Frequency of atrial septal aneurysms in patients with cerebral ischemic events.
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BACKGROUND: Atrial septal aneurysm (ASA) is a putative risk factor for cardioembolism. However, the frequency of ASA in the general population has not been adequately determined. Therefore, the frequency in patients with cerebral ischemic events, compared with the frequency in the general population, is poorly defined. We sought to determine the frequency of ASA in the general population and to compare the frequency of ASA in patients with cerebral ischemic events with the frequency in the general population. METHODS AND RESULTS: The frequency of ASA in the population was determined in 363 subjects, a sample of the participants in the Stroke Prevention: Assessment of Risk in a Community study (control subjects), and was compared with the frequency in 355 age- and sex-matched patients undergoing transesophageal echocardiography in search of a cardiac source of embolism after a focal cerebral ischemic event. The proportion with ASA was 7.9% in patients versus 2.2% in control subjects (P=0.002; odds ratio of ASA, 3.65; 95% CI, 1.64 to 8.13, in patients versus control subjects). Patent foramen ovale (PFO) was detected with contrast injections in 56% of subjects with ASA. The presence of ASA predicted the presence of PFO (odds ratio of PFO, 4.57; 95% CI, 2.18 to 9.57, in subjects with versus those without ASA). In 86% of subjects with ASA and cerebral ischemia, transesophageal echocardiography did not detect an alternative source of cardioembolism other than an associated PFO. CONCLUSIONS: The prevalence of ASA based on this population-based study is 2.2%. The frequency of ASA is relatively higher in patients evaluated with transesophageal echocardiography after a cerebral ischemic event. ASA is frequently associated with PFO, suggesting paradoxical embolism as a mechanism of cardioembolism. In patients with cerebral ischemia and ASA, ASA (with or without PFO) commonly is the only potential cardioembolic source detected with transesophageal echocardiography. (+info)
Manganese superoxide dismutase mediates the early release of mitochondrial cytochrome C and subsequent DNA fragmentation after permanent focal cerebral ischemia in mice.
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Recent studies have shown that release of mitochondrial cytochrome c is a critical step in the apoptosis process. We have reported that cytosolic redistribution of cytochrome c in vivo occurred after transient focal cerebral ischemia (FCI) in rats and preceded the peak of DNA fragmentation. Although the involvement of reactive oxygen species in the cytosolic redistribution of cytochrome c in vitro has been suggested, the detailed mechanism by which cytochrome c release is mediated in vivo has not yet been established. Also, the role of mitochondrial oxidative stress in cytochrome c release is unknown. These issues can be addressed using knock-out mutants that are deficient in the level of the mitochondrial antioxidant manganese superoxide dismutase (Mn-SOD). In this study we examined the subcellular distribution of the cytochrome c protein in both wild-type mice and heterozygous knock-outs of the Mn-SOD gene (Sod2 -/+) after permanent FCI, in which apoptosis is assumed to participate. Cytosolic cytochrome c was detected as early as 1 hr after ischemia, and correspondingly, mitochondrial cytochrome c showed a significant reduction 2 hr after ischemia (p < 0.01). Cytosolic accumulation of cytochrome c was significantly higher in Sod2 -/+ mice compared with wild-type animals (p < 0.05). N-benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone (z-VAD.FMK), a nonselective caspase inhibitor, did not affect cytochrome c release after ischemia. A significant amount of DNA laddering was detected 24 hr after ischemia and increased in Sod2 -/+ mice. These data suggest that Mn-SOD blocks cytosolic release of cytochrome c and could thereby reduce apoptosis after permanent FCI. (+info)
Hyperhomocysteinemia: a risk factor for ischemic stroke in children.
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BACKGROUND: Moderate hyperhomocysteinemia is a risk factor for arterial vascular disease and venous thrombosis in adults. We performed a case-control study to assess a possible relation between moderate hyperhomocysteinemia and ischemic stroke in Dutch children (age range, 0 to 18 years). METHODS AND RESULTS: We measured plasma total homocysteine levels (tHcy) in 45 patients with ischemic stroke and in 234 controls. Hyperhomocysteinemia was defined as a tHcy above the 95th percentile regression line for the respective age of the controls. Hyperhomocysteinemia was present in 8 (18%) of the 45 patients with ischemic stroke. The odds ratio was 4.4 (95% CI, 1.7 to 11.6). CONCLUSIONS: We conclude that moderate hyperhomocysteinemia is a risk factor for ischemic stroke in children. (+info)
Protection against ischemic damage by adenosine amine congener, a potent and selective adenosine A1 receptor agonist.
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Although the selectivity and potency of adenosine amine congener (ADAC) at adenosine A1 receptors are similar to other highly selective agonists at this receptor type, the chemical structure of the N6 substituent is completely different. We now demonstrate that the characteristics of the therapeutic profile of ADAC are distinct from those observed during our previous studies of adenosine A1 receptor agonist-mediated neuroprotection. Most significantly, chronic treatment with low microgram doses of ADAC (25-100 microg/kg) protects against both mortality and neuronal damage induced by 10 min bilateral carotid occlusion in gerbils. At higher chronic doses, the statistical significance of the protective effect is lost. Acute preischemic administration of the drug at 75-200 microg/kg also results in a statistically significant reduction of postischemic mortality and morbidity. These data indicate that, contrary to other adenosine A1 receptor agonists whose chronic administration enhances postocclusive brain damage, ADAC may be a promising agent in treatment of both acute (e.g., cerebral ischemia) and chronic (seizures) disorders of the central nervous system in which adenosine A receptors appear to be involved. (+info)
Hyperhomocysteinemia and hypofibrinolysis in young adults with ischemic stroke.
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BACKGROUND AND PURPOSE: Data from epidemiological and case-control studies suggest that increased total homocysteine (tHcy) levels are associated with increased risk for thromboembolic disease. The mechanisms by which hyperhomocysteinemia contributes to thrombogenesis are incompletely understood. The main objectives of this study of young ischemic stroke patients were (1) to examine fasting and post-methionine load levels of tHcy, (2) to ascertain the genotype frequency of the C677CT mutation in the methylenetetrahydrofolate reductase gene (TT genotype), and (3) to study the possible interaction between plasma tHcy levels and fibrinolytic factors. METHODS: This case-control study was based on 80 consecutive patients aged 18 to 44 years admitted between January 1992 and May 1996 as a result of a first-ever ischemic stroke. Forty-one healthy control subjects were recruited. Measurement of fasting tHcy and post-methionine load levels and evaluation of the fibrinolytic system were undertaken at least 3 months (mean, 5.1+/-1. 9 months) after admission. Genotyping of the methylenetetrahydrofolate reductase gene was performed. RESULTS: Although the increase after methionine loading (ie, postload tHcy minus fasting-level tHcy) was significantly higher among patients, there was no difference in fasting and postload tHcy levels. After adjustment for conventional risk factors, elevated postload increase tHcy levels were associated with a 4.8-fold increased risk of ischemic stroke. There was no difference between patients and control subjects in either TT genotype frequency or T allele frequency. Abnormal response to methionine loading was associated with higher tissue plasminogen activator (tPA) mass concentration, higher plasminogen activator inhibitor-1 levels, and lower tPA activity. After adjustment for age, sex, body mass index, serum cholesterol, and triglycerides, an abnormal increase in postload tHcy levels remained significantly associated with tPA mass concentration levels (P=0.03). CONCLUSIONS: A moderately elevated increase in tHcy levels after methionine loading was associated with an increased risk for ischemic stroke in young adults. In contrast, fasting tHcy levels did not differ between patients and controls. A moderately elevated increase in tHcy after methionine loading may provide a additional thrombogenic risk mediated in part by interactions with the fibrinolytic system. In young stroke patients, a methionine loading test to detect hyperhomocysteinemia should always be considered in the convalescent phase of the disease. (+info)
C-reactive protein and outcome after ischemic stroke.
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BACKGROUND AND PURPOSE: Elevated concentrations of the acute-phase reactant C-reactive protein (CRP) predict ischemic cardiac events in both hospital- and population-based studies and may signify a role for inflammation in the destabilization of cardiovascular disease. We examined the relationship between CRP and outcome after acute ischemic stroke. METHODS: This was a subgroup analysis from a prospective observational study based in a University Hospital Acute Stroke Unit serving a population of approximately 260 000. Survival time and cause of death for up to 4 years after the index stroke were determined and related to CRP concentration within 72 hours of stroke and known prognostic variables by a Cox proportional hazards regression model. RESULTS: Ischemic stroke was diagnosed in 228 of 283 consecutive admissions. Median follow-up was 959 days. Geometric mean CRP concentration was 10.1 mg/L. Survival in those with CRP >10.1 mg/L was significantly worse than in those with CRP 10.1 mg/L and 63% of deaths in those with CRP +info)
Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke.
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BACKGROUND AND PURPOSE: Diaspirin cross-linked hemoglobin (DCLHb) is a purified, cell-free human hemoglobin solution. In animal stroke models its use led to a significant reduction in the extent of brain injury. The primary objective of this study was to evaluate the safety of DCLHb in patients with acute ischemic stroke. METHODS: DCLHb or saline was administered to 85 patients with acute ischemic stroke in the anterior circulation, within 18 hours of onset of symptoms, in a multicenter, randomized, single-blind, dose-finding, controlled safety trial, consisting of 3 parts: 12 doses of 25, 50, and 100 mg/kg DCLHb over 72 hours. RESULTS: DCLHb caused a rapid rise in mean arterial blood pressure. The pressor effect was not accompanied by complications or excessive need for antihypertensive treatment. Two patients in the 100 mg/kg group had adverse events that were possibly drug related: one suffered fatal brain and pulmonary edema, the other transient renal and pancreatic insufficiency. Multivariate logistic regression analysis showed that a severe stroke at baseline and treatment with DCLHb (OR, 4.0; CI, 1.4 to 12.0) were independent predictors of a worse outcome (Rankin Scale score of 3 to 6) at 3 months. CONCLUSIONS: Outcome scale scores were worse in the DCLHb group, and more serious adverse events and deaths occurred in DCLHb-treated patients than in control patients. We recommend that additional safety studies be performed, preferably with a second generation, genetically engineered hemoglobin. (+info)
Ischemic stroke. Impact of a recent myocardial infarction.
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BACKGROUND AND PURPOSE: The risk of ischemic stroke is increased after a myocardial infarction. We quantified the stroke risk and evaluated ischemic stroke characteristics after an acute myocardial infarction. METHODS: A case-control study including patients with first-ever stroke was undertaken. Cases (n=103) were recorded prospectively in the population-based Northern Sweden World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study. Two controls per case with a stroke but without a recent myocardial infarction were matched for age, sex, and year of stroke onset. RESULTS: The sudden onset of neurological symptoms (76.7% versus 54.9%, P<0.001), impairment of consciousness (35.0% versus 18.4%, P<0.01), and a progression in neurological deficits (19.4% versus 8.7%, P<0.01) were more common in cases, while the onset of stroke during sleep was rarer in cases (6.8% versus 21.4%, P<0.01). In cases and controls, the clinical subclasses of stroke were as follows: total anterior circulation infarcts, 51.5% versus 37.9% (P<0.05); partial anterior circulation infarcts, 28.2% versus 26.7% (P=NS); lacunar infarcts, 4.8% versus 27.2% (P<0.001); and posterior circulation infarcts, 15.5% versus 8.2% (P=0.051). During the first 28 days after myocardial infarction, the daily rate of stroke declined rapidly from approximately 9 to 1 stroke per 10 000 myocardial infarction patients compared with an age-adjusted average daily stroke rate of 0.14 per 10 000 in the MONICA population. CONCLUSIONS: We conclude that the clinical characteristics of the stroke differ between patients with and without a recent myocardial infarction. The risk of a first-ever ischemic stroke is highest during the first few days after a myocardial infarction, but it then declines rapidly, and the absolute number of stroke events is low. (+info)