shukoor65/lab-rag-model huggingface dataset:
Functional, biochemical, and histopathologic consequences of high-dose interleukin-2 administration in rats. A variety of side effects have been reported with the use of interleukin-2 alone or in combination with lymphokine-activated killer cells in patients with disseminated neoplasms. The present study was undertaken to determine the effects of high-dose interleukin-2 administration in normal rats. Sprague-Dawley rats were treated with intravenous recombinant interleukin-2 (900,000 IU/kg/day) for 9 consecutive days. Animals were placed in individual metabolic cages, and arterial blood pressure, food intake, body weight, and urine output were monitored. On day 10, animals were killed by exsanguination, various tissues were harvested, and a variety of hematologic and chemical assays were performed. The results were compared with those of placebo-injected normal control and pair-fed groups. The interleukin-2-treated group exhibited anorexia, weight loss, hypotension, anemia, leukocytosis, lymphocytosis, eosinophilia, hypercalcemia, azotemia, and a marked urinary concentration defect. Histologic examination of various tissues revealed widespread infiltration with mono-nuclear cells and eosinophils in most organs, especially in the lungs and liver of interleukin-2-treated animals. Other abnormalities included severe panlobular hepatitis, hepatocellular necrosis, and thymic involution. Renal involvement was mild and consisted of focal interstitial infiltration by mononuclear cells. According to these observations, administration of high-dose interleukin-2 in normal rats results in a score of significant functional, biochemical, and histologic abnormalities.
Frequency of the hypercalcemia-leukocytosis syndrome in oral malignancies. There have been a number of reports over the last 15 years of patients with cancer who develop both leukocytosis and hypercalcemia, particularly in patients with cancers of the oral cavity. In this study, the authors report the frequency of hypercalcemia and leukocytosis in 225 patients with oral malignancies. Ten patients (4.4%) had hypercalcemia, 11 patients (4.9%) had leukocytosis, and five (2.2%) had both hypercalcemia and leukocytosis. The occurrence of these two distinct paraneoplastic syndromes in the same patients was greater than could have been expected from chance alone (chi-square = 45.8, P less than 0.0001). This study demonstrates that although hypercalcemia and leukocytosis are relatively uncommon in oral cancers, when they do occur they are frequently associated. To the knowledge of the authors, this is the first report in which the frequency of the association hypercalcemia and leukocytosis is studied in detail in large numbers of patients with oral cancer.
Lack of correlation between P pulmonale and right atrial overload in chronic obstructive airways disease. The correlation between P pulmonale and right atrial overload in chronic lung disease was studied. Right atrial pressure, pulmonary artery pressure, and cardiac output were measured with a Swan-Ganz catheter in nine patients with chronic lung disease and P pulmonale on the electrocardiogram (P wave amplitude of greater than or equal to 2.5 mm (0.25 mV) in leads II, III, and a VF. The results were compared with those in six patients with an atrial septal defect (left to right shunt greater than or equal to 50%) and six patients with pulmonary hypertension (mean pressure greater than or equal to 30 mm Hg without left sided heart disease). Right atrial volume and wall thickness were measured in 10 cases of P pulmonale among 1000 necropsy cases and compared with 141 normal hearts from the same series. The patients with P pulmonale did not show a significant increase in right atrial or pulmonary artery pressures. None of the patients with an atrial septal defect or pulmonary hypertension had P pulmonale on the electrocardiogram. In the necropsy cases of P pulmonale mean (1 SD) in right atrial volume (32 (12) ml) and wall thickness (1.5 (0.7) mm) were not significantly increased (40 (14) ml and 1.4 (0.5) mm in the normal hearts). There was a significant inverse relation between the presence of P pulmonale and the cardiothoracic ratio. In all the patients with P pulmonale chest x ray showed a low cardiothoracic ratio, a considerably depressed diaphragm, and a pendulous heart. This study showed no correlation between P pulmonale and right atrial overload in chronic lung disease.
Alteration of whole-body protein kinetics according to severity of surgical trauma in patients receiving total parenteral nutrition. This study was conducted to clarify the mechanisms of body nitrogen losses according to the severity of surgical trauma. Thirteen male patients who underwent operation for esophageal cancer (group E), and 11 men (who underwent gastric or colorectal surgeries (group GC) were studied. The measurement of whole-body protein turnover, synthesis, and breakdown were made preoperatively on the 3rd and 10th postoperative day with constant infusion of [15N]glycine during isocaloric and isonitrogenous total parenteral nutrition. Significant increases in the rates of whole-body protein turnover (flux) and breakdown were seen in group E on the 3rd postoperative day (p less than 0.01, p less than 0.01, respectively), whereas the increases were not significant in group GC. The rates of whole-body protein flux and breakdown were significantly greater in group E than group GC (p less than 0.01, p less than 0.01, respectively). The rate of protein synthesis significantly increased in group E (p less than 0.05), but did not alter or slightly decreased in group GC. The rates of whole-body protein flux and breakdown in group E were still significantly greater on the 10th postoperative day than preoperatively. It was concluded that unchanged or slightly decreased rates of whole-body protein synthesis with slightly increased breakdown were seen in the group of patients who underwent gastric or colorectal surgery, whereas synthesis increased significantly with a greater increase of breakdown in patients receiving severe surgical procedures, esophagectomy for esophageal cancer.
Benefits of implantable defibrillators are overestimated by sudden death rates and better represented by the total arrhythmic death rate Benefits of the implantable defibrillator on survival were studied in 56 consecutive patients (concomitant coronary bypass or arrythmia surgery in 15) during an 8 year period between 1982 and 1990. During a follow-up period of 29 +/- 25 months, six patients had a sudden death and eight patients had a nonsudden cardiac death. Nonsudden cardiac deaths included three surgical deaths (death within 30 days after the surgery; two in patients without and one in a patient with concomitant cardiac surgery), one arrhythmia-related nonsudden death (death within 24 h after an arrhythmic event despite initial termination of the arrhythmia by the implantable defibrillators) and four nonarrhythmic cardiac deaths. The actuarial survival rate free of events at 1, 2 and 3 years was 96%, 96% and 92%, respectively, for sudden death, 91%, 91% and 87% for sudden death and surgical mortality and 89%, 89% and 85% for total arrhythmic death (sudden death, surgical mortality and arrhythmia-related nonsudden death). Thus, in patients treated with an implantable defibrillator, 1) the rate of sudden death is low (8% at 3 years); 2) 50% of nonsudden cardiac deaths are causally related to arrhythmia (surgical mortality or arrhythmia-related nonsudden death); 3) the total arrhythmic death rate is substantially higher than the sudden death rate; and 4) benefits of an implantable defibrillator are overestimated by reported sudden death and nonsudden cardiac death rates. The benefits may be better represented by the total arrhythmic death and nonarrhythmic cardiac death rates.
Stroke from other etiologies masquerading as migraine-stroke. There has been a recent increase in the number of studies dealing with migraine-stroke. I describe five patients in whom migraine-stroke was the clinical diagnosis but in whom the subsequent clinical events or autopsy showed a different mechanism for the cerebral infarction. Three patients had arterial dissection (one proven at autopsy), one had marantic endocarditis that had been missed on two echocardiograms (proven at autopsy), and one had generalized atherosclerosis and diabetes. These patients demonstrate that important and different etiologies may produce what seems to be the migraine-stroke syndrome. The result may be failure to recognize specific therapeutic measures that could have vitally important benefit to the patient.
Low peptic ulcer and high gastric cancer prevalence in a developing country with a high prevalence of infection by Helicobacter pylori. We compared the prevalence rates of peptic ulcer (duodenal and gastric) and gastric cancer in 1,796 dyspeptic Peruvian patients with those reported in 2,883 similar patients from developed countries. The prevalence of total peptic ulcer was significantly lower, and that of gastric cancer significantly higher, in the Peruvian patients. The prevalence of gastric ulcer was lower but not significantly so. We deduced that the significantly lower prevalence of total peptic ulcer was directly related to the low prevalence rate of duodenal ulcer. We hypothesize that the reason for these differences was probably a higher prevalence of Helicobacter pylori-associated chronic atrophic gastritis with hypochlorhydria in the Peruvian patients. Hypochlorhydria decreases the predisposition to peptic ulcer (especially duodenal ulcer), and chronic atrophic gastritis may predispose an individual to gastric cancer.
Clinical implications of late proven patency after successful coronary angioplasty. BACKGROUND. The introduction of percutaneous transluminal coronary angioplasty (PTCA) has changed the pattern of intervention in coronary artery disease. However, the long-term results in patients undergoing successful, elective, native-vessel PTCA are not yet fully characterized. Because the healing and subsequent proliferative response after angioplasty are time related, it was the purpose of the present study to determine the long-term outcome in patients whose dilated arteries have been demonstrated to be patent 4-12 months after successful, uncomplicated PTCA. METHODS AND RESULTS. The patients were grouped on the basis of the 4-12 month catheterization into those whose vessels were angiographically "normal" or had luminal irregularities only at the PTCA sites (396 patients), those whose vessels also had luminal irregularities elsewhere with or without PTCA site luminal irregularities (680 patients), and those with significant obstructive disease (more than 50% diameter narrowing) at sites other than the PTCA sites (426 patients). Of 1,502 such patients, long-term follow-up was available in 1,491. At the time of the original angioplasty, the normal patients had a 1.8% incidence of multivessel disease; luminal irregularity patients, 9.4%; and obstructive disease patients, 58.7%. At angiographic restudy, 16.4% of the obstructive disease patients continued to have multivessel disease. The patients were followed for the events of death, myocardial infarction, coronary surgery, and repeat PTCA. The 6-year survival rate was 95%; cardiac survival, 96%; and freedom from all events, 65%. The strongest correlate of events during follow-up was the angiographic status of the undilated segments. At 6 years, freedom from cardiac events was noted in 77% of the normal group, 61% of the luminal irregularity group, and 55% of the obstructive disease group. Diabetes and hypertension were also independent correlates of events. CONCLUSIONS. Results from the present study show that associated disease in undilated segments is a strong predictor of late events in patients after successful, uncomplicated, reatenosis-free PTCA. However, the need for further revascularization was frequent even in patients without obstructive disease. Completeness of revascularization is appropriate when possible, and limiting progression of coronary disease at sites remote from those dilated should improve on these late results.
Pressure therapy for the control of hypertrophic scar formation after burn injury. A history and review. Devastating functional problems can result from the formation of hypertrophic scar tissue after burn injury. Although a patient with burns may have several medical problems to contend with because of the injury, most ongoing rehabilitation difficulties are a consequence of the continual wound contraction that occurs in immature burn scars. Treatment of hypertrophic burn scar consists of several surgical options and of pressure therapy, which traditionally involves wearing garments made from elasticized fabric. This article reviews the treatment of hypertrophic scar tissue, with emphasis on its history and on nonsurgical methods of managing the burn scar.
Repolarization inhomogeneities in ventricular myocardium change dynamically with abrupt cycle length shortening. BACKGROUND. In single heart cells, abrupt changes in stimulation rate elicit complex alterations in repolarization. The effects of rate change on dispersion of repolarization, however, have not been well characterized. METHODS AND RESULTS. To determine the effects of abrupt cycle length (CL) shortening on spatial inhomogeneity of repolarization in a syncytium of ventricular cells, 124 action potentials were simultaneously recorded from Langendorff-perfused guinea pig hearts using high-resolution optical mapping with voltage-sensitive dye. The distribution of ventricular action potential durations (APDs) mapped during each cardiac cycle was used to calculate mean APD and repolarization dispersion index (DI), defined as the variance of the distribution. After abruptly shortening CL from 500 to 300 msec, mean APD declined exponentially in normoxic controls (by 23 +/- 3 msec, p less than 0.0001). This response was characterized by beat-to-beat oscillations of APD that were synchronized at all ventricular sites. After 30 minutes of hypoxia, mean APD decreased from 175.0 +/- 13.3 to 76 +/- 25.7 msec. However, during hypoxia, abrupt CL shortening lowered mean APD by only an additional 6 +/- 6 msec, and APD oscillations were no longer synchronized throughout the ventricle. In controls, beat-to-beat DI decreased significantly (-51.0 +/- 6.8%, p less than 0.01) by the sixth post-CL shortening beat and then recovered (by 15-20 beats). In contrast, DI failed to decrease during hypoxia (+7.1 +/- 23%). Two mechanisms for the transient decline of DI in controls were identified: synchronous APD oscillations and transient diminution of the apical-to-basal ventricular APD gradient. CONCLUSIONS. These data demonstrate that inhomogeneity of ventricular repolarization, as measured by DI, changes dynamically with CL shortening. Furthermore, the hypoxic ventricle does not attenuate DI after abrupt CL shortening and thereby lacks a physiological response expected to diminish vulnerability to arrhythmias.
Physical activity on the job and cancer in Missouri. We conducted a series of case-control studies to investigate the risks of 16 cancer types in relation to occupational physical activity. These studies were based on Missouri Cancer Registry data for 17,147 White male cancer patients registered between 1984 and 1989. Colon cancer risk was increased for both the moderate (odds ratio (OR) = 1.1; 95% confidence interval (CI) = 1.0, 1.3) and low (OR = 1.2; 95% CI = 1.0, 1.5) activity levels. Similar elevations were observed for prostate cancer at the moderate (OR = 1.1; 95% CI = 1.0, 1.3) and low (OR = 1.5; 95% CI = 1.2, 1.8) levels of activity, and for cancer of the testis at the low activity level (OR = 2.2; 95% CI = 1.3, 3.7). An opposite trend (p less than 0.01) was noted for lung cancer, which showed decreased risk at the moderate (OR = 0.9; 95% CI = 0.8, 1.0) and low (OR = 0.8; 95% CI = 0.6, 0.9) activity levels. These associations suggest that further study of the relationship between physical activity and site-specific cancer risk is warranted.
Interaction between free radicals and excitatory amino acids in the formation of ischemic brain edema in rats. Both oxygen free radicals and excitatory amino acids have been implicated as important cellular toxins in ischemic brain. Recent in vitro studies suggest that there may be a mutual interaction between these two mediators. We explored the relation between oxygen free radicals and excitatory amino acids in the development of ischemic brain edema in vivo. Male Sprague-Dawley rats were treated with the free radical scavenger dimethylthiourea 1 hour before ischemia or with the excitotoxin antagonist MK-801 30 minutes before ischemia produced by occlusion of the middle cerebral artery. Groups of seven or eight animals were treated with vehicle, low-dose (375 mg/kg) dimethylthiourea, high-dose (750 mg/kg) dimethylthiourea, low-dose (0.5 mg/kg) MK-801, high-dose (2.0 mg/kg) MK-801, or both high-dose dimethylthiourea and low-dose MK-801. After 4 hours of ischemia, brain water content was determined. In eight vehicle-treated controls, mean +/- SEM water content of tissue in the center of the ischemic zone was 83.29 +/- 0.18%. A significant reduction of brain edema was observed in all drug-treated groups: for example, 50.2% (p less than 0.001) in the high-dose dimethylthiourea group, 53.7% (p less than 0.001) in the low-dose MK-801 group, and 66.4% (p less than 0.001) in the combined dimethylthiourea and MK-801 group. Combined treatment with dimethylthiourea and MK-801 provided no significant additive effect over that resulting from treatment with MK-801 alone.
A mathematical computer stimulation model for the development of colonic polyps and colon cancer. Currently known information about the development and progression of colon polyps and cancer is summarized and organized into a mathematical computer simulation model that successfully predicts the natural history of colon polyp and cancer development for an average patient with (1) familial polyposis coli (2) genetic susceptibility as measured by a positive family history, and (3) negative family history with a high fat diet. The mathematical model uses four distinct types of cells (normal, transformed, polypoid, and cancerous) and two kinetic processes (mutation and promotion). Arachidonic acid metabolites play a role in the model in the promotion of cancer from polyps, and account for that promotion through: (1) their effect on encouraging more polypoid cells in mitosis to move toward cancer; and (2) their immunosuppressive effect over time. The model also shows that one defect in allowing more cells to mutate to the transformed state is sufficient to account for the chain of events leading to the clinical sequelae of familial polyposis coli. A second genetic effect at another point in the process is unnecessary. The mechanism of action of Sulindac on colon polyps is explained by the model through inhibition of production of arachidonic acid metabolites, most notably prostaglandin E.
Antibodies against acetaldehyde-modified epitopes: presence in alcoholic, non-alcoholic liver disease and control subjects. Several studies have recently shown the presence of antibodies against acetaldehyde-modifications in the sera of alcoholic patients. To assess the specificity of this immune response, plasma immunoreactivity with proteins modified in vitro by acetaldehyde was measured using an enzyme-linked immunosorbent assay in 97 alcoholic patients with varying degrees of alcoholic liver disease, in 35 patients with non-alcoholic liver diseases and in 33 control subjects who were social drinkers. All three groups showed some response against acetaldehyde-modified epitopes. The highest plasma reactivities were found in alcoholics, especially those with steatosis and alcoholic hepatitis. Plasma from patients with non-alcoholic liver disease and control subjects also reacted with the acetaldehyde conjugates, but to a lesser extent than plasma from alcoholics. The reliability of these antibodies as markers of either alcohol abuse or alcoholic liver disease therefore appears to be low. However, further studies using more precisely modified proteins or elucidation of the classes of immunoglobulin involved in the immune response against the modified proteins may give clearer differences between the three groups.
Activation of cardiac sympathetic afferents during coronary occlusion. Evidence for reflex activation of sympathetic nervous system during transmural myocardial ischemia in the dog. BACKGROUND. Left ventricular sympathetic afferent nerves are located mainly in superficial epicardial layers. Reflex excitatory responses mediated by sympathetic afferent nerves have been observed during myocardial ischemia in cats and humans but not in dogs. Previous canine studies have induced ischemia by occlusion of a coronary artery. Extensive collateral circulation in the canine heart may limit ischemia of epicardial layers during simple coronary occlusion, resulting in little stimulation of sympathetic afferent nerves and minimal reflex excitatory responses. METHODS AND RESULTS. In anesthetized dogs with sinoaortic and vagal deafferentation, we determined whether reflex sympathoexcitatory responses mediated by sympathetic afferents occurred during transmural myocardial ischemia. Reflex sympathoexcitation was quantitated by direct recording from either efferent renal (n = 20) or cardiac (n = 5) sympathetic nerves. Responses of arterial pressure and efferent sympathetic nerve activity were measured during simple occlusion of the anterior descending artery (LAD alone) and during LAD occlusion with a circumflex stenosis (LAD + CIRC). This circumflex stenosis was adjusted to abolish coronary vasodilator reserve without reducing basal flow. We observed significantly greater reflex increases in renal (32 +/- 5%) and cardiac (58 +/- 15%) nerve activity during LAD + CIRC than during LAD alone (14 +/- 6% and 8 +/- 7%, respectively). Reflex changes in renal nerve activity during LAD + CIRC were abolished by interruption of cardiac sympathetic afferent pathways (n = 5). In eight experiments, myocardial blood flow was measured during the two coronary occlusions. These experiments confirmed that LAD + CIRC elicited more transmural ischemia in the LAD distribution than did LAD alone. However, these experiments also revealed that LAD + CIRC elicited endocardial ischemia in the circumflex distribution. In five additional experiments, regional sympathetic deafferentation of the posterior left ventricle by epicardial application of 88% phenol along the atrioventricular groove had no significant effect on renal nerve responses to LAD + CIRC (36 +/- 5% increase before phenol versus 31 +/- 3% increase after phenol). These results indicate that endocardial ischemia in the circumflex distribution did not contribute to the reflex increases in nerve activity that were noted during LAD + CIRC. CONCLUSIONS. Reflex sympathoexcitation mediated by cardiac sympathetic afferents can be elicited in dogs. However, these responses are significant only during ischemia that is transmural and involves the superficial epicardial layers of the left ventricle.