shukoor65/lab-rag-model huggingface dataset:
Histological and immunohistochemical study of the gall bladder lesion in primary sclerosing cholangitis. The histological features and type of mononuclear cell infiltrate in gall bladders from six patients with primary sclerosing cholangitis were studied using routine staining techniques and immunohistochemistry. Control studies were performed using the gall bladders from six patients (age and sex matched) with chronic cholecystitis and four with primary biliary cirrhosis. A range of histological abnormalities was present in gall bladders from patients with primary sclerosing cholangitis including a mild to moderate degree of epithelial hyperplasia, pseudogland formation, and mononuclear cell infiltrate of the epithelium; moderate to severe chronic inflammatory cell infiltrate and fibrosis affecting the superficial and deep layers of the gall bladder wall; and minimal smooth muscle hypertrophy. These abnormalities were non-specific and were also present in gall bladders from patients with chronic cholecystitis and primary biliary cirrhosis. Vasculitis and granulomas were not present in the patients with primary sclerosing cholangitis. Immunohistochemistry showed that the superficial and deep mononuclear cell infiltrate in primary sclerosing cholangitis gall bladders was composed predominantly of lymphocytes, in contrast to chronic cholecystitis where macrophages were found in similar or greater numbers. Moreover, T lymphocytes (activated and resting) were present throughout the lymphocytic infiltrate and were apposed to the base and interdigitated between the biliary epithelial cells in significantly greater numbers than in chronic cholecystitis gall bladders. B lymphocytes were present only in lymphoid follicles. Comparative studies using liver biopsy specimens from three of the primary sclerosing cholangitis patients showed a similar T lymphocyte portal tract infiltrate.
Testolactone, sulindac, warfarin, and vitamin K1 for unresectable desmoid tumors. Ten patients with large inoperable desmoid tumors in various body locations were treated with testolactone. Four tumors (40%) responded with major regressions, i.e., more than 50% reduction in volume. Eight patients received nonsteroid anti-inflammatory drugs (indomethacin, sulindac, or sulindac with warfarin and vitamin K1 [Mephyton]) for periods of 2 to 91 months. There was one major regression, one partial regression, and three instances of tumor growth arrest over periods up to 8 years. Seven patients were treated with nonsteroid anti-inflammatory drugs concurrent with or after testolactone or tamoxifen. There were five major regressions and one partial regression with extensive central necrosis of an enormous intra-abdominal tumor. The last patient has been treated for only 12 months, with no change in tumor volume. It appears that estrogens function as growth factors for desmoid tumors, and that minimization of these effects inhibits tumor growth in some, but not all, cases. In those instances where antiestrogens were not effective as single agents, the tumors usually responded to subsequent nonsteroid anti-inflammatory drug therapy. Withdrawal of estrogen may be followed by inhibition of transcription of genes that support tumor cell proliferation, and sulindac and indomethacin may augment these effects by inhibiting prostaglandin and cyclic AMP synthesis and the activity of protein kinase C. Warfarin may function as a protonophore to acidify the cytoplasm and prevent the alkalinization that is necessary to initiate DNA synthesis and cell cycle progression, again an impairment of the transcription process.
The clinical heterogeneity of hypertension. More than the character of the blood pressure elevation, the cardiovascular risk profile should be the prognostic guide for antihypertensive therapeutic decision-making. Hypertension tends to occur in association with other risk factors which augment the risk and need to be considered in evaluating the hazard of hypertension, the urgency for treatment, and the choice of treatment. Elevated blood pressure is often accompanied by blood lipid abnormality, obesity, electrocardiograph (ECG) abnormality, glucose intolerance, and elevated fibrinogen and hematocrit, all of which enhance the risk of cardiovascular sequelae of hypertension. Hypertensive patients at particularly increased risk of cardiovascular events are those with an increased total/HDL-cholesterol ratio, ECG abnormality, impaired glucose tolerance, or the cigarette smoking habit. The risk of a cardiovascular event among hypertensive patients varies over more than a 10-fold range depending on the number of these coexistent risk factors. Multivariate risk formulations are available to allow a composite estimate of the joint conditional probability of a cardiovascular outcome in hypertensive patients with multiple risk factors. Since some antihypertensive agents can adversely affect blood lipids, glucose tolerance, or uric acid values, the risk profile must also be taken into account in choosing the optimal antihypertensive therapy. Also, hypertension is commonly associated with angina, myocardial infarction, left ventricular hypertrophy, stroke, or cardiac failure. These too must be taken under consideration in judging the urgency for treatment and the choice of agents. Thus, hypertension is best regarded as a component of a cardiovascular risk profile in implementing optimal therapy and in assessing its efficacy.
Comparative efficacy of daptomycin, vancomycin, and cloxacillin for the treatment of Staphylococcus aureus endocarditis in rats and role of test conditions in this determination. The in vivo efficacy of daptomycin, a new cell wall-active anti-gram-positive-bacterial agent, was compared to those of cloxacillin and vancomycin in a rat model of Staphylococcus aureus endocarditis. Both methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains were used. When therapy was initiated early (8 h) after infection, at the time when valvular bacterial counts were relatively low (approximately 10(6) CFU/g of vegetation), 3 days of therapy was found to be effective against the MSSA strains whatever the antibiotic regimen. In contrast, when the onset of therapy was delayed up to 15 h after infection, so that higher bacterial counts could develop on the valves (approximately 10(9) CFU/g of vegetation), a longer period of treatment (6 days) was required to cure infection. Under these conditions after 3 days of therapy, daptomycin was more effective than cloxacillin and vancomycin against the MSSA strains. Similarly, daptomycin showed a greater activity than vancomycin against the MRSA strain after 3 days of treatment, but after 6 days both antibiotics were equally effective. Decreasing doses of daptomycin showed decreasing activity: 10 mg/kg of body weight every 12 h (q12h) was better than 5 mg/kg q12h, whereas 5 mg/kg q24h (providing drug levels in blood detectable only during the first 12 h) failed to cure infection. In vitro, daptomycin was highly bactericidal at high concentrations (25 and 60 micrograms/ml, corresponding to peak levels in serum after doses of 5 and 10 mg/kg, respectively) and bacteriostatic at lower concentrations (0.5 to 2.5 micrograms/ml, corresponding to trough levels in serum).
9p monosomy in a patient with Gilles de la Tourette's syndrome. Gilles de la Tourette's syndrome (GTS) is a genetic disorder characterized by multiple motor and vocal tics, obsessive-compulsive disorder, and attention-deficit disorder. Family studies support the presence of an autosomal dominant gene; however, to date, an assignment for the GTS locus has not been made. We present the case of a boy with GTS and a deletion of the terminal portion of the short arm of chromosome 9, del(9)(qter----p2304:).
Are there interactions and relations between genetic and environmental factors predisposing to high blood pressure? An overview of published observations suggests that both genetic predisposition and environment work together to produce hypertension in most persons. High blood pressure before age 55 occurs 3.8 times more often among persons with a strong positive family history of high blood pressure. Much of the total variability in blood pressure in modern populations seems attributable to genetic factors. Estimates of the proportion of the variance attributable to all genetic factors (heritability [H2]) vary from 25% in pedigree studies to 65% in twin studies for sitting diastolic blood pressure. Several biochemical traits associated with high blood pressure are highly genetic (H2, 78-84%) and may help elucidate the pathophysiology of high blood pressure. While pertinent environmental factors such as salt intake, alcohol use, and amount of exercise also correlate significantly among relatives, only 7% of the total variance of diastolic blood pressure seems attributable to all shared environmental factors in family households. Thus most familial aggregation of high blood pressure appears to be due to genes rather than shared family environment. Practical benefit may result from identifying familial predisposition in multiple siblings with high blood pressure before age 55 and lipid abnormalities (labeled "familial dyslipidemic hypertension"). About 12% of high blood pressure patients have familial dyslipidemic hypertension and also have high risk of early coronary heart disease. Hyperinsulinemia and central obesity as well as high triglycerides and low high density lipoprotein cholesterol are prominent features of familial dyslipidemic hypertension.
Piezoelectric biliary lithotripsy: an in vitro study of factors affecting gallstone fragmentation. Factors affecting the fragmentation of gallstones with piezoelectric lithotripsy were studied in vitro, with a goal of providing data that will help direct treatment with piezoelectric lithotriptors. Two hundred fifty-seven stones from 50 patients were treated with the EDAP LT.O1 lithotriptor until all fragments measured 2 mm or less in diameter. The fragmentation process was observed, and two patterns were evident: central fragmentation and peripheral chipping. The majority of stones fragmented centrally. Fragmentation characteristics in different stones from the same patient were compared with those from different patients. Stone diameter, shock-wave frequency and power, and CT appearance were examined and correlated with fragmentation. Gallstones from the same patient showed uniform fragmentation patterns and consistent relationships between fragmentation time and gallstone size, shock-wave frequency, and power. In stones from the same patient, gallstone size had a marked effect on fragmentation time, which correlated with the cube of the stone diameter, and shock-wave frequency and power had a proportional inverse linear relationship with fragmentation time. When controlling for stone size and treatment parameters, stones from multiple patients showed marked differences in fragmentation time, and because of this, poor correlation between stone size and fragmentation time. Stones grouped according to CT pattern and attenuation showed wide variation and no correlation between CT characteristics and fragmentation pattern or fragmentation time. Our results show that a great variability exists in fragmentation time of gallstones, making it impossible to accurately predict fragmentation time at a given stone size. Only rough estimates of longer fragmentation times with increasing stone size can be made. The linear relationships between shock-wave frequency or power and fragmentation time allow one to easily predict the effect of manipulating these variables and to tailor treatment to each patient's tolerance. Finally, CT appearance does not appear to be predictive of fragmentation outcome.
Prospects for the use of antagonists to the platelet glycoprotein IIb/IIIa receptor to prevent post-angioplasty restenosis and thrombosis. Despite many advances since its inception in humans in 1977, coronary angioplasty continues to be limited by the problems of abrupt arterial closure and late restenosis. Excessive platelet deposition at the site of angioplasty undoubtedly plays an important role in the pathophysiology of both of these problems. Monoclonal antibodies and snake venom-derived or synthetic peptides directed against a common protein recognition sequence on the platelet glycoprotein IIb/IIIa receptor are currently in the early stages of preclinical and clinical testing and hold promise of preventing abrupt closure and restenosis by inhibiting platelet function. Whether any of these agents will eventually be commonly used in clinical practice will depend on their effects on the complex pathophysiology of these problems and on their safety profile when administered to patients who are likely to receive other antithrombotic medications and who are instrumented for coronary angioplasty.
Muscle damage induced by eccentric contractions of 25% strain. Contractile and morphological properties were measured in the rabbit tibialis anterior muscle 1 h after isometric contraction (IC), passive stretch (PS), or eccentric contraction (EC). Maximal tetanic tension (Po) was reduced after 30 min of PS (P less than 0.001), IC (P less than 0.001), or EC (P less than 0.0001). However, the magnitude of the force deficit was a function of the treatment method. After 30 min of cyclic PS, Po decreased by 13%, whereas after IC or EC, Po decreased by 31 and 69%, respectively. The time course of tension decline in the various groups suggested that the EC-induced injury occurred during the first few minutes of treatment. Although the morphology of samples from the PS and IC groups appeared normal, eccentrically exercised muscles exhibited portions of abnormally large fibers (diam greater than or equal to 110 microns) when viewed in cross section. Examination of 231 such fibers from 6 muscles revealed that all enlarged fibers were exclusively of the fast-twitch glycolytic fiber type. Although no ultrastructural abnormalities were observed in any of the muscles from the IC or PS groups, a significant portion of the fibers in the EC group displayed various degrees of disorganization of the sarcomeric band pattern. Taken together, these studies highlight the importance of fiber oxidative capacity in EC-induced injury, which may be related to the damage mechanism.
Diaphragmatic performance during recovery from acute ventilatory failure in Guillain-Barre syndrome and myasthenia gravis. Diaphragmatic muscle performance during acute ventilatory failure due to Guillain-Barre syndrome and myasthenia gravis was assessed to evaluate (1) diaphragmatic function during weaning from ventilatory support and (2) diaphragmatic tension-time integral (TTdi) during ventilatory failure. We used a multilumen nasogastric tube and a pneumotachograph to measure transdiaphragmatic pressure per breath (Pdi), maximum transdiaphragmatic pressure (Pdimax), tidal volume (VT), and inspiratory time fraction during 74 spontaneous breathing trials in nine patients. Diaphragmatic performance was poor in all patients. The Pdi, Pdimax, and VT improved significantly, but values for Pdi and Pdimax remained low even after weaning. Improvement in Pdimax was the best predictor of recovery (r = 0.48; p less than 0.001). Maximal inspiratory force correlated with Pdimax (r = 0.48; p less than 0.005), but FVC did not. The TTdi rarely exceeded the expected fatigue threshold of 0.15 in spite of the patient's inability to sustain ventilation. Although our patients demonstrated diaphragmatic weakness, TTdi did not demonstrate diaphragmatic fatigue.
A new approach to the resection of pulmonary osteosarcoma metastases. Results of aggressive metastasectomy. Pulmonary metastases are the primary cause of death from bone and soft-tissue sarcoma. Recognition that even multiple resections of metastases can improve survival has led to a more aggressive surgical approach to these patients. The authors instituted an aggressive approach and a new technique and retrospectively analyzed the results of multiple, pulmonary metastasectomies for pulmonary metastases in 34 patients, 21 of whom had osteogenic sarcoma (OGS). A number of cases were referred from other institutions, where they had been considered inoperable because of extensive or recurrent disease. Using lateral thoracotomies, laser technique with minimal parenchymal excision, and thin gloves for palpation, aggressive metastectomy was carried out. A mean of 3.1 thoracotomies were performed, with an average of 10.6 nodules resected per thoracotomy. Operative morbidity and mortality were minimal. Evaluation of potential prognostic factors revealed no statistically significant survival difference on the basis of disease-free interval (DFI), number of nodules resected, number of thoracotomies, or size of largest nodule resected. There was a clear trend toward decreased survival of patients with larger nodules (greater than 2 cm), but because of the small number of patients in this group, no firm conclusions can be drawn. Five-year survival was 49% for the study group as a whole, and 39% for the OGS patients. Aggressive surgical resection of pulmonary metastases from bone and soft-tissue sarcoma should be considered when there is control of local disease, no evidence of extrapulmonary metastasis, and adequate postresection pulmonary reserve. The presence of bilateral, extensive, or recurrent disease is not a contraindication to thoracotomy.
Adult chronic lead intoxication. A clinical review. A stained-glass artisan with depression and a retired junkyard worker with congestive cardiomyopathy had increased mobilizable body burdens of lead by calcium ethylenediaminetetaacetic acid testing. Although both patients improved with several months of intramuscular chelation therapy, the efficacy of such therapy in chronic lead poisoning is controversial. Recognition of unusual manifestations of chronic lead poisoning may at least interrupt further exposure, even if specific therapy is not undertaken.
Translaminar facet joint screw fixation for lumbar and lumbosacral fusion. A clinical and biomechanical study. Various systems of supplementing bone grafts with internal fixation in the lumbosacral spine have been used in an effort to improve fusion rates. This study reports biomechanical data of cyclic loading cadaveric spines instrumented with translaminar facet screws as well as early clinical results on this technique. Static loading tests comparing uninstrumented and instrumented spinal motion units show that a ninefold increase in flexion load is necessary for constant displacement after facet screw fixation. Repetitive loading tests show only a small decrease in stiffness of instrumented segments even after 5,000 cycles. To date, 35 patients have undergone fusion by this technique as performed by one surgeon. After excluding Workers' Compensation cases and cases with less than 2 years follow-up, there were 18 cases available for review. Twelve of these 18 cases were two-level fusions. Ten patients underwent concomitant discectomy or nerve root decompression. There were no cases of iatrogenic neurologic injury or pseudoarthrosis. It is concluded that translaminar facet screws have a sound biomechanical basis and are a valuable addition to lumbar fusion procedures.
Autoantibodies to the presumptive cytoplasmic domain of platelet glycoprotein IIIa in patients with chronic immune thrombocytopenic purpura. Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder due to autoantibodies against platelets that result in their destruction. In some patients, these autoantibodies bind to platelet glycoprotein (GP) IIIa. With the aim of better defining the antigenic epitopes, plasma from 13 selected patients with chronic ITP known to have anti-GPIIb/IIIa autoantibodies was tested for reactivity with nine synthetic peptides corresponding to different regions of the GP IIIa molecule. Of these plasmas, five bound significantly (P less than .001) with either peptide 8 (amino acids 721-744) or peptide 9 (amino acids 742-762), which together form most of the carboxyterminal region presumed to be the cytoplasmic domain. Three of these positive plasmas, were tested further. In two of these positive plasmas, the anti-peptide antibodies represented greater than 80% of the detectable circulating autoantibody. To further evaluate the importance of the carboxyterminal region as an antigenic site, the chronic ITP plasmas were tested against Chinese hamster ovary cells transfected with GPIIb and either whole GPIIIa or GPIIIa lacking amino acids 728 to 762. Ten of the 13 plasmas required the presence of this region for significant autoantibody binding. We conclude that the carboxyterminal region is an important area for stimulating antiplatelet autoantibody formation in some patients with chronic ITP. It is not known whether these autoantibodies to the presumed cytoplasmic domain play an important role in the pathogenesis of the disease or occur as a secondary phenomenon during the course of platelet destruction.
Reversible and irreversible elongation of ischemic, infarcted, and healed myocardium in response to increases in preload and afterload. BACKGROUND. Left ventricular aneurysm formation after myocardial infarction (MI) has been associated with elongation of infarcted tissue in response to wall stress. Such elongation most commonly occurs in acutely infarcted or partially healed regions during the early post-MI period; however, recent reports have indicated that mature (15-week-old) healed infarct regions also undergo elongation after stress. METHODS AND RESULTS. To assess factors contributing to post-MI left ventricular aneurysm formation, we subjected isolated strips (n = 50) of rabbit myocardial tissue from acutely ischemic (noninfarcted left ventricular), acutely infarcted (24 hours after MI), and healed infarct (3 and 15 weeks after MI) regions to a range of loading conditions and measured the reversible and irreversible length changes that occurred. The isolated strips were repetitively stretched for 1 hour at 4 Hz to impose cyclical physiological peak and resting stresses of 2.0 and 0.2 g/mm2. During a second hour, either peak stress ("afterload") or resting stress ("preload") was tripled, and the increase in strip length (strain) was measured. During a third hour, peak and resting stresses were returned to the initial values to assess the reversibility of length changes occurring during increased load. Elongation was expressed as the increase in natural strain from the first hour. Increasing afterload caused similar irreversible length increases of 4-5%/hr in acutely infarcted and 3- and 15-week-old healed infarct strips; acutely ischemic tissue length increased by 7.4%/hr (p less than 0.05 versus acutely infarcted tissue and scars). Increasing preload in acutely ischemic and acutely infarcted tissue caused a reversible length increase of less than 1%/hr. (Scar strips were not tested for the effect of preload.) CONCLUSIONS. Since an irreversible length increase may represent an early event in aneurysm formation, our results suggest that 1) afterload increases are more likely to lead to aneurysm development than preload increases, 2) acutely ischemic tissue is the most vulnerable to increased afterload, and 3) for a given wall stress level, healing scar tissue is as susceptible to irreversible length changes as is acutely infarcted tissue. The observation that even mature post-MI scar elongated in response to increases in afterload implies that long-term pharmacological management of afterload in post-MI patients may be beneficial in preventing tissue elongation and aneurysm formation and that factors that increase wall stress (e.g., hypertension and exercise stress) have the potential to promote aneurysm formation in healed infarct scars.