Modification of postoperative tendon adhesions by ancrod defibrinogenation.
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Biomedical subjects
Publications and source records attributed to W R Bell.
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Analysis of 182 patients with chronic disseminated intravascular coagulopathy and malignancy shows common features. Migratory thrombophlebitis occurred in 96 patients while at least a single episode of thrombophlebitis was noted in 113. Seventy-five of the patients bled and 45 had arterial emboli in various organs. Twelve patients had the triad of thrombophlebitis, hemorrhage, and arterial emboli, often sequentially. Hematologic data showed derangements associated with intravascular coagulation, the most prominent of which were hypofibrinogenemia and thrombocytopenia. Other abnormalities included prolonged prothrombin time, increased fibrinogen-fibrin degradation products, decreased levels of factors V and VIII, cryofibrinogenemia, and microangiopathic hemolytic anemia. Forty-one patients had lesions of non-bacterial thrombotic endocarditis at autopsy; 31 of these had arterial emboli during life. None of the lesions were infected. Mitral and aortic valves were most frequently involved. No single mechanism that causes the disseminated intravascular coagulopathy has been identified. However, cell products--secretions and enzymes--and the cells themselves have been proposed as the procoagulant(s) responsible for the syndrome. In addition to treatment of the underlying neoplasm, symptomatic disseminated intravascular coagulopathy should be controlled. Heparin is the drug of choice for treatment of this problem, very little benefit having been observed with warfarin therapy. Long-term use of anticoagulants is potentially feasible for control of chronic disseminated intravascular coagulopathy, but without effective control of the underlying tumor ultimately will be unsuccessful.
An elderly man with procainamide hydrochloride-induced lupus syndrome had a circulating anticoagulant against factor XI and a biologic false-positive (BFP) test result for syphilis. This was not associated with hemorrhagic problems. The activity of the circulating anticoagulant and the BFP disappeared within days following discontinuation of procainamide and the administration of corticosteroids.
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In Phase I of this study of 160 patients with pulmonary embolism, it was demonstrated that of 12 hours of urokinase accelerated the resolution of pulmonary thromboemboli compared to heparin alone. Phase II compared 12 hours of urokinase, 24 hours of urokinase and 24 hours of streptokinase in 167 patients. All patients had a clinical history and angiographic diagnosis of pulmonary embolism. Patients were randomly allocated to treatment. All physicians making patient observations were unaware of drug assignment. Resolution of the thromboembolism 24-30 hours after therapy had been instituted was determined by pulmonary angiography, lung perfusion scans and cardiopulmonary hemodynamics. Twenty-four hours of urokinase did not demonstrate greater clot resolution than 12 hours of urokinase. Twenty-four hours of urokinase resulted in greater improvement than streptokinase in lung perfusion scans, but not in angiograms. In patients with massive embolism, this difference was statistically significant. Hemodynamic differences varied. Bleeding complications and morbidity due to allergic reactions with streptokinase and urokinase were minimal. There was no statistically significant difference in mortality in the three threatment groups. From the Phase I and Phase II data it is reasonable to conclude that all three regimens of thrombolytic therapy are more effective than heparin alone in accelerating resolution of pulmonary emboli. Thrombolytic therapy offers the clinician an alternative to pulmonary embolectomy.
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Pulmonary angiograms and pulmonary lung perfusion scans on 162 patients with pulmonary embolism were comparatively analyzed. Among the expert angiographic panel members who independently evaluated the studies there was consistent agreement on the diagnosis, size of the emboli, and severity. Consistency of agreement among the expert pulmonary lung perfusion scan panelists was considerably less. These data demonstrate that, in addition to the lack of specificity of the lung perfusion scan for the diagnosis of pulmonary thromboemboli, there is a considerable problem of interpretation in this patient population.
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In a group of 52 patients receiving continuous intravenous heparin, 16 developed thrombocytopenia (platelets less than 100 000/mm3). Ten of the 16 patients who had thrombocytopenia had elevated titers of fibrinogen-fibrin degradation products, and five of these 10 patients also had a reduction in plasma fibrinogen. The abnormalities disappeared after the heparin preparation was discontinued. These occurrences could not be attributed to drugs other than heparin, to the dose of heparin administered, or to prior exposure to heparin. The mechanism by which the heparin preparation may induce these changes is not known.
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The controlled clinical trials of thrombolytic agents in the United States have been carried out in two phases, under the auspices of the National Heart and Lung Institute. Phase I was devoted to the comparison of 12-hour Urokinase (12h-UK) followed by heparin (H) with heparin alone in patients with acute pulmonary embolism (Walsh et al. 1969). The results showed that pateints treated with UK had more rapid and gretaer resolution of pulmonary thromboemboli in the first twenty-four hours of therapy than patients treated with H alone, as assessed by serial pulmonary angiography, hemodynamics and lung scanning (The Urokinase Pulmonary Embolism Trial, 1970, 1973; Hyers et al. 1970). Because of the ralatively small size of the Trial and the low mor tality of treated pulmonary embolism, mortality differences were not sought-nor was one found. Although there was early difference in amount of clot resolution, patients treated with H alone showed similar improvement by two weeks. The phase II Urokinase-Streptokinase Pulmonary Embolism Trial (USPET) was begun to assess the comparative results of UK and Streptokinase (SK) therapy. Because of favorable results obtained with SK in other countries, it was deemed necessary to make this comparison (Browse and James, 1964; Hirsh et al. 1968; Miller et al. 1969, 1971; Chesterman et al. 1969). A third group, 12-hour UK, was added to relate this study (24-hour UK and SK) with the Phase I results which employed only a 12-hour infusion of UK. This Phase II Trial represents the first controlled, randomized study of UK and SK in thromboembolic disorders.
Seventy-four patients, from 16 to 20 weeks pregnant, received intra-amniotic urea (80 Gm.) and intravenous oxytocin for the purpose of inducing abortion. Seventy-one of the 74 patients were successfully aborted by the primary method with a mean injection-to-abortion interval of 18.33 hours. There were no serious side effects, and the mean hospital stay was 32 hours. Following urea injection, the mean serum urea nitrogen rose to 33 mg. per cent at 4 hours. Maximum changes in serum electrolytes occurred at 8 to 12 hours after injection and included a decrease in the mean concentrations of sodium, chloride, and carbon dioxide and an increase in serum potassium. An increase in the urinary excretion of urea began within 4 hours, but significant diuresis did not occur in the presence of intravenous oxytocin administration. There was a significant increase in the leukocyte concentration while hematocrit values remained unchanged. Beginning approximately 8 hours following urea injection, the mean plasma fibinogen concentrations decreased by approximately 15 per cent and the mean platelet count showed a drop of approximately 18 per cent. Fibrinogen-fibrin degradation products were significantly increased in 36 per cent of the patients studied.
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