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

Low dose urokinase-lys plasminogen was used to treat 10 patients with acute ischemia of lower limbs. Preliminary results are reported and indications defined, the combination producing effective relief and being very well tolerated biologically and clinically. All patients presented clear signs of ischemia provoking a short term risk for the limb. Direct femoral puncture arteriography of the ischemic limb was an essential pretreatment investigation. A thin catheter left in contact with the thrombus allowed localized fibrinolysis to be performed. Follow up arteriography examinations assessed clinicopathologic results, while biologic surveillance of principal coagulation parameters showed a lack of significant alterations during treatment. Ischemic signs were totally relieved in 7 cases, with arterial repermeabilization allowing recuperation of one (3 cases) or both (2 cases) distal pulses. Persistence of a popliteal thrombus in one case required a fogarty after a direct approach and the limb was saved. Two patients had to be amputated because of delayed treatment. These encouraging results suggest that this procedure of local thrombolysis be reserved for popliteal or infra-popliteal occlusions accompanied by sensory-motor signs and of recent (less than 72 hours) onset. Follow up for 8 months is insufficient but has shown the absence of deterioration, but this is obviously a function of the natural course of the underlying atheromatous disease.
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PMID:[Indications and results of combined urokinase-lys plasminogen in acute ischemic pathology of the legs]. 409 20

Sixty nine patients were treated with local intra-arterial urokinase (37,500 U/CTA. hr-1) for recent severe ischemia of lower limbs: 27 (40%) ultimately required amputation. The difference of amputation rate between the groups with and without thrombolysis was not significant (33% v. 42%). A biological study in 6 patients showed that local arterial plasminemia occurred in only 1 patient. Local urokinase does not strongly stimulate "endogenous" thrombolysis and enhances "exogenous" thrombolysis only very inconstantly. A better adaptation of urokinase dosage or the use of an agent with higher affinity for fibrin might improve the efficiency of local thrombolytic therapy.
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PMID:Effect of local urokinase on arterial occlusion of lower limbs. 702 40

Early postinfarction angina implies an unfavorable prognosis. Most published information on this outcome represents data collected in the prethrombolytic era, in which definitions and populations differed considerably. Our purpose was to evaluate the incidence and importance of recurrent ischemia after administration of thrombolytic therapy. We studied patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction studies. Patients were enrolled into 5 studies with similar entry criteria; 552 patients were treated with tissue plasminogen activator (t-PA), 293 were treated with urokinase, and 385 received both thrombolytic agents. Recurrent ischemia was defined as symptoms in association with electrocardiographic changes; reinfarction was defined as a reelevation of creatine kinase myocardial band isoenzyme in an appropriate clinical setting. Both recurrent ischemia and reinfarction occurred in 42 patients (3.4%), recurrent ischemia alone occurred in 226 (18%), whereas neither occurred in 964 (78%). Although baseline characteristics were similar among the 3 groups, in-hospital cardiac events (total 73 deaths, 253 heart failure episodes) were not: in-hospital mortality in patients with reinfarction was 21%; with recurrent ischemia, 11%; and with neither event, 4% (p < 0.0001). The in-hospital heart failure rate of patients with reinfarction was 50%; with recurrent ischemia alone, 31%; and with neither event, 17% (p < 0.0001). As expected, median in-hospital costs were highest in patients with reinfarction ($26,802), intermediate for those with recurrent ischemia alone ($18,422), and lowest in patients with neither event ($15,623). Recurrent myocardial ischemia after thrombolytic therapy is a frequent, important, and expensive adverse clinical outcome, making it a critical target for therapeutic intervention.
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PMID:Frequency, significance, and cost of recurrent ischemia after thrombolytic therapy for acute myocardial infarction. TAMI Study Group. 748 52

The enhancement of blood flow in experimental skin flaps following postischemic perfusion washout was investigated in rats. Unilateral island skin flaps based on the superficial epigastric vessels were raised and subjected to 6 hr of primary ischemia. Group 1 was designated as a control and did not undergo postischemic perfusion washout. In the remaining rats, postischemic washout was performed with one of five agents: Group 2--lactated Ringer's solution; Group 3--University of Wisconsin solution, an organ preservation medium; Group 4--verapamil, a calcium channel blocker; Group 5--urokinase, a thrombolytic agent; Group 6--iloprost, a stable prostacyclin analog. Two hours following perfusion washout, fluorometric analysis revealed a statistically significant enhancement of blood flow in Groups 4, 5, and 6, compared to Groups 2 and 3 (p < 0.05). Furthermore, a significant increase in skin surface fluorescence was demonstrated in all the flaps that underwent perfusion washout, compared to the control flaps (p < 0.05). By analyzing skin surface fluorescence, the enhancement of nutritive blood flow in flaps, following postischemic perfusion washout, was evaluated. This is the first study in which the above pharmacologic agents were compared in a quantitative manner.
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PMID:Enhancement of fluorescein perfusion in experimental skin flaps following postischemic washout with iloprost, urokinase, verapamil, and University of Wisconsin solution. 750 90

The ability of the prostacyclin analogue iloprost to improve survival of ischemic experimental skin flaps was investigated. Unilateral island skin flaps based on the superficial inferior epigastric vessels were raised in 70 rats and subjected to varying lengths of primary ischemia. The flaps were divided into the following four groups: group I, no perfusion washout; group II, postischemic washout with lactated Ringer's solution; group III, postischemic washout with urokinase; and group IV, postischemic washout with iloprost. Flap survival rates for group IV were significantly higher than all other groups (p < 0.05). The primary ischemia time at which 50% of the flaps failed was 8.9 hours for group I, 9.5 hours for group II, 13.3 hours for group III, and 15.3 hours for group IV. This is the first study to investigate the effect of iloprost on skin flap survival. Iloprost was found to be significantly more effective than urokinase in salvaging ischemic experimental skin flaps.
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PMID:Iloprost improves survival of ischemic experimental skin flaps. 752 Feb 20

The chief aim of this study was to maximize flap survival by counteracting the pathophysiological changes occurring during ischemia-reperfusion. Rabbit epigastric skin flaps given 21 hours of ischemia were infused intra-arterially with selected drugs at the start of reperfusion. Compared with control infused ischemic flaps, which had a 33% survival rate on day 7 post-ischemia, significant improvement was found with vasodilators nitrendipine (61%) and prostacyclin (65%) and the thrombolytic agent urokinase (65%); marginal improvement with the free radical scavenger desferrioxamine (53%); but no change with streptokinase (44%), heparin (21%), and ATP-MgCl2 (35%). A drug mixture comprising all of these agents except streptokinase and urokinase produced 87% survival, suggesting an additive effect. Biochemical assays on skin homogenates and blood implicated oxygen free radicals, neutrophil infiltration, and thromboxane in flap failure. These results imply that multiple factors are responsible for ischemic flap failure and that a mixture of drugs needs to be infused to counteract all of the detrimental changes.
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PMID:Drug mixture which improves survival of ischemic rabbit epigastric skin flaps. 753 75

The authors' experience with 46 patients treated over 8.5 years was reviewed to determine the optimal secondary revascularization procedure after occlusion of a unilateral aortobifemoral graft limb. A total of 64 procedures was performed on these patients to restore and maintain graft patency. Repetitive operations for reocclusion were needed in 14 patients (30%). Transcatheter thrombolytic therapy was used in 14 patients, four as sole therapy and 10 in conjunction with operation. The mean time from aortofemoral grafting to presentation with graft limb occlusion was 59.4 months. Rest pain or severe ischemia was present in 85%, and severe claudication in the remainder. Some 78% had urgent operation after diagnostic angiography and catheter-directed thrombolytic therapy was attempted in 22%. The etiology of graft thrombosis was outflow obstruction in 78.2% of cases. Inflow was obtained by surgical thrombectomy in 35 and by lytic therapy in 13. Extra-anatomic inflow was used in 11 and intra-abdominal thrombectomy or redo aortofemoral grafting in five. Outflow procedures, mainly profundaplasty, were performed in all but five cases (four urokinase and one surgical). Infrainguinal bypass was needed in 10 cases in addition to the groin reconstruction. Catheter-directed thrombolysis was successful in 13 of 14 instances; however, in nine of these residual stenosis was disclosed in the outflow requiring surgical repair. Ultimately, 12 of 14 cases treated with thrombolysis required surgical intervention. Cumulative patency for all procedures was 68%. Complications were seen in 14% of cases. Operative mortality was 5%, and limb salvage was obtained in 85%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aortofemoral graft occlusion: strategy and timing of reoperation. 765 41

To determine whether pharmacologic reperfusion to Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow during acute myocardial infarction confers the same clinical benefit as restoration of TIMI 3 flow, in-hospital clinical and angiographic outcomes in 1,229 patients prospectively enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction trials were analyzed. Patients were treated with intravenous tissue plasminogen activator or urokinase, or both. Angiography of the infarct-related artery 90 minutes after initiation of thrombolytic therapy demonstrated TIMI grades 0, 1, 2, or 3 flow in 20%, 7%, 17%, and 55% of vessels, respectively. Rescue or adjunctive coronary angioplasty was performed in 80%, 27%, and 16% of patients with TIMI 0/1, 2, or 3 flow, respectively. Predischarge angiography was performed in 963 patients. A significant gradient of increasing mortality was seen in patients with lower TIMI flow (4.3%, 6.1%, and 10.1% with TIMI 3, 2, and 0/1 flow, respectively, p = 0.002). The incidence of congestive heart failure and recurrent ischemia was significantly higher in patients with TIMI 2 than with TIMI 3 perfusion (26% vs 19% for heart failure, p = 0.03; 23% vs 17% for recurrent ischemia, p = 0.05). Acute left ventricular ejection fraction and infarct zone regional wall motion were also significantly improved in patients with TIMI 3 than with TIMI 2 flow, with trends toward better improvement in global and regional function in the TIMI 3 group. These findings were not affected by the use of acute coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Significance of a coronary artery with thrombolysis in myocardial infarction grade 2 flow "patency" (outcome in the thrombolysis and angioplasty in myocardial infarction trials). Thrombolysis and Angioplasty in Myocardial Infarction Study Group. 773 92

The purpose of this prospective study was to determine the value of intraoperative intra-arterial fibrinolytic therapy (IIFT) in patients with acute arterial ischemia as an adjunct to mechanical thromboembolectomy. Sixty-six femoropopliteal or distal acute arterial occlusions were assessed by means of arteriography and Doppler imaging pre- and postoperatively. Two groups of patients were compared: one (n = 35) in which mechanical thromboembolectomy was applied as the single technique and another (n = 31) in which 250,000 IU of urokinase diluted in 250 ml of normal saline solution was instilled at the end of mechanical thromboembolectomy over a 30-minute period with the arterial inflow occluded. Candidates for IIFT were selected according to a nonrandomized method. Intraoperative arteriography showed residual thrombus in 20 (30.3%) patients and unsuspected arterial lesions in 23 (34.8%). Thrombosis recurrence was associated with residual thrombus (p < 0.001) and amputation (p < 0.001). The ankle/brachial index increased significantly (p < 0.05) in the patients who received IIFT (0.88 +/- 0.03) in comparison with those who underwent mechanical thromboembolectomy (0.75 +/- 0.05). Although the percentages of distal revascularization and amputation did not differ significantly between the two groups, quantitatively the results were better in the IIFT group (80.65% success and 9.68% failure) compared to the mechanical thromboembolectomy group (60% success and 22.86% failure). There was no bleeding due to IIFT. Significant variables in our study were diabetes (p < 0.05), the time period of 12 to 24 hours before the surgery (p < 0.05), and the severity of the ischemia in association with rest pain (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraoperative fibrinolytic therapy for salvage of limbs with acute arterial ischemia: an adjunct to thromboembolectomy. 778 4

Prolonged intravascular infusion of urokinase has proven beneficial in reestablishing patency of chronically occluded peripheral arteries and saphenous vein grafts. This study was performed to assess the efficacy and safety of prolonged urokinase infusion as a prelude to angioplasty in chronically occluded native coronary arteries, that had failed standard angioplasty techniques. Twenty-five patients with objective evidence for ischemia in the distribution of a chronic coronary occlusion were referred for percutaneous intervention. Patients were assessed for any potential exclusions from lytic therapy. Urokinase infusion through both a SOS wire and a stable guiding catheter was continued at 100,000-240,000 units/hr for 8-25 hr; patients then underwent attempted balloon angioplasty. Mean duration of urokinase infusion was 20.6 +/- 7.7 hr (total dose 163,000 +/- 52,447 units/hr). Fibrinogen levels dropped slightly with this (300 +/- 129 to 203 +/- 81 mg/dl, P = 0.02). Angiography posturokinase showed improvement in 7 (28%) with regard to coronary flow (> or = 1 TIMI-grade). Angioplasty was successful in 13 (52%), with final angiographic result revealing thrombus in 5 (20%), or dissection 8 (32%). The infusions were well-tolerated with a low incidence of chest pain, 2 (8%) or ischemic ECG response, 2 (8%); myocardial infarction, 2 (8%); or significant bleeding 2 (8%). All patients survived the procedure, with a length-of-hospital stay = 5.1 +/- 4 days. Use of prolonged preangioplasty intracoronary urokinase infusion can be done safely with success in roughly one-half of patients with chronic total native coronary occlusions who have failed prior attempts at percutaneous intervention.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prolonged urokinase infusion for chronic total native coronary occlusions: clinical, angiographic, and treatment observations. 778 87


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