Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Binding of iodine-125-labeled thrombin to fibrin clots from two siblings with juvenile stroke was 30% of normal, and abnormally high amounts of the radioligand (not adsorbed by fibrin) were found in the supernatant. In concordance with this finding, supernatants from the patients' fibrin clots caused abnormal enhancement of platelet aggregation, ATP secretion, and binding of 125I-fibrinogen to platelets exposed to subthreshold concentrations of ADP or epinephrine. Hirudin suppressed the enhancing effect of the patients' supernatants, and substitution of gamma-thrombin for alpha-thrombin led to normalization of platelet responses. Under some experimental conditions, degradation of the patients' fibrinogen by plasmin was impaired. However, the euglobulin lysis time, the rate of fibrin degradation by plasmin, and the lysis of the patients' plasma clots by human melanoma tissue-type plasminogen activator were normal. Patients' plasmas, as well as purified fibrinogen, showed a prolonged thrombin time (partially corrected by 10 mM CaCl2) and an impaired release of fibrinopeptide A in response to thrombin. However, the release in response to reptilase was normal, and the reptilase, ancrod, and thrombin coagulase times were within control (normal) values. In addition, the patients' fibrinogen showed normal polymerization of preformed fibrin monomers, normal sialic acid content, and normal binding to ADP or epinephrine-stimulated platelets. Our studies support the concept that thrombin and platelets play an important role in the occurrence of stroke in these patients and suggest a direction to be followed to identify the mechanism(s) contributing to thrombosis in subjects with abnormal fibrinopeptide release.
 ...
PMID:A role for platelets and thrombin in the juvenile stroke of two siblings with defective thrombin-adsorbing capacity of fibrin(ogen). 182 31

By increasing local cerebral blood flow to ischemic brain tissue in a timely fashion, impending cerebral infarction can be reversed. Aggressive, early intervention is the key to overall neurological improvement of stroke patients. Ancrod, a purified protein fraction of venom from the Malayan pit viper, has been shown to produce rapid and effective defibrinogenation in humans. A current clinical trial with ancrod in patients with acute or progressing nonhemorrhagic ischemic stroke requires an onset to treatment time of no more than 6 hours. Ancillary hospital personnel, physicians and nurses all play important roles in expediting study treatment. Nurses must assess ancrod study patients for potential bleeding problems. Community awareness and education about the warning signs of impending stroke are factors important to insuring early intervention and improving neurological outcome of stroke victims.
 ...
PMID:Experimental ancrod (Arvin) for acute ischemic stroke: nursing implications. 183 48

Clot lysis is desirable in patients with thrombi in arteries and arterioles by a safe rapidly-acting thrombolytic agent. Ancrod cleaves fibrinogen; the resulting circulating ancrod-fibrin stimulates fibrinolysis. Ancrod action and effect were studied in 20 patients with acute developing stroke in a double-blind, placebo-controlled study. Patients were randomly assigned to one of two treatment groups, and received either normal saline or ancrod 0.5 mu/kg in normal saline administered as a constant-rate intravenous infusion over 6 hours. Subsequent doses of ancrod (or saline placebo) were determined daily thereafter for a total treatment period of 7 days. Neither bleeding nor re-thrombosis occurred within the 90 day follow-up period. That ancrod acted rapidly was shown by a significant decrease in functional plasminogen activator inhibitor (PA-I) within 60 minutes, and by significant elevations of fibrin(ogen) degradation products (FDP) and D-dimer within 3 and 4 hours. The biological effect of fibrinolysis in ancrod infused patients was demonstrated by a greater improvement in stroke score when compared to those infused with saline.
 ...
PMID:Ancrod causes rapid thrombolysis in patients with acute stroke. 218 30

The standard of care for acute thromboembolic stroke is changing rapidly with the advent of new pharmacologic therapies. The deterioration of focal cerebral ischemia to infarction can be lessened with timely restoration of cerebral blood flow. As pharmacologic therapy of acute stroke evolves, emergency physicians will increasingly facilitate its implementation. The purpose of this study was to elucidate those factors significantly affecting the acute stroke patient's emergency department (ED) evaluation time. The pretreatment ED evaluations of 20 patients entered in an ongoing trial of a fibrinolytic agent (ancrod) for acute ischemic stroke were reviewed. Pretreatment screening factors included the assessment of hematologic status, concurrent illness, and potential neoplastic disease or cerebral hemorrhage as the etiology for the neurological deficit. The following factors had a statistically significant effect on pretreatment evaluation time (range, 2.6 to 11.4 hours) by multiple linear regression analysis: time from arrival until bleeding time completed (P less than .005), time from arrangement of computed head tomography until its completion (P less than .05), chosen site of treatment (ED v neurological step-down unit; P less than .005), order of patient entry (P less than .01), and time from arrival until completion of fibrinogen level assay (P less than .05). These results emphasize the need to coordinate and streamline the clinical evaluation process. The use of the ED as the site of treatment, abbreviating the time until pharmacologic therapy, has not been previously documented. Expedient completion of an evaluation compatible with safe pharmacologic therapy of acute ischemic stroke will dictate the time of definitive therapy. These results should assist other institutions considering rapid pharmacologic therapy for acute ischemic stroke.
 ...
PMID:Stroke patient evaluation in the emergency department before pharmacologic therapy. 264 55

Ancrod has been used in Europe for over 15 years for peripheral vascular disease, deep vein thrombosis, and central retinal venous thrombosis, and in patients at risk for thromboembolism. In a double-blind, randomized, placebo-controlled study at University Hospitals in Cincinnati, 20 acute cerebral infarction patients received a series of IV infusions of ancrod (ten) or placebo (ten) for seven days. Early fibrinolysis with a small decrease in fibrinogen was observed, and d-dimers were elevated at four hours, indicating early clot lysis. At three months, patients with moderate to severe strokes (less than 40 on the Scandinavian Stroke Scale) in the ancrod group showed average improvement by a factor of 3 over the placebo group. No bleeding, abnormal laboratory results, or deaths occurred, but ancrod was discontinued in one patient who had seizures. As a result of this study, a double-blind multicenter international clinical trial to further assess the safety and effectiveness of ancrod is being planned.
 ...
PMID:Use of ancrod in acute or progressing ischemic cerebral infarction. 305 31

Traditionally, blood rheology tests have been used in diagnosis and monitoring of infection, rheumatic diseases and malignancy, and are still of clinical value in these conditions. In the last twenty years, clinical and epidemiological studies have shown that the haematological determinants of blood flow resistance (haematocrit, fibrinogen, white cell count and altered red and white cell rigidity) are also associated with nutritional, metabolic, endocrine and vascular disorders. Decreased red cell deformability may contribute to reduced red cell survival and anaemia in burns, malaria, liver disease and kidney failure. In trauma and inflammatory disease, overt hyperviscosity is usually prevented by vasodilatation and reduction in the haematocrit. However, low-flow states may arise systemically from haemoconcentration (contracted plasma volume, Chapter 3) in severe burns, inappropriate red cell transfusion, or dehydration due to illness; systemically in circulatory shock; and locally in venous thrombosis or arterial disease. In such circumstances, the intrinsic flow resistance of blood may perpetuate flow disturbance, ischaemia and thrombosis. Conversely, optimal levels of haematocrit, fibrinogen and white cell count may be lower than normal in low-flow states. Haemodilution by colloid infusion is beneficial in burns, shock, major surgery, prevention of postoperative venous thrombosis, chronic stable claudication and possibly in acute stroke and retinal vein thrombosis. Plasma exchange may be beneficial in severe Raynaud's phenomenon. Defibrination with ancrod is effective in prevention and treatment of venous thrombosis but its role in arterial disease is unproven. The benefits of streptokinase therapy in venous thrombo-embolism and acute myocardial infarction may be partly rheological, due to fibrinogen depletion. Drugs with rheological effects may be beneficial in intermittent claudication.
 ...
PMID:Blood rheology in general medicine and surgery. 332 67

In a randomized, single-blind study, 30 patients with acute ischemic stroke were treated with either low-molecular weight dextran and mannitol alone (group A, mean age, 63.3 +/- 11.8 years, n = 15) or in combination with the viper venom enzyme ancrod (group B, mean age, 67.9 +/- 7.6 years, n = 15). Lowering of plasma fibrinogen levels to 100-130 mg/dL with ancrod resulted in a significant reduction of the apparent blood viscosity, ie, of 37% at a shear rate of 0.03 s-1, compared with only 7% in group A. Fibrin degradation products increased considerably from 3.1 +/- 0.4 to 154.3 +/- 31.6 mg/L on day 3, while plasminogen decreased from 98.2% +/- 2.0% to 79.8% +/- 2.9% in group B. Global coagulation and platelet function tests were not influenced by either treatment. Neurological score improved by 1.1 arbitrary units (AU) in group A and by 2.6 AU in group B. Five patients in group A and two in group B died during the first two weeks. This preliminary study indicated a slightly better outcome in the ancrod treated patients. The beneficial effect may be due to the anticoagulative and fibrinolytic activity of ancrod rather than its effect on blood viscosity.
 ...
PMID:Controlled trial of ancrod in ischemic stroke. 619 6

Risk factors, pathogenesis, clinical manifestations, diagnosis, and surgical and pharmacological treatment of ischemic stroke are reviewed. Risk factors play an important part in the pathogenesis of ischemic stroke. Knowledge of the complex metabolic and cellular changes that occur during ischemic stroke is rapidly growing. Choosing the correct treatment is dependent upon obtaining a thorough and accurate clinical assessment of the patient. Diagnostic tests help in determining the size, location, etiology, and characteristics of the lesion. Currently no single agent or mode of therapy appears to be most efficacious. Many drugs are still in the human clinical testing stage; promising agents include thrombolytics, low-molecular-weight heparin, and heparinoids. Hemodilution, pentoxifylline, epoprostenol, nimodipine, naloxone, and GM1 therapy have had mixed results in clinical trials, partly because some of these agents were not tested in enough patients to provide an accurate assessment of their efficacy. Atenolol and propranolol are ineffective. Ticlopidine and aspirin decrease the incidence of subsequent stroke but have not been tested in acute ischemic stroke. Heparin may be effective in preventing further cardioembolic stroke or in treating stroke in progress. Nondrug therapies include carotid endarterectomy and surgical decompression for cerebellar stroke. No single agent can be recommended for treatment of ischemic stroke at this time. Promising regimens include ancrod, low-molecular-weight heparin and heparinoids, or thrombolytics.
 ...
PMID:Pathophysiology and treatment of acute ischemic stroke. 831 20

Stroke is an emergency. Ischemic stroke is similar to myocardial infarction in that the pathogenesis is loss of blood supply to the tissue, which can result in irreversible damage if blood flow is not restored quickly. Public education is needed to emphasize the warning signs of stroke. Patients should seek medical help immediately, using emergency transport systems. Therapy geared toward minimizing the damage from an acute stroke should be started without delay in the emergency room. This includes measures to protect brain tissue, support perfusion pressure, and minimize cerebral edema. Strategies for improving recovery should also begin immediately. All major medical centers need stroke teams and stroke units. Stroke prevention should be given high priority as a public health strategy. Risk factor management should be part of general health care and should begin in childhood, with emphasis on nutrition, exercise, weight control, and avoidance of tobacco. Health screening and early treatment of hypertension and hypercholesterolemia has decreased the incidence of stroke and heart disease, but these efforts need to be expanded to reach all segments of the population. Basic research has opened the door to new therapies aimed at re-establishing blood flow and limiting tissue damage. Clinical trials have already led to changes in stroke prevention, including studies of carotid endarterectomy and ticlopidine and warfarin therapy (for patients with atrial fibrillation). Trials in progress are testing the usefulness of ancrod, neuroprotective agents, antioxidant agents, anti-inflammatory agents, low-molecular-weight heparin, thrombolytic drugs, and angioplasty. Any delay starting therapy after an acute stroke will result in progressive, irreversible loss of brain tissue. Clinicians should remember that for a stroke patient, time is brain tissue.
 ...
PMID:Stroke is an emergency. 860 65

In vivo magnetic resonance imaging was used to study the effect of ancrod (CAS 9046-56-4, Arwin), a plasma fibrinogen level lowering agent, on brain lesion in two rat models of acute focal cerebral ischaemia. Total lesion volume was determined by multislice T2-weighted magnetic resonance imaging 24 h after permanent middle cerebral artery occlusion. Intravenous infusion of ancrod starting 30 min after middle cerebral artery occlusion at dosages of 10, 30, 50 or 70 IU/kg (n = 9/group) significantly diminished cerebral lesion volume by 20 to 33% as compared to vehicle-infused controls (n = 12). None of the ancrod-treated rats showed evidence of intracerebral bleeding on T2-weighted magnetic resonance images taken after 24 h. In photochemically induced (rose bengal) unilateral thrombotic cortical infarction brain damage was displayed by multislice diffusion-weighted magnetic resonance imaging after 24 h. Again, post treatment with ancrod reduced total volume of cerebral lesion dose-dependently from 142 +/- 28 mm3 in the controls (n = 10) to 121 +/- 28 mm3 (n = 10) and 111 +/- 20 mm3 (n = 11, p < 0.05) in rats treated with 10 and 30 IU/kg ancrod, respectively (means +/- S.D.). These results suggest cerebroprotection in focal cerebral ischaemia by improvements in the cerebral microcirculation which may offer a potential and safe approach for therapy of acute stroke.
 ...
PMID:Magnetic resonance imaging studies on the effect of the fibrinogen-lowering agent ancrod on cerebral lesions in two rat models of acute stroke. 929 73


1 2 3 Next >>