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

To improve the efficacy of local intraarterial fibrinolysis (LIF), we compared different fibrinolytic drugs in a cerebral circulation model in the laboratory. The technical efficacy of fibrinolysis, defined as the clot volume lysed per unit time, was found to be optimal with r-tissue plasminogen activator (TPA) activated lys-plasminogen (= plasmin). Subsequently, 20 patients with stroke due to carotid artery territory occlusion were treated by local intraarterial fibrinolysis using the plasmin regimen. The angiographic data and clinical outcome of these patients were compared with those of 40 patients who received plasminogen activators (urokinase or r-TPA) only. Laboratory and clinical data confirmed that plasmin lysis is superior to treatment using only plasminogen activators.
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PMID:Lys-plasminogen as an adjunct to local intra-arterial fibrinolysis for carotid territory stroke: laboratory and clinical findings. 869 37

The use of fibrinolytic agents in acute ischemic stroke has received increasing attention due to the completion of several prospective studies examining the efficacy and safety of these drugs in this clinical setting. Experience with plasminogen activators indicates that recanalization of carotid and vertebrobasilar territory occlusion is feasible within 4-6 hours of symptom onset. The optimal plasminogen activator, its dose-rate and delivery system, however, is not known. The phase III trial of the European Cooperative Acute Stroke Study (ECASS) suggests potential modest benefit in outcome, although recombinant tissue plasminogen activator (rt-PA) had an increased risk of hemorrhage attributable to those patients with early CT-scan signs of ischemia. Complete cervical internal carotid artery occlusions by in situ thrombosis appear more resistant to thrombolysis than occlusions of the stem and major branches of the middle cerebral artery. The issue of hemorrhagic transformation is unsettled. It seams to be increased by delayed intervention on the one hand, but it is not different from that observed in placebo patients in phase I/II series.
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PMID:Thrombolysis in acute stroke. 871 49

Therapy for stroke is undergoing major changes. Many of the changes parallel the advances made in the therapy for myocardial infarction. Acute intervention with cytoprotective and thrombolytic agents is undergoing active investigation. Cytoprotective therapy includes drugs that act to prevent cell death during ischemia and reperfusion. These agents include calpain inhibitors, voltage-sensitive calcium- and sodium-channel antagonists, receptor-mediated calcium-channel antagonists [including N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) antagonists], glutamate-synthesis inhibitors, glutamate-release antagonists, gamma-aminobenzoic acid (GABA) antagonists, 5-HT (serotonin) receptor agonists, gangliosides, antioxidants, growth factors, antiapoptotic agents, and antiadhesion molecules. Thrombolysis is effective in myocardial infarction. Thrombolysis is undergoing evaluation in stroke with streptokinase, anisoylated plasminogen streptokinase activator complex (APSAC), tissue plasminogen activator (t-PA; including recombinant t-PA), urokinase, and single-chain urokinase (scu-PA). Both systemic and selective administration are being evaluated. Preventive therapy with both antiplatelet and anticoagulant drugs sheds new light on how best to stratify patients in terms of a risk-benefit ratio. Continuing public education will be essential as stroke therapy advances.
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PMID:Medical therapy for ischemic stroke. 877 66

Clinical experience suggests that thrombolytic-induced bleeding is associated with systemic activation of the thrombolytic system. Using fibrin specific variants of tissue-type plasminogen activator (t-PA) and making use of the apparent fibrin specificity of streptokinase (SK) in the rabbit we tested the hypothesis that minimizing systemic plasmin production and fibrinogenolysis will decrease hemorrhages in models of peripheral bleeding and embolic stroke. t-PA consumed 51% of the available fibrinogen; caused cerebral bleeds and increased peripheral bleeding time. Fibrin-specific variants of t-PA depleted less than 20% of the fibrinogen and did not cause peripheral or cerebral bleeding. However, an equipotent dose of SK converted only 12% of the available fibrinogen but increased bleeding time and caused hemorrhagic conversion in 75% of embolic stroke model animals treated. The data suggest that bleeding associated with tissue-type plasminogen activators is linked to systemic plasmin generation and subsequent fibrinogenolysis. This hypothesis does not explain the mechanism(s) of SK-induced bleeding.
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PMID:Limiting systemic plasminogenolysis reduces the bleeding potential for tissue-type plasminogen activators but not for streptokinase. 882 86

Thrombolysis today has become a routine option not only in the treatment of acute myocardial infarction but also in many other manifestations of thromboembolic disease. Until one decade ago, only two plasminogen activators, streptokinase and urokinase, were available for clinical use. They were characterized by limited thrombolytic potencies and major side effects including systemic fibrinogen breakdown, bleeds and stroke. This has prompted the search for new plasminogen activators with better pharmacological and clinical profiles. The first such new plasminogen activators were Anistreplase, a chemically modified version of the streptokinase-plasminogen-activator-complex and tissue-type plasminogen-activator produced by recombinant technology. Both new substances have fueled the development in modern thrombolytic treatment. While the clinical progress with t-PA was confirmed in large, double-blind, randomized, multicenter trials, no real superiority of anistreplase over the traditional plasminogen activators urokinase and streptokinase has been substantiated. While the clinical use of t-PA today has been established for acute myocardial infarction, pulmonary embolism and deep vein thrombosis, current research is focused on further plasminogen activators with further improved thrombolytic properties. This review summarizes the current knowledge on the biochemical and pharmacological properties of the first, second and future generation of plasminogen activators.
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PMID:Thrombolytic agents--an overview. 885 12

It is likely that thrombolytic agents will play a role in the management of acute ischemic stroke in well-selected patients, intravenous administration is most practicable. However, intra-arterial administration via superselective catheterization is an alternative option that may offer advantages is certain settings (e.g., angiography suite, intraoperatively). Tissue plasminogen activators appear safer than streptokinase. Fibrinolytic agents offer the unproven potential for improving stroke outcome with less risk of intracranial bleeding. LMWHs can be administrated subcutaneously with minimal blood monitoring. These agents may prove more useful for secondary stroke prevention rather than acute treatment. Introduction of other agents like monoclonal antibodies directed against leukocyte adhesion molecules, aspirin, or ticlopidine offer other potential approaches to improving stroke outcome.
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PMID:Acute stroke therapies. 887 43

The use of thrombolytic agents (plasminogen activators) in the early moments of ischemic stroke to achieve recanalization and potential neurologic improvement has been actively studied over the past 10 years. In the same period, endovascular techniques for cerebral revascularization have evolved significantly. Recent phase III studies, following angiography-based phase I and II studies of plasminogen activators in stroke, have described evidence of clinical benefit and contributors to morbidity (i.e., symptomatic hemorrhage) and mortality that limit the applicability of this approach. The limited formalized experience with percutaneous transluminal balloon angioplasty and stent placement in the carotid artery and cerebral circulation has given rise to concerns about the safety and appropriateness of the procedures in this territory. However, several prospective series support the feasibility of well-designed clinical trials.
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PMID:New interventions in cerebrovascular disease: the role of thrombolytic therapy and balloon angioplasty. 888 83

Seasonal influence on mortality from cardiovascular and cerebrovascular diseases is well documented. Understanding the seasonal variations in cardiovascular risk factors can shed light on this phenomenon. Elevation of coagulation factors during cold weather may in part explain the higher mortality from myocardial infarction and stroke in winter. The Cardiovascular Disease Risk Factors Community Study (CVDFACTS) included subjects belonging to 2 cohorts located in northern and southern Taiwan. This study included 2877 subjects aged 18 and above whose blood levels were examined for various coagulating factors. Besides measuring conventional cardiovascular risk factors including: blood pressure, body mass index and total cholesterol, values for blood fibrinogen, factor VII activity, factor VIII activity, plasminogen, antithrombin III, prothrombin time and activated partial thromboplastin time were determined for all subjects. Of these hemostatic parameters, levels of all, except prothrombin time, were statistically different between days with mean temperature > 20 degrees C and days with temperature < or = 20 degrees C (P < 0.01). In cold weather, a greater tendency to clot in circulatory system was demonstrated in this study, indicating seasonal variations may be demonstrated in this subtropical region.
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PMID:Values of blood coagulating factors vary with ambient temperature: the Cardiovascular Disease Risk Factor Two-Township Study in Taiwan. 890 10

Lipoprotein(a) [Lp(a)] represents an LDL-like particle to which the Lp(a)-specific apolipoprotein(a) is linked via a disulfide bridge. It has gained considerable interest as a genetically determined risk factor for atherosclerotic vascular disease. Several studies have described a correlation between elevated Lp(a) plasma levels and coronary heart disease, stroke, and peripheral atherosclerosis. In healthy individuals, Lp(a) plasma concentrations are almost exclusively controlled by the apo(a) gene locus on chromosome 6q2.6-q2.7. More than 30 alleles at this highly polymorphic gene locus determine a size polymorphism of apo(a). There exists an inverse correlation between the size (molecular weight) of apo(a) isoforms and Lp(a) plasma concentrations. The standardization of Lp(a) quantification is still an unresolved task due to the large particle size of Lp(a), the presence of two different apoproteins [apoB and apo(a)], and the large size polymorphism of apo(a) and its homology with plasminogen. A working group sponsored by the IFCC is currently establishing a stable reference standard for Lp(a) as well as a reference method for quantitative analysis. Aside from genetic reasons, abnormal Lp(a) plasma concentrations are observed as secondary to various diseases. Lp(a) plasma levels are elevated over controls in patients with nephrotic syndrome and patients with end-stage renal disease. Following renal transplantation, Lp(a) concentrations decrease to values observed in controls matched for apo(a) type. Controversial data on Lp(a) in diabetes mellitus result mainly from insufficient sample sizes of numerous studies. Large studies and those including apo(a) phenotype analysis came to the conclusion that Lp(a) levels are not or only moderately elevated in insulin-dependent patients. In noninsulin-dependent diabetics, Lp(a) is not elevated. Conflicting data also exist from studies in patients with familial hypercholesterolemia. Several case-control studies reported elevated Lp(a) levels in those patients, suggesting a role of the LDL-receptor pathway for degradation of Lp(a). However, recent turnover studies rejected that concept. Moreover, family studies also revealed data arguing against an influence of the LDL receptor for Lp(a) concentrations. Several rare diseases or disorders, such as LCAT- and LPL-deficiency as well as liver diseases, are associated with low plasma levels or lack of Lp(a).
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PMID:Lipoprotein(a) in health and disease. 898 7

The blood clotting enzyme thrombin plays a central role in the aetiology of occlusive disorders such as stroke and acute myocardial infarction. During fibrinolytic therapy with plasminogen activators, thrombin is neutralized by anticoagulative drugs. In order to combine plasminogen-activating and thrombin-inhibitory activities we constructed chimeric derivatives of recombinant single-chain, urokinase-type plasminogen activator (rscu-PA) which comprise the kringle and protease domain of rscu-PA fused via a linker sequence to a thrombin-inhibitory domain. The inhibitory domain contains a sequence element directed to the active site of thrombin and a sequence taken from either hirudin or the human thrombin receptor both binding to the fibrinogen recognition site of thrombin. Analysing different sets of point mutants showed that the linker between the protease domain and the active site-directed sequence is contributing significantly to the thrombin-inhibitory potential. Kinetic analysis of thrombin inhibition revealed that most of the chimeras tested competitively inhibit the thrombin-mediated cleavage of a peptide substrate in a concentration-dependent manner; however, in two examples the insertion of one glycine residue into the active site directed-sequence abolished the blockade of the active site. This supports the conclusion that the chimeras with high thrombin-inhibitory potential interact with the active site and the fibrinogen recognition site of thrombin.
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PMID:Construction and structure-activity relationships of chimeric prourokinase derivatives with intrinsic thrombin-inhibitory potential. 900 43


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