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)

A 68-year-old man who presented with unstable angina had had cardiac bypass surgery 12 years earlier and successful angioplasty of a native circumflex lesion 18 months previously. Repeat catheterization showed a widely patent angioplasty site but interval closure of a saphenous vein graft to a large marginal branch that was totally occluded proximally. A stress test revealed significant myocardial ischemia. Severe peripheral peripheral vascular disease with known bilateral iliac artery occlusions mandated a brachial approach. Because of his high risk for repeat cardiac surgery, it was elected to attempt saphenous graft angioplasty following a prolonged urokinase infusion. After an infusion of urokinase for 36 hr, antegrade flow was restored and angioplasty was carried out successfully on a discrete mid-graft legion. Subsequent stress testing showed resolution of the ischemia. There were no vascular complications.
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PMID:Successful angioplasty of a chronically occluded saphenous vein graft using a prolonged urokinase infusion from the brachial route. 207 Mar 99

The failure of balloon angioplasty to provide a durable result has led to the development of other methods of catheter-associated interventional therapy. In this study, 112 patients with superficial femoral artery stenosis or occlusion were treated with percutaneous atherectomy. Patients were considered to have a simple lesion if the occluded or stenotic arterial segment was less than 5 cm, and a complex lesion if the length of the occluded segment was greater than 5 cm. All atherectomies were performed in the superficial femoral and popliteal arteries; urokinase thrombolysis was used in conjunction with atherectomy in 16 patients. Atherectomy was considered successful if there was less than 20% residual stenosis determined by arteriography. Initial atherectomy results (30 day patency) were 100% successful in the group with a simple lesion and 93% successful in the group with a complex lesion. At a mean follow-up period of 12 months (range 5 to 24), there was a continued patency rate of 93% and 86%, respectively, in the simple and complex groups. In the patients who had restenosis, all pathologic specimens obtained during the second procedure demonstrated myointimal hyperplasia and organized thrombus. Eight major complications (7.1%) occurred, including one fatal myocardial infarction. The complication rate was 3.5% in the simple group and 8.3% in the complex group. With the exception of the myocardial infarction, all complications were associated with catheter entry site hematomas. Femoropopliteal atherectomy has a high rate of success and low morbidity and mortality for both simple and complex lesions and is a viable and competitive alternative therapy for patients with severe peripheral vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transluminal atherectomy for occlusive peripheral vascular disease. 218 87

Balloon angioplasty and bypass graft surgery are common procedures for treating vascular occlusive disease. The purpose of this preliminary investigation was to evaluate the effectiveness and the safety of a new catheter system, first introduced by KR Kensey. The system involves a flexible catheter with a high speed rotating tip, driven by an electrical motor. The tip is cooled by a continuous flow of sterile saline containing dextran 40, heparin and urokinase. Radiopaque contrast medium may be infused through the catheter to allow the device to be guided and to detect lesions and to evaluate the efficacy of treatment. The system was applied in three patients with occlusive vascular disease (Stage IIb) and segmental or total occlusion of the superficial femoral artery (SFA). The milling catheter was introduced percutaneously into the common femoral artery and guided to the area of occlusion under DSA control. In two patients total recanalisation was achieved after passage of the milling catheter. In one patient the totally occluded SFA could not be cannulated and a femoro-popliteal bypass was performed one week later. Complications such as perforation of the vessel or peripheral embolisation were not observed. Pedal pulses were improved significantly in one patient. Further investigations will be necessary to demonstrate whether the milling catheter can be safely used to revascularise patients with limb threatening peripheral vascular disease.
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PMID:Dynamic angioplasty--a milling catheter for transcutaneous and intraoperative treatment of vascular occlusive disease. 297 85

Because of the success of urokinase therapy, the expectation is that more patients with peripheral vascular disease will be treated with urokinase or another thrombolytic agent. For that reason, nurses must become proficient in caring for these patients. The standing orders and care map, along with the appropriate nursing diagnoses, offer the nurse concrete guidelines for the care of these patients.
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PMID:Peripheral intra-arterial thrombolytic therapy for acute arterial occlusion. 785 65

Intra-arterial thrombolytic therapy is an important advance in the treatment of arterial occlusive disease. Reports of results, morbidity, and mortality have been highly variable. This review was undertaken to assess the recent results of thrombolytic therapy with urokinase (UK) at our institution. From 1988-1992, 42 lower extremities in 41 patients with severe peripheral vascular disease underwent intra-arterial thrombolytic therapy. Sites of occlusion consisted of 6 iliac, 21 superficial femoral, 11 popliteal, and 20 infra-popliteal segments. Lytic therapy consisted of a regional infusion of UK with concomitant heparin anticoagulation. The most common UK loading dose was 250,000 units (60,000-750,000) followed by a continuous infusion of approximately 100,000 units/hour (60,000-240,000) for up to 72 hours. Technical success, defined as partial or total resolution of the arterial occlusions, occurred in 26 (62%) limbs. A concomitant endovascular procedure was required in 19 extremities following successful lysis. Immediate clinical success, defined as restitution of a distal pulse or increase in ABI > 0.10, occurred in 22 of 26 technically successful procedures. The four clinical failures and all 16 technical failures required either a major amputation or revascularization. There were 18 major complications in 18 patients (43%): seven thromboembolic, two arterial dissections, nine hemorrhagic. Seven hemorrhagic complications required transfusion of 1-6 units of blood, and two deaths occurred due to postprocedural hemorrhage, shock, and myocardial infarction. Hemorrhage was not related either to the dose of UK or the duration of UK infusion. A combination of thrombolysis and endovascular intervention can be of significant benefit in selected patients with extremity ischemia. However, complications are frequent and may be lethal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombolytic therapy for arterial occlusion: a mixed blessing. 816 Oct 90

Ancrod is a purified coagulant venom which renders blood incoagulable by cleaving fibrinopeptide A (FPA) from fibrinogen, but the mechanism involved in the clearance of fibrin from the circulation is unknown. To investigate the fibrinolytic response to ancrod, and to increase understanding of clearance mechanisms, six patients with peripheral vascular disease causing claudication were infused with ancrod at 2 u/kg over 6 h followed by 2 u/kg at 12 h intervals for 38 h. Venous blood samples were taken at time 0, 3, 6, 25 and 49 h for assay of fibrinogen (Fbg), fibrinopeptide A (FPA), total fibrin(ogen) degradation products (TDP), fibrin degradation products (FbDP), fibrinogen degradation products (FgDP), cross-linked fibrin degradation products (XL-FDP), tissue plasminogen activator (tPA), urinary type plasminogen activator (u-PA), plasminogen, alpha 2 antiplasmin (alpha 2 AP) and plasminogen activator inhibitor-1 (PAI-1). Fibrinogen (median and range) was 2.3 (1.4-3.90) g/l at time 0 and thereafter was undetectable. FPA rose from 2.5 (1.8-3.6) to 600 and 188 pmol/l at 3 h and 6 h and remained elevated. TDP, FbDP and FgDP increased greatly following ancrod while there was no evidence of XL-FDP. The surprising increase in FgDP during defibrination suggests either that fibrinogen is digested following its incorporation into circulating fibrin protofibrils or that some of the fibrin subunits in the photofibril retain one of the two fibrinopeptide A's. tPA and uPA remained unchanged. Plasminogen fell from 125 (100-155)% to 79 (40-118)% at 49 h and alpha 2 AP fell from 91 (75-107)% to 24 (10-35)% at 49 h. The level of PAI-1 was depressed during defibrination, with the exception of the 6 h data. The results demonstrate that ancrod removes FPA from fibrinogen to produce non-cross-linked (soluble) fibrin. This is cleared from the circulation without evidence of an increase in the circulating activities of the plasminogen activators, tPA or UK, but with evidence of plasminogen activation and consumption.
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PMID:The fibrinolytic response to ancrod therapy: characterization of fibrinogen and fibrin degradation products. 845 76

A new device that enables closure of the femoral artery puncture site by percutaneous placement of two nonabsorbable sutures (Prostar) was evaluated. Our initial experience included 32 insertion attempts at 29 femoral arterial puncture sites and one femoral venous puncture site. The device was applied at arterial puncture sites that had been used to carry out 12 balloon angioplasties (41%), seven intracoronary stent placements (24%), five intraaortic balloon pump insertions (17%), four diagnostic angiographies (14%), and one rotational ablation (3%). The venous access site closed was in a patient who had undergone balloon angioplasty and intracoronary thrombolysis. Most patients were anticoagulated with an average activated clotting time (ACT) of 306 +/- 123 sec (12 patients) or an average PTT of 68 +/- 29 sec (14 patients). There were four failures to achieve hemostasis using the device due to: inability to place the device because of peripheral vascular disease, entrapment of cutaneous tissue in the suture, a suture break that prevented hemostasis from being achieved, and avulsion of the sutures from the needles. Although three other suture breaks occurred, these did not prevent hemostasis from being achieved. Thus, 88% (28/32) of attempted uses were successful, and by using a second device in two of the failed attempts, 94% (30/32) of the puncture sites were successfully closed using the device. There was one late rebleed that required 1 hr of groin clamp pressure in an angioplasty patient who had received intracoronary urokinase. An ooze of blood occurred in 4 patients, but in only 2 was this more than trivial, resulting in discontinuation of heparin in one patient and a small hematoma in the other. We conclude that this device can be used safely and effectively, even in fully anticoagulated patients who have undergone complex procedures. The ultimate role of the device will require further experience and appropriate randomized studies.
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PMID:Initial experience using Prostar: a new device for percutaneous suture-mediated closure of arterial puncture sites. 872 93

The role of percutaneous angioplasty in the management of chronic iliac artery occlusions is controversial. This article reviews 7 years of experience in treating patients with complete chronic iliac artery occlusions (n = 99) by using thrombolysis and angioplasty. Patients were not excluded due to age or length of the lesion, or severity of underlying peripheral vascular disease. Thrombolysis was conducted with infusion of urokinase at a rate of 60,000-80,000 IU/h for 24 hours. Angioplasty was then performed irrespective of the results of thrombolysis. Seventy-nine percent of patients responded to urokinase, with complete lysis achieved in 55%. Angioplasty was successful in all patients with complete thrombolysis and in 88% of those with partial thrombolysis. The overall success rate was 86%, and more than 80% of surviving patients were symptom free at 5 years. There were seven complications, and the 30-day mortality rate was 2%. Our present results confirm the efficacy of thrombolysis/angioplasty for chronic arterial occlusions.
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PMID:Thrombolysis and angioplasty of chronic iliac artery occlusions. 877 Aug 45

When urokinase was withdrawn from the market, alternative thrombolytics such as alteplase and reteplase needed to be evaluated for peripheral vascular disease (PVD). The efficacy, safety, and cost of these agents were evaluated formally by the Department of Pharmacy and presented to the Pharmacy and Therapeutics Committee. No published data support a difference in efficacy or safety between these agents. A cost analysis estimated the average total cost of care was higher for patients treated with reteplase ($4,556) compared with alteplase ($2,139). Therefore, alteplase was determined to be a more cost-effective thrombolytic agent to treat PVD.
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PMID:Using efficacy, safety, and cost data to support a formulary decision regarding thrombolytic therapy. 1140 91

Plasminogen activator inhibitor-1 (PAI-1) is a physiological inhibitor of urokinase (uPA), a serine protease known to promote cell migration and invasion. Intuitively, increased levels of PAI-1 should be beneficial in downregulating uPA activity, particularly in cancer. By contrast, in vivo, increased levels of PAI-1 are associated with a poor prognosis in breast cancer. This phenomenon is termed the "PAI-1 paradox". Many factors are responsible for the upregulation of PAI-1 in the tumor microenvironment. We hypothesize that there is a breast cancer predisposition to a more aggressive stage when PAI-1 is upregulated as a consequence of Metabolic Syndrome (MetS). MetS exerts a detrimental effect on the breast tumor microenvironment that supports cancer invasion. People with MetS have an increased risk of coronary heart disease, stroke, peripheral vascular disease and hyperinsulinemia. Recently, MetS has also been identified as a risk factor for breast cancer. We hypothesize the existence of the "PAI-1 cycle". Sustained by MetS, adipocytokines alter PAI-1 expression to promote angiogenesis, tumor-cell migration and procoagulant microparticle formation from endothelial cells, which generates thrombin and further propagates PAI-1 synthesis. All of these factors culminate in a chemotherapy-resistant breast tumor microenvironment. The PAI-1 cycle may partly explain the PAI-1 paradox. In this hypothesis paper, we will discuss further how MetS upregulates PAI-1 and how an increased level of PAI-1 can be linked to a poor prognosis.
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PMID:Breast cancer and metabolic syndrome linked through the plasminogen activator inhibitor-1 cycle. 1787 97


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