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

Tissue plasminogen activator (tPA), the serine protease that converts inactive plasminogen to the protease plasmin, was recently shown to mediate neurodegeneration in the mouse hippocampus. Mice deficient in tissue plasminogen activator (tPA) display a dramatic resistance to a paradigm of excitotoxic neuronal death that involves intrahippocampal injection of the excitotoxin. This model is thought to reproduce the mechanism of neuronal death observed during acute (such as ischemic stroke) and degenerative (such as amyotrophic lateral sclerosis) diseases of the nervous system. The requirement for the proteolytic activity of tPA to mediate neuronal death is acute in the adult mouse. Serine protease inhibitors, specific for tPA or the tPA/plasmin proteolytic cascade, are effective in conferring extensive neuroprotection following the excitotoxic injection. These findings suggest possible new ways for interfering with the neuronal death observed in the hippocampus as a result of excitotoxicity. In addition, tPA is produced in the hippocampus primarily by microglial cells, which become activated in response to the neuronal injury. Blocking microglial activation has been shown in other injury paradigms to protect against neuronal death, therefore suggesting another way to retard neurodegeneration in the CNS. Furthermore, after the insult has been inflicted and in the presence of a compromised blood-brain barrier macrophages (cells deriving from the same lineage as microglia) migrate into the brain, where they are thought to contribute to the neuronal cell loss by secreting neurotoxic molecules. If these macrophages/microglia expressed, however, a tPA inhibitor, rather than the possibly neurotoxic tPA, they might be able to protect the neurons from dying.
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PMID:Clinical implications of the involvement of tPA in neuronal cell death. 918 75

Although stroke is a major cause of morbidity and mortality, it is only relatively recently that a concerted effort has been made to develop acute treatments. Thrombolytics, such as recombinant tissue plasminogen activator (rt-PA), may benefit selected patients within 3 h of cerebral infarction. CUrrently, rt-PA is only licensed for use in the United States. Many potential strategies for neuroprotection exist and are currently under investigation. Because the mechanisms of neurotoxicity involve numerous interdependent processes, it may be that the interpretation of a single site in the cascade of events is insufficient to provide effective neuroprotection. Drugs acting at several sites in the neurotoxic cascade may be more effective, and the results of Phase III studies with the novel neoroprotectant lubeluzole are anticipated.
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PMID:The rationale for new therapies in acute ischaemic stroke. 920 64

We present a case of acute asymmetric angioneurotic edema associated with the use of recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke. rtPA was administered for an acute ischemic stroke in accordance with the recently reported National Institute of Neurological Disorders and Stroke protocol, after which marked asymmetric angioedema requiring upper-airway control developed. Although atypical and anaphylactoid reactions have been reported with the use of rtPA for acute myocardial infarction, to our knowledge this is the first case report of asymmetric angioedema associated with the use of rtPA for acute ischemic stroke.
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PMID:Asymmetric angioneurotic edema associated with thrombolysis for acute stroke. 925 Jun 52

Ischemic stroke occurs after an abrupt reduction in cerebral blood flow, usually related to thrombosis of an intracranial or extracranial artery. The presenting symptoms and signs of stroke vary greatly, depending on the region of the brain involved. Most individuals are unaware of the warning signs or symptoms of stroke and do not seek medical care immediately after stroke onset. Recently, thrombolytic therapy with intravenous tissue plasminogen activator (t-PA) has been shown to be effective for treatment of selected stroke patients if administered <3 hours after stroke onset. This therapy is now approved for stroke treatment, but relatively few stroke patients currently receive t-PA. Neuroprotective agents that improve the intrinsic ability of brain parenchyma to withstand ischemia are currently undergoing intensive clinical evaluation. Their development has been facilitated by significant scientific advances in the understanding of the pathophysiology of acute ischemic neuronal injury. Strategies aimed at interfering with these fundamental processes of ischemic neuronal injury have shown encouraging results in several preliminary clinical trials. However, these agents probably must also be administered within a few hours of stroke onset to be beneficial. Eventually, combined neuroprotective and thrombolytic therapy will likely be used for acute stroke treatment. This strategy's success will depend on increased public and professional education efforts dealing with stroke recognition, evaluation, and treatment.
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PMID:Rationale for early intervention in acute stroke. 928 38

We conducted a MEDLINE search of new treatment strategies and experimental agents for treating acute ischemic stroke published from 1989-1996. Clinical trials involving thrombolytics, glutamine release inhibition, N-methyl-D-aspartate receptor antagonism, opioid antagonism, calcium channel blockade, free radical scavenging, membrane stabilization, intercellular adhesion molecule-1 antagonism, ganglioside administration, and growth factor administration were included. Basic research articles were selected based on progress of the therapeutic class toward clinical trials. Approval of tissue plasminogen activator indicates progress in new treatments for acute ischemic stroke. Experimental therapies with potential may become available soon. Recognizing signs and symptoms of stroke is crucial to ensure prompt administration of these agents. The time to diagnosis determines the therapeutic approach for acute ischemic stroke.
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PMID:New and investigational treatment options for ischemic stroke. 932 84

Medical treatment of acute stroke with tissue plasminogen activator (tPA) was recently approved in the United States, and neuroprotective agents are being developed. Should all patients with stroke, regardless of severity, receive such treatment? In the Copenhagen Stroke Study we studied the prognosis of stroke in 1,351 unselected patients from a well-defined catchment area treated in a community-based stroke unit from the time of acute admission to death or the end of rehabilitation. Outcome measures were mortality, discharge rates to the patients' own home or to a nursing home, length of hospital stay, and neurological and functional outcomes. Prognosis was stratified according to initial stroke severity measured by the Scandinavian Neurological Stroke Scale (SSS) on admission. We estimated the effect of medical treatment on prognosis and health care utilization by assuming a medically induced decrease in initial stroke severity by 5 and 10 points in the initial SSS score. This mild and moderate decrease in initial stroke severity corresponded to an overall improvement in outcome and an overall cost reduction through shorter hospital stays. This was also true in patients with both mild and moderate stroke. However, in patients with severe stroke, survival increases expenses because of an increased discharge rate to a nursing home and an increase in the cost of acute care and rehabilitation. Future medical stroke trials should therefore focus on the effect and cost of treatment, especially in patients with severe stroke, and search for factors predictive of good clinical outcome in this group.
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PMID:Acute stroke: prognosis and a prediction of the effect of medical treatment on outcome and health care utilization. The Copenhagen Stroke Study. 937 18

Roughly 80% of patients with acute stroke have thromboocclusive disease and may benefit from clot lysis with recombinant tissue plasminogen activator. To be effective, however, such treatment must be administered within three hours of stroke onset in carefully selected patients. Hospital protocols that mobilize an acute stroke team to minimize delays are needed nationwide.
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PMID:Thrombolytic therapy for stroke: the new paradigm. 938 14

Patients with atrial fibrillation have been reported to exhibit abnormal hemostasis. Since nitric oxide (NO) exerts antithrombotic effects and attenuates platelet function, we evaluated two indicators of plasma NO levels, the plasma levels of nitrite and nitrate (NOx), and the levels of cGMP in platelets. We also examined whether indicators of plasma NO levels were associated with abnormalities in parameters related to platelet function, blood coagulation, and fibrinolysis. We evaluated 45 patients with chronic sustained atrial fibrillation (33 men and 12 women, age range 63 +/- 2 years) compared with 45 sex- and age- (+/- 2 years) matched nonhospitalized subjects with sinus rhythm. There were no significant differences between the two groups in the incidence of risk factors for stroke except for ischemic heart disease or in echocardiographic parameters. Plasma levels of NOx measured using the Greiss reagent (mean [interquartile range]: 15.6 [9.5 to 25.7] versus 24.1 [14.2 to 40.8] mumol/L, n = 45) and the platelet cGMP levels (0.33 [0.16 to 0.67] versus 0.63 [0.31 to 1.29] pmol/10(9) platelets, n = 9) were significantly (P < .05) lower in the patients with atrial fibrillation than in the control subjects. Plasma levels of D-dimer, beta-thromboglobulin, and fibrinogen were significantly (P < .05) higher in the patients with atrial fibrillation. The two groups did not differ as to the plasma levels of tissue plasminogen activator or plasminogen activator inhibitor-1. Our findings suggest that a decrease in plasma NO levels may account for the hemostatic abnormalities observed in patients with atrial fibrillation.
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PMID:Plasma levels of nitrite/nitrate and platelet cGMP levels are decreased in patients with atrial fibrillation. 940 10

Plasma fibrinogen is a consistent predictor of ischemic heart disease (IHD) in prospective studies, but there are fewer data relating other hemostatic variables to IHD and also to stroke. We therefore studied the relationships of plasma fibrinogen, von Willebrand factor antigen, tissue plasminogen activator (TPA) antigen, factor VII, and fibrin D-dimer to incidence of IHD and stroke and determined whether any associations could be explained by conventional risk factors and baseline heart disease. In the Edinburgh Artery study, 1592 men and women aged 55 to 74 years, randomly sampled from the general population, were followed prospectively over 5 years to detect fatal and nonfatal IHD and stroke events. During the 5 years, 268 new vascular events were identified. Baseline plasma fibrinogen was independently related to risk of stroke in multivariate analysis that adjusted for cigarette smoking, LDL-cholesterol, systolic blood pressure, and preexisting IHD (relative risk [RR] 1.52, 95% confidence interval [CI] 1.17, 1.98). TPA antigen, and fibrin D-dimer were also independently associated with risk of stroke (RR 1.69,95% CI 1.22,2.35 and RR 1.96, 95% CI 1.12,3.41, respectively). Significant relationships were found between TPA antigen and myocardial infarction (P < or = .05). In older men and women, increased coagulation activity and disturbed fibrinolysis are predictors of future vascular events (both IHD and stroke).
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PMID:Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study. 940 28

We carried out a case-control study to determine whether von Willebrand factor (vWF) antigen (and factor VII and tissue plasminogen activator [tPA] antigens) are associated with ischemic stroke. Ninety-five patients with transient ischemic attack or minor ischemic stroke recruited from the Oxfordshire Community Stroke Project and one neurology clinic were compared with 236 controls, group-matched for age and sex, from the same general practitioners as the incident cases. In crude analyses, concentrations of vWF antigen were significantly higher in cases than in controls (p = 0.004). The age- and sex-adjusted odds ratios from lowest (referent) to highest quartile of vWF antigen were 1.00, 1.15, 2.34, and 2.36 (trend test, p = 0.006). Factor VII antigen and tPA antigen were not significantly different between cases and controls. Although adjustment for other potential risk factors abolished the statistical significance of the association between vWF and disease, this was largely due to the influence of history of ischemic heart disease. We conclude that vWF is a potent and independent risk factor for transient ischemic attack, minor ischemic stroke, and, by extrapolation, ischemic stroke in general. The data also suggest that vWF may be a risk factor for both ischemic stroke and ischemic heart disease. We found no evidence to implicate factor VII and tPA as risk factors for ischemic stroke.
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PMID:Von Willebrand factor and risk of ischemic stroke. 940 45


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