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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sepsis and endotoxaemia initiate the generation of thrombin, which is responsible for the conversion of fibrinogen to fibrin, platelet aggregation and acts as an inflammatory mediator affecting numerous types of cells, including myocardial, smooth muscle and endothelial cells. Human Gram-negative septic shock, frequently seen in intensive care units, is a condition with high mortality. This condition can be replicated in the endotoxaemic pig. As many of the toxic effects of sepsis are due to thrombin generation, it was of interest to study, using this porcine experimental septic shock model, whether inhibition of thrombin could alleviate the effects of endotoxaemia. For this purpose melagatran, a direct synthetic thrombin inhibitor with a molecular weight of 429 Da, was employed. Melagatran does not significantly interact with any other enzymes in the coagulation cascade or fibrinolytic enzymes aside from thrombin. Furthermore, melagatran does not require endogenous co-factors such as antithrombin or heparin co-Factor II for its antithrombin effect, which is important, as these inhibitors are often consumed in septic patients. We have shown that melagatran exerts a beneficial effect on renal function, as evaluated by plasma creatinine and urinary output, during experimental septic shock. These effects were most pronounced during the later phase of the experimental period, after the infusion of melagatran had been discontinued. Prevention of intrarenal coagulation may be attributable to this finding. In addition, melagatran had beneficial effects on systemic haemodynamics (left ventricular stroke work index, pulmonary capillary wedge pressure and systemic vascular resistance index) in endotoxaemic pigs. This result may be explained by the ability of melagatran to inhibit thrombin, thereby counteracting thrombin's cellular effects. Thus, it can be seen, using this experimental model of septic shock, that melagatran may help to alleviate some of the damaging effects of endotoxaemia, although more research is required to test this further.
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PMID:Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock. 1106 Jul 33

The aim of this study was to identify hereditary and acquired risk-factors as they are related to the occurrence of stroke in children. We identified 21 children with stroke. A search of the Factor V Leiden mutation, the Factor II G20210A variant, and the thermolabile variant of methylenetetrahydrofolate reductase was performed in patients and in a control group (n = 115). We identified risk factors of acquired and/or hereditary nature for stroke in 19 of 21 children. Eleven children had three or more risk factors, seven had two risk factors, and one child had only one risk factor. We found three carriers (14.3%) of the Factor V Leiden mutation, two carriers (9.5%) of the Factor II G20210A variant, eleven (52.4%) thermolabile variant of methylenetetrahydrofolate reductase heterozygote carriers, and one (4.8%) homozygotes for this variant. Frequencies of the Factor V Leiden mutation and the Factor II variant were higher in patients than in controls, suggesting that these variants are associated with an increased risk of stroke in childhood. Homozygosity for the thermolabile variant of methylenetetrahydrofolate reductase was equally frequent amongst patients and controls. Our study confirms that stroke in children is commonly associated with a combination of multiple risk factors, both genetic and acquired, and that the Factor V Leiden mutation and the Factor II G20210A variant are predisposing factors for this situation.
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PMID:Inherited and acquired risk factors and their combined effects in pediatric stroke. 1269 65

Hyperhomocysteinemia is an independent risk factor for atherothrombotic cerebral stroke. Vitamin B12 and folic acid are important determinants of homocysteine metabolism. We aimed to evaluate the relationship, if present, between vitamin B12 and folic acid levels and acute cerebral stroke in this study. Blood aliquots drawn within 24 hours after the stroke from hospitalized patients (n=66) with the diagnosis of acute ischemic cerebrovascular episode and also blood samples from 38 healthy controls without any vascular risk factor were analyzed. With a competitive, chemoluminescence assay, serum levels of vitamin B12 and folic acid were measured in blood samples taken within 24 hours after the stroke. The differences and correlations were tested using frequency test, student-t test and multivariate analysis. Mean serum vitamin B12 levels were significantly lower in the patients than in the control subjects, 245.40 (S.D.: 72.9) and 343.2 (S.D.: 113.0) pg/ml respectively (p=0.0001). This difference was independent from other risk factors. Likewise, mean serum folic acid levels were lower in the patients than in the control subjects, 4.62 (S.D.: 1.94) and 5.97 (S.D.: 1.19) ng/ml, respectively (p=0.003). Mean serum levels of vitamin B12 and folate at the convalescence phase were 253.05 (S.D.: 68.78) pg/ml and 4.48 (S.D.: 2.08) ng/ml, respectively; the values obtained at the acute phase were not significantly different from the values obtained at the convalescence phase. We conclude that low vitamin B12 and folic acid concentrations are associated with an increased risk of stroke, and the relationship for vitamin B12 is independent from the other known modifiable stroke risk factors. For understanding the effects of B12 and folate in stroke patients, more detailed follow-up studies with long period are needed.
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PMID:Serum vitamin B12 and folic Acid levels in acute cerebral atherothrombotic infarction. 1538 96

The present review focuses on the B-vitamins, i.e. folate, vitamin B12, vitamin B6 and riboflavin, that are involved in homocysteine metabolism. Homocysteine is a S-containing amino acid and its plasma concentrations can be raised by various constitutive, genetic and lifestyle factors, by inadequate nutrient status and as a result of systemic disease and various drugs. Hyperhomocysteinaemia is a modest independent predictor of CVD and stroke, but causality and the precise pathophysiological mechanism(s) of homocysteine action remain unproven. The predominant nutritional cause of raised plasma homocysteine in most healthy populations is folate insufficiency. Vitamin B12 and, to a lesser extent, vitamin B6 are also effective at lowering plasma homocysteine, especially after homocysteine lowering by folic acid in those individuals presenting with raised plasma homocysteine. However, riboflavin supplementation appears to be effective at lowering plasma homocysteine only in those individuals homozygous for the T allele of the C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. This gene codes for the MTHFR enzyme that produces methyltetrahydrofolate, which, in turn, is a substrate for the remethylation of homocysteine by the vitamin B12-dependent enzyme methionine synthase. Individuals with the MTHFR 677TT genotype are genetically predisposed to elevated plasma homocysteine, and in most populations have a markedly higher risk of CVD.
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PMID:B-vitamins, homocysteine metabolism and CVD. 1583 Nov 32

Genetic factors are involved in the individual predisposition to develop ischemic stroke (IS). In the present study we tested the role of the Factor VII G10976A and -C122T polymorphisms on the susceptibility to develop IS in a genetically homogenous and clinically well ascertained case-control study including 294 cases (median age 75 years; 176 males/118 females) and 286 controls (median age 73 years; 163 males/123 females) in Sardinia, Italy. In addition, we carried out an exploratory analysis with respect to other frequently studied polymorphisms of haemostatic factor genes:Factor II G20210A, Factor V G1691A,,Fibrinogen alpha-chain Thr312Ala, Fibrinogen beta-chain -C148T, Factor XIII G185T, GPIIb/IIIa T1565C. Among all the genes tested, FVII -C122T showed a significant, independent contribution to IS predisposition both in crude and adjusted analyses (crude OR 1.52, 95% CI 1.09-2.10, P=0.013; adjusted OR 1.48, 95% CI 1.04-2.09, P=0.028, respectively). Haplotype analyses revealed a conserved population structure with high linkage disequilibrium between both FVII mutations tested. Blood levels of FVII had an inverse relationship with the polymorphism involved. Apart from genetic influence, there was a significant role for hypertension (OR=1.7, 95% CI 1.19-2.43, P=0.003), hypercholesterolemia (OR=2.21, 95% CI 1.38-3.54, P=0.001) and atrial fibrillation (OR=1.66, 95% CI 1.06-2.58, P=0.026) on IS occurrence. In summary, we describe evidence for a possible direct association of FVII gene molecular variants with the occurrence of IS in a genetically homogenous human sample.
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PMID:Polymorphisms in prothrombotic genes and their impact on ischemic stroke in a Sardinian population. 1596 94

Only one mutation in the prothrombin gene (Factor II), 20210G>A, has been definitively associated with an increased risk for venous thrombosis. Using hybridization probe analysis for mutation detection on the LightCycler (Roche Molecular Biochemicals), we identified seven patient samples with atypical melt curve patterns. Sequence analyses of each of these samples revealed heterozygosity for a C to T transition at position 20209. As in other reported cases, each of the apparently unrelated patients was of African-American descent, suggesting that the variant is population specific. Two patients were referred for testing due to a history of stroke, one with a right major coronary artery embolic stroke and the other with a right cerebellar stroke. A third patient had chronic renal failure secondary to hypertension with a reported family history of renal failure. Three patients had a history of multiple pregnancy losses. The last patient had a kidney transplant for end stage renal disease secondary to glomerulonephritis. She was being evaluated for a second transplant, but to our knowledge, had a negative history of venous thrombosis. The prevalence and the clinical significance of the prothrombin 20209C>T mutation is unknown. Recently reported functional studies revealed conflicting results. The clinical utility of testing for and reporting this variant remains unresolved.
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PMID:The Prothrombin 20209C>T Sequence Variant: To Test or Not to Test. 1763 Apr 71

The long-term outcome of patients with methylmalonic aciduria (MMA) is still uncertain due to a high frequency of complications such as chronic renal failure and metabolic stroke. The understanding of this disease is hampered by a huge variation in the management of these patients. The major aim of this study was to evaluate the current practice in different European metabolic centres. A standardized questionnaire was sent to 20 metabolic centres asking for standard procedures for confirmation of diagnosis, testing cobalamin responsiveness, dietary treatment, pharmacotherapy, and biochemical and clinical monitoring. Sixteen of 20 metabolic centres (80%) returned questionnaires on 183 patients: 89 of the patients were classified as mut(0), 36 as mut(-), 13 as cblA, 7 as cblB, and 38 as cblA/B. (1) Confirmation of diagnosis: All centres investigate enzyme activity by propionate fixation in fibroblasts; six centres also perform mutation analysis. (2) Cobalamin response: Ten centres follow standardized protocols showing large variations. A reliable exclusion of nonspecific effects has not yet been achieved by these protocols. (3) Long-term treatment: In cobalamin-responsive patients, most centres use hydroxocobalamin (1-14 mg/week i.m. or 5-20 mg/week orally), while two centres use cyanocobalamin. All cobalamin-nonresponsive patients and most cobalamin-responsive patients are supplemented with L: -carnitine (50-100 mg/kg per day). Fourteen centres use intestinal decontamination by antibiotic therapy. Most centres follow D-A-CH (n = 6) or Dewey (n = 4) recommendations for protein requirements. Fourteen centres regularly use precursor-free amino acid supplements. Standardized monitoring protocols are available in seven centres, again showing high variability.
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PMID:Diagnostic work-up and management of patients with isolated methylmalonic acidurias in European metabolic centres. 1856 34

This study examined a possible association between the mutations related to Factor V Leiden and Factor II (prothrombin) and stroke in Saudi neonates. A multiplex PCR was established to detect Factor V Leiden G1691A and prothrombin G20210A mutations in 72 neonatal stroke subjects and 70 healthy adult controls with no family history of thromboembolic diseases. The frequency of the homozygous normal genotype (GG) of both genes was found to be significantly lower in the stroke subjects than in the controls (P < 0.0001). The stroke cases also had higher frequencies of the combined Factor II heterozygous mutant form (GA) and the homozygous normal Factor V (GG) (P < 0.0001) and of the combined heterozygous Factor V and the homozygous normal Factor II genotypes (GG) (P = 0.0) than controls. The study concluded that prothrombin and Factor V Leiden may be important risk factors for neonatal stroke in Saudi children.
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PMID:Molecular characterization of factor V leiden G1691A and prothrombin G20210A mutations in Saudi newborns with stroke. 2146 67

Stroke in children is a heterogeneous disorder. Over 100 risk factors for stroke have been reported and genetic predisposition to stroke has been established. The most frequently reported risk factors are congenital heart malformations, hemolytic anemias, collagen vascular diseases, some rare inborn metabolic disorders, trauma, infection and thrombophilia. The aim of this article is to provide an overview of investigated inherited prothrombotic risk factors in children with first ischemic stroke. Various prothrombotic risk factors have been investigated in pediatric stroke including elevated homocysteine and lipoprotein (a), antithrombin, protein C and protein S deficiency, Factor V Leiden, Factor II G20210A and plasminogen activator inhibitor-1 4G/5G polymorphism. Despite similar criteria for inclusion of different studies in meta-analyses investigating first ischemic stroke in children, the obtained results were not consistent for all prothrombotic risk factors. The discrepancies found could be explained by methodological issues like different sample sizes, patient populations included and lack of controls. In order to provide the necessary power for randomized control trials, multi-center, multi-national approaches like International Pediatric Stroke Study have been initiated with the aim to describe risk factors for childhood stroke and explore their relationship with presentation, age, geography, and infarct characteristics. Although it is evident from numerous studies that the frequency of inherited prothrombotic factors is increased in pediatric stroke, single thrombophilia does not fully explain stroke in a child as it represents only a mild risk factor. Further studies are needed, as improved understanding of underlying mechanisms will improve primary and secondary prevention of childhood stroke.
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PMID:Inherited prothrombotic risk factors in children with first ischemic stroke. 2309 62

We report three male patients of younger age group presented with acute vein thrombosis of different sites, right lower limb, cortical venous sinuses thrombosis with cerebral vascular accident and third case is mesenteric vein thrombosis. All patients were Vegetarian, had low level of cobalamin with marked hyper homocysteinemia with normal serum and red cell folic acid. The low Cobalamin level was not suspected secondary to pernicious anemia, based on the fact that there was no evidence of atrophic gastritis and an absence of antiparietal cell antibodies. There were no evident of immobilization, recent surgery, malignancy, antiphospholipid antibody, myeloproliferative disorder, and hormone replacement therapy. No deficiencies in protein C, protein S, or antithrombin III, normal factor V Leiden, no prothrombin gene mutation 20210A and no clone for paroxysmal nocturnal hemoglobin-urea were detected, no cause was found for the thrombosis apart from their secondary hyperhomocysteinemia.
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PMID:Three different presentation of same pathophysiology. 2332 77


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