shukoor65/lab-rag-model huggingface dataset:
Effect of intrathecal fibrinolysis on cerebrospinal fluid absorption after experimental subarachnoid hemorrhage. The effect of intrathecal fibrinolysis on cerebrospinal fluid (CSF) absorption was investigated after experimental subarachnoid hemorrhage (SAH). In 11 cats, SAH was induced by intracisternal application of 1 to 4 ml of fresh autologous blood. Thirty minutes after the experimental SAH, the CSF outflow resistance was found to be elevated from a median of 77 mm Hg/ml/min (range 41.3 to 109 mm Hg/ml/min) to a median of 580 mm Hg/ml/min (range 104 to 7000 mm Hg/ml/min). A logarithmic relationship could be demonstrated between the volume of subarachnoid blood and the elevation of the CSF outflow resistance. The intrathecal application of 2 mg of recombinant tissue plasminogen activator (rt-PA), which is a fibrinolytic substance suitable for lysis of subarachnoid blood clots in man, resulted in an almost total restoration of CSF absorption after experimental SAH. The CSF outflow resistance after SAH was lowered by application of rt-PA from a median of 1028.05 mm Hg/ml/min (range 394 to 7000 mm Hg/ml/min) to 79 mm Hg/ml/min (range 56.7 to 223 mm Hg/ml/min). It is concluded that the impairment of CSF absorption after SAH may play an important role in the pathogenesis of post-hemorrhagic vasospasm.
Chronic reversal of hemifield loss after intraocular pressure lowering in advanced glaucoma. Lowering intraocular pressure in two cases of severe glaucoma was associated with a chronic reversal of hemifield loss, as documented by automated threshold perimetry. In the first case, a small central 10 degrees island of vision expanded to 40 degrees in both hemifields eight months after intraocular pressure lowering by filtration surgery. The mean deviation of the central 30 degrees field improved by more than 14dB or 1.4 log units. To our knowledge, this case represents the greatest degree of reversal of chronic visual field loss reported in the literature. In the second case, a small central 10 degrees island of vision slowly expanded to 40 degrees in the inferior hemifield over a three-year period.
IIB osteosarcoma. Current management, local control, and survival statistics--Sao Paulo, Brazil. Ninety-two patients with IIB osteosarcoma of the extremities were treated with intraarterial (IA) cisplatinum (CDDP) followed by surgery [amputation (61.6%) or resection with endoprosthesis (38.4%)]. Postoperative chemotherapy alternating adriamycin and CDDP was used. The total three-year survival was 62.1%, and the disease-free survival was 41.1%. The pathologic evaluation of the degree of tumor necrosis in response to the IA CDDP showed that in 53.2%, the necrosis was over 90%. The multivariate analysis of prognostic factors has shown that the highest survival was among females with tumors smaller than 15 cm. Patients with lesions equal to or larger than 15 cm were three times as likely to die of the disease. A second, more aggressive study is now underway, in which high dose methotrexate (HDMTX) is preoperatively combined with adriamycin and CDDP. Following operation, ifosfamide is added to the cases with a smaller degree of tumor necrosis, while the other group of patients will continue with HDMTX, in addition to CDDP and adriamycin (these last two drugs are used in both arms). Until now, complete remission has been achieved in 82% and 86%, respectively, with a follow-up examination varying from four to 26 months (average, 14 months). This is of extreme importance, because the majority of the authors' patients have tumors at initial evaluation larger than 10 cm in diameter.
Expression of the c-myc proto-oncogene in multiple myeloma and chronic lymphocytic leukemia: an in situ analysis. The c-myc gene plays a pivotal role in mediating the competence state for cell cycle transversion. This biologic role is in contradiction to reports of elevated expression of the gene in multiple myeloma, a tumor with restricted self-renewal capacity. To more clearly define the role of this gene in plasma cells of myeloma patients, c-myc messenger RNA (mRNA) and/or oncoprotein expression were semiquantitatively analyzed on the single cell level in 19 cases of multiple myeloma, among them 1 biclonal case and 1 case with coexistent chronic lymphocytic leukemia (CLL). Performing anti-sense/mRNA in situ hybridization, mature c-myc gene transcripts were detected in 92% (12 of 13) of cases and could definitely be attributed to the plasma cells by our study. The number of Ki 67-positive plasma cells actively passing the cell cycle was less than 1% and independent of c-myc gene expression. However, because the presence of the 152-c-MYC epitope was correlated to extent of marrow plasmacytosis (r = .64; P = .043) and content of plasmablasts (P = .09), the c-myc gene might serve a function different from proliferative activity, but also associated with tumor cell mass. In CLL cells (21 of 22 cases) and their benign counterparts, ie, bone marrow and peripheral blood lymphocytes, the anti-sense/c-myc mRNA hybridization signals remained below the threshold considered as cutpoint between negative and positive. The low amounts of c-myc transcripts were correlated to neither stage of disease (P = .52) nor lymphocyte counts (P = .24). Because the numbers of peripheral blood lymphoma cells were independent of tumor mass and of c-myc gene transcripts expressed, peripheral blood lymphocytosis might more likely reflect homing processes than proliferative activity in CLL.
The diabetic foot: consequences of delayed treatment and referral. The pathophysiology of foot problems in diabetic patients is poorly understood by many physicians. Two major factors that frequently lead to a delay in appropriate treatment with subsequent limb loss are failure to appreciate the presence and severity of underlying infection and attribution of gangrene of the toe and forefoot to microvascular disease. To evaluate the consequences of delayed recognition and treatment, we reviewed the records of 55 diabetic patients with localized gangrene or infection of the forefoot in 62 limbs, treated consecutively on a single vascular surgical service over a 2-year period using a standard protocol. All appropriately treated neuropathic ulcers and forefoot infections healed in patients with palpable pedal pulses. If foot pulses were absent and arteriography confirmed large-vessel occlusive disease, foot lesions and infections likewise healed if concomitant revascularization was done. In our series, 33 bypasses were required because of severe atherosclerotic occlusive disease. Only one patient had "unreconstructable" arterial disease. Limb salvage was 86% at a mean follow-up of 12.4 months. In 16 of the patients (29%), there was a prolonged delay between initial treatment and referral for definitive care. The specific causes of delay were underestimation of the severity of foot infection in 10 patients, and lack of recognition of ischemia due to large-vessel occlusive disease in six. These delays led to more proximal levels of amputation in six patients, including three below-knee amputations in patients with limbs that were initially salvageable.
Efficacy and toxicity of pentostam against Panamanian mucosal leishmaniasis. We tested the World Health Organization (WHO) recommended treatment for mucosal leishmaniasis in 16 Panamanians with disease due to Leishmania braziliensis panamensis. Disease was mild in this population because it was limited to the nasal mucosa and only one patient had septal perforation. The patients were administered 20 mg antimony (in the form of Pentostam) per kg intravenously each day for 28 days. Ten patients completed therapy and were cured at 12 month follow-up. Three patients completed therapy, healed their lesions, but relapsed at the six or 12 month follow-up. Three patients terminated therapy prematurely because of liver enzyme elevations in conjunction with either EKG abnormalities or musculoskeletal complaints; none of these patients were healed. This study indicates that in patients with mild mucosal leishmaniasis, the WHO regimen is curative in 77% patients who complete treatment and in 63% of all patients.
Intracoronary thrombus formation causes focal vasoconstriction of epicardial arteries in patients with coronary artery disease. BACKGROUND. Experimental studies have demonstrated that intracoronary platelet aggregation and thrombus formation may induce marked vasoconstriction of epicardial arteries with endothelial injury. METHODS AND RESULTS. To examine the effects of intracoronary thrombus formation on coronary vasomotor tone of human epicardial arteries in vivo, we studied 15 patients who developed intracoronary thrombi adherent to the guide wire during balloon dilatation. Epicardial artery luminal area was evaluated by quantitative coronary angiography proximal and distal to the site of intracoronary thrombus formation and in a reference vessel before and after thrombus formation as well as after intracoronary injection of 0.2-0.3 mg nitroglycerin. All artery segments distal to the site of thrombus formation showed vasoconstriction with a luminal area reduction of -27.4 +/- 17.1% (p less than 0.001), whereas proximal vessel segments and reference vessels not manipulated during percutaneous transluminal coronary angioplasty did not demonstrate any significant luminal area changes during thrombus formation. Angiographic measurements after advancing the guide wire with the adherent thrombus (performed in six of the 15 patients) revealed in all patients that vasoconstriction did develop at a new site distal to the thrombus persistence of the initial vasoconstriction now residing proximal to the thrombus. Thus, there was a sequential association between thrombus formation and subsequent distal vasoconstriction. Intracoronary injection of nitroglycerin abolished the thrombus-induced vasoconstriction. No significant luminal area changes were observed in 20 patients without angiographic evidence of intracoronary thrombus formation. CONCLUSIONS. Intracoronary thrombus formation during percutaneous transluminal coronary angioplasty causes focal vasoconstriction of epicardial arteries in patients with coronary artery disease. Although caution must be advised in the extrapolation of this phenomenon, which was observed in a manipulated artery during coronary angioplasty, the vasoconstrictor response to intracoronary thrombus formation in vivo may play an important role in the dynamic mechanisms of acute coronary heart disease syndromes.
Overview: rationale of thrombolysis in treating acute myocardial infarction. Treatment of coronary thrombosis with thrombolytic agents was first introduced in the 1950s. Clinical trials, primarily with streptokinase during the 1960s and 1970s, addressed the effects of thrombolysis on mortality rates after acute myocardial infarction, but were inconclusive and largely ignored. In 1976, Chazov et al. from the Soviet Union demonstrated that intracoronary streptokinase could produce prompt recanalization of a totally occluded infarct-related artery. In 1980, DeWood et al. demonstrated that 87% of patients with classic Q-wave myocardial infarction had total occlusion from coronary thrombosis of the infarct-related artery when studied during the first 4 hours of their infarction and that 65% of these arteries were still occluded when patients were studied between 12 and 24 hours after infarction. These observations stimulated renewed interest in thrombolytic therapy for acute myocardial infarction. Mortality trials have subsequently demonstrated that agents such as recombinant tissue plasminogen activator, streptokinase, and anisoylated plasminogen streptokinase activator complex remarkably reduce early mortality rates among patients with acute myocardial infarction when treatment is instituted within the first 6 hours of infarction. Benefit has yet to be demonstrated, however, in patients with acute myocardial infarction characterized by ST-segment depression. This whole area is currently under study by the TIMI investigators. TIMI-3B is a mortality study in which patients with either non-Q-wave myocardial infarction or unstable angina with rest pain are randomly assigned to receive either tissue plasminogen activator or placebo. Results of this trial will help us in the future to determine the appropriate role of thrombolytic therapy in treating acute ischemic syndromes other than transmural myocardial infarction.
Expression of HIV-1 in the cerebrospinal fluid detected by the polymerase chain reaction and its correlation with central nervous system disease. The polymerase chain reaction (PCR) was used to detect HIV-1 sequences (gag, pol, and env) in the cerebrospinal fluid (CSF) and serum samples from 53 HIV-1-positive patients and the results correlated with clinical evidence of neurological disease. Twenty-three out of 24 patients with neurological disease had HIV-1-specific sequences in CSF compared with four out of 20 asymptomatic patients who had no evidence of neurological involvement. The detection of HIV RNA sequences by PCR in the CSF of HIV-positive patients may provide early, rapid and direct evidence of neurological involvement in asymptomatic subjects.
Autocrine stimulation by erythropoietin and autonomous growth of human erythroid leukemic cells in vitro. Autonomous colony formation is a frequent event in erythroleukemia. In 13 cases of early erythroid leukemias, we investigated whether erythropoietin (Epo) autocrine stimulation was responsible for the growth factor autonomy. Epo transcripts were detected by Northern blotting in cells from one patient. These cells also expressed an Epo receptor (1,000 receptors per cell) with a 420-pM affinity and Epo was detected in the supernatant of cultured cells. In 8 of the 13 cases, Epo transcripts were revealed by the polymerase chain reaction ranging from 0.5 to 500 copies per cell. In situ hybridization proved that these Epo transcripts were present in the blast cells. No Epo gene abnormalities were detected by Southern blotting. In two cases, leukemic cells were grown in the presence of Epo-neutralizing antibodies or Epo antisense oligomers. In one case, the antibody significantly reduced autonomous growth. In contrast, the antibody had no effect in the second case in which blast cells transcribed the Epo gene at a low level. However, Epo antisense oligomers partially inhibited autonomous growth. This inhibition was reversed by addition of exogenous Epo. Overall, these results suggest that an extracellular or intracellular autocrine Epo stimulation occurs in some cases of erythroid malignancies.
Edematous pancreatitis associated with intravenous pentamidine. A 37-year-old black man with presumed Pneumocystis carinii pneumonia who was treated with systemic IV pentamidine had fatal pancreatitis and massive hepatomegaly. Fatal pancreatitis can occur with no hemorrhagic changes seen at autopsy. Awareness of the relationship between pentamidine and pancreatitis should be emphasized. With current clinical trials testing other routes of administration, fatal complications associated with IV pentamidine therapy will be minimized.
A component of calcium-activated potassium channels encoded by the Drosophila slo locus. Calcium-activated potassium channels mediate many biologically important functions in electrically excitable cells. Despite recent progress in the molecular analysis of voltage-activated K+ channels, Ca(2+)-activated K+ channels have not been similarly characterized. The Drosophila slowpoke (slo) locus, mutations of which specifically abolish a Ca(2+)-activated K+ current in muscles and neurons, provides an opportunity for molecular characterization of these channels. Genomic and complementary DNA clones from the slo locus were isolated and sequenced. The polypeptide predicted by slo is similar to voltage-activated K+ channel polypeptides in discrete domains known to be essential for function. Thus, these results indicate that slo encodes a structural component of Ca(2+)-activated K+ channels.
The effects of benzodiazepine-receptor antagonists and partial inverse agonists on acute hepatic encephalopathy in the rat. Two benzodiazepine-receptor partial inverse agonists (Ro 15-4513, Ro 15-3505) and one benzodiazepine-receptor antagonist (flumazenil) were administered to rats with hepatic encephalopathy due to acute liver ischemia. Significant improvement (P less than 0.002) of both the clinical grade of hepatic encephalopathy and the electroencephalographic abnormalities was observed after administration of the benzodiazepine-receptor partial inverse agonists: comatose rats with no spontaneous righting reflex regained consciousness immediately after injection of the drug. Only slight improvement in clinical hepatic encephalopathy grade was seen after administration of 25 mg/kg of flumazenil. The present data strongly support a role of increased gamma-aminobutyric acid-ergic tone in the pathogenesis of acute hepatic encephalopathy and provide a rationale for trials of benzodiazepine-receptor partial inverse agonists to restore consciousness in hepatic encephalopathy in humans in the near future.
Treatment of primary sclerosing cholangitis with oral methotrexate. Ten patients with well-documented primary sclerosing cholangitis who had no signs of portal hypertension or liver failure were treated with oral pulse methotrexate for at least 1 yr. The methotrexate dose averaged 15 mg/wk (0.2 mg/kg/wk). All six patients who were symptomatic became asymptomatic within 1-5 months of starting methotrexate. Biochemical tests of liver function improved in all patients. The alkaline phosphatase value decreased from a mean (+/-SD) of 373 +/- 210 IU to 140 +/- 77 IU (p = 0.0008), the mean alanine aminotransferase (ALT) from 115 +/- 74 to 76 +/- 79 U/L (p = 0.005), and the mean aspartate aminotransferase (AST) value from 88 +/- 37 to 57 +/- 40 U/L (p = 0.007). The improvement in mean bilirubin (1.19 +/- 1.41 to 0.67 +/- 0.25 mg/dl) was not statistically significant. Serum albumin remained normal (3.97 +/- 0.46 to 4.22 +/- 0.36 g/dl). Nine patients had a repeat liver biopsy after 1 yr of methotrexate therapy. Six of the nine showed histologic improvement with a reduction in inflammation. The other three liver biopsies were unchanged. Repeat cholangiograms were done in six patients. Two showed improvement. In one of the two, who had early disease, the cholangiogram became normal, and the liver biopsy was markedly improved. The other four cholangiograms showed no progression of disease. No toxicity was detected in these 10 patients. These results suggest that low-dose oral methotrexate therapy is effective in primary sclerosing cholangitis if treatment is begun before signs of portal hypertension or liver failure occur.
Molecular basis for elliptocytosis associated with glycophorin C and D deficiency in the Leach phenotype. Glycophorin C (GPC) and glycophorin D (GPD) are highly glycosylated integral membrane proteins of human erythrocytes encoded by the same gene and associated with expression of Gerbich blood group system antigens. GPC/D deficiency (the Leach phenotype) is a rare condition usually found after identification of Gerbich blood group system antibodies in persons undergoing prenatal or pretransfusion evaluation. In all cases, the Leach phenotype has been associated with elliptocytosis. Characterization of the molecular basis of this phenotype in three previously uninvestigated families has shown that the most common genetic basis of GPC/D deficiency is deletion of exons 3 and 4 of the GPC gene. However, in one family, the Leach phenotype appeared due to a deletion of one nucleotide in exon 3, causing a frameshift mutation in the messenger RNA and premature generation of a stop codon. The GPC and GPD protein sequences are therefore interrupted in the extracellular domain and probably intracellularly degraded.
A prospective evaluation of elevated serum theophylline concentrations to determine if high concentrations are predictable. PURPOSE: To evaluate prospectively whether serum theophylline concentrations of 25 mg/L and greater were predictable (and presumably preventable) by use of basic pharmacokinetic calculations. DESIGN: Prospective study. PATIENTS: Fifty-five patients with a serum theophylline concentration of at least 25.0 mg/L were evaluated initially and if subsequent elevated theophylline concentrations occurred. INTERVENTIONS: The predicted steady-state serum theophylline concentration was calculated from the dosage rate divided by the predicted clearance to determine how many elevated concentrations (greater than 20 mg/L) were predictable. Predicted clearances were 0.04 L/kg/hour for normal subjects less than 70 years of age and 0.02 L/kg/hour for patients with congestive heart failure, chronic obstructive pulmonary disease, or liver disease. Estimated clearances were determined and compared with predicted clearances. If patients did not have steady-state concentrations, additional calculations were made. MAIN RESULTS: From 6,368 consecutive theophylline determinations, 69 (1.08%) samples from 55 patients were 25 mg/L or higher. Predictably high concentrations occurred in 23 of 33 (69.7%) fully evaluable cases. These concentrations occurred because of a failure to consider decreased elimination clearance from congestive heart failure, chronic obstructive pulmonary disease, or hepatic disease. Five fatalities occurred, and in two cases, theophylline appeared to contribute to the patient's death. Three other patients experienced syncope. The predicted elimination clearance of theophylline of 0.02 L/kg/hour was too high in eight patients over 70 years old with cardiac or pulmonary disease. Nursing and pharmacy oversights were identified as three patients were given two theophylline products simultaneously. CONCLUSIONS: Most elevated theophylline concentrations are predictable (and preventable) by basic pharmacokinetic calculations. Patients experiencing elevated theophylline concentrations often had comorbid conditions and were greater than 60 years of age. The dosage rate of theophylline (mg/hour) can be estimated from predicted clearance (L/kg/hour) times desired steady-state serum concentration (mg/L).
Primary pulmonary hypertension. Its association with microangiopathic hemolytic anemia and thrombocytopenia. Four patients with primary pulmonary hypertension, microangiopathic hemolysis, and thrombocytopenia were seen at the Charleston (WVa) Area Medical Center between 1983 and 1988. Characteristic laboratory and clinical features of these patients were the following: mild anemia, reticulocytosis, low serum haptoglobin value, microangiopathic red blood cell changes on peripheral blood smear, mild to moderate thrombocytopenia, normal clotting studies (ie, prothrombin time, partial thromboplastin time, fibrinogen), negative direct Coombs' test, negative glucose water test, normal serum urea nitrogen and creatinine levels, lack of improvement of hemolysis and thrombocytopenia in response to vasodilators or calcium channel blockers, and severe plexiform lesions in the pulmonary vasculature with fibrin deposition at autopsy. The hemolysis and thrombocytopenia probably developed as a result of flow through the fibrin deposition in the plexiform lesions in the pulmonary circulation and subsequent shearing of red blood cells and platelets.