shukoor65/lab-rag-model huggingface dataset:
Effects of calcium-free solution, calcium antagonists, and the calcium agonist BAY K 8644 on mechanical responses of skeletal muscle from patients susceptible to malignant hyperthermia. The purpose of this investigation was to determine if alteration in the function of the dihydropyridine receptor may in turn modify halothane-induced contractures in muscle bundles from patients susceptible to malignant hyperthermia (MH). The effects of Ca(2+)-free Krebs Ringer (KR) solution, 5 microM verapamil, 5 microM nifedipine, and 10 microM of the Ca2+ agonist BAY K 8644 on halothane-induced contracture were therefore investigated. The halothane-induced contracture was prevented in the absence of extracellular Ca2+ and significantly reduced in the presence of verapamil or nifedipine. BAY K 8644 significantly enhanced the 0.5-, 1.0-, and 1.5-vol % halothane-induced contracture in MH-susceptible muscle bundles. When BAY K 8644 was dissolved in Ca(2+)-free KR solution, no contracture was observed in MH-susceptible muscle bundles. These results on cut MH-susceptible human muscle bundles support the hypothesis that halothane-induced contracture in MH can be modified by the binding of Ca2+ agonists or antagonists to the dihydropyridine receptor. The role of Ca2+ entry phenomena remains unclear, but the results suggest that extracellular Ca2+ is required to reprime or to bind to some sites of the dihydropyridine receptors.
Regulation of MHC class II antigen expression. Opposing effects of tumor necrosis factor-alpha on IFN-gamma-induced HLA-DR and Ia expression depends on the maturation and differentiation stage of the cell. MHC class II induction by cytokines has been suggested to play a major role in the initiation and propagation of immune and autoimmune processes. TNF-alpha has been found both to enhance and also to inhibit IFN-gamma-induced MHC class II expression. In the present studies, the effect of TNF-alpha on IFN-gamma induced MHC class II expression was tested in various cell lines. On the basis of the data, we propose that, depending on the stage of differentiation and maturation of the cells, TNF-alpha might synergize or antagonize the affects of IFN-gamma on the regulation of MHC class II expression. Thus, in immature cells such as HL-60 or THP-1, TNF-alpha enhances IFN-gamma-induced class II expression. However, when differentiation was induced in these cells by TPA or IFN-gamma, the additive effect of TNF-alpha on the IFN-gamma induced DR expression was eliminated. Furthermore, TNF-alpha down-regulates the IFN-gamma-induced class II expression in differentiated cells such as human skin fibroblasts or activated macrophages. In bone marrow cells induced to differentiate in vitro, TNF-alpha decreased the IFN-gamma-induced MHC class II expression in a maturation-dependent fashion. These results provide a rational explanation for the conflicting reports regarding the effect of TNF-alpha on IFN-gamma-induced class II expression. But more importantly they may be relevant to the biologic function of TNF-alpha. Thus, we show that TNF-alpha-treated mice have reduced level of Ia expression on peritoneal macrophages and in vivo treatment with TNF-alpha antagonizes the ability of IFN-gamma to induce class II expression on these macrophages.
Endoscopic injection sclerotherapy versus conservative treatment for patients with unresectable hepatocellular carcinoma and bleeding esophageal varices. We performed endoscopic injection sclerotherapy (EIS) in the treatment of 37 patients with bleeding esophageal varices due to unresectable hepatocellular carcinoma (HCC). The results were compared with those in another 33 HCC patients treated only conservatively, without EIS, during the same period. A majority of both groups died within 3 weeks after treatment. Comparing the two groups, there was no significant difference in fatal bleeding (66% vs 75%), but significantly fewer of the EIS patients died of the index hemorrhage (43% vs. 83%; p less than 0.01). Also, in the absence of portal vein thrombosis, EIS significantly reduced the risk of fatal bleeding (31% vs. 73%; p less than 0.25). The mean days of survival were 32 +/- 15 (range, 2 to 320) in the EIS group and 10 +/- 14 (range, 2 to 270) in the compared group (p less than 0.001). We conclude that EIS provides temporary control of acute esophageal variceal bleeding in patients with unresectable HCC. The major factors contributing to EIS failure are the lethal propensity of the underlying disease and portal vein thrombosis.
A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome. The relationship between tubulointerstitial nephritis and proteinuria was characterized in experimental nephrosis in rats. In one group, proteinuria induced by aminonucleoside of puromycin (PAN) was reduced by using an 8% protein diet and adding the angiotensin I-converting enzyme (ACE) inhibitor enalapril to the drinking water. Two control groups were injected with saline and PAN, respectively, and fed a 27% protein diet. The first group had significantly reduced albuminuria and a definite attenuation of tubular cell injury. There was a strong positive correlation between the number of interstitial macrophages and albuminuria. The beneficial effect was reproduced by dietary-protein restriction alone, whereas ACE inhibition alone had an insignificant effect on the degree of proteinuria. Depletion of circulating T lymphocytes in one group of nephrotic rats eliminated interstitial lymphocytes but did not affect interstitial macrophage influx. Inhibition of the in situ proliferation of resident interstitial macrophages by unilateral kidney irradiation failed to change the intensity of the macrophage infiltration. Treatment of rats with sodium maleate produced proximal tubular cell toxicity but interstitial inflammation did not develop, suggesting that the latter is not a nonspecific response to tubular injury. These studies demonstrate a strong relationship between tubulointerstitial nephritis and the severity of proteinuria in experimental nephrosis.
The dizzy patient: etiologic treatment. The basis for the vestibular complaint in dizzy patients should be viewed as having an etiology rather than a description of its clinical presentation. Effective treatment of vestibular disorders is based on the stabilization of the vestibular abnormality, to allow for central vestibular compensation. While not all of the etiologies for dizziness have been described, there are effective etiologic treatments available. These fit into categories of neurotransmitters, blood sugar and blood fat control, hormones, minerals, and treatments for autoimmune dizziness.
Contractile response of aorta to alpha 1-adrenergic stimulation in Ca(2+)-free medium is reduced in spontaneous hypertension. Vascular responses of aortic rings to alpha 1-adrenergic stimulation by phenylephrine (Phe) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were studied in Ca(2+)-containing medium and Ca(2+)-free medium plus 50 mumol/L EGTA. Although there was no difference in the sustained force development between SHR and WKY vessels in response to 100 mmol/L KCl or 10 mumol/L Phe in Ca(2+)-containing medium, the transient contractile response to 10 mumol/L Phe in Ca(2+)-free medium was substantially smaller in SHR compared to that in WKY. Subsequent addition of 2.5 mmol/L Ca2+ restored the sustained contractile response to a similar level in both SHR and WKY vessels. The transient contractile response to Phe in Ca(2+)-free medium containing EGTA, presumably due to the release of intracellular Ca2+, decreased progressively with preincubation time in Ca(2+)-free medium, indicating intracellular Ca2+ depletion. Such a temporal change of aortic response was more pronounced in SHR than in WKY. The subsequent response to Ca2+ repletion in the presence of Phe, on the other hand, increased progressively with Ca(2+)-depletion period and was higher in SHR than in WKY. The rate of relaxation after washout of Phe was slower in SHR aorta compared to WKY aorta. These results, together with our earlier findings, collectively suggest that the previous known deficiency in Ca2+ pumping mechanisms of vascular muscle microsomes leading to a reduced functional size of intracellular Ca2+ pool may account for the smaller contractile response of SHR aorta to alpha 1-adrenergic stimulation in Ca(2+)-free medium and the slower rate of relaxation.
The occurrence of epilepsy and febrile seizures in Virginian and Norwegian twins. Twin studies provide an efficient method for examining the importance of genetic and environmental factors in the etiology of disorders such as epilepsy. Population-based twin registries are especially valuable for studies of this type since effects of reporting and self-selection biases on the resulting data are minimized. Among 14,352 twin pairs contained in the Virginia and Norwegian twin panels for whom questionnaire information was available, there was a history of epilepsy in one or both members of 286 pairs; febrile seizures were reported in 257 pairs. Analyses of questionnaire data revealed no significant differences in concordance rates between Virginian and Norwegian twins for either epilepsy or febrile seizures. Probandwise concordance rates for epilepsy were 0.19 in monozygotic twins and 0.07 in dizygotic twins. Analogous rates for febrile seizures were 0.33 (monozygotic) and 0.11 (dizygotic). These results provide further evidence that genetic factors do have a role in the expression of epilepsy and febrile seizures.
Retinal migraine, chorea, and retinal artery thrombosis in a patient with primary antiphospholipid antibody syndrome. We report the case of a patient with the unusual combination of migraine, chorea, and retinal arterial thrombosis along with laboratory evidence of autoimmunity. In the absence of systemic lupus erythematosus, the clinical manifestations suggest the presence of the primary antiphospholipid antibody syndrome.
Inability of coronary blood flow reserve measurements to assess the efficacy of coronary angioplasty in the first 24 hours in unselected patients. To determine functional and anatomic changes in the first 24 hours after coronary angioplasty, we studied at random 15 patients (9 men, mean age 60 years) who underwent coronary angioplasty of 16 coronary arteries. Quantitative coronary angiography and coronary flow reserve measurements from digitized coronary angiograms were performed before, immediately after, and 24 hours after coronary angioplasty. Calculated were the minimal luminal diameter, obstruction area, and percentage diameter stenosis from two preferably orthogonal projections. Prior myocardial infarction in the myocardial region of interest was present in four patients. Seven patients had multivessel disease. Collateral vessels supplying the compromised flow region were observed in three patients. Six patients had refractory unstable angina pectoris. After coronary angioplasty, angiographically visible dissection was noted in six patients, whereas side branch occlusion was observed in one. Minimal luminal diameter before, immediately after, and 24 hours after was 0.93 +/- 0.18 mm, 1.53 +/- 28 mm, and 1.53 +/- 0.21 mm, respectively; obstruction area was 0.70 +/- 0.26 mm2, 1.92 +/- 0.69 mm2, and 1.87 +/- 0.51 mm2, respectively; diameter stenosis was 60.4 +/- 8.0%, 36.8 +/- 11.4%, and 37.6 +/- 5.3%, respectively. The coronary flow reserve (lower limit of normal with this technique 3.4) was essentially the same before and immediately after coronary angioplasty (1.26 +/- 0.59 vs 1.30 +/- 0.42, p = NS) with a slight improvement to 1.78 +/- 0.90 (p less than 0.05) 1 day later. Coronary artery dimensions correlated poorly with coronary blood flow reserve before and after angioplasty.
Posterior cortical dementia with alexia: neurobehavioural, MRI, and PET findings. A progressive disorder of relatively focal but asymmetric biposterior dysfunction is described in a 54 year old right handed male. Initial clinical features included letter-by-letter alexia, visual anomia, acalculia, mild agraphia, constructional apraxia, and visuospatial compromise. Serial testing demonstrated relentless deterioration with additional development of transcortical sensory aphasia, Gerstmann's tetrad, and severe visuoperceptual impairment. Amnesia was not an early clinical feature. Judgment, personality, insight, and awareness remained preserved throughout most of the clinical course. Extinction in the right visual field to bilateral stimulation was the sole neurological abnormality. Early CT was normal and late MRI showed asymmetrical bioccipitoparietal atrophy with greater involvement of the left hemisphere. Results from positron emission tomography (PET) showed bilaterally asymmetric (left greater than right) occipitotemporoparietal hypometabolism. The metabolic decrement was strikingly asymmetric with a 50% reduction in glucose consumption confined to the left occipital cortex. The picture of occipitotemporoparietal compromise verified by MRI, PET, and neurobehavioural testing would be unusual for such degenerative dementias as Alzheimer's (AD) and Pick's disease, although atypical AD with predominant occipital lobe involvement cannot be excluded. This case supports the concepts of posterior cortical dementia (PCD) as a clinically distinct entity and for the first time documents its corresponding metabolic deficit using PET.
Evaluation of salvage surgery in heavily irradiated cancer of the buccal mucosa. This report describes the authors' experience with salvage surgery in 78 patients with carcinoma of the buccal mucosa who failed after high-dose radical radiation therapy at Regional Cancer Centre, Trivandrum, India. Forty-four patients (56%) required a hemimandibulectomy for adequate tumor clearance. Fifty-four patients (69%) required a primary reconstructive procedure for wound closure. Follow-up periods ranged from 28 months to 63 months (median follow-up, 41 months). Thirteen patients (17%) developed nonfatal postoperative complications. Thirty-one patients recurred after surgery, five of whom were again salvaged by further surgery. Overall, the recurrence rate was 36%. Most of the recurrences (26/31) were at the primary site. The overall 5-year actuarial disease-free survival after salvage surgery was 59.7%. T stage of the recurrent tumor and its skin infiltration emerged as factors which significantly influenced disease-free survival (P less than 0.05).
Reactive astrogliosis is widespread in the subcortical white matter of amyotrophic lateral sclerosis brain. Widespread astrogliosis exists in the subcortical white matter in amyotrophic lateral sclerosis (ALS). As revealed by glial fibrillary acidic protein (GFAP) immunostaining, the gliosis has the morphological properties of an active process. It is present in the midfrontal, inferior parietal, temporal, cingulate, and occipital cortices, as well as in the motor cortex. Compared to matched regions from other neurological diseases, the gliosis in ALS does not appear to be the nonspecific result of a progressive, degenerative disease. In cell number and apparent cell size, the gliosis is comparable to that present in neurological diseases known to have white matter gliosis. Cytologically, the gliosis most closely resembles that present in cases of cerebral infarction. The basis for this similarity is unknown.
Reversibility of cardiac abnormalities in human immunodeficiency virus (HIV)-infected individuals: a serial echocardiographic study. Seventy adults who tested positive for human immunodeficiency virus (HIV) were prospectively studied with serial echocardiography to better define the prevalence and progression of cardiac disease in such patients. Fifty outpatients (Group A), including 44 with acquired immunodeficiency syndrome (AIDS) and 6 with AIDS-related complex, and 20 additional patients (Group B) with asymptomatic HIV infection had baseline echocardiographic studies at a time when no patient had symptomatic heart disease. Follow-up studies were performed at 9 +/- 3 months in 52 patients (74%) and again at 15 +/- 3 months after baseline studies in 29 patients (41%). During the study, 22 patients (44%) in Group A and 1 patient (5%) in Group B died. Cardiac abnormalities were noted in 26 patients (52%) in Group A and 8 patients (40%) in Group B (p = NS) on initial or follow-up study. An abnormal left ventricular ejection fraction (less than 45%) or fractional shortening (less than 28%) was seen in seven patients in Group A; of these, three had normal left ventricular function on a later echocardiogram. One patient in Group B had persistent left ventricular dysfunction. All patients in Group A with left ventricular dysfunction on two serial studies died within 1 year after the initial echocardiogram. Ejection fraction did not change between baseline and two follow-up studies in either group (A: 52 +/- 9 vs. 56 +/- 9 vs. 55 +/- 5%, p = NS; B: 58 +/- 6 vs. 58 +/- 5 vs. 59 +/- 6%, p = NS). Right-sided cardiac enlargement resolved in 18 patients (44%), including 5 of 10 in Group A and 3 of 8 in Group B.
Intestinal permeability after single dose gluten challenge in coeliac disease. The changes of intestinal permeability before and after a gluten load were studied. The study group comprised 27 patients with coeliac disease (mean age 12.3 years) and 19 healthy controls matched by sex and age. Intestinal permeability was studied by measuring the urinary excretion of two sugars, lactulose and L-rhamnose, before and six hours after the ingestion of five palatable biscuits made with 50 g of gluten powder. The patients with coeliac disease had been on a gluten free diet during the previous two years. After the gluten load lactulose and L-rhamnose urinary excretion changed significantly in patients, and a significant increase in the lactulose: L-rhamnose ratio was also observed. No significant changes were observed in the controls. In view of the modification of the three biopsies diagnostic protocol made by the European Society for Paediatric Gastroenterology and Nutrition, permeability tests associated with single gluten challenges may be an added contribution to the accuracy of the diagnosis in childhood.
Clinical course and outcome in class IC antiarrhythmic overdose. 120 cases of class IC antiarrhythmic overdose, including propafenone, flecainide, ajmaline and prajmaline overdose, were evaluated with respect to clinical course, therapy and outcome. Whereas drug overdose in general has an overall mortality of less than 1%, intoxication with antiarrhythmic drugs of class IC was associated with a mean mortality of 22.5%. Nausea, which occurred within the first 30 minutes after ingestion, was the earliest symptom. Spontaneous vomiting probably led to self-detoxication in about half the patients. Cardiac symptoms including bradycardia and, less frequently, tachyrhythmia occurred after about 30 minutes to 2 hours. Therapeutic measures included administration of activated charcoal, gastric lavage and a saline laxative, catecholamines, and in some patients, hypertonic sodium bicarbonate, insertion of a transvenous pacemaker and hemoperfusion. Fatal outcome was mainly due to cardiac conduction disturbances progressing to electromechanical dissociation or asystolia. Resuscitation, which had to be performed in 29 patients, was successful in only two of them. No correlation was found between fatal outcome, the type of antiarrhythmic, and ingested dose. Since a specific treatment is not available and resuscitive procedures including sodium bicarbonate and insertion of a pacemaker are of limited therapeutic value, early diagnosis and primary detoxification are most important for prevention of fatal outcome.
A pilot study of sphincter-sparing management of adenocarcinoma of the rectum. After analysis of 26 prospectively accrued patients with distal rectal adenocarcinomas who underwent sphincter preservation treatment, we have concluded that tumors that invade only the submucosa can safely be treated with surgery alone and that tumors that invade the muscularis or further can be safely treated with surgery combined with chemoradiotherapy. None of the patients had either local or distant recurrence, with a median follow-up of 21 months. All patients have been fully continent. The results, although preliminary, imply that resection of distal rectal adenocarcinoma with sphincter preservation, and adjuvant therapy when appropriate, have achieved local and distant control equal to the conventional Miles' abdominoperineal resection, but without the need for a permanent colostomy.
Value of transesophageal echocardiography as an adjunct to transthoracic echocardiography in evaluation of native and prosthetic valve endocarditis. To determine if transesophageal echocardiography provides better visualization of valvular vegetations than transthoracic echocardiography, we used both methods to evaluate 24 consecutive patients (mean age, 54 years; 15 female patients and nine male patients) referred for symptoms suggestive of infectious endocarditis. Ten of the 24 patients had one or more valvular prostheses. Echocardiograms were classified as positive or negative based on visualization of valvular vegetations or abscesses. Of ten patients with a final diagnosis of infectious endocarditis on extended follow-up, transthoracic echocardiography was positive in five patients. Transesophageal echocardiography not only yielded abnormal findings in all ten of these patients, but also revealed additional information in four of the five patients with abnormal transthoracic echocardiographic examinations. Among the 14 patients who, on subsequent follow-up, were found not to have infectious endocarditis, transthoracic echocardiography was normal in 13 and falsely abnormal in one. Transesophageal echocardiography revealed no evidence of infectious endocarditis in any of these patients. The ten patients who were determined to have infectious endocarditis all had positive blood cultures and no alternative cause for their clinical presentation; in seven patients in this group who underwent operative or postmortem evaluation, infectious endocarditis was confirmed. All patients without infectious endocarditis were demonstrated to have other causes for their clinical presentation. We conclude that transesophageal echocardiography is a highly valuable test in the work-up of patients with suspected infectious endocarditis, especially those patients with inconclusive or normal transthoracic echocardiograms. In addition, transesophageal echocardiography may be of benefit to patients with previously documented infectious endocarditis and a complicated clinical course in whom additional cardiac lesions are suspected but not demonstrated by transthoracic echocardiography.