shukoor65/lab-rag-model huggingface dataset:
Assessing drugs for the treatment of heart failure. The aims of treatment in patients with heart failure, as with any other condition, are to relieve symptoms and prolong life. A secondary objective is to do so at the lowest possible economic cost. When treatment of the cause of heart failure is possible--which usually means some form of surgery, but could include treatment of a primary disease, such as thyrotoxicosis--then this is obviously the treatment of choice. In patients for whom there is no such definitive treatment, a wide and increasing variety of drugs are available. When new antifailure drugs are to be developed there are therefore two problems: first, to ensure that they are more effective than placebo treatment, and second, to compare them with existing drugs. Both of these tests can present ethical difficulties, for it is unreasonable to withhold established effective treatment in order to conduct a placebo-controlled trial, and when drugs are being compared, it is unlikely that any new medication will be dramatically superior to an old one. The more effective the treatments already available, the harder it becomes to evaluate a new drug.
The extent and time course of motoneuron involvement in amyotrophic lateral sclerosis. The numbers and relative sizes of motor units have been estimated in 373 muscles of 123 patients with ALS: 74 of the muscles were examined on more than one occasion. The median duration between the onset of symptoms and the initial examination was 12 months; by this time, approximately 90% of the tested muscles showed losses of motor units. The evoked motor unit potentials continued to enlarge in most, but not all, muscles as the disease progressed. Once a muscle became affected by the disease process, the average time-course was such that the motor unit population halved in each 6-month period of the first year and diminished more slowly thereafter. A small proportion of patients was encountered in whom the disease progressed much more slowly and there were occasional large fluctuations in the motor unit estimates suggestive of reversible motoneuron dysfunction.
Prostacyclin production and mediation of adenylate cyclase activity in the pulmonary artery. Alterations after prolonged hypoxia in the rat. Prostacyclin is a critical mediator of structure and function in the pulmonary circulation, causing both the inhibition of vascular smooth muscle growth and vasodilation via the stimulation of adenylate cyclase. To examine the potential role of alterations in prostacyclin production or mechanism of action in chronic hypoxic pulmonary hypertension, we determined the effects of prolonged (7 d) in vivo hypoxia on in vitro prostacyclin synthesis and mediation of adenylate cyclase activity in rat main pulmonary arteries. In control arteries prostacyclin production exceeded that of prostaglandin (PG) E2 by 25-fold, with 42% originating from the endothelium. Studies utilizing indomethacin revealed that endogenous prostaglandins mediate at least 69% of basal adenylate cyclase activity. Prostacyclin-stimulated enzyme activity was enhanced by exogenous GTP, indicating that this is a receptor-mediated process involving G protein amplification. Comparable dose-related responses to prostacyclin and PGE2 suggest that these agents may activate a common receptor. After 7 d of in vivo hypoxia there was a 2.7-fold increase in in vitro prostacyclin production, with equivalent increases in synthesis in the endothelium and vascular smooth muscle. However, despite this increase there was no change in basal adenylate cyclase activity, and this was associated with attenuated sensitivity of the enzyme to prostacyclin stimulation. Concomitant diminution of the response to beta-adrenergic stimulation, with previously-demonstrated beta receptor downregulation and unaltered postreceptor-mediated activity, suggests that the blunted response to prostacyclin is due to receptor downregulation. Parallel studies of the thoracic aorta indicated that these changes are specific to the pulmonary artery. It is postulated that attenuation of the response of adenylate cyclase to prostacyclin may contribute to the structural changes and hypertension observed in the pulmonary vasculature of the rat with chronic hypoxia.
Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease BACKGROUND. The treadmill exercise test identifies patients with different degrees of risk of death from cardiovascular events. We devised a prognostic score, based on the results of treadmill exercise testing, that accurately predicts outcome among inpatients referred for cardiac catheterization. This study was designed to determine whether this score could also accurately predict prognosis in unselected outpatients. METHODS. We prospectively studied 613 consecutive outpatients with suspected coronary disease who were referred for exercise testing between 1983 and 1985. Follow-up was 98 percent complete at four years. The treadmill score was calculated as follows: duration of exercise in minutes--(5 x the maximal ST-segment deviation during or after exercise, in millimeters)--(4 x the treadmill angina index). The numerical treadmill angina index was 0 for no angina, 1 for nonlimiting angina, and 2 for exercise-limiting angina. Treadmill scores ranged from -25 (indicating the highest risk) to +15 (indicating the lowest risk). RESULTS. Predicted outcomes for the outpatients, based on their treadmill scores, agreed closely with the observed outcomes. The score accurately separated patients who subsequently died from those who lived for four years (area under the receiver-operating-characteristic curve = 0.849). The treadmill score was a better discriminator than the clinical data and was even more useful for outpatients than it had been for inpatients. Approximately two thirds of the outpatients had treadmill scores indicating low risk (greater than or equal to +5), reflecting longer exercise times and little or no ST-segment deviation, and their four-year survival rate was 99 percent (average annual mortality rate, 0.25 percent). Four percent of the outpatients had scores indicating high risk (less than -10), reflecting shorter exercise times and more severe ST-segment deviation; their four-year survival rate was 79 percent (average annual mortality rate, 5 percent). CONCLUSIONS. The treadmill score is a useful and valid tool that can help clinicians determine prognosis and decide whether to refer outpatients with suspected coronary disease for cardiac catheterization. In this study, it was a better predictor of outcome than the clinical assessment.
Radioimmunodetection of neuroblastoma with iodine-131-3F8: correlation with biopsy, iodine-131-metaiodobenzylguanidine and standard diagnostic modalities. Iodine-131-3F8, a murine IgG3 monoclonal antibody specific for ganglioside GD2 was evaluated by radioimmunoscintigraphy in 42 patients with neuroblastoma. Comparison was made with 131I-metaiodobenzylguanidine (MIBG), 99mTc-methylene diphosphonate (MDP) bone scans, as well as computed axial tomography (CT) or magnetic resonance imaging (MRI). Iodine-131-3F8 detected more abnormal sites (283) than [131I] MIBG (138) or 99mTc-MDP (69), especially in patients with extensive disease. In 20 patients with soft-tissue tumors demonstrated by CT/MRI, 131I-3F8 detected the disease in 18. Upon surgical resection, two tumors interpreted as negative with 131I-3F8 imaging revealed ganglioneuroma, one showing microscopic foci of neuroblastoma. In contrast, 131I-3F8 imaging identified tumors that were confirmed histologically as neuroblastomas. In 26 patients with evidence of marrow disease by antibody scans, 14/26 had confirmation by iliac crest marrow aspirate/biopsy examinations. We conclude that 131I-3F8 scintigraphy has clinical utility in the management of patients with neuroblastoma by improving the sensitivity of tumor detection.
Prognostic significance of the number of metastatic lymph nodes in patients with gastric cancer. To confirm the prognostic significance of the number of the metastatic lymph nodes (MLN) in cases of gastric cancer, the results of surgical treatment of 668 patients with primary gastric cancer were analyzed retrospectively. Five-year survival rates were calculated with reference to the number of MLN, namely, none (89.2%), one to three (77.4%), four to six (55.8%), and seven or more (36.2%). Furthermore, even when the cancer had invaded the serosa, 5-year survival was significantly more frequent in patients with one to three MLN (71.7%) than in those with four to six (35.5%) or more than six (31.5%) (P less than 0.01), and the 5-year survival was close to that of patients with no MLN (70.5%). Not only qualitative but also quantitative evaluation of lymph node metastasis is essential for estimating the prognosis of patients with gastric cancer.
Culture, illness, and the biopsychosocial model. Family medicine has appropriated the biopsychosocial model as a conceptualization of the systemic interrelationships among the biological, the psychological, and the social in health and illness. For all its strengths, it is questionable whether this model adequately depicts the centrality of culture to the human experience of illness. Culture (as meaning system) is not an optional factor that only sometimes influences health and illness; it is prerequisite for all meaningful human experience, including that of being ill. A more adequate model of the relationship between culture and illness would demonstrate the preeminence of culture in the experience of illness among all people, not just members of "exotic" cultures; would view healers as well as patients as dwellers in culture; would incorporate the role of culture as meaning system in linking body, mind, and world; and would promote the significance of the cultural context as a resource for research and therapy.
von Willebrand factor and factor VIII in renal transplant recipients under immunosuppression with cyclosporine and steroids. Sequential measurements over 4 months in 17 patients. In 17 consecutive cadaver kidney transplant recipients treated with cyclosporine (CsA) and steroids, the median of antigenic and functional levels of von Willebrand factor (vWF) and factor VIII (FVIII) before transplantation were elevated (vWF:Ag: 206%, vWF:RCof: 202%; FVIII:Ag: 248%, FVIII:C: 224%; normal values 50-150%). Sequential measurements after transplantation and during CsA treatment revealed a transient significant increase of median values with highest amounts of vWF:Ag of 362% (2 p less than 0.0001), FVIII:Ag of 398% (2 p less than 0.001) and FVIII:C of 360% (2 p less than 0.0001) (Friedman test). vWF:RCof did not show statistically significant changes. After 4 months, levels of vWF and FVIII comparable to those obtained before transplantation were observed. In univariate statistical analysis no correlation was found between vWF of FVIII on the one hand and plasma creatinine levels, CsA dose or CsA whole blood through levels on the other hand. However, multivariate statistics revealed to some extent a positive influence of CsA blood levels on vWF:Ag levels. Patients with vascular rejection or chronic CsA nephrotoxicity showed significantly lower levels of vWF:Ag as compared with patients without endothelial cell damage in the kidney (2 p less than 0.05). However, the difference in vWF:Ag levels already existed before transplantation. In contrast to recent reports, plasma vWF levels were not indicative of vascular injury in kidney graft recipients nor was the marked elevation of vWF and FVIII associated with thromboembolic complications ascribed to CsA treatment.
Liver involvement in Alpers disease. Alpers disease consists of diffuse cerebral degeneration manifested as developmental delay, seizures, vomiting, and progressive neuromuscular deterioration, with liver disease and death. We report the clinical course of the liver disease, histologic progression of the hepatic lesions, and etiologic investigations in five patients (four girls, three kinships). All had grown and developed normally until seen at 6 to 36 months of age (mean 20 months), with vomiting (n = 5), progressive hypotonia (n = 3), or seizures (n = 2). All had been given anticonvulsants, including valproic acid in three. Liver disease was noted at a mean age of 35 months (range 9 to 67 months), with hepatomegaly (two patients), abnormal hepatic synthetic function (three) or transaminase values (three), and cirrhosis in one. Patients survived for a mean of 4.6 weeks (range 1 to 8 weeks) after the identification of liver disease; all died of hepatic failure. Results of evaluation for infectious and metabolic causes of liver disease and causes of degenerative neuromuscular disease were negative in all patients. Premortem liver biopsy specimens (n = 3) demonstrated an early lesion consisting of lobular disarray, microvesicular steatosis, periportal acute and chronic inflammation, and individual hepatocyte necrosis. Autopsy findings (n = 5) consisted of macrovesicular steatosis, massive hepatocyte dropout, and proliferation of bile ductular elements, with almost complete replacement of hepatocytes by proliferating bile ductular elements in two patients. Brain showed characteristic neuronal degeneration. We conclude that Alpers disease can be a cause of rapidly progressive liver failure in early childhood. Although the cause of this autosomal recessive disease is not known, it does not appear to be related to peroxisomal dysfunction.
Vulnerability of nerve fibres to ischaemia. A quantitative light and electron microscope study. In order to learn more about the vulnerability of nerve fibres to ischemia, a quantitative study of nerve fibre abnormalities was performed on biopsy specimens of the superficial branch of the peroneal nerve from 26 patients with vasculitic neuropathy: 20 had necrotizing arteritis, 5 a lymphocytic, and 1 a leucocytoclastic vasculitis on nerve and/or muscle biopsy. The density of myelinated fibres ranged from 25 to 7880 per mm2 (n = 8470 +/- 706 (SD]. There was a marked inequality in the density of nerve fibres between the fascicles of individual nerves with a mean coefficient of variation of 41 +/- 37 (SD) % versus 7.4 +/- 3.0% in controls. Loss of myelinated fibres, which was greater for fibres larger than 7 microns in diameter, was more severe than that for unmyelinated axons. Regeneration, which was assessed by the number of clustered axons, decreased when the density of myelinated fibres decreased, suggesting that severe nerve ischaemia precludes axonal regeneration. Wallerian degeneration affected on average 58% (range 5-100%) and segmental demyelination, mainly of the secondary type, on average 1.94% (range 1-10%) of teased fibres. It was concluded that (1) myelinated fibres are more vulnerable to ischaemia than unmyelinated axons; (2) large myelinated fibres are affected before the smaller ones; (3) segmental demyelination is uncommon in this context; (4) severe nerve ischaemia precludes axonal regeneration.
The role of endogenous free radical scavengers on tissue recovery in the experimental ulcer model. The role of lipid peroxidation and endogenous oxygen-derived free radical scavengers on ischemia-reperfusion injury and tissue recovery in rat ulcer model corresponding to the gastric histopathology was investigated. Male Wistar rats weighting 200-250 g were heparinized before occlusion of the celiac axis for 1.5 h. Endogenous CuZn-superoxide dismutase (SOD), Mn-SOD, glutathione peroxidase, fumarase, cytochrome c oxidase, and thiobarbituric acid-reactive compounds as lipid peroxidation products were measured in the gastric tissue at 3 h, and 1, 2, 4, and 7 days after release and in the controls (no occlusion). At 3 h after release, erosion of the gastric mucosa was observed, and gastric ulcers beyond the muscularis mucosae were present in the gastric body 2 days later. Seven days after release, gastric ulcers had disappeared. Activity levels for all five enzymes (CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase) were low for days 1-4 after release and did not return to control levels by the seventh day. It was observed that the ulcer formation, as evidenced by the histopathology, was significantly related to the levels of endogenous CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase activities. Thiobarbituric acid-reactive compounds were also low through the entire course of ulcer formation. The study concludes that decreases in the levels of these oxygen-derived free radical scavengers may result in the formation of gastric ulcers; however, endogenous free-radical scavengers may not correspond with tissue recovery. Lipid peroxidation may not be related to ulcer formation.
Comparison of intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. Urochinasi per via Sistemica nell'Infarto Miocardico (USIM) Collaborative Group. In a randomized trial of the effects on in-hospital mortality of intravenous urokinase plus heparin versus heparin alone, 2,531 patients with acute myocardial infarction in 89 coronary care units were enrolled for greater than 30 months. Patients admitted within 4 hours of the onset of pain were randomized to receive either intravenous urokinase (a bolus dose of 1 million U repeated after 60 minutes) plus heparin (a bolus dose of 10,000 U followed by 1,000 IU/hour for 48 hours) or heparin alone (infused at the same rate). Complete data were obtained in 2,201 patients (1,128 taking urokinase and 1,073 taking heparin). At 16 days, overall hospital mortality was 8% in the urokinase and 8.3% in the heparin group (p = not significant). Among patients with anterior infarction, mortality was 10.3% in the urokinase and 13.9% in the heparin group (p = 0.09; relative risk = 0.73). The incidence of major bleeding (urokinase 0.44%, heparin 0.37%) as well as the overall incidence of stroke (urokinase 0.35%, heparin 0.20%) was similar in the 2 groups. The rates of major in-hospital cardiac complications (reinfarction, postinfarction angina) were also similar.
Language functions in progressive supranuclear palsy. Language functions were studied in 6 patients with clinically diagnosed progressive supranuclear palsy who conformed to the characteristic pattern of 'subcortical dementia'. Dysarthria, reading difficulties and disturbances of handwriting were present in all patients. Some patients showed additional deficits including visual dyslexia, constructional dysgraphia and an increased rate of self-corrections and misnamings in object confrontation naming. In most instances, the naming errors referred to an object visually similar to the target object, suggesting that visual misperception is the major cause of the naming disorder. It is concluded that a variety of language impairments may develop secondary to other neurological and neuropsychological changes in progressive supranuclear palsy.
Periodic and chaotic host-parasite interactions in human malaria. It has been recognized since ancient times that malaria fever is highly periodic but the mechanism has been poorly understood. Malaria fever is related to the parasite growth cycle in erythrocytes. After a fixed period of replication, a mature parasite (schizont) causes the infected erythrocyte to rupture, releasing progeny that quickly invade other erythrocytes. Simultaneous rupture of a large number of schizonts stimulates a host fever response. Febrile temperatures are damaging to Plasmodium falciparum, particularly in the second half of its 48-hr replicative cycle. Using a mathematical model, we show that these interactions naturally tend to generate periodic fever. The model predicts chaotic parasite population dynamics at high multiplication rates, consistent with the classical observation that P. falciparum causes less regular fever than other species of parasite.
Effect of hypotensive epidural anaesthesia on acetabular cement-bone fixation in total hip arthroplasty. We selected 20 matched pairs of patients who had had total hip arthroplasty by the same surgeon using the same cemented technique. Matching was by age, sex, height, weight and diagnosis. One of each pair had received hypotensive epidural anaesthesia, with less than 300 ml blood loss: the other had normotensive general anaesthesia with more than 500 ml of blood loss. Early postoperative radiographs were evaluated independently by three blinded observers, using a scoring criteria which assessed the quality of the cement-bone interface. The results showed that patients who had received epidural anaesthesia had significantly better radiographic scores (p less than 0.02). Our findings suggest that hypotensive anaesthesia facilitates penetration of cement into bone.
Echocardiographic estimation of critical left ventricular size in infants with isolated aortic valve stenosis. With the current trend to performing surgical valvotomy for infantile aortic stenosis without cardiac catheterization, there is a need to develop echocardiographic criteria for adequacy of left ventricular size. The echocardiograms and catheterization data of all 25 infants less than 3 months of age undergoing aortic valvotomy for isolated aortic valve stenosis from September 1980 through July 1990 were reviewed. Significant differences (p less than 0.05) between the survivors and nonsurvivors were noted for age at operation (30 +/- 28 vs. 3 +/- 1.5 days), mitral valve diameter (10.1 +/- 1.7 vs. 7.7 +/- 1.5 mm), left ventricular end-diastolic dimension (18.4 +/- 6.4 vs. 11.4 +/- 3 mm), left atrial dimensions (15.3 +/- 3.8 vs. 10 +/- 2.4 mm), left ventricular cross-sectional area on the parasternal long-axis echocardiogram (4 +/- 1.9 vs. 2 +/- 1.9 cm2) and angiographically determined left ventricular end-diastolic volume (43 +/- 23 vs. 11 +/- 5 ml/m2). There was no difference with respect to patient weight, body surface area, aortic root dimension or left ventricular ejection fraction. Left ventricular cross-sectional area less than 2 cm2 as measured on the parasternal long-axis echocardiogram was found in 5 of 7 nonsurvivors and 0 of 12 survivors, making this a risk factor for perioperative death (p less than 0.05). Left ventricular end-diastolic dimension less than 13 mm was found in 5 of 6 nonsurvivors and 2 of 17 survivors, making this another risk factor for early mortality (p less than 0.05).
Acute effects of intravenous nicardipine on hemodynamics and cardiac function in patients with a healed myocardial infarction and no evidence of congestive heart failure. Acute effects of intravenous nicardipine (10 micrograms/kg) on systemic hemodynamics and cardiac function were evaluated in 17 patients with a healed myocardial infarction and no evidence of congestive heart failure. Mean New York Heart Association functional class was 1.6 +/- 0.5 (mean +/- standard deviation). Aortic systolic pressure (p less than 0.001) and left ventricular end-diastolic pressure decreased (10 +/- 3 to 8 +/- 3 mm Hg, p less than 0.01), and systemic vascular resistance decreased significantly (p less than 0.001), whereas pulmonary and right atrial pressure and pulmonary arteriolar resistance did not change. Cardiac and stroke indexes showed biphasic changes. Although positive and negative maximal rate of left ventricular pressures decreased significantly (p less than 0.05 and p less than 0.01, respectively), they did not change significantly when aortic systolic pressure was corrected. There was a significant inverse correlation between the negative rate of left ventricular pressure/aortic systolic pressure before nicardipine infusion and its maximal percent increase after infusion (r = -0.56, p less than 0.05), indicating a beneficial effect on diastolic relaxation in patients with impaired diastolic function. Our data show that a low dose (10 micrograms/kg) of intravenous nicardipine exerts a favorable effect on impaired diastolic function, but depresses left ventricular pump function with much less effect on right heart circulation.