shukoor65/lab-rag-model huggingface dataset:
Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis, complement, and renal function after cardiopulmonary bypass. The use of aprotinin to reduce blood loss after cardiopulmonary bypass is under debate. Concern has been raised about the renal effects of aprotinin. We administered a mean aprotinin dose of 4.2 x 10(6) kallikrein-inhibiting units to 13 patients with coronary disease undergoing cardiopulmonary bypass for 74 +/- 5 minutes (mean +/- standard error of the mean); 13 comparable patients having cardiopulmonary bypass served as control subjects, and all were studied postoperatively for 24 hours. Aprotinin reduced postoperative blood loss by 50% (p = 0.0082). Two of the 13 patients who received aprotinin needed one red cell unit each versus a total of 18 units in eight of 13 control patients (p = 0.0096). Blood pressure, hemoglobin value and serum protein concentration were higher after operation in the aprotinin group (p less than 0.05 to p less than 0.01). Platelet counts did not differ, but plasma thromboxane was lower in aprotinin recipients (p less than 0.001). In control patients fibrinogen degradation products (D dimer) doubled, and alpha 2-antiplasmin activity was halved during and after cardiopulmonary bypass (p less than 0.01 to p less than 0.001), whereas aprotinin patients showed no changes. The complement breakdown products C4a, C3a, and C3dg as well as C9 neoantigen increased from prebypass baseline in both groups (p less than 0.001); the increment of C3a and C3dg was greater in the aprotinin than in the control patients (p less than 0.001). Serum electrolytes, osmolality, and creatinine remained normal in both groups of patients. Creatinine clearance was normal or above normal and virtually identical in both groups. Osmolar clearance and fractional sodium excretion were higher in the aprotinin group than in the control group shortly after cardiopulmonary bypass (p less than 0.05 to p less than 0.01); renal function was unremarkable the next morning. No adverse clinical effects attributable to aprotinin were seen. In summary, aprotinin offers advantages for cardiopulmonary bypass.
Naevocytic naevi with vascular-like spaces. Fourteen cases of naevocytic naevi with anastomising lacunae suggestive of vascular spaces are reported. The cells lining these lacunae were consistent with naevus cells, being positive for vimentin and S100 protein and negative for factor VIII-related antigen and Ulex europaeus I. The cells were not surrounded by laminin or type IV collagen. We suggest the formation of these vascular-like spaces may be due to defective production or increased degradation of components of the basement membrane with a consequent lack of cohesion.
The effect of ethanol on the uptake, binding, and desialylation of transferrin by rat liver endothelium: implications in the pathogenesis of alcohol-associated hepatic siderosis. Chronic alcoholism has been reported to be associated with a reduced carbohydrate content of transferrin (TF), particularly, its reduced sialylation state. Low sialylation state of TF now serves as an objective marker of chronic alcohol abuse. To investigate the pathophysiological significance of this finding in relation to hepatic siderosis, also commonly associated with chronic alcoholism, the authors have investigated the effect of ethanol on the uptake, binding, and desialylation of transferrin by isolated rat liver endothelium in vitro. In pulse-chase experiments, transferrin labeled with either 125I (protein-labeled) or 3H (sialic acid-labeled) was incubated with isolated, fractionated liver endothelium with and without ethanol, and the supernates were subjected to column chromatography using RCA120- agarose. Incubation of the endothelium with increasing concentrations of ethanol resulted in a progressive increase in the desialylation rate of transferrin which was maximal when 160 mM concentration of ethanol was used. These data indicate that ethanol significantly promotes the desialylation of transferrin by rat liver endothelium. The implications of these findings in the pathogenesis of hepatic siderosis of the alcoholic are discussed.
Endothelial cell damage by Walker carcinosarcoma cells is dependent on vitronectin receptor-mediated tumor cell adhesion. The transport of cancer cells from blood vessels to extravascular tissue is a critical step in metastasis, where endothelial cells and the vascular basement membrane act as barriers to cell traffic. Because endothelial injury can facilitate the metastasis of intravascular cancer cells in vivo, the authors have studied in vitro the free-radical-mediated endothelial damage caused by the rat Walker 256 carcinosarcoma (W256) cell after stimulation with 10(-6) mol/l (molar) phorbol ester. Here the authors have examined the hypothesis that W256 cell-mediated endothelial injury is dependent on adhesion between the effector and target cells. Attachment of phorbol 12-myristate, 13-acetate (PMA)-stimulated W256 cells to endothelial monolayers was increased 1.8 +/- 0.1-fold and damage (3H-2-deoxyglucose release from labeled endothelium) 1.4 +/- 0.1-fold after 4-hour pretreatment of the endothelium with 10 ng/ml recombinant human interleukin-1 alpha (rIL-1 alpha). Under various assay conditions, the release of 3H-2-deoxyglucose correlated directly with tumor cell adhesion (r = 0.98, P less than 0.005). In the presence of a polyclonal anti-vitronectin receptor antiserum, adhesion of stimulated W256 cells to rIL-1 alpha-treated monolayers was inhibited by 39% +/- 2%, and 3H-2-deoxyglucose release was inhibited by 53% +/- 13%. Immunoblot analysis and immunofluorescence flow cytometry demonstrated that the endothelial cells but not the W256 cells expressed vitronectin receptor (VnR) on their cell surface. The surface expression of VnR by endothelial cells was increased 1.9 +/- 0.1-fold after 4 hours' incubation with rIL-1 alpha. The authors conclude that W256 cell-mediated endothelial damage is dependent on cell adhesion, which, in turn, is partly regulated by the expression of VnR on the endothelial cell surface.
Prospective neuropathological validation of Hachinski's Ischaemic Score in dementias. The sensitivity and specificity of Hachinski's Ischaemic Score (IS) in the diagnosis of the vascular aetiology of dementia was studied in a series of 32 demented patients, dementia of the Alzheimer type (16), multi-infarct dementia (7), mixed dementia (6), Pick's disease (3), with neuropathological diagnosis as the point of reference. The IS distinguished between primary degenerative dementia and multi-infarct or mixed dementia. As single features of the IS "a positive history of stroke" and "a fluctuating course" showed differing prevalences in the latter two diagnostic categories. The IS labelled 21% of patients with primary degenerative dementia as having a vascular aetiology. The uncritical application of the IS to large samples in epidemiological studies may cause incorrect labelling of a significant proportion of patients with primary degenerative dementia as vascular dementia. These results are based on observations of long-term inpatients and depend on neuropathological criteria. While the definite diagnosis of DAT by threshold criteria concerning plaque and tangle counts is well established, neither clinical nor pathological evidence of stroke necessarily means that cerebrovascular disease has anything to do with a patient's dementia.
Adrenergic receptor responsiveness and congestive heart failure. Our knowledge and understanding of the structure, mechanism of action and regulation of receptor-adenylate cyclase systems have increased dramatically in the last few years. A family of receptors (including the beta-adrenergic receptors) and guanine nucleotide regulatory proteins (G proteins) have been purified and cloned. Structure-function studies are beginning to provide insight into how the various components of the transmembrane signaling apparatus interact to promote alterations in the activity of the effector systems. Much effort has been devoted to understanding how various pathophysiologic conditions, such as ischemia or congestive heart failure, and the therapeutic methods used to treat such conditions perturb or regulate receptor systems. It has become abundantly clear that such regulation does occur but is not restricted to simple alterations in receptor number, and may well involve covalent modification (phosphorylation) of receptors or alteration in the ability of receptors to interact with G proteins. In addition, regulation of the quantity or functionality of the various G proteins and the catalytic unit of adenylate cyclase itself appear to occur. For example, recent evidence suggests that congestive heart failure in humans is associated with a decreased number of beta-adrenergic receptors as well as an increased quantity of the inhibitory G protein (Gi). These alterations may provide important insight into how to develop new therapeutic methods. Mechanisms generally responsible for transmembrane signaling, how the components are regulated by pathophysiologic conditions, and drugs used to treat disease states are discussed in detail.
Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A. recombinant Factor VIII Study Group BACKGROUND. Current treatment of hemophilia A, a hereditary disorder affecting approximately 1 in 10,000 males, relies on plasma-derived factor VIII concentrates. We tested the safety and efficacy of a recombinant factor VIII preparation for the treatment of this disorder. METHODS. We conducted the investigation in three stages: comparing the pharmacokinetics of plasma-derived and recombinant factor VIII, assessing the efficacy of recombinant factor VIII for home therapy, and assessing its efficacy for major surgical procedures and hemorrhage. A total of 107 subjects with hemophilia, 20 of whom had not been treated previously, enrolled in the investigation. RESULTS. The in vivo recovery and elimination half-lives of recombinant factor VIII equaled or exceeded those of plasma-derived factor VIII. Seventy-six subjects participated in a home-treatment program, using recombinant factor VIII for 69 to 807 days (median, 618); home diaries of 56 subjects treated for 5 months were analyzed. Of 540 bleeding episodes, 399 (73.9 percent) required only one treatment with recombinant factor VIII. The projected annual consumption of recombinant factor VIII was similar to that of plasma-derived factor VIII concentrate. Twenty-six subjects received recombinant factor VIII for 22 surgical procedures and 10 serious hemorrhages; hemostasis was excellent in all cases. De novo formation of inhibitors occurred in only 1 of 85 previously treated subjects. Inhibitor antibodies also developed in 6 of 21 children, 20 of whom had not previously been treated; 5 had low levels (less than or equal to 7.5 Bethesda units) despite continued treatment with recombinant factor VIII. There was no evidence of new formation of antibody to foreign proteins, and recombinant factor VIII was well tolerated. CONCLUSIONS. Recombinant factor VIII has biologic activity comparable to that of plasma factor VIII and is safe and efficacious for the treatment of hemophilia A.
The time course and magnitude of spontaneous recovery of parkinsonism produced by intracarotid administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to monkeys. We studied rhesus monkeys with hemiparkinsonism or bilateral parkinsonism produced by unilateral or bilateral intracarotid administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Using a standardized clinical rating scale, 4 hemiparkinsonian monkeys showed a 13 to 56% (mean, 36%) spontaneous improvement during an observation period of up to 25 weeks. Generally, recovery leveled off after 14 weeks. Four bilaterally parkinsonian monkeys showed a 5 to 42% (mean, 22%) improvement over a period of up to 30 weeks. Our findings emphasize that spontaneous recovery is a potentially confounding characteristic of this monkey model when used for assessing novel antiparkinsonian therapies.
The value of MCA, CA 15-3, CEA and CA-125 for discrimination between metastatic breast cancer and adenocarcinoma of other primary sites. MCA, CA 15-3, CEA and CA 125 were determined in the serum of 49 patients with metastatic breast cancer and 38 patients with metastatic adenocarcinoma of other primary sites. By using the 99th percentile of the normal value distribution as the cut-off point, the positive predictive value (PV+) was found to be 85% (95% CI 76-94) for MCA, and 71% (95% CI 61-81) for CA 15-3. When receiver-operating-characteristic (ROC) curves were constructed, the PV+ for CA 15-3 was increased to 82% (95% CI 72-92), using 60 U ml-1 as the cut-off point. With the exception of two patients who had a slightly elevated MCA, MCA and CA 15-3 identified the same patients with breast cancer. By combining a positive MCA or CA 15-3 with a negative CEA and CA 125, further improvement of the PV+ could be achieved; 100% (95% CI 91-100). We conclude that MCA and CA 15-3 may play a useful role in discrimination between patients with metastatic breast cancer and those with adenocarcinoma of other primary sites.
A comparison of the caffeine halothane muscle contracture test with the molecular genetic diagnosis of malignant hyperthermia Malignant hyperthermia (MH) is currently diagnosed by the caffeine-halothane contracture (CHC) test. In a previous study, this test was used to establish linkage between the human gene for MH susceptibility and the ryanodine receptor (RYR) gene. The current study extends the genetic linkage analysis to a large French-Canadian kindred. In this family, genetic linkage between RYR and MH genes was not demonstrable using the currently recommended limits of normal for the CHC test in the identification of MH-susceptible individuals. With CHC test threshold limits below those currently recommended, however, complete linkage between the RYR and MH genes was seen. Comparisons of CHC test results with genetic linkage studies will increase the diagnostic accuracy of both tests as well as generate new insights into the biology of MH.
Risk factors and the natural history of coronary heart disease in blacks. Contrary to early impressions of blacks' relative immunity to CHD, it is now clear that African Americans experience greater mortality from CHD than whites. The natural history of CHD differs between blacks and whites in three important respects: First, greater prevalence of established risk factors among blacks suggests that they may be at greater risk for heart disease than their white counterparts. Second, health care seeking differences are evident between blacks and whites, leading to lower rates of identification of early disease and slower seeking of services for acute events. However, risk factor differences and health care seeking behaviors do not appear to account for all of the differences in the natural history of heart disease between the ethnic groups, such as survival rate differences during treatment. Economic factors appear to account for only a portion of these differences in risk factors and health care seeking. Beyond differences in risk factors and health care seeking, other, as yet undetermined, factors seem to be involved. These unknown influences could include physiologic, behavioral, and/or psychologic differences.
Cough-variant asthma in children and adults: case reports and review. Two cases of cough-variant asthma are presented, one in an adult and one in a child. We discuss the diagnosis, treatment, and course of this common, yet often unrecognized entity. The keys to diagnosis are a typical history, clinical suspicion, and subsequent response to bronchodilator therapy. Treatment of cough-variant asthma is no different from that of classic asthma.
Intentional and unintentional ureteral surgical treatment in gynecologic procedures. During a period of slightly over nine years, 4,195 extensive gynecologic procedures were performed and 40 patients required ureteral operations, with the ureteral injury unintentional in 16 patients. Extensive complications occurred in seven of 40 patients; in two of three patients in whom the injury was recognized postoperatively, nephrectomy was required. Roentgenographic imaging of the genitourinary tract prior to operation did not prevent injury nor did attempts at identification of the ureter. The majority of ureteral repairs were accomplished by ureteroneocystotomy. In selected patients, placement of percutaneous or indwelling ureteral stent prevented extensive surgical intervention.
Localization and in vitro actions of atrial natriuretic peptide in the cat carotid body. Previous studies of atrial natriuretic peptide (ANP) have indicated that its release from the heart and from discrete areas of the central nervous system evokes coordinated physiological and behavioral adjustments that mitigate the adverse hypertensive effects of volume overload and/or acute increases in sodium intake. Because the reflex activity initiated by arterial chemoreceptors of the carotid body directly contributes to the integrated regulation of systemic blood pressure, we have investigated the possibility that ANP has a significant role in the chemosensory process as well. Our immunocytochemical studies show that ANP-like immunoreactivity is present in the preneural chemosensitive type I cells in the cat carotid body. Furthermore we found that the biologically active ANP fragment atriopeptin III is a potent inhibitor of carotid sinus nerve activity evoked by hypoxia. Our findings suggest that circulating and/or endogenous ANP may modulate carotid body function as part of a coordinated response to changes in systemic volume and solute balance.
An apparent cluster of congenital hypopituitarism in central Massachusetts: magnetic resonance imaging and hormonal studies. Between 1980 and 1989, five infants (four males and one female) with congenital hypopituitarism were born within a relatively sparsely populated area of central Massachusetts, an incidence 25-fold greater than expected. In all infants the pituitary stalk was undetectable on magnetic resonance imaging, and a bright spot on T-1 weighted imaging, probably representing posterior pituitary tissue, was found ectopically located inferior to the median eminence. The height of the anterior pituitary remnant on magnetic resonance imaging varied from undetectable to 4 mm, and similarly, on hormonal testing a spectrum of deficiencies of GH, TSH, ACTH, and gonadotropin was observed. The magnitude of the hypopituitarism was less in the three patients whose anterior pituitary remnant was greater than 2 mm, and in them, TRH testing resulted in exaggerated TSH and PRL responses, suggestive of hypothalamic disease. In contrast, in the other two patients in whom the anterior pituitary remnant was less than 2 mm in height, hypopituitarism was more severe, and TRH administration resulted in little if any TSH or PRL response, characteristic of pituitary disease. The size of the anterior pituitary remnant correlated significantly with that of the ectopic posterior pituitary bright spot (P less than 0.005). We conclude that patients with congenital hypopituitarism may exhibit a spectrum of hormonal responses, varying from findings typical of hypothalamic to those characteristic of primary pituitary disease. The pattern of hormonal responsiveness is dependent on the quantity of residual anterior pituitary tissue and probably results from abnormal transport of the hypothalamic hypophyseal releasing hormones rather than to any putative hypothalamic abnormality. The significant correlation between the size and function of the anterior pituitary gland and the size of the ectopic posterior pituitary remnant suggests that the fetal pituitary gland may secrete a factor necessary for the growth and descent of the neuroepithelium to form the infundibulum and posterior pituitary gland.
Dyslipidemic effects of cigarette smoking on beta-blocker-induced serum lipid changes in systemic hypertension. To assess the effects of beta blockers on lipids and apolipoproteins in cigarette smokers and nonsmokers, 330 patients with systemic hypertension received 1 month of placebo and 6 months of beta-blocker monotherapy. Serum total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoproteins A1 and B were measured. Total cholesterol increased with propranolol (smokers vs nonsmokers, 8 vs 2%); increased for smokers and decreased for nonsmokers with atenolol (8 vs -3%), metoprolol (6 vs -1%) and pindolol (7 vs -6%); and decreased for both groups with celiprolol (-3 vs -10%). HDL cholesterol decreased with propranolol (smokers vs nonsmokers, -8 vs -18%), atenolol (-7 vs -2%) and metoprolol (-12 vs -1%); increased for smokers and decreased for nonsmokers with pindolol (11 vs -2%); and increased for both groups with celiprolol (5 vs 6%). Similar trends were observed with LDL cholesterol and the total/HDL cholesterol ratio. It is concluded that early noncardioselective beta blockers such as propranolol have significant dyslipidemic effects in both smokers and nonsmokers. Cardioselective drugs such as atenolol and metoprolol, or drugs with partial agonist activity such as pindolol, have variable effects. Celiprolol, a new, highly cardioselective beta 1 blocker with partial beta 2 agonist activity and vasodilatory properties, has favorable effects on lipids and minimizes the dyslipidemic effects associated with smoking.
A combined approach for purging multidrug-resistant leukemic cell lines in bone marrow using a monoclonal antibody and chemotherapy. Selective removal of malignant cells (purging) from bone marrow (BM) is a concern in autologous BM transplantation (ABMT). Use of vincristine, etoposide, or doxorubicin for purging could be rendered ineffective by the presence of multidrug-resistant (MDR) tumor cells. To circumvent this particular problem, we investigated whether 17F9, a monoclonal IgG2b antibody directed against the cell surface product of the MDR gene, P-glycoprotein, is effective in selective removal of MDR cells from BM when used with rabbit complement (C'). Using two different cell lines we have demonstrated that 17F9 + C' selectively lyses MDR-positive cells. Three rounds of antibody + C' resulted in 96.4% +/- 3.6% kill of K562/DOX and 100% +/- 0% of CEM/VLB cells. Mixtures of malignant cells and normal BM resulted in 99.85% removal of K562/DOX and 99.91% removal of CEM/VLB clonogenic cells. This treatment did not affect normal committed precursors compared with C' alone. The addition of the cytotoxic agent etoposide (VP-16) following antibody purging results in a 4.6 log reduction of malignant cells. Furthermore, this antibody was effective when used against patients' leukemic blasts. These results suggest the use of 17F9 + C' is effective and selective for removal of MDR cells from BM before ABMT and the addition of VP-16 enhances the purging efficacy.
Nontraumatic surgical emergencies in children. Clinical conditions that require operative intervention are frequent causes of emergency department visits. Common causes such as pyloric stenosis, intussusception, inguinal hernias, torsion of the testicle, and ingested foreign bodies are discussed, and aids in diagnosis and early intervention are addressed. Conditions that mimic surgical problems also are mentioned.