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

The past year has seen tremendous progress in developing new therapies aimed at reversing the effects of acute stroke. Thrombolytic therapy with various agents has been extensively studied in stroke patients for the past 7 years. Tissue plasminogen activator (t-PA) received formal US Food and Drug Administration approval in June 1996 for use in patients within 3 hours of onset of an ischemic stroke. Treatment with t-PA improves neurologic outcome and functional disability to such a degree that, for every 100 stroke patients treated with t-PA, an additional 11-13 will be normal or nearly normal 3 months after their stroke. The downside of t-PA therapy is a 6% rate of symptomatic intracerebral hemorrhage (ICH) and a 3% rate of fatal ICH. Studies are under way to determine whether t-PA can be administered with an acceptable margin of safety within 5 hours of stroke, to evaluate the therapeutic benefits of intraarterial pro-urokinase, and to assess the use of magnetic resonance spectroscopy to identify which patients are most likely to benefit from thrombolysis. Combination thrombolytic-neuroprotectant therapy is also being studied. In theory, patients could be given an initial dose of a neuroprotectant by paramedics and receive thrombolytic therapy in the hospital. We are now entering an era of proactive, not reactive, stroke therapies. These treatments may reverse some or all acute stroke symptoms and improve functional outcomes.
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PMID:Hyperacute stroke therapy with tissue plasminogen activator. 928 41

The mechanism of action of currently available thrombolytic agents, such as streptokinase, urokinase, alteplase (recombinant tissue-type plasminogen activator; rt-PA) and anistreplase (anisoylated plasminogen streptokinase activator complex; APSAC), involves conversion of inactive plasminogen to plasmin, a potent fibrinolytic. However, the relatively weak substrate specificity of first generation agents (streptokinase and urokinase) can result in a state of systemic fibrinolysis and associated bleeding complications. The second generation drugs such as alteplase were developed in an attempt to enhance fibrin specificity, so that only enzymatic conversion of fibrin-complexed plasminogen would take place, thus avoiding systemic fibrinolysis. Results from large clinical trials have failed to consistently show any significant differences between first and second generation thrombolytic agents in the incidence of bleeding. In the clinical setting, thrombolytic agents have been evaluated primarily in patients with acute myocardial infarction and have been shown to significantly reduce morbidity and mortality compared with conservative treatment. The focus of current and future research is to investigate these agents in patients with other vaso-occlusive or ischaemic conditions (e.g. stroke), and also to evaluate different drug administration regimens and the use of adjunctive therapies such as aspirin (acetylsalicylic acid) and heparin.
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PMID:Evaluation of thrombolytic agents. 936 Aug 48

Approximately 80 to 90% of cerebral ischaemic events that occur within 24 hours of symptom onset are due to atherothrombotic or thromboembolic occlusions. This forms the rationale for the use of thrombolytic agents in patients with acute ischaemic stroke. Early studies determined that recanalisation occurred in approximately 21 to 72% of patients with occluded cerebral arteries after intra-arterial or intravenous administration of streptokinase, urokinase, alteplase (recombinant tissue-type plasminogen activator; rt-PA) or duteplase (a 2-chain rt-PA). Initial reports suggested that frequencies of haemorrhagic transformation and parenchymatous haematoma in the carotid territory were similar whether patients with middle cerebral artery stroke received thrombolysis via intra-arterial or intravenous administration. The Multicentre Acute Stroke Trial-Europe (MAST-E), the Australia Streptokinase (ASK), and the Multicentre Acute Stroke Trial-Italy (MAST-I) trials, which evaluated intravenous streptokinase 1.5 x 10(6) IU in patients with acute ischaemic stroke, were terminated prematurely because of excessive early mortality and symptomatic intracranial haemorrhage in streptokinase recipients compared with those treated with placebo. However, those studies had not been preceded by dose-ranging trials. Intravenous administration of alteplase 0.9 mg/kg within 3 hours [National Institute of Neurological Disorders and Stroke (NINDS) trial], or 1.1 mg/kg within 6 hours [European Cooperative Acute Stroke Study (ECASS)], of symptom onset in patients with acute ischaemic stroke resulted in an absolute 11 to 13% treatment-associated improvement in clinical measurement scales; such as the modified Rankin scale and Barthel index, compared with placebo recipients. In the ECASS trial, those results were limited to a 'target population' restricted to those who satisfied all entry criteria. In both trials, the frequency of symptomatic haemorrhage was greater in patients treated with alteplase than with placebo and reinforced the importance of careful patient selection. Strict patient selection remains central to the success of this approach.
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PMID:Thrombolytic therapy in the treatment of stroke. 936 Aug 56

Thrombolytic therapy in acute ischemic stroke is safe and effective in a defined subgroup of stroke patients. Until now, different fibrinolytic substances including urokinase, streptokinase and recombinant tissue plasminogen activator (rt-PA) have been tested regarding safety, efficacy, dosage and economic parameters in patients suffering from both carotid and basilar artery territory strokes. Recently, two large multicenter placebo-controlled intravenous rt-PA studies were published. The results show that thrombolysis of acute carotid territory strokes (European Cooperative Acute Stroke Study) and of strokes with a deficit measurable on the NIH Stroke Scale (National Institute of Neurological Disorders and Stroke rt-PA Stroke Study) improves clinical and economic outcome parameters in patients who were treated within 6 hours of the onset of symptoms and had that no signs of extended early infarction on the initial CT-scan. The occurrence of intracranial hemorrhages is more frequent after thombolytic therapy, but the majority of bleeding complications referred to petechial or more confluent hemorrhage limited to the infarcted tissue, without clinical deterioration. However, the identification of the appropriate patients is difficult and depends on the level of clinical and diagnostic experience. In vertebrobasilar artery territory stroke, local intraarterial thrombolysis with urokinase or streptokinase is performed in most cases. Thrombolytic treatment within twelve hours of the onset of symptoms was associated with significantly better results concerning both survival and neurological recovery.
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PMID:[Thrombolytic therapy in ischemic infarct]. 945 30

In this study, the clinical effects were compared between a thromboxane synthetase inhibitor (sodium ozagrel) and a thrombolytic agent (urokinase) in patients with acute cerebral infarction. The subjects consisted of 598 patients admitted on the day of the onset of the cerebral infarction in the territory of the internal carotid artery who showed a low density area on CT images within 5 days. Of these patients, 300 were treated with sodium ozagrel and classified as Group Oz, while the remaining 298 were treated with urokinase and classified as Group Ur. The results were as follows: 1. In group Oz, complete recovery of motor impairment was seen in 209 (69.7%) patients. Complete recovery within 3 weeks after onset was seen in 186 (62.0%) patients. In group Ur, complete recovery of motor impairment was seen in 175 (58.7%) patients. Complete recovery within 3 weeks after onset was seen in 120 (40.3%) patients. Therefore, a higher incidence of complete recovery of the motor impairment was noted in group Oz [p < 0.001: chi 2 test]. Similarly, complete recovery within 3 weeks after onset was more frequent in group Oz [p < 0.001: chi 2 test]. 2. In group Oz, complete recovery was made contribution statistically by Anosognosia (Ag) and unilateral neglect (UN) on admission [multivariate analysis: p < 0.01]. In group Ur, complete recovery was made contribution statistically by Ag (p < 0.01), UN (p < 0.01) and aphasia (p < 0.05). 3. Progressive stroke was observed in 29 (9.5%) patients in the group Oz and in 71 (23.0%) patients in group Ur. There was a higher incidence of progressive stroke in group Ur [p < 0.001: chi 2 test] 4. All patients with progressive stroke had initial evidence of deterioration of neurological deficits within 6 days after the onset in group Oz, and within 5 days after the onset in group Ur. The maximal period from the beginning to the end of the deterioration of neurological deficit was 7 days. 5. In group Oz, progressive stroke was only seen in 29 (29.9%) of the patients who were admitted with motor disturbances and unilateral neglect. In group Ur, progressive stroke was seen in 8 (4.3%) of the 187 patients with motor disturbances without higher cortical dysfunction, in 17 (47.2%) of the 36 patients with motor disturbances and higher cortical dysfunction without unilateral neglect and was seen in 46 (61.3%) of the patients with motor disturbances and unilateral neglect. 6. Hemorrhagic infarction was observed in 14 (4.6%) patients in group Oz and in 31 (10.0%) patients in group Ur. There was a higher incidence of hemorrhagic infarction in group Ur [p < 0.001: chi 2 test]. 7. In group Oz, there was a higher incidence of hemorrhagic infarction among patients with atrial fibrillation (Af) on the ECG [p < 0.001: chi 2 test]. Similarly, in group Ur, hemorrhagic infarction was more frequent among patients with atrial fibrillation (Af) on the ECG [p < 0.001: chi 2 test]. Therefore, sodium ozagrel was clinically more efficient and safer than urokinase in patients with acute cerebral infarction.
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PMID:[Clinical effects of sodium ozagrel and urokinase in patients with acute cerebral infarction in the territory of the internal carotid artery]. 951 4

Arterial thrombosis is the underlying cause of a wide variety of cardiovascular diseases such as myocardial infarction, stroke and pulmonary thromboembolism. All the currently used thrombolytic agents are plasminogen activators, which are very efficient in restoring the blood flow. The fibrinolytic system comprises an inactive proenzyme plasminogen, that is converted by plasminogen activators to the enzyme plasmin, that degrades fibrin. Despite the widespread use of established thrombolytic agents such as streptokinase, tissue-plasminogen activator and urokinase, all these agents suffer from a number of inadequacies including resistance to reperfusion, occurrence of acute coronary reocclusion and bleeding complications. The quest continues for thrombolytic agents with a higher potency, specific thrombolytic activity and fibrin selectivity. Several lines of research towards improvement of thrombolytic agents are being explored including the construction of mutants and variants of plasminogen activators, chimeric plasminogen activators and conjugates of plasminogen activators with monoclonal antibodies. Newer molecules such as pro-urokinase, saruplase, alteplase, K1K2Pu and staphylokinase have shown promise in animal models of arterial and venous thrombosis and also in pilot scale clinical studies in patients with myocardial infarction. However, more clinical trials are needed to determine whether these novel recombinant thrombolytic agents shows improved efficacy and fibrin specificity with minimal bleeding tendencies.
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PMID:Newer thrombolytic drugs for acute myocardial infarction. 953 45

The development of promising acute stroke treatments is the fruit of the growing appreciation for the complex biochemical processes within neuronal tissue that commence immediately after the onset of ischemia. These biochemical cascades can be modified either by direct pharmacologic mitigation or by rapid restoration of perfusion and oxygenation. With both interventions, the ischemic tissue can remain viable and regain neurologic function rather than progress to infarction. Today the two major pharmacologic approaches to stroke therapy are neuroprotectants and thrombolytics. Neuroprotectants enable neuronal tissues to tolerate periods of minimal perfusion better, whereas thrombolytics facilitate reperfusion by disrupting the fresh thrombus. Important classes of neuroprotectants include calcium channel antagonists, N-methyl-D-aspartate (NMDA) receptor antagonists, benzothiazoles, and free radical scavengers. Pro-urokinase is a potentially important investigational thrombolytic. Ancrod, a defibrinogenating agent, is also currently being evaluated in acute stroke.
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PMID:The stroke pharmacopeia: promising experimental therapies. 961 94

Tissue plasminogen activator (t-PA) is expressed by hypothalamic and peripheral sympathetic neurons. The sympathetic axons that permeate artery walls have not been investigated as possible sources of intramural t-PA. The plasmin produced by such a system would locally activate both fibrinolysis and matrix metalloproteinases that regulate arterial collagen turnover. To assess this neural t-PA production, we investigated the capacity of rat cervical sympathetic ganglion neurons to synthesize and release t-PA, and the expression of the enzyme in carotid artery and the iris-choroid microvascular tissues that receive the ganglion axon distribution. Functional studies confirmed that (i) the ganglion neuron cell bodies synthesize t-PA mRNA, (ii) cultured ganglion carotid artery and iris-choroid microvascular explants predominantly release t-PA rather than urokinase, (iii) microvascular tissues release approximately 20 times more t-PA per milligram than carotid explants (which accords with the higher innervation density of small vessels), and (iv) removal of the endothelium did not cause major reductions in the t-PA release from carotid and microvascular explants. Immunolocalization studies then confirmed a strong expression of the enzyme within the ganglion axons, the carotid adventitia that receives these axons, and the predominantly sympathetic axon terminals in the iris-choroid microvasculature. These data indicate the existence of a previously undescribed system for the delivery of neural t-PA to vessel walls. The intramural production of plasmin induced by this system represents a novel principle for the regulation of arterial matrix flexibility, especially in the media of densely innervated small arteries and resistance arterioles involved in the pathogenesis of stroke, hypertension, and vascular aging. Thus, the data suggest an important new interface between neuroscience and vascular biology that merits further exploration.
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PMID:Functional and morphologic evidence of the presence of tissue-plasminogen activator in vascular nerves: implications for a neurologic control of vessel wall fibrinolysis and rigidity. 971 Feb 64

In the management of acute major vessel occlusion, the use of fibrinolytic agents such as recombinant tissue plasminogen activator (rt-PA), urokinase or streptokinase is widely accepted. Today, the spectrum of indications for thrombolytic drugs comprises acute myocardial infarction, lung embolism, ischaemic stroke, deep vein thrombosis and acute arterial occlusions of the lower limbs. In view of the histopathological and clinical features of retinal vessel occlusion, fibrinolysis aimed at early restoration of blood flow appears to be a promising therapeutic approach. Basically, it is of some concern that the systemic administration of fibrinolytic agents is associated with a haemorrhagic risk. Since this includes cerebral haemorrhage or gastrointestinal bleeding, the choice of an appropriate intravenous thrombolytic therapy in a non-life threatening situation such as central retinal artery occlusion (CRAO) or central retinal vein occlusion (CRVO) should be based on minimising the risk of adverse events. Furthermore, the fibrinolytic treatment of choice should be able to produce rapid and complete restoration of retinal capillary and arterial or venous blood flow and maintain patency long enough for retinal salvage to take place. In this article, we review several studies of fibrinolytic therapy in patients with retinal vessel occlusion to determine whether this treatment is likely to improve major clinical outcomes. Moreover, we review the large scale trials of fibrinolysis in myocardial infarction and acute ischaemic stroke to evaluate safety and efficacy of various thrombolytic regimens. Furthermore, we report on our results of fibrinolytic therapy with low dose rt-PA in patients with retinal artery occlusion and ischaemic central retinal vein occlusion. In light of the fact that the occurrence of bleeding complications constitutes a dose dependent problem, we conclude that the use of low dose regimens should be the ideal approach to fibrinolysis in retinal vessel occlusion. Although the results of our pilot studies must be interpreted with caution, we believe that the administration of low-dose rt-PA (50 mg) in a frontloaded manner (= simultaneous administration of rt-PA and intravenous heparin) constitutes a reasonable treatment option in patients with central retinal artery occlusion (CRAO) or ischaemic retinal vein occlusion (RVO), recent onset of symptoms (CRAO < or = 12 h, RVO < or = 11 d) and severe visual loss (< or = 20/50). Because of these limitations and the numerous contraindications of fibrinolytic therapy, only a limited number of patients will be suitable for this treatment. In view of the poor visual and ocular prognosis in severe retinal vessel occlusion, controlled clinical trials are needed to determine the benefit of thrombolysis in the management of this disease.
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PMID:[Systemic lysis therapy in retinal vascular occlusions]. 978 35

The treatment options and management of ischemic and hemorrhagic stroke are expanding. Neuroradiologic interventions are being used in acute care settings to change the course of these devastating processes. These interventions include the injection of intra-arterial urokinase for ischemic stroke, use of coils to secure aneurysms, and balloon angioplasty for increasing the lumen of spastic cerebral arteries in patients with cerebral vasospasm. Using a case study approach, these three options for managing stroke patients will be integrated, and nursing strategies for delivering care to the stroke patient will be profiled.
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PMID:Case presentations of neuroradiologic interventions for acute cerebrovascular disease. 978 1


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