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Results of contemporary radical cystectomy for invasive bladder cancer: a clinicopathological study with an emphasis on the inadequacy of the tumor, nodes and metastases classification. We reviewed 261 patients who underwent a radical operation at a single institution as definitive treatment of invasive bladder cancer to evaluate the survival and accuracy of the tumor, nodes and metastasis system in characterizing the prognosis. Between January 1979 and June 1987 the 261 evaluable patients underwent 1-stage radical cystectomy with pelvic node dissection and urinary diversion. No chemotherapy and/or radiation therapy was given before or after the operation. The postoperative mortality rate was 1.8%. The over-all staging error between clinical and pathological stages was as high as 44%. The over-all actuarial 5-year survival rate was 54.5%. The 5-year survival rates were 75% for stage pT1, 63% for stage pT2, 31% for stage pT3 and 21% for stage pT4 disease. A significant difference in the survival (p less than 0.002) was observed in stage pT3 by dividing tumors confined within the bladder wall (pT3a, 50%) from those extending throughout the bladder wall (pT3b, 15%). A careful evaluation of transitional cell involvement of the prostate in stage pT4a cancer led to the identification of 2 different patterns: 1) contiguous when a bladder tumor extended directly into the prostate through the bladder wall and 2) noncontiguous when a bladder tumor and a transitional cell carcinoma of the prostate were found simultaneously. These patterns had completely different (p less than 0.05) survival rates (6 versus 37%). The patients with high grade tumors had a worse prognosis in comparison with those with grades 1 and 2 tumors (41 versus 56%, p less than 0.005). The over-all 5-year survival of patients with positive nodes was 4% in comparison with 60% of those without nodal involvement (p less than 0.001). Despite current optimal surgical treatment, nearly 50% of all patients with invasive bladder cancer continue to die. The need for a modification of the current tumor, nodes and metastasis tumor classification to provide the clinician a more reliable staging system for planning treatment modalities is indeed mandatory.
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Intraluminal pressure adjacent to left colonic anastomoses. A cumulative total of 89 h of pressure data was acquired from both sides of a left colonic anastomosis in 15 patients over a median period of 7 postoperative study days. Patients had a colonic ileus lasting 3-10 days and during this proximal and distal inactivity the intraluminal pressure remained within 6 mmHg of atmospheric pressure. After recovery of activity, pressures proximal to the anastomosis in excess of 10 mmHg occurred during less than 1 per cent of the recording time. Distal peak pressures were significantly elevated with respect to the proximal site (P less than 0.001). Two-thirds of the distal pressures recorded were between 10 and 20 mmHg and 98 per cent were less than 50 mmHg; the peak distal pressure was 90 mmHg. Four patients had distal repetitive tonic contractions creating a pressure difference across the anastomosis with a mean of 20 mmHg and a peak of 45 mmHg. Each contraction persisted for 15-20 min. Intraluminal pressures are unlikely to play a role in anastomotic dehiscence.
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The Greenfield filter as the primary means of therapy in venous thromboembolic disease. During a five year period at Akron City Hospital, 165 Greenfield filters were placed in 165 patients. Of this group, 78 patients were available for long term analysis, and of these, 42 did not receive anticoagulation treatment for venous thromboembolic diseases, either acutely or on an outpatient basis. An analysis of the outcome for these 42 patients who had the Greenfield filter only as the primary mode of therapy for the disease included chart review and asking each person a standard set of questions. Leg swelling was the most common complaint, occurring in 33 per cent of patients. Venous stasis ulceration occurred in two patients and recurrent deep venous thrombosis occurred in one patient. When compared with a historical control group with venous thromboembolic disease that was treated with anticoagulation alone, the incidence of these sequelae in Greenfield-treated patients was not significantly different. Finally, in this review, the Greenfield filter is better than 95 per cent effective in the prevention of pulmonary embolism. This is no less effective than anticoagulation alone, the efficacy of which is 95 to 98 per cent. The placement of a Greenfield filter is a safe procedure that can usually be done after a local anesthetic was administered to the patient with a complication rate of less than 10 per cent. Unfortunately, major complications of anticoagulation (usually hemorrhage) are relatively common at a rate of 2 to 15 per cent, and occur more frequently in the older population. It is for reasons of safety of therapy and of an equal or better efficacy that the Greenfield filter is recommended in a broader range of clinical circumstances. In particular, it is concluded that the Greenfield filter should be used as a primary means of therapy in venous thromboembolic disease, particularly in those patients who are more than 65 years of age, when the risks of anticoagulation are most threatening.
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Effectiveness of periodic checkup by ultrasonography for the early diagnosis of hepatocellular carcinoma. Periodic checkup by ultrasonography was conducted on patients with chronic liver diseases for early detection of hepatocellular carcinoma. In 19 months, a total of 2004 examinations were performed on a total of 660 cases (179 cases with liver cirrhosis in the compensatory stage, younger than 70 years; 481 cases with chronic hepatitis, aged 40 to 70 years for men and 50 to 70 years for women). Of the 660 cases, 22 HCC cases (3.3%) were detected and finally diagnosed by angiography and/or histologic examination. Four of those cases (18%) had a single nodule smaller than 1 cm in diameter, and 11 cases (50%) had a single nodule smaller than 2 cm. Surgical resection was performed on 12 cases (55%). In comparison with the control group (83 HCC cases not receiving any periodic checkup), the frequency of small liver cancer and the surgical resection rate in the study group were significantly higher. This examination system by periodic ultrasonography checkup of patients with chronic hepatic diseases was effective for early detection and permitted aggressive therapy of hepatocellular carcinoma.
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Deep venous thrombosis. Implications after open heart surgery. We reviewed the cases of 10,638 cardiac surgical patients to determine the incidence of deep vein thrombosis (DVT) after open heart surgery (OHS). Seventy-seven patients (0.7 percent) had DVT. Group 1 included 36 patients who had DVT without pulmonary embolism (PE). Occurrence was equal in either leg. Anticoagulation with heparin and warfarin sodium (Coumadin) was employed as treatment. Extension of hospital stay was 10.8 days. Group 2 consisted of 41 patients who experienced PE 9.9 days after OHS. Sixteen patients had known DVT and were receiving heparin. In 25 patients, PE was the first event. Risk factors for PE included perioperative myocardial infarction (16 percent), atrial fibrillation (41 percent); blood type A (70 percent) (p less than 0.05), and coronary artery bypass graft (CABG) (98 percent). Twenty-four patients were treated with anti-coagulation alone. Six died of recurrent PE; mortality was 25 percent. Seventeen patients received anticoagulation plus inferior vena cava (IVC) interruption using a Hunter balloon. There were no recurrent PEs and there was one death from myocardial infarction (6 percent). Deep vein thrombosis and PE are rare complications of OHS. Routine prophylaxis with either heparin or warfarin is unnecessary. Patients with DVT, atrial fibrillation (AF), and perioperative myocardial infarction are at high risk of PE. Aggressive diagnosis to identify major venous thrombi along with anticoagulation and early consideration of IVC interruption are recommended for these patients. Patients who have undergone OHS and who have PE are at an unusually high risk for recurrent PE with death and are more safely treated with IVC interruption and anticoagulation than anticoagulation alone.
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Metastatic small cell tumor of bone with 'true' rosettes and glial fibrillary acidic protein positivity. A 15-year-old black girl was admitted to St. Jude Children's Research Hospital with a lytic lesion involving the right fourth metacarpal bone with a solitary metastasis to the ipsilateral axillary lymph node. Histologic examination of both the primary lesion and metastasis revealed a primitive small round cell lesion. Abundant rosettes with central lumina were present in the metastasis. Immunohistochemical stains performed on sections of the metastasis were strongly positive for glial fibrillary acidic protein (GFAP) and negative for neuron-specific enolase (NSE), S-100 protein, and Leu-7. Electron microscopic examination of the metastasis revealed lumen formation with apical microvilli and juxtaluminal junctional complexes. This tumor exhibits features that are suggestive, but not definitive, of primitive ependymal differentiation and further expands the morphologic and immunophenotypic range of small round cell tumors of bone.
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Indications for computed tomography in children with blunt abdominal trauma. This investigation was undertaken to identify clinical variables, alone or in combination, that could be used to assign children to high- and low-risk categories for intra-abdominal injury following blunt trauma. Six hundred consecutive children who were examined with computed tomography (CT) following blunt trauma were enrolled. Complete data sets were available on 375 children. Stepwise logistic regression was used to identify predictor variables for the presence of abdominal injury. There were 174 children with abdominal injury detected by CT. Of these, 95 were classified as having significant injury. Indicators associated with significantly higher risk of abdominal injury included the following: more than three clinical indications given (odds likelihood ratio [OLR] = 4.60, 95% confidence interval [95% Cl] = 2.29, 9.21, p less than 0.001); gross hematuria (OLR = 5.80, 95% Cl = 2.51, 13.4, p less than 0.001); lap belt injury (OLR = 12.2, 95% Cl = 2.22, 66.8, p less than 0.01); assault or abuse as the mechanism of injury (OLR = 5.08, 95% Cl = 1.07, 24.2, p less than 0.05); abdominal tenderness (OLR = 2.73, 95% Cl = 1.296, 5.82, p less than 0.01); and Trauma Score less than or equal to 12 (OLR = 2.27, 95% Cl = 1.006, 5.13, p less than 0.01). No child with asymptomatic hematuria (n = 56), regardless of grade or neurologic impairment in the absence of abdominal findings (n = 15), had an abnormal CT examination. These data are useful as an adjunct to clinical judgment in triage when the availability of CT equipment is limited or there are competing extra-abdominal injuries.
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Multiple noncontiguous spine fractures. The data from a prospective study of 508 spine injuries were reviewed to determine the incidence of multiple noncontiguous spine fractures. All patients were examined at admission and at 1 and 2 years postinjury. This series identified 77 (15.2%) multilevel fractures. Motor vehicle accidents were the primary cause of these fractures. The incidence of neurologic injury was not significantly different between multiple noncontiguous and single fractures. Failure to use seat belts and ejection from the vehicle were the main factors associated with multiple noncontiguous spine injuries. Seven major fracture patterns were identified, which accounted for 60% of these injuries. The prognosis for multilevel spine fractures was not significantly worse that that for single-level injuries.
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The comportmental learning disabilities of early frontal lobe damage. Two adult patients are described who suffered bilateral prefrontal damage early in life and who subsequently came to psychiatric attention because of severely aberrant behaviour. A battery of developmental psychology paradigms (not previously used to assess neurologically impaired individuals) showed that social and moral development of these 2 patients was arrested at an immature stage. In comparison with other types of brain damage which disrupt cognitive development, frontal damage acquired early in life appears to provide the neurological substrate for a special type of learning disability in the realms of insight, foresight, social judgement, empathy, and complex reasoning.
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Natural killer cell activity in patients with liver cirrhosis relative to severity of liver damage. To evaluate the role of severe liver damage on natural killer cell activity, 29 patients with liver cirrhosis were examined. The natural killer cell activity was measured with a 4-hr chromium release assay, and the K562 cell line was employed as target cells. The natural killer cell activity was significantly decreased in cirrhotic patients compared with normal controls and patients with chronic active hepatitis. Cirrhotic patients with Pugh's C grade of severity of liver disease had lower natural killer cell activity. The depression of natural killer cell activity in cirrhotic patients was inversely correlated with prothrombin time ratios, and the natural killer cell activity in cirrhotic patients with hepatic encephalopathy was lower than in patients without hepatic encephalopathy. Thus, the diminished natural killer cell activity in cirrhotic patients might be related to the severity of liver damage.
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Course of diabetic retinopathy following cataract surgery Five patients with mild to moderate retinopathy to both eyes underwent complication-free cataract surgery in one eye. Within three months of surgery deterioration of the retinopathy was observed in the operated eye only. In four patients there was an increase of intraretinal haemorrhages and hard exudates, accompanied by clinically significant macular oedema manifested as retinal thickening and extensive fluorescein leakage from both the macular and the peripapillary capillary networks. Of these four patients one also developed retinal ischaemia, evident ophthalmoscopically by flame-shaped haemorrhages and cotton-wool spots and angiographically by areas of capillary non-perfusion. The fifth patient showed proliferation of new blood vessels and vitreous haemorrhage. Diabetic patients scheduled for cataract surgery should undergo a thorough preoperative evaluation of any existing retinopathy. Postoperatively they should be followed up at close intervals so that any progression of retinopathy can be promptly detected and considered for laser treatment.
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Spontaneous perinephric hemorrhage: imaging and management. We report on 10 patients with spontaneous perinephric hemorrhage associated with underlying disease, including renal cell carcinoma (5), angiomyolipoma (2), malignant melanoma (1), periarteritis nodosa (1) and severe portal hypertension (1). The etiology could not be identified with computerized tomography (CT) in 5 cases (50%), including 2 renal cell carcinomas, 1 angiomyolipoma, 1 periarteritis nodosa and 1 portal hypertension. Arteriography demonstrated underlying lesions in 4 of these 5 cases (80%) including the case of vasculitis. CT combined with magnetic resonance imaging is accurate for the diagnosis of spontaneous perinephric hemorrhage but the underlying pathological condition is often undetectable in the acute phase due to the perinephric blood. CT should be the first study performed if this diagnosis is suspected. Arteriography is recommended if a renal mass is not detected. If a mass is not identified with these 2 imaging studies and the patient is clinically stable, followup thin slice CT should be performed.
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Reduction of gastric ulcer recurrence after suppression of Helicobacter pylori by cefixime. The effect on the recurrence of gastric ulcers after suppression of Helicobacter pylori by combined treatment with cimetidine and the antimicrobial drug cefixime was investigated. Twenty one of 43 patients with endoscopically proved gastric ulcer and H pylori infection were randomly assigned to receive cimetidine 800 mg daily for 12 weeks; the remaining 22 patients received cimetidine 800 mg daily for 12 weeks plus cefixime 100 mg daily for the last two weeks. After treatment, 88% of 17 patients on cimetidine only remained H pylori positive, whereas combined administration of cimetidine and cefixime had suppressed H pylori in 78% of 18 patients (p less than 0.05). Seventeen patients in the former group whose ulcers healed but who remained H pylori positive and 18 patients in the latter group whose ulcers healed and who were no longer infected with H pylori continued to be followed after treatment. These patients underwent endoscopy to detect ulcer recurrence if symptomatic, or at 12 and 24 weeks if asymptomatic. At 12 weeks, recurrence was observed in seven of 15 (47%) patients in whom H pylori persisted, but in only one of 14 (7%) patients in whom H pylori had been suppressed (p less than 0.05). At 24 weeks, however, recurrence rates were similar between the two groups. These findings indicate that H pylori infection may be closely related to early ulcer recurrence.
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Total knee arthroplasty in rheumatoid arthritis. A comparison of the polycentric and total condylar prostheses. From 1971 to 1985, 393 total knee arthroplasties (TKAs) were performed in patients for rheumatoid arthritis. Of these, 112 used polycentric prostheses and 131 used total condylar prostheses. One hundred seven of the patients with polycentric prostheses and 102 of the patients with total condylar prostheses were followed for a minimum of two years (average, 61 and 55 months, respectively). At the time of the latest examination, nine knees with polycentric prostheses required revision surgery: six for tibial component loosening and instability and three for patellofemoral pain. Five knees with total condylar prostheses required revision: one for chronic instability, one for a late posttraumatic patellar fracture, and three for late hematogenous infections. The total condylar prostheses with patellar resurfacing had better scores for pain (8.5 points) than the polycentric prosthesis without patellofemoral resurfacing (7.0 points). The total condylar prosthesis appeared more durable in terms of fixation, with no evidence of aseptic loosening of femoral or tibial components noted in this series thus far.
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Long-term follow-up of the first 56 patients treated with intracoronary self-expanding stents (the Lausanne experience). Fifty-six patients treated with the self-expanding intracoronary stent for acute occlusion during percutaneous transluminal coronary angioplasty (PTCA) or restenosis were followed for 24 to 43 months (mean 34). Successful deployment and positioning were achieved in 55 of 56 patients. Occlusion of the stent was documented in 8 patients, the earliest occurring 30 minutes and the latest 8 months after implantation. Three of the occluded stents were recanalized by PTCA. Coronary artery bypass grafts (CABG) were required in 4 patients: 1 for symptomatic restenosis, 1 for left main stenosis adjacent to the stent and 2 for acute ischemia during the in-hospital stay (less than 7 days). Myocardial infarction occurred in the territory of the stented vessel in 8 patients. Seven patients died between 1 day and 19 months after implantation. Local bleeding complications occurred in 10 patients, with 5 requiring blood transfusion. Restenosis within the stent was angiographically documented in 5 patients (9%). A new lesion in the treated vessel was found in 10 patients, followed by implantation of a second stent in 5 and a third stent in 1 patient. Medical treatment was instituted in the remaining 4 patients. Forty-nine patients (88%) are alive. Twenty-nine patients (51%) remained asymptomatic, and 44 (78%) are in a better functional class than before the implantation. Eleven of 15 (79%) major complications (acute occlusions or deaths) occurred in patients who received a stent in the left anterior descending coronary artery. In conclusion, implantation of the self-expanding intracoronary stent appears to be a new therapeutic option for treating acute occlusion or restenosis after PTCA.
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Enlarged cisterna magna and the Dandy-Walker malformation: factors associated with chromosome abnormalities. Thirty-three fetuses with an enlarged cisterna magna (10 mm or more) were evaluated to determine factors that might be associated with an underlying chromosome abnormality. Eighteen fetuses (55%) proved to have a chromosome abnormality, including trisomy 18 or trisomy 18 variant (12), trisomy 13 (three), Turner syndrome (one), or other rearrangements (two). Among various risk factors analyzed, the absence of ventricular dilatation correlated most strongly with a chromosome abnormality. Chromosome abnormalities were found in 17 of 22 fetuses (77%) lacking ventricular dilatation, compared with only one of 11 fetuses (9%) with ventricular dilatation (P less than .001). Other factors statistically associated (P less than .01) with an underlying chromosome abnormality included mild enlargement of the cisterna magna (10-14 mm), concurrent anomalies detected sonographically, and fetal growth retardation. However, stepwise logistic regression showed that only the absence of ventricular dilatation and the presence of concurrent anomalies were significant when multiple factors were evaluated. These observations support the utility of evaluating the cisterna magna as part of a routine anatomical survey.
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Intestinal perforation due to cytomegalovirus infection in patients with AIDS. Intestinal perforation due to cytomegalovirus (CMV) infection in patients with AIDS is the most common life-threatening condition requiring emergency celiotomy in these patients. The authors describe a patient with AIDS with intestinal perforation due to CMV infection, and review 14 additional cases reported in the English-language surgical literature. The diagnostic triad of pneumoperitoneum on x-ray, evidence or history of CMV infection, and AIDS occurred in 70 percent of patients. The most common site of intestinal perforation was the colon (53 percent), followed in frequency by the distal ileum (40 percent) and appendix (7 percent); perforation usually occurred between the distal ileum and splenic flexure of the colon. Colonoscopy, rather than sigmoidoscopy, is recommended as a screening examination in patients with AIDS suspected of having colonic ulceration due to CMV infection. Multiple biopsies of ulcerated tissue should be obtained. Gross and microscopic analyses of involved intestinal tissue reveal the characteristic findings of ulceration and CMV infection. Despite aggressive therapy, the operative mortality rate in patients with AIDS with intestinal perforation due to CMV infection was 54 percent and the overall mortality rate was 87 percent. Postoperative complications occurred in most patients and consisted mainly of systemic sepsis and pneumonia caused by Pneumocystis carinii infection. An increased awareness of this syndrome by physicians frequently called on to manage patients with AIDS is recommended.
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Validation of intermediate end points in cancer research. Investigations using intermediate end points as cancer surrogates are quicker, smaller, and less expensive than studies that use malignancy as the end point. We present a strategy for determining whether a given biomarker is a valid intermediate end point between an exposure and incidence of cancer. Candidate intermediate end points may be selected from case series, ecologic studies, and animal experiments. Prospective cohort and sometimes case-control studies may be used to quantify the intermediate end point-cancer association. The most appropriate measure of this association is the attributable proportion. The intermediate end point is a valid cancer surrogate if the attributable proportion is close to 1.0, but not if it is close to 0. Usually, the attributable proportion is close to neither 1.0 nor 0; in this case, valid surrogacy requires that the intermediate end point mediate an established exposure-cancer relation. This would in turn imply that the exposure effect would vanish if adjusted for the intermediate end point. We discuss the relative advantages of intervention and observational studies for the validation of intermediate end points. This validation strategy also may be applied to intermediate end points for adverse reproductive outcomes and chronic diseases other than cancer.
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Loss of expression of blood group antigen H is associated with cellular invasion and spread of oral squamous cell carcinomas. Membrane-bound carbohydrates may influence the metastatic behavior of cancer cells. Forty-two squamous cell carcinomas (SCC) of the buccal and maxillary alveolar mucosa were studied retrospectively using a monoclonal antibody (BE2) that reacts with blood group H (type 2 chain) structure. H-antigen staining within the entire tumor did not correlate with the stage of the tumor, i.e., spread of the tumors. However, loss of staining within the most invasive sites of the tumors correlated significantly with the stage of tumor development and histologic grade of malignancy. These findings support the view that features relating to the cells of deeper parts of the carcinomas are very important for the clinical behavior of the tumors, and that loss of H-antigen expression is related to the stage of tumor and invasion of carcinoma cells.
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Nonsteroidal antiinflammatory drug-induced colonic strictures: a case report. Adverse effects of nonsteroidal antiinflammatory drugs can occur throughout the whole gastrointestinal tract. Recently, several cases of "diaphragmlike" thin ileal strictures have been reported. These strictures seem to result from nonsteroidal antiinflammatory drug-induced inflammatory changes and apparently represent a newly recognized nosological entity. The case of a 61-year-old man who gradually developed similar inflammatory changes in the ascending colon during prolonged intake of a slow-release form of diclofenac is presented, and the literature on nonsteroidal antiinflammatory drug-induced intestinal strictures is briefly reviewed.
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Spontaneous pneumothorax: marker gas technique for predicting outcome of manual aspiration [published erratum appears in BMJ 1991 Mar 23;302(6778):697] OBJECTIVE--To determine whether in a patient with spontaneous pneumothorax the presence or absence of a pleural leak can be shown at the time of manual aspiration by use of a marker gas. Also, to find out if the technique can predict whether manual aspiration will be successful, hence avoiding the need for intercostal tube drainage. DESIGN--Prospective study of 25 episodes of pneumothorax during which patients breathed air from a Douglas bag that contained chlorofluorocarbon gases from a metered dose inhaler while the pneumothorax was aspirated. SETTING--Medical unit of a district general hospital. PATIENTS--22 patients who presented over nine months with acute pneumothorax. MAIN OUTCOME MEASURES--Presence or absence of chlorofluorocarbon marker gases in the aspirate. Presence or absence of sustained re-expansion of the affected lung in the chest radiograph. RESULTS--Marker gas was detected in the aspirate from 16 out of 25 pneumothoraces. Of these, 13 required intercostal tube drainage because of failure of the lung to re-expand. Marker gas was not detected in nine cases, and in all of these cases manual aspiration resulted in sustained re-expansion of the lung. CONCLUSIONS--The presence or absence of a pleural leak during manual aspiration of spontaneous pneumothorax can be shown by using this technique. The absence of marker gas in the aspirate implies that manual aspiration will be successful, whereas its presence predicts, in most cases, either failure of manual aspiration to expand the lung or early re-collapse of the lung.
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Kaposi's sarcoma of the colon in a young HIV-negative woman with Crohn's disease. We report a case of isolated colonic Kaposi's sarcoma in a 36-year-old HIV-negative woman with refractory Crohn's disease of the colon and perineum following 11 months' treatment with azathioprine. The clinical features of this case are quite different from those classically described in Kaposi's sarcoma. Among the known risk factors, iatrogenic immunosuppression would appear to be the most probable.
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Dissecting aneurysm of the pulmonary artery with pulmonary hypertension. Pulmonary artery dissection was observed in a 64-yr-old female patient with severe pulmonary hypertension, which was probably primary (pulmonary vascular resistance, 817 dyn.s.cm-5; normal range less than or equal to 200 dyn.s.cm-5). The patient was admitted to the hospital because of severe dyspnea on exertion. Echocardiography demonstrated a dissecting aneurysm of the pulmonary artery. Right heart catheterization revealed severe pulmonary hypertension (mean pulmonary artery pressure, 64 mm Hg; normal range, 10 to 22 mm Hg); dissection of the pulmonary artery was confirmed by pulmonary arteriography. One-year follow-up was uneventful. In the literature, 28 patients with dissecting aneurysm of the pulmonary artery are reviewed. The dissection has only been diagnosed in life in one patient (by echocardiography).
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Gene mapping and other tools for discovery. Genetic mapping provides a means of understanding the molecular basis of inherited diseases whose biochemistry is unknown. Adequate pedigrees, informative genetic markers, and accurate identification of the disease phenotype are necessary. For dominant inheritance, mapping studies can be done in a single large pedigree; the larger the number of affected individuals sampled the better the estimate of recombination between the gene causing the disease and one or more nearby genetic markers. For recessive inheritance, nuclear families with more than one affected sibling provide the best information. The development of many polymorphic DNA markers on the human genome has contributed to the success of mapping unknown genes because, as the genome is now densely covered with markers, the probability is good that at least one marker will be linked to the disease locus in a family that is segregating a disease allele. Most genetic markers now in use depend upon restriction fragment length polymorphisms (RFLPs), which are either the result of single-base-pair substitution or the presence of a variable number of tandemly repeated oligonucleotide units at a locus (VNTRs). RFLPs can be recognized by digesting DNA with restriction enzymes and separating the fragments by size on an electrophoretic gel. VNTRs can vary widely among individuals, and they provide more linkage information than single-site polymorphic markers because family members are more likely to be heterozygous. Genetic maps of each chromosome, constructed from linkage data relating marker loci to one another in normal reference families, permit rational choices of markers for disease-mapping studies.
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Analysis of 24-hour esophageal pressure and pH data in unselected patients with noncardiac chest pain. Fourty-four unselected patients with noncardiac chest pain were studied using conventional manometry with additional edrophonium provocation and 24-hour ambulatory esophageal pH and pressure recording with a system developed by our group. New, fully automated techniques of statistical analysis of the complete set of esophageal pressure and pH signals were used to examine the temporal relation between pain, esophageal motility disturbances, and gastroesophageal reflux. The analysis used the 97.5th percentile of amplitude and duration of all esophageal contractions in each patient as well as a chi 2 test of the distribution of contraction types to determine whether a pain episode was related to abnormal motility or not. The edrophonium test results were positive in 2 patients. Only 25 patients (56.8%) had at least one pain episode (total, 111 episodes) during 24-hour recording. Thirty-three percent of the pain episodes were related to reflux and 23.4% to abnormal motility, and 43.2% were not related to an esophageal function disturbance. In the patient-oriented analysis in this study, it was required for a positive correlation that the symptom index (percentage of related pain episodes) was higher than 75%. It was found that the pain was related to reflux in 2 patients (4.6%), to reflux and motor abnormalities in 4 (9.2%), and to motor abnormalities in 2 patients (4.6%). In 36 patients (81.8%), no relation with an esophageal abnormality could be established, either because the patients had no pain during the 24-hour study, or because the pain seemed unrelated to reflux or abnormal motility.
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Are measurements of height made by health visitors sufficiently accurate for routine screening of growth? To find out whether measurements of height made by health visitors are sufficiently accurate for use in routine screening of children we carried out an interobserver and intraobserver reliability study. Height measurements were made on a group of 10 children aged 3 years old and 10 aged 4.5 years old by two sets of four health visitors. They used a Microtoise or wall chart and the measurements were compared with those made by a trained auxologist with a Harpenden stadiometer. For a single assessment of height both pieces of equipment gave reasonably accurate results. In a child aged 3 years, with height measured on the Microtoise as 100 cm, the true height could be expected--with 95% probability--to lie between 99.2 cm-101.8 cm. At the age of 4.5 years, if the measurement was 110 cm, the child's true height could be expected to lie between 108.9 cm and 111.9 cm. The narrowest confidence interval for the growth rate from 3 to 4.5 years was achieved with the Microtoise, taking the mean of three measurements. We conclude that measurements made by health visitors are sufficiently accurate for routine screening of height, and the use of such measurements for the calculation of height velocity could be improved by more structured training.
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Indomethacin responsive hypercalcaemia associated with a renal sarcoma. An infant presented with a non-metastatic renal spindle cell sarcoma and hypercalcaemia, which resolved after treatment with indomethacin. There was in vivo and in vitro evidence that hypercalcaemia was mediated by circulatory prostaglandins.
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The effect of nightly nasal CPAP treatment on underlying obstructive sleep apnea and pharyngeal size. Nasal continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea (OSA). It is usually prescribed for nightly use; however, recent studies show that patients often do not wear the appliance consistently. Previous studies have also suggested that nasal CPAP may improve a patient's underlying OSA even when the mask is not in place. We investigated 12 men with OSA to see if nasal CPAP used nightly for six weeks would improve their underlying sleep-disordered breathing. We also studied pharyngeal volumes measured using magnetic resonance imaging and a computer-controlled digitizing pad. Patients with more severe OSA had improvement after six weeks; however, they still demonstrated significant OSA. Patients with less severe OSA did not have significant change. We were unable to show a significant difference in any patient's awake pharyngeal volumes. We conclude that patients with OSA should be encouraged to wear their nasal CPAP machines regularly.
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Reperfusion inhibits elevated splanchnic prostanoid production after hemorrhagic shock [published erratum appears in Ann Surg 1991 Feb;213(2):91] The effect of reperfusion following hemorrhagic shock on splanchnic prostanoid release was studied. Anesthetized male rats were bled to a mean arterial blood pressure of 30 mmHg for 30 minutes and either killed or treated with shed blood for 60 minutes and then killed. The superior mesenteric arterial bed was cannulated and perfused in vitro with oxygenated Krebs. Collected venous effluent (up to 180 minutes) was analyzed for 6-keto-PGF1 alpha (PGI2 metabolite), PGE2, PGF2 alpha, and thromboxane B2 by radioimmunoassay in shock, shock plus reperfusion, and sham groups. The major prostanoid released was 6-keto-PGF1 alpha and was three times higher in the shock group compared to the sham group (p less than 0.05). Reperfusion of shed blood abolished the increase in 6-keto-PGF1 alpha found in the shock group (p less than 0.05). These data show that the attempt of the rat splanchnic bed to compensate for hemorrhagic shock by increasing release of PGI2 (potent vasodilator) was abolished during reperfusion of blood.
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Nonhomologous chromatid exchange in hereditary and sporadic renal cell carcinomas. For the development of renal cell carcinomas, it has been suggested that a germ-line or somatic mutation occurs on one of the homologous chromosomes 3p, and subsequently the other 3p segment is lost. We have examined the karyotype and/or the allelic combination on chromosomes 3 and 5 by restriction fragment length polymorphism analysis in normal kidney and tumor samples from 28 renal cell carcinomas that developed in two patients with von Hippel-Lindau disease; we then compared the results to those of sporadic tumors. An unbalanced translocation between chromosome 3p and 5q or other chromosomes was found to be the most common aberration. We developed a model of nonhomologous chromatid exchange involving breakpoint clusters at chromosomes 3p13, 3p11.2, 5q22, and 8q11.2. Subsequent chromatid segregation may result in net loss of the 3p segment either (i) in one step or (ii) after a nondisjunctional loss of the derivative chromosome carrying the 3p segment. This general mechanism could also be implicated to explain genetic changes occurring in other types of solid tumors.
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The evaluation of the abdominal aorta: a "how-to" for cardiac sonographers. A thorough evaluation of the abdominal aorta can be readily achieved by use of the standard views of the echocardiographic examination. The ultrasound evaluation of the abdominal aorta represents a logical extension of the standard echocardiographic examination of the adult patient. This article provides the information needed to carry out a complete ultrasound examination of the abdominal aorta including the anatomy, the vascular disease, and the steps involved in accomplishing the ultrasound examination of the abdominal aorta.
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Median nerve somatosensory evoked potentials and the Glasgow Coma Scale as predictors of outcome in comatose patients with head injuries. Median nerve somatosensory evoked potential (SSEP) grades and Glasgow Coma Scale (GSC) scores were obtained from 51 patients with head injuries within 1 week after the injury to determine the relationship of these scores, both individually and combined, to outcome scores obtained more than 6 months after the injury. SSEP grading was based on the presence or absence of the cortical evoked potential, the amplitude of the early cortically generated P22 wave form, and the conduction time through the brain (P/N13-N20 interpeak latency). SSEP responses from both sides of the brain were combined and graded from 1 to 6. The GCS was graded without the verbal component (maximum score, 10), because all patients were intubated. All patients were unresponsive to commands. Median SSEP grades correlated better with Glasgow Outcome Scale and Barthel Index scores (R = 0.57 and 0.64, respectively; P less than 0.00001) than GCS scores did (R = 0.35 and 0.37, respectively, P less than 0.00001), and combining SSEP grades and GCS scores did not improve the predictive power of the model (R = 0.57 and 0.64, respectively; P less than 0.00001). All SSEP Grade 1 patients (n = 13) either died or remained in a vegetative state. In contrast, all SSEP Grade 6 patients (n = 7) had a moderate disability or good recovery. This study demonstrates the prognostic value of early quantitative median nerve SSEP grading for patients with head injuries who are unresponsive to commands within 1 week after the injury.
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Diet and female sex hormone concentrations: an intervention study for the type of fat consumed. A possible mechanism by which dietary fat may influence the development of breast cancer is by influencing the concentration of female sex hormones. This study investigated the effect of alteration in the type of fat consumed on concentrations of female sex hormones in serum. Female volunteers were randomly assigned to continue on their usual meat-eating diet, change to a vegetarian diet, or change to a diet that was predominantly vegetarian but where fish was consumed at least three times per week. Change to the vegetarian or fish diet had little effect on diet total hormone concentrations; however, the amount of estradiol was significantly decreased in the vegetarian group. When nutrient consumption was correlated with hormone concentrations, prolactin was directly associate with fat consumption, sex-hormone-binding globulin was inversely associated with fat consumption (particularly cholesterol consumption), and the proportion of nonprotein-bound estradiol was directly associated with complex carbohydrate consumption.
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The 1989 presidential address. International Society for the Study of Vulvar Disease. Major changes in the terminology for vulvar disease have taken place in the past 20 years under the influence of the members of the International Society for the Study of Vulvar Disease. Major terminology changes have been made for vulvar nonneoplastic disorders, vulvar intraepithelial neoplasia and superficially invasive squamous cell carcinoma.
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Underdiagnosis and undertreatment of chronic sinusitis in children. A review of outpatients diagnosed with sinusitis during the previous year by the allergy services of Childrens Hospital of Los Angeles and Kaiser Permanente, Orange County, revealed 34 patients who had protracted discomforting and debilitating symptoms. The mean duration of symptoms was approximately six months (range 1-14 months). None had been previously diagnosed as having sinusitis or received appropriate treatment. Although all were referred for evaluation of allergic rhinitis and/or asthma, approximately 1/3 were found to have neither of these conditions. Among patients who had asthma, their asthmatic symptoms were aggravated by the sinusitis. All patients eventually responded favorably to appropriate antibiotic therapy. Earlier diagnosis and appropriate therapy would have foreshortened the course of this very discomforting condition. In recent years, we have observed a marked increase in the number of patients referred with the chief complaint of "worsening allergy" and who were subsequently found to have sinusitis. Most of the patients experienced significant incapacitation for protracted periods before a correct diagnosis was made and treatment instituted. In all but a few cases, prompt and sustained improvement followed appropriate therapy. The purpose of this report is to present a retrospective review of 34 illustrative cases.
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Prognostic significance of carcinoembryonic antigen in colorectal carcinoma. Serum levels before and after resection and before recurrence. The use of carcinoembryonic antigen was evaluated in 425 patients with a mean follow-up of 48 months. The preoperative and postoperative carcinoembryonic antigen levels were predictive of recurrence and survival independent of the tumor stage. In a multivariate regression analysis of age, location, tumor stage, and preoperative and postoperative carcinoembryonic antigen levels, the latter three factors were significant prognostic variables with respect to the adjusted survival. Recurrent disease was found in 42% of patients, excluding patients with stage IV disease. The carcinoembryonic antigen level at recurrence was greater than 5 ng/mL in 79% of the patients and in 89% of the intra-abdominal recurrences. Carcinoembryonic antigen level at recurrence was not predictive of postrecurrence survival except in the subgroup of locoregional disease. The life span in patients with liver and lung metastases was not influenced by carcinoembryonic antigen level at recurrence. Preoperative and postoperative carcinoembryonic antigen levels can indicate a poorer prognostic group of patients with colorectal cancer who may benefit from adjuvant treatment. The carcinoembryonic antigen at recurrence can be used effectively to diagnose intra-abdominal recurrences and project survival after development of local/regional disease.
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Determinants and significance of diltiazem plasma concentrations after acute myocardial infarction. The Multicenter Diltiazem Postinfarction Trial Research Group. A total of 1,975 plasma diltiazem concentrations were obtained from 1,067 patients enrolled in a multicenter secondary intervention study of diltiazem after acute myocardial infarction. To evaluate the determinants and significance of diltiazem concentrations in this patient population, we related drug concentrations to a variety of clinical variables recorded on the case history forms. Multiple linear regression analysis showed that (1) time from the last drug dose, (2) drug dose taken, (3) patient height (an index of lean body weight), and (4) patient age were important determinants of plasma concentration. For an equivalent dose, plasma diltiazem concentrations in a 75-year-old patient were about double those of a 25-year-old patient. Total weight and drug dose prescribed did not significantly affect plasma concentrations. Whereas drug concentrations were higher (p = 0.01) among patients with left-sided heart failure, they were not altered by renal dysfunction, hepatic disease or beta blockers. Diltiazem concentrations were a significant determinant of diastolic arterial pressure (p less than 10(-9), but neither systolic pressure nor heart rate were significantly related to diltiazem concentration. The overall incidence of adverse experiences was not related to drug concentrations, but the occurrence of second- and third-degree atrioventricular block in the coronary care unit and the need for a temporary pacemaker were substantially higher among patients with a drug concentration greater than 150 ng/ml (7.4 and 1.9%, respectively) than among patients with lower concentrations (2.6% for atrioventricular block, 0.3% for pacemaker; p = 0.02 for each). The risk of atrioventricular block was particularly increased by high diltiazem concentrations in the face of acute inferior infarction. These results suggest that diltiazem's pharmacologic and clinical effects in a large population are concentration-related, and that the consideration of patient size, age, and left ventricular function in selecting a diltiazem dose may allow for effective drug therapy with a reduced likelihood of adverse effects.
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Echocardiographic diagnosis of a ruptured aneurysm of the sinus of Valsalva: operation without catheterisation in seven patients. A ruptured aneurysm of the sinus of Valsalva was diagnosed by Doppler, colour, and cross sectional echocardiography in a consecutive series of seven patients. The diagnoses were confirmed at operation without cardiac catheterisation. Examination by pulsed and continuous Doppler echocardiography showed continuous turbulence in six patients with aneurysms rupturing into the right ventricular outflow tract and in the patient with rupture of an aneurysm of the non-coronary sinus into the right atrium. Colour Doppler echocardiography showed turbulent flow across the defects in all seven patients. A ventricular septal defect with aortic regurgitation was detected in one patient and an associated ventricular septal defect in another. Doppler, colour, and cross sectional echocardiography were useful non-invasive techniques for diagnosing a ruptured aneurysm of the sinus of Valsalva without the need for cardiac catheterisation.
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Ventilatory function as a predictor of fatal stroke. OBJECTIVE--To investigate the relation between ventilatory function and subsequent mortality due to cerebrovascular disease. DESIGN--Prospective longitudinal study. SUBJECTS--A total of 18,403 male civil servants aged 40-64 years at entry examination for the Whitehall study. MAIN OUTCOME MEASURE--Mortality from cerebrovascular disease (ICD8 430-438) after 18 years of follow up. RESULTS--In all, 262 men with sinus rhythm at entry died due to stroke during the 18 years of follow up. Compared with men with a forced expiratory volume in one second of greater than or equal to 3.5 litres those with a value of less than 3.0 litres were almost twice as likely to die of cerebrovascular disease (rate ratio adjusted for age and systolic blood pressure = 1.88, 95% confidence interval 1.32 to 2.69). This increased risk occurred within each tertile of systolic blood pressure. Nested case-control analyses were used to control precisely for confounding effects of age, height, and smoking (by matching) and employment grade and physiological risk factors (by modelling). The effect of forced expiratory volume in one second was independent of age, height, smoking habits, employment grade, blood pressure, weight, cholesterol concentration, glucose tolerance, electrocardiographic abnormalities, history of chest pain, and history of intermittent claudication. CONCLUSIONS--Measurements of ventilatory function may assist clinical decisions about whether to treat mild hypertension. Impaired ventilatory function and stroke may share common causes.
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Pressure-curve variations after trabeculectomy for chronic primary open-angle glaucoma. We report the results of a 5-year study of the influence of trabeculectomy on the maximum intraocular pressure (IOP) and the amplitude of its diurnal oscillation in 26 eyes (14 patients) with open-angle glaucoma. Pressure-curves were recorded before surgery and at 1 year and 5 years after surgery. The latter two pressure-curves demonstrated that trabeculectomy significantly reduced both the maximum IOP and the amplitude of the oscillations below preoperative values.
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Lung vascular injury after administration of viable hemolysin-forming Escherichia coli in isolated rabbit lungs. Escherichia coli hemolysin, a transmembrane pore-forming exotoxin, is considered an important virulence factor. In the present study, the possible significance of hemolysin production was investigated in a model of septic lung failure through infusion of viable bacteria in isolated rabbit lungs; 10(4) to 10(7) E. coli/ml perfusate caused a dose- and time-dependent appearance of hemolysin, accompanied by release of potassium, thromboxane A2, and PGI2 into the perfusate. Concomitantly, marked pulmonary hypertension developed. Inhibitor studies suggested that the pressor response was predominantly mediated by pulmonary thromboxane generation. Administration of hemolysin-forming E. coli additionally caused a protracted, dose-dependent increase in the lung capillary filtration coefficient, followed by severe edema formation. The permeability increase was independent of lung prostanoid generation. An E. coli strain that releases an inactive form of hemolysin completely failed to provoke the described biophysical and biochemical responses. Preapplication of 2 x 10(8) human granulocytes was without effect in the present experimental model. We conclude that the hemolysin produced by low numbers of E. coli organisms can provoke thromboxane-mediated pulmonary hypertension and severe vascular leakage. E. coli hemolysin and, possibly, other related cytolysins may thus contribute directly to the pathogenesis of acute respiratory failure under conditions of sepsis or pneumonia.
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Prospective observations of 100 high-risk neonates by high-field (1.5 Tesla) magnetic resonance imaging of the central nervous system: I. Intraventricular and extracerebral lesions. The results of observations of the first 100 neonates at the University of Texas Health Science Center (Houston) who received magnetic resonance imaging of the central nervous system by means of a high-field image (1.5 T) are reported. All were assessed prospectively to be at risk neurodevelopmental delay. This first report specifically addresses the appearance of primarily hemorrhagic intracranial lesions, including intraventricular hemorrhage (n = 28), and extracerebral lesions, which include 3 cases of venous sinus thrombosis (n = 20). The signal intensities of hemorrhage underwent a characteristic evolution with time with only minor variations in the study group. Magnetic resonance imaging detected direct evidence of hemorrhage for up to 2 months, but hemosiderin was detected as a late indicator of hemorrhage for up to 9 months. Magnetic resonance imaging was equal in benefit to head ultrasonography and computed tomography for the diagnosis of intraventricular hemorrhage, but magnetic resonance imaging was also able to approximate the time of onset of hemorrhage. Magnetic resonance imaging was superior for the evaluation of extracerebral hemorrhage; ultrasonography failed to detect any of these lesions and computed tomography detected only 3 of 7. Short-term neurological abnormality was assessed, but the ability of magnetic resonance imaging to predict long-term neurodevelopmental delay is unknown and is the subject of an ongoing project.
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Giant cell versus lymphocytic myocarditis. A comparison of their clinical features and long-term outcomes BACKGROUND. Giant cell myocarditis has rarely been diagnosed premortem, and little is known about its natural history. In addition, no comparative studies with lymphocytic myocarditis exist. METHODS AND RESULTS. The clinical features, serial change in left ventricular fraction (LVEF), and outcomes of all patients with histologically verified myocarditis were retrospectively evaluated. Ten patients (22%) were found to have giant cell myocarditis (group 1), whereas the remaining 36 (78%) had lymphocytic myocarditis (group 2). Age at presentation, gender distribution, duration of symptoms, initial LVEF, and resting hemodynamics did not differ between groups. Ventricular tachycardia was detected in 90% of group 1 patients compared with only 25% of group 2 (p = 0.0007). Atrioventricular block that required pacemaker insertion was also more common in group 1 (60%) than in group 2 (8.3%) (p = 0.001). Left ventricular systolic function declined during follow-up in group 1 patients (LVEF, 0.43 +/- 0.07-0.26 +/- 0.05, p = 0.11) but increased in group 2 patients (LVEF, 0.33 +/- 0.03-0.41 +/- 0.03, p = 0.02). When the net change between initial and final LVEF was assessed, a significant difference was evident (giant cell group, -0.17 +/- 0.06; lymphocytic group, +0.07 +/- 0.03; p = 0.0008). Although a greater proportion of patients in group 1 died or required transplantation (seven of 10 versus 11 of 36, p = 0.03), actuarial survival over 4 years was not different for the giant cell group (50%) than for the lymphocytic group (62%). CONCLUSION. Giant cell myocarditis was more prevalent than previously recognized and highly associated with both ventricular tachycardia and pacemaker requirement. The likelihood of an adverse event, either cardiovascular mortality or cardiac transplantation, was significantly greater for patients with giant cell myocarditis than for those with lymphocytic myocarditis, perhaps because of the progressive decline in left ventricular systolic function that was observed in those with giant cell myocarditis.
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Cerebral infarction: early detection by means of contrast-enhanced cerebral arteries at MR imaging. The authors describe a new magnetic resonance (MR) imaging sign of acute cerebral ischemia/infarction. Abnormally contrast material-enhanced curvilinear structures were demonstrated in eight patients in the evolving area of cerebral ischemia/infarction within 26 hours after the ictus on contrast-enhanced, high-field-strength (1.5-T), T1-weighted spin-echo images. The abnormal enhancement is considered to represent cortical arterial vessels of markedly slowed circulation in areas of underlying brain injury, which will eventually progress to frank brain infarction. This was demonstrated at computed tomographic (CT) and follow-up MR examinations. Characteristically, the degree of the contrast enhancement of vessels appeared most intense in the proximal portions, and the intensity of enhancement gradually diminished in the more distal portions of these vessels as they pass over the convexities and finally disappear.
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Inflation pressure requirements during coronary angioplasty. To examine the balloon inflation pressures required for successful percutaneous transluminal coronary angioplasty (PTCA), the maximal inflation pressure required for 477 coronary lesions in 200 consecutive patients was determined retrospectively. When graded balloon inflations just sufficient to achieve full expansion were used, the maximal inflation pressure used was less than or equal to 8 atm in 412 stenoses (86%) and was less than or equal to 10 atm in 463 stenoses (97%). Successful PTCA was achieved in 98% of lesions with a 3.5% major procedural complication rate. In a second group of 100 patients studied prospectively, the inflation pressure required to achieve full balloon expansion was less than or equal to 8 atm in 214 of 232 stenoses (92%) and less than or equal to 10 atm in 228 stenoses (98%). Thus, PTCA of coronary stenoses can be achieved with high success rates and low complication rates when graded inflations to pressures just sufficient to achieve full balloon expansion are performed. Most coronary stenoses will respond to pressures less than or equal to 8-10 atm.
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Assessment of the components of observed chronic pain behavior: the Checklist for Interpersonal Pain Behavior (CHIP). This article describes the development of the Checklist for Interpersonal Pain Behavior (CHIP), an observation scale which assesses overt pain behavior. The study is an extension of an earlier study in which the dimensions and components of observed chronic pain behavior were examined. A broad definition of pain behavior is chosen (interpersonal pain behavior), namely the interaction between the pain patient and his/her direct environment. The list of pain behaviors, taken from the earlier study, has been transformed into a 78-item global rating scale to be used by nurses to quantify observed pain behavior in a clinical setting. Six studies examine the factor structure and the psychometric properties of this behavioral observation method. In the first study, 6 internally reliable factors are derived using factor analytic techniques from a sample of 152 chronic pain patients. They are labeled as: 'distorted mobility,' 'verbal complaints,' 'non-verbal complaints,' 'nervousness,' 'depression' and 'day sleeping.' Internal consistency of all factors, except 'day sleeping' was excellent. The following studies show that the CHIP is sufficiently reliable and valid. After a discussion on the advantages of this observation scale, the conclusion seems justified that the CHIP is a useful tool in pain assessment that can easily be used by nurses.
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Intraoperative scintigraphy for active small intestinal bleeding. Localizing active sites of bleeding within the small intestine remains a difficult task. Endoscopic, angiographic or scintigraphic studies may point to the small intestine as the site of blood loss, but at operation, without a palpable lesion, the exact site of bleeding remains elusive. Patients are managed at laparotomy with intraoperative endoscopy, angiography, multiple enterotomies, "blind" resections, or placement of an enterostomy. We describe two patients in whom intraoperative scintigraphy accurately identified active sites of bleeding in the small intestine when other modalities failed. Intraoperative scintigraphy is rapid, easy to perform and is an effective means of identifying active sites of bleeding within the small intestine.
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Proximal esophageal pH-metry in patients with 'reflux laryngitis'. Fiberoptic laryngoscopic examinations were performed on 40 patients with gastroesophageal reflux disease, 25 of whom had persistent laryngeal symptoms (dysphonia, cough, globus sensation, frequent throat clearing, or sore throat) and 15 without laryngeal symptoms who served as disease controls. Ten patients with laryngeal symptoms but none of the controls had laryngoscopic findings consistent with reflux laryngitis. Dual-site ambulatory pH recordings were obtained with the pH electrodes spaced 15 cm apart and with the proximal sensor positioned just distal to the upper esophageal sphincter. Patients in the three groups (disease controls: group 1; patients with symptoms but without laryngoscopic findings: group 2; and patients with both laryngeal symptoms and findings: group 3) were comparable in terms of age, smoking habit, the presence of esophagitis, and distal esophageal acid exposure. Proximal esophageal acid exposure was, however, significantly increased in groups 2 and 3, and nocturnal proximal esophageal acidification occurred in over half of these patients but in none of the group 1 patients. We conclude that the subset of reflux patients who experience laryngeal symptoms show significantly more proximal esophageal acid exposure (especially nocturnally) and often have laryngoscopic findings of posterior laryngitis not observed in control reflux patients.
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CD11c (LEU-M5) expression characterizes a B-cell chronic lymphoproliferative disorder with features of both chronic lymphocytic leukemia and hairy cell leukemia. Chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL) are two common chronic lymphoproliferative disorders, each having characteristic clinical, morphologic, and immunologic features. Phenotypically, CD5 reactivity in CLL and CD11c (Leu-M5) reactivity in HCL have characterized these two leukemias among B-cell disorders. In this study, we report 14 cases of a novel chronic lymphoproliferative disorder characterized by lymphocytosis and CD11c expression, but morphologically similar to CLL. The patients' ages ranged from 46 to 81 years (median 62). Eleven had palpable splenomegaly, five with markedly enlarged spleens; only one patient had generalized lymphadenopathy. The white blood cell count ranged from 5.2 to 131.0 x 10(9)/L (median 20.8). The morphologic diagnosis in all cases was CLL, with the cells usually having abundant cytoplasm. No morphologic features, of hairy cells were evident; tartrate-resistant acid phosphatase cytochemistry was negative in all cases. Bone marrow biopsies were available in 8 of 14. Four showed focal nodular infiltrates and two had diffuse infiltrates similar to CLL; two showed only minimal interstitial involvement. All cases expressed multiple B-cell markers, and 12 of 14 had monoclonal surface immunoglobulin. The leukemic cells of all cases strongly expressed CD11c, while CD5 was expressed in 7 of 14; only 1 of the 14 cases expressed the lymph node homing receptor, Leu-8. This unique group of leukemias appears to represent the malignant transformation of lymphocytes arising from a stage of lymphocyte differentiation between that found in typical cases of CLL and that of HCL. CD11c is known to have an important function in cellular adhesion and may be important in determining the pattern of lymphocyte tissue distribution found in this group of patients.
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Aminocaproic acid prophylaxis in traumatic hyphema. Oral aminocaproic acid has been shown to be effective in clot stabilization and in the reduction of secondary bleeding rates in cases of traumatic hyphema. In a retrospective study of 105 patients treated during a 1-year period, we found the incidence of rebleeding in patients with traumatic hyphema who received aminocaproic acid prophylaxis was 2%; the incidence in those who did not was 25%.
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Single photon emission computed tomography and positron emission tomography in cancer imaging. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are now being used to improve the information available from radioisotopic imaging of patients with cancer. These nuclear medicine techniques offer the potential for studying regional function and biochemistry by using radiolabeled substrates. The chemical changes of malignancy precede anatomic changes, and PET and/or SPECT may detect these changes before anatomic changes have occurred. The superiority of SPECT compared with planar imaging has been demonstrated for cardiac and brain imaging. Radiopharmaceuticals containing technetium 99 m (99mTc) are best suited for SPECT imaging because large amounts of radioactivity are administered and the collimator-camera systems are optimized for the 140 keV photons of 99mTc. The current interest in imaging cancer with SPECT relates to the use of gallium 67 citrate and monoclonal antibodies labeled with iodine 123 or indium 111. SPECT can image these radioisotopes, but the advantages compared with planar imaging have not been clearly defined. Furthermore, the ability to quantitate the distribution of single photon emitters other than 99mTc has not been demonstrated. New SPECT systems with three heads or rings of detectors offer promise for improved, quantitative imaging. PET has the capability of imaging tracers with the biologically important elements C-11, N-13, O-15, and F-18 used for positron labeling. These radioisotopes have short half-lives and require a cyclotron close to the PET facility. The most prominently used radiopharmaceutical for PET is F-18 fluorodeoxyglucose (FDG). PET studies with FDG in patients with primary brain tumors have demonstrated the ability to determine the degree of malignancy, to differentiate necrosis from recurrent tumor after radiation therapy or chemotherapy, and to predict prognosis. Other metabolic functions of cancer have been studied, including amino acid accumulation, thymidine uptake, oxygen utilization, intermediary metabolism, and receptor status. PET has the potential to make a major impact on the characterization of a malignancy and the effect of therapy.
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Isolated calf venous thrombosis: diagnosis with compression US. Compression ultrasound (US) is an excellent means of evaluating the femoral and popliteal veins but is generally regarded as inadequate for the diagnosis of calf vein thrombosis. This prospective study evaluated compression sonography of the calf veins in 45 symptomatic patients with normal femoral and popliteal veins. All patients underwent correlative venography. Compression US enabled identification of 15 of 17 patients with calf vein thrombosis (sensitivity, 88%). The two false-negative results were in patients with small isolated thrombi. Compression US results were true-negative in 26 of 27 patients with normal venograms (specificity, 96%). If these results can be duplicated by other investigators in larger series of patients, compression US will be an adequate screening modality for calf vein thrombosis.
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Life-threatening hemorrhage after placement of an endosseous implant: report of case This article reports an unusual but dangerous complication of implant surgery. Minimal perforations of the lingual plate and inferior border of the mandible had been considered previously to be benign occurrences. This report demonstrates the importance of managing acute airway problems resulting from perforations.
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Bacteriologic findings with ectopic pregnancy. The fallopian tubes and peritoneum of 27 patients were cultured at the time of salpingotomy/salpingectomy to determine if active tubal infection was the cause of post-operative temperature elevations. Infection was documented in six patients (22%). Previous exposure to Chlamydia trachomatis was documented with 2 endocervical cultures and 17 serum specimens positive for IgG antibody. The culture results, however, did not correlate with the postoperative febrile morbidity.
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Aortobronchial fistula after an aortic operation. A 71-year-old man with a postoperative aortobronchial fistula was successfully treated. The fistula occurred between the left lower lobe and the descending thoracic aorta, to which a distal anastomosis of a temporary bypass graft had been placed during thoracic aortic aneurysmectomy 3 years before. For saving patients with this complication, early surgical treatment during episodes of intermittent hemoptysis is important. The use of an omentum pedicle flap for the isolation of the suture line is a important adjunct.
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Herpes simplex keratitis in renal transplant patients. Five out of 430 patients (1.16%) undergoing kidney transplantation developed an atypical clinical picture of herpetic dendritic keratitis within four weeks after surgery. It was manifested by multiple dendrites, located mainly in the corneal periphery or the limbus, developing in relatively uninflamed eyes. The response to acyclovir therapy was prolonged and took at least three weeks. Additionally, subepithelial infiltrates with ultimate scarring developed in all patients. Disciform keratopathy was not found. This clinical course is ascribed to the patients' immunosuppressed state.
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Use of a probe to repeat sequence of the Y chromosome for detection of host cells in peripheral blood of bone marrow transplant recipients. In situ hybridization for the Y chromosome (Y-ISH) was used to identify residual host cells in the peripheral blood of 51 recipients of sex-mismatched allogeneic marrow not depleted of T cells following conditioning with high-dose cyclophosphamide and total body irradiation (TBI). One patient who rejected the graft showed rapid reappearance of host cells after transient donor marrow engraftment. Host cells were detected at low levels in 49 of the remaining 50 patients. Host peripheral blood mononuclear cells (PBMC) decreased with time and reached a plateau at 1.0 +/- 0.2% within four weeks after transplantation, while the percentage of host granulocytes (GRAN) reached a plateau at background level. The mean absolute numbers of host PBMC or GRAN were less than 0.015 x 10(9)/L and did not vary significantly over the period studied. Neither the percentages nor the absolute numbers of host PBMC or GRAN were significantly affected by HLA-matching, TBI dose-intensity, pretransplant remission status, subsequent development of acute or chronic graft-versus-host disease or relapse after transplantation. The authors conclude that it is common to find a few residual host cells in the peripheral blood of allogeneic marrow transplant recipients, and the presence of these cells has no clinical significance.
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Acute upper airway obstruction following Teflon injection of a vocal cord; the value of nebulized adrenaline and a helium/oxygen mixture in its management A 67-year-old man presented with a 45-year history of a week voice. This was result of polio which had left him with a right vocal cord palsy. The patient underwent a Teflon injection of the right vocal cord under general anaesthesia to improve the quality of his voice. In the immediate post-operative period, he suffered acute upper airway obstruction. The problem of acute upper airway obstruction following Teflon injection is considered and its management with nebulized adrenaline and a helium/oxygen mixture is discussed.
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Neuromesenchymal hamartoma of the small bowel. We present the case of a long small bowel stricture with pathological features similar to those described as "neuromuscular and vascular hamartoma," showing in addition extensive fatty submucosal infiltration and fibrous intramural nodules. In the controversy about the nature of this disorder, we consider it a separate entity. Taking into account that other mesenchymal tissues than the originally described can participate, we propose the alternative term of "neuromesenchymal hamartoma" of the small bowel.
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Flow cytometric determination of breast tumor heterogeneity. Flow cytometric analysis was done on the DNA content of nuclei obtained from different sites of small breast tumors. Although specimens for analysis were obtained within a few millimeters of each other, dramatic differences were occasionally observed in the DNA histograms. In a limited study involving 141 consecutive breast specimens submitted for flow cytometry, 52% (74) were found to have at least one DNA aneuploid population. In 18% of DNA aneuploid tumors, one or more specimens from areas grossly identified as tumor had no DNA aneuploid population. Because of the proposed correlation of aneuploidy with a poorer prognosis and possible responsiveness to chemotherapy, multiple sites should be assayed when flow cytometric DNA analysis is done.
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Esophageal reflux before and after isolated myotomy for achalasia. Four patients with achalasia underwent 24-hour esophageal pH measurements as ambulatory patients before and after limited myotomy without fundoplication. Resting lower esophageal sphincter pressure was reduced from 24.3 +/- 1.3 mm Hg to 7.5 +/- 4.3 mm Hg. No significant differences (p greater than 0.05) were found before and after operation in the total 24-hour pH data distribution (pH 6.24 +/- 0.84 vs 5.75 +/- 1.03), the fraction of time below pH 4.0 (4.8% +/- 5.3% vs 8.0% +/- 6.9%), or the mean duration of reflux episodes greater than 5 minutes (22.8 +/- 18.8 minutes vs 23.0 +/- 10 minutes), all +/- SD. Effective relief of esophageal obstruction in achalasia is feasible by isolated limited myotomy without producing gastroesophageal reflux.
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Supraventricular tachycardia due to Wolff-Parkinson-White syndrome in children: early disappearance and late recurrence The clinical course of 140 patients with Wolff-Parkinson-White syndrome who had their initial episode of supraventricular tachycardia before 18 years of age was reviewed. Among those whose tachycardia began at age 0 to 2 months, it disappeared in 93% and persisted in 7%. In 31%, it disappeared and reappeared at an average age of 8 years. Among patients whose tachycardia was present after age 5 years, it was persistent in 78% at a mean follow-up period of 7 years. Accessory connection location was mapped by electrophysiologic study in 87 patients and estimated by electrocardiography in 53 patients. There were no differences in tachycardia onset or recurrence based on accessory connection location. Congenital heart defects were present in 37% of all patients, 23% of whom had Ebstein's anomaly. Among all patients who underwent cardiac catheterization, 63% of those with a congenital heart defect had a rightsided accessory connection, whereas 61% of patients with a normal heart had a left-sided connection (p less than 0.01). Multiple accessory connections were found in 12% of patients with a congenital heart defect compared with 6% of those without such a defect. In conclusion: 1) supraventricular tachycardia due to Wolff-Parkinson-White syndrome that begins in infancy may disappear, but it frequently recurs in later childhood; 2) if tachycardia is present after age 5 years, it persists in greater than 75% of patients; and 3) the location of the accessory connection does not affect the clinical course of tachycardia in children with Wolff-Parkinson-White syndrome.
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Quality-of-life-adjusted survival for comparing cancer treatments. A commentary on TWiST and Q-TWiST. In chronic disease situations where treatment comparisons favor no particular therapy, or where definitive outcome requires a considerable follow-up period, it is useful to have additional and perhaps intermediate endpoints of relevant clinical significance to compare treatments. One such endpoint is Time Without Symptoms and Toxicity (TWiST) which, together with Q-TWiST, attempts to address the quality of life of patients receiving the competing regimens. This paper provides a commentary on these techniques with an emphasis on the problems inherent in implementing Q-TWiST, a measure that attempts to incorporate patient value preferences into TWiST. It is argued that while Q-TWiST is intuitively appealing in the clinical setting, there are formidable design and psychometric hurdles that must be overcome to fully operationalize the concept.
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Occurrence of hypercalcemia and leukocytosis with cachexia in a human squamous cell carcinoma of the maxilla in athymic nude mice: a novel experimental model of three concomitant paraneoplastic syndromes. Hypercalcemia and leukocytosis may occur in conjunction as paraneoplastic syndromes associated with malignant disease. Here we describe a human squamous cell carcinoma of the maxilla that was associated with hypercalcemia and leukocytosis, and also cachexia. The primary tumor was surgically removed and established in permanent cell culture. When either primary tumors or cultured tumor cells were inoculated into nude mice, the nude mice developed the same paraneoplastic syndromes as those which occurred in the patient from whom the tumor was originally derived. The plasma calcium was increased two and one-half-fold and the WBC count 30-fold, and the body weight was decreased by 45% in tumor-bearing animals. Each of these paraneoplastic syndromes was alleviated by surgical excision of the tumor, indicating that the paraneoplastic syndromes were due to a factor or factors produced by the primary tumor. The development of each of these paraneoplastic syndromes in nude mice correlated positively with the other two syndromes. We examined the organs of tumor-bearing mice and found striking histopathologic abnormalities in the bones, spleen, and liver, but no infiltration with tumor cells. The bones showed marked evidence of osteoclastic bone resorption. This model of a human tumor associated with the hypercalcemia-leukocytosis paraneoplastic syndrome, together with cachexia, should make it possible to determine the mechanisms responsible for these paraneoplastic syndromes and their relationship to each other.
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Dyspareunia. Tracing the cause. Difficult or painful sexual intercourse is a sensitive topic for most women. The causes range from inflammation of the vulva and interstitial cystitis to marital discord. To exclude an organic disorder, a detailed pelvic examination with good lighting and magnification is in order. Dr DeWitt describes the technique for meticulous examination and discusses the diagnoses that need to be considered.
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Quantitative proton magnetic resonance imaging in focal cerebral ischemia in rat brain. Proton magnetic resonance (MR) imaging has been recommended as a diagnostic tool for the detection of focal cerebral ischemia. We compared microscopic MR images of rat brains after focal cerebral ischemia with evidence of histological damage found on corresponding silver-impregnated or cresyl violet-stained brain sections. Ten male Wistar rats were subjected to permanent unilateral occlusions of the right middle cerebral and common carotid arteries under halothane anesthesia. Twenty-four hours later the area of injury on MR images amounted to 26% of the total slice area, whereas only 9% of the total slice area was necrotic on histological sections from the same animals. The infarcted areas on tissue sections were surrounded by regions of selective neuronal injury in the cerebral cortex and occasionally in the hippocampus. The area of injury on MR images was larger than the combined areas of infarction and selective neuronal injury on histological sections. Areas of increased T2 values on MR images extended medially into noninfarcted striatum and laterally and dorsally into noninfarcted cortex. The lateral and dorsal areas on MR images frequently coincided with cortical areas in which considerable selective neuronal injury was present in the upper cortical layers. We hypothesize that the abnormal areas on MR images above histologically normal brain tissue represent the ischemic penumbra. If true, this is the first demonstration of the ischemic penumbra by MR imaging and may reflect our use of Wistar rats, a new image analysis technique, and ultra-high resolution MR imaging.
3
Salicylate poisoning from enteric-coated aspirin. Delayed absorption may complicate management. Acute salicylate poisoning with enteric-coated aspirin may result from accidental ingestion, a suicide attempt, or a complication of long-term therapy. Because absorption of enteric-coated aspirin is delayed, use of the Done nomogram to determine toxicity may lead to underestimating the severity of the poisoning. Treatment options include induction of emesis or diuresis, gastric lavage, administration of activated charcoal, and surgery.
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Prevalence of angioid streaks and other ocular complications of Paget's disease of bone. Seventy randomly selected patients with Paget's disease of bone were examined for ocular complications. The prevalence of macular degeneration and cataract was 24.3%. Only one patient was found to have angioid streaks. Eight patients had peripapillary chorioretinal atrophy. These findings suggest that the prevalence of serious ocular complications of Paget's disease is not as high as previously thought. The significance of peripapillary chorioretinal atrophy requires further evaluation.
5
Hemorrhoidectomy during pregnancy: risk or relief? Acute hemorrhoidal crisis can occur in the pregnant female. When medical therapy fails to relieve pain, operative intervention may be necessary. The surgeon, however, may be reluctant to operate due to potential complications to the mother and fetus. From July 1983 to July 1989, hemorrhoidectomy was performed in 25 of 12,455 pregnant women (0.2 percent) who delivered in our institution. Twenty-two women were in their third trimester, 80 percent were multiparous, and each had a remote history of hemorrhoidal symptoms, including intermittent pain, bleeding, and protrusion. Closed hemorrhoidectomy was performed under local anesthesia. The surgery was directed at removing only symptomatic disease, which included three quadrants in 14 patients, two quadrants in seven patients, and one quadrant in four patients. All patients experienced relief of intractable pain the day after surgery, except one patient who required a hemostatic packing during the immediate post-operative period. There were no other maternal or fetal complications. Subsequent follow-up for anorectal disease ranged from 6 months to 6 years. Six (24 percent) patients required additional hemorrhoid treatment. Hemorrhoidectomy in selected pregnant patients is safe in our experience.
5
Structure, expression and function of a schwannoma-derived growth factor. During the development of the nervous system, cells require growth factors that regulate their division and survival. To identify new growth factors, serum-free growth-conditioned media from many clonal cell lines were screened for the presence of mitogens for central nervous system glial cells. A cell line secreting a potent glial mitogen was established from a tumour (or 'schwannoma') derived from the sheath of the sciatic nerve. The cells of the tumour, named JS1 cells, were adapted to clonal culture and identified as Schwann cells. Schwann cells secrete an autocrine mitogen and human schwannoma extracts have mitogenic activity on glial cells. Until now, neither mitogen has been purified. Here we report the purification and characterization of a mitogenic molecule, designated schwannoma-derived growth factor (SDGF), from the growth-conditioned medium of the JS1 Schwann cell line. SDGF belongs to the epidermal growth factor family, and is an autocrine growth factor as well as a mitogen for astrocytes, Schwann cells and fibroblasts.
3
Acute obstructive jaundice in the multiple trauma patient. The appearance of acute jaundice in the multiple trauma patient may result from obstruction of the common bile duct by clot. Management of this problem may be hindered by a delay in diagnosis, especially where alterations in pigment load and hepatic clearance may have produced the jaundice. A high index of suspicion combined with the judicious use of various noninvasive imaging modalities may be helpful in making the diagnosis. The progression of jaundice in a patient suspected of having acute obstructive hemobilia should prompt rapid operative intervention. At laparotomy, cholangiography or common bile duct exploration should be done. Persistent bleeding should be managed initially with angiographic localization and transcatheter embolization; its failure would necessitate surgical control of the source.
5
Meningitis in the neurosurgical patient. In the patient with a basilar skull fracture and CSF leak, the risk of meningitis is greatly increased. The diagnosis of both leak and infection can be obscured by the patient's other injuries, and requires aggressive investigation of symptoms that suggest infection. Although the diagnosis is made with CSF cultures, when clinically suspected, treatment should begin after appropriate cultures have been obtained. Treatment should be directed against the most likely organisms, Streptococcus pneumoniae, Haemophilus influenzae, and the other organisms common to the upper respiratory tract. There are no good indications for prophylactic antibiotic usage in patients with known CSF leaks. The patient with a shunt or other CNS prosthetic device may have various manifestations of infection, depending on the type of device and its termination. Frank meningitis or ventriculitis is not always present. Diagnosis requires direct culturing of the shunt milieu, with the most frequent isolates being staphylococcal species and gram-negative enteric bacilli. The most effective therapy, for both eradication of the infection and minimization of the duration and morbidity of therapy, involves removal of the infected shunt, external drainage during parenteral antibiotic therapy, and complete replacement of hardware at the time of internalization. The postsurgical patient will not develop meningitis very frequently, but like the posttrauma patient, concurrent factors can make the diagnosis difficult. Differentiating infectious from chemical meningitis must often be initially based on CSF cell counts and chemistries alone. Treatment to cover the most likely organism, staphylococcal species and respiratory flora, should be started before the culture results are finalized.
5
Cyclosporine-induced thrombotic microangiopathy resulting in renal allograft loss and its successful reuse: a report of two cases. Cyclosporine-induced thrombotic microangiopathy is a rare complication of renal transplantation. It commonly leads to graft loss. The mechanism of this entity is unknown. Factors intrinsic to the donor kidney appear to play an important role. We describe two cases of renal transplant patients who lost their first grafts secondary to cyclosporine-induced thrombotic microangiopathy. These patients were successfully retransplanted with an immunosuppressive protocol that included long-term cyclosporine. We conclude that graft loss from this entity is not a contraindication to subsequent successful transplantation with cyclosporine.
4
Endoscopic retrograde cholangiopancreatography in infantile cholestasis. The difficulty of distinguishing surgically correctable causes of conjugated hyperbilirubinaemia in infants from other causes means that some infants may undergo laparotomy and intraoperative cholangiography unnecessarily, and others may be referred for surgery too late. In an attempt to improve the diagnostic accuracy in infants with conjugated hyperbilirubinaemia when standard methods produced equivocal results, we have been using prototype paediatric duodenoscopes (PJF 7.5 and XPJF 8.0; Olympus) to perform endoscopic retrograde cholangiopancreatography (ERCP). From 159 infants with conjugated hyperbilirubinaemia, 11 were referred for ERCP, which was performed in nine. In four in whom bile ducts were definitely visualised laparotomy was avoided. Operative cholangiography confirmed patent bile ducts in one in whom visualisation had been uncertain. Three of four in whom bile ducts were not seen had extrahepatic biliary atresia. Visible bile drainage in the fourth excluded atresia. No major complications ensued but there was radiological evidence of gall bladder perforation in one (common hepatic duct block) and overinflation with air was a problem until finer cannulae (Wilson-Cook) were introduced. In appropriately selected patients with conjugated hyperbilirubinaemia, ERCP with paediatric duodenoscopes in experienced hands may provide useful diagnostic information.
2
Avoiding interpretive pitfalls when assessing arrhythmia suppression after myocardial infarction: insights from the long-term observations of the placebo-treated patients in the Cardiac Arrhythmia Pilot Study (CAPS) The Cardiac Arrhythmia Pilot Study (CAPS) was a 1 year trial that analyzed the safety and effectiveness of arrhythmia suppression in 502 patients surviving acute myocardial infarction who had greater than or equal to 10 ventricular premature depolarizations/h or greater than or equal to 5 runs of ventricular tachycardia on a Holter recording obtained 6 to 60 days after the acute infarction. Because 100 of these patients received placebo in a double-blind fashion for 1 year, a comprehensive objective analysis was performed of spontaneous arrhythmia changes based on real data rather than statistical estimates. In the CAPS placebo group, 19% developed some serious clinical event in 1 year (death, heart failure, proarrhythmia) that could likely be attributable to antiarrhythmic drug toxicity. A significant reduction in the frequency of ventricular premature depolarizations (p = 0.004) occurred in the first few weeks of "therapy" with a further significant (p less than 0.04) decrease between 3 to 12 months. After initiation of placebo antiarrhythmic therapy, 27% had "apparent ventricular premature depolarization suppression" (greater than or equal to 70% reduction) after one Holter recording evaluation and nearly half (48%) after six Holter recordings to assess suppression were performed.
4
Cancer in relatives of survivors of childhood sarcoma. Relatives of 88 long-term survivors of childhood sarcoma were examined for the familial cancer syndrome of sarcoma, breast cancer, and other neoplasms (Li-Fraumeni syndrome). Twenty-six of 402 close relatives developed cancer (expected, 23.8), including breast cancer in four mothers (expected, 3.1). Two sarcoma probands who developed second malignant tumors have multiple relatives with cancer and might have an inherited predisposition. An increased cancer risk and exceptional requirement for disease screening appear to be confined to first-degree relatives of a small fraction of children with sarcoma, notably probands with second cancers.
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Questionable role of CNS radioprophylaxis in the therapeutic management of childhood rhabdomyosarcoma with meningeal extension. A series of 15 consecutive children with head and neck nonorbital rhabdomyosarcoma (RMSA) with meningeal extension were prospectively treated with chemotherapy consisting of Adriamycin (doxorubicin; Adria Laboratory, Columbus, OH) (ADM), vincristine (VCR), cyclophosphamide (CPM), and dactinomycin (DACT) followed by radiotherapy (60 Gy) to the primary tumor volume, along with intrathecal methotrexate (IT MTX). Thirteen of 15 responded to preradiation chemotherapy. Four of 13 relapsed. Relapse occurred at the level of the primary tumor in three of four. The 3-year progression-free survival (PFS) was 59%, similar to that achieved in a previous series treated with a comparable therapeutic approach that also included whole-brain radiotherapy as a prophylaxis of possible occult meningeal seeding. It is concluded that CNS prophylaxis with radiotherapy is questionable in the management of childhood RMSA with meningeal extension.
3
A multifactorial analysis of mortality and morbidity in perforated peptic ulcer disease. Perforated peptic ulcer disease remains a source of considerable morbidity and mortality, and the suggested methods of surgical therapy are diverse. We reviewed the course of 113 patients who were treated surgically and identified 14 factors that influenced the morbidity or mortality rates, or both. Multiple regression analysis showed that the number of coexisting medical conditions, a lower mean blood pressure level and the duration of acute perforation were independent risk factors for death, while age, use of a bronchodilator, a lower mean blood pressure level and the number of coexisting medical conditions correlated positively with all complications. A duodenal site was independently favorable with respect to all complications. The type of operation performed either simple closure, vagotomy and drainage or resection, did not influence morbidity or mortality. The most severely ill patients also did not benefit from any particular type of operation in the short term. Long term results were improved with definitive operation, as measured by the Visick classification and the need for reoperations. Definitive operations are recommended for virtually all patients with perforated peptic ulcer.
2
Transoesophageal echocardiogram may fail to diagnose perioperative myocardial infarction. We report a case in which a 55-yr-old man undergoing aortocoronary bypass was monitored with electrocardiogram and transoesophageal echocardiogram. Intraoperative electrocardiogram and simultaneous ECG recordings using the Holter monitor showed an ST elevation of greater than 2 mm and new Q wave formation in leads AVF and V5 during skin closure. However, the transoesophageal echocardiogram showed no wall motion abnormalities. No significant haemodynamic abnormalities were observed during the period of intraoperative ECG changes. He was treated with nitroglycerin infusion. Confirmation of a perioperative myocardial infarct was documented by postoperative 12-lead ECG and CPK-MB. A post-operative transthoracic echocardiogram showed a hypokinetic left ventricle with an anteroapical infarct. Thus transoesophageal echocardiography failed to detect an apical wall motion abnormality when the probe was placed at the midpapillary level. This limitation can be overcome by periodically obtaining apical views or by using probes with more than one imaging plane.
4
Nitrite from inflammatory cells--a cancer risk factor in ulcerative colitis? Elevated levels of luminal nitrite and a lowered luminal pH were found in 77 percent of patients with acute ulcerative colitis. No luminal nitrite was found in healthy control subjects. Nitrites are a secretory product of activated macrophages and neutrophils of the lamina propria, whereas the lowered luminal pH is due to diminished bicarbonate formation by impaired colonocytes. A hypothesis is put forward that nitrites, lowered pH, and bacterial amines are conducive to formation of carcinogenic n-nitroso compounds, which reflect a cancer risk in patients with ulcerative colitis dependent on the type and extent of inflammatory cell activation as well as metabolic impairment of colonic epithelial cells.
2
Duodenal-caval fistula. Duodenal-caval fistula is a rare, often lethal disease that requires prompt diagnosis and surgical correction. A case of duodenal-caval fistula due to duodenal ulceration is presented and discussed.
2
Reconstitution of high-affinity opioid agonist binding in brain membranes. In synaptosomal membranes from rat brain cortex, the mu selective agonist [3H]dihydromorphine in the absence of sodium, and the nonselective antagonist [3H]naltrexone in the presence of sodium, bound to two populations of opioid receptor sites with Kd values of 0.69 and 8.7 nM for dihydromorphine, and 0.34 and 5.5 nM for naltrexone. The addition of 5 microM guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]) strongly reduced high-affinity agonist but not antagonist binding. Exposure of the membranes to high pH reduced the number of GTP[gamma-35S] binding sites by 90% and low Km, opioid-sensitive GTPase activity by 95%. In these membranes, high-affinity agonist binding was abolished and modulation of residual binding by GTP[gamma S] was diminished. High-affinity (Kd, 0.72 nM), guanine nucleotide-sensitive agonist binding was reconstituted by polyethylene glycol-induced fusion of the alkali-treated membranes with (opioid receptor devoid) C6 glioma cell membranes. Also restored was opioid agonist-stimulated, naltrexone-inhibited GTPase activity. In contrast, antagonist binding in the fused membranes was unaltered. Alkali treatment of the glioma cell membranes prior to fusion inhibited most of the low Km GTPase activity and prevented the reconstitution of agonist binding. The results show that high-affinity opioid agonist binding reflects the ligand-occupied receptor-guanine nucleotide binding protein complex.
1
Randomized comparison of ceftriaxone and cefotaxime in Lyme neuroborreliosis. In this prospective, randomized, open trial, 33 patients with Lyme neuroborreliosis were assigned to a 10-day treatment with either ceftriaxone, 2 g intravenously (iv) every 24 h (n = 17), or cefotaxime, 2 g iv every 8 h (n = 16). Of the 33 patients, 30 were eligible for analysis of therapeutic efficacy. Neurologic symptoms improved or even subsided in 14 patients of the cefotaxime group and in 12 patients of the ceftriaxone group during the treatment period. At follow-up examinations after a mean of 8.1 months, 17 of 27 patients examined were clinically asymptomatic. In one patient Borrelia burgdorferi was isolated from the cerebrospinal fluid (CSF) 7.5 months after ceftriaxone therapy. CSF antibiotic concentrations were above the MIC 90 level for B. burgdorferi in nearly all patients examined. Patients with Lyme neuroborreliosis may benefit from a 10-day treatment with ceftriaxone or cefotaxime. However, as 10 patients were symptomatic at follow-up and borreliae persisted in the CSF of one patient, a prolongation of therapy may be necessary.
3
Progress in psychosocial and behavioral cancer research. The need for enabling strategies. A major component of the Second Workshop on Methodology in Behavioral and Psychosocial Cancer Research was a discussion of enabling strategies, that is, strategies by which future goals and needs in the area of psychosocial and behavioral oncology might be accomplished. This report describes and comments on the discussion that took place at a special plenary session at which representatives from four funding agencies, the American Cancer Society, National Cancer Institute, National Institute of Mental Health, and National Science Foundation, presented their views and their agencies' programs for promoting research in psychosocial and behavioral oncology. It is concluded that much progress has been made in the field and that strategies are in place for ensuring continued progress. However, suggestions are also made for new strategies that might accelerate and broaden that progress.
1
Intracranial hemorrhage from aneurysms and arteriovenous malformations during pregnancy and the puerperium. Intracranial hemorrhage (ICH) from an intracranial aneurysm or arteriovenous malformation is a grave complication of pregnancy and is responsible for 5 to 12% of all maternal deaths. We critically analyzed 154 cases of verified ICH during pregnancy from an identified intracranial lesion, including 2 patients treated at our institution and 152 cases previously reported in the literature in English. Aneurysms were responsible for ICH in 77% of patients, and arteriovenous malformations in 23%. Hemorrhage occurred antepartum in 92% of patients and postpartum in 8%. Women with angiomatous hemorrhage were younger than those with aneurysmal hemorrhage; however, in contrast to previous reports, we found no differences between angiomatous and aneurysmal hemorrhage with respect to parity or gestational age at the time of the initial hemorrhage. Hypertension and/or albuminuria were present at some time during the pregnancy in 34% of patients with documentation, which sometimes made it difficult to differentiate angiomatous or aneurysmal ICH from that associated with eclampsia. In a logistic regression analysis, surgical management of aneurysms, but not arteriovenous malformations, was associated with significantly lower maternal and fetal mortality, independent of other covariants. For those patients with a lesion not operated on, cesarean delivery afforded no better maternal or fetal outcome than did vaginal delivery. We conclude that the decision to operate after ICH during pregnancy should be based upon neurosurgical principles, whereas the method of delivery should be based upon obstetrical considerations. The perioperative and anesthetic management of the pregnant patient with a neurosurgical complication is discussed.
5
Near fatal subacute thallium poisoning necessitating prolonged mechanical ventilation. The authors describe a case of severe sensory-motor polyneuropathy caused by subacute thallium-intoxication rapidly progressing to respiratory failure due to complete muscle paralysis. After more than 2 months of mechanical ventilation, weaning from the ventilator was possible. Further intensive physical rehabilitation required an additional 6 months hospital stay, and 18 months later, neurological recovery was complete except for the distal lower limbs muscles. The authors discuss the different forms of thallotoxicosis and the present treatment is reviewed. Maximal prolonged therapeutic support should be offered in severe thallotoxicosis because of possible near complete recovery.
5
Diclofenac-associated hepatotoxicity Diclofenac sodium, a phenylacetic acid-derived nonsteroidal anti-inflammatory drug (NSAID) recently released in the United States, was associated with the development of significant hepatitis in seven patients, with one associated death. Signs and symptoms developed within several weeks of initiation of drug use and generally resolved 4 to 6 weeks following discontinuation of use of the drug. The only patient rechallenged with the drug developed a recurrence of her hepatic abnormalities. In one patient, fatal, fulminant hepatitis developed despite early withdrawal of the drug. Review of the European literature disclosed three additional fatalities associated with diclofenac therapy. It is unclear whether the incidence of hepatotoxicity is higher with this drug compared with other nonsteroidal anti-inflammatory drugs. Careful patient monitoring is advised, and prompt discontinuation of the drug is suggested when signs or symptoms of liver disease develop.
3
Atrioventricular septal defects. Analysis of short- and medium-term results. Atrioventricular septal defects were repaired in 87 patients from 1981 to 1988. Interventricular communications were present in 73 patients, and major associated anomalies were present in 17 (tetralogy of Fallot in four, double-outlet right ventricle in two, multiple ventricular septal defects in 11). Five deaths occurred in the hospital (5.7%; 70% confidence limits, 3.2% to 9.7%). A preoperative New York Heart Association class V functional condition was the only incremental risk factor (p = 0.02) for death in the hospital. No patient (0%; 70% confidence limits, 0% to 2.15%) had complete heart block. Actuarial survival rate at 80 months was 81.4%. The only incremental risk factor (p = 0.005) leading to reoperation was a preoperative valve incompetence. Actuarial rate at 80 months for freedom from reoperation was 84.2% in the overall group of patients after repair of atrioventricular septal defect. We conclude that an improvement in survival and success rates should be found when a policy of earlier repair is followed.
4
In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells. Cloned integrin alpha 2 subunit complementary DNA was expressed on human rhabdomyosarcoma (RD) cells to give a functional VLA-2 (alpha 2 beta 1) adhesion receptor. The VLA-2-positive RDA2 cells not only showed increased adhesion to collagen and laminin in vitro, but also formed substantially more metastatic tumor colonies in nude mice after either intravenous or subcutaneous injection. These results show that a specific adhesion receptor (VLA-2) can markedly enhance both experimental and spontaneous metastasis. In contrast to the metastasis results, there was no difference in either the in vitro growth rate or apparent in vivo tumorigenicity of RD and RDA2 cells.
5
The fallacy of the screening interval for cervical smears. One hundred seventy-four women with invasive cervical carcinoma were interviewed about their cervical smear histories to assess the accuracy of self-reporting and to relate the smear history with patient and tumor characteristics. Patients reported significantly more frequent, more recent, and more normal smears than were documented in medical records. The interval between onset of cancer symptoms and previous smear correlated directly with advanced stage. Sixteen women with normal smears within 36 months had significantly more advanced cancers than did 25 women with recent abnormal smears. Women with recent normal and abnormal smears had similar sociodemographic and behavioral characteristics. Because of inaccuracies in patients' self-reported smear histories and cancers developing in women with recent normal smears, we conclude that a specific screening interval should not be relied upon.
1
Lacunar transient ischaemic attacks: a clinically useful concept? Lacunar ischaemic stroke syndromes are clinically, pathophysiologically, and prognostically distinguishable from cortical ischaemic stroke syndromes. Could cerebrovascular transient ischaemic attacks (TIAs) share similar heterogeneity? 130 patients with TIAs were prospectively studied, 71 of whom underwent carotid angiography. Symptoms were associated with a 50% or greater stenosis of the ipsilateral internal carotid artery in 36 (67%) of 54 patients with presumed cortical TIAs, but in only 1 (6%) of 17 patients with presumed lacunar TIAs (p less than 0.0001). These findings support the view that cortical TIAs are associated with ipsilateral extracranial internal carotid artery atheromatous disease, whereas patients with lacunar TIAs may have absent or insignificant large-vessel disease, and probable intracranial small-vessel disease. Accurate distinction between lacunar and cortical events may have implications for investigation and treatment of patients with TIAs.
4
An evolutionary perspective on salt, hypertension, and human genetic variability. Natural selection for electrolyte conservation has likely been the norm throughout human evolutionary history. However, the current patterns of excessive dietary salt intake create the potential for salt overload. Under these conditions, hypertension may be considered an expected pathological response to an evolutionarily new constraint. The transatlantic Middle Passage may have created a genetic bottleneck for salt conservation in African-Americans. Although the initial consequences of this important historical event probably constricted genetic variability and further magnified the potential for salt-sensitive hypertension, the Middle Passage undoubtedly also served as a more generalized major source of environmental stress and may have stimulated subsequent hereditary diversity in the survivors of this holocaust and their descendants. Accelerated rates of mutation, genetic recombination, and transposable genetic elements in conjunction with enhanced opportunities for gene flow, new selective pressures, and drift have all contributed to the tremendous heterogeneity of contemporary African-Americans. It is unlikely that a single genetic event, even of the severity of the Middle Passage, can account comprehensively for the apparent susceptibility of this macroethnic group to high blood pressure and hypertension.
4
Anton's syndrome in a patient with posttraumatic optic neuropathy and bifrontal contusions. We describe a patient who manifested Anton's syndrome after sustaining head trauma that resulted in optic nerve damage and bifrontal contusions. Denial of monocular blindness, generalized anosognosia, and confabulation were prominent neurobehavioral features. Anton's syndrome is most commonly encountered in patients with bilateral occipital cortex lesions. Patients previously described who demonstrated Anton's syndrome secondary to a peripheral lesion have had an associated delirium or profound dementia. Our case demonstrates that Anton's syndrome may occur in association with blindness from a peripheral lesion, even in the absence of a delirium or significant dementia. We suggest that the bifrontal dysfunction may have been a critical factor in the production of Anton's syndrome. Implications for the role of frontal lobe dysfunction in the genesis of anosognosia and confabulation are discussed.
3
Outcome of cataract surgery in central India: a longitudinal follow-up study. An epidemiological follow-up study of patients who had intracapsular cataract extraction in a voluntary hospital and its associated eye camps in Central India has for the first time evaluated the outcome one year after surgery in terms of visual acuity, use of spectacles, and improvement in income and mobility. The findings indicate that under these fairly typical conditions, 92% of the cases have adequate vision of 6/18 or better one year after surgery. Information on high usage of spectacles and on considerable improvements in income and mobility after cataract surgery is also reported. The outcome for patients operated upon in eye camps was almost as favourable as for those operated upon in hospital. Although the small differences are not statistically significant, the comparative findings require cautious interpretation and give rise to the epidemiological issues which are briefly discussed in this paper.
5
Limitations of electroencephalographic monitoring in the detection of cerebral ischemia accompanying carotid endarterectomy. An analysis was undertaken of 458 consecutive carotid endarterectomies performed over 6 years with the patient under general anesthesia and with electroencephalographic monitoring. Seventy patients (15%) had electroencephalographic changes suggestive of ischemia with carotid clamping and had shunts placed. Ischemic encephalographic changes occurred in 26% of patients with an occluded contralateral carotid artery, 21% of patients with a prior stroke history, and 12% of patients with no stroke history and a patent contralateral carotid artery. Nineteen strokes (4.1%), nine transient deficits (2.0%), and one death (0.2%) occurred in the 458 endarterectomies in this experience. Ten of the 19 strokes and five of nine transient deficits were immediately apparent when patients awoke from anesthesia. Five of 10 patients with immediate strokes and all five patients with immediate transient deficits had no ischemic electroencephalographic changes during the procedure. Two other patients with immediate strokes initially had ischemic electroencephalographic changes after carotid clamping that reversed with increased blood pressure or shunting. Therefore 7 of 10 patients with immediate strokes and all 5 patients with immediate transient deficits had electroencephalographs unchanged from baseline at completion of the procedure, and thus deficits not manifest by operative electroencephalographic changes developed. Our data do not support the tenet that electroencephalographic monitoring will always predict neurologic deficits accompanying carotid endarterectomy.
5
Molecular localization of the t(11;22)(q24;q12) translocation of Ewing sarcoma by chromosomal in situ suppression hybridization. Chromosome translocations are associated with a variety of human leukemias, lymphomas, and solid tumors. To localize molecular markers flanking the t(11;22) (q24;q12) breakpoint that occurs in virtually all cases of Ewing sarcoma and peripheral neuroepithelioma, high-resolution chromosomal in situ suppression hybridization was carried out using a panel of cosmid clones localized and ordered on chromosome 11q. The location of the Ewing sarcoma translocation breakpoint was determined relative to the nearest two cosmid markers on 11q, clones 23.2 and 5.8, through the analysis of metaphase chromosome hybridization. By in situ hybridization to interphase nuclei, the approximate physical separation of these two markers was determined. In both Ewing sarcoma and peripheral neuroepithelioma, cosmid clone 5.8 is translocated from chromosome 11q24 to the derivative chromosome 22 and a portion of chromosome 22q12 carrying the leukemia inhibitory factor gene is translocated to the derivative chromosome 11. The physical distance between the flanking cosmid markers on chromosome 11 was determined to be in the range of 1000 kilobases, and genomic analysis using pulsed-field gel electrophoresis showed no abnormalities over a region of 650 kilobases in the vicinity of the leukemia inhibitory factor gene on chromosome 22. This approach localizes the Ewing sarcoma breakpoint to a small region on chromosome 11q24 and provides a rapid and precise technique for the molecular characterization of chromosomal aberrations.
1
Continuous muscle fiber activity, peripheral neuropathy, and thymoma. Two patients, one of them with myasthenia gravis, presented symptoms of continuous muscle fiber activity syndrome before discovery of a thymoma. Peripheral neuropathy was present in both patients, with axonal and demyelinating lesions in sural nerve biopsy. The syndrome remained unchanged or worse after thymectomy. Both patients died of associated complications.
3
The surgical treatment of atrial fibrillation. II. Intraoperative electrophysiologic mapping and description of the electrophysiologic basis of atrial flutter and atrial fibrillation. Computerized mapping of atrial fibrillation was performed in animals and man. To study atrial fibrillation in a systematic manner, we developed a clinically relevant experimental model of atrial fibrillation. Chronic mitral regurgitation was created surgically in 25 dogs without opening the pericardium. After several months of chronic mitral regurgitation, the atria became enlarged and sustained atrial fibrillation could be induced by standard programmed electrical stimulation techniques. Computerized isochronous activation maps of the atria were recorded during atrial fibrillation from 208 bipolar electrodes simultaneously. In a parallel study, human atrial fibrillation was mapped with a separate 160-channel intraoperative mapping system in patients with paroxysmal atrial fibrillation who were undergoing surgical correction of the Wolff-Parkinson-White syndrome. The canine activation sequence maps demonstrated a spectrum of rhythm abnormalities ranging from simple atrial flutter to complex atrial fibrillation. They also showed that macroreentrant circuits within the atrial myocardium were responsible for the entire spectrum of arrhythmias. Atrial reentry was also documented during human atrial fibrillation. All patients had nonuniform conduction around regions of bidirectional block in both atria resulting in multiple discrete wave fronts. In addition, six patients had a single reentrant circuit in the right atrium in which bidirectional block of the activation wave front occurred along the sulcus terminals between the venae cavae. The left atrium in all patients demonstrated multiple wave fronts and conduction block, but left atrial reentry could not be detected. Both the experimental study and the clinical study demonstrated that multiple wave fronts, nonuniform conduction, bidirectional block, and large (macroreentrant) reentrant circuits occur during atrial fibrillation. The presence of macroreentrant circuits and the absence of either microreentrant circuits or evidence of atrial automaticity suggests that atrial fibrillation should be amenable to surgical ablation.
4
Doxazosin effects on insulin and glucose in hypertensive patients. The Finnish Multicenter Study Group. This study investigates the effects of prolonged doxazosin treatment on serum lipids, glucose, serum insulin, and blood pressure in hypertensive patients. Following 26 weeks of treatment with doxazosin, supine and standing blood pressures were significantly decreased at a final mean daily dose of 6.4 mg. Blood glucose levels were significantly lower at 26 weeks than after the initial placebo period (p less than 0.05) or after 4 weeks' treatment with doxazosin (p less than 0.001). There was a significant (p less than 0.05) decrease in serum insulin levels following 4 weeks of treatment, and a highly significant (p less than 0.001) decrease after 26 weeks. In addition, doxazosin produced a significant reduction in total cholesterol (p less than 0.05) and low-density lipoprotein (LDL) cholesterol (p less than 0.01) after 26 weeks, although the levels of high-density lipoprotein (HDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, and triglycerides showed no significant change. There was a tendency for the ratio of HDL: total cholesterol to increase. The combined changes in blood pressure, blood glucose levels, serum insulin, and serum lipids favorably affect the probability of developing coronary heart disease (CHD).
4
Spirometric criteria for hospital admission of patients with acute exacerbation of COPD. Recent studies have demonstrated that there is a high relapse rate for patients discharged from the Emergency Department (ED) following treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD). Objective criteria have not been established to determine when to hospitalize these patients. This study evaluated spirometric criteria for that use. Eighty-three patients with an acute exacerbation of COPD were studied; 45 percent were admitted to the hospital while 17 percent of the patients who were discharged suffered a relapse. An FEV1 of less than 40 percent of predicted normal identified patients who required hospital admission or suffered a relapse with a sensitivity of 0.96, specificity of 0.58, and overall accuracy of 0.78. Combining clinical assessment with spirometry led to an improvement in specificity to 0.73 with a minimal decrease in sensitivity. Patients with an FEV1 of 40 percent or greater of predicted normal or no clinical evidence of respiratory distress after treatment may be safely discharged from the hospital. Patients not meeting these criteria are at high risk for relapse and should either be admitted or have further aggressive ED therapy.
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