion conspicuity.

Identification and characterization of a pan-allergen profilin, a major allergen from Caryota mitis pollen. Caryota mitis is a common plant in tropical and subtropical areas. It produces larger amount of pollen, which has great potential for allergenicity in the pollination season. This study aims to identify the components of Caryota mitis pollen contributing to human allergic diseases. The sera from 20 patients with a positive skin prick test to Caryota mitis pollen crude extract (CmPCE) were collected; the allergic components were determined by the forming of immune complexes in the sera and CmPCE. The results were confirmed by the immune competitive inhibitory assay. Sixteen out of 20 collected serum samples reacted to a 14 kDa protein fractioned from CmPCE; this 14 kDa antigen also had positive reactions to CmPCE in an ELISA assay. 12 samples from 20 collected serums positively reacted to recombinant CmProfilin (rCmProfilin), as shown by Western blotting, and also showed positive reactivity in ELISA. Preincubation of sera with rCmProfilin eliminated the reactivity of the patients' sera to this 14 kDa band. A 14 kDa protein from the CmPCE was identified as the major allergic component of CmPCE.

Animal models of induced apoptotic death in the substantia nigra. Apoptosis is a form of cell death in which genetically regulated programs intrinsic to the cell bring about its own demise. In recent years, there has been a tremendous growth of interest in apoptosis as a mechanism of disease in a wide range of human disorders including the neurodegenerative diseases, such as Parkinson's disease (PD) (1). This growth of interest has spawned an extraordinary number of recent discoveries about the molecular basis of apoptosis. It is important to emphasize, however, that much of this new knowledge has been attained in the study of relatively simple systems, such as invertebrate models or mammalian nonneural cell culture systems. Less is known about these mechanisms in neural cells, and much of what is known is based on studies of peripheral neural cells (such as sympathetic ganglia and PC 12 cells) in tissue culture. Much less is known about central neurons; in particular, we know little about the regulation of apoptotic death in central neurons in living animals. It is especially important to try to identify the mechanisms of cell death in central neurons of known phenotype, particularly those implicated in human neurodegenerative disease, such as the dopamine neurons in PD. The purpose of the models we have developed of induced apoptosis in dopamine neurons of the substantia nigra (SN) is to try to translate what is being learned about the molecular mechanisms of apoptosis in simpler systems to these neurons.

[Side-effects of frequently administered hypnotics and sedatives as well as of anxiolytics. Results from a Comprehensive Hospital Drug Monitoring (CHDM) program]. The occurrence and age distribution of patients with adverse drug reactions (ADR) were studied on the basis of a total of 17,653 admissions to the medical divisions of the Zieglerspital Bern and the Anna-Seiler-Haus, Inselspital Bern, during the period 1976-1982. Among this population 12,424 patients (70.4%) happened to have been treated with hypnotics, sedatives or anxiolytics. Results are as follows: 1. The occurrence rate of psychic and neurologic symptoms (with the exception of somnolence and hangover) is 0.14% of all treatments if the casualty category "definitely or probably drug-induced" is considered. For "other ADR" (non-psychic, non-neurologic) the rate is 0.16%. For the benzodiazepine preparations, the psychic and neurologic ADR occurred at about the same rate as for the neuroleptic drugs studied, whereas "other ADR" related to benzodiazepines were observed in only 0.04% of treatments. 2. There is a marked difference in ADR symptoms between benzodiazepines and neuroleptics. With benzodiazepines the most severe reactions were two episodes of shortlived respiratory arrest immediately after intravenous administration. With neuroleptic drugs the most severe symptoms were choreoathetosis, dyskinesia, hyperkinesia and Parkinson's syndrome. There was no fatal reaction. 3. With benzodiazepines there is a slight but significant increase in the occurrence of psychic and neurologic symptoms in the older group of patients, as compared to the younger patients, whereas with neuroleptics there is no age dependence.

The anterior wall of the third cerebral ventricle and homeostatic responses to dehydration. Within the anterior wall of the third cerebral ventricle, structures are found which have been implicated in the regulation of fluid and electrolyte balance. These structures include the subfornical organ (SFO), preoptic medianus nucleus (PMN) and the organum vasculosum of the lamina terminalis (OVLT). In sheep, the OVLT rises from the ventricular floor over the optic chiasma and occupies most of the midline ventricular wall up to the level of anterior commissure. It contains a plexus of blood vessels at its base which possess fenestrated endothelial cells, and appears to lack ependyma. The SFO of sheep bulges into the third ventricle above the anterior commissure and the PMN is situated between the SFO and OVLT, surrounding the rostral edge of the midline anterior commissure. Like most mammals, water deprivation in sheep results in hypertonicity of body fluids, thirst and graded increase in plasma concentration of vasopressin (AVP). Dehydration also causes a natriuresis in these animals. In sheep with combined ablation of OVLT/PMN tissue, the volume of water drunk, the increases in plasma vasopressin (AVP) level, and the natriuresis in response to dehydration were considerably attenuated, and extreme hypernatremia resulted. Additionally, ablation of OVLT/PMN tissue almost abolished water drinking and AVP secretion in response to systemic infusion of hypertonic NaCl, but did not diminish AVP secretion in response to haemorrhage. In other animals, the OVLT and PMN were individually ablated. While partial osmoregulatory deficits were observed in each case, these deficits were smaller than those observed with combined OVLT/PMN ablation. In contrast to these results, the homeostatic responses to dehydration were not diminished in sheep with combined SFO/PMN lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin resistance in the St. Thomas' mixed hyperlipidaemic (SMHL) rabbit, a model for familial combined hyperlipidaemia. The St. Thomas mixed hyperlipidaemic (SMHL) rabbit exhibits an inherited hyperlipidaemia similar to that seen in familial combined hyperlipidaemia (FCHL). In this study, we investigated whether the SMHL rabbit is insulin resistant, a condition often associated with FCHL. Six young and six mature combined hyperlipidaemic SMHL rabbits, age/sex matched New Zealand White (NZW) control rabbits and six young hypercholesterolaemic Watanabe heritable hyperlipidaemic (WHHL) control rabbits were fed a 0.08% (w/w) cholesterol-enriched diet for at least 1 month prior to the start of the experiment. We performed an oral glucose tolerance test after an overnight fast by dosing the rabbits with a solution of 1 g of glucose per kg body weight. Blood was withdrawn just before and 15, 30, 45, 60 and 120 min after administration of the oral glucose dose. Plasma glucose levels were similar in SMHL, WHHL and NZW rabbits throughout the oral glucose tolerance test. Fasting glucose levels were slightly increased in WHHL rabbits but not in young and adult SMHL rabbits as compared to NZW rabbits. The area under the curve (AUC) for the insulin response was significantly increased for both young (P<0.05) and mature (P<0.05) SMHL rabbits, and in WHHL rabbits, compared with NZW rabbits. The AUC for the ratio of glucose:insulin response to the glucose dose was decreased in young and mature SMHL rabbits (P<0.05 and P<0.01, respectively) and in young WHHL rabbits (P<0.05), compared with NZW rabbits. Only WHHL rabbits showed an increased AUC for the non-esterified fatty acid response compared to NZW rabbits. Log-transformed plasma triglycerides values were significantly correlated with the log-transformed AUC for the insulin response in young SMHL rabbits (r=0.81; P<0.05) and with the AUC for the insulin response in mature SMHL rabbits (r=0.84; P<0.05). WHHL rabbits showed no significant correlation. In conclusion, SMHL rabbits are insulin resistant, the severity of which appears to increase with age. Therefore, the SMHL rabbit offers a valuable animal model in which to study the relation between hypertriglyceridaemia and insulin resistance.

Modifications of abdominal fat and hepatic insulin clearance during severe caloric restriction. Using computed tomography on 19 obese female subjects, we determined abdominal adipose tissue, both subcutaneous and visceral adipose tissue, before and after 2 weeks of a very low caloric diet (VLCD). The following parameters were also determined before and after 15-20 days of VLCD: plasma glucose and insulin levels, oral glucose tolerance test, basal pancreatic insulin secretion estimated by fasting C peptide (Cp), and fasting insulin hepatic clearance calculated by Cp/insulin molar ratio. After VLCD the body weight and body mass index significantly declined (p less than 0.01); whereas abdominal adipose tissue and visceral abdominal tissue (VAT) significantly decreased (p less than 0.01), modifications of subcutaneous abdominal tissue (SAT) were not significant. Fasting insulin levels and plasma glucose response to oral glucose load significantly decreased (p less than 0.05). Insulin response remained unchanged. Cp immunoreactive insulin (IRI) significantly increased (p less than 0.01). A significant positive correlation was found between delta VAT and delta Cp/IRI before and after VLCD (p less than 0.01). Our data seem to suggest that the weight loss induced by VLCD fundamentally involves a decrease in VAT. The reduction in visceral fat could be associated with an increase in hepatic insulin clearance.

[Practical experiences in the execution of transurethral prostate resection]. In comparison to the open adenomectomy the transurethral electroresection of the prostate demands extraordinarily high technical abilities of the operator and at the same time he is confronted with a considerable psychic and physical stress. But almost inversely proportional to this personal engagement is the minimum stress of the patient after operation, the nursing staff and the economy of the hospital. From the point of view of a clinical urological department with a profile of general care the author adopts a definite attitude to the problems of the establishment of the transurethral electroresection of the prostate.

[Cytomegalovirus and arterial disease. Current aspects]. The cytomegalovirus (CMV) is the only microbial agent implicated in three particular types of arterial disease: coronary disease of the transplanted heart, post-angioplasty restenosis and atherosclerosis. The object of this article is to analyse the recent data on the role of CMV in these pathologies with an exhaustive review of the literature. The available data is mainly epidemiological but the interpretation is difficult because of the multiplicity and imperfections of the diagnostic techniques of the infection. However, the results are quite concordant in favour of a real association. Different physiopathological mechanisms are proposed. In coronary disease of the transplanted heart, the lesions could be initiated by an inflammatory process. In post-angioplasty restenosis, the virus seems able to trigger cellular proliferation by inhibiting the mechanisms of apoptosis. Finally, in atherosclerosis, CMV infection seems to promote atherothrombotic processes and accelerate the progression of atherosclerotic plaques by activating inflammatory cells. Direct methods of detection of viral DNA show the presence of the virus within these lesions. There is, therefore, epidemiological, anatomo-pathological and physiopathological evidence in favour of a relationship between CMV infection and these three forms of arterial disease.

Potential cost-effectiveness of colorectal cancer chemoprevention with nonsteroidal anti-inflammatory drugs. Colorectal cancer is the second leading cause of cancer-related death in the Western world. Screening for colorectal neoplasia, including the removal of adenomas, is highly effective and cost-effective in reducing colorectal cancer incidence and mortality. However, only a minority of the population is currently screened. Based on data from animal models, observational studies and randomized trials in humans, nonsteroidal anti-inflammatory drugs appear to have great promise as chemopreventive agents against colorectal cancer. The critical factors that will determine the roles of aspirin, other nonselective nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors in colorectal cancer chemoprevention include the magnitude of their protective effect, their risks, their costs, the treated population's characteristics, treatment adherence rates and how chemoprevention compares with established screening strategies.

[Immunological mechanisms of specific hyposensitization in allergic diseases of an infectious nature. II. A correlative analysis of the interrelationships between different immunological processes during autovaccine immunotherapy]. The results of the correlative analysis carried out in the study of the character of relationship between characteristics indicating different forms of immune response (cellular and humoral immunity, sensitization) in 30 patients with infectious allergic bronchial asthma before and after therapy with autovaccine are summarized. The analysis has revealed the features of interrelations between the characteristics under the study and pointed out that the character of relationship between different characteristics may change under the influence of autovaccinal therapy. The data thus obtained are used for elucidating the mechanism of autovaccinal therapy and for the evaluation of its efficiency.

Photoaffinity labelling of the human platelet thromboxane A2/prostaglandin H2 receptor. The synthesis, binding and photoincorporation of a thromboxane A2/prostaglandin H2 (TXA2/PGH2) analog (9,11-dimethylmethano-11,12-methano-16-(3-[125I]iodo-4-azidophenyl )-13,14- dihydro-13-aza-15 alpha beta-omega-tetranor-TXA2) [( 125I]PTA-Azido) to washed human platelets was characterized. Kinetic analysis of the binding of [125I]PTA-Azido at 30 degrees C yielded a k1 of 1.83.10(7) M-1.min-1 and k -1 of 0.195 min-1, Kd = k -1/k1 = 11 nM. Incubation of washed human platelets with [125I]PTA-Azido followed by photolysis resulted in the radiolabelling of a number of platelet proteins as assessed by SDS-PAGE autoradiography. The radiolabelling of three of these protein bands could be either uniformly blocked or reduced with a series of structurally dissimilar TXA2/PGH2 receptor antagonists or agonists and corresponded to proteins with a molecular mass of 43, 39 and 27 kDa. In addition, the incorporation of [125I]PTA-Azido into the three proteins was stereoselectively blocked by a pair of optically active stereoisomers that are TXA2/PGH2 receptor antagonists. Two-dimensional gel electrophoresis indicated that the 43 kDa protein possessed a pI value of 5.6 and that the 27 kDa protein exists in at least three isoforms with pI values of 4.9, 5.1 and 5.3. The labelling pattern was not altered by a mixture of proteinase inhibitors. The data suggest that one or more of these specifically radiolabelled proteins may represent the human platelet TXA2/PGH2 receptor.

Comparison of novel methods for predicting the risk of pro-inflammatory clinical infusion reactions during monoclonal antibody therapy. Two methods for predicting the risk of pro-inflammatory clinical infusion reactions during monoclonal antibody therapy were evaluated. In the first, the antibody of interest is immobilised by air-drying onto 96-well plates prior to the addition of human peripheral blood mononuclear cells (PBMCs). In the second, the antibody is added in aqueous phase to a co-culture of human PBMCs and human endothelium-derived cells. In both methods the cells are incubated with the antibody to allow the accumulation of pro-inflammatory cytokines, quantified by enzyme-linked immunosorbent assay (ELISA). The antibodies associated with clinical infusion reactions, Herceptin, Campath-1H and TGN1412, gave the largest responses taking into account the data for all readouts (tumour necrosis factor-α, TNF, interleukin-6, IL-6, IL-8, IL-2 and cell proliferation) for both methods. Overall, the antibodies tested could be ranked as follows: Tysabri<Avastin<Herceptin<Campath-1H<TGN1412, with only the "superagonistic" CD28 monoclonal antibody (TGN1412) stimulating IL-2 release and cell proliferation.

Chronic levodopa therapy enhances dopa absorption: contribution to wearing-off. Effects of the chronic administration of levodopa on its peripheral pharmacokinetics and the contribution of the pharmacokinetics to the pathogenesis of the wearing-off phenomenon are re-evaluated. The concentration of plasma levodopa and clinical symptoms were determined 4 hours after oral levodopa (levodopa 100 mg + benserazide 25 mg) administration on 55 parkinsonian patients. Long-term levodopa therapy markedly increased the peak levodopa concentration (Cmax) and the area under the time-concentration curve (AUC); whereas, it decreased time to the peak concentration (Tmax) and the elimination half-life (T1/2). These results suggest that long-term levodopa therapy accelerates the absorption of levodopa. The wearing-off group (n = 23), however, had a markedly higher Cmax and AUC, and a shorter Tmax and T1/2 than the stable group (n = 32). We speculate that the clinical expression of "stable" or "wearing-off" depends on the absorption of levodopa as well as the presynaptic terminal and post synaptic receptors.

Haem precursors and porphobilinogen deaminase in erythrocytes and lymphocytes of patients with acute intermittent porphyria. Patients with AIP can be subdivided into three different groups concerning their PBGD activity in erythrocytes: The first of which has lowered, the second overlapping and the third normal PBGD activity. Out of 385 AIP patients 87% had lowered, 8% had overlapping and 5% had normal PBGD activity. Gene carriers of AIP having slight, moderate or high metabolic aberrations of excretion parameters are recognized by analysis of urinary haem precursors and faecal porphyrins. The haem precursor excretion of the groups with lowered, overlapping and normal PBGD activity in erythrocytes compared to each other is not significantly different but differs significantly (p < 0.001) from the normal values. One individual suffering from AIP was detected in a family with normal PBGD. Lymphocytes can be stored in liquid nitrogen for 3 months without loss of PBGD activity. Specific PBGD activity in lymphocytes is 5% from specific PBGD activity in erythrocytes. In AIP patients with lowered specific PBGD activity in erythrocytes specific PBGD activity is lowered to the same extent in their lymphocytes.

Postmeningitis subdural fluid collection in infants: changing pattern and indications for surgery. Postmeningitis subdural fluid collection (PMSFC) is a classic complication of bacterial meningitis in infants. When the diagnosis was based solely on subdural puncture (SDP), its incidence was estimated to be as high as one half of the cases of meningitis, with Haemophilus influenzae as the most common causative bacterium. Knowledge concerning the diagnostic and bacteriological characteristics of PMSFC has expanded greatly since the introduction of computerized imaging and the use of the anti-H. influenzae vaccine; however, in no recent study have the authors reappraised this clinical entity with regard to diagnosis, bacteriology, and indications for surgery. The authors reviewed their cases of PMSFC in infants in which a diagnosis was made based on computerized tomography findings and confirmed with SDP. They treated PMSFC using placement of a subdural drain whenever the collection was either clinically eloquent or exerted a mass effect on the brain. In the 26 years preceding the study, the authors had treated 29 patients younger than 16 months of age for PMSFC. Eight patients required SDP only, 20 underwent surgical drainage, and five required craniotomy. In six cases, the fluid was grossly purulent; in the others, it was clear, xanthochromatic, or hemorrhagic. Cultures were positive for Streptococcus pneumoniae in only two cases. Although H. influenzae was the most common bacterium at the beginning of the series, Neisseria meningitidis has become more prevalent since vaccination against the former became widespread. Based on their data the authors estimate that 5% of N. meningitidis infections in infants are complicated by a significant PMSFC. At present, PMSFCs are most often caused by N. meningitidis. Temporary surgical drain placement is advised for all cases in which a significant mass effect is apparent on imaging.

Permanent antimicrobial cotton fabrics obtained by surface treatment with modified guanidine. Antimicrobial cotton fabrics received much attention for the demand of health and hygiene fields. In this work, an antimicrobial copolymer was prepared via a reaction between polyhexamethylene guanidine hydrochloride and polypropylene glycol diglycidyl ether. The copolymer has amphiphilic characteristic and excellent antimicrobial properties. When the copolymer was adhered onto cotton fabrics through physical adsorption and chemical bonding using dipping-drying method, the resultant cotton fabrics had excellent and durable antimicrobial properties. The antimicrobial rates against Escherichia coli and Staphylococcus aureus were higher than 99.99% when the adsorption amount of the copolymer was above 35.5mg/g. The antimicrobial cotton fabrics remained the excellent antimicrobial properties even after laundered with detergent solution.

Laboratory markers of perinatal acidosis are poor predictors of neurodevelopmental impairment in very low birth weight infants. In asphyxiated term and near-term infants, therapeutic hypothermia increases survival without neurologic morbidity, and extending this new treatment to preterm infants is being debated. To investigate the association of low pH and base excess (BE) at birth or admission, as used as entry criteria in cooling trials, and evolving brain damage in preterm infants. Rates of death and neurodevelopmental impairment at 12 and 20 months corrected age were assessed in a cohort of 1137 preterm infants with a gestational age <35 weeks and birth weight <1500 g in relation to severe perinatal acidosis (umbilical artery pH≤7.0, pH at admission ≤7.0, BE at admission ≤-16 mmol/l, lowest BE during first 12 h of life ≤-16 mmol/l). Umbilical artery pH was not linked to death or neurodevelopmental impairment. There was only weak predictive power of pH or BE at admission for death (positive predictive values [PPV] 0.36/0.30, receiver operator characteristics [ROC] areas 0.591/0.701), and lowest 12-h BE for death or neurodevelopmental impairment at 12 or 20 months (PPV 0.29/0.30/0.27, ROC 0.720/0.656/0.658). In very preterm infants, there is little association between laboratory markers of severe perinatal acidosis and neurodevelopmental outcome at 12 or 20 months.

Complications of adenotonsillectomy in patients younger than 3 years. To evaluate the complication rate for adenotonsillectomy in children younger than 3 years, without a diagnosis of severe obstructive sleep apnea, to assess the necessity for postoperative inpatient admission. Retrospective medical record review (January 1, 2003, through October 31, 2009). Tertiary care academic medical center. Retrospective medical record review of 105 patients younger than 3 years who underwent adenotonsillectomy performed by a single surgeon. Nineteen patients were excluded from our review because of incomplete medical records or severe underlying disease, leaving a total of 86 patients with medical records available for inclusion in our study. Patient medical records were deidentified and reviewed for age, sex, indications for surgery, intraoperative and perioperative interventions, and postoperative complications. One child with a diagnosis of severe obstructive sleep apnea was excluded from the study. Complications, including bleeding, dehydration requiring admission, and airway intervention, during the intraoperative or perioperative period were recorded. The mean age of the study population was approximately 27.5 months (range, 13-35 months), with most children (76.5%) between 23 and 31 months of age. Among the patients whose records were reviewed, 80 (93.0%) did not experience any intraoperative or postoperative complications. Dehydration was the most common complication and was the cause of all documented readmissions (4.7%) in our patients who ranged in age from 14 to 30 months. Two patients had other complications, reactive airway disease (n=1) and postoperative fever (n=1), which were identified and treated in the postanesthesia care unit, resulting in same-day discharge. No airway complications were noted in our study. Our study reveals a low complication rate in children younger than 3 years. The recommendations for mandatory admission for children younger than 3 years should be reexamined. Criteria for inpatient admission for children younger than 3 years should be based on preoperative and postoperative clinical evaluation of the patient and an evaluation of the family resources for adequately caring for young children at home in the postoperative period. These recommendations apply only to otherwise healthy children (American Society of Anesthesiologists classifications I and II) without a diagnosis of severe obstructive sleep apnea syndrome.

Age and ideal chunk size. We tested young, middle-aged, and older adults for ability to organize six-letter sequences when these subjects were not externally induced to chunk the letter sets. In order to determine whether subjects would use optimal chunk sizes of two, three, or six letters, a serial recall task on which subjects were cued using digits was employed. From these data, the total number of correctly recalled sequences was computed, in addition to global and stop transitional error probabilities (TEPs). The results indicated that older adults recalled fewer correct sequences than did the young adults. However, both the global and stop TEP analyses demonstrated that all three age groups were chunking the six-letter sequences into two sets of three letters each. The present study (along with Allen & Coyne, 1988a, 1989) suggests that there are no appreciable age differences in functional chunk capacity, but that older adults exhibit poorer serial recall than younger adults.

Biochemical changes in Glomus fasciculatum colonized roots of Lycopersicon esculentum in presence of Meloidogyne incognita. Glasshouse experiments were conducted to elicit biochemical substantiation for the observed difference in resistance to nematode infection in roots colonized by mycorrhiza, and susceptibility of the fresh flush of roots of the same plant that escaped mycorrhizal colonization. Tomato roots were assayed for their biochemical profiles with respect to total proteins, total phenols, indole acetic acid, activities of polyphenol oxidase, phenylalanine ammonia lyase and indole acetic acid oxidase. The roots of the same plant (one set) received Glomus fasciculatum and G. fasciculatum plus juveniles of Meloidogyne incognita separately; and half the roots of second set of plants received G. fasciculatum while the other half of roots did not receive any treatment. Roots colonized by G. fasciculatum recorded maximum contents of proteins and phenols followed by that of the roots that received G. fasciculatum plus M. incognita. However, IAA content was lowest in the roots that received mycorrhiza or mycorrhiza plus juveniles of root-knot nematode and correspondingly. Roots that received juveniles of root-knot nematode recorded maximum IAA content and per cent increase over healthy check and mycorrhiza-inoculated roots. The comparative assay on the activities of PPO, PAL and IAA oxidase enzymes in treated and healthy roots of tomato, indicated that PAL and IAA oxidase activities were maximum in G. fasciculatum colonized roots followed by the roots that received mycorrhiza plus juveniles of root-knot nematode, while the activity of PPO was minimum in these roots. The roots that received juveniles of root-knot nematode recorded minimum PAL and IAA oxidase activities and maximum PPO activity. Since the roots of same plant that received mycorrhiza and that did not receive mycorrhiza; and the plant that received nematode alone and mycorrhiza plus nematode recorded differential biochemical contents of proteins, total phenols and IAA, and differential activities of enzymes under study, it was evident that the biochemical defense response to mycorrhizal colonization against root-knot nematodes was localized and not systemic. This explained for the response of plant that differed in root galling due to nematode infection in presence of mycorrhizal colonization. The new or fresh roots which missed mycorrhizal colonization, got infected by nematodes and developed root galls.

Peritoneoscopy of the liver stained by intravenous injection of indocyanine green-experimental and clinical studies. Liver surface patterns were observed by peritoneoscopy after intravenous injection of indocyanine green (ICG). The normal rat liver was diffusely stained dark greenish-brown 5 minutes after the injection of ICG 25 mg/kg body weight into the tail vein. Green spots persisted longer in the centrolobular area, clearly revealing lobular markings. This regional difference in hepatocyte staining suggested differing abilities of hepatocytes to take up or excrete ICG. This dyeing technique was applied to liver disease patients. The liver was diffusely stained light greenish-brown 5 minutes after the injection of ICG 5 mg/kg body weight. In patients, especially those with obscure lobular markings before ICG injection, lobules were clearly demarcated by reddish terminal portal veins against a green background. This simplified detection of lobular distortions. Prenodular patches (Kalk's Bunteflecke) on the liver surface were stained green more intensely than surrounding areas, which supports the hypothesis that patches are composed of active hepatocytes.

Prevalence of steatosis and insulin resistance in patients with chronic hepatitis B compared with chronic hepatitis C and non-alcoholic fatty liver disease. The association of NAFLD with chronic hepatitis C (CHC) has been extensively studied but little is known about its coexistence with chronic hepatitis B (CHB). To investigate the prevalence and determinants of steatosis and insulin resistance (IR) in CHB and its consequences on liver injury compared with CHC and NAFLD. Patients with CHB (N=110), CHC (N=111) and NAFLD (N=136) were evaluated by biomarkers of steatosis (SteatoTest>0.38 as a surrogate for steatosis >5%), IR (HOMA-IR>2.7 as a surrogate for IR) and fibrosis (FibroTest>0.48 as a surrogate for significant fibrosis, ≥F2). HOMA-IR gradually increased in CHB, CHC and NAFLD: 2.3±1.8; 3±2.6 and 3.8±2.7 (p<0.001). The prevalence of steatosis >5% was 21% (CHB), 43% (CHC) and 82% (NAFLD), (p<0.001). The prevalence of fibrosis≥F2 was 10% (CHB), 42% (CHC) and 21% (NAFLD), p<0.001. In CHB, IR was related to host and not viral factors. CHB patients with steatosis had higher BMI (29±5.7kg/m(2) vs. 24±4kg/m(2), p<0.001), waist circumference (96±14cm vs. 84±11cm, p=0.001) and HOMA-IR (3.9±2.6 vs. 1.8±1.2, p<0.001) than those without steatosis. HOMA-IR independently predicted steatosis in CHB (OR=1.9, 95% CI, 1.09-3.27, p<0.05) and CHC (OR=1.38; 95% CI, 1.07-1.78, p<0.02). In CHB, metabolic risk factors and HOMA-IR were not associated with significant fibrosis. HOMA-IR was an independent predictor of fibrosis in CHC. Steatosis may co-exist in CHB patients but with a lower prevalence than in CHC and NAFLD. In CHB steatosis is related to host and not viral factors, and is not associated with the severity of fibrosis.

Self-perception of dentofacial attractiveness among patients requiring orthognathic surgery. To test the hypothesis that the self-perception of dental and facial attractiveness among patients requiring orthognathic surgery is no different from that of control patients. Happiness with dental and facial appearance was assessed using questionnaires completed by 162 patients who required orthognathic treatment and 157 control subjects. Visual analog scale, binary, and open response data were collected. Analysis was carried out using a general linear model, logistic regression, and chi-square tests. Orthognathic patients were less happy with their dental appearance than were controls. Class II patients and women had lower happiness scores for their dental appearance. Among orthognathic patients, the "shape" and "prominence" of their teeth were the most frequent causes of concern. Older subjects, women, and orthognathic patients were less happy with their facial appearance. Class III orthognathic patients, older subjects, and women were more likely to have looked at their own face in profile. A greater proportion of Class II subjects than Class III subjects wished to change their appearance. The hypothesis is rejected. The findings indicate that women and patients requiring orthognathic surgery had lower levels of happiness with their dentofacial appearance. Although Class II patients exhibited the lowest levels of happiness with their dental appearance, there was some evidence that concerns and awareness about their facial profile were more pronounced among the Class III patients.

Association between methylene tetrahydrofolate reductase and glutathione S-transferase M1 gene polymorphisms and chronic myeloid leukemia in a Brazilian population. Chronic myeloid leukemia is a hematopoietic stem cell disorder that causes uncontrolled proliferation of white blood cells. Although the clinical and biological aspects are well documented, little is known about individual susceptibility to this disease. We conducted a case-control study analyzing the prevalence of the polymorphisms MTHFR C677T, MTHFR A1298C, del{GSTM1}, del{GSTT1}, and haptoglobin in 105 patients with chronic myeloid leukemia (CML) and 273 healthy controls, using PCR-based methods. A significant association with risk of developing CML was found for MTHFR 1298AA (odds ratio (OR) = 1.794; 95% confidence interval (CI) = 1.14-2.83) and GSTM1 non-null (OR = 1.649; 95%CI = 1.05-2.6) genotypes, while MTHFR 1298AC (OR = 0.630; 95%CI = 0.40-0.99) and GSTM1 null (OR = 0.606; 95%CI = 0.21-0.77) genotypes significantly decreased this risk. There appeared to be selection for heterozygosity at the MTHFR 1298 locus. The considerable range of variation in this and other human populations may be a consequence of distinctive processes of natural selection and adaptation to variable environmental conditions. The Brazilian population is very mixed and heterogeneous; we found these two loci to be associated with CML in this population.

Between credit claiming and blame avoidance: the changing politics of priority-setting for Korea's National Health Insurance System. Priority-setting involves diverse parties with intense and often conflicting interests and values. Still, the political aspects of priority-setting are largely unexplored in the literature on health policy. In this paper, we examine how policy makers in Korea changed their strategies as the policy context for priority setting changed from only expanding benefits to a double burden of benefit expansion plus cost containment. This analysis shows that priority-setting is a profoundly political process. The policy context shapes how policy makers choose their political strategies. In particular, we find that policy makers sway between "credit claiming" and "blame avoidance" strategies. Korean policy makers resorted to three types of political strategies when confronted with a double burden of benefit expansion and cost containment: delegating responsibility to other institutions (agency strategies), replacing judgment-based decisions with automatic rules (policy strategies), and focusing on the presentation of how decisions are made (presentational strategies). The paper suggests implications for future studies on priority-setting in the Korean health care system and in other countries that face similar challenges, and concludes that Korean policy makers need to put more effort into developing transparent and systematic priority-setting processes, especially in times of double burden of benefit expansion and cost containment.

Treatment of fully edentulous patients with ITI implants. The use of ITI implants for rehabilitation of the edentulous patient has shown predictable results not only in the standard sites but also in cases of advanced alveolar ridge atrophy. Preoperative analysis, including clinical and radiological evaluation, implant selection, and determination of implant number and distribution in the edentulous maxilla and mandible, is described in this article. The surgical procedures used in standard sites are presented, the benefits of a nonsubmerged surgical approach in these cases are emphasized, and a protocol for postoperative management is recommended. Augmentation procedures in advanced osseointegration surgery call for submerged ITI implants when a simultaneous approach is chosen. Several types of advanced implant surgery that can be used are described, including membrane technique, sinus lift procedures, vertical ridge augmentation with iliac bone grafts, and correction of sagittal jaw relationship.

Involvement of mitogen-activated protein kinases and nuclear factor-kappa B activation in nitric oxide-induced interleukin-8 expression in human pulp cells. This study examined the effect of nitric oxide (NO) on interleukin-8 (IL-8) production and the involvement of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kappaB) signaling pathways in primary cultured human pulp cells. IL-8 production was measured using enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. MAPK activation and IkappaB degradation and phosphorylation were determined by western blotting. Sodium nitroprusside (SNP), an NO donor, has increased IL-8 secretion and mRNA expression in a dose- and time-dependent manner. SNP induced the phosphorylation of p38 MAPK and extracellular-regulated kinase (ERK), degradation and phosphorylation of IkappaB, and activation of NF-kappaB. Furthermore, inhibition of the ERK, p38, and NF-kappaB pathways blocked SNP-induced IL-8 secretion. Human pulp cells showed NO-induced IL-8 expression via the MAPK and NF-kappaB pathways, which may play an important role in the inflammatory responses of pulp and periapical lesions.

Bone health in Down syndrome. Patients with Down syndrome have a number of risk factors that theoretically could predispose them to osteoporosis, such as early aging, development disorders, reduced physical activity, limited sun exposure, frequent comorbidities and use of drug therapies which could affect bone metabolism. In addition, the bone mass of these people may be affected by their anthropometric and body composition peculiarities. In general terms, studies in adults with Down syndrome reported that these people have lower areal bone mineral density (g/cm2) than the general population. However, most of them have not taken the smaller bone size of people with Down syndrome into account. In fact, when body mineral density is adjusted by bone size and we obtain volumetric body mineral density (g/cm3), the difference between both populations disappears. On the other hand, although people with Down syndrome have risk factor of hypovitaminosis D, the results of studies regarding 25(OH)D in this population are not clear. Likewise, the studies about biochemical bone markers or the prevalence of fractures are not conclusive.

[Late thrombosis of sirolimus-eluting stent occurring in the perioperative period]. We report a late thrombosis of sirolimus-eluting stent 6 months after implantation of a drug-eluting stent. A 70-year-old man (52 kg, 148 cm) was diagnosed as acute cauda equina syndrome, and spinal surgery was scheduled. One week before the operation, the patient's aspirin and clopidogrel regimen was replaced with heparin injection, which was then discontinued 8 hours before the operation. The operation was completed uneventfully. The patient complained of severe chest pain 1 hour after the end of operation. Coronary angiography demonstrated stent thrombosis. PCI (removal of the thrombosis and plain old balloon angioplasty) was performed, and incomplete stent apposition was diagnosed with coronary angiography.

Synthesis, structure, anion binding, and sensing by calix[4]pyrrole isomers. The synthesis, structure, and anion binding properties of chromogenic octamethylcalix[4]pyrroles (OMCPs) and their N-confused octamethylcalix[4]pyrrole isomers (NC-OMCPs) containing an inverted pyrrole ring connected via alpha'- and beta-positions are described. X-ray diffraction analyses proved the structures of two synthesized isomeric pairs of OMCPs and NC-OMCPs. The addition of anions to solutions of chromogenic OMCPs and NC-OMCPs resulted in different colors suggesting different anion-binding behaviors. The chromogenic NC-OMCPs showed significantly stronger anion-induced color changes compared to the corresponding chromogenic OMCP, and the absorption spectroscopy titrations indicated that chromogenic OMCPs and NC-OMCPs also possess different anion binding selectivity. Detailed NMR studies revealed that this rather unusual feature stems from a different anion-binding mode in OMCPs and NC-OMCPs, one where the beta-pyrrole C-H of the inverted pyrrole moiety participates in the hydrogen-bonded anion-NC-OMCP complex. Preliminary colorimetric microassays using synthesized chromogenic calixpyrroles embedded in partially hydrophilic polyurethane matrices allow for observation of analyte-specific changes in color when the anions are administered in the form of their aqueous solutions and in the presence of weakly competing anions.

Copper-catalyzed direct C-H arylation of pyridine N-oxides with arylboronic esters: one-pot synthesis of 2-arylpyridines. The first example of the copper-catalyzed direct C-H arylation of pyridine N-oxides with arylboronic esters has been developed, leading to a wide range of 2-arylpyridines in a one-pot synthesis with moderate to good yields without an additional reductant. This transformation allows for rapid access to a variety of 2-arylpyridines using an inexpensive catalytic system that would be more difficult to access with traditional methods. Thus, this method represents a simple and practical procedure to access 2-arylpyridines.

Factor analysis of the Montgomery Asberg Depression Rating Scale in 251 bipolar II and 306 unipolar depressed outpatients. Symptomatological differences between bipolar II (n = 251) and unipolar (n = 306) depressed outpatients, interviewed with the Structured Clinical Interview for DSM-IV, were studied by Montgomery Asberg Depression Rating Scale factor analysis. Different factors were found in bipolar II [factor 1 (apparent sadness, reported sadness), factor 2 (reduced sleep, reduced appetite), factor 3 (concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts)], and in unipolar [factor 1 (apparent sadness, reported sadness, inability to feel, suicidal thoughts), factor 2 (concentration difficulties, lassitude, inability to feel, pessimistic thoughts), factor 3 (inner tension, reduced sleep)]. Different factor structure (between bipolar II and unipolar depression) supports previous findings that response to antidepressants and biology may be different in bipolar II and unipolar depression.

Composting of waste paint sludge containing melamine resin and the compost's effect on vegetable growth and soil water quality. Melamine resin (MR) is introduced to the environment from many industrial effluents, including waste paint sludge (WPS) from the automobile industry. Melamine resin contains a high nitrogen (N) content and is a potential N source during composting. In this study, two carbon sources, waste paper (WP) and plant residue (PR), were used to study their effects on composting of WPS. Additional work tested the WPS-composts effects on plant growth and soil water quality. After 84 days of composting, 85% and 54% of the initial MR was degraded in WP- and PR-composts, respectively. The limiting factor was that the MR created clumps during composting so that decomposition was slowed. Compared to the untreated control, both WP- and PR-composts increased growth of cucumber (Cucumis sativus), radish (Raphanus sativus) and lettuce (Lactuca sativa). Concentrations of trace elements in plants and soil water did not rise to a level that would preclude WPS-composts from being used as a soil amendment.

Role of bacterial translocation in necrotizing enterocolitis. The intestinal mucosa functions as a major local defense barrier preventing bacteria that colonize the gut from invading organs and tissues. Under certain circumstances, bacteria colonizing the gastrointestinal tract can cross the gut mucosal barrier to infect the mesenteric lymph node and systemic organs via a process termed bacterial translocation. Factors that promote the translocation of bacteria or endotoxin from the gut include bacterial overgrowth with gram-negative enteric bacilli, impaired host immune defenses and injury to the gut mucosa resulting in increased intestinal permeability. These same promoting factors are present in patients at increased risk of developing necrotizing enterocolitis. Consequently, this review focuses on the potential role of bacterial and endotoxin translocation from the gut in the pathogenesis of necrotizing enterocolitis.

Attitudes and prescribing patterns of extended-cycle oral contraceptives. The survey was conducted to assess attitudes and patterns of health care providers (HCPs) prescribing extended regimen oral contraceptives (OCs). A prospective, anonymous, written survey that assessed attitudes and prescribed preferences of extended-cycle OCs was distributed at six educational conferences. An estimated 90% of the conference attendees participated in the survey. Of the 799 HCPs surveyed, 92% have recommended extended-cycle regimens with ob/gyn practitioners most likely to recommend their use (p<.05). The most commonly prescribed extended regimen remains an 84-day active pill cycle followed by a 7-day hormone-free interval (49%). The majority of HCPs (73.5%) continue to prescribe OCs which induce monthly withdrawal bleeds as their most common regimen. While HCPs appear to be recommending extended OC regimens more often, monthly cyclic regimens are the most commonly prescribed.

Soluble endoglin and transforming growth factor-β₁ and the development of vasospasm after spontaneous subarachnoid hemorrhage: a pilot study. Cerebral vasospasm (CVS) and cerebral infarction due to vasospasm (CIV) are major complications after spontaneous subarachnoid hemorrhage (SAH). Alteration of vasomotor tone has been postulated as an important factor in the pathogenesis of CVS. Members of the transforming growth factor-β (TGF-β) family and their receptors have been implicated in the regulation of vascular tone. Serum levels of soluble endoglin (sEng) and plasma levels of TGF-β(1) of 20 consecutive SAH patients were analyzed within 15 days after SAH using ELISA and correlated with CVS, CIV and outcome. Twenty voluntary age- and sex-matched blood donors served as healthy controls (HCs). SAH patients showed significantly lower sEng serum levels and higher TGF-β(1) plasma levels compared to HCs. Patients who developed Doppler sonographic CVS (dCVS) had significantly higher TGF-β(1) levels. Patients with CIV and patients with hydrocephalus showed significantly lower sEng levels. On day 3, pSAH sEng levels below 3.88 ng/ml or TGF-β(1) levels higher than 7.2 ng/ml had a predictive value for the development of CIV. Low mean sEng levels over the study period were highly predictive of poor long-term functional outcome (modified Rankin Scale ≥2) at 6 months after SAH. Concentrations of the vasoactive factors sEng in serum and TGF-β(1) in plasma are significantly altered in SAH patients compared to HCs. The results of this pilot study indicate that sEng could represent a novel prognostic biomarker for the onset of secondary complications and long-term functional outcome after SAH.

Methods to study the occurrence and the evolution of pseudogenes through a phylogenetic approach. During the last few years, the study of pseudogenes has excited enthusiasm, because it has been proven that at least some of them are involved in important biological processes. An accurate detection and analysis of pseudogenes can be achieved using comparative methods, but only the use of phylogenetic tools can provide accurate information about their birth, their evolution and their death, hence about the impact that they have on genes and genomes. Here, phylogenetic methods that allow studying pseudogene history are described.

Lack of Exuberance in Clustered Intrinsic Connections in the Striate Cortex of One-month-old Kitten. The topographies of the intrinsic tangential connections in layers II - IVab of one-month-old and adult cat's striate cortex were compared by plotting the distribution of retrogradely labelled neurons following injection of small amounts of wheat-germ agglutinin - horseradish peroxidase. In both cortices, the tracer reveals the characteristic cluster-like arrangement of intrinsic tangential connections. No differences were found between the two age groups in terms of either the numbers of cell clusters, their periodicities or their profiles, nor was there any difference in the lateral extent of the tangential connections. We conclude that one month postnatally, tangentially projecting intrinsic networks in the upper layers of the cat striate cortex lack exuberance and have an adult-like topography.

[Challenges facing Food and Nutrition Security in the Amazon: availability and consumption in households with adolescents]. Food and nutritional insecurity remains a challenge to the accomplishment of the right to adequate food in the Brazilian scenario. The scope of this study was to analyze the food and nutrition insecurity situation of adolescents both in households and on an individual level. A cross-sectional population-based study was conducted with 363 households and 95 adolescents in urban municipalities of the Brazilian Amazon. Food and nutrition insecurity was measured using the Brazilian Food Insecurity Scale. Linear regression was used in the analysis of the gross and adjusted effect of food and nutrition insecurity on availability and consumption. The prevalence of food and nutrition insecurity in households was 51.8%, increased availability and consumption of food sources of energy and low consumption of vegetables, fruits and legumes. The linear model analysis of variance showed dependency between food insecurity and the effect of the frequency of availability of food and food consumption. The results highlight the challenge of implementing public policies, in the light of unhealthy food consumption as an aspect of permanent nutritional, corporal and emotional impairment in adulthood.

2-Methoxyestradiol confers neuroprotection and inhibits a maladaptive HIF-1α response after traumatic brain injury in mice. HIF-1α is pivotal for cellular homeostasis in response to cerebral ischemia. Pharmacological inhibition of HIF-1α may reduce secondary brain damage by targeting post-translational mechanisms associated with its proteasomal degradation and nuclear translocation. This study examined the neuroprotective effects of 2-methoxyestradiol (2ME2), the involved HIF-1α-dependent response, and alternative splicing in exon 14 of HIF-1α (HIF-1α∆Ex14) after traumatic brain injury (TBI) in mice. Intraperitoneal 2ME2 administration 30 min after TBI caused a dose-dependent reduction in secondary brain damage after 24 h. 2ME2 was physiologically tolerated, showed no effects on immune cell brain migration, and mitigated trauma-induced brain expression of neuropathologically relevant HIF-1α target genes encoding for Plasminogen activator inhibitor 1 and tumor necrosis factor alpha. Moreover, TBI-induced expression of pro-apoptotic BNIP3 was attenuated by 2ME2 treatment. Alternatively, spliced HIF-1α∆Ex14 was substantially up-regulated from 6 to 48 h after TBI. In vitro, nuclear location and gene transcription activity of HIF-1α∆Ex14 were impaired compared to full-length HIF-1α, but no effects on nuclear translocation of the transcriptional complex partner HIF-1β were observed. This study demonstrates that 2ME2 confers neuroprotection after TBI. While the role of alternatively spliced HIF-1α∆Ex14 remains elusive, the in vivo data provide evidence that inhibition of a maladaptive HIF-1α-dependent response contributes to the neuroprotective effects of 2ME2. We examined neuroprotective effects of 2-methoxyestradiol (2ME2) and the hypoxia-inducible factor 1-α (HIF-1α) response following traumatic brain injury in mice. Early 2ME2 administration reduced the secondary brain damage and neuronal HIF-1α probably involving ubiquitin proteasome system-mediated degradation. The up-regulation of neuropathological HIF-1α target genes and pro-apoptotic BNIP3 protein was attenuated. We propose that the inhibition of a maladaptive HIF-1α response may contribute to 2ME2-mediated neuroprotection.

Alpha-1-antitrypsin (SERPINA1) mutation spectrum: Three novel variants and haplotype characterization of rare deficiency alleles identified in Portugal. Alpha-1-antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 mutations, which culminates into lower protease inhibitor activity in the serum and predisposes affected individuals to emphysema. Clinical manifestations of AATD are often associated to ZZ (p.Glu342Lys) and SZ (p.Glu264Val) genotypes and less frequently to rare deficiency or null alleles in heterozygous and homozygous states. We sequenced SERPINA1 (approximately 8 kb) and genotyped two microsatellites located upstream and downstream of the gene (195 and 5.6 kb, respectively) in a cohort of 51 AATD patients found to carry different rare alleles. A meta-analysis of SERPINA1 mutation spectrum was also performed. We detected a total of 14 rare alleles including 3 defined by novel mutations (p.Glu162Gly, p.Arg281Lysfs*17 and p.Met374Leufs*19) and 11 characterized by previously described variants (c.-5+2dupT, p.Arg39Cys, p.Phe52del, p.Thr68Ile, p.Asp256Val, p.Leu263Pro, p.Glu264Val, p.Leu353Phefs*24, p.Pro369Ser and p.Pro369Leu) but in several instances differing in their molecular backgrounds. So far, SERPINA1 has 132 low-frequency variants (<1%), where AATD mutations are not evenly distributed across the three-dimensional structure and tend to cluster in functional domains like the gate or the shutter. The contribution of rare SERPINA1 alleles into AATD should not be neglected in the diagnosis practice given there is a wide spectrum of variants originated by mutation and sometimes shuffled between chromosomes by recombination. Even though many of the rare variants are likely to be recent and population specific others seems to be as old as the Z allele and dispersed across European populations.

Myofascial Release for Vulvar Pain and Pubic Shear After a Straddle Injury in a 3-Year-Old Girl. Pelvic malalignment is a somatic dysfunction that can lead to pelvic discomfort, despite normal genital examination findings. A 3-year-old girl presented with vulvar discomfort after a straddle injury sustained while riding a tricycle. The symptoms persisted despite standard medical treatment for vulvovaginitis and chronic vulvar irritation. An osteopathic structural examination revealed distortions of the bony pelvis, often associated with genitourinary complaints. After 5 osteopathic manipulative treatment sessions, the patient experienced significant relief. With persistent vulvar pain, somatic dysfunction should be considered in the differential diagnosis. A brief musculoskeletal examination of the pubic tubercles, iliac crest, and iliac spines can help to identify somatic dysfunction in a gynecologic patient with symptoms that are unresponsive to standard treatments.

Galectins and neuroinflammation. Galectins, β-galactoside-binding lectins, play multiple roles in the regulation of immune and inflammatory responses. The major galectins expressed in the CNS are galectins 1, 3, 4, 8, and 9. Under normal physiological conditions, galectins maintain CNS homeostasis by participating in neuronal myelination, neuronal stem cell proliferation, and apical vesicle transport in neuronal cells. In neuronal diseases and different experimental neuroinflammatory disease models, galectins may serve as extracellular mediators or intracellular regulators in controlling the inflammatory response or conferring the remodeling capacity in damaged CNS tissues. In general, galectins 1 and 9 attenuate experimental autoimmune encephalomyelitis (a model of multiple sclerosis), while galectin-3 promotes inflammation in this model. In brain ischemic lesions, both galectins 1 and 3 are induced to help neuronal regeneration. The expression of galectin-1 is required for astrocyte-derived neurotrophic factor secretion, and recombinant galectin-1 promotes neuronal regeneration. Galectin-3 promotes microglial cell proliferation and attenuates ischemic damage and neuronal apoptosis after cerebral ischemia. In amyotrophic lateral sclerosis models, galectin-3 is deleterious to neuroregeneration, while intramuscular administration of oxidized galectin-1 can improve neuromuscular disorders. In axotomy and Wallerian degeneration, galectin-3 helps phagocytosis of macrophages to clear degenerate myelin in the injured PNS or CNS. Thus, galectins are important modulators participating in homeostasis of the CNS and neuroinflammation. Continued investigations of the roles of galectins in neuroinflammation promise to provide a better understanding of the mechanism of this process and lead to new therapeutic approaches.

Moderate-intensity Arm-cranking Exercise may not Improve Arterial Function in Healthy Adult Men. Endurance exercises, such as cycling or running, are useful for improving arterial function. However, people suffering from partial paralysis or arthritis are unable to perform these kinds of lower-limb exercises. In the present study, we explored the acute effect of upper-arm exercise on arterial stiffness in healthy men. Fourteen healthy adult men performed two experimental trials. The order of experiments was randomized between a 30-min arm-cranking exercise at 50% V̇O2max (A-trial) and a 30-min leg-cycling exercise at 50% V̇O2max (C-trial). The brachial to ankle pulse wave velocity (baPWV), brachial systolic/diastolic blood pressure and heart rate were obtained with subjects in the supine position. The baseline hemodynamic values were not markedly different between the two trials. Compared with the baseline value, the baPWV was significantly reduced at 30 and 60 min after the C-trial. In the A-trial, however, there were no significant changes in the baPWV throughout the trial. These results indicate that acute 50% V̇O2max arm-cranking exercise induced relatively little change in the baPWV, which was the opposite of the finding observed with leg-cycling exercise. Therefore, in order to improve arterial function via aerobic upper-arm exercises, the exercise mode/intensity or other approaches should be considered.

Imaging of Scrub Typhus by PET/CT. A 19-year-old man had an unexplained fever, dizziness, headache, fatigue, and pain in the scrotum. An FDG PET/CT imaging was acquired to assess fever of unknown origin. The images showed multiple foci of increased FDG activity in the enlarged lymph nodes in the body. In addition, mildly increased activity in the enlarged spleen and lung bases was also noted. The patient was eventually diagnosed with scrub typhus based on positive results of the Weil-Felix agglutination test, eschar in the scrotum, and effective therapy.

Analysis of the fetal placental vascular tree by X-ray micro-computed tomography. The current understanding of the placental vascular tree largely derives from time-consuming morphometric analyses performed by conventional histology, electron microscopy of corrosion casts and three-dimensional reconstructions based on physical tissue sections. In the present study, we demonstrate for the first time that micro-computed tomography (micro-CT) emerges as a new, non-destructive and fast tool for imaging and quantifying fetoplacental vasculature. Term placentae (n=5) were perfused with contrast agent consisting of barium-sulfate, gelatine and thymol shortly after Caesarean-section-delivery. Samples (1 cm(3)) from eight different regions of the placenta were subsequently scanned in a micro-CT. Using tomographic reconstruction algorithms, three dimensional images were obtained by micro-CT allowing total stereoscopic visualization and continuous quantitative analysis of the vascular structure of the investigated samples. These samples were compared regarding vascular surface (VS) and vascular density (vascular volume fraction, TCVF). Quantitative assessment showed an average vascular density of 16 per cent (SD+/-0.4) and a vascular surface of 475 mm(2)(SD+/-8) per total tissue volume (including intervillous space) of 125 mm(3). Micro-CT image-analysis showed no significant differences in the fetal vascularization among term placentae. Micro-CT imaging is feasible for imaging and analysis of the villous vascular tree, allows further morphologic studies and immunohistochemistry of the placental specimens and may emerge as an additional tool in the investigation of the physiology and pathophysiology of the placental vasculature.

Multivalent-Counterion-Induced Surfactant Multilayer Formation at Hydrophobic and Hydrophilic Solid-Solution Interfaces. Surface multilayer formation from the anionic-nonionic surfactant mixture of sodium dodecyl dioxyethylene sulfate, SLES, and monododecyl dodecaethylene glycol, C12E12, by the addition of multivalent Al(3+) counterions at the solid-solution interface is observed and characterized by neutron reflectivity, NR. The ability to form surface multilayer structures on hydrophobic and hydrophilic silica and cellulose surfaces is demonstrated. The surface multilayer formation is more pronounced and more well developed on the hydrophilic and hydrophobic silica surfaces than on the hydrophilic and hydrophobic cellulose surfaces. The less well developed multilayer formation on the cellulose surfaces is attributed to the greater surface inhomogeneities of the cellulose surface which partially inhibit lateral coherence and growth of the multilayer domains at the surface. The surface multilayer formation is associated with extreme wetting properties and offers the potential for the manipulation of the solid surfaces for enhanced adsorption and control of the wetting behavior.

Latency effect of the pitch response due to variations of frequency and spectral envelope. A clear definition of pitch and timbre is still an open debate and often both terms are mixed up in investigations of tone height. However, fundamental frequency (f(0)) and spectral envelope of a sound play a major role in the perception of tone height. Recent electrophysiological experiments showed that one sub-component of the complex N 100-signal was found to be highly correlated to the perceived tone height. Tone height was independently varied by both, a change of f(0) and spectral envelope in order to disentangle the influence of both parameters. Relative tone height was determined psychoacoustically. Neuromagnetic responses were evaluated using source-analysis. Perceived tone height increases with increasing f(0) or spectral envelope. Latency of the pitch change response (PCR) reacts oppositely for the two modi of tone height change. For increasing f(0) and fixed bandpass condition, tone height increases and the latency of the PCR decreases. In contrast, for increasing the center frequency of the bandpass with fixed f(0), tone height increases, but the latency of the PCR increases. The neuromagnetic pitch response is influenced by both, f(0) and spectral envelope. Further investigations of the influence of pitch and timbre on neurophysiological pitch responses have to take into account that both, f(0) and spectral envelope, affect tone height and latency of the PCR.

In situ studies of pellicle formation on hydroxyapatite discs. The formation of acquired enamel pellicle on hydroxyapatite (HA) discs of known surface area carried in the mouth was studied; discs were carried in the mouth for 30 s, 1, 5, 10 and 20 min. Similar amounts of protein were found on the discs at each time-point, as determined by ninhydrin analyses. The amounts of amylase and lysozyme detected remained stable after 5 min of exposure of the discs to the mouth. Assay of the discs for fructosyl- and glucosyltransferase activities revealed that fructosyltransferase activity increased up to 1 min of exposure to the mouth and decreased when kept in the mouth for longer periods; glucosyltransferase activity, in contrast, increased the longer the discs were kept in the mouth. This in situ model provides insight into the activities of various enzymes during the first 20 min of pellicle formation. The effects of rinsing with sucrose and sugar alcohols on pellicle formation on the discs were also explored. The discs were placed in the mouth for 30 s, 1, 5, 10 and 20 min, preceded by rinsing with either distilled deionized water, sucrose, sorbitol, xylitol or phosphate-buffered saline. Western blot analyses of disc eluates with antiserum/antibody preparations to various salivary components revealed distinct patterns of deposition of bacterial and salivary components depending on the composition of the rinse. These studies confirm that salivary molecules and bacteria are deposited on apatitic surfaces in a selective manner and reveal that pellicle formation may be influenced by composition of diet. It is apparent that this in situ model could be used in screening potential antiplaque agents.

Rubella as a teratogen. The clinical, epidemiologic and laboratory information available in the Johns Hopkins Rubella Study forms the basis for discussion of the pathogenesis of congenital rubella, the varied clinical characteristics of the phenotype and the substantial risk of fetal loss and abnormality when maternal rubella occurs in the first half of pregnancy.

Cardiac vagal regulation and early peer status. A sample of 341 5 (1/2) -year-old children participating in an ongoing longitudinal study was the focus of a study on the relation between cardiac vagal regulation and peer status. To assess cardiac vagal regulation, resting measures of respiratory sinus arrhythmia (RSA) and RSA change (suppression) to 3 cognitively and emotionally challenging tasks were derived. Results indicated that vagal regulation was positively associated with peer status. In addition, mediational analyses revealed that the relation between vagal regulation and peer status was mediated through better social skills for girls and better social skills and fewer behavior problems for boys. These findings are discussed in terms of the role of vagal regulation in the facilitation of children's positive social behavior.

Biomechanical study on the effect of five different lumbar reconstruction techniques on adjacent-level intradiscal pressure and lamina strain. The objectives of this study were to compare the biomechanical effects of five lumbar reconstruction models on the adjacent segment and to analyze the effects of three factors: construct stiffness, sagittal alignment, and the number of fused segments. Nondestructive flexion-extension tests were performed by applying pure moments to 10 calf spinal (L3-S1) specimens. One-segment (L5-6) or two-segment (L5-S1) posterior fusion methods were simulated: 1) one-segment posterolateral fusion (PLF); 2) one-segment PLF with interbody fusion cages (one-segment PLIF/PLF); 3) two-segment PLF; 4) two-segment PLIF/PLF; and 5) two-segment PLF in kyphosis (two-segment kyphotic PLF). The range of motion (ROM) of the reconstructed segments, intradiscal pressure (IDP), and lamina strain in the upper (L4-5) adjacent segment were analyzed. The ROM was significantly decreased in the PLIF/PLF models compared with that in the PLF alone models after both the one- and two-segment fusions. If the number of fused segments was increased, the pressure and strains were also increased in specimens subjected to the PLIF/PLF procedure, more so than the PLF-alone procedure. In the one-segment PLIF/PLF model the authors observed a reduced IDP and lamina strain compared with those in the kyphotic two-segment PLF model despite the latter's higher levels of initial stiffness. If the number of fused levels can be reduced by using PLIF to correct local kyphosis, then this procedure may be valuable for reducing adjacent-segment degenerative changes.

Gastric cancer in the young: An advanced disease with poor prognostic features. Gastric cancer in young patients is rare. We analyzed the clinicopathological features and prognosis of early-onset gastric carcinoma. We retrospectively reviewed patients with gastric adenocarcinoma aged ≤45 years and >45 years at our institution over a 17-year period. Clinicopathological features were compared and survival analysis was performed using Kaplan-Meier curves. A total of 121 patients with gastric carcinoma aged ≤45 years were identified. The young group (YG) had a higher incidence of stage III/IV disease (86.8% vs. 57.9%, P < 0.001), poorly-differentiated carcinoma (95.9% vs. 74.4%, P < 0.001), and signet-cell type tumor (88.4% vs. 32.2%, P < 0.001) relative to the older group (OG). The majority of tumors were in the middle third of the stomach in both groups (P = 0.108). Three-year survival in the YG was 87.1%, 32.2%, and 6.9% in stage I/II, III, and IV disease, respectively. Surgical intervention in young patients with advanced carcinoma was not associated with improved survival. Although median survival was shorter in the YG compared to the OG (11.7 vs. 41.0 months, P < 0.001), stage-specific survival was similar. Early-onset gastric cancer demonstrates advanced stage of disease, and a high incidence of poorly-differentiated and signet-cell type carcinoma. Overall survival is poor with no added benefit to surgical intervention in advanced disease.

Assessment of the treat-to-target strategy in patients with refractory rheumatoid arthritis. A prospective study on efficacy and safety in a Saudi population. The goal of the present study was to prospectively assess the long-term clinical outcome of biologic modifying drug therapy in a population of Saudi rheumatoid arthritis (RA) patients. This is the first prospective, long-term report on the efficacy and safety of biologic therapy in Saudi RA patients. It is a single center, observational study with a follow-up period of 3 years. Enrolled were 120 biologic naïve patients (94 women, 78.3 %; mean age 48.4 ± 17.9 years, mean disease duration 7.3 ± 3.9 years) with the diagnosis of RA (ACR/EULAR, 2010 criteria) who were inadequate responders to methotrexate and synthetic DMARDs. After 3 years, the mean Disease Activity Index-28 (DAS-28), Health Assessment Questionnaire (HAQ), Pain Score, ESR, and CRP values improved significantly. Of the 99 patients completing the 3-year follow-up, 35.3 % of patients achieved DAS-28 remission and 53.5 % achieved low disease activity, and 11.1 % of patients had moderate to high activity scores. At the 3-year follow-up, 80 % of patients had no evidence of significant radiographic progression (achieved < 0.5 of the mean total Sharp score). Infections were reported in 11.7 % and significantly correlated with conjugate use of oral prednisolone at doses above 5 mg/day, with chest infections being the most common type of infection (6.7 %). The results of this study can be understood as real-life clinical experience displaying the incremental benefit of biologic therapy in refractory disease when it is added to other optimal strategies. The study showed satisfying clinical and functional benefit with considerable safety.

Development of glucose sensor using two-photon adsorbed photopolymerization. A novel glucose sensor was constructed, and its analytical potential examined. A chip-type three-electrode system for use in a flow-type electrochemical glucose sensor was fabricated using a UV lithography technique on a glass slide. An Ag/AgCl reference electrode was made by electroplating silver onto a Pt electrode and dipping in a saturated KCl solution for 30 min. In addition, a glucose-sensing electrode was fabricated using a two-photon adsorbed photopolymerization technique with a photo-reactive resin containing a glucose oxidase enzyme, ferrocene mediator, non-ionic surfactant, and carbon nanotubes. The cyclic voltammetry of the potassium ferrocyanide in the Pt sensor system showed a stable electrode condition. The response of the modified Pt sensor confirms the feasibility of using a two-photon adsorbed photopolymerization technique for the easy fabrication of functional biosensors.

Anti-tumor and anti-angiogenic effects of Phyllanthus urinaria in mice bearing Lewis lung carcinoma. Phyllanthus urinaria, a widely used herb medicine in Asia, was tested for its anti-tumor effect in vivo for the first time. The anti-tumor activity in P. urinaria extract was evaluated by its effect on tumor developed in C57BL/6J mice with implantation of Lewis lung carcinoma cells. The oral administration of P. urinaria to mice caused significant inhibition of tumor development with lower occurrence rate and markedly reduced tumor size. Neither the total body weight of mouse nor the weights of organs including heart, lung, liver, spleen and kidney revealed any difference between two groups, suggesting limited in vivo cytotoxic effect of P. urinaria in mice. TUNEL assay demonstrated the increase of apoptosis in tumor sections prepared from P. urinaria-treated mice compared with control mice. It is worth of note that the neovascularization in tumor was inhibited in P. urinaria-treated mice, which implicated the potential anti-angiogenic effect of P. urinaria. Further study using an in vitro matrix-induced tube formation of HUVECs again confirmed the anti-angiogenic action of P. urinaria. P. urinaria exerted no inhibitory effect on the growth of HUVECs, however, the migration of HUVECs as analyzed using transwell assay was suppressed markedly by P. urinaria in a dose-dependent manner. All together, the present study indicated that P. urinaria extract is an anti-tumor and anti-angiogenic agent, which can be used safely in animals.

A comparison of sagittal short T1 inversion recovery and T2-weighted FSE sequences for detection of multiple sclerosis spinal cord lesions. Multiple sclerosis (MS) is the most common disabling CNS disease of young adults. MRI is routinely used for the detection of MS plaques in the brain and spinal cord. A significant portion of patients with MS demonstrates spinal cord lesions at the time of initial workup, and these lesions are an important part of the McDonald criteria for diagnosis. However, whereas brain imaging sequences are now fairly standardized, there continues to be debate about the optimal sequences for imaging the spinal cord. The short T1 inversion recovery (STIR) sequence has been shown in the current literature to improve lesion detection with its additive T1/T2 weighting, but current spinal cord imaging protocols from the Consortium on MS Center Consensus Guidelines do not include the STIR sequence. We demonstrate that not only do STIR sequences improve lesion detection when compared directly with conventional T2-weighted sequences, but that they also significantly improve lesion conspicuity, facilitating earlier positive diagnosis and management. Dedicated MR spinal cord imaging of twenty-nine sequential patients with clinically confirmed multiple sclerosis was retrospectively analyzed by two independent neuroradiologists in a novel study design. Sagittal T2-weighted and STIR sequence images from the same study for each patient were examined for MS plaques using a double-blinded review of individual images 'separated in time and space', such that STIR and T2 image pairs were never analyzed simultaneously. Number of lesions and lesion conspicuity for each lesion, using a subjective scale (1-5), were tallied for each sequence. Averages for each observer were compared using a paired t-test analysis for statistical significance, and assessment of inter-rater agreement was assessed using Cohen's kappa index. Significantly, more MS lesions were detected on STIR than on T2-weighted sequences for both observers (P = 0.001 and P = 0.005). In seven patients, the conventional T2 sequence detected no lesions at all, whereas STIR sequences showed significant cord involvement. Lesion conspicuity was also significantly better on STIR for both observers (P < 0.0005). This improved conspicuity leads to more uniform lesion detection. On the conventional T2-weighted sequence, there was a statistically significant difference in the number of lesions detected between the two observers (P = 0.003), but there was no statistically significant difference on STIR (P = 0.43). The kappa index showed greater interobserver agreement in both lesion count and lesion conspicuity on the STIR sequence as compared with T2. Short T1 inversion recovery sequence imaging not only significantly improves detection of MS lesions within the spinal cord, but also provides better contrast and conspicuity of visible lesions, creating a more confident diagnostic measure of MS extent and progression. Short T1 inversion recovery sequences of the spinal cord should be routinely obtained during initial and routine follow-up of MS.

Metabolomic responses of mussel Mytilus galloprovincialis to fluoranthene exposure under different nutritive conditions. Biomarkers are useful tools to assess biological effects of pollutants that are extensively used in monitoring programs to assess ecosystem health. However, they are strongly affected by mussel physiological state, especially nutritive status, which has led to the search of new biological indicators of chemical pollutants exposition. Environmental metabolomics is an approach for examining the metabolic responses (measurement of low molecular weight endogenous metabolites) of an organism to both natural and anthropogenic stressors that can occur in its environment. The aim of the present work was to assess the effect of the polycyclic aromatic hydrocarbon fluoranthene (FLU) exposure on the metabolomic profiles of mussel digestive glands under different nutritive conditions. To achieve this objective, mussels were reared, for a period of 56 days, under three different food rations in order to obtain a gradient of nutritive status (negative, zero and positive energy balance), and after that, they were exposed, during 3 weeks, to a nominal concentration of 3 μg FLU L-1. A total of 43 metabolites, including aminoacids (Ala, Val, Leu, Ile, etc.), energy metabolism related metabolites (ATP, AMP, etc.), organic osmolytes (taurine, etc.), redox metabolism (GSH, NADP+) and nucleotides, were identified and quantified in the digestive glands of the mussels. Principal Component Analysis (PCA) defined two principal components (PC1 and PC2) that explained 55.6% of the total variance, although the first component explains more than 80% of this variance, this being related to the mussel nutritive condition. The effect of the toxicant, explained by the PC2, is similar to that produced under conditions of food restriction, which masks the effect of the toxicant under these conditions. As the feeding conditions are more favorable, the toxic effect becomes more apparent. Therefore, the great influence of nutritive condition on mussel metabolome implies a handicap for the use of metabolomic biomarkers, as previously demonstrated for biochemical and other molecular biomarkers, in large-scale monitoring programs in which several food conditions coexist with pollution levels.

Harvest of autologous clavipectoral fascia for use in duraplasty: cadaveric feasibility study. Techniques and materials for repair of dural defects following neurosurgical procedures vary. Given higher complication rates with nonautologous duraplasty materials, most authors strongly recommend autologous grafts. To expand the arsenal of possible materials available to the neurosurgeon, we propose the use of autologous clavipectoral fascia as an alternative donor for duraplasty. Eight embalmed adult cadavers underwent dissection of the pectoral region. A 12-cm curvilinear skin incision was made 2 cm inferior to the nipple in males and along the inferior breast edge in females. Dissection was continued until the clavipectoral fascia was encountered, and a tissue plane was developed between this fascia and the deeper pectoralis major muscle. Sections of clavipectoral fascia were used for duraplasty in the same specimens. In all specimens, removal of clavipectoral fascia was easily performed with tissue separation between the overlying fascia and underlying muscle. Only small adhesions were found between the fascia and underlying muscle, and these were easily transected. No obvious gross neurovascular injuries were identified. Large portions of clavipectoral fascia were available, and at least a 10 × 10-cm piece (average thickness, 1.2 mm) was easily harvested for all specimens. Clavipectoral fascia shares characteristics with materials such as pericranium and fascia lata that have been used successfully in duraplasty, and most importantly, it is autologous. Theoretically, using clavipectoral fascia would reduce the risk of muscle herniation. It offers an alternative source for autologous dural grafting when other sources are unavailable or exhausted. Clinical experience with this fascia is warranted.

The StLAC2 gene is required for cell wall integrity, DHN-melanin synthesis and the pathogenicity of Setosphaeria turcica. Laccases are blue multicopper oxidases, play important roles in various biological processes. These processes include fungal dihydroxynaphthalene (DHN)-melanin biosynthesis and pathogenicity, cellular growth, morphogenesis, and differentiation. This study investigated functions of the laccase gene StLAC2 in Setosphaeria turcica. The Δlac2 mutant colony color was distinct from that of the S. turcica wild-type (WT) isolate, and the mutants exhibited defective conidial formation. In contrast to the WT, the mutants exhibited a lighter color on the 2, 2-azino-di-[3-ethylbenzo-thia-zolin-sulphonate] (ABTS) plates, and the intracellular laccase activity was lower. Notably, StLAC2 gene loss correlated with decreased DHN-melanin biosynthesis and affected the integrity of the cell wall, where the StLAC2 gene mutants showed thinner, more transparent walls with a higher number of mitochondria than the WT. The Δlac2 mutants also lost their pathogenicity in maize. The results indicated that the StLAC2 gene involved in cell wall integrity, melanin biosynthesis and appressorial and conidial formation.

[The etiology research progress of oculo-auriculo-vertebral spectrum]. Oculo-auriculo-vertebral spectrum (OAVS), also known as Goldenhar syndrome, hemifacial microsomia, oculo-auriculo-vertebral dysplasia and facio-auriculo-vertebral spectrum, is a developmental disorder associated with the first and second branchial arches. Most cases are sporadic, while some familial instances observed suggested that the etiology of OAVS heterogeneous. In this review, we summarize the OAVS epidemiology, classification and mainlyheterogeneous etiology.

Effects of beta-alanine supplementation on muscle function during recovery from resistance exercise in young adults. β-Alanine supplementation has been shown to increase muscle carnosine levels and exercise performance. However, its effects on muscle recovery from resistance exercise (RE) remains unknown. The purpose of this study was to investigate the effects of β-alanine supplementation on muscle function during recovery from a single session of high-intensity RE. Twenty-four untrained young adults (22.1 ± 4.6 years old) were assigned to one of two groups (N = 12 per group): a placebo-supplement group (4.8 g/day) or an β-alanine-supplement group (4.8 g/day). The groups completed a single session of high-intensity RE after 28 days of supplementation and were then evaluated for muscle function on the three subsequent days (at 24, 48, and 72 h postexercise) to assess the time course of muscle recovery. The following indicators of muscle recovery were assessed: number of repetitions until failure, rating of perceived exertion, muscle soreness, and blood levels of creatine kinase (CK). Number of repetitions until failure increased from 24 to 48 h and 72 h of recovery (time P < 0.01), with no difference between groups. There was a significant increase in the rating of perceived exertion among the sets during the RE session (time P < 0.01), with no difference between the groups. No difference was observed over time and between groups in rating of perceived exertion in the functional tests during recovery period. Blood CK levels and muscle soreness increased at 24 h postexercise and then progressively declined at 48 and 72 h postexercise, respectively (time P < 0.05), with no difference between groups. In conclusion, our data indicate that β-alanine supplementation does not improve muscle recovery following a high-intensity RE session in untrained young adults.

Left insular cortex and left SFG underlie prismatic adaptation effects on time perception: evidence from fMRI. Prismatic adaptation (PA) has been shown to affect left-to-right spatial representations of temporal durations. A leftward aftereffect usually distorts time representation toward an underestimation, while rightward aftereffect usually results in an overestimation of temporal durations. Here, we used functional magnetic resonance imaging (fMRI) to study the neural mechanisms that underlie PA effects on time perception. Additionally, we investigated whether the effect of PA on time is transient or stable and, in the case of stability, which cortical areas are responsible of its maintenance. Functional brain images were acquired while participants (n=17) performed a time reproduction task and a control-task before, immediately after and 30 min after PA inducing a leftward aftereffect, administered outside the scanner. The leftward aftereffect induced an underestimation of time intervals that lasted for at least 30 min. The left anterior insula and the left superior frontal gyrus showed increased functional activation immediately after versus before PA in the time versus the control-task, suggesting these brain areas to be involved in the executive spatial manipulation of the representation of time. The left middle frontal gyrus showed an increase of activation after 30 min with respect to before PA. This suggests that this brain region may play a key role in the maintenance of the PA effect over time.

Safety and efficacy of a recombinant DNA Plasmodium falciparum sporozoite vaccine. A recombinant DNA Plasmodium falciparum sporozoite vaccine produced in Escherichia coli (FSV-1) was tested in doses of 10 micrograms to 800 micrograms protein in fifteen volunteers. No serious adverse reactions occurred. Antibodies that reacted with P falciparum sporozoite antigens by enzyme-linked immunoassay developed in twelve of the volunteers. The highest antibody titres induced were similar to those resulting from lifelong natural exposure to sporozoite-infected mosquitoes. Postimmunization serum samples from a majority of volunteers mediated the circumsporozoite (CS) precipitation reaction and inhibited sporozoite invasion of hepatoma cells in vitro. Serum from the three volunteers who received 800 micrograms doses reacted with the surface of sporozoites in an immunofluorescence assay. Six immunised volunteers receiving a fourth dose of FSV-1 and two non-immunised controls were challenged by bites of mosquitoes infected from cultured P falciparum gametocytes. Parasitaemia did not develop in the volunteer with the highest titre of CS antibodies, and parasitaemia was delayed in two other immunised volunteers. This study confirms that human beings can be protected by CS protein subunit vaccines and provides a framework for the further development and testing of more immunogenic sporozoite vaccines.

CNS repurposing - Potential new uses for old drugs: Examples of screens for Alzheimer's disease, Parkinson's disease and spasticity. Drug repurposing is recently gaining increasing attention, not just from pharmaceutical companies but also from government agencies in an attempt to generate new medications to address increasing unmet medical needs in a cost effective and expedite manner. There are several approaches to identify novel indications for known drugs. Many are based on rational selection e.g. the known or a new mechanism of action of a drug. This review will focus rather on phenotypic or high content screening of compounds in models that are believed to be predictive of effectiveness of compounds irrespective of their mechanism of action. Three short cases studies of screens for Alzheimer's disease, Parkinson's disease and spasticity will be given as examples. This article is part of the Special Issue entitled 'Drug Repurposing: old molecules, new ways to fast track drug discovery and development for CNS disorders'.

Occupational exposure to electromagnetic fields and sex-differential risk of uveal melanoma. The association between occupational exposure to electromagnetic fields (EMF) and the risk of uveal melanoma was investigated in a case-control study in nine European countries. Incident cases of uveal melanoma and population as well as hospital controls were included and frequency matched by country, 5-year birth cohort and sex. Subjects were asked whether they had worked close to high-voltage electrical transmission installations, computer screens and various electrical machines, or in complex electrical environments. Measurements of two Scandinavian job-exposure matrices were applied to estimate lifelong cumulative EMF exposure. Unconditional logistic regression analyses, stratified by sex and eye colour were calculated, adjusting for several potential confounders. 293 patients with uveal melanoma and 3198 control subjects were interviewed. Women exposed to electrical transmission installations showed elevated risks (OR 5.81, 95% CI 1.72 to 19.66). Positive associations with exposure to control rooms were seen among men and women, but most risk increases were restricted to subjects with dark iris colour. Application of published EMF measurements revealed stronger risk increases among women compared to men. Again, elevated risks were restricted to subjects with dark eye colour. Although based on a low prevalence of exposure to potential occupational sources of EMF, our data indicate that exposed dark-eyed women may be at particular risk for uveal melanoma.

A Bayesian approach to establishing sample size and monitoring criteria for phase II clinical trials. Thall and Simon propose a Bayesian approach to phase II clinical trials with binary outcomes and continuous monitoring. The efficacy theta E of an experimental treatment E is evaluated relative to that of a standard treatment S based on data from an uncontrolled trial of E, an informative prior for theta S, and a noninformative prior for theta E. The trial continues until E is shown with high posterior probability to be either promising or not promising, or until a predetermined maximum sample size is reached. Operating characteristics are evaluated under fixed values of the success probability of E. In this paper, we propose two extensions of this decision structure, describe sample size and monitoring criteria, and provide numerical guidelines for implementation. The first extension gives criteria from early termination of trials unlikely to yield conclusive results, based on the marginal (predictive) distribution of the observed success rate. The second extension allows early termination only if E is found to be not promising compared to S. Operating characteristics of each of these designs are evaluated numerically over a range of design parameterizations. We also examine the effects of intermittent monitoring on the design's properties. An application of this approach to a leukemia biochemotherapy trial is described.

Selective venous sampling for ACTH in Cushing's syndrome: differentiation between Cushing disease and the ectopic ACTH syndrome. We performed selective venous catheterization and sampling for ACTH in six patients with ACTH-secreting pituitary adenomas (Cushing's disease) and four patients with occult ectopic ACTH-secreting neoplasms. In five patients with Cushing's disease in whom the inferior petrosal sinus could be catheterized, ACTH levels were unequivocally higher than simultaneous peripheral values: The ratio was greater than 2.0, with a range of 2.2 to 16.7. In contrast, the inferior petrosal sinus-to-peripheral ACTH ratio in three patients with ectopic ACTH secretion was less than 1.5. In the fourth patient, an arteriovenous gradient of 6.8 was shown 2 years before a bronchial carcinoid tumor was clinically apparent. Central-to-peripheral ACTH ratios at the level of the jugular bulb and jugular vein were not diagnostic. We conclude that selective venous ACTH sampling from the inferior petrosal sinus is a reliable and useful aid in the differential diagnosis of Cushing's syndrome when standard clinical and biochemical studies are inconclusive.

[Study of collisional broadening of spectral line by optical-optical double resonance]. The collisional broadening of the 2(1)sigma+ --> 6(1)sigma+ line of NaK molecule was studied using the optical-optical double resonance technique. A single-mode diode laser was set to a particular 1(1)sigma+ (v", J") --> 2(1)sigma+ (v',J') transition. Another single-mode diode laser was then used to excite the molecule from 2(1)sigma+ (v', J') level to the rovibrational level of 6(1)sigma+. The two laser beams counterpropagated through the cell. The broadening rate coefficient was determined from the slope of the total linewidth versus potassium density curve. The rate coefficient, k(br) = (1.4+/-0.7) x 10(-8) cm3 x s(-1), was obtained. The collisional excitation transfer between rotational levels of the 2(1)sigma+ state [i. e., 2(1)sigma+ (v = 8, J = 12) --> 2(1)sigma+ (v = 8, J = 13, 14)] was also investigated. The rates can be determined from the relative intensities of the main peak and satellite lines, combined with a rate equation model. The rates are 6.1 x 10(6) and 5.2 x 10(6) s(-1) respectively.

Cardiac sodium channel dysfunction in sudden infant death syndrome. Mutations in genes responsible for the congenital long-QT syndrome, especially SCN5A, have been identified in some cases of sudden infant death syndrome. In a large-scale collaborative genetic screen, several SCN5A variants were identified in a Norwegian sudden infant death syndrome cohort (n=201). We present functional characterization of 7 missense variants (S216L, R680H, T1304M, F1486L, V1951L, F2004L, and P2006A) and 1 in-frame deletion allele (delAL586-587) identified by these efforts. Whole-cell sodium currents were measured in tsA201 cells transiently transfected with recombinant wild-type or mutant SCN5A cDNA (hH1) coexpressed with the human beta1 subunit. All variants exhibited defects in the kinetics and voltage dependence of inactivation. Five variants (S216L, T1304M, F1486L, F2004L, and P2006A) exhibited significantly increased persistent sodium currents (range, 0.5% to 1.7% of peak current) typical of SCN5A mutations associated with long-QT syndrome. These same 5 variants also displayed significant depolarizing shifts in voltage dependence of inactivation (range, 5 to 14 mV) and faster recovery from inactivation, but F1486L uniquely exhibits a depolarizing shift in the conductance-voltage relationship. Three alleles (delAL586-587, R680H, and V1951L) exhibited increased persistent current only under conditions of internal acidosis (R680H) or when expressed in the context of a common splice variant (delQ1077), indicating that they have a latent dysfunctional phenotype. Our present results greatly expand the spectrum of functionally characterized SCN5A variants associated with sudden infant death syndrome and provide further biophysical correlates of arrhythmia susceptibility in this syndrome.

Characterization of monomeric L1 metallo-beta -lactamase and the role of the N-terminal extension in negative cooperativity and antibiotic hydrolysis. The L1 metallo-beta-lactamase from Stenotrophomonas maltophilia is unique among this class of enzymes because it is tetrameric. Previous work predicted that the two regions of important intersubunit interaction were the residue Met-140 and the N-terminal extensions of each subunit. The N-terminal extension was also implicated in beta-lactam binding. Mutation of methionine 140 to aspartic acid results in a monomeric L1 beta-lactamase with a greatly altered substrate specificity profile. A 20-amino acid N-terminal deletion mutant enzyme (N-Del) could be isolated in a tetrameric form but demonstrated greatly reduced rates of beta-lactam hydrolysis and different substrate profiles compared with that of the parent enzyme. Specific site-directed mutations of individual N terminus residues were made (Y11S, W17S, and a double mutant L5A/L8A). All N-terminal mutant enzymes were tetramers and all showed higher K(m) values for ampicillin and nitrocefin, hydrolyzed ceftazidime poorly, and hydrolyzed imipenem more efficiently than ampicillin in contrast to wild-type L1. Nitrocefin turnover was significantly increased, probably because of an increased rate of breakdown of the intermediate species due to a lack of stabilizing forces. K(m) values for monomeric L1 were greatly increased for all antibiotics tested. A model of a highly mobile N-terminal extension in the monomeric enzyme is proposed to explain these findings. Tetrameric L1 shows negative cooperativity, which is not present in either the monomer or N-terminal deletion enzymes, suggesting that the cooperative effect is mediated via N-terminal intersubunit interactions. These data indicate that while the N terminus of L1 is not essential for beta-lactam hydrolysis, it is clearly important to its activity and substrate specificity.

Two new alkaloids from Crinum asiaticum var. sinicum. Two new alkaloids (1, 2) were isolated from the whole plants of Crinum asiaticum var. sinicum together with seven known alkaloids. The structures of the new alkaloids were elucidated by spectroscopic analyses and chemical conversions from known alkaloids. New alkaloid 1 was isolated for the first time as a natural product, although it has been prepared as a synthetic product.

Perceived benefits and challenges of an oncology nurse support group. This study explores the perceived benefits and barriers of participating in a monthly oncology nurse support group. Ten oncology nurses participated in an average of seven support group meetings over a one-year period. Interviews were conducted, transcribed, analyzed, and thematized using qualitative descriptive methods. Clear benefits for oncology nurses are indicated; participants described a reduction in end-of-life care stress, an increase in self-care, and improved patient and team care. Barriers include scheduling and compensation, as well as group leadership labors. This study provides further confirmation that oncology nurses receive multiple benefits from the support group structure. Peer support groups for oncology nurses seem a promising and economical communication intervention for mitigating burnout, professional dissatisfaction, patient care distress, and interprofessional communication deficits.

Evaluating operational vacuum for landfill biogas extraction. This manuscript proposes a practical methodology for estimating the operational vacuum for landfill biogas extraction from municipal landfills. The procedure is based on two sub-models which simulate landfill gas production from organic waste decomposition and distribution of gas pressure and gas movement induced by suction at a blower station. The two models are coupled in a single mass balance equation, obtaining a relationship between the operational vacuum and the amount of landfill gas that can be extracted from an assigned system of vertical wells. To better illustrate the procedure, it is applied to a case study, where a good agreement between simulated and measured data, within +/- 30%, is obtained.

Hyperproduction of the sigma subunit of RNA polymerase in a mutant of Escherichia coli. A mutant of Escherichia coli K12 is described in which sigma and alpha subunits of the DNA-dependent RNA polymerase (EC 2.7.7.6) are produced at the rates much higher than in the normal strain. The rate of synthesis for sigma subunit was found to be at least 10-times higher, though the rapid degradation of sigma polypeptides accompanied with the accelerated synthesis precludes accurate estimation of the extent of hyperproduction. The alpha subunit synthesis was about 5-times higher in this mutant than in the control, and excess alpha polypeptides produced were as stable as the bulk of protein under the conditions employed. Genetic analyses of the mutant by conjugation and by transduction with phage P1 revealed that at least three distinct but closely linked mutations are responsible for hyperproduction of the sigma subunit; one (sig-1) is located very close to rif, and the others (sig-2 and sig-3) at the argH-bfe and metB regions, respectively. The results further indicate that the accelerated synthesis of alpha subunit is due to a mutation also located at the metB region. The present finding suggests that the synthesis of sigma subunit is subject to a complex control that can be affected by a number of cellular processes. The possible involvement of the core polymerase in determining the rate of synthesis of sigma subunit is discussed.

A genome scan for loci influencing anti-atherogenic serum bilirubin levels. Epidemiological studies have shown an association of decreased serum bilirubin levels with coronary artery disease. Two segregation analyses in large pedigrees have suggested a major gene responsible for high bilirubin levels occurring in about 12% of the population. Based on a recessive model from a previous segregation analysis, we performed a genome scan using 587 markers genotyped in 862 individuals from 48 Utah pedigrees to detect loci linked to high bilirubin levels. As a complementary approach, non-parametric linkage (NPL) analysis was performed. These two methods identified four regions showing evidence for linkage. The first region is on chromosome 2q34-37 with multipoint LOD and NPL scores of 3.01 and 3.22, respectively, for marker D2S1363. This region contains a previously described gene, uridine diphosphate glycosyltransferase 1, which has been associated with high bilirubin levels. A polymorphism in the promoter of this gene was recently shown to be responsible for Gilbert syndrome which is associated with mild hyperbilirubinemia. The other regions were found on chromosomes 9q21, 10q25-26, and 18q12 with maximum NPL scores of 2.39, 1.55, and 2.79, respectively. Furthermore, we investigated in these pedigrees the association between bilirubin levels and coronary artery disease. One-hundred and sixty-one male and 41 female subjects had already suffered a coronary artery disease event. Male patients showed significantly lower bilirubin concentrations than age-matched controls. This association, however, was not observed in females. These results provide evidence that loci influencing bilirubin variation exist on chromosomes 2q34-37, 9q21, 10q25-26, and 18q12 and confirms the association of low bilirubin levels with coronary artery disease in males.

Looking back to look forward: protein-protein interactions and the evolution of development. The evolutionary modification of development was fundamental in generating extant plant diversity. Similarly, the modification of development is a path forward to engineering the plants of the future, provided we know enough about what to modify. Understanding how extant diversity was generated will reveal productive pathways forward for modifying development. Here, I discuss four examples of developmental pathways that have been remodeled by changes to protein-protein interactions. These are cases where changes to developmental pathways have been paralleled by recent changes, selected for or engineered by humans. Extant plant diversity represents a vast treasure trove of molecular solutions to ecological problems. Mining this treasure trove will allow for the intentional modification of plant development for solving future problems.

A comparative study of ultrasonication, Fenton's oxidation and ferro-sonication treatment for degradation of carbamazepine from wastewater and toxicity test by Yeast Estrogen Screen (YES) assay. A comparative study of ultrasonication (US), Fenton's oxidation (FO) and ferro-sonication (FS) (combination of ultrasonication and Fenton's oxidation) advanced oxidation processes (AOPs) for degradation of carbamazepine (CBZ) from wastewater (WW) is reported for the first time. CBZ is a worldwide used antiepileptic drug, found as a persistent emerging contaminant in many wastewater treatment plants (WWTPs) effluents and other aquatic environments. The oxidation treatments of WW caused an effective removal of the drug. Among the various US, FO and FS pre-treatments carried out, higher soluble chemical oxygen demand (SCOD) and soluble organic carbon (SOC) increment (63 to 86% and 21 to 34%, respectively) was observed during FO pre-treatment process, resulting in higher removal of CBZ (84 to 100%) from WW. Furthermore, analysis of by-products formed during US, FO and FS pre-treatment in WW was carried out by using laser diode thermal desorption-atmospheric pressure chemical ionization (LDTD-APCI) coupled to tandem mass spectrometry (MS/MS). LDTD-APCI-MS/MS analysis indicated formation of two by-products, such as epoxycarbamazepine and hydroxycarbamazepine due to the reaction of hydroxyl radicals (OH) with CBZ during the three types of pre-treatment processes. In addition, the estrogenic activity of US, FO and FS pre-treated sample with CBZ and its by-products was carried out by Yeast Estrogen Screen (YES) assay method. Based upon the YES test results, none of the pre-treated samples showed estrogenic activity.

Treatment of spinal fractures in ankylosing spondylitis. Ankylosing spondylitis (AS) is a chronic inflammatory spondyloarthropathy with the potential for progressive spinal stiffness that ultimately makes patients susceptible to spinal fractures with traumatic spinal cord injury from even low-energy trauma. Treatment of patients with AS and spinal fractures (AS+FX) is controversial because, although these patients need especially rigorous stabilization, surgery has been associated with an increased risk of complications and persistent neurological deficits. The purpose of this retrospective case series was to profile patients with AS+FX from a 19-year period within the authors' county hospital system, including differences of neurological status in patients treated operatively vs nonoperatively. The study group comprised 11 patients with AS+FX (9 men and 2 women; mean age, 63 years [range, 38-91 years]). The authors reviewed available clinical notes and imaging reports. Six patients had posterior operative fixation, and 5 were stabilized nonoperatively. By the time of either discharge or final follow-up, 3 of the patients treated operatively deteriorated neurologically (2 of them preoperatively) and 3 remained stable. Of the patients treated nonoperatively, 3 remained neurologically intact, 1 deteriorated, and 1 recovered completely. The most common complications in all patients were pneumonia and urinary tract infection. Operative and nonoperative management produced acceptable outcomes in most patients. The authors recommend individualized treatment, accounting for patient preferences and comorbidities.

Life and limb. Clinical nurse specialist Philippa Bridgeman supports patients through the lengthy treatment required to save a limb following a complex fracture. Up to 20 per cent of her patients at Queen Elizabeth Hospital Birmingham are injured soldiers.

Can Chlorella pyrenoidosa be a bioindicator for hazardous solid waste detoxification? Four kinds of solid waste residue (SWR, S1 to S4) from different stages in a sequential detoxification process were chosen. The biotoxicity of the leachates from S1 to S4 was tested by Chlorella pyrenoidosa. The growth inhibition, the chlorophyll a (chla) and chlorophyll b (chlb) concentrations, and the ultrastructural morphology of cells of C. pyrenoidosa were studied. It shows that the growth inhibition of C. pyrenoidosa significantly increased with increasing leachate concentration when exposed to the leachates from S1, S2, S3, and S4, respectively. It well reflects the toxicity difference of leachate from SWR at different treatment stages, namely S1>S2>S3>S4. Correspondingly, the chla and chlb concentrations of C. pyrenoidosa increased gradually as SWR was treated deeply. Leachate disrupted chlorophyll synthesis and inhibited cell growth. The changing of the ultrastructural morphology of cells under different leachate exposures, such as volume of chloroplasts and quantity of thylakoids reducing, confirmed the toxicity decrease of leachates from different stages. C. pyrenoidosa is a good bioindicator for hazardous solid waste detoxification. The EC(50) at difference scenarios also suggests that it was feasible to estimate ecological toxicity of leachates to C. pyrenoidosa after exposure times of 72h. C. pyrenoidosa can be introduced to evaluate the effect of hazardous solid waste disposal by biotoxicity assessment.

A bioinformatics analysis of alternative exon usage in human genes coding for extracellular matrix proteins. Alternative splicing increases protein diversity through the generation of different mRNA molecules from the same gene. Although alternative splicing seems to be a widespread phenomenon in the human transcriptome, it is possible that different subgroups of genes present different patterns, related to their biological roles. Analysis of a subgroup may enhance common features of its members that would otherwise disappear amidst a heterogeneous population. Extracellular matrix (ECM) proteins are a good set for such analyses since they are structurally and functionally related. This family of proteins is involved in a large variety of functions, probably achieved by the combinatorial use of protein domains through exon shuffling events. To determine if ECM genes have a different pattern of alternative splicing, we compared clusters of expressed sequences of ECM to all other genes regarding features related to the most frequent type of alternative splicing, alternative exon usage (AEU), such as: the number of alternative exon-intron structures per cluster, the number of AEU events per exon-intron structure, the number of exons per event, among others. Although we did not find many differences between the two sets, we observed a higher frequency of AEU events involving entire protein domains in the ECM set, a feature that could be associated with their multi-domain nature. As other subgroups or even the ECM set in different tissues could present distinct patterns of AEU, it may be premature to conclude that alternative splicing is homogeneous among groups of related genes.

Clinical experience with perindopril in patients nonresponsive to previous antihypertensive therapy: a large US community trial. A subgroup analysis of a large US community trial was conducted to evaluate the antihypertensive efficacy and safety of perindopril, an angiotensin-converting enzyme inhibitor (ACEI), in 3159 patients who lacked blood pressure (BP) control at entry with previous antihypertensive therapy. Patients received 4 mg perindopril daily for 6 weeks. Based on physicians' assessment of BP response, the patients were then either maintained on 4 mg daily (group 1) or the dose was increased to 8 mg daily (group 2) for an additional 6 weeks. The mean baseline sitting BP was 158.2/92.9 mm Hg. Perindopril monotherapy produced a significant BP decrease from baseline of 11.6/6.5 mm Hg and 14.9/8.4 mm Hg at weeks 6 and 12, respectively. In group 1 patients, the majority of BP decrease occurred at week 6 (17.3/9.5 mm Hg) and was maintained until the end of week 12 (18.2/10.1 mm Hg). In group 2 patients, the BP decrease on the 4-mg dose was modest at week 6 by 5.2/3.1 mm Hg. However, further dose up-titration of perindopril to 8 mg resulted in a clinically significant BP decrease of 11.9/6.8 mm Hg from baseline to week 12. Significant antihypertensive effects of perindopril were also demonstrated in the special patient populations of elderly (>or=65 years), black, isolated systolic hypertension, patients with concomitant cardiovascular diseases, and patients nonresponsive to other ACEI therapy. Overall, BP control (<140/<90 mm Hg) was achieved in 40.0% of patients at week 12. Perindopril was well tolerated with cough and angioedema reported in 8.5% and 0.4% patients, respectively. Physicians assessed therapeutic response to perindopril as satisfactory in 73.8% patients who were nonresponsive to previous antihypertensive therapy. These results suggest that, in a community-based practice, perindopril monotherapy (4-8 mg/d) is an effective and safe therapeutic option in patients nonresponsive to previous antihypertensive therapy.

Computed axial tomography-MIBI image fusion for preoperative localization in primary hyperparathyroidism. An imaging-guided unilateral surgical approach in patients with primary hyperparathyroidism (HPTH) requires reliable preoperative localization procedures. Using present imaging techniques, 60% to 80% of patients with primary HPTH can be treated successfully with limited surgery. Thus, further improvement of diagnostic accuracy is required. Computed axial tomography (CAT)-MIBI image fusion was introduced as a new technique for localizing enlarged parathyroid glands. We describe the new method and present its first results. Six consecutive patients with primary HPTH underwent CAT-MIBI image fusion for preoperative parathyroid localization. CAT and technetium-99m-sestamibi scan were performed separately. The patient's head and neck were fixed with the noninvasive Vogele-Bale-Hohner Head Holder (VBH HeadFIX; Medical Intelligence, Schwabmünchen, Germany) and the BodyFIX (Medical Intelligence) vacuum cushion. Radiographic and scintigraphic markers were mounted at the head holder and the patient. CAT and MIBI images were fused by overlaying radiographic markers using a commercial software and workstation. In 5 patients, localization and dimension of the solitary adenomas were exactly predicted. In 1 patient with multiglandular disease (3 enlarged glands), CAT-MIBI image fusion was not able to predict multiple gland involvement. However, in a retrospective analysis of the localization study, the other two enlarged parathyroid glands could be correctly identified regarding their site and size. First results of CAT-MIBI image fusion are promising. The new technique provides a higher image resolution and better delimitation of enlarged parathyroid glands and adjacent anatomic structures than conventional scintigraphic methods.

Multifocal corneal ablation for hyperopic presbyopes. To investigate the clinical results of multifocal wavefront-guided corneal ablation with a central near zone in hyperopic presbyopes. Twenty-seven patients (54 eyes) were analyzed retrospectively. Monocular near and distance uncorrected visual acuity (UCVA) and binocular near and distance UCVA were measured preoperatively, and the near addition power and the manifest refraction were obtained. Measurements of spherical aberration, coma, total higher order aberration, and contrast sensitivity for high and low photopic conditions were performed. All patients received multifocal corneal ablations with a central near zone using the VISX CustomVue System and were examined at 1 month (48 eyes), 2 months (42 eyes), and 6 months (28 eyes) after surgery. Of 14 patients, 9 (64.3%) achieved both 0.8 or better in binocular distance UCVA and 0.65 or better in binocular near UCVA, and the spherical equivalent refraction and near addition power decreased from +1.16+/-0.82 diopters (D) to +0.33+/-0.45 D and from 2.35+/-0.44 D to 1.42+/-0.62 D at 6 months after surgery, respectively. No significant changes were noted in total higher order aberration and contrast sensitivity, whereas spherical aberration coefficients (Z-12) changed from positive to negative. Multifocal wavefront-guided refractive surgery in presbyopia offered effective correction in hypermetropia and satisfactory near vision without significant increase in comeal total higher order aberration or significant decrease in contrast sensitivity.

Preference for a cocaine-associated environment is attenuated by augmented accumbal serotonin in cocaine withdrawn rats. Recent studies have found decreased serotonin (5-HT) transmission within the nucleus accumbens following withdrawal from chronic cocaine. We sought to investigate whether increasing brain 5-HT levels would decrease behavioral responses that occur following cocaine withdrawal, namely increased preference for a cocaine environment and anxiety. The conditioned place preference and the defensive burying paradigms were used to measure the behavioral responses that occur 1 week following cocaine withdrawal. We show that pharmacological agents that increase 5-HT transmission (sertraline or 5-hydoxytryptophan, 5-HTP) abolish the preference of subchronically cocaine-treated, abstinent rats for a cocaine-associated environment. Similar results were seen when sertraline was microinjected into the nucleus accumbens. Conversely, rats acutely conditioned with cocaine showed an increased preference for a cocaine-associated environment when pretreated with these drugs. Sertraline also decreased the heightened anxiety-like behaviors found in subchronically treated cocaine rats. These results indicate that drugs that augment 5-HT function may reduce the desire for cocaine following cocaine withdrawal, and thus facilitate cocaine abstinence in dependent subjects.

Division of the nucleolus and its release of CDC14 during anaphase of meiosis I depends on separase, SPO12, and SLK19. Disjunction of maternal and paternal centromeres during meiosis I requires crossing over between homologous chromatids, which creates chiasmata that hold homologs together. It also depends on a mechanism ensuring that maternal and paternal sister kinetochore pairs attach to oppositely oriented microtubules. Proteolytic cleavage of cohesin's Rec8 subunit by separase destroys cohesion between sister chromatid arms at anaphase I and thereby resolves chiasmata. The Spo12 and Slk19 proteins have been implicated in regulating meiosis I kinetochore orientation and/or in preventing cleavage of Rec8 at centromeres. We show here that the role of these proteins is instead to promote nucleolar segregation, including release of the Cdc14 phosphatase required for Cdk1 inactivation and disassembly of the anaphase I spindle. Separase is also required but surprisingly not its protease activity. It has two mechanistically different roles during meiosis I. Loss of the protease-independent function alone results in a second meiotic division occurring on anaphase I spindles in spo12delta and slk19delta mutants.