123rc/medical_text huggingface dataset:
Discordant nephron function. A pathogenic factor in hypertension and its vascular complications of stroke and heart attack. Morphologic evidence from patients with essential hypertension and Goldblatt-type hypertension reveals a subpopulation of narrowed afferent arterioles to ischemic nephrons. These ischemic nephrons, responding individually to their perception of underperfusion, secrete renin. In response, the normal nephrons are in adaptive natriuresis and have appropriately shut off their renin production. Nevertheless, they are affected adversely by the discordant renin-angiotensin II arising from the ischemic nephrons' presence, which exerts an unwanted sodium-retaining effect on the proximal tubules of the adapting nephrons. The end result is elevated blood pressure from too much sodium retention for the level of renin activity, that is, an abnormal renin-sodium product. Thus, "normal" renin levels in a hypertensive individual are abnormal because healthy kidneys shut off renin production entirely when blood pressure rises. This construction explains why angiotensin converting enzyme inhibition often corrects "normal" renin hypertension. Although such hypertension may be partly sodium-mediated as a consequence of inappropriate sodium retention by the normal and ischemic nephrons, the source of the problem lies in the renin production from ischemic nephrons. The correct treatment, then, is an antirenin therapy designed to block renin synthesis or secretion or angiotensin II formation or action. In view of modern studies suggesting that renin excesses also correlate with an increased risk of heart attack and stroke, the role of antirenin and antiangiotensin agents in treatment assumes additional relevance.
Association of p60c-src with polyoma virus middle-T antigen abrogating mitosis-specific activation. Polyoma middle-T antigen is required for tumorigenesis in animals and for viral transformation of a variety of cells in culture (reviewed in ref. 1). Middle-T associates with and thereby activates p60c-src, a cellular tyrosine kinase homologous to the oncogene product of Rous sarcoma virus. Activation of p60c-src by middle-T is accompanied both by dephosphorylation of tyrosine 527, a site which negatively regulates src kinase src kinase activity (reviewed in refs 4-6) and by autophosphorylation on tyrosine 416 (refs 7-10). Phosphoprotein p60c-src is subject to cell cycle-specific regulation. It is most active during mitosis and repressed in interphase. Here we report that mitotic p60c-src is dephosphorylated at tyrosine 527. We also show that in cells expressing middle-T, src kinase activity is high both in mitosis and during interphase. An oncogenic mutant src protein, p60c-src(527F), where tyrosine 527 is substituted by phenylalanine, is also highly active in all phases of the cell cycle.
Cytogenetic analysis of 750 spontaneous abortions with the direct-preparation method of chorionic villi and its implications for studying genetic causes of pregnancy wastage. Altogether, 750 cases of spontaneous abortion between the fifth and 25th week of gestation were analyzed cytogenetically by the direct-preparation method using chorionic villi. The majority of cases (68%) were derived from early abortions before the 12th week of gestation. The frequency of abnormal karyotypes was 50.1%; trisomy was predominant (62.1%), followed by triploidy (12.4%), monosomy X (10.5%), tetraploidy (9.2%), and structural chromosome anomalies (4.7%). Among trisomies, chromosomes 16 (21.8%), 22 (17.9%), and 21 (10.0%) were prevalent. The frequency of chromosomally abnormal abortions increased with maternal age but only because of an increase of trisomy. Polyploidy and monosomy X, however, decreased. Mean maternal age was significantly increased for trisomies 16, 21, and 22 and was highest for trisomies 18 and 20. The results obtained are within the range of variability reported earlier from tissue culture-type studies. A consistent feature during our study is the excess of females in chromosomally normal abortions (male:female sex ratio 0.71). According to the methodology applied, maternal cell contamination and undetected 46,XX molar samples cannot have influenced the sex ratio. However, a bias introduced by social status or maternal age cannot be excluded. With the more rapid and convenient direct preparation of chorionic villi, reliable cytogenetic data on causes of spontaneous abortions can be obtained.
Allogeneic marrow transplantation in patients positive for hepatitis B surface antigen. Twenty patients who were positive for hepatitis B surface antigen (HBsAg) underwent allogeneic marrow transplant for malignancy or other underlying hematologic disease between 1975 and 1986. After transplant, one patient had serologic evidence of hepatitis B virus (HBV) reactivation whereas three patients had evidence of an immune response to HBV. Among four patients with serologic follow-up of 1 year or more, three remained positive for HBsAg and one became HBsAg negative. Six patients (30%) developed clinical evidence of venocclusive disease and seven patients (35%) developed acute graft-versus-host disease involving the liver, but the incidence of these complications was similar to that expected among patients who are not carriers of HBsAg. Three patients died with hepatorenal failure, but all three had venocclusive disease and the contribution of HBV infection to liver failure was unclear. Available liver specimens obtained at autopsy (six patients) or biopsy (two patients) all showed either HBsAg (one specimen) or hepatitis B core antigen (four specimens) or both (three specimens) by immunoperoxidase staining. Although HBV reactivation leading to hepatic failure has been reported among allogeneic marrow transplant recipients as well as other immunocompromised patients, we did not observe an increase in the incidence of severe liver disease after transplant among these 20 patients positive for HBsAg at the time of transplant, and do not consider positivity for HBsAg to be a contraindication to allogeneic marrow transplantation.
Rationale and efficacy of conservative therapy for gastroesophageal reflux disease. Major recent advances in the diagnosis and understanding of gastroesophageal reflux disease have afforded the practicing clinician a number of therapeutic options to treat the increasingly recognized affected patient population. With highly effective acid-suppressive therapies available, simple life-style modifications, such as selective food and medicine avoidance, weight loss, smoking cessation, elevation of the head of the bed, and the judicious use of antacids and alginate, have been relegated to a minor, if any, role in the management of these patients. The validity of these recommendations, however, remains consistent with our current understanding of the pathogenesis of gastroesophageal reflux disease. Although few well-designed placebo-controlled trials have been conducted, a review of the medical literature indicates an appreciable efficacy of these interventions, which are founded on well-studied physiologic determinants of gastroesophageal reflux. Most patients with gastroesophageal reflux disease can be managed by reassurance and simple life-style adjustments alone. The therapy for those with chronic or relapsing disease should always include the adjunctive reinforcement of these simple, efficacious, and cost-effective measures.
Cancer antigen 125, carcinoembryonic antigen, and carbohydrate determinant 19-9 in ovarian tumors. The authors studied data of combination assays of tumor markers, because simultaneous elevation of different types of tumor markers in the serum was puzzling. They interpreted such phenomena regarding cancer antigen 125, carcinoembryonic antigen, and carbohydrate determinant 19-9 in ovarian tumors. The tissue expression of the antigens was compared with preoperative serum levels. Several different factors were found to cause the simultaneous elevation of two or three of these markers in the serum. Furthermore, even when the levels of some of the tumor markers were raised in the serum, the ovarian tumor did not always produce the marker by itself. This study indicates that immunohistochemical identification of a marker in tumor tissue is prerequisite to the use of that marker in the serum to monitor disease status.
Deficiency of complex III of the mitochondrial respiratory chain in a patient with facioscapulohumeral disease. Facioscapulohumeral disease (FSHD), an inherited neuromuscular disorder, is characterized by progressive wasting of specific muscle groups, particularly the proximal musculature of the upper limbs; the primary defect in this disorder is unknown. We studied a patient with FSHD to determine whether the mitochondrial respiratory chain was functionally abnormal. Muscle biopsy revealed fiber atrophy with patchy staining for oxidative enzymes. Electron microscopy of a liver section showed many enlarged mitochondria with paracrystalline inclusions. Decreased oxidation of the respiratory substrates-alanine and succinate-in skin fibroblasts suggested a deficiency of complex III of the electron-transport chain; cytochrome c oxidase activity (complex IV) was in the normal range. Biochemical analysis of liver supported the fibroblast data, since succinate oxidase activity (electron-transport activity through complexes II-IV) was reduced, whereas complex IV activity was normal. Furthermore, analysis of the cytochrome spectrum in liver revealed typical peaks for cytochromes cc1 and aa3, whereas cytochrome b (a component of complex III) was undetectable. Southern blot analysis of fibroblast mtDNA revealed no major deletions or rearrangements. Our study provides the first documentation of a specific enzyme-complex deficiency associated with FSHD.
Effect of thiopental on neurologic outcome following coronary artery bypass grafting To determine if thiopental reduces the incidence of neurologic sequelae after coronary artery surgery, we prospectively studied 300 patients undergoing coronary artery bypass grafting. Patients who had no history of neurologic or psychiatric illness were randomly assigned to receive either a thiopental infusion or a saline placebo infusion beginning with the administration of heparin and ending just after aortic decannulation. The patients received an opioid-relaxant anesthetic administered by an anesthesiologist who was not involved in this investigation and who was blinded to the test infusion. One of the investigators infused either saline or thiopental to produce an isoelectric electroencephalogram with 30-45 s between bursts. Standardized neurologic examinations were performed preoperatively and on the 2nd and 5th postoperative days by one of the blinded investigators. The group of patients receiving thiopental required a longer time for awakening (6.4 +/- 3.9 vs. 4.0 +/- 2.4 h, mean +/- SD, P less than 0.05) and for tracheal extubation (22.4 +/- 18.4 vs. 17.4 +/- 9.6 h, P less than 0.05), and a greater number of these patients were lethargic on the 2nd postoperative day. More patients receiving thiopental required vasoconstrictors during the thiopental loading and cardiopulmonary bypass (CPB) periods, while a greater number of patients receiving placebo required vasodilators. A greater number of patients receiving thiopental required inotropic drugs during separation from CPB. Despite the above differences, only 2 of the 151 patients in the placebo group (1.3%) and 5 of the 149 patients in the thiopental group (3.3%) experienced strokes (P = 0.2535).
Posthospital course and outcome in schizophrenia. To study the early course of schizophrenia, we assessed 79 early phase, young, DSM-III schizophrenic patients at two successive posthospital follow-ups, 2.5 and 5.0 years after index hospitalization. More than 50% of the sample had poor overall outcome, with either severe impairment in functioning and symptoms, or suicide, in the follow-up period. Rehospitalization rates decreased significantly during the course of the two posthospital assessments, despite the sample showing persisting psychosis. Only a small group of schizophrenic patients showed complete remission: 10% at the first follow-up and 17% at the second follow-up, when patients who suicided are excluded from consideration. While progressive deterioration is not common in schizophrenia, our relatively negative findings challenge the conclusions of some other longitudinal studies. Implications of our data on schizophrenic course are discussed.
Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction. Comparison of thallium scintigraphy with reinjection and PET imaging with 18F-fluorodeoxyglucose In patients with chronic coronary artery disease and left ventricular dysfunction, the distinction between ventricular dysfunction arising from myocardial fibrosis and ischemic, but viable, myocardium has important clinical implications. By positron emission tomography (PET), enhanced fluorine-18-labeled fluorodeoxyglucose (FDG) uptake in myocardial segments with impaired function and reduced blood flow is evidence of myocardial viability. Reinjection of thallium-201 at rest immediately after stress-redistribution imaging may also provide evidence of myocardial viability by demonstrating thallium uptake in regions with apparently "irreversible" defects. To compare these two methods, we studied 16 patients with chronic coronary artery disease and left ventricular dysfunction (ejection fraction, 27 +/- 9%), all of whom had irreversible defects on standard exercise-redistribution thallium single-photon emission computed tomography (SPECT) imaging. Thallium was reinjected immediately after the redistribution study, and SPECT images were reacquired. The patients also underwent PET imaging with FDG and oxygen-15-labeled water. A total of 432 myocardial segments were analyzed from comparable transaxial tomograms, of which 166 (38%) had irreversible thallium defects on redistribution images before reinjection. FDG uptake was demonstrated in 121 (73%) of these irreversible defects. Irreversible defects were then subgrouped according to the degree of thallium activity, relative to peak activity in normal regions. Irreversible defects with only mild (60-85% of peak activity) or moderate (50-59% of peak) reduction in thallium activity were considered viable on the basis of FDG uptake in 91% and 84% of these segments, respectively. In contrast, in irreversible defects with severe reduction in thallium activity (less than 50% of peak), FDG uptake was present in 51% of segments. In such severe defects, an identical number of segments (51%) demonstrated enhanced uptake of thallium after reinjection. In these severe "irreversible" defects, data on myocardial viability were concordant by the two techniques in 88% of segments, with 45% identified as viable and 43% identified as scar on both PET and thallium reinjection studies. These observations suggest that thallium imaging can be used to identify viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction. Most irreversible defects with only mild or moderate reduction in thallium activity represent viable myocardium as confirmed by FDG uptake.(ABSTRACT TRUNCATED AT 400 WORDS).
Long-term (5 to 20 years) Evolution of nongrafted aplastic anemias. The Cooperative Group for the Study of Aplastic and Refractory Anemias. In the presence of aplastic anemia (AA), therapeutic choices should be determined while taking into account not only changes for immediate improvement, but also both the risks for late-occurring complications and the following quality of life. We report here data concerning a long-term clinical survey (5 to 18 years with a median of 12 years) including 156 nongrafted patients receiving androgen therapy; all patients were alive more than 5 years after diagnosis (40% of patients included at time of diagnosis in our multicentric analysis). Between the 5th and the 13th year follow-up, 21 patients died of various causes either related to AA or to its treatment: 12 of infection or hemorrhage secondary to pancytopenia (6 relapses and 6 that had never been improved; 2 with paroxysmal nocturnal hemoglobinuria [PNH]); 5 of leukemia; 1 of a non-Hodgkin's lymphoma; 2 of late side effects following transfusion (1 acquired immunodeficiency syndrome and 1 chronic B hepatitis); and a single case of myocardial infarction (the latter could possibly result of androgen therapy). Thirteen patients in total developed PNH (among which 10 had clinical symptoms including 2 deaths, and 3 exhibited only biologic abnormalities). Few long-term side effects of androgens could be noticed. Adult height was normal in patients treated during childhood and so was young women's fertility. No malignant hepatoma occurred. This survey allows the recording of late spontaneous hematologic improvement (between 5 and 10 years of evolution). This occurred in 50% of patients that had remained cytopenic 5 years after diagnosis. Although bone marrow stem cell concentration remained abnormal after 10 years of evolution. 85% of patients had a normal red blood cell count, 80% a normal polymorphonuclear count, and 66% a normal platelet count. All patients who did not show late complications had an excellent quality of life.
Severe anterior segment inflammation following corneal surgery for keratoconus. We present three keratoconus patients who experienced severe anterior segment inflammation, two following penetrating keratoplasty, and one following epikeratoplasty. A favorable response to indomethacin therapy in the second eyes of these patients suggests that the inflammation in the first ones was prostaglandin mediated.
Long-term evaluation of indobufen in peripheral vascular disease. Indobufen--an inhibitor of platelets aggregation--has been used in 306 patients with intermittent claudication due to peripheral vascular disease. Patients were treated and followed up for one year. One patient of every 3 treated with indobufen was treated with ASA, and a control group of patients receiving no treatment was also followed up. The authors studied by means of a treadmill exercise test the pain-free walking distance (PFWD), the global walking distance (GWD), and the recovery time after exercise. The treatment period was completed by 290 patients: 204 claudicants, 51 claudicants with diabetes, and 35 with a short PFWD and GWD (greater than 150 m). Indobufen was more effective than ASA in improving the PFWD and GWD in all groups. There were also fewer side effects with indobufen, and cardiac morbidity and mortality was also reduced. In conclusion indobufen showed its activity and safety in chronic treatment of patients with peripheral disease, and we suggest that it may be used for long periods without side effects.
Complement activation is a secondary rather than a causative factor in rabbit pulmonary artery ischemia/reperfusion injury. We have previously demonstrated that reperfusion of a rabbit lung in vivo after 24 h of unilateral pulmonary artery occlusion results in edema, transient leukopenia, and intravascular leukocyte aggregation. We hypothesized that complement was activated by reperfusion and that this in turn contributed to lung injury. In the preliminary phase of the study, we found that ischemia followed by reperfusion resulted in a drop in C3 to 15 +/- 10% (mean +/- SEM) of the prereperfusion value as compared with no change in a group of control animals that had undergone an identical thoracotomy but without pulmonary artery occlusion and reperfusion (p less than 0.05). We then studied three groups of animals to determine if complement depletion with cobra venom factor (CVF) prior to ischemia and reperfusion would prevent the injury. Rabbits treated with CVF but without occlusion and reperfusion did not develop significant lung edema, with left and right lung wet/dry ratios of 5.32 +/- 0.11 and 5.26 +/- 0.12, respectively. For rabbits that were not treated with CVF but underwent ischemia and reperfusion, the comparable numbers were 6.15 +/- 0.36 and 5.19 +/- 0.32 (p less than 0.05 for right versus left). For CVF-treated rabbits that underwent ischemia and reperfusion, the right/left difference persisted (6.77 +/- 0.48 versus 5.35 +/- 0.14, p less than 0.01). Immunocytochemistry documented C3 deposition in non-CVF rabbits that underwent ischemia and reperfusion but not in CVF-treated rabbits. We conclude that ischemia/reperfusion of the lung results in complement activation, but it is not a complement-dependent injury.
Genetic data and natural history of Friedreich's disease: a study of 80 Italian patients. The clinical and genetic features of 80 patients with Friedreich's disease from 64 families are described. Diagnostic criteria were: no evidence of dominant inheritance, onset by the age of 20 years, progressive unremitting ataxia of limbs and gait, and absence of knee and ankle jerks. Furthermore, at least one of the following accessory signs was present: dysarthria, extensor plantar response and echocardiographic evidence of hypertrophic cardiomyopathy. Two peaks of onset age were evident at 6-9 and 12-15 years. Analysis of intra-family variation of onset age and absence of clustering of cardiomyopathy and diabetes did not suggest genetic heterogeneity. Peripheral nerve impairment was an early finding and showed slight further progression, whereas involvement of the cerebellar and corticospinal pathways appeared later and mainly accounted for the progressive worsening of the disease.
Obesity and body fat distribution and breast cancer prognosis. This study addresses the effect of obesity and body fat distribution on axillary lymph node involvement, tumor size, and estrogen receptor (ER) level in breast cancer patients. Anthropometric measurements were prospectively obtained on 248 consecutively and newly diagnosed women with invasive breast cancer. The anthropometric measurements evaluated were abdomen, thigh, subscapular, and midaxillary skinfolds; weight; and height. Weight and Quetelet Index (kg/m2) were significantly (P = 0.001) associated with lymph node involvement in postmenopausal patients. The abdomen:thigh skinfold ratio was significantly higher in premenopausal patients (P = 0.004) and postmenopausal (P = 0.03) without axillary node involvement compared with women with 4+ axillary node involvement. The abdomen:thigh skinfold was higher (P = 0.05) in women with smaller breast cancers (less than 2.0 cm) and higher ER levels. Weight and Quetelet Index did not affect tumor size or ER level. This study demonstrated that obese postmenopausal women who developed breast cancer tend to have more axillary node involvement than their leaner counterparts. Generalized obesity did not affect tumor size or ER level. Premenopausal and postmenopausal women with upper body fat distribution appear to be a subset of women who have a more favorable prognosis as measured by less lymph node involvement, smaller tumors, and higher levels of ER in their tumors.
Significance of discordant ST alternans in ventricular fibrillation. With the use of epicardial mapping, we investigated the electrical alternans of the ST segment during acute myocardial ischemia and studied the difference in ST alternans between dogs with resultant ventricular fibrillation and those without it. During the 7-minute occlusion of the left anterior descending coronary artery below its first diagonal branch, 60 epicardial unipolar electrograms were recorded simultaneously at 1-minute intervals by a computerized mapping system. ST alternans was found in the eight dogs we observed. The amplitude of ST alternans (difference in the ST segment elevation of two consecutive electrograms) was greater in dogs with ventricular fibrillation (n = 4) than in those without it (n = 4) (3.92 +/- 1.24 versus 0.58 +/- 0.49 mV, p less than 0.05). Three of the four dogs with ventricular fibrillation demonstrated discordant ST alternans (i.e., adjacent leads were out of phase). Results from the present study indicate that an increased amplitude and discordance of ST alternans during acute myocardial ischemia are related to ventricular fibrillation and act as indicators of time and spatial unevenness of ventricular repolarization.