Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dissolution of pulmonary emboli with heparin and urokinase is ascribed, respectively, to anticoagulation and fibrinolysis. Since truly independent assessment of these effects in man is lacking, we administered each drug alone. Fibrinogen and plasminogen plasma levels and the resolution of pulmonary emboli were measured in three randomized groups of 10 patients each: groups A and C infused with small repeated doses of urokinase and a large single dose of urokinase, respectively, and group B who received heparin. After 6 h of treatment, fibrinogen fell in all the groups, while, after 12 h, remained equally reduced in groups A and B and declined further in group C. Plasminogen behaved similarly. Up to 60 h, statistical analysis showed that these effects were related to timing and amounts of urokinase and heparin infusion. These observations suggest that heparin may induce a lytic state. As to signs of pulmonary emboli resolution, no differences between groups were found in lung perfusion and gas exchange recovery at any time (from 1 day to 1 year) and in pulmonary artery pressure reduction at 1 week. The greater angiographic and scintigraphic recovery observed with urokinase, versus heparin alone, after 1 day of treatment in the Urokinase Pulmonary Embolism Trial may be ascribed to a synergistic effect with urokinase of heparin administered during the diagnostic work-out. The indications of heparin and urokinase should be evaluated in the light of these results.
 ...
PMID:Fibrinolytic effects of urokinase and heparin in acute pulmonary embolism: a randomized clinical trial. 307 63

Blood samples from 24 patients who received recombinant human tissue-type plasminogen activator (rt-PA) for angiographically documented acute pulmonary embolism were examined to identify and quantify fibrinolysis. Before and after the intravenous administration of 50 mg rt-PA over a 2 hr period, levels of total fibrinogen, fibrin(ogen) degradation products (FDP), and cross-linked fibrin degradation products (XDP) were measured in each patient. Elevated levels of XDP were found in all patients before treatment (mean 2.0 micrograms/ml, normal less than 0.2 microgram/ml), and these increased 12-fold with treatment. Fibrinogen levels fell 30% and FDP levels increased 24-fold for the entire group of patients. Over this 2 hr period, 10 of 24 patients (responders) demonstrated 25% or greater improvement in the extent of pulmonary artery thrombus as quantified by Urokinase Pulmonary Embolism Trial score, and these patients were found to have a significantly lower XDP/FDP ratio after rt-PA (p less than .04) than those patients who failed to respond. These data suggest that the intravenous administration of pharmacologic doses of rt-PA in patients with pulmonary embolism produces both fibrinolysis and fibrinogenolysis, successful thrombolysis in these patients is associated with a preponderance of fibrinogenolysis over fibrinolysis, the XDP/FDP ratio is a useful indicator of fibrinolytic specificity, and in patients with acute pulmonary embolism the endogenous fibrinolytic pathways are activated, albeit ineffectively, as indicated by the increased circulating XDP levels seen in all 24 patients before the administration of rt-PA.
 ...
PMID:Recombinant tissue plasminogen activator in patients with pulmonary embolism: correlation of fibrinolytic specificity and efficacy. 310 14

To determine if pulmonary perfusion was improved in acute pulmonary embolism after therapy with recombinant human tissue-type plasminogen activator (rt-PA), lung scans were obtained before and a mean of 22 hours after therapy in 19 patients. The posttherapy lung scans were compared with baseline, pretherapy scans with use of two semiquantitative methods--an anteroposterior view method, similar to that used in the Urokinase Pulmonary Embolism Trial, and a segmental method that emphasized pulmonary anatomy. There was an improvement in the defect score from 0.35 to 0.14 (P less than .01) when the anteroposterior view method was used and from 0.37 to 0.16 (P less than .01) when the segmental method was used. These encouraging results in the early posttherapy period suggest that rt-PA is especially effective in improving regional perfusion after pulmonary embolism and that a larger controlled trial of therapy with rt-PA for acute pulmonary embolism should be performed. Scoring lung scans with a segmental method is feasible and appropriate for present-day lung scan technique and should be considered in future studies.
 ...
PMID:Pulmonary perfusion after rt-PA therapy for acute embolism: early improvement assessed with segmental perfusion scanning. 312 66

Use of urokinase to treat heparin-associated thrombocytopenia and thrombosis in one patient is described, and various treatments proposed for this syndrome are discussed. A 56-year-old man received an intravenous bolus dose of heparin sodium at his local hospital and was transferred to another institution for treatment of suspected pulmonary embolism; he had received heparin two weeks earlier during coronary angiography. The patient's platelet count was reported to be normal before heparin administration. When embolism was confirmed, heparin was discontinued and streptokinase was given for 24 hours. Heparin infusion was then restarted at 1000 units/hr and continued for four days. Platelet count on admission to the second hospital was 47,000/cu mm; 12 hours later it was 19,000/cu mm, and it remained low despite platelet transfusions. Five days after admission, deep-vein thrombosis developed in the left leg. Heparin was discontinued and urokinase and warfarin were started. Urokinase was infused at 320,000 IU/hr for 12 hours and continued at dosages of 160,000-320,000 IU/hr for a total of 40 hours. The initial warfarin sodium dose was 15 mg, followed by a dosage of 10 mg/day. Symptoms of deep-vein thrombosis improved within 12 hours and platelet count increased after heparin was discontinued. If it is recognized early enough, heparin-associated thrombocytopenia can be reversed by discontinuation of heparin. Transfusions of platelets are of little benefit. Dipyridamole, cyclo-oxygenase inhibitors such as aspirin, and protamine sulfate may be useful. Long term anticoagulation with warfarin is recommended to prevent recurrent thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Thrombolytic therapy in heparin-associated thrombocytopenia with thrombosis. 348 69

In 1933 Streptokinase (SK) was isolated from bacterial strains of haemolytic Streptococci. Since then it has become the widest spread drug for fibrinolysis. SK, a protein, consists of 415 aminoacids and has a molecular weight of 47,000u. Together with the plasminogen (PLG) of the blood it forms activator complexes, which then convert other PLG molecules of the blood to plasmin. Plasmin attacks and dissolves fibrin deposits. As a substance produced by bacteria SK stimulates antibody formation in the body, the titer will increase during therapy, and SK lysis should be terminated after 6 days of treatment. Usually SK is administered intravascularly to treat a wide range of diseases, associated with pathological activation of hemostasis, like deep vein thrombosis, pulmonary embolism, myocardial infarction etc.. Contraindications can be traced back to the effects of SK on coagulation and the immune system. Bleeding is the most common side effect, but also a few anaphylactic reactions, caused by massive antigen-antibody precipitation have been observed. The rate of lethality of the treatment was established at 0.7% of the cases. To reduce the incidence of side effects modifications of the drug have been proposed, such as activator complex, light B chain SK, and acylated activator therapy. Compared with Urokinase, SK shows a higher rate of side effects, especially in the field of the immune system. Therapy with Urokinase can be controlled more easily. Nevertheless because of considerable price differences and logistics, SK is preferred in Europe and the USA. If strict guidelines in therapeutic use are followed, the rate of side effects of the drug can be curtailed and will be comparable to those of Urokinase.
 ...
PMID:Review and current status of thrombolytic therapy with streptokinase. 354 44

Considerable interest in plasminogen activators as human thrombolytic drugs has stimulated rapid biotechnologic progresses. These enzymes have been classified in two immunochemically distinct groups: "urokinase-like" activators or u-PA which do not interact with fibrin and "tissue activator-like" activators or t-PA which interact with fibrin. Plasminogen activators are widely distributed in normal and malignant tissues and they are implicated in various physiological and pathological processes. They maintain the functional integrity of the vascular system and their presence may be of importance in tissue remodeling and cell migration. Urokinase and streptokinase are used in human thrombolytic therapy. However, the properties displayed by t-PA suggest that this enzyme may be a superior fibrinolytic agent. The primary structures of urokinase and t-PA are known; both enzymes have been synthesized by DNA technology. In order to produce t-PA in large quantities by gene cloning, intensive studies are conducted by pharmaceutical industries. Clinical trials using t-PA for dissolving thrombi in coronary heart disease, strokes and pulmonary embolism are in progress. This review presents the molecular and structural properties of plasminogen activators, as well as related physiological, pathological and therapeutic aspects.
 ...
PMID:[Plasminogen activators: general aspects and recent developments]. 391 65

The case of a young man hospitalised for bilateral lower limb deep vein thrombosis is reported. None of the usual causes were found after systematic wide-ranging investigation. The only abnormality on admission was a spontaneous increase in the cephalin-kaolin time to 65 seconds compared to a control time of 40 seconds. Measurements of the clotting factors showed a moderate and isolated deficiency in factor XII (30 p. 100), also present in a brother (50 p. 100) and a sister (42.5 p. 100). Fibrinolytic therapy was administered : an initial course of Streptokinase was followed by extension of a left femoral vein thrombosis and pulmonary embolism. Two courses of Urokinase were given with an eight day interval without significantly improving the venous circulation. This case is an example of thrombogenic disease due to a deficiency of a clotting factor resulting in non-activation of physiological fibrinolysis.
 ...
PMID:[Thrombophlebitis and pulmonary embolism in congenital factor XII deficiency]. 392 76

Eight patients with massive pulmonary thromboembolism documented by angiography were treated with Urokinase (UK) 4.400 IU/Kg/hr for 12 hours. UK i.v. infusion was started immediately after angiographic evaluation (Miller index) and was followed by anticoagulant therapy with heparin and sodium warfarin. All patients survived even though 4 pts. were in shock before treatment. Significant reduction of pulmonary obstruction (reduction of Miller index) was obtained in 7 patients with 48 hours from withdrawal of the drug. Mild superficial bleedings which did not influence the clinical course were the only complication recorded. Neither bleedings nor angiographic improvement showed a correlation with thrombin time prolongation. Indications for thrombolytic therapy of pulmonary embolism and particularly prevention of the major haemorrhagic complications are briefly discussed. It is concluded that the high doses of UK suggested by Food and Drug Administration may be used safely in patients affected by massive pulmonary thromboembolism with or without shock, if patients are adequately selected and prevention of major haemorrhagic complications is continued throughout treatment.
 ...
PMID:[Thrombolytic therapy with urokinase in 8 patients with massive pulmonary thromboembolism]. 409 13

Urokinase, a plasminogen activator found in urine is used in the treatment of pulmonary embolism, and is supplied commercially by several companies in Europe, U.S.A. and Japan. It exists in two forms, of molecular weights 50-55 000 and 33 000 daltons, which may differ in their therapeutic efficiency. A variety of assay systems exist to measure plasminogen activator activity--clot lysis, casein hydrolysis, amidolytic cleavage of synthetic peptide substrates. These assays are time-consuming, relatively insensitive, and cannot accurately assess the amount of the two molecular species in any preparation of urokinase. Standardization therefore presents a problem to manufacturers, control agencies, and clinicians. We have prepared a variety of monoclonal antibodies to human urokinase and have assessed their value as standardizing different commercial preparations of urokinase and measurement of urokinase for therapeutic monitoring.
 ...
PMID:Possible use of monoclonal antibodies to standardize the production and use of human urokinase. 654 1

Urokinase treatment, previously employed with success in the declotting of deep venous thrombosis and arteriovenous shunts in patients undergoing regular dialytic treatment (RDT), was used in 23 cases of arteriovenous fistula thrombotic occlusion in 18 RDT patients. The treatment was successful in 65.2% of the cases without any negative side effects, except 1 case which may have developed a pulmonary embolism. Patients with severe hypofibrinolysis may need larger doses or may have a recurrence of the thrombotic episode. All therapeutic failures correlated with the presence of fibrosis or sclerosis.
 ...
PMID:Urokinase treatment for arteriovenous fistulae declotting in dialyzed patients. 669 Oct 3


<< Previous 1 2 3 4 5 Next >>