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

This study investigates retrospectively, in selected patients, the ischemic outcome (reversible ischemia, infarction, and hemorrhage) and neurologic outcome of acute stroke treated with intra-arterial thrombolysis and the predictive value of pretreatment single-photon emission-computed tomography (SPECT). Thirty patients with complete recanalization within 12 hours were analyzed. The extent of ischemia was outlined on SPECT, and two CBF parameters were calculated: the ratio of ischemic regional activity to CBF in the cerebellum and the asymmetry index. Reversible ischemia, infarction, and hemorrhage were identified by comparing SPECT and follow-up computed tomography. Nine patients (30%) had no or small infarction, 14 (47%) had medium or large infarction, and seven (23%) had hemorrhage. Forty-two lesions were identified (22 reversible ischemia, 13 infarction, and 7 hemorrhage). Duration of ischemia, urokinase dose, disease type, and occlusion site were nonsignificant factors, whereas neurologic outcome and CBF parameters were significant among the three patient groups and three types of ischemic lesions. Ischemic tissue with CBF greater than 55% of cerebellar flow still may be salvageable, even with treatment initiated 6 hours after onset of symptoms. Ischemic tissue with CBF greater than 35% of cerebellar flow still may be salvageable with early treatment (less than 5 hours). Ischemic tissue with with CBF less than 35% of cerebellar flow may be at risk for hemorrhage within the critical time window. Pretreatment SPECT can provide useful parameters to increase the efficacy of thrombolysis by reducing hemorrhagic complications and improving neurologic outcome.
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PMID:Outcome in acute stroke with successful intra-arterial thrombolysis and predictive value of initial single-photon emission-computed tomography. 988 60

Saruplase (unglycosylated human-type high molecular weight single-chain urokinase-type plasminogen activator) was given to 1698 patients in the open-label Practical Applicability of Saruplase Study (PASS), which assessed the safety and efficacy of saruplase in the treatment of acute myocardial infarction. Thirty-seven hospitals in Europe participated in the study. All patients received 20 mg saruplase as a bolus followed by an infusion of 60 mg saruplase over 1 hour. Prior to the infusion of saruplase, 62% of the patients received a bolus of 5000 U of heparin, and after saruplase a 24-hour intravenous infusion of heparin was given to 95% of patients. The mean age of the patients was 59 years and 80.1% were male. The median delay from the onset of chest pain to the start of saruplase infusion was 145 minutes. Acute angiography was performed in 8 of the participating 37 centers in 350 patients (20.6%), on average 85 minutes (median) after the start of the saruplase infusion. TIMI 3 flow was obtained in 186 patients (53.1%) and TIMI 2 flow in 61 patients (17.4%). Patency rates were similar for patients with anterior and inferior infarction. ECG signs suggestive of reperfusion were seen in 63% of the patients. In-hospital mortality was low (92 patients; 5.4%), and nonfatal recurrent myocardial infarction was seen in 60 patients (3.5%). Severe bleeding complications occurred in 92 patients (5.4%), 21 of whom (1.2%) needed a blood transfusion. An intracerebral hemorrhage was observed in eight patients (0.5%), and seven patients (0.4%) suffered from a thromboembolic stroke. At discharge 85.9% of the patients were in NYHA functional class I. One-year mortality was low (142 patients; 8. 4%). Mortality was high in patients with TIMI 0 or 1 flow at the acute angiography who did not undergo rescue PTCA (9/39; 23.1%), lower in patients with TIMI 0 or 1 flow followed by successful rescue PTCA (7/64; 10.9%), and low in patients with TIMI 2 flow (1/61; 1.6%) or with TIMI 3 flow (2/186; 1.1%). Patency rates and (bleeding) complications did not differ between patients with a body weight greater than or less than 70 kilograms. No antibodies against saruplase were detected in samples from 455 patients. In conclusion, it can be stated that saruplase, given in combination with aspirin and intravenous heparin, can be given safely and effectively to patients with acute myocardial infarction.
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PMID:Saruplase is a safe and effective thrombolytic agent; observations in 1,698 patients: results of the PASS study. Practical Applications of Saruplase Study. 1043 45

The purpose of this study was to determine the efficacy of intraoperative intraarterial urokinase (UK) in patients who suffered an acute stroke immediately following carotid endarterectomy (CEA). From January 1995 to March 1998, 823 carotid endarterectomies were performed. The subsequent results showed that intraarterial UK in the setting of early post-CEA neurologic events appears to be safe and may be a useful adjunct to re-exploration in improving neurologic outcomes.
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PMID:Intraoperative intraarterial urokinase in early postoperative stroke following carotid endarterectomy: a useful adjunct. 1054 7

This study was designed to investigate possible diurnal fluctuations in the efficacy of thrombolysis with streptokinase and whether they follow the circadian periodicity which has already been well documented for the time of onset of acute myocardial infarction, transient myocardial ischaemia, sudden cardiac death, thrombotic stroke, and for the efficacy of thrombolysis with tissue-type plasminogen and urokinase. A total of 156 consecutive patients treated with streptokinase were studied retrospectively; success or failure of thrombolysis was determined according to accepted clinical and angiographic criteria. A definite time peak for successful thrombolysis could be detected at the late afternoon and early evening hours; between 16.00 and 20.00 h, 30.2% of all successful thrombolysis cases were observed compared with 7.0% between 20.00 and 24.00 (p < 0.05) or 10.5% between 00.00 and 04.00 (p < 0.05). Between 16.00 and 20.00 h, 75.8% of treated patients had successful thrombolysis compared to 15.2% of failed treatments and 9% equivocal results (p < 0.001). Multiple regression analysis showed that the independent factor with the major impact on successful reperfusion was the actual time of thrombolysis (p = 0.037), followed by the time delay from pain onset to streptokinase administration (p = 0.020), while age and gender had much lesser impact (p = 0.328 and 0.215, respectively) and the individual risk factors even less. These findings may have several clinical implications; dose adjustment for the time of day may be required, with higher doses during morning hours, or preference for primary coronary angioplasty in order to avoid the increase in bleeding complications related to higher doses of thrombolytic agents.
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PMID:Circadian fluctuations in the efficacy of thrombolysis with streptokinase. 1062 77

Abciximab decreases ischemic complications during angioplasty. Intracoronary urokinase lyses intracoronary thrombus. We studied the combination of both drugs. Twenty-six consecutive patients with acute coronary syndromes and intracoronary thrombus underwent intervention with abciximab and intracoronary urokinase. All received aspirin and IV heparin. The dose of abciximab was a weight-adjusted bolus and a 12-hr infusion. The dose of urokinase was 250,000 to 633,000 units. Hemorrhagic complications were classified according to the TIMI study group. Hemoglobin and platelet counts were measured before and 12 and 48 hr after the procedure. Procedural success was achieved in 24 patients. There were no deaths or repeat interventions. No patient had a major bleeding complication. Only two had minor complications. One patient needed blood transfusion. None had a stroke or thrombocytopenia. The use of abciximab and intracoronary urokinase in the presence of intracoronary thrombus is associated with encouraging efficacy and few complications. Cathet. Cardiovasc. Intervent. 49:113-116, 2000.
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PMID:Safety and efficacy of abciximab use in conjunction with intracoronary urokinase in patients requiring angioplasty. 1062 83

Intra-arterial thrombolytic therapy has replaced systemic intravenous infusion of thrombolytic agents as a treatment modality for arterial occlusion in the limbs. Several catheter-guided techniques and various infusion methods and schemes have been developed. At present there is no scientific proof of definite superiority of any agent in terms of efficacy or safety but clinical practice favours the use of urokinase or alteplase. Studies which compared thrombolysis to surgical intervention suggest that thrombolytic therapy is an appropriate initial management in patients with acute occlusion of a native leg artery or a bypass graft. Underlying causative lesions are treated in a second step by endovascular or open surgical techniques. Severe bleeding is the most feared complication: the risk of hemorrhagic stroke is 1-2%.
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PMID:Thrombolysis in arterial occlusion. 1069 98

The angiopoietin/Tie receptor system may contribute to angiogenesis and vascular remodeling by mediating interactions of endothelial cells with smooth muscle cells and pericytes. The temporal expression of angiopoietin-1 (Angpo-1), angiopoietin-2 (Angpo-2), Tie-1, and Tie-2 mRNA was studied in a focal cerebral ischemia model in rats. The cDNA fragments obtained from reverse transcription polymerase chain reaction amplification were cloned and used as a probe to detect individual genes. Northern blot analysis showed a delayed increase of a 4.4-kb Angpo-1 transcript for up to 2 weeks after ischemia, eightfold higher than the values of the sham-operated controls. A biphasic expression of a 2.4-kb Angpo-2 transcript was noted, peaking at 24 hours (6.4-fold) and 2 weeks (4.6-fold) after ischemia. The expression of Tie-2 mRNA (4.3 kb), a receptor for Angpo-1, and Tie-1 mRNA (4.3 kb) also increased starting 24 hours after reperfusion and remained elevated for up to 2 weeks after ischemia. The temporal profiles of the expression of these genes were different from those of other angiogenic genes such as basic fibrobast growth factor/fibroblast growth factor receptor and vascular endothelial growth factor/vascular endothelial growth factor receptor and proteolytic enzymes (tissue-type plasminogen activator and urokinase plasminogen activator) and their inhibitors (plasminogen activator inhibitor-1). The expression patterns of these genes could be related to progressive tissue liquefaction and neovascularization after ischemia in this stroke model. Differential expression of these angiogenesis genes suggests the involvement of complex regulatory mechanisms that remain to be characterized.
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PMID:Induction of angiopoietin and Tie receptor mRNA expression after cerebral ischemia-reperfusion. 1069 77

Thrombolysis is increasingly being used in treating acute ischemic stroke but it is also accompanied with a serious complication of cerebral hemorrhage in a dose-dependent fashion. As a lower dose may result in decreased effectiveness, we tested the efficacy of combining a neuroprotective agent, topiramate (TPM), with lower doses of intra-arterial urokinase in an embolic stroke model. Focal ischemia was produced by introduction of an autogenous thrombus into the right middle cerebral artery. Urokinase was infused via the ipsilateral internal carotid artery and neuroprotective agent, TPM, was administrated intra-peritoneally 2 h following ischemic insult. The animals were assigned to five groups: (1) control group (n=6); (2) urokinase 5000 units/kg (n=8); (3) urokinase at 2500 units/kg (n=8); (4) topiramate at 20 mg/kg (n=8); (5) urokinase at 2500 units/kg and topiramate at 20 mg/kg (n=8). Neurobehavioral outcome and the degree of brain infarct volume were assessed at 24 h. Three animals in the group treated by high dose urokinase developed intracranial hemorrhage but none in other groups. Animals in all medication-groups showed significant improvement in neurobehavioral score. Post-ischemia treatment with urokinase or TPM alone significantly attenuated brain infarct volume (low-dose urokinase, 39.1+/-13.0%, p<0.05; high-dose, 18.4+/-8.5%, p<0.001; TPM, 20. 1+/-11.2%, p<0.001) when compared to the control (54.2+/-9.04%). Addition of TPM to low dose urokinase achieved better neuroprotection (8.2+/-6.0%) than any single-drug-treated groups. Our data suggests that combination of low dose urokinase with a neuroprotective agent may benefit ischemic stroke treatment by improving neurologic recovery, attenuating infarction size, and reducing the risk of cerebral hemorrhage.
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PMID:Enhanced neuroprotection and reduced hemorrhagic incidence in focal cerebral ischemia of rat by low dose combination therapy of urokinase and topiramate. 1069 54

Clinical trials in the 1990s of intravenous thrombolysis for ischaemic stroke have involved over 3000 patients. Alteplase given within 3 hours of onset significantly reduces the combined end-point of death and disability. Although alteplase appears safe when given up to 6 hours after onset, individual trials have failed to confirm efficacy beyond 3 hours. Meta-analysis indicates that intravenous alteplase given up to 6 hours after stroke onset significantly reduces death or dependence 3 months after stroke. Two trials of intra-arterial pro-urokinase confirm benefits of treatment up to 6 hours in highly selected patients with angiographically confirmed proximal middle cerebral occlusion. Streptokinase increased the risk of early death significantly in 3 trials, with no overall reduction in eventual death and disability. Patients over 80 years have been excluded from most trials of alteplase, and experience in this age group is minimal. Increased incidence and poorer functional outcome in the elderly mean that thrombolysis may have greater absolute benefit in this group than in the young, but there is also a higher prevalence of absolute or relative potential contraindications to treatment (ranging from increased use of anticoagulant drugs to higher prevalence of atrial fibrillation). Further trials are necessary to address age restrictions and other important issues in the use of alteplase. Thrombolysis is likely to remain feasible for a minority of stroke patients of all ages, and there is a need for other acute treatment options.
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PMID:Thrombolytic therapy for stroke: a review with particular reference to elderly patients. 1073 63

Neuroserpin, a recently identified inhibitor of tissue-type plasminogen activator (tPA), is primarily localized to neurons within the central nervous system, where it is thought to regulate tPA activity. In the present study neuroserpin expression and its potential therapeutic benefits were examined in a rat model of stroke. Neuroserpin expression increased in neurons surrounding the ischemic core (ischemic penumbra) within 6 hours of occlusion of the middle cerebral artery and remained elevated during the first week after the ischemic insult. Injection of neuroserpin directly into the brain immediately after infarct reduced stroke volume by 64% at 72 hours compared with control animals. In untreated animals both tPA and urokinase-type plasminogen activator (uPA) activity was significantly increased within the region of infarct by 6 hours after reperfusion. Activity of tPA then decreased to control levels by 72 hours, whereas uPA activity continued to rise and was dramatically increased by 72 hours. Both tPA and uPA activity were significantly reduced in neuroserpin-treated animals. Immunohistochemical staining of basement membrane laminin with a monoclonal antibody directed toward a cryptic epitope suggested that proteolysis of the basement membrane occurred as early as 10 minutes after reperfusion and that intracerebral administration of neuroserpin significantly reduced this proteolysis. Neuroserpin also decreased apoptotic cell counts in the ischemic penumbra by more than 50%. Thus, neuroserpin may be a naturally occurring neuroprotective proteinase inhibitor, whose therapeutic administration decreases stroke volume most likely by inhibiting proteinase activity and subsequent apoptosis associated with focal cerebral ischemia/reperfusion. (Blood. 2000;96:569-576)
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PMID:Neuroserpin reduces cerebral infarct volume and protects neurons from ischemia-induced apoptosis. 1088 20


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