Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report on the successful repeated treatment of a patient with rapidly progressive severe brain-stem stroke by application of I.V. tissue plasminogen activator (tPA). This treatment twice led to a prompt remission of severe brain-stem symptoms, although a permanent therapeutic success could not be achieved. Unfortunately, the patient died a few days later from pneumonia and sepsis. Necropsy revealed bilateral partial brain-stem infarctions and a subtotal stenosis of the vertebrobasilar junction with superimposed fresh thrombus. The clinically dramatic response to tPA indicates that this type of treatment is potentially successful in high-grade subtotal basal cerebral artery stenosis with progressive stroke symptoms. In particular, application of tPA should be considered if stroke progression cannot stopped by therapeutic heprinization. A prospective randomized oligocentric study is advocated.
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PMID:[Repeated treatment of subtotal vertebrobasilar stenosis with tissue plasminogen activator (tPA)]. 149 91

The potential importance of pleural fibrin deposition in the pathogenesis of pleural injury is supported by both clinical and experimental observations. We hypothesized that the local equilibrium between procoagulant and fibrinolytic activities is disrupted to favor fibrin deposition in exudative pleuritis. To test this hypothesis, we characterized procoagulant and fibrinolytic activities in pleural exudates from patients with pneumonia, lung cancer, or empyema and transudates from patients with congestive heart failure. Procoagulant activity was generally increased in exudative processes and was due mainly to tissue factor. All effusions contained antithrombin III and inhibited factor Xa and thrombin, but endogenous prothrombinase or thrombin activities were variably detected. Pleural fluid fibrinolytic activity was increased in congestive heart failure and was due to both tissue plasminogen activator and urokinase. Depressed fibrinolytic activity was found in pleural exudates despite increased concentrations of plasminogen, mainly glu-1-plasminogen, and was due to inhibition of plasminogen activation by plasminogen activator inhibitors 1 and 2 and of plasmin, in part by alpha 2-antiplasmin. Concentrations of PAI-1 in exudative pleural fluids were increased up to 913-fold, compared with normal pooled plasma. Exudative pleural effusions are characterized by increased procoagulant and depressed fibrinolytic activity, favoring fibrin deposition in the pleural space. The balance of these activities is reversed and favors fibrin clearance in congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormalities of pathways of fibrin turnover in the human pleural space. 206 28

The mean levels of fibrinopeptide A (FPA), thrombin-antithrombin complex (TAT), and soluble fibrin (tPA method) in cancer patients (n = 32) were intermediate between those of patients with cerebral infarction and pancreatitis who had the most abnormal results and patients with myocardial infarction and pneumonia who had the least abnormal results. Patients with disseminated malignancies (n = 16) had significantly higher mean levels of FPA (10.6 vs. 5.3 nmol/l) and TAT (11.0 vs. 4.4 pmol/l) than patients with limited malignancies (n = 16). The difference in soluble fibrin (fibrin monomer, FM; 22.1 vs. 18.0 nmol/l) was not significant. The values of FPA, FM, and TAT in the patient population correlated significantly. There was a negative correlation between the level of antithrombin and test results for FPA (-0.69), FM (-0.48), and TAT (-0.38) in the cancer patients. Even cancer patients with locally limited disease may have elevated FPA, FM, and TAT test results, indicating a state of definite hypercoagulation.
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PMID:Indices of hypercoagulation in cancer as compared with those in acute inflammation and acute infarction. 228 6

Low dose intra-arterial thrombolysis is too slow for many patients with severe acute limb ischaemia. Accelerated thrombolysis with high dose bolus t-PA was used in a consecutive series of 43 patients. Complete or clinically useful lysis was achieved in 39 patients, with a median duration of 7 h. Lysis occurred in 46% in under 4 h. Fifty-six per cent of patients required further procedures after lysis. Eleven per cent suffered a major bleed. The limb salvage rate at 30 days was 56%. Amputation was required in 22% and 22% died. Most deaths were due to associated thrombotic conditions: myocardial infarction (5), pulmonary embolism (1) and malignant thrombosis (1). One patient died from pneumonia two weeks after lysis and two died from renal failure within a week of thrombolysis. The high mortality rate was not associated with bleeding but may reflect the high risks involved in treating this group of patients. High dose bolus t-PA infusion appears to predict immediate outcome of thrombolysis as well as reducing infusion times. It may expand the indications for the non-surgical treatment of acute limb ischaemia to include most patients with the condition. Careful case selection is still necessary for optimal results.
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PMID:Accelerated thrombolysis with high dose bolus t-PA extends the role of peripheral thrombolysis but may increase the risks. 748 22

Ten allogeneic bone marrow transplant (BMT) recipients with hepatic venoocclusive disease (VOD) were treated with recombinant human tissue plasminogen activator (rt-PA). Two of them subsequently underwent orthotopic liver transplantation (OLT). One additional patient with VOD underwent OLT without prior rt-PA treatment. Treatment with rt-PA was started a median of 14 (1--35) days after BMT. The dose of rt-PA given to adults was 10-50 mg i.v. and that given to children was 3-10 mg i.v. Treatment was given for 2-4 days. In three patients, the dose was administered over a longer period or it was repeated. Four patients responded to rt-PA therapy and six did not. Eight patients suffered from hemorrhages, one intracranial and three gastrointestinal. Four patients required blood transfusions. Four had minor subcutaneous hemorrhages and/or epistaxis. One patient died of intracranial hemorrhage and five from hepatic and/or multiorgan failure. Two patients treated with rt-PA, 10 mg/day for 4 days, are alive; one is alive and well 3 months after BMT, the other has relapsed after 7 months. The three patients undergoing OLT died of chronic hepatic failure, cerebral edema, and pneumonia. Our experience suggests that rt-PA should not be administered in high doses and that the treatment should not be given over a longer period, because of the risk of severe hemorrhages.
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PMID:Treatment of hepatic venoocclusive disease with recombinant human tissue plasminogen activator or orthotopic liver transplantation after allogeneic bone marrow transplantation. 890 Mar 5

We described an autopsy case of a ruptured aneurysmal subarachnoid hemorrhage treated with endovascular embolization by interlocking detachable coils. An 85-year-old male presented with sudden onset of severe subarachnoid hemorrhage. Cerebral angiogram revealed a right internal carotid-posterior communicating artery aneurysm. Post-operative angiogram revealed complete obliteration of the aneurysm, except for its orifice. Following the embolization of the aneurysm, tissue plasminogen activator was intrathecally perfused for anti-vasospasm treatment. Follow-up angiogram showed stable obliteration of the aneurysm, and no particular findings of cerebral vasospasm. The patient had been recovering without any neurological deficits, but died from pneumonia on the 25th day after the embolization. Autopsy findings revealed the disappearance of the subarachnoid hemorrhage, and no visible finding of cerebral infarction or edema. The inner lumen of the aneurysm was occupied by a mixture of the coils and the clots. The surface of the embolized coils was directly observed through the orifice of the aneurysm without any membranous substance from the inner lumen of the internal carotid artery. This pathological finding is different from the previously reported animal models in which the surface of the embolized coils was covered with endothelial membrane 2 weeks after embolization. Further examinations are required to clarify the pathogenesis of the endothelial regrowth.
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PMID:[An autopsy case of a ruptured cerebral aneurysm treated with interlocking detachable coils]. 930 Apr 53

The importance of measuring healthcare performance and outcome rapidly grows around the world. As hospital information systems (HIS) become more commonplace, their use as clinical research tools can be easily developed. This is demonstrated in the article by two examples of clinical outcomes research undertaken on the world's largest HIS database. The research studies described in the article were on: (1) The effect of hospital 'experience' on inpatient mortality rates for patients with HIV-related pneumocystis carinii pneumonia, and (2) The effect of streptokinase and tPA on post-acute myocardial infarction survival rates.
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PMID:Using HIS data for health care research. 1017 Dec 44

Changes in the alveolar hemostatic balance in severe pneumonia were compared with those in the acute respiratory distress syndrome (ARDS). Analysis was performed in bronchoalveolar lavage fluids (BALF) of patients with ARDS triggered by nonpulmonary underlying events in the absence of lung infection (ARDS; n = 25), pneumonia demanding mechanical ventilation (PNEU-vent; n = 114), spontaneously breathing patients with pneumonia (PNEU-spon; n = 40), and ARDS in combination with lung infection (ARDS+PNEU; n = 43); comparison with healthy control subjects (n = 35) was performed. In all groups of patients, BALF total procoagulant activity was increased by nearly two orders of magnitude, being largely attributable to the tissue factor pathway of coagulation. Concomitantly, markedly reduced overall fibrinolytic capacity (fibrin plate assay) was noted in the lavage fluids of all patients. BALF levels of urokinase-type plasminogen activator were significantly reduced throughout, whereas the lavage concentrations of tissue-type plasminogen activator did not differ from those in control subjects. In addition, markedly enhanced levels of plasminogen activator- inhibitor I and alpha(2)-antiplasmin were noted in ARDS, ARDS+PNEU, and PNEU-vent, but not in PNEU-spon. In all groups of patients, the changes in the lavage enzymatic activities were paralleled by manifold increased BALF concentrations of fibrinopeptide A and D-dimer, reflecting in vivo coagulation processes. Within the overall number of patients with pneumonia, changes in the alveolar hemostatic balance were more prominent in alveolar and interstitial pneumonia than in bronchopneumonia. Acute inflammatory lung injury, whether triggered by nonpulmonary systemic events or primary lung infection, is thus consistently characterized by both enhanced procoagulant and depressed fibrinolytic activities in the alveolar lining layer, with the appearance of fibrin formation in this compartment. Profile and extent of changes in severe pneumonia demanding respirator therapy are virtually identical to those in ARDS, whereas somewhat less prominent alterations of the alveolar hemostatic balance are noted in spontaneously breathing patients with pneumonia.
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PMID:Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome. 1067 85

A 6-month-old male Quarter Horse was evaluated for chronic respiratory tract disease. Diagnostic investigations revealed pulmonary inflammation; Pneumocystis carinii was detected within macrophages. Lymphocyte subpopulation phenotyping and immunoglobulin concentration analysis were performed and results suggested immune suppression. Trimethoprim-sulfamethoxazole administration was initiated; the colt was discharged but was reexamined 8 days later because of profuse diarrhea and endotoxemia. Bacterial culture of feces recovered Salmonella spp resistant to trimethoprim-sulfamethoxazole, and a diagnosis of antimicrobial-associated colitis was made. Bilateral fibrinous hypopyon developed and was treated with topical medication and intracameral injections of human recombinant tissue plasminogen activator. Dapsone (3 mg/kg [1.4 mg/lb], PO, q 24 h; dose extrapolated from human data) was administered for treatment of P carinii pneumonia (56-day treatment period). The colt recovered from the pneumonia and diarrhea. Dapsone may be a useful adjunct to traditional treatment for P carinii pneumonia in horses or as a sole medication for horses that cannot tolerate other treatments.
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PMID:Use of dapsone in the treatment of Pneumocystis carinii pneumonia in a foal. 1476 1

Pneumonia with complicated parapneumonic effusion is a significant source of morbidity in children seen in our institution. This affords us the opportunity to evaluate new treatment options. In an effort to ensure that we provide quality care to these pediatric patients presenting with complicated parapneumonic effusions, we performed a retrospective review of patient records as well as our interventional radiology database. Fifty-eight patients were identified who were treated with intrapleural placement of pigtail catheters and administration of tPA. Successful drainage and resolution of 54 of the 58 effusions were achieved with percutaneous methods alone. There was no mortality or 30-day recurrence. Mean hospital stay was 9.1 days (range 5-21). On average, the chest catheter was removed on day 6 postplacement (range 1.5-20). tPA was administered intrapleurally, utilizing a standardized hospital protocol developed conjointly by Interventional Radiology and Thoracic Surgery. Patients were afebrile within 72 hours. In most patients, one catheter was placed. However, five patients had more than one catheter placed initially. Of the four patients that failed percutaneous tube therapy, three underwent video-assisted thoracic surgery (VATS) and one had open thoracotomy with decortication. The complication associated with this treatment was an average drop in hemoglobin of 2 g/mL. Based on our experience, tPA administered through a small-bore chest tube for drainage of complicated parapneumonic effusions has become our standard practice.
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PMID:Management of complicated parapneumonic effusions in children. 1476 52


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