Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of thrombolytic therapy to treat AMI has reawakened interest in thrombolysis for acute pulmonary embolism (PE). We have investigated the use of recombinant human tissue-type plasminogen activator (rtPA) in patients with acute PE. In an open label study, rtPA achieved more than 90% efficacy and safety. In a trial comparing rtPA with an FDA-approved dose of urokinase (UK), rtPA appeared more rapid and safer. We are now conducting a comparative trial of rtPA with a novel dosing regimen of UK. In addition, a concurrent trial is comparing rtPA vs heparin for improvement in right ventricular function, assessed by echocardiography, among PE patients. However, the greatest challenge in PE research is to undertake a large-scale trial that compares thrombolysis and heparin for reduction of clinically relevant end points such as mortality and recurrent PE.
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PMID:Tissue plasminogen activator in acute pulmonary embolism. 249 13

Many investigators have reported about beneficial results with thrombolytic therapy in patients with acute pulmonary embolism. Streptokinase and urokinase have been used for more than 15 years, but the conditions of use of these agents still remain controversial. Optimal dosage and treatment schedule are still evolving. For streptokinase most investigators adopt a fixed dosage schedule: a loading dose of 250,000 units followed by a maintenance infusion of 100,000 units per hour for 24 to 72 hours. For urokinase numerous dosage regimens have been used such as: high dosage schedule 4,400 units per kilogram per hour for twelve to 24 hours with or without loading dose; moderate dosage 1,600 to 2,000 units per kilogram per hour for 24 hours and low dosage in bolus. With these treatments there is a trend to reduced in-hospital-mortality in massive pulmonary embolism; the early pulmonary revascularization and the hemodynamic improvement are higher than those noticed with heparin. These results are obtained with a minimum of complication essentially bleeding in 10 or 15%; most bleeding being located at puncture site. More recently, new thrombolytic agents have been used in acute pulmonary embolism. Only four studies have tested rt-PA which is effective and relatively safe, but the optimal dose regimens remain to be determined. Less information is available concerning Anisoylated Plasminogen Streptokinase Activator Complex (APSAC), the angiographic improvement seems to be rapid and important (50% on average) but the decrease of fibrinogen is important too and comparable with streptokinase. Considering the good results of thrombolytic treatment of acute submassive and massive pulmonary embolism, there is a doubt as to whether the pulmonary embolectomy has any place in the pulmonary embolism patients except in those with cardiac arrest. In the near future new thrombolytic drugs could be more efficient on pulmonary embolism and deep venous thrombosis, and thus the bleeding risk might be decreased.
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PMID:Thrombolytic treatment of acute pulmonary embolism. 250 Mar 88

The age of the thrombus is probably a very important determinant of the outcome of thrombolysis. The clinical potential for rapidly dissolving thrombi by thrombolytic therapy is considerable because restoration of the blood flow can rescue the jeopardized district served by the occluded vessel such as for myocardial infarction, deep vein thrombosis, arterial thrombosis, pulmonary embolism, and occlusion of retinal vessels. Defibrotide was effective against 3-, 7-, or 10-day-old thrombi; its ED50s were 32, 65, or 118 mg/kg-1 hour-1, respectively, suggesting that the age of the thrombus could play a role in the outcome of thrombolysis. A similar pattern was also shown for urokinase.
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PMID:Thrombolytic activity of defibrotide against old venous thrombi. 251 Mar

In the 1970s controlled studies in acute massive and submassive pulmonary embolism demonstrated by angiography, scintiscan and hemodynamic measurements that urokinase (UK) and streptokinase (SK) induce a more rapid dissolution of thrombotic material in the pulmonary circulation than heparin. Thousands of individuals would have been needed to prove a statistically significant reduction in the relatively low mortality (10-20%) in the study population. However, in massive pulmonary embolism with right ventricular overload, the advantage of thrombolysis is clearly evident. As confirmed by treatment series of varying size, SK and UK usually require 1-3 days for extensive clearance accompanied by impressive functional improvement. If contraindications are observed and invasive procedures avoided, the bleeding risk is acceptable. Acute severe pulmonary embolism with marked pulmonary hypertension but stable circulation should be treated with conventional doses of SK or UK for several days. In cases with unstable circulation or established shock vital improvement may be obtained by bolus injection (into pulmonary artery, right atrium or i.v.) of 2 m I.U. UK or by short i.v. infusion of 100 mg tissue plasminogen activator. Rapid reduction of pulmonary vascular resistance to a less critical value will prevent right ventricular decompensation and save time for embolectomy or subsequent conventional thrombolytic therapy.
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PMID:[The value of thrombolysis for the treatment of acute pulmonary embolism]. 251 56

Pulmonary embolism can produce severe cardiopulmonary dysfunction characterized by pulmonary artery hypertension, right ventricular failure, and hypoxemia. The search for the source of a pulmonary embolus, by exploration of the veins of the lower limbs and the inferior vena cava should be systematically carried out in all cases of pulmonary embolus which are not immediately life-threatening to the patient. The treatment of deep vein thrombosis associated with pulmonary embolism with thrombolytic agents has been proposed and utilized for approximately 20 years. Although superior results have been claimed with thrombolytic agents, the use of this type of treatment remains limited to massive or sub-massive pulmonary embolism. Fibrinolytic agents with high specificity for fibrin in the thrombi and little systemic activation of the fibrinolytic system have been developed and tested in preliminary clinical trials of patients with acute pulmonary embolism. The largest published experience available has been with recombinant tissue plasminogen activator (rtPA). The acylated streptokinase-plasminogen complex (APSAC) and pro-urokinase also gave promising results. All these agents were accompanied by unexpectedly high incidence of systemic activation of the fibrinolytic system and by hemorrhagic complications with frequencies similar to those that follows the use of first generation products (urokinase and streptokinase). Hence, their superior clinical efficacy must be clearly proven before they are substituted for a more widely available and less expensive drug, such as streptokinase.
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PMID:Pathogenesis and management of acute pulmonary embolism. 251 49

Two recipients of orthotopic liver transplants (OLT) underwent intra-arterial thrombolytic treatment for hepatic artery thrombosis. Complete clot lysis was achieved in both using infusion of high-dose urokinase directly into the thrombus for 12 and 3 hours, respectively. Percutaneous transluminal angioplasty (PTA) was later carried out successfully on various strictures. Doppler ultrasonography confirmed arterial permeability one month after treatment. Liver transplantation is now an accepted therapeutic option in some patients with irreversible liver failure. Although the results of this procedure have improved radically since cyclosporine was introduced in 1978, life-threatening postoperative complications still occur. The one with the worst prognosis is hepatic artery thrombosis (HAT), with 64% mortality despite retransplantation. HAT was found in 7.4% of liver transplant recipients in a recent review of the most important group of these patients. Fibrinolytic treatment using an exogenous plasminogen activator, urokinase (UK), is effective and safe in the thrombotic obstruction of acute pulmonary embolism, acute myocardial infarction, and graft or peripheral arterial occlusion. We used intra-arterial thrombolysis in two patients with HAT of the liver graft, to avoid retransplantation and to treat a complication secondary to percutaneous transluminal angioplasty (PTA) of an anastomotic stricture, respectively. To our knowledge, this is the first report of treatment of HAT by direct infusion of urokinase in liver transplantation.
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PMID:High-dose intra-arterial urokinase for the treatment of hepatic artery thrombosis in liver transplantation. 261 76

The difficulty in making an accurate diagnosis of acute pulmonary embolism is well known. To clarify the role of echocardiography, including Doppler echocardiography, in acute pulmonary embolism, we examined hemodynamic and echocardiographic parameters in 9 patients with acute pulmonary embolism just before and after treatment with urokinase. As hemodynamic parameters normalized after treatment, echocardiographic parameters such as deformity index of the left ventricle (LV-DI), end-diastolic dimension of the right ventricle (RVDd), the left ventricle (LVDd), the inferior vena cava, and RVDd/LVDd all significantly changed toward normal. Highly significant correlations were found between the echocardiographic and hemodynamic parameters, the best of which was between the LV-DI and systolic pulmonary artery pressure (r = -0.885, p less than 0.001). Doppler echocardiography quantitatively evaluated the grade of tricuspid regurgitation, and accurately estimated systolic pulmonary artery pressure. We conclude that echocardiography, including Doppler echocardiography, sensitively reflects the right ventricular pressure and volume overload of acute pulmonary embolism, is quite useful for its diagnosis which is often difficult, and is suitable for noninvasive follow up of these patients.
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PMID:Role of echocardiography in acute pulmonary embolism. 261 28

A 78-year-old woman, suffering from acute massive pulmonary embolism, was successfully treated with transvenous pulmonary embolectomy by catheter. This patient had been suffering from oppressive chest sensations during exercise, and diagnosed and treated as angina pectoris at a nearby clinic. She consulted our hospital complaining that her chest pains were increasing in frequency. She was admitted to our hospital on July 7, 1988, for coronary angiography (CAG), which she underwent on July 8 by the right femoral approach. After the CAG, she was ordered to rest in bed overnight, with the right inguinal region compressed. 18 hours later, the compression was removed and she was allowed to walk. Soon after she walked to the toilet, she complained of chest discomfort and fell into shock (systolic blood pressure was 60 mmHg). An ECG examination showed a right bundle branch block and an inverted T wave in lead V1-3. An echocardiography showed normal contraction of the left ventricle, but an enlargement of the right ventricle and a flattened interventricular septum. An analysis of arterial blood gas showed hypoxia (Pao2 52.5 mmHg, Paco2, 30.9 mmHg). Acute pulmonary embolism was suspected. 240,000 units of urokinase were administered intravenously, and pulmonary angiography was performed immediately. It revealed that the bilateral pulmonary arteries were almost completely obstructed. Although 720,000 units of urokinase were infused into the pulmonary artery, the obstruction did not improve. At that time, we performed a transvenous pulmonary embolectomy. We used a Judkins R 4 guiding catheter for PTCA made by USCI. The catheter was inserted into the pulmonary artery and clots were aspirated with a syringe.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of acute massive pulmonary embolism successfully treated with transvenous pulmonary embolectomy by catheter]. 261 14

After a brief mention of new advances in the pathophysiology of fibrinolysis, the authors outline the pharmacological properties of the new thrombolytic agent rt-pA versus classic thrombolytic agent urokinase and streptokinase. Thereafter they report a case of acute pulmonary embolism with severe hypoxemia in a patient with a history of recent traumatic cerebral bleeding. Thrombolytic treatment with rt-pA (100 mg/2 h) resulted in a satisfactory clinical outcome without appreciable worsening of intracranial injury.
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PMID:[A clinical case of pulmonary thromboembolism in a patient at risk treated with rt-pA]. 263 76

It has been shown in animals that acute obstruction of pulmonary artery branches is followed by an early but shortly lived increase in blood levels of thromboxane B2 and a subsequent longer-lasting increase in blood levels of 6-keto-PGF1 alpha. Our study was conducted on twelve patients with acute pulmonary embolism. Nine were treated with urokinase; three could not be given thrombolytic or anticoagulant drugs due to bleeding peptic ulcer (2 cases) or recent cerebral hemorrhage (1 case). HPLC and RIA tests were performed on arterial blood samples at diagnosis and after 1, 6, 12 and 24 hours. Findings were compared with those in a control group of 6 healthy subjects. There was a difference in prostanoid behaviour between the untreated and urokinase treated patients. Among the former mean TxB2 was significantly raised at clinical onset and began to decline after 6-12 hours, approaching the mean level found among the controls after 24 hours. In contrast 6-keto-PGF1 alpha was raised after 1 hour and gradually declined thereafter. In the subjects treated with urokinase TxB2 was already close to the mean control level after 1 hour; 6-keto-PGF1 alpha had increased after 1 hour but had returned near the control level after 12. The behaviour of prostanoids appears to match the clinical course.
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PMID:The release of thromboxane B2 and 6-keto-PGF1 alpha following pulmonary embolism. 263 7


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