Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aspirin is only modestly effective in the secondary prevention after cerebral ischemia. Studies in other vascular disorders suggest that anticoagulant drugs in patients with cerebral ischemia of presumed arterial (noncardiac) origin might be more effective. The aim of the Stroke Prevention in Reversible Ischemia Trial (SPIRIT) therefore was to compare the efficacy and safety of 30 mg aspirin daily and oral anticoagulation (international normalized ratio [INR] 3.0-4.5). Patients referred to a neurologist in one of 58 collaborating centers because of a transient ischemic attack or minor ischemic stroke (Rankin grade < or =3) were eligible. Randomization was concealed, treatment assignment was open, and assessment of outcome events was masked. The primary measure of outcome was the composite event "death from all vascular causes, nonfatal stroke, nonfatal myocardial infarction, or nonfatal major bleeding complication." The trial was stopped at the first interim analysis. A total of 1,316 patients participated; their mean follow-up was 14 months. There was an excess of the primary outcome event in the anticoagulated group (81 of 651) versus 36 of 665 in the aspirin group (hazard ratio, 2.3; 95% confidence interval [CI], 1.6-3.5). This excess could be attributed to 53 major bleeding complications (27 intracranial; 17 fatal) during anticoagulant therapy versus 6 on aspirin (3 intracranial; 1 fatal). The bleeding incidence increased by a factor of 1.43 (95% CI, 0.96-2.13) for each 0.5 unit increase of the achieved INR. Anticoagulant therapy with an INR range of 3.0 to 4.5 in patients after cerebral ischemia of presumed arterial origin is not safe. The efficacy of a lower intensity anticoagulation regimen remains to be determined.
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PMID:A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group. 940 77

Rats were subjected to transient cerebral ischemia by four-vessel occlusion of 30 min duration, followed by 2, 4, 8 or 24 h of recovery. Total RNA was isolated from the cerebral cortex and hippocampus, and reverse transcribed into cDNA. Hsp40 mRNA levels of samples were evaluated by quantitative PCR. Transient cerebral ischemia caused a marked increase in hsp40 mRNA levels to about 250% and 500% of control in the cortex and hippocampus respectively. Since hsp40 exerts a critical regulatory function in the HSC70/HSP70 ATPase cycle, an ischemia-induced rise of hsp40 mRNA levels could mark the onset of the recovery process after transient ischemia. On the other hand, the inhibitory action of hsp40 on P58 (a protein that activates protein synthesis by blocking the interferon-induced double-stranded RNA-activated protein kinase PKR) implies that the rise in hsp40 expression may equally well contribute to the post-ischemic suppression of protein synthesis.
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PMID:Effects of transient cerebral ischemia on hsp40 mRNA levels in rat brain. 958 51

The aim of this study was to define the accuracy of 99mTc-ethyl cysteinate dimer-single photon emission computed tomography (99mTc-ECD-SPECT) in distinguishing transient ischemic attack from completed ischemic stroke at early stages after the onset of symptoms. In a prospective study we examined 82 patients within 6 hours after the onset of symptoms (neurologic deficit caused by middle cerebral artery ischemia) using both 99mTc-ECD-SPECT and computed tomography (CT). The follow-up was based on Scandinavian Stroke Scale (SSS) 24 hours and 5-7 days, as well as on CT 7 days, after the event. SPECT evaluation was performed both visually and using semiquantitative region-of-interest (ROI) analysis. According to visual SPECT analysis, on admission 59 of 82 patients had activity deficits in the symptomatic hemisphere. After 7 days, all these patients had neurologic symptoms (SSS 28 +/- 12 points), caused by a cerebral infarction as evidenced with CT. Twenty-three of 82 patients displayed no early activity deficit despite clinical symptoms. None of these patients had neurologic symptoms after 7 days (indicating transient ischemic attack or prolonged reversible ischemic neurologic deficit). In the semiquantitative SPECT analysis, all patients had abnormal count densities in the respective ROI (activity < 90% compared with the contralateral side). All patients with transient ischemia (n = 23) had count rate densities more than 70% of the respective contralateral ROI, whereas all patients with subsequent infarction (n = 59) had values < 70%. Use of 99mTc-ECD-SPECT allows transient ischemia to be distinguished from ischemic infarction using relative regional activity thresholds within the first 6 hours after onset of symptoms.
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PMID:Differentiation between transient ischemic attack and ischemic stroke within the first six hours after onset of symptoms by using 99mTc-ECD-SPECT. 970 54

The concept of ischemic penumbra has extended our understanding of the focal ischemic process and in many ways has revitalized our research. Simply stated, the penumbra is the part of the brain that is sandwiched between brain regions committed to die and those that receive enough blood to communicate. Therefore, it is ischemic brain tissue that has just enough energy to survive for a short time but not enough to communicate and function. The life expectancy of the penumbra is short. Although the penumbra is an elegant concept, in practice it has been a difficult one to exploit. For one thing, it is unstable in both time and space. Depending on the severity and the duration of the focal ischemia, it may be anywhere in the ischemic brain. We believe that nimodipine binding experiments have taught us a great deal about the ischemic penumbra. Second, cells in the penumbra may die not by necrosis but by apoptosis. If that is true, then our concepts about the benign transient ischemic attack may need revision. Third, the penumbra may regain its ability to survive not only through reperfusion but also by interrupting the process of commitment to apoptosis.
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PMID:Ischemic penumbra: the therapeutic window. 974 33

The expression of the gene encoding the C/EBP-homologous protein (CHOP), which is also known as growth arrest and DNA-damage-inducible gene 153 (gadd153), has been shown to be specifically activated under conditions that disturb the functioning of the endoplasmic reticulum (ER). To investigate a possible role of ER dysfunction in the pathological process of ischemic cell damage, we studied ischemia-induced changes in gadd153 expression using quantitative PCR. Transient cerebral ischemia was produced in rats by four-vessel occlusion. In the hippocampus, ischemia induced a pronounced increase in gadd153 mRNA levels, peaking at 8 h of recovery (6.4-fold increase, p<0.01), whereas changes in the cortex were less marked (non-significant increase). To elucidate the possible mechanism underlying this activation process, gadd153 mRNA levels were also evaluated in primary neuronal cell cultures under two different conditions, both leading to a depletion of ER calcium pools in the presence or absence of an increase in cytoplasmic calcium activity. The first procedure, exposure to thapsigargin, an irreversible inhibitor of ER Ca2+-ATPase, caused a marked increase in gadd153 mRNA levels both in cortical and hippocampal neurons, peaking at 12-18 h after treatment. The second procedure, immersion of cells in calcium free medium supplemented with EGTA, caused only a transient increase in gadd153 mRNA levels, peaking at 6 h of recovery, indicating that a depletion of ER calcium stores in the absence of an increase in cytoplasmic calcium activity is sufficient to activate neuronal gadd153 expression. The results imply that transient cerebral ischemia disturbs the functioning of the ER and that these pathological changes are more pronounced in the hippocampus compared to the cortex.
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PMID:Activation of gadd153 expression through transient cerebral ischemia: evidence that ischemia causes endoplasmic reticulum dysfunction. 974 29

Transient cerebral ischemia (5 min) releases unesterified fatty acids from membrane phospholipids, increasing brain concentrations of fatty acids for up to 1 h following reperfusion. To understand the reported anti-ischemic effect of Ginkgo biloba extract (EGb 761), we monitored its effect on brain fatty acid reincorporation in a gerbil-stroke model. Both common carotid arteries in awake gerbils were occluded for 5 min, followed by 5 min of reperfusion. Animals were infused intravenously with labeled arachidonic (AA) or palmitic acid (Pam), and rates of incorporation of unlabeled fatty acid from the brian acyl-CoA pool were calculated by the model of Robinson et al. (1992), using quantitative autoradiography and biochemical analysis of brain acyl-CoA. Animals were treated for 14 d with 50 or 150 mg/kg/d EGb 761 or vehicle. Ischemia-reperfusion had no effect on the rate of unlabeled Pam incorporation into brain phospholipids from palmitoyl-CoA; this rate also was unaffected by EGb 761. In contrast, ischemia-reperfusion increased the rate of incorporation of unlabeled AA from brain arachidonoyl-CoA by a factor of 2.3-3.3 compared with the control rate; this factor was further augmented to 3.6-5.0 by pretreatment with EGb 761. There is selective reincorporation of AA compared with Pam into brain phospholipids following ischemia. EGb 761 further accelerates AA reincorporation, potentially reducing neurotoxic effects of prolonged exposure of brain to high concentrations of AA and its metabolites.
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PMID:Effects of EGb 761 on fatty acid reincorporation during reperfusion following ischemia in the brain of the awake gerbil. 977 47

Death from acute hemispheric infarction is commonly associated with stroke size, but the potential role of the internal carotid artery (ICA) in this phenomenon is poorly understood. The aim of the present study was to analyse the relation between the degree of ipsilateral and contralateral ICA stenosis, infarct type and death. We studied 2,148 first-ever stroke patients with anterior circulation infarction from the Lausanne Stroke Registry. Doppler ultrasonography with frequency spectral analysis and Duplex-scanning were performed systematically during the acute phase of stroke. The patients were divided into groups according to the degree of ipsilateral and contralateral ICA stenosis. The case fatality ratios (CFR) at hospital discharge were obtained for each group. Several clinical features including age, stroke topography, level of consciousness, limb weakness on admission, type of onset, hyperglycemia, previous transient ischemic attack, cardiac ischemia, cardiac arrhythmia and left ventricular hypertrophy were also studied. Mortality increased significantly with ipsilateral ICA stenosis: </=50% stenosis, 2.8%, (44/1,549); >50% and </=90% stenosis, 3.5%, (6/170); >90% stenosis, 5.6%, (24/429); p = 0.026, but not significantly with contralateral ICA stenosis. However, patients without ipsilateral ICA stenosis had significantly higher mortality when contralateral stenosis was present: 16.7% (3/18) versus 2.7% (41/1,531), p = 0.013. This corresponded to an increased frequency of strokes involving the whole middle cerebral artery territory, with impaired consciousness at onset of stroke. Patients with ipsilateral stenosis had similar CFR independently of the presence or absence of contralateral stenosis. In conclusion, patency of the contralateral ICA may be an important contributory factor of larger infarction and indirectly of stroke mortality in patients with no ipsilateral stenosis.
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PMID:Death from ischemic stroke in the anterior circulation: the contralateral carotid matters. 988 23

Transient ischemic attack (TIA) is defined as "an episode of focal loss of brain function attributed to ischemia that lasts less than 24 hours, is localized to a portion of the brain supplied by one vascular system, has no persistent deficit, and is not attributable to any other cause." Most TIAs are caused by small thromboemboli that originate in atheromatous areas in neck vessels or the heart. Other mechanisms include nonatherosclerotic vascular diseases, mitral valve prolapse, hematologic diseases, and abnormal blood pressure fluctuations. Even in series of fully investigated cases, there remains a group in which no cause can be found. The great majority of TIAs are extremely brief. In one series, 24% ended within 5 minutes, 39% in 15 minutes, 50% in 30 minutes, and 60% in 1 hour.
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PMID:Morbidity and mortality associated with transient ischemic attack (TIA). 1016 48

Seventy-six patients undergoing carotid endarterectomy were studied to estimate the effect of operation, evaluate the accessible methods of examination and disclose the complications owing to the operation. In addition, the hypothesis that the pulsatility index in MCA measured by the Doppler method could disclose severe ischemia and risk of complications during endarterectomy was tested. The study was a prospective study of patients operated at the University Hospital in Odense in the years 1991-1996. Data collected included demographics, operative indications, complications, follow-up extra/transcranial Doppler examinations, cerebrovascular reactivity investigations, recurrent symptoms and deaths. Concerning the carotid stenosis, a fairly good correlation was found between the results of extracranial Doppler examinations, Duplex and carotid angiography. Serious complications after surgery were few. One patient, who had a coronary by-pass operation consecutive to the endarterectomy, died 3 weeks after the operation, owing to a hematothorax. Five patients (7%) suffered a stroke. Only 2 patients needed rehabilitation, and they came out with minor disturbances in the use of a hand. Recurrent stenosis in excess of 69% emerged in 3% of the patients. All were hemodynamically insignificant. One patient had a new TIA during the observation time of 3-60 months. After the operation she had a thrombosis in the operated carotid artery. Thus our results, a perioperative stroke rate of 7% and a mortality rate of 1%, are in line with the average results in multicenter trials. In addition a PI below 0.60 in the MCA seemed to be a warning of the risk of postoperative cerebral hyperemia.
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PMID:Outcome for patients with carotid stenosis undergoing carotid endarterectomy, the cerebral condition followed by extra/intracranial ultrasound examinations. 1057 67

Activated leukocytes are believed to be involved in the pathogenesis and progression of atherosclerotic vascular disease and its consequences. In a 4-year observational follow-up study, we investigated whether markers for systemic leukocyte activation (leukocyte-derived inflammatory mediators) were related to cardiovascular mortality after cerebrovascular ischemia. Using enzyme-linked immunosorbent assays, we measured the plasma levels of soluble tumor necrosis factor receptor protein-1 (sTNFR-1), neutrophil gelatinase-associated lipocalin (NGAL) and neutrophil protease-4 (NP4) in 144 patients (90 stroke, 54 transient ischemic attack) 1-3 days after cerebral ischemia. During the 4 years of follow-up, 42 (29%) of the 144 patients died; 38 of cardiovascular causes and 4 of other causes. Patients with evidence of higher leukocyte activation (n = 47) had a higher 4-year cardiovascular mortality rate than those without evidence of leukocyte activation (n = 97; p < 0.005). Logistic regression analysis with age, sex and other significant predictors as covariates showed higher plasma levels of sTNFR1 and NGAL both to be significant independent predictors of cardiovascular mortality, the respective odds ratio, 95% confidence intervals, and p values being 2.0, 1.2-3.4, p < 0.01, and 3.6, 1.2-10.5, p = 0.02, respectively. We concluded that in patients with acute cerebral ischemia, plasma markers of leukocyte activation were significant predictors of long-term cardiovascular mortality. This may indicate an important role of activated leukocytes in the progression of these diseases.
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PMID:Leukocyte activation: relation to cardiovascular mortality after cerebrovascular ischemia. 1068 47


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