Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Intraarterial thrombolytic therapy can be life-saving in patients with vertebrobasilar occlusion. Thrombotic occlusions of the internal carotid artery or middle cerebral artery often result in disabling ischemic cerebral infarctions. Local fibrinolysis may help to minimize the neurological sequelae. Indications and contraindications for such a therapy are not yet well established, and more discussion is needed. During the last 2 years we have treated 18 patients with occlusions of vessels supplying the brain by means of local intraarterial thrombolytic therapy with urokinase. These included 5 patients who presented with internal carotid/middle cerebral artery occlusions, 3 of whom left the hospital with only minor neurological deficits while 2 died despite therapy. The other 13 patients had acute vertebrobasilar occlusion: 6 patients survived, 3 with a good general condition and 2 with locked-in syndrome. Technique, dosage of urokinase and patient selection are discussed as well as the outcome.
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PMID:[Intra-arterial thrombolysis of vessels supplying the brain]. 206 83

Thrombotic obstruction frequently prohibits infusion through or withdrawal of blood from central venous catheters and can occur in conjunction with symptomatic thrombosis of the subclavian vein. Thirty catheters were radiographically proved to be obstructed by thrombus and had not responded to at least one instillation of 5000 units of urokinase. All catheters were treated with a 12-hour infusion of urokinase at the rate of 40,000 units/hour. The obstructing thrombus was either eliminated or reduced in size in all instances and full function was restored in all but one catheter. No bleeding complications were seen. Six patients with obstructed catheters also had symptoms of subclavian vein thrombosis. All patients with symptoms of subclavian vein obstruction became asymptomatic on anticoagulant therapy even though no attempt at dissolving the thrombus obstructing the subclavian vein was made. A 12-hour infusion of low doses of urokinase can safely salvage function of obstructed catheters that otherwise may require replacement. Patients with concomitant subclavian vein thrombosis become asymptomatic on anticoagulant therapy without need to dissolve the obstructing thrombus.
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PMID:Obstructed central venous catheters. Restoring function with a 12-hour infusion of low-dose urokinase. 212 25

Thrombotic complications of cardiovascular disease are a main cause of death and disability and, consequently, thrombolysis could favorably influence the outcome of such life-threatening diseases as myocardial infarction, cerebrovascular thrombosis and venous thromboembolism. Thrombolytic agents are plasminogen activators that convert plasminogen, the inactive proenzyme of the fibrinolytic system in blood, to the proteolytic enzyme plasmin. Plasmin dissolves the fibrin of a blood clot, but may also degrade normal components of the hemostatic system and predispose to bleeding. Currently, five thrombolytic agents are either approved for clinical use or under clinical investigation in patients with acute myocardial infarction. These include streptokinase, urokinase, recombinant tissue-type plasminogen activator (rt-PA), anisoylated plasminogen streptokinase activator complex (APSAC) and single chain urokinase-type plasminogen activator (scu-PA, prourokinase). The first generation thrombolytic agents, streptokinase (and probably also urokinase), are only moderately efficacious and their administration is associated with extensive systemic fibrinogen breakdown. In comparative studies performed in patients with acute myocardial infarction, recombinant tissue-type plasminogen activator (rt-PA) is a more effective and fibrin-specific thrombolytic agent than streptokinase. The acylated plasminogen streptokinase activator complex (APSAC) has a profile of thrombolytic efficacy and fibrin-specificity that is similar or somewhat better than that of streptokinase, but has the advantage that it can be administered by bolus injection. Single chain urokinase-type plasminogen activator is more fibrin-specific than urokinase. Comparative data on the efficacy and safety of this agent are limited as it is in the early stage of clinical investigation. Reduction of infarct size, preservation of ventricular function and/or reduction in mortality has been observed with streptokinase, rt-PA and APSAC. Therefore, thrombolytic therapy will probably become routine therapy for early acute myocardial infarction. In patients with acute myocardial infarction, intravenous streptokinase recanalizes 40-45 percent of occluded coronary arteries and reduces mortality by 25 percent; it costs approximately $200 for a therapeutic dose of 1,500,000 units. Recombinant tissue-type plasminogen activator (rt-PA) is more potent for coronary arterial thrombolysis, producing both more rapid and more frequent (65-70 percent) reperfusion, but it costs over $1,000 for a therapeutic dose of 100 mg. Side effects (mainly bleeding) and the incidence of reocclusion associated with the use of streptokinase and rt-PA are not markedly different. Whether the higher efficacy of rt-PA will translate into a comparably larger reduction of mortality remains to be determined in large comparative clinical trials.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New developments in thrombolytic therapy. 212 72

We evaluated our experience over a 4-year period with a silicone dual-lumen catheter with a Dacron cuff (SDLCDC) to determine if the catheter represents an alternative to the polytetrafluoroethylene graft for long-term vascular access for hemodialysis patients. Records of 131 patients who used 168 catheters were reviewed for catheter function, duration of use, and occurrence and response to treatment of complications. Eighty-five percent of catheters functioned adequately until their use was no longer required or the end of the study. One-year catheter survival estimate was 65% and median survival estimate was 18.5 months. Mean blood flow rate achieved was 243 mL/min and recirculation was 7.5%. Exit-site infection occurred in 21% of patients and bacteremia in 12%. There were significantly more exit-site infections in diabetics than nondiabetics (33% v 11%, P less than 0.02). Exit-site infections resolved with parenteral antibiotic therapy in 90% and bacteremia in 25% of cases without catheter removal. Unresolved bacteremia was the most common cause of catheter removal and led to the loss of 7% of catheters. Thrombotic complications occurred in 46% of catheters. Urokinase instillation successfully treated catheter occlusion in 81% of cases. When urokinase instillation failed, streptokinase infusion restored catheter patency 97% of the time. The literature on the polytetrafluoroethylene (PTFE) graft was reviewed, and the SDLCDC was found to be similar to the graft in function, duration of use, and frequency of infectious and thrombotic complications. We conclude that the catheter represents an alternative to the graft for long-term vascular access in hemodialysis patients. Because of the frequent complications with both accesses, neither should be considered optimal. Further research is required to improve vascular access for patients in whom placement of an arteriovenous fistula is not possible.
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PMID:Use of a silicone dual-lumen catheter with a Dacron cuff as a long-term vascular access for hemodialysis patients. 214 8

Thrombotic complications of cardiovascular disease are a main cause of death and disability and, consequently, thrombolysis could favorably influence the outcome of such life-threatening diseases as myocardial infarction, cerebrovascular thrombosis and venous thromboembolism. Thrombolytic agents are plasminogen activators that convert plasminogen, the inactive proenzyme of the fibrinolytic system in blood, to the proteolytic enzyme plasmin. Plasmin dissolves the fibrin of a blood clot, but may also degrade normal components of the hemostatic system and predispose to bleeding. Currently, five thrombolytic agents are either approved for clinical use or under clinical investigation in patients with acute myocardial infarction. These include streptokinase, urokinase, recombinant tissue-type plasminogen activator (rt-PA), anisoylated plasminogen streptokinase activator complex (APSAC) and single chain urokinase-type plasminogen activator (scu-PA, prourokinase). The first generation thrombolytic agents, streptokinase (and probably also urokinase), are only moderately efficacious and their administration is associated with extensive systemic fibrinogen breakdown. In comparative studies performed in patients with acute myocardial infarction, recombinant tissue-type plasminogen activator (rt-PA) is a more effective and fibrin-specific thrombolytic agent than streptokinase. The acylated plasminogen streptokinase activator complex (APSAC) has a profile of thrombolytic efficacy and fibrin-specificity that is similar or somewhat better than that of streptokinase, but has the advantage that it can be administered by bolus injection. Single chain urokinase-type plasminogen activator is more fibrin-specific than urokinase. Comparative data on the efficacy and safety of this agent are limited as it is in the early stage of clinical investigation. Reduction of infarct size, preservation of ventricular function and/or reduction in mortality has been observed with streptokinase, rt-PA and APSAC. Therefore, thrombolytic therapy will probably become routine therapy for early acute myocardial infarction. In patients with acute myocardial infarction, intravenous streptokinase recanalizes 40-45 percent of occluded coronary arteries and reduces mortality by 25 percent; it costs approximately $200 for a therapeutic dose of 1,500,000 units. Recombinant tissue-type plasminogen activator (rt-PA) is more potent for coronary arterial thrombolysis, producing both more rapid and more frequent (65-70 percent) reperfusion, but it costs over $1,000 for a therapeutic dose of 100 mg. Side effects (mainly bleeding) and the incidence of reocclusion associated with the use of streptokinase and rt-PA are not markedly different. Whether the higher efficacy of rt-PA will translate into a comparably larger reduction of mortality remains to be determined in large comparative clinical trials. Both agents are available for clinical use.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New developments in thrombolytic therapy. 218 Jan 14

Thrombotic disorders such as myocardial infarction and stroke are the leading causes of death and disability in industrialized nations. Timely institution of thrombolytic therapy can achieve a reduction of infarct size, a preservation of left ventricular function, and a reduction in mortality. The administration of streptokinase, urokinase, and acylated plasminogen-streptokinase activator complex (APSAC) can be associated with a complete breakdown of the hemostatic system. Tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA, prourokinase) are more fibrin specific; however, at the large dosages of activator needed for therapeutic efficacy, bleeding complications are still a problem. New approaches to optimizing the risk/benefit ratio for the patient by improving efficacy without sacrificing specificity include the use of synergistic combinations of plasminogen activators, mutants of t-PA and scu-PA, chimeric molecules, and antibody-targeted thrombolytic agents. The last approach opens the possibility of targeting several different components of the clot with either fibrinolytic or antiplatelet effector functions in one optimized molecule.
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PMID:Future directions in plasminogen activator therapy. 218 64

Peripheral arterial occlusions, with the exception of those induced mechanically or by vasospasm, are invariably caused by a blood clot resulting from either in-situ thrombosis or embolism. More than 10% of embolic occlusions in otherwise healthy arteries undergo spontaneous lysis due to the organisms tissue plasminogen activator. In thrombotic occlusion of arteriosclerotic vessels, probably due to insufficient activator release from the diseased arterial wall, spontaneous lysis is much less common. For more than 25 years, lysis has been aided with streptokinase (SK) or urokinase (UK) which, until eight years ago, had only been given systemically with a standard dosage of 2.4 million units daily for up to five days. Thrombotic femoral artery occlusions of up to six weeks old were successfully lysed in 48%, six to twelve weeks old in 25% and, in those older than twelve weeks only in exceptional cases. With embolic occlusion, systemic lysis is contraindicated due to the possibility of provoking new emboli. With conventional systemic SK treatment, in 7% of the patients there was severe bleeding which in 1.12% was fatal. The ultrahigh SK treatment (nine million units in six hours) has substantially fewer bleeding complications but no better rate of success. Systemic administration of SK and UK leads to activation of the entire circulating plasminogen and the correspondingly-associated clotting defects. Recombinant tissue plasminogen activator (rt-PA), the production of which was rendered possible by genetic engineering, is identical to human tissue activator, has a high affinity to fibrin-bound plasminogen, less affinity to circulating plasminogen. After systemic administration, however, the plasminogen in every vascular clot is activated such that, even without alteration of the clotting system, bleeding the emboli can be provoked. With local application of the activator, even extensive clots, provided they contain lysable fibrin, can be dissolved within one-half to three hours with comparably minimal doses. For local lysis treatment of peripheral arterial occlusions, SK, UK and rt-PA are well-suited. With a total dose of maximally 30,000 units SK, in contrast to the initially-used higher doses, there were no bleeding complications in more than 300 patients. Even with a total doses of 100,000 to 300,000 UK, albeit in a relatively small number of patients, and a total dose of 2.5 to 7.5 mg rt-PA which was given within three hours maximally to 85 patients, there were no bleeding complications.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Local thrombolysis in peripheral arterial occlusion]. 252 76

Thrombotic occlusion is a frequent complication associated with the use of central venous catheters. The purpose of this study was to evaluate the efficacy of a continuous infusion of low-dose urokinase (200 U/kg/h) in clearing catheters that had not cleared after two bolus doses of urokinase in a pediatric oncology population. Fifty-eight incidents of catheter-related occlusions (49 Hickman-type catheters/nine implantable ports) as documented by radiographic dye study occurred in 227 pediatric oncology patients with 254 central venous catheters during a 1-year period. Fourteen of 58 catheters failed to clear after two bolus instillations of urokinase (5,000 U and 10,000 U). Thirteen catheters were treated for 24 hours with urokinase, 200 U/kg/h, and one catheter with urokinase, 100 U/kg/h for 24 hours. Twelve catheters were used for study. Coagulation studies were monitored preinfusion, 12 hours into the infusion, and postinfusion. Patency was reestablished in 11/12 catheters (92%) with a mean infusion time of 28.7 hours. No coagulation abnormalities or clinical bleeding associated with the urokinase infusion occurred. Only one patient exhibited a prolonged partial thromboplastin time (greater than 150 seconds); this was associated with a heparin effect. These data indicate that low-dose urokinase may be a safe and effective means to clear occluded central venous catheters in children.
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PMID:Continuous infusion of low-dose urokinase in the treatment of central venous catheter thrombosis in infants and children. 265 25

Thrombotic complications of cardiovascular disease are a main cause of death and disability and, consequently, thrombolytic therapy with plasminogen activators could favorably influence the outcome of such life-threatening diseases as acute myocardial infarction (AMI). Five thrombolytic agents are either available or under clinical investigation: streptokinase (SK), urokinase (UK), recombinant tissue-type plasminogen activator (rt-PA), anisoylated plasminogen streptokinase activator complex (APSAC) and single chain urokinase-type plasminogen activator (scu-PA, pro-urokinase). The first generation thrombolytic agents, SK (and probably also UK), are only moderately efficacious; rt-PA is a more effective and fibrin-specific thrombolytic than SK; APSAC has a thrombolytic efficacy and fibrin-specificity that is probably similar or somewhat superior to that of SK and can be administered by bolus injection; scu-PA is more fibrin-specific than UK but it is only in the early stage of clinical investigation. Reduction of infarct size, preservation of ventricular function and/or reduction in mortality has been observed with SK, rt-PA and APSAC, but comparative trials with mortality endpoints are not yet available. Intravenous SK recanalizes 40-45 percent of occluded coronary arteries in patients with AMI and reduces mortality by 25 percent. rt-PA produces both more rapid and more frequent (65-70 percent) reperfusion. The choice of agent for the treatment of AMI at present must be based on considerations of lower cost of streptokinase versus higher efficacy for coronary recanalization of rt-PA. All available thrombolytic agents suffer shortcomings, including submaximal efficacy, limited fibrin-specificity and bleeding side effects. New developments towards improved efficacy and fibrin-specificity include combinations of synergistic thrombolytic agents, mutants of t-PA or scu-PA, chimeric t-PA/scu-PA molecules, antibody-targeted thrombolytic agents, and/or combinations of fibrin-dissolving agents with anti-platelet strategies.
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PMID:New developments in thrombolytic therapy. 268 61

Thrombotic occlusion of Hickman and Broviac central venous catheters is a serious obstacle to their long-term use. Because resistance to flow (R) through a catheter of lumen radius, r, is proportional to 1/r4, we hypothesized that measurement of R would provide an objective and sensitive monitor for partial occlusions. Our measurements showed that median R at a flow of 17 mL/min was 0.7 cmH2O/mL/min in normally functioning Hickman catheters, and 4.1 cmH2O/mL/min in Broviac catheters. In obstructed catheters, which by subjective standards resisted flushing or blood withdrawal, median R was 3.0 cmH2O/mL/min for Hickman and 5.6 cmH2O/mL/min for Broviac catheters, representing significant increases. In a series of obstructed lines in which urokinase was administered, R decreased from 7.7 to 4.5 in Hickman catheters and from 5.6 to 4.2 in obstructed Broviac catheters. The elevated resistance in Hickman catheters after urokinase suggested that residual catheter obstruction was present even though catheter function returned to normal. Elevated R was seen with abnormal venograms in seven of 13 patients. Four patients had normal R values and abnormal venograms, and two patients had elevated R values with normal venograms. Measurement of resistance in Hickman and Broviac catheters provides a simple technique that can supplement or replace venography in the serial assessment and treatment of partial obstruction.
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PMID:Early detection and simplified management of obstructed Hickman and Broviac catheters. 270 89


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