shukoor65/lab-rag-model huggingface dataset:
A tRNA(Lys) mutation in the mtDNA is the causal genetic lesion underlying myoclonic epilepsy and ragged-red fiber (MERRF) syndrome. Skeletal muscle mtDNA of three patients with mitochondrial encephalomyopathy, characterized clinically by myoclonic epilepsy and ragged-red fiber (MERRF) syndrome, has been sequenced to determine the underlying molecular defect(s). An A-to-G substitution of nt 8344 in the tRNA(Lys) gene, a substitution suggested to be associated with MERRF encephalomyopathy, was detected in these patients. Abnormal patterns of mitochondrial translation products were observed in the skeletal muscle of patients, consistent with the expected consequential defect in protein synthesis. The genealogical studies of the three patients, as well as mtDNA from one published MERRF patient and from nine other normal and disease controls, revealed that the tRNA(Lys) mutations in the MERRF patients have arisen independently. These observations provided evidence that the base substitution is a causal mutation for MERRF.
Screening for dementia and investigating its causes. OBJECTIVE: To examine, from the perspective of primary care physicians, the value of mental status findings and ancillary tests in diagnosing dementia or its causes. DATA SOURCES: Studies identified using MEDLINE and bibliographies of pertinent articles. STUDY SELECTION: Selection based on availability of information on specific findings or tests, the criterion standard used to confirm diagnoses, the disease spectrum, and the richness of the reported data. DATA EXTRACTION: Data collected on sensitivity and specificity. In many cases, the originally reported data are re-analyzed to illustrate the usefulness of alternative cut-off values or to answer specific clinical questions. Likelihood ratios estimated to summarize test results. DATA SYNTHESIS: Probability of dementia is greatly reduced (likelihood ratio, 0.06 to 0.2) when either normal serial 7s, 7-digit span, 3-item recall, or clock drawing test results are obtained; abnormal results only moderately increase the odds of disease. Low (less than or equal to 20), intermediate (21 to 25), or high (greater than or equal to 26) scores on the Mini-Mental State Examination (MMSE) increase (likelihood ratio greater than or equal to 8.2), have little effect (likelihood ratio, 1.3 to 2.4), or decrease (likelihood ratio, 0.06 to 0.1) the odds of disease. The usefulness of tests to investigate the cause of dementia varies depending on the pretest probability of the specific condition. CONCLUSIONS: Several useful methods exist to screen for cognitive impairment, and clinicians need to be familiar with the strengths and limitations of their preferred screening methods. In investigating the cause of dementia, routinely obtaining a VDRL test, cerebral imaging studies, serum cobalamin level, or folate level is unwarranted.
Fluticasone propionate in Crohn's disease. Fluticasone propionate, a topically active corticosteroid of low systemic bioavailability after oral administration, has been used in a pilot study for the treatment of mild and moderately active Crohn's disease. Twelve patients received oral fluticasone propionate for three weeks, and the effects were monitored using the Crohn's disease activity index and by 111In granulocyte scanning, assessing inflammation from scan appearances, four day faecal excretion of radioactivity, and whole body excretion of radioactivity. All patients completed the trial. No serious side effects were reported. There was a significant fall in Crohn's disease activity index values over the three week treatment period (193 (84) v 122 (51), p less than 0.01). 111In leucocyte scan images were improved (seven patients) or unchanged (five patients). There was a significant fall in excretion of injected radioactivity calculated from whole body data (28 (21)% v 14 (0.7)%, p less than 0.05). There were no changes in plasma cortisol values, either basal or synacthen stimulated. Fluticasone propionate is a promising therapeutic agent for Crohn's disease that offers the possibility of controlling inflammation without inducing systemic corticosteroid side effects and which merits evaluation in a double blind trial versus conventional corticosteroids.
Intravenous phentolamine test: diagnostic and prognostic use in reflex sympathetic dystrophy. In some patients, ongoing and evoked neurogenic pain is relieved by pharmacological or destructive block of the sympathetic innervation of the affected part. In others, sympatholysis is ineffective. The present report shows that these two groups of patients can be distinguished by a safe and simple diagnostic test. Individuals in whom the pain was transiently relieved by intravenous phentolamine (Regitine) were very likely to respond favourably to subsequent sympatholytic treatment with i.v. regional guanethidine. Individuals in whom the phentolamine test was negative did not enjoy pain relief from this type of sympatholysis.
The moving, projected, annual total. A kinetic prognostic entity. A simple, inexpensive method of prognostically calculating and graphically recording annual case loads of the various deaths investigated by today's medicolegal offices is presented. Graphic depiction of the numerical data provides a convenient way to compare current prognostications with the records of preceding years.
Interleukin-2-induced lung injury is mediated by oxygen free radicals. Interleukin-2 therapy leads to respiratory dysfunction caused by increased vascular permeability. This study examines the role of oxygen-derived free radicals (OFR). Sheep (n = 6) with chronic lung lymph fistulae were given interleukin-2, 10(5) units/kg, as an intravenous bolus. The mean pulmonary artery pressure rose from 13 to 23 mm Hg (p less than 0.05) at 1 hour and remained elevated for 4 hours, although the pulmonary artery wedge pressure was unchanged at 4 mm Hg. Arterial oxygen tension fell from 88 to 77 mm Hg (p less than 0.05). Lung lymph flow rose from 2.2 to 6.4 ml/30 min (p less than 0.05) at 3 hours. This rise coincided with an increase in the lymph/plasma protein ratio from 0.67 to 0.77 (p less than 0.05) and lymph protein clearance from 1.5 to 4.4 ml/30 min (p less than 0.05), indicating increased lung microvascular permeability. Interleukin-2 led to transient increases in plasma thromboxane B2 from 168 to 388 pg/ml (p less than 0.05) and lung lymph thromboxane B2 from 235 to 694 pg/ml (p less than 0.05). The leukocyte count fell from 8156 to 4375/mm3 (p less than 0.05) primarily caused by a 78% drop in lymphocyte count. Platelet count declined from 292 to 184 X 10(3)/mm3 (p less than 0.05). Pretreatment with the hydroxyl radical scavenger dimethylthiourea, 1 gm/kg, intravenously, (n = 6) prevented the interleukin-2-induced increase in mean pulmonary artery pressure, lung lymph flow, lymph/plasma protein ration, lymph protein clearance, and thromboxane B2 levels in plasma and lung lymph. The arterial oxygen tension decreased from 85 to 80 mm Hg (p less than 0.05). The leukocyte count declined from 7854 to 6229/mm3 (p less than 0.05), but this was not as low nor as prolonged as the interleukin-2 group. Further, the decrease in platelet count was prevented (p less than 0.05). Interleukin-2 incubated with sheep or human leukocytes led to a dose-dependent increase in intracellular hydrogen peroxide production by neutrophils as measured by flow cytometry of dichlorofluorescein oxidation. These data indicate that interleukin-2 stimulates OFR generation and that OFR moderate the interleukin-2-induced increased lung permeability.
Alterations in circulating lymphocyte number and function after circulation through colorectal carcinomas. Thirty-six patients undergoing curative resection for colorectal cancer were studied to determine the effect of the tumor on lymphocytes circulating through it. In the venous blood draining the tumor, there was an increased percentage of natural killer (NK) cells (p = 0.001), no difference in overall NK cell function, and decreased T-lymphocyte activation (p = 0.035) and proliferation (p = 0.002) compared with the lymphocytes in the arterial blood supplying the tumor. There were no significant differences in the control group of 16 patients. Local effects of colorectal cancer may include the ability to down-regulate T and NK cell function while increasing the number of NK cells. Means of enhancing antitumor activity therapeutically in an adjuvant setting, possibly through the portal vein during surgery, need to be considered, especially in the light of the immunosuppressive effects of surgery.
Conventional therapy for idiopathic nephrotic syndrome in children. In children, the most frequent type of idiopathic nephrotic syndrome is the minimal-change nephrotic syndrome (MCNS). Its treatment is aimed at inducing remission, preventing relapses and avoiding side-effects. Minimal-change disease is responsive to immunosuppressive therapy. The conventional treatment consists of glucocorticosteroids and the most widely used derivative is prednisone. Initial treatment should be intensive, for example, prednisone for 12 weeks, in order to reduce the risk of subsequent relapse. Treatment of relapses should be standardized in order to categorize the patient's disease for further treatment. If a frequent relapser develops signs of steroid toxicity, alkylating drugs should be prescribed: cyclophosphamide or chlorambucil for eight weeks for frequent relapsers who are not steroid-dependent; cyclophosphamide for 12 weeks for those who are. In steroid-resistant cases, a renal biopsy is indicated and treatment should be administered according to histological changes.
Intravenous adenosine in the emergency department management of paroxysmal supraventricular tachycardia. STUDY PURPOSE: To evaluate the efficacy of adenosine in the treatment of emergency department patients with spontaneous paroxysmal supraventricular tachycardia (PSVT). DESIGN: An eight-month prospective outcome study. POPULATION: Patients 16 or more years old with PSVT by surface ECG criteria. Patients were excluded if there was clinical or hemodynamic evidence of hypoperfusion. MEASUREMENTS: Patient age, sex, PSVT rate, pretreatment blood pressure, history of cardiac disease, chronic drug therapy, and response to IV adenosine. RESULTS: Twenty-three patients with 27 episodes of suspected PSVT met inclusion criteria. After IV adenosine, two patients were found to have atrial flutter, and one was found to have ventricular tachycardia. Twenty-four episodes of PSVT were diagnosed in the remaining 21 patients. There were eight male and 13 female patients with a mean age of 51 +/- 19 years (range, 16 to 80 years). Sixteen patients related a history of cardiovascular disease. The mean QRS rate during PSVT was 181 +/- 23. Twenty-three of 24 episodes (96%) were converted to sinus rhythm within 20 to 45 seconds of adenosine therapy. However, 13 of 23 of initial conversions (57%) were followed by recurrence of PSVT within five minutes. All 13 recurrences required therapy with other antiarrhythmic drugs for conversion to and maintenance of sinus rhythm. Complications of adenosine were noted in only four patients and were transient and clinically unimportant. CONCLUSION: IV adenosine effectively terminates PSVT in ED patients with spontaneous PSVT; recurrence of PSVT after adenosine is common in the ED population and should be treated with other antiarrhythmic agents, not repeated doses of adenosine; adenosine is useful in the differential diagnosis of tachyarrhythmias; and doubling the initial dose of adenosine to 12 mg would increase the likelihood of conversion with the first dose.
Effect of taurine on total parenteral nutrition-associated cholestasis. A decrease in the formation/secretion of bile has been well documented in animals on total parenteral nutrition (TPN). Either an excess or an imbalance of amino acids (AA) has been most often implicated. In view of recent work showing that taurine promotes bile flow, bile acid secretion, and protects against hepatotoxic bile acids, the effect of adding taurine (15 mg/dL) to an AA solution was examined in guinea pigs on TPN for 3 days. The TPN-taurine group had a larger bile flow than the group without taurine and had bile acid secretory rates (BASR) similar to those of controls who were on saline by central catheter and had free access to food. Bile composition showed an increase in the secondary bile acid, 7-ketolithocholate and a concomitant decrease in chenodeoxycholate (CDC) in both experimental groups. Taurine led to a reversal of the usual predominance of glycine over taurine conjugated bile acids as well as to increases in HCO3 in cholesterol secretion. In response to a challenge with a large load of CDC, the TPN-taurine animals increased their BASR beyond those observed in the two other groups. These observations suggest that the addition of taurine to TPN solutions could play a role in the prevention of altered biliary function associated with AA solutions.
Prognosis of unresectable hepatocellular carcinoma: an evaluation based on multivariate analysis of 90 cases. A multivariate analysis of data from 90 patients with unresectable hepatocellular carcinoma was performed using Cox's regression model to identify factors possibly affecting their prognoses. Thirty-one patients underwent arterial anticancer chemotherapy, and the remaining 59 patients received transcatheter arterial embolization with anticancer agents. Four of 27 variables tested for all the patients (i.e., encapsulation [p less than 0.05], gross appearance of hepatocellular carcinoma [p less than 0.01], clinical stage [p less than 0.01] and therapy [p less than 0.01]) were found to be prognostically significant. Five of 27 variables tested were prognostically significant for the transcatheter arterial embolization group; they were an extension rate of hepatocellular carcinoma (p less than 0.01), encapsulation (p less than 0.01), alpha-fetoprotein (p less than 0.01), prothrombin time (p less than 0.01) and serum sodium (p less than 0.01). Regression equations were used to describe a prognostic index. A prognostic index was defined as the regression equation derived from the results of a total of 90 patients; PI-1 = eY, where PI-1 = prognostic index 1 Y = 1.549 (gross appearance of hepatocellular carcinoma - 1.344) + 0.778 (encapsulation - 1.622) + 0.818 (clinical stage - 1.800) + 1.760 (therapy - 1.344) and prognostic index 2, the regression equation derived from the results of the transcatheter arterial embolization group of patients; PI-2 = eY, where PI-2 = prognostic index 2 Y = 1.210 (extension rate of hepatocellular carcinoma - 1.576) + 1.179 (encapsulation - 1.475) + 0.0001277 (alpha-fetoprotein - 1420.792) -0.039 (prothrombin time - 72.237) - 0.214 (serum sodium - 138.427).
alpha 1-antagonists in the treatment of hypertension. A number of agents are now available to treat hypertension. One relatively new class of agents is the selective alpha 1-inhibitors, which have distinct advantages over earlier nonselective alpha-adrenergic receptor-blocking agents. Three alpha 1-inhibitors are reviewed in this article: prazosin, terazosin, and doxazosin. These alpha 1-inhibitors are similar in chemical structure and pharmacological action. alpha 1-Inhibitors lower blood pressure by reducing vascular tone in resistance and capacitance vessels. alpha 1-Inhibitors are similar in effectiveness in blood pressure lowering to other commonly used antihypertensive agents like the thiazide diuretic drugs and beta-blockers, which are efficacious as monotherapy in lowering pressure, as initial agents, or in combination with other antihypertensive agents in multidrug therapeutic regimens. alpha 1-Inhibitors are associated with a reasonably low incidence of serious adverse effects and are essentially free of any adverse metabolic effects. alpha 1-Inhibitors have been shown to beneficially effect blood lipids in several studies. The favorable lipid effect makes alpha 1-inhibitors especially appropriate to use in diabetic hypertensive and other patients with elevated serum lipid levels. The beneficial lipid effects may enhance the ability of alpha 1-inhibitors to prevent coronary heart disease, an outcome that has been difficult to demonstrate in thiazide-based trials.
Glycolytic inhibition and calcium overload as consequences of exogenously generated free radicals in rabbit hearts. Free radicals have been implicated in the pathogenesis of reperfusion injury, but it is unclear how they exert their deleterious effects on cellular metabolism. Several lines of indirect evidence suggest that free radicals elevate intracellular Ca2+ concentration ([Ca2+]i) and inhibit glycolysis as part of their mechanism of injury. We tested these ideas directly in hearts subjected to hydroxyl radicals produced by the Fenton and Haber-Weiss reactions. Nuclear magnetic resonance spectra were obtained from Langendorff-perfused rabbit hearts before, during, and after 4 min of perfusion with H2O2 (0.75 mM) and Fe(3+)-chelate (0.1 mM). Isovolumic left ventricular pressure exhibited progressive functional deterioration and contracture after exposure to H2O2 + Fe3+. Phosphorus nuclear magnetic resonance (NMR) spectra revealed partial ATP depletion and sugar phosphate accumulation indicative of glycolytic inhibition. To measure [Ca2+]i, fluorine NMR spectra were acquired in a separate group of hearts loaded with the Ca2+ indicator 5F-BAPTA [5,5'-difluoro derivative of 1,2-bis-(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid]. Mean time-averaged [Ca2+]i increased from 347 +/- 14 nM in control to 1,026 +/- 295 nM 4 min after free radical generation (means +/- SEM, n = 7), and remained elevated thereafter. We conclude that free radicals induce clear-cut, specific derangements of cellular metabolism in the form of glycolytic inhibition and calcium overload. The observed increase in [Ca2+]i suggests that the deleterious effects of free radicals are at least partially mediated by secondary changes in cellular calcium homeostasis.
Expression of specific UDP-glucuronosyltransferase isoforms in carcinogen-induced preneoplastic rat liver nodules. The expression of specific UDP-glucuronosyltransferase isoforms in 2-acetylaminofluorane-induced rat liver preneoplastic nodules was studied; livers from pair-fed littermates were used as controls. For comparison, liver and kidney from 3-methylcholanthrene-treated or untreated (control) rats were used. Steady-state UDP-glucuronosyltransferase mRNA levels were determined by Northern blot analysis or in situ hybridization of tissue sections using a 30-mer oligonucleotide specific for the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase (which is active toward 4-nitrophenol) or a double-stranded cDNA probe specific for androsterone-UDP-glucuronosyltransferase. For 3-methylcholanthrene-inducible UDP-glucuronosyltransferase, the mRNA level was very low in control liver; there was a 15-fold increase after 3-methylcholanthrene treatment. This mRNA was present at relatively high concentration in the kidney and there was a threefold increase after 3-methylcholanthrene administration. In livers with preneoplastic nodules 1 mo after cessation of carcinogen administration, this mRNA concentration was approximately 15 times greater than in control liver. Similar changes in the level of the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase were also observed by in situ hybridization of tissue sections. Immunocytochemical studies using an antiserum that recognizes the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase showed a marked increase in the concentration of this isoform in preneoplastic nodules compared with the adjacent nonnodular liver.
Developing anxiety-reduction procedures for a ventilator-dependent pediatric patient. This study evaluated two strategies to reduce anxiety behaviors which interfered with the daily tracheostomy care and ventilator maintenance of an eight-year-old ventilator-dependent boy. A multiple-baseline design (across ventilator and tracheostomy procedures) was used to evaluate the effectiveness of an information-only procedure and combined relaxation and cognitive distraction procedures. Partial-interval recording was used to measure heart rate, disruptive mouth noises, and demands and complaints to staff members. The patient's behavior did not change during a no-intervention baseline or during the information-only condition. Cognitive distraction and relaxation procedures were introduced, first during ventilator checks and then during tracheostomy care; corresponding decreases in heart rate, mouth noises, and demands and complaints were noted. Gains were maintained at one year follow-up. Results suggest that information alone may not effectively reduce anxiety behaviors for some ventilator-dependent patients unless additional anxiety-reduction procedures are implemented.
Comparative effects of oral molsidomine and nifedipine on methylergometrine-induced coronary artery spasm. Twelve consecutive patients (10 men and 2 women, mean +/- standard deviation age 49 +/- 9 years) with chest pain, angiographically normal coronary arteries and coronary artery spasm documented by methylergometrine testing received a single oral dose of molsidomine (4 mg) or nifedipine (10 mg) in a randomized, double-blind, crossover fashion at a 24-hour interval. Coronary artery spasm was documented during coronary angiography in 6 patients (left anterior descending artery, 3; right coronary artery, 2; left circumflex, 1). In the remaining 6 patients, coronary artery spasm was documented by a positive methylergometrine test performed at the bedside, which provoked ST-segment elevation in the inferior (n = 3), anterior (n = 1) or lateral (n = 2) leads. Ninety minutes after administration of the study medication, methylergometrine testing was performed at the bedside, using incremental doses of up to 0.4 mg of methylergometrine. After molsidomine, 10 patients (83%) had a negative and 2 had a positive test; after nifedipine, 9 patients (75%) had a negative and 3 a positive test. Only 1 patient had a methylergometrine test that remained positive after either molsidomine or nifedipine. Therefore, molsidomine appears as effective as nifedipine in suppressing methylergometrine-induced coronary artery spasm in patients with variant angina. In addition, patients not responding to 1 of the study medications may respond to the other.
Characterisation of inflammatory cells associated with "idiopathic retroperitoneal fibrosis". During ureterolysis in a patient with "idiopathic retroperitoneal fibrosis", fresh samples of peri-ureteric and peri-aortic tissue were obtained. An abdominal CT scan confirmed the peri-aortic distribution of the inflammation associated with advanced abdominal aortic atherosclerosis. Histology confirmed the presence of fibrosis and a variable chronic inflammatory cell infiltrate. Monoclonal antibodies were used to identify the inflammatory cells. B and T lymphocytes were present with the majority of T lymphocytes of the T helper phenotype. The majority of lymphocytes and macrophages and most vascular endothelial cells were HLA-DR positive. Ki67 and BerH2 staining was found in B cells and T helper cells, indicating that these cells were proliferating and activated. These findings compare with the characterisation of inflammatory cells associated with "inflammatory aneurysms" and with the inflammatory cells present in the spectrum of inflammation seen as a complication of advanced atherosclerosis--conditions known as "chronic peri-aortitis". It is suggested that our findings support the view that idiopathic retroperitoneal fibrosis represents clinical chronic peri-aortitis seen in an undilated aorta.
Internal jugular vein thrombosis after ovulation induction with gonadotropins. An unusual case of ovarian hyperstimulation syndrome complicated by internal jugular vein and mediastinal thrombosis is presented. Hemoconcentration and perhaps immobilization appear to be the most probable causative factors. The patient was successfully treated with heparin anticoagulation. An uneventful twin pregnancy resulted from the stimulation cycle.