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)

The authors investigated the behaviour of some markers of the haemostatic balance in a group of patients with acute focal cerebral vasculopathy. The series consists of 70 female patients (mean age: 61 +/- 5), 25 of whom suffering from TIA and 45 from thrombotic stroke; 40 normal controls (mean age 43 +/- 5) were also considered. For each patient after an overnight fasting a withdrawal of venous blood was done within 24-36 hours after the admission. For each sample the determination of seven prothrombotic markers [(fibrinogen (F), factor VII (F VII), antithrombin III (AT III), protein C (PC), protein S (PS) (coagulometric method IL), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) (ELISA method Boehringer)] and of three prethrombotic markers [(fibrinopeptide A (FPA), beta-thromboglobulin (BTG) and D-dimer (D-D) (ELISA method, Boehringer)] was performed. The results obtained in the group of the cerebrovasculopathic patients compared to the controls showed a significant increase of F (p < 0.001), F VII (p < 0.005), BTG (p < 0.05) and D-D (p < 0.01), whereas significant differences regarding AT III, PC, PS, t-PA, PAI and FPA were not observed. The authors hypothesized that the increased levels of fibrinogen and factor VII in the cerebrovascular subjects, globally considered, may depend on a marked prothrombotic state, linked in a pathogenetic sense to the vascular disease; the existence of a prethrombotic state is also documented by the increase of betathromboglobulin and D-dimer.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Haemostatic balance in patients with acute focal cerebral vasculopathy. 760 35

Streptokinase and alteplase are established therapies in acute myocardial infarction. Reteplase is a new thrombolytic agent that can be given as a double bolus. This trial was designed to determine whether the effect of reteplase on survival was at least equivalent (within 1% of fatality rate) to that of a standard streptokinase regimen. Patients from 208 centres in nine countries (n = 6010) with symptoms and electrocardiographic criteria consistent with acute myocardial infarction were randomised to receive double-blind either streptokinase 1.5 MU intravenously over 60 min or reteplase two boluses of 10 MU given 30 min apart. Treatment could be started up to 12 h from onset of symptoms. All patients received intravenous heparin for at least 24 h. The primary endpoint was 35-day outcome. There were 270 deaths (9.02%) in the reteplase and 285 deaths (9.53%) in the streptokinase group, a non-significant difference (95% CI -1.98% to 0.96%). Among patients who received treatment (98.8%) there were 263 deaths (8.90%) in the reteplase compared with 279 deaths (9.43%) in the streptokinase group (a difference of -0.53%). Because the upper limit of the 90% CI for this difference is 0.71%, this result shows that reteplase is at least as effective as streptokinase. In-hospital stroke rates were 1.23% for reteplase and 1.00% for streptokinase. Bleeding events were similar in the two treatment groups (0.7% reteplase, 1.0% streptokinase). The incidence of recurrent myocardial infarction was similar, but there were significantly fewer cases of atrial fibrillation, asystole, cardiac shock, heart failure, and hypotension in the reteplase group. We conclude that reteplase is an effective drug in the treatment of acute myocardial infarction. It is clinically safe, its administration is simple, and it will be a useful addition to the range of thrombolytic agents available.
 ...
PMID:Randomised, double-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction (INJECT): trial to investigate equivalence. International Joint Efficacy Comparison of Thrombolytics. 1111 34

This study investigated the efficacy and safety of delayed therapy with tissue-plasminogen activator (t-PA) in a rabbit model of thromboembolic stroke. The t-PA therapy was started 3, 4, or 5 hours after autologous clot embolization. New Zealand rabbits were randomized to receive a 2-hour intravenous infusion of either t-PA (6.3 mg/kg) or a saline solution (0.9% saline) after an autologous clot had embolized the anterior cerebral circulation. Regional cerebral blood flow (rCBF), intracranial pressure (ICP), and infarct size were measured to determine the effects of the delayed administration of the t-PA after intracranial embolization. Additionally, the following physiological parameters were monitored throughout the protocol: mean arterial pressure, hematocrit, arterial blood gases, glucose, and core and brain temperatures. All animals were studied for 4 hours after the administration of the t-PA or control solution; thus, the duration of each experiment was 7, 8, or 9 hours after autologous clot embolization. In control animals, brain infarct size and final ICP values were directly related to the length of time studied after clot embolization; among control animals, the largest infarct size and greatest rise in ICP were seen 9 hours after embolization.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Delayed tissue-plasminogen activator therapy in a rabbit model of thromboembolic stroke. 764 99

We studied a series of hemostasis factors in a group of patients selected from a cohort of 916 patients affected by MI from the GISSI-2 study population. Following a case-control design, 73 patients with a family history of thrombosis (the presence of at least two first degree relatives affected by MI and/or stroke before 65 years) were matched with MI patients with no family history of thrombosis. Blood collection could be performed 6 +/- 1 months after the acute phase following MI in 53 pairs of such patients. The presence of mixed disulphides (MDS) was significantly higher in patients with family history than in controls; MDS were detected in 7 cases and only in 1 control. No difference was found in contrast in the distribution of fibrinogen, factor VII, factor VIII, vWF, protein C, protein S, AT III, HC II, PAI-1, lipoprotein (a). Nevertheless, independently from the family history, in the whole population of MI patients studied, 21 cases of suspected deficiency of protein C were found. Sixteen out of 53 patients with family history of MI and/or stroke had a family history of MI only. In patients with family history of MI the t-PA antigen levels were significantly lower than in the control group (7.5 +/- 4.4 vs 11.1 +/- 3.5 ng/ml, t = -2.6, p < 0.02). In the whole population of MI patients and in patients with a family history of thrombosis t-PA antigen was positively correlated with PAI-1 antigen and vWF. The correlation with PAI-1 was lost in patients with family history of MI.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Hemostatic factors and family history of thrombosis in patients with a myocardial infarct: a case-control study. The participants in GISSI-2-Efrim. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico]. 764 26

Management of thromboembolic disease involves administration of anticoagulants, thrombolytics or antiplatelet agents to lyse or prevent thrombus extension. Despite widespread use and decades of experience with some of these agents, much is unknown about the effects of dose and plasma concentration on patient response. Unfractionated heparin (UFH) improves outcome in many thromboembolic disorders when administered to a target activated partial thromboplastin time (aPTT) or plasma heparin concentration. UFH exhibits dose-dependency both with absorption from subcutaneous sites and elimination. Doses based on bodyweight or estimated blood volume attain therapeutic aPTTs faster than fixed or standard doses. Low molecular weight heparins (LMWHs) were developed to increase the anti-factor Xa:anti-factor IIa activities. Several different LMWHs are as effective as UFH in treating deep venous thrombosis. Evidence fails to support a relationship between anti-factor Xa activity and either thrombosis evolution or bleeding. No comparisons have been made between bodyweight-based and anti-factor Xa activity-based doses. The dose of orally administered warfarin is adjusted to achieve a target International Normalised Ratio (INR). Maintenance doses are estimated on the basis of the patient's INR during the first 3 days of therapy: the dose required to achieve an optimal INR decreases with age > 50 years. The thrombolytic agents are administered in standard doses to achieve rapid thrombolysis with minimal alteration in systemic haemostasis. Accelerated intravenous alteplase may result in the highest rate of coronary artery reperfusion. Nevertheless, standard doses of streptokinase, anisoylated plasminogen streptokinase complex and alteplase result in similar 1-month mortality rates. The minimal advantage seen with alteplase is offset by higher rates of stroke. Future trials will focus on administration strategies achieving rapid thrombolysis, while minimising the risk of serious bleeding. With the antiplatelet agents, unpredictability in the pharmacokinetic parameters of different products has confounded interpretation of published reports. Optimal aspirin (acetylsalicylic acid) administration would include administration of an initial dose of 160 to 325mg after an acute vascular event, followed by maintenance dosages of approximately 75 mg/day for prophylaxis or treatment. Ticlopidine does not exhibit a relationship between either plasma concentration or dose and adverse effects, while pharmacodynamic effects may be dose-, but not plasma concentration-, dependent. The correlation between the concentration of dipyridamole and some of its antiplatelet effects may be the strongest amongst all the antiplatelet agents. However, unfortunately all clinical trials used standard doses and the current consensus is that dipyridamole alone is not an effective antiplatelet agent.
 ...
PMID:Pharmacokinetic optimisation of the treatment of embolic disorders. 771 62

We evaluated the ability of monoclonal antibodies directed against leukocyte adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], CD18) to enhance the efficacy of thrombolysis in a rabbit cerebral embolism stroke model. Both tissue-type plasminogen activator (tPA) and anti-CD18 (alpha-CD18) monoclonal antibody administered 5 minutes after embolization increased the quantity of clots required to produce neurologic damage, although the combination was no more effective than either substance alone. Neither alpha-CD18 nor anti-ICAM-1 (alpha-ICAM-1) improved neurologic outcome at postischemic delays of 15 or 30 minutes. However, the combination of alpha-ICAM-1 (15 minutes after embolization) and tPA (2 hours after embolization) significantly improved neurologic outcome even though neither substance was effective alone at these postembolization delays. These findings suggest that prevention of leukocyte adhesion increases the postischemic duration at which thrombolytic therapy remains effective.
 ...
PMID:Monoclonal antibodies preventing leukocyte activation reduce experimental neurologic injury and enhance efficacy of thrombolytic therapy. 772 76

The introduction of thrombolysis has reduced the mortality of acute myocardial infarction (MI) by 25%. Large-scale studies have revealed that especially patients over 65 benefit from this therapy. Nevertheless, many centers apply an age limit for thrombolytic therapy due to the higher risk of stroke or bleeding in elderly patients. In 1993 181 patients suffering from acute MI were admitted to the intensive care unit of the University Clinic of Internal Medicine, Graz, and 54 (29.4%) of them were treated with fibrinolytic drugs. In this paper we report on the successful thrombolytic management of acute MI in two male patients (87 and 88 years old) who were treated with 100 mg recombinant tissue-type plasminogen activator complex. As a sign of successful reperfusion a rapid increase in plasma creatinine kinase levels and fast amelioration of the ischemia-related ECG changes were observed. In the follow-up examination after four months the first patients showed only minimal exertional dyspnea and was otherwise well. The second patient died one month after MI following a laparotomy for ileus. We draw the conclusion that patients of advanced age also benefit from thrombolytic treatment of acute myocardial infarction, but the indications and contraindications have to be carefully observed.
 ...
PMID:[Thrombolytic therapy of acute myocardial infarct in advanced age (based on 2 case reports)]. 773 94

Intracerebral hemorrhagic transformation is one of the most important complications of thrombolytic therapy for acute ischemic stroke. The relationship between changes in markers for the coagulation and fibrinolytic systems and occurrence of hemorrhagic transformation was determined after local intra-arterial thrombolytic therapy using urokinase (UK) (24 patients) or recombinant tissue plasminogen activator (t-PA) (10 patients) within 6 hours of onset. All 34 patients had no hypodensity areas on initial computed tomography scans. Plasma concentrations of fibrinogen-fibrin degradation products (FDP), fibrinogen, alpha 2-plasmin inhibitor (alpha 2-PI), plasmin-alpha 2 plasmin inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), and D-dimer were measured. Hemorrhagic transformation occurred in seven patients (21%) with complete or partial recanalization; four in the UK group and three in the t-PA group. Doses of the thrombolytic agents did not correlate with the incidence of hemorrhagic transformation. The FDP levels in the hemorrhagic transformation group treated with UK significantly increased immediately and 1 hour after the therapy. The alpha 2-PI activities decreased and PIC levels increased in both the hemorrhagic transformation and the nonhemorrhagic groups after the therapy. The TAT levels in both groups tended to be higher than the normal range, but there was no significant difference from the pretreatment levels. The D-dimer levels in the hemorrhagic transformation group were higher than those in the nonhemorrhagic group at 24 hours after the therapy. Furthermore, the D-dimer levels were significantly higher in patients with complete recanalization compared with those with none or partial recanalization.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Changes in coagulation and fibrinolytic system after local intra-arterial thrombolysis for acute ischemic stroke. 777 Jan 6

Thrombolytic therapy remains a mainstay for the treatment of patients with acute myocardial infarction. This therapy has been the subject of intense investigation and multiple studies as well as substantial controversy. Controversial issues include, among others, the specific drug, need for heparin, the relation between time to treatment and outcome and risk/benefit considerations. The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial of 41,021 patients addressed many of these issues. The results of the main trial were conclusive--treatment with accelerated tissue-type plasminogen activator (t-PA) resulted in a decreased mortality rate with a 15% reduction (95% confidence interval 5.9 to 21.3) compared with the two streptokinase monotherapy strategies (p = 0.001). Virtually all subgroup analyses, including age, nonanterior infarction location, patients undergoing bypass graft surgery and hypertensive patients, showed remarkable consistency with improved outcome with accelerated t-PA. This reduction in all-cause mortality with accelerated t-PA was associated with a small (absolute 0.2%) but significant increase in hemorrhagic stroke (p = 0.03). A combined end point of death or disabling stroke, or both, was still decreased in the accelerated t-PA group compared with the streptokinase group (p = 0.006). The angiographic substudy evaluated the mechanism of improved outcome and documented that reperfusion therapy works by restoring Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow early, improving left ventricular function and improving mortality. The most favorable outcome seen with t-PA was related to the finding that it resulted in improved TIMI grade 3 flow compared with that for streptokinase.
 ...
PMID:Lessons we have learned from the GUSTO trial. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries. 777 8

The effect of thrombolytic therapy is well-documented in acute myocardial infarction. In acute cerebral infarction, thrombolytic therapy has been evaluated in small series of patients. The point of thrombolytic therapy is to avoid or reduce ischemic damage of neuronal tissue by rapid arterial recanalization. In thrombolytic therapy of cerebral vascular occlusion, the pathophysiology of reperfusion needs further investigation and documentation. This review describes studies of thrombolysis in embolic stroke using animals embolized by intracarotid injections of blood clots. Vascular occlusion was demonstrated by angiography and measurement of cerebral blood flow. Thrombolytic therapy with recombinant tissue-type plasminogen activator was initiated after varying periods of time. Reperfusion, cellular function, and brain damage were examined by angiography and by clinical and pathoanatomical examination. Based mainly on results from our own investigations, the following theses concerning ischemic stroke were made: (a) Cerebral infarction caused by arterial occlusion is due to delayed, incomplete, or no reperfusion. Spasms, or hemodynamic mechanisms, seem to be of only minor importance. (b) Early thrombolytic therapy in animal models increases the degree of reperfusion and reduces brain damage, clinical deficits, and mortality. (c) Early arterial reperfusion reduces cerebral infarction and related edema. With early reperfusion, the extent of brain damage correlates to the length of the delay from onset of ischemia. (d) Cerebral stunning is caused by arterial occlusion followed by very early spontaneous or induced reperfusion, as neurons temporarily lose their functional capabilities without dying. (e) Multiple embolic microclots in experimental stroke result in more brain damage than a single macroclot, and with clots the extent of brain damage is dependent on the structural composition and volume of emboli. (f) The ability to recanalization in experimental embolic stroke is related to the amount of red cells in the emboli and inversely related to the volume of emboli and to the fibrin content and density of the clots. (g) Infarct-limiting effects in experimental stroke can be obtained by ischemic neuroprotectants or by hypothermia, either alone or with thrombolytic therapy, which then reduces brain damage further.
 ...
PMID:Thrombolytic therapy in experimental embolic stroke. 781 66


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>