1: Nippon Rinsho. 2004 Oct;62 Suppl 10:645-52. [Treatment of venous thromboembolism in cancer patients] [Article in Japanese] Okugawa T, Tabata T, Yamada N. Department of Obstetrics and Gynecology, Mie University School of Medicine. Publication Types: Review Review, Tutorial PMID: 15535325 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 2: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2003 Apr;25(2):190-2. [Diagnosis and treatment of mesenteric venous thrombosis: analysis of eleven cases] [Article in Chinese] Liu B, Li YJ, Zheng YH, Liu CW, He XD, Zheng CJ, Zhao YP, Guan H. Department of Vascular Surgery, PUMC Hospital, CAMS, PUMC, Beijing 100730, China. liubao1972@sohu.com OBJECTIVE: To evaluate the diagnosis and treatment of mesenteric venous thrombosis. METHODS: The clinical data of 11 cases diagnosed as mesenteric venous thrombosis between 1992 and 2001 in PUMC Hospital were analyzed retrospectively. RESULTS: Postoperative state(27.3%), especially cirrhosis and portal hypertension, and other history of thrombosis (27.3%) were the most common causes. Thrombolysis was performed successfully in two of the eleven cases. The rest of them were misdiagnosed in other hospitals and operated. No patient died after operation, and one (11.1%) recurrence was found. CONCLUSIONS: Early application of anticoagulant is necessary for patients with thrombosis risks. For suspected patients, early computed tomography (CT) and DSA examination should be performed, and prompt thrombolysis and anticoagulation therapy can be performed to avoid the bowel resection after definite diagnosis. To reduce the recurrence, anticoagulant should be maintained for a proper time. PMID: 12905718 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 3: Ann Transplant. 2002;7(1):44-51. The effect of chronic allograft rejection on plasma regulators of fibrinolysis. Perkowska A, Elhasade A, Durlik M, Placha G, Galazka Z, Lao M, Gaciong Z. Transplantation Institute, Warsaw Medical University, Warsaw, Poland. agape@poczta.wp.pl Chronic renal allograft rejection is often associated with the presence of fibrin thrombi in the microcirculation. Our purpose was to evaluate the influence of chronic rejection on fibrinolytic regulators in plasma of renal allograft recipients. We evaluated the concentration and activities of tPA, uPA and PAI-I in plasma from kidney allograft recipients. We studied 64 patients who underwent kidney transplantation from cadaveric allograft donors. At the time of the study 38 patients had stable graft function for at least 6 months proceeding the study, and 26 recipients had biopsy-proven chronic rejection of the kidney transplant. Control group included 30 healthy blood donors. In kidney transplant recipients we found significantly higher plasma tPA activity (median: 0.99 IU/ml; range: 0-3.8 IU/ml) in comparison to healthy controls (median: 0.15 IU/ml; range: 0-2.8 IU/ml) (p = 0.002) as well as significantly lower plasma PAI-I activity (median: 7.06 U/ml; range: 0-33.2 U/ml) in comparison to healthy controls (median: 21.8 U/ml; range: 0-36.7 U/ml), (p = 0.0001). Among transplant recipients, PAI-I plasma activity in recipients with chronic graft rejection (median: 10.16 U/ml; range: 0-33.2 U/ml) was significantly higher than in patients with stable graft function (median: 4.83 U/ml; range: 0-22.9 U/ml), (p = 0.01). In transplant recipients with stable graft function and poorly controlled hypertension we found significantly higher PAI-I plasma activity in comparison to recipients with normal blood pressure (p = 0.006). In kidney transplant recipients there was a positive correlation between the dose of prednisone and PAI-I activity in plasma (p = 0.01) and an association between BMI value and plasma PAI-I activity (p = 0.008), as well as an association between BMI value and plasma tPA-Ant concentration (p = 0.006). Among transplant recipients, patients treated with ACE inhibitors had significantly lower uPA plasma activity than the rest of the group (p = 0.003). In recipients with stable graft function we found a correlation between CsA concentration and tPA activity (p = 0.04), as well as an association between the dose of CsA and uPA-Ant concentration in plasma (p = 0.049). In patients with chronic graft rejection we found a negative correlation between the dose of prednisone and uPA-Ant plasma level (p = 0.004). Renal allograft recipients have higher tPA and lower PAI-I activities in plasma in comparison to healthy individuals. Chronic allograft rejection, is as well as poorly controlled hypertension, seem to be associated with an increase PAI-I plasma activity. In kidney graft recipients there is a relation between the value of BMI and the activity and concentration of tPA-Ant as well as the value of BMI and the PAI-I activity in plasma. Poorly controlled hypertension is associated with an increase in PAI-I plasma activity. The results of our study suggest a stimulatory effect of CsA on tPA and PAI-I plasma activities as well as on uPA-Ant concentration, while prednisone in turn seems to enhance PAI-I activity in plasma and decrease uPA expression. In renal allograft recipients ACE inhibitors seem to reduce uPA plasma activity. PMID: 12221903 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 4: J Vasc Interv Radiol. 2002 Feb;13(2 Pt 1):163-9. Mechanical and enzymatic thrombolysis for massive pulmonary embolism. De Gregorio MA, Gimeno MJ, Mainar A, Herrera M, Tobio R, Alfonso R, Medrano J, Fava M. Department of Interventional Radiology, Hospital Clinico Universitario, Avda Gomez Laguna s/n., Zaragoza, Spain. mgregori@separ.es PURPOSE: To assess the efficacy and safety of mechanical fragmentation combined with intrapulmonary thrombolysis in massive pulmonary thromboembolism (PTE) with hemodynamic impairment. MATERIALS AND METHODS: Fifty-nine patients diagnosed with massive PTE with hemodynamic impact were treated. The initial clinical symptoms were shock in 23 patients (38.9%), syncope in eight (13.5%), and dyspnea at rest in 28 (47.4%). Mean O2 saturation was 67.8%. Mean pulmonary artery pressure (PAP) was 42.1 mm Hg. During fragmentation, thrombolysis was administered in the form of a urokinase bolus of 200,000-500,000 U in 57 patients and 20 mg of recombinant tissue plasminogen activator (rt-PA) in two patients. The mean urokinase dose used was 2,500,000 IU, whereas the total dose of rt-PA was 100 mg. Heparin sodium infusion was performed to reach activated partial thromboplastin time ratios of 2. The follow-up consisted of clinical assessment, pulmonary scintigraphy, and echocardiography. The patients received treatment with dicoumarin for 6 months after the procedure. RESULTS: Clinical improvement was seen in 56 patients (94%). Three patients died. The mean PAP after the treatment was 21.8 mm Hg. The mean posttreatment Miller index was 0.35. Technical success was achieved in all cases and clinical symptoms improved in all cases except those in which the patients died. Pulmonary scintigraphy showed improved perfusion in all cases. Echocardiography was performed after 3-6 months, showing a mean pressure of 22.8 mm Hg (corrected values). There were no signs of recurrent PTE or arterial hypertension in the follow-up. CONCLUSION: The data provided confirm the efficacy and safety of mechanical fragmentation and pharmacologic thrombolysis in the treatment of massive PTE with hemodynamic impairment, showing improvement of symptoms and a decrease in PAP. PMID: 11830622 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 5: Minerva Cardioangiol. 2000 Dec;48(12 Suppl 1):27-35. [Evidence-based guidelines for prevention and therapy of venous thromboembolism] [Article in Italian] Falciani M, Dilaghi B, Conti AA, Caciolli S, Gensini GF. Scuola di Specializzazione in Medicina Interna, Istituto di Clinica Medica e Cardiologia, Azienda Ospedaliera Careggi, Universita degli Studi, Firenze. Recently, evidence-based guidelines for the prevention and therapy of venous thromboembolism have been published. Prophylaxis: in General Surgery patients with moderate to severe risk need to be treated with unfractioned (UFH) or low molecular weight (LMWH) heparin. Non pharmacological methods must be reserved to patients with high hemorrhagic risk and in association to heparin to patients with particularly high thromboembolic risk. In high risk Ortopedic Surgery prophylaxis with high doses LMWH or oral anticoagulants (OA) is indicated. Il Neurosurgical Surgery and in politraumatized patients prophylaxis must be individualized taking account of hemorrhagic risk; patients with acute medullary lesion with paraplegia must be treated with LMWH. In Internal Medicine conditions which determine prolonged bed rest need prophylaxis with UFH or LMWH. In pregnancy, pharmacological prophylaxis is indicated only in cases of preceding thrombotic events or documented congenital risk factors. Therapy: deep venous thrombosis or sub-massive pulmonary embolism must be treated with anticoagulant doses of UFH or LMWH (100 U antiXa/Kg twice daily). OA must be continued for a time identifiable on the basis of underlying disease. In massive or sub-massive pulmonary embolism with hemodynamic instability thrombolysis is indicated. In heparin induced thrombocytopenia alternative antithrombotic treatments must be employed. PMID: 11253337 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 6: Vasc Med. 2000;5(2):91-5. Long-term benefit of thrombolytic therapy in patients with pulmonary embolism. Sharma GV, Folland ED, McIntyre KM, Sasahara AA. Department of Veterans Affairs Medical Center, Harvard Medical School, Boston, MA, USA. A total of 23 of the 40 patients who had angiographically proven pulmonary embolism and who had initially been randomized to an IV infusion of heparin (n = 11) or a thrombolytic agent (urokinase or streptokinase, n = 12) were restudied after a mean follow-up of 7.4 years to measure the right-sided pressures and to evaluate their response to exercise during supine bicycle ergometry. Results showed that, at rest, the pulmonary artery (PA) mean pressure and the pulmonary vascular resistance (PVR) were significantly higher in the heparin group compared with the thrombolytic group (22 vs. 17 mmHg, p<0.05, and 351 vs. 171 dynes s(-1) cm(-5), p<0.02, respectively). During exercise both parameters rose to a significantly higher level in the heparin group (from rest to exercise, PA: 22-32 mmHg, p<0.01; PVR: 351-437 dynes s(-1) cm 5, p<0.01, respectively), but not in the thrombolytic group (rest to exercise, PA: 17-19 mm Hg, p = NS; PVR: 171-179 dynes s(-1) cm(-5), p = NS). It is concluded that thrombolytic therapy preserves the normal hemodynamic response to exercise in the long term and may prevent recurrences of venous thromboembolism and the development of pulmonary hypertension. Publication Types: Clinical Trial Controlled Clinical Trial Multicenter Study Randomized Controlled Trial PMID: 10943585 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 7: J Thromb Thrombolysis. 1999 Oct;8(3):223-6. Randomized clinical trial of urokinase versus heparin in unstable angina. Chen JL. Collaborative Research Group of National Project, Beijing, China. The aim of this study was to evaluate the clinical effect of urokinase (UK) in unstable angina (UA). This study was a multicenter, single-blind, heparin-controlled, randomized clinical trial. Entry criteria was that effort angina was significantly aggravated within 96 hours and angina attack at rest within 24 hours. In addition to the control group, thrombolytic therapy was divided into two groups according to the dose of UK. The high-dose group was 18,000 IU/kg, and the total dose was no more than 1.5 million IU (no bolus of heparin in this dose). The low-dose group was 14,000 IU/kg, and the total dose was no more than 1 million IU. All patients were treated by aspirin 300 mg/day and heparin 3000 U IV bolus before thrombolytic therapy (except for the high-dose group), then subcutaneous heparin 7,500 U q12h. The primary endpoint for the comparison between the thrombolytic and control groups was death and AMI (cardiac event) within 30 days of enrollment. Five hundred and fifty-six patients with UA were selected, and 272 and 284 patients were enrolled in thrombolytic group and control groups, respectively. The 30-day incidence of cardiac events was a little higher, but not significantly, in the thrombolytic group than in the control group (7.0% vs. 5.3%, ns), but the rate for cardiac events was much lower in the low-dose UK group than in the high-dose UK group. The difference was significant (3.3% vs. 10.0%, P < 0.05). Even if the rate was also lower than in the control group, this difference was not significant (3.3% vs. 5.3%, P > 0.05). The time interval between enrollment and the AMIs was quite different in these two groups. The majority of AMIs (73.7%) occurred within 24 hours, including 37% of AMIs that occurred within 2 hours after the beginning of thrombolytic therapy in the UK group. However, only small number of AMIs (20%) occurred within 24 hours of enrollment in the control group. The increase in AMI risk on the first day of thrombolytic therapy in this study might be closely related to thrombolysis and to the lack of strong antithrombin therapy. The risk of AMI might be remarkably reduced by using low-dose UK in combination with antithrombin therapy before thrombolytic therapy. Publication Types: Clinical Trial Multicenter Study Randomized Controlled Trial PMID: 10500312 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 8: Surgery. 1998 Aug;124(2):336-41; discussion 341-2. Acute lower limb ischemia: determinants of outcome. Ouriel K, Veith FJ. Department of Surgery, University of Rochester, NY 14642, USA. BACKGROUND: Previous studies have documented high rates of morbidity and death after acute peripheral arterial occlusion. To date, however, few studies have identified parameters predictive of successful therapy. METHODS: The Thrombolysis or Peripheral Arterial Surgery Trial of intraarterial recombinant urokinase or immediate operation for acute lower extremity arterial occlusion provided data on 544 patients randomized at 113 centers. A Cox proportional hazards multifactor analysis was performed to identify those main effects predictive of amputation-free survival and to document any baseline variables useful in deciding whether a patient would be treated best initially with thrombolysis or operation. RESULTS: Of 28 variables analyzed, eight main effects were predictive of amputation-free survival. These included two demographic factors: white race (risk ratio [RR] = 1.75; p = 0.003) and younger age (RR = 1.015; p = 0.046). Comorbidities comprised four of the main effects: history of central nervous system disease (RR = 1.726; p = 0.005), history of malignancy (RR = 1.615; p = 0.024), congestive heart failure (RR = 2.202; p < 0.001), or low body weight (RR = 1.007 per pound; p = 0.006). The severity of the process was also predictive, as gauged by the presence of skin color changes (RR = 1.585, p = 0.007) or pain at rest (RR = 0.503; p = 0.003). All eight effects were similar in the two treatment groups; none of these variables predicted improved outcome with one form of initial therapy over the other (i.e., there was no therapy-by-variable interaction). The length of occlusion, however, predicted whether a patient would fare better with thrombolysis or operation. With a threshold occlusion length of 30 cm, the RR for longer occlusions to shorter occlusions was 43% better in patients who received thrombolysis, whereas the situation was reversed for those who were randomized to operation. CONCLUSIONS: A variety of baseline variables can be identified that are predictive of outcome after treatment for acute lower extremity ischemia. In addition, the length of the occlusive process appears to predict whether a patient will be best served with thrombolysis or operative intervention; longer occlusions appear to respond best with an initial thrombolytic strategy. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 9706157 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 9: Vasc Med. 1996;1(2):159-61. Thrombolysis or operation for peripheral arterial occlusion. Ouriel K. Department of Surgery, University of Rochester, NY 14642, USA. Patients with peripheral arterial occlusion may be treated with one of three distinct treatment strategies: observation and/or anticoagulation alone, operative intervention, or catheter-directed thrombolytic therapy. The severity of symptoms is the most important clinical parameter with which to formulate clinical strategies. Patients with non-lifestyle limiting claudication may be best managed without arteriographic investigation, managing symptoms conservatively with exercise, cessation of smoking, and occasionally the oral pharmacologic agent pentoxifylline. Patients with threatened limbs in the form of rest pain or tissue loss carry a high risk of limb loss without intervention. These patients should undergo arteriography with consideration of endovascular intervention for focal lesions and bypass grafting for more diffuse disease. Patients with more acute symptoms may be best treated with catheter-directed thrombolytic therapy, addressing unmasked lesions responsible for the occlusion with an operative or endovascular approach. In all cases, the appropriate therapy must be tailored to the clinical presentation, the anatomic distribution of disease, and the experience of the clinical team. Publication Types: Review Review, Tutorial PMID: 9546932 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 10: Arch Biochem Biophys. 1997 Sep 15;345(2):289-98. Cancer cells release a covalent complex containing disulfide-linked domains from urinary plasminogen activator, neural cell adhesion molecule, and haptoglobin alpha and beta chains. Harvey SR, Nayak SK, Markus G, Ouhammouch M, Hemperly JJ, Dillman RO, Doyle DJ. Department of Biological Sciences, State University of New York at Buffalo, 14260, USA. We have previously reported on the secretion of a family of high Mr plasminogen activators (PAs) by a human lung cancer cell line [Harvey et al. (1991) Biochim. Biophys. Acta 1078, 360-368]. We have now extended these studies to several human cancer cell lines and a human embryonic lung cell line. In the present study with HPL-SK-1 lung cancer, A431 epidermoid cancer, ovarian carcinoma, and embryonic lung cell lines, we show that the 900- and the 660-kDa PAs are disulfide-bonded multiprotein oligomeric complexes. They are functionally and immunologically related to human urinary PA (uPA). Their size and PA activity are not destroyed by strong denaturants such as 8 M urea or 2% sodium dodecyl sulfate (SDS), suggesting that the uPA moiety is covalently associated with the rest of the molecule. It is only under strong denaturing conditions with 1.4 M beta-mercaptoethanol and 2% SDS that the uPA moiety could be released as a 21- to 23-kDa fragment along with two major polypeptide chains of 70 and 40 kDa, respectively. The presence of the uPA active center in the reduced PA660 was demonstrated by [3H]diisopropylphosphorofluoridate labeling and by Western blot using a monoclonal antibody to uPA B chain. N-terminal amino acid sequencing of the 70- and 40-kDa polypeptides, respectively, showed homology to the neural cell adhesion molecule and the beta chain of haptoglobin. A minor fragment of 18 kDa obtained under strong reduction conditions was also sequenced and shown to share homology with the alpha chain of haptoglobin. Western blot analysis of the reduced PAs with monoclonal antibody to the neural cell adhesion molecule and rabbit anti-haptoglobin confirmed the homologies obtained by the sequence data. Further, immobilized monoclonal antibodies to the neural cell adhesion molecule, uPA B chain, and rabbit anti-haptoglobin bound the multiprotein complexes with uPA activity, from A431, ovarian cancer, and embryonic lung cell lines. The bound material, after dissociation, exhibited PA activity that was inhibited by monoclonal antibody to the uPA B chain. These data suggest that in tumor and embryonal cell lines, in addition to proper folding and assembly of proteins by intramolecular disulfide bond formation in the endomembrane compartment, intermolecular disulfide bonds could also occur, producing multiprotein oligomers as in the present case. Formation of such oligomers may have a selective advantage for such cells in the focalization of proteolytic activity through the interaction of the neural cell adhesion molecule domain with the extracellular matrix and in immunosuppression of lymphocytes by the haptoglobin portion of the complex. PMID: 9308901 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 11: Clin Hemorheol Microcirc. 1997 Jan-Feb;17(1):59-66. Low-dose intermittent urokinase therapy in chronic symptomatic end-stage arterial disease--clinical relevance for patients with coronary artery disease or peripheral arterial occlusive disease. Leschke M, Schoebel FC, Strauer BE. Medizinische Klinik und Poliklinik B - Klinik fur Kardiologie, Pneumologie und Angiologie, Heinrich-Heine Universitat Dusseldorf, Germany. Symptomatic end-stage arterial disease in coronary artery or peripheral arterial occlusive disease represents an increasing clinical problem as cardiovascular mortality in these patient groups has declined due to improved secondary prevention. While in peripheral arterial occlusive disease amputation with subsequent life-long physical disability is the major problem, patients with end-stage coronary artery disease and refractory angina pectoris repeatedly report to the emergency ward with the clinical symptoms of unstable coronary syndromes, but myocardial infarction is generally ruled out. For these patients long-term intermittent urokinase therapy has been developed as an alternative treatment modality. Potential mechanisms for clinical effectiveness include improvement of rheological blood properties, thrombolysis of non-occluding arterial thrombi and possibly plaque regression. In coronary artery disease urokinase is applied as an intravenous bolus injection of 500,000 IU urokinase three times a week over a period of 12 weeks. This leads to a marked reduction of fibrinogen by about 35% and of clinical symptoms by around 70% accompanied by a reduction of exercise-induced myocardial ischemia. In observational studies in patients with peripheral arterial occlusive disease injections of 500,000 IU of urokinase were usually given daily for a shorter time period of three to four weeks with a clinical success rate, defined as a cessation or marked reduction of rest pain and/or salvage of a limb, of around 50%. Given the state of critical ischemia in both entities of atherosclerotic disease, long-term intermittent urokinase therapy represents a promising antiischemic approach. In particular in patients with peripheral arterial occlusive disease randomized controlled trials with prolonged treatment periods, which are likely to improve clinical results, are warranted. Publication Types: Review Review, Tutorial PMID: 9181759 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 12: Z Kardiol. 1997;86 Suppl 1:85-94. [Chronic intermittent urokinase therapy: anti-ischemic and hemodynamic effects] [Article in German] Leschke M, Schoebel FC, Schannwell CM, Peters AJ, Jax TW, Mecklenbeck W, Strauer BE. Klinik fur Kardiologie, Pneumologie und Angiologie, Heinrich-Heine Universitat, Dusseldorf. Long-term intermittent urokinase therapy has been developed for patients with severe coronary artery disease and refractory angina pectoris. This therapeutic approach is predominantly effective at the microcirculatory level based on a combination of rheologic and fibrinolytic effects; furthermore, plaque regression seems to be a possible mechanism. Patients with refractory angina pectoris are characterized by severe coronary artery disease without a therapeutic option for conventional revascularization procedures, only slight impairment of left ventricular systolic function and hyperfibrinogenemia, which results in further enhancement of myocardial ischemia due to microcirculatory impairment of blood flow. In this article data on the anti-ischemic effectiveness as well as first results on the impact of this therapeutic approach on hemodynamics are described. A dose-response study, which compared 3 x 50,000 IU with 3 x 500,000 IU urokinase three times a week over a treatment period of 12 weeks demonstrated subjective as well as objective antiischemic effectiveness. Only patients who were treated with 500,000 IU per injection achieved marked increases in exercise capacity, while some patients in the low-dose group presented even with a deterioration of exercise performance. First hemodynamic studies could not show marked changes of systolic parameters, either at rest or during exercise. But a decrease of pulmonary capillary wedge pressure at rest after treatment with 500,000 IU per injection indicates an improvement of diastolic function as a result of enhanced myocardial perfusion. Echocardiographic measurements of transmitral Doppler flow in 21 patients with end-stage coronary artery disease demonstrated normalization of early and late diastolic filling rates in most cases. These changes were accompanied by a reduction of clinical signs of heart failure. Long-term intermittent urokinase therapy is a valuable approach as it not only improves quality of life during the actual treatment period but by the persistence of therapeutic effects following the cessation of therapy. Publication Types: Review Review, Tutorial PMID: 9173724 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 13: Int J Cancer. 1996 Dec 20;69(6):475-9. Expression of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in benign, borderline, malignant primary and metastatic ovarian tumors. van der Burg ME, Henzen-Logmans SC, Berns EM, van Putten WL, Klijn JG, Foekens JA. Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) Academic Hospital, The Netherlands. BURG@onch.azr.nl Elevated levels of expression of the urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 have shown to be related to poor prognosis in a variety of cancer types. In the present study, cytosolic levels of uPA and PAI-1 were determined with enzyme-linked immunosorbent assays in cytosols prepared from 244 human ovarian tissues of different histological sub-types. Both uPA and PAI-1 were significantly associated with the malignant progression of ovarian tissues; the levels were increased going from normal tissue, via benign and borderline adenomas, to primary and metastatic adenocarcinomas. For the 90 patients (34 early-stage and 56 patients with advanced disease) from whom the primary adenocarcinoma tissues were examined, uPA and PAI-1 levels were evaluated for their association with clinicopathological parameters and with progression-free and overall survival. Neither uPA nor PAI-1 were significantly associated with the age of the patient, FIGO stage, tumor grade, tumor rest, the presence of ascites, or with progression-free or overall survival. On the other hand, age, FIGO stage/tumor rest and the presence of ascites, were significantly related to the length of both progression-free and overall survival in univariate analyses. Tumor grade was of prognostic significance in the analysis for progression-free survival, but not for overall survival. After adjustment for FIGO stage/tumor rest, only age retained its prognostic significance, in the analysis for progression-free survival and in that for overall survival. PMID: 8980250 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 14: Tidsskr Nor Laegeforen. 1996 Oct 20;116(25):3011-3. [Intra-arterial thrombolysis in peripheral bypass and arterial occlusions. Preparation and practical procedure] [Article in Norwegian] Sandbaek G, Staxrud LE. Rontgenavdelingen, Aker sykehus, Oslo. The aim of this article is to describe our technique for performing intra-arterial thrombolysis. This way of treating arterial and graft occlusions demands close cooperation between interventional radiologist and vascular surgeon. The intra-arterial thrombolysis is preceded by clinical examination, haematological tests, angiography and information to the patient. The main indications are pain at rest and serious claudication due to acute or subacute occlusion of grafts or native arteries to the lower extremities. The most important contraindications are conditions predisposing to bleeding. The most common adjunct percutaneous treatment is balloon angioplasty. Surveillance is compulsory in order to discover complications at an early stage. PMID: 8975426 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 15: J Biol Chem. 1996 Sep 13;271(37):22885-94. Domain interplay in the urokinase receptor. Requirement for the third domain in high affinity ligand binding and demonstration of ligand contact sites in distinct receptor domains. Behrendt N, Ronne E, Dano K. Finsen Laboratory, Rigshospitalet, Strandboulevarden 49, Building 7. 2, DK-2100 Copenhagen O, Denmark. The urokinase plasminogen activator receptor (uPAR) is a membrane protein comprised of three extracellular domains. In order to study the importance of this domain organization in the ligand-binding process of the receptor we subjected a recombinant, soluble uPAR (suPAR) to specific proteolytic cleavages leading to liberation of single domains. Treatment of the receptor with pepsin resulted in cleavage between residues 183 and 184, thus separating the third domain (D3) from the rest of the molecule, which was left as an intact fragment (D(1 + 2)). D(1 + 2) proved capable of ligand binding as shown by chemical cross-linking, but quantitative binding/competition studies showed that the apparent ligand affinity was 100- to 1000-fold lower than that of the intact suPAR. This loss of affinity was comparable with the loss found after cleavage between the first domain (D1) and D(2 + 3), using chymotrypsin. This result shows that in addition to D1, which has an established function in ligand binding (Behrendt, N., Ploug, M., Patthy, L., Houen, G., Blasi, F., and Dano, K. (1991) J. Biol. Chem. 266, 7842-7847), D3 has an important role in governing a high affinity in the intact receptor. Real-time biomolecular interaction analysis revealed that the decrease in affinity was caused mostly by an increased dissociation rate of the ligand complex of D(1 + 2). Zero length cross-linking, using carbodiimide-induced, direct condensation, was used to identify regions within suPAR engaged in molecular ligand contact. The purified suPAR was cross-linked to the radiolabeled amino-terminal fragment (ATF) of urokinase, followed by cleavage with chymotrypsin. In accordance with the cleavage pattern found for the uncomplexed receptor, this treatment led to cleavage between D1 and D(2 + 3). Analysis of the radiolabeled fragments revealed the expected ligand labeling of D1 but a clear labeling of D(2 + 3) was also found, indicating that this part of the molecule is also situated in close contact with ATF in the receptor-ligand complex. The latter contact site may contribute to the role of molecular regions outside D1 in high affinity binding. PMID: 8798468 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 16: Acta Radiol. 1996 May;37(3 Pt 1):299-304. Factors predicting the outcome of intraarterial thrombolysis in peripheral arterial and graft occlusions. Sandbaek G, Staxrud LE, Rosen L, Bay D, Stiris M, Gjolberg T. Department of Radiology, Aker University Hospital, Oslo, Norway. PURPOSE: To determine the association between successful intraarterial thrombolysis and the following factors: sex, age, symptoms, duration of symptoms, length of occlusion, conduit type, runoff, and catheter localization. MATERIAL AND METHODS: Forty-six patients with acute or subacute occlusions of peripheral native arteries and grafts were treated with continuous intraarterial infusion of streptokinase or urokinase. A univariate chi-square test and logistic regression analysis were used. RESULTS: Successful lysis was achieved in 27 of 46 patients (59%). The logistic regression analysis revealed a significant association between successful thrombolysis and good runoff (p < 0.01). A catheter position above the occlusion resulted in lysis in only one of 11 patients. The variables rest pain and claudication were slightly significant (p = 0.07). None of the other variables were significant, but a trend toward a separate effect of duration of occlusion was found. CONCLUSION: Good runoff and intrathrombotic infusion are virtual necessities in obtaining a positive immediate outcome in peripheral arterial and graft occlusions. In our study, other factors were less important. PMID: 8845257 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 17: J Am Coll Cardiol. 1995 Oct;26(4):961-6. Angioplasty of complex lesions in ischemic rest angina: results of the Thrombolysis and Angioplasty in Unstable Angina (TAUSA) trial. Mehran R, Ambrose JA, Bongu RM, Almeida OD, Israel DH, Torre S, Sharma SK, Ratner DE. Department of Medicine, Mount Sinai Hospital, New York, New York, USA. OBJECTIVES. This study sought to analyze the role of complex lesion morphology on the acute results of angioplasty. BACKGROUND. Acute complications of angioplasty are higher in unstable than in stable angina. The unstable culprit lesion is usually complex, indicative of plaque disruption and thrombus formation. Previous nonrandomized studies have shown that the presence of intracoronary thombus increases morbidity after coronary angioplasty. The role of complex morphology in coronary angioplasty outcome was studied in a prespecified subgroup analysis of a large multicenter coronary angioplasty trial. METHODS. The results of coronary angioplasty from the Thrombolysis and Angioplasty in Unstable Angina (TAUSA) trial were analyzed. This large trial randomized 469 patients in double-blinded manner to receive either intracoronary urokinase or placebo during coronary angioplasty of the culprit lesion in ischemic rest angina with or without recent infarction. The study presented here analyzes in detail the results of coronary angioplasty in complex versus simple lesions in the urokinase and placebo groups. Complex lesions were defined before angioplasty by a core laboratory as having one or more of the following: irregular borders, overhanging edges, ulcerations or intraluminal filling defects proximal or distal to the lesion. RESULTS. Of the 469 patients, 458 had identifiable culprit lesions, of which 245 were complex and 213 were simple. Complex lesions were associated with a higher abrupt closure rate than simple lesions (10.6% vs. 3.3%, respectively, p < 0.003). Patients with complex lesions also had higher recurrent in-hospital angina (p < 0.02) and emergent bypass surgery (p < 0.02). Further analysis of complex lesions revealed that abrupt closure was particularly high in the urokinase group (15.0% vs 5.9% for the placebo group, p < 0.03), and most abrupt closures were thrombotic. Composite clinical end points were also significantly higher with complex lesions and urokinase. In the placebo group, complex lesions had a higher abrupt closure rate as well as postcoronary angioplasty filling defects, but clinical end points were not significantly different. CONCLUSIONS. Complex lesions before coronary angioplasty increase acute complication rates after coronary angioplasty. Urokinase as administered in the TAUSA trial had significant adverse effects, especially in complex lesions. However, even in the placebo arm, complex lesions were associated with higher complication rates than simple lesions. Newer antithrombotic measures that particularly target the platelet may eventually decrease complication rates in these lesions. Publication Types: Clinical Trial Multicenter Study Randomized Controlled Trial PMID: 7560624 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 18: Cancer. 1995 Apr 1;75(7):1627-33. The significance of urokinase- type plasminogen activator, its inhibitors, and its receptor in ascites of patients with epithelial ovarian cancer. Chambers SK, Gertz RE Jr, Ivins CM, Kacinski BM. Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA. BACKGROUND: Strong correlations have been reported between expression of urokinase-type plasminogen activator (uPA) and poor prognosis in several human carcinomas. The clinical significance of secreted levels of uPA, its receptor (uPAR), and its inhibitors (PAI-1 and PAI-2) in the ascites of patients with epithelial ovarian cancer patients was investigated. METHODS: uPA, uPAR, PAI-1, and PAI-2 were measured in the primary ascites of 36 patients with epithelial ovarian cancer by enzyme-linked immunosorbent assay, and normalized to protein content. The relationship between levels of these factors in ascites and clinicopathologic variables, survival, and disease free interval (DFI) was studied. Because high levels of macrophage colony stimulating factor (CSF-1) in ascites is a known poor prognostic indicator for ovarian cancer, the effect of CSF-1 on secretion of PAI-2 by ovarian cancer cells was also examined in vitro. RESULTS: High uPA levels per se did not correlate with either survival or DFI. However, the ratio of uPAR normalized for uPA content correlated inversely with FIGO stage and residual disease, with a significant association between high uPAR/uPA level and prolonged survival and DFI. High PAI-1 levels (> 0.120 ng/mg) proved to be a good prognostic factor, correlating with both prolonged DFI and residual disease < or = 5 cm among Stage 3 patients. Conversely, high levels of PAI-2 (> 0.061 ng/mg) indicated a poor prognosis in Stage 3 patients, as high PAI-2 levels were associated with shorter DFI and survival. CSF-1 stimulated the secretion of PAI-2 by 2.4-fold in Bix3 ovarian carcinoma cells. Multivariate analysis revealed that the two independent prognostic factors for DFI in Stage 3 patients were PAI-1 and PAI-2; Stage 3 patients with high secreted PAI-1 and low PAI-2 levels have a median DFI that was prolonged by 30 months relative to the rest of the group. CONCLUSION: Secreted uPAR/uPA appears to measure tumor burden and predicts prolonged DFI and survival, but was not found to be an independent prognostic factor on multivariate analysis. High levels of PAI-1 in ascites were independently associated with prolonged DFI among Stage 3 patients. Therefore, secreted uPAR and PAI-1 may modulate uPA activity and lead to improved outcome. This contrasts with the finding that secreted PAI-2 is an independent factor indicating poor prognosis, which may relate in part to the actions of CSF-1. This study emphasizes the importance of uPA, its receptor, and its inhibitors in patients with epithelial ovarian cancer. PMID: 8826920 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 19: Yan Ke Xue Bao. 1995 Mar;11(1):57-60. The modality of huoxue-huayu in treatment of retinal vein occlusion. Deng Y, Wang M, Duan J. Department of Ophthalmology, Teaching Hospital of Chengdu College of TCM, China. BACKGROUND: There were some reports in China about Huoxue-Huayu therapy on retinal vein occlusion (RVO), but prospective and systematic studies are very few. The curative effect and mechanism of this therapy on RVO have not been reported previously. METHODS: 80 patients with RVO were randomly divided into 2 groups, Fundus III (group A) and urokinase group (group B). Group A was treated by Fundus III oral liquid (a composite herbal recipe for Huoxue-Huayu or invigoration of blood circulation and reduction of blood stasis) 10ml/time P.O. t.i.d. The treatment course was 1 mouth. Group B was treated by urokinase. The urokinase that produced in China was used 10,000 u + 5% glucose 500ml/day i.v. drip for 5 days in a course, the rest 5 days going on another course. The total treatment courses lasted 1 month, too. RESULTS: The visual acuity in group A was remarkably improved while that in group B did not change. The extravasated retinal blood was evidently absorbed in 92.7% of the cases in group A and in 66.7% of those in group B. The difference was significant. Fundus III also improved the retinal circulation, decreased the whole blood viscosity and fibrinogen and reduced leakage of the retinal capillaries. The total effective rates were 83.7% in group A and 53.7% in group B with significant statistical difference between the 2 groups (P < 0.01). CONCLUSION: Fundus III may alleviate retinal edema and necroses, improve the recovering of visual acuity, the retinal microcirculation, the rate of absorbing of retinal haemorrhage and treat RVO, and the curative effect is better than urokinase. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 8575610 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 20: Ann Vasc Surg. 1995 Mar;9(2):179-86. Intraoperative fibrinolytic therapy for salvage of limbs with acute arterial ischemia: an adjunct to thromboembolectomy. Gonzalez-Fajardo JA, Perez-Burkhardt JL, Mateo AM. Division of Vascular Surgery, Hospital Universitario Valladolid, Spain. 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) Publication Types: Clinical Trial Controlled Clinical Trial PMID: 7786704 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 21: Eur J Surg. 1994 Nov;160(11):593-7. Local intra-arterial thrombolysis with urokinase combined with balloon angioplasty in the lower extremities. Christensen ED, Christensen J, Thomsen MB. Department of Surgery, County Hospital, Kristianstad, Sweden. OBJECTIVE: To assess the effect of thrombolysis with urokinase in the treatment of acute and subacute arterial thrombosis or graft occlusion. DESIGN: Open study. SETTING: County hospital, Sweden. SUBJECTS: 20 selected patients with lower limb arterial or graft occlusions of less than six months' duration, 17 of whom presented with rest pain (four with ulceration) and the rest with claudication. INTERVENTIONS: High dose urokinase (4,000 IU/minute for up to 8 hours) given intra-arterially, followed by oral anticoagulation for 6 months. MAIN OUTCOME MEASURES: Patency at one month and one year, morbidity and mortality. RESULTS: At one month 6/17 who presented with rest pain could walk unlimited distances, 8 had claudication between 50 and 500 m, and 3 had no improvement; 2 had had below knee amputations. At one year only 4 could walk unlimited distances, 5 had claudication between 50 and 500 m, 2 had rest pain, 4 had had major amputations, and 1 was dead and 1 was lost to follow up. Five patients had had 10 additional procedures. Of the 3 who presented with claudication, 2 improved their walking distance to at least 100 m, and one had total relief of symptoms after one month; after a year one had no symptoms, one had mild claudication, and one had severe claudication (120 m). Three developed complications: one bleeding 12 hours after treatment was successfully treated by transfusion, one embolism to the midpopliteal artery was successfully treated by embolectomy, and one episode of bleeding during lysis ceased when treatment was stopped. CONCLUSION: Thrombolysis is at best only an adjunct to balloon angioplasty or traditional vascular operations. PMID: 7858043 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 22: J Endovasc Surg. 1994 Sep;1:81-7. PTA and thrombolysis in leg salvage. Motarjeme A. Midwest Vascular Institute of Illinois, Chicago, USA. PURPOSE: The goals of any treatment for ischemic vascular disease are to relieve pain, allow wound healing, and regain/maintain ambulatory abilities. To determine if endovascular therapy could accomplish these goals in patients with limbs at risk, we undertook a retrospective analysis of the results of percutaneous transluminal angioplasty (PTA) and thrombolysis in leg salvage. METHODS: Over an 8-year period ending in 1993, 327 patients (209 males, 118 females) with limb-threatening ischemia (defined as one or more of the following: ischemic rest pain, ischemic ulceration, or gangrene) in 361 limbs were seen. These patients had an ankle-brachial index < or = 0.40 in nondiabetic patients and/or toe-brachial index < or = 0.30 in diabetic patients. The patients were treated with thrombolysis and/or PTA according to standard techniques; intravascular stenting was used occasionally as required to treat PTA deficiencies or inadequate recanalization. RESULTS: Among the 327 patients, 805 arteries and 25 thrombosed arterial grafts were treated. The arteries treated were: 6 aorta (0.75%), 75 iliac (9.3%), 34 common femoral (4.2%), 3 deep femoral (0.4%), 235 superficial femoral (29.2%), 219 popliteal (27.2%), 193 infrapopliteal (24.0%), and 40 pedal (5.0%). The patients were treated primarily with PTA (n = 307); urokinase thrombolysis (n = 99) and stents (n = 12) were used less frequently. Procedural success was 92.5%. Patients were followed from 6 months to 8 years (mean 3 years). Eighty-three patients were retreated during this time. Of the 249 patients available for this follow-up, total salvage was achieved in 181 (72.7%). Nineteen patients (7.6%) underwent minor amputations (e.g., toes); 4 patients (1.6%) had transmetatarsal amputation. Fifteen patients (3.6%) had above-knee amputation despite successful recanalization. In all, 32 patients (8.8%) had the amputation level extended from above to below knee, bringing the total leg salvage rate to 82% (defined as patients able to ambulate without any prosthesis). Using life-table analysis, the 5 year survival rate was 71%. CONCLUSION: This study shows that endovascular therapy for leg salvage is as effective as reconstructive vascular surgery in achieving wound healing and maintaining ambulation and has a more favorable 5-year survival rate. PMID: 9234108 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 23: Circulation. 1994 Jul;90(1):69-77. Adjunctive thrombolytic therapy during angioplasty for ischemic rest angina. Results of the TAUSA Trial. TAUSA Investigators. Thrombolysis and Angioplasty in Unstable Angina trial. Ambrose JA, Almeida OD, Sharma SK, Torre SR, Marmur JD, Israel DH, Ratner DE, Weiss MB, Hjemdahl-Monsen CE, Myler RK, et al. Department of Medicine, Mount Sinai Medical Center, New York, NY 10029. BACKGROUND: Acute closure is increased after angioplasty in unstable angina, and adjunctive intracoronary thrombolytic therapy has been used successfully to increase angiographic success. The role of prophylactic thrombolytic therapy during angioplasty in unstable angina is unknown. METHODS AND RESULTS: Four hundred sixty-nine patients with ischemic rest pain with or without a recent (< 1 month) infarction were randomized in double-blind fashion to intracoronary urokinase or placebo. Randomization was carried out in two sequential phases. In phase I, 257 patients were randomized to 250,000 U of urokinase or placebo given in divided doses at the time of angioplasty. In phase II, 212 patients were randomized to 500,000 U of urokinase or placebo in divided doses. All patients were pretreated with aspirin, and activated clotting times were followed to maintain them at > 300 seconds during angioplasty. Angiographic end points of thrombus after angioplasty were insignificantly decreased by urokinase (30 [13.8%] versus 41 [18.0%] with placebo; P = NS). Acute closure, on the other hand, was increased with urokinase (23 [10.2%] versus 10 [4.3%] with placebo; P < .02). The difference in acute closure between urokinase and placebo was more striking at the higher dose of urokinase (P < .04) than in phase I at the lower urokinase dose (P = NS). Adverse in-hospital clinical end points (ischemia, infarction, or emergency coronary artery bypass surgery) were also increased with urokinase versus placebo (30 [12.9%] versus 15 [6.3%], respectively; P < .02). Angiographic and clinical end points were worse with urokinase in unstable angina without recent infarction than with angioplasty after a recent infarction. CONCLUSIONS: Adjunctive urokinase given prophylactically during angioplasty for ischemic rest angina as administered in this trial is associated with adverse angiographic and clinical events. These detrimental effects may be related to hemorrhagic dissection, lack of intimal sealing, or procoagulant or platelet-activating effects of urokinase. Publication Types: Clinical Trial Multicenter Study Randomized Controlled Trial PMID: 8026054 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 24: Hinyokika Kiyo. 1994 Jun;40(6):525-8. Acute pulmonary embolism after conservative surgery for renal cyst: a case report. Satake I, Nakagomi K, Tari K. Urology Clinic, Saitama Cancer Center. A case of acute pulmonary embolism which developed one week after conservative surgery of the renal cyst is reported. He was 41 years old and had a long habit of cigarette smoking. He underwent wedge resection of the renal mass which was proved to be a multilocular renal cyst pathologically. The acute pulmonary embolism which developed on the seventh postoperative day was confirmed by lung scintigraphy. The patient recovered from the disease by thrombolytic therapy. Postoperative bed rest seemed to be closely associated with the incidence in this case. Early ambulation is recommended. In addition, the thromboprophylactic therapy may be justified in patients undergoing kidney-sparing surgery which requires postoperative bed rest. Publication Types: Case Reports PMID: 8073962 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 25: G Ital Cardiol. 1993 Sep;23(9):865-70. [The prognostic value of the ejection fraction at rest and under stress assessed by nuclear angiography in myocardial infarct patients] [Article in Italian] Azzolini P, Speciale G, Risa MP, Puglisi A, Ricci R, Neja CP, Fioranelli M, Sgreccia F, Uthurralt N, Angrisani G. Divisione di Cardiologia e UTIC, Ospedale S. Giovanni Calibita Fatebenefratelli, Isola Tiberina, Roma. BACKGROUND. The aim of this study was to assess the utility of ejection fraction at rest (rEF) and its change during stress (delta EF) as a predictor of cardiac events during the follow-up of patients (pts) with myocardial infarction. METHODS. 74 pts (44 treated with thrombolytic therapy (TR), and 30 not (noTR)), were studied with 99mTcPYP angiography within 2 +/- 1 months, after AMI. By 20 +/- 10 months, 41 pts had no events (Group A) while 33 pts experienced cardiac events (3 deaths, 16 angina, 12 CABG, and 2 PTCA). RESULTS. rEF was similar in both Groups A and B (A 47 +/- 8 vs B 45 +/- 10 p. ns), 44 +/- 15 vs B-noTR 46 +/- 12 p. ns). delta EF was different between Groups A and B. Group A showed a positive delta EF (3.2 +/- 6), and this result was more evident in thrombolyzed AMI (A-TR 4.4 +/- 4.5 vs A-noTR 1.16 +/- 3.9 p. < 0.01). Group B showed a negative delta EF (-4.4 +/- 5.3), and this result was more evident in non thrombolyzed AMI (B-TR -2 +/- 6.4 vs B-noTR -5.8 +/- 8 p. < 0.01). CONCLUSIONS. A decrease in EF during exercise radionuclide angiography is useful in identifying pts with high risk of cardiac events after AMI. Thrombolytic therapy improves stress EF in both Groups A and B. PMID: 8119515 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 26: Angiology. 1993 Jul;44(7):574-9. Complete recanalization of total occlusion in abdominal aorta by intra-aortic infusion of a thrombolytic agent--a case report. Ashida K, Imaizumi M, Isaka Y, Moriwaki H, Matushita K, Iichi O. Department of Internal Medicine, Osaka National Hospital, Japan. Complete recanalization was achieved by intra-aortic infusion of urokinase in a case of complete occlusion of the abdominal aorta. The patient was a fifty-nine-year-old man with atrial fibrillation, hypertension, and diabetes mellitus who was admitted because of intermittent claudication and pain in both lower extremities at rest. Angiography demonstrated complete obstruction of the abdominal aorta, but the bilateral iliac arteries were visualized via collaterals. Urokinase was administered intra-aortically in a total dose of 1,200,000 U during the first day and a total dose of 960,000 U during the second day. The aorta and the iliac arteries recanalized after this treatment, and complete recanalization associated with disappearance of subjective symptoms was observed after one month of treatment with warfarin. The present case suggests the usefulness of intra-arterial infusion of urokinase for the treatment of complete occlusion of the abdominal aorta. Publication Types: Case Reports PMID: 8328687 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 27: Jpn Circ J. 1993 Jan;57(1):27-36. Implications of delayed image on simultaneous thallium-201/technetium-99m pyrophosphate dual emission computed tomography early after acute myocardial infarction. Sakata K, Yoshida H, Ono N, Ohtani S, Mori N, Yokoyama S, Hoshino T, Kaburagi T, Kurata C. Department of Cardiology, Shizuoka General Hospital, Japan. This study aimed investigate whether thallium-201 and technetium-99m pyrophosphate dual rest-redistribution emission computed tomography early after intracoronary thrombolysis may provide supplementary information for the management of patients with acute myocardial infarction. Fifty patients who received intracoronary thrombolysis underwent simultaneous dual emission computed tomography 3 days after first acute myocardial infarction. All patients who had a technetium-99m pyrophosphate accumulation were selected. Thallium-201/technetium-99m pyrophosphate overlap in the initial and delayed images early after intracoronary thrombolysis identified successful recanalization with sensitivities of 68% and 90% (p < 0.05), specificities of 47% 79% (p < 0.05), positive predictive accuracies of 68% and 88%, negative predictive accuracies of 47% and 80% (p < 0.05), and overall accuracy of 60% and 86% (p < 0.01), respectively. The patients were divided into 3 groups according to the change in thallium-201 uptake from the initial image to the delayed image on dual emission computed tomography: 20 patients had no change in thallium-201 uptake (fixed type), 16 had increases in thallium-201 uptake (redistribution type), and 14 had decreases in thallium-201 uptake (reverse redistribution type). The number of patients with successful recanalization was significantly higher in the redistribution type than in the other types (redistribution type vs reverse redistribution type or fixed type; p < 0.01, respectively). In the redistribution type a frequency of reinfarction in the same infarcted area during the hospital course was significantly higher than in the other types (redistribution type vs reverse redistribution type or fixed type; p < 0.05, respectively), which was mainly due to the patients having high grade residual stenosis. Thus, a thallium-201/technetium-99m pyrophosphate overlap in the delayed image early after acute myocardial infarction can be used as an index for predicting successful early recanalization and probably viable myocardium. In addition, the redistribution patterns on thallium-201 emission computed tomography early after intracoronary thrombolysis can be helpful in identifying patients with successful early recanalization and a high risk subset. PMID: 8437339 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 28: Thromb Haemost. 1992 Nov 10;68(5):550-5. Influence of heparin and a low molecular weight heparinoid on specific endogenous and exogenous fibrinolytic factors during rest and exercise. de Boer A, Kluft C, Dooijewaard G, Kasper FJ, Kroon JM, Breimer DD, Stiekema JC, Cohen AF. Centre for Human Drug Research, University Hospital Leiden, The Netherlands. The effects of heparin (5,000 IU i.v.) and the low molecular weight heparinoid Org 10172 (Orgaran) (3,250 anti-Xa units i.v.) on components of the fibrinolytic system were studied in two double-blind, randomised, placebo-controlled, cross-over trials using healthy subjects. In study A (n = 6) the effects were studied during rest and standardized exercise and in study B (n = 6) during a low dose infusion of recombinant tissue-type plasminogen activator (rt-PA; 80 micrograms over 16 min). At rest, heparin and Org 10172 did not influence the plasma concentrations of endogenous t-PA antigen and activity, urokinase-type PA (u-PA) antigen, plasmin activatable pro-urokinase (scu-PA), active urokinase (tcu-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen. Recombinant t-PA antigen and activity during rt-PA infusion were also not affected. During exercise, neither heparin nor Org 10172 influenced the area under the curve (AUC) of t-PA and u-PA antigen and t-PA activity when compared with placebo. Unexpectedly, after heparin the AUC of t-PA activity was 49% larger (range +19 to +245%) than after Org 10172 (p < 0.05). The last difference was considered spurious, scu-PA, tcu-PA and PAI-1 antigen levels at 2 min after termination of exercise were unaffected by both compounds (p > 0.05). Sulphated polysaccharides do not increase fibrinolytic activity of the plasma by changing the concentrations of the components of the fibrinolytic system. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 1280862 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 29: J Am Coll Cardiol. 1992 Nov 1;20(5):1197-204. Adjunctive thrombolytic therapy for angioplasty in ischemic rest angina: results of a double-blind randomized pilot study. Ambrose JA, Torre SR, Sharma SK, Israel DH, Monsen CE, Weiss M, Untereker W, Grunwald A, Moses J, Marshall J, et al. Department of Medicine, Mount Sinai Medical Center, New York, New York 10029. OBJECTIVES. A multicenter pilot study was instituted to assess the role of intracoronary thrombolytic therapy during angioplasty for ischemic rest angina. BACKGROUND. Acute thrombotic coronary occlusion is increased during angioplasty for unstable angina, and intracoronary thrombolytic agents have been used to maintain patency. Prophylactic use of intracoronary thrombolytic agents has been advocated in certain high risk subgroups, although no studies have randomized therapy. METHODS. Ninety-three patients with either unstable angina and pain at rest (trial A, 66 patients) or postinfarction pain at rest (trial B, 27 patients) were randomized in double-blind fashion to administration of either intracoronary urokinase, 150,000 U, or saline solution placebo given immediately before angioplasty. Cineangiograms of the culprit lesion were recorded and analyzed in blinded fashion by a core laboratory for definite or possible (haziness) filling defects 15 min after angioplasty or after acute closure. RESULTS. Urokinase decreased filling defects at 15 min after angioplasty in comparison with placebo (14% vs. 29%, respectively, p = 0.08). Four patients in each treatment group developed acute vessel closure. However, although urokinase significantly reduced the incidence of filling defects in trial A (3% vs. 23%, p = 0.03), the drug had no effect at the selected dose in trial B (42% vs. 43%, respectively). Acute vessel closure occurred significantly more frequently in trial B than in trial A, and urokinase at the selected dose also had no effect. Ischemic events after angioplasty appeared to be related more to dissection than to thrombosis, although redilation, which was more frequent after placebo administration, may have reduced their incidence as well as that of acute closure. CONCLUSIONS. These data suggest a possible role for intracoronary urokinase during angioplasty for unstable angina. The lack of effect after infarction may represent a greater thrombus burden or degree of plaque disruption. A trial utilizing higher doses of urokinase in a larger patient group is in progress. Publication Types: Clinical Trial Multicenter Study Randomized Controlled Trial PMID: 1401622 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 30: J Vasc Interv Radiol. 1992 Aug;3(3):475-83. Erratum in: J Vasc Interv Radiol 1992 Nov;3(4):724. Low-dose urokinase regimen for the treatment of lower extremity arterial and graft occlusions: experience in 132 cases. LeBlang SD, Becker GJ, Benenati JF, Zemel G, Katzen BT, Sallee SS. Miami Vascular Institute, Baptist Hospital of Miami, FL 33176. In a retrospective review, a low-dose urokinase (UK) infusion regimen (mean, 87,000 U of UK per hour and 100 U of heparin per hour) was evaluated for lower extremity arterial and graft occlusions. Results of 132 infusions in 111 patients were analyzed to determine efficacy, limb salvage, and complications. Angiographic success was achieved with 126 infusions (95%), and amelioration of presenting signs and symptoms was achieved after 116 infusions (88%). Patients who underwent additional percutaneous procedures were more likely to have a successful outcome. There was no significant difference in success rates for patients receiving low-dose heparin through the arterial sheath (n = 101) versus those receiving concomitant systemic heparinization (n = 29), (P = .08) [corrected]. Of 88 threatened extremities (with rest pain, cold, ulcers, or gangrene), nine were amputated (limb salvage = 90%), accounting for 82% (nine of 11) of amputations in the overall study. Patients with zero- or one-vessel runoff before infusion were more likely to require limb amputation compared with the group with two- or three-vessel runoff before infusion (P less than .01). Major periprocedural complications occurred in nine of 132 (7%) infusions, five of which necessitated specific surgery and/or transfusion for bleeding. Pericatheter thrombosis was not encountered in either subgroup. This standard local low-dose infusion represents a safe and effective treatment for lower extremity arterial and graft occlusions. Publication Types: Review Review of Reported Cases PMID: 1515719 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 31: Nippon Ronen Igakkai Zasshi. 1992 Mar;29(3):202-6. [A case of complete recanalization in the lower abdominal aorta by intraaortic infusion of a thrombolytic agent] [Article in Japanese] Ashida K, Imaizumi M, Isaka Y, Ishida M, Matsushita K, Nakayama H. Cardiovascular Division, Osaka National Hospital. Intraarterial infusion of thrombolytic agent is useful in the treatment of obstructive arterial diseases in various vessels. However, few studies have shown that this treatment is useful for aortic occlusion. We report the case with complete recanalization in the lower abdominal aorta following intraaortic infusion of a thrombolytic agent. A 59-year-old man was admitted because of weakness and pain in the bilateral lower limbs at rest. Aortography showed complete occlusion of the abdominal aorta proximal to the inferior mesenteric artery. Both external arteries were supplied via rich collaterals. He was treated by intraaortic urokinase infusion of 2,100,000 units. Total recanalization in the abdominal aorta and both common iliac arteries was obtained. Intraaortic infusion of urokinase was shown to be effective treatment of occlusion in the abdominal aorta. Publication Types: Case Reports PMID: 1593791 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 32: J Biol Chem. 1991 Apr 25;266(12):7842-7. The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator. Behrendt N, Ploug M, Patthy L, Houen G, Blasi F, Dano K. Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark. The purified urokinase plasminogen activator receptor (u-PAR) was cleaved into two fragments by mild chymotrypsin treatment. The smaller fragment (apparent Mr 16,000) possessed the ligand-binding capability, as shown by chemical cross-linking analysis. This fragment constituted the NH2-terminal part of the intact receptor, probably including the whole sequence 1-87, and contained N-linked carbohydrate. After detergent phase separation in the Triton X-114 system, the fragment was present in the water phase where its binding activity could be demonstrated in the absence of the rest of the protein. An analysis of internal homology in the amino acid sequence of u-PAR revealed the presence of three repeats of approximately 90 residues each. The ligand-binding fragment corresponds to the first repeat, supporting that this unit is a structurally autonomous domain. Domains homologous with the internal repeats of u-PAR constitute the extracellular part of Ly-6 antigens and of the squid glycoprotein Sgp-2. Like u-PAR, these proteins are attached to the membrane by a glycosyl-phosphatidylinositol anchor. The hydrophilic, ligand-binding u-PAR domain identified in the present study has potential applications in interfering with cell-surface plasmin-mediated proteolysis. PMID: 1850423 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 33: Thromb Haemost. 1991 Jan 23;65(1):82-6. Physical exercise induces enhancement of urokinase-type plasminogen activator (u-PA) levels in plasma. Dooijewaard G, de Boer A, Turion PN, Cohen AF, Breimer DD, Kluft C. Gaubius Institute TNO, Leiden, The Netherlands. The enhancement of the blood fibrinolytic potential by physical exercise is generally attributed to the release of tissue-type plasminogen activator (t-PA) from the vessel wall. In this study we have investigated the possible contribution of urokinase-type plasminogen activator (u-PA). Six healthy male volunteers (age 21-25 years) were screened for their ability to perform maximal exercise for their age-group for 12 min on a bicycle ergometer. Subsequently, on one occasion they were required to remain supine for 2 h (from 8.30 a.m. onwards) an on another they performed maximal exercise (from 9.00 a.m. onwards). During exercise an increase in u-PA antigen and plasmin-activatable pro-urokinase (proUK) activity, concurrent with t-PA antigen and euglobulin t-PA activity, was observed in all six volunteers, while at rest these parameters remained unaffected. Mean u-PA- and t-PA antigen increased, respectively, from 4.2 +/- 1.0 ng/ml and 5.8 +/- 2.1 ng/ml before exercise to 9.8 +/- 3.0 ng/ml and 18.3 +/- 3.8 ng/ml (peak). Mean plasmin-activatable proUK activity and t-PA activity increased, respectively, from 2.1 +/- 0.4 ng/ml and 0.3 +/- 0.2 ng/ml before exercise to 4.3 +/- 1.7 ng/ml and 7.2 +/- 4.0 ng/ml (peak). The increases were statistically significant throughout (paired t-test, pre vs post, antigen P less than 0.005 and activity P less than 0.02). After cessation of exercise u-PA and t-PA declined concurrently to normal values with a 50% decay in about 5 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID: 1902597 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 34: No Shinkei Geka. 1989 Jun;17(6):533-7. [Pulmonary embolism as a complication in neurosurgical patients] [Article in Japanese] Meguro K, Matsuki T, Higuchi O, Nakada Y, Fukuda I, Wada M. Department of Neurosurgery, Tsukuba Medical Center. The overall incidence of pulmonary embolism (PE) among neurosurgical in-patients, whose ages ranged from 23 to 80, was 0.7%. Our report here is based on five cases of patients with PE. Four of these five patients were over 50 years of age. They had been admitted because of such reasons as brain tumor, spinal cord injury, intracerebral hematoma, and venous sinus thrombosis. Deep vein thrombosis (DVT) was seen in four but none were diagnosed before they had developed PE. Decreased level of consciousness and prolonged bed rest appeared to be common risk factors for PE. Mean duration between admission and onset of PE was 31 days. Although non-specific, tachycardia, tachypnea and hypoxemia were the most common signs and symptoms. As a definitive diagnostic procedure, pulmonary angiography was performed in most of cases. One patient required surgical embolectomy and others were treated with anticoagulation or fibrinolytic agents. In order to prevent recurrent thromboembolic phenomena, ligation of the inferior vena cava was a useful mode of treatment when anticoagulation was not indicated. And this approach seemed to be valid in most neurosurgical patients. We conclude that PE and DVT were not uncommon complications among Japanese neurosurgical patients and they can be treated successfully in collaboration with a cardiovascular surgeon if the diagnosis can be made correctly. PMID: 2615903 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 35: Thromb Haemost. 1988 Apr 8;59(2):299-303. Fibrinolysis in normal subjects--comparison between plasminogen activator inhibitor and other components of the fibrinolytic system. Nicoloso G, Hauert J, Kruithof EK, Van Melle G, Bachmann F. Departement de Medecine Interne, CHUV, Lausanne, Switzerland. We analyzed fibrinolytic parameters in 20 healthy men and 20 healthy women, aged from 25 to 59, before and after 10 and 20 min venous occlusion. The 10 min post-occlusion fibrinolytic activity measured directly in diluted unfractionated plasma by a highly sensitive 125I-fibrin plate assay correlated well with the activity of euglobulins determined by the classical fibrin plate assay (r = 0.729), but pre-stasis activities determined with these two methods did not correlate (r = 0.084). The enhancement of fibrinolytic activity after venous occlusion was mainly due to an increase of t-PA in the occluded vessels (4-fold increase t-PA antigen after 10 min and 8-fold after 20 min venous occlusion). Plasminogen activator inhibitor (PAI) activity and plasminogen activator inhibitor 1 (PAI-1)1 antigen levels at rest showed considerable dispersion ranging from 1.9 to 12.4 U/ml, respectively 6.9 to 77 ng/ml. A significant increase of PAI-1 antigen levels was observed after 10 and 20 min venous occlusion. At rest no correlation was found between PAI activity or PAI-1 antigen levels and the fibrinolytic activity measured by 125I-FPA. However, a high level of PAI-1 at rest was associated with a high prestasis antigen level of t-PA and a low fibrinolytic response after 10 min of venous stasis. Since the fibrinolytic response inversely correlated with PAI activity at rest, we conclude that its degree depends mainly on the presence of free PAI. PMID: 3133812 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 36: Circulation. 1988 Mar;77(3):526-34. The role of intracoronary thrombus in unstable angina: angiographic assessment and thrombolytic therapy during ongoing anginal attacks. Gotoh K, Minamino T, Katoh O, Hamano Y, Fukui S, Hori M, Kusuoka H, Mishima M, Inoue M, Kamada T. First Department of Medicine, Osaka University Medical School, Japan. Intracoronary thrombus is regarded as a potentially important factor in the etiology of unstable angina, but the incidence of intracoronary thrombus in unstable angina has not been clearly defined. To determine the occurrence of intracoronary thrombus during ongoing angina pectoris, coronary angiography was performed during spontaneous ischemic attacks in 37 patients with prolonged rest angina. All patients exhibited significant (greater than 50%) stenoses of at least one major coronary artery. Of the 37 patients, 21 (57%) had intracoronary thrombus in major coronary arteries, whereas 14 (38%) had fixed narrowings without evidence of intracoronary thrombus and two exhibited coronary spasm. ST segment elevation was observed in 16 of 21 patients with thrombus and in all of the patients with coronary spasm, but all the patients with organic stable obstruction showed ST segment depression. Twenty of the 21 patients with thrombus improved after thrombolytic therapy with intracoronary injection of urokinase; obstructed arteries were reopened, or narrowings were attenuated, with relief of ischemic symptoms. In patients with fixed obstructions, the rate-pressure product during active symptoms was significantly higher than during an asymptomatic period, indicating that a transient increase in myocardial oxygen demand may contribute to the ischemic attack in these patients. A high incidence (71%) of recurrent symptoms was observed in patients with intracoronary thrombus even after successful thrombolysis, in contrast to a much lower incidence (36%) in those without intracoronary thrombus. Myocardial infarction within 4 weeks after catheterization was observed more frequently in patients with intracoronary thrombus (24%) than in those without thrombus (7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID: 3342483 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 37: Schweiz Med Wochenschr. 1988 Jan 31;118(4):122-4. [Differentiation of a normal population and of a cohort of patients presenting with a history of idiopathic thromboembolism as identified with fibrinolytic tests] [Article in French] Nicoloso G, Hauert J, Kruithof EK, van Melle G, Bachmann F. Departement de medecine, CHUV, Lausanne. To identify persons at risk for development of thromboembolic disease, fibrinolytic and blood coagulation parameters of normal controls (n = 40) and patients (n = 40) have been compared. Four fibrinolytic parameters, i.e. fibrinolytic activity at rest (FAr), fibrinolytic response after 10 minutes of venous occlusion (delta FA10'), and resting antigenic levels of the plasmatic inhibitor of the plasminogen activators (PAI-1) and of urokinase (u-PA), showed significant differences between the two study groups. The separate and combined discriminant analysis of FAr and delta FA10' values revealed that individuals with FAr below 0.63 UI/ml or a delta FA10' below 0.98 UI/ml are at risk for development of thromboembolic disease. PMID: 3125604 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 38: South Med J. 1987 Apr;80(4):479-82. Intra-arterial thrombolysis for acute limb ischemia: a three-year experience. Battey PM, Fulenwider JT, Smith RB 3rd, Martin LG, Stewart MT, Perdue GD. Peripheral arterial thromboembolism and thrombosis of arterial grafts continue to threaten viability of extremities. Percutaneous intra-arterial thrombolysis (IAT) and angiodilatation have afforded limb salvage in some of these patients. Proper patient selection appears to be the hallmark of success with IAT. During a recent three-year period, we used IAT in 32 extremities in 28 patients who had acute arterial insufficiency. Before IAT, 16 extremities were painful at rest, and 16 had incapacitating claudication. The overall success rate was 38%, but some degree of thrombolysis occurred in 88%. Limb salvage was achieved in 27 of 32 extremities (84%). Only five of 17 limbs (29%) with arterial graft thrombosis required no operation or an operation of lesser magnitude than predicted before IAT. Of six extremities with native arterial embolism, four (67%) were completely cleared with IAT. Major complications occurred in eight cases (25%), with two IAT-related deaths (6%). This study suggests that IAT is best reserved for individuals with acute limb ischemia caused by arterial embolus, those whose degree of ischemia would tolerate a 24-hour trial of IAT, and those whose femoral or tibial runoff is not likely to require remedial operation. PMID: 3563582 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 39: Angiology. 1985 Oct;36(10):720-35. Therapy of atherosclerotic arteriopathy of lower limbs. Aspects and results. Tesi M, Bronchi GF, Carini A, Karavassili M. As far as therapy is concerned, atherosclerotic arteriopathy may be divided into acute and chronic forms. In acute embolic forms, therapy should be surgical. Only in cases of peripheral embolism or polyembolism, and in rare cases for which vascular surgery cannot be adopted, can thrombolysis be carried out with UK. In acute thrombotic forms, therapy should be medical, because a thrombus of recent formation is rich in fibrin and may be lyzed by UK. Total recanalization takes place in 61% of cases treated, partial recanalization in 23%. Subsequently perviousness is maintained by adequate antithrombotic therapy. In chronic arteriopathy, the thrombus is lacking or almost lacking in fibrin and thrombolytic therapy is not indicated. Special therapeutic combinations are used containing platelet inhibitors (ticlopidine), antifibrin drugs (subcutaneous heparin), minor fibrinolytic agents (mesoglycan) and hemorheological drugs (pentoxyphylline). This therapy seems to give good results, as showed by the low percentage in amputation calculated on 2,565 patients treated and kept under observation for 5 years. Finally let us consider chronic progressive arteriopathy. This term indicates a very advanced stage, characterized by a gradual irreversible change for the worse leading towards gangrene. As a last resort, before amputating, a thrombolytic therapy with UK was tried to see if with strong fibrinolysis continued for 3 days amputation might be avoided. In a pilot study carried out on 12 patients, the angiographic data showed only partial lysis in small arteries or arterial branches. Clinical data showed reduction or disappearance of pain at rest in 80% of cases. In 70% of cases gangrene disappeared if it was initial and superficial, it was delimited if already in progress. Publication Types: Clinical Trial PMID: 2932987 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 40: Dtsch Med Wochenschr. 1985 Feb 22;110(8):293-7. [Long-term results after local thrombolysis in acute massive pulmonary embolism] [Article in German] Schwarz F, Stehr H, Zimmermann R, Manthey J, Harenberg J, Kubler W. Intrapulmonary arterial infusions of urokinase (mean 1724 IU/kg X h) and heparin (mean 17 IU/kg X h) were given to 7 patients with acute massive pulmonary embolism. Pulmonary angiography and pulmonary artery pressure measurements were performed before, during and 15 months after the drug infusion. During the acute phase, pulmonary artery pressures were recorded daily while urokinase and heparin were administered until the pressures had become normal (after a mean of 6 days). 15 months later right heart catheterization was undertaken before and after ergometric exercise as well as bilateral leg venography. Before treatment pulmonary angiography demonstrated massive vascular obstruction which regressed markedly during and after drug infusion. Treatment also led to normalization of previously elevated pulmonary artery pressures. In addition, pulmonary artery mean pressures and total pulmonary vascular resistance became normal both at rest and on exercise in 6 patients. All patients had signs of acute leg vein thrombosis before treatment, but 15 months later phlebography demonstrated normal findings in 4 and residual findings of previous thrombosis in 3. Local thrombolysis of acute massive pulmonary embolism is thus a highly successful form of treatment. Publication Types: Case Reports PMID: 3971880 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 41: Circulation. 1985 Jan;71(1):117-23. Sustained improvement of pulmonary hemodynamics in patients at rest and during exercise after thrombolytic treatment of massive pulmonary embolism. Schwarz F, Stehr H, Zimmermann R, Manthey J, Kubler W. This study assessed the long-term effects of thrombolytic treatment in patients with acute massive pulmonary embolism (PE). Seven patients with PE that followed deep-vein thrombosis underwent pulmonary angiography and pressure measurements before and 6 +/- 3 days (mean +/- SD) and 15 +/- 4 months after treatment with intrapulmonary infusions of urokinase (average dose 1724 U/kg X hr) and heparin (average dose 17 U/kg X hr). Treatment was guided by daily measurements of pulmonary arterial (PA) pressure and was continued until PA pressure had normalized (average of 6 days). Late after treatment patients returned for pulmonary angiographic examination, right heart catheterization at rest and during bicycle exercise, and phlebography of the deep veins of both legs. Pulmonary angiograms showed massive obstruction before therapy (Walsh index 15 +/- 2 points of a maximum of 18 points), which was improved 6 days (3 +/- 3 points) and 15 months (1 +/- 2 points) after therapy. Mean PA pressure declined from 37 +/- 9 to 13 +/- 3 mm Hg after 6 days and to 15 +/- 3 mm Hg after 15 months. No recurrence of PE was observed. In six of seven patients at rest and during bicycle exercise (up to 100 W) in the supine position mean PA pressure and total pulmonary resistance remained within normal limits. Over the short term all patients showed clinical signs of deep-vein thrombosis; 15 months later four patients had normal deep veins, but three patients had still phlebographic signs of old thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID: 3964712 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 42: Biochem J. 1984 Oct 1;223(1):169-77. Identification of molecular forms of plasminogen and plasmin-inhibitor complexes in urokinase-activated human plasma. Mullertz S, Thorsen S, Sottrup-Jensen L. Urokinase-activated human plasma was analysed by acetic acid/urea/polyacrylamide-gel electrophoresis. The bands representing plasminogen, the plasmin-alpha 2-plasmin inhibitor and plasmin-alpha 2-macroglobulin complexes were identified by immunoprecipitation with specific antibodies and by comparison with purified components. Plasminogen and the plasmin-inhibitor complexes were isolated from plasma or thrombin-clotted plasma containing 125I-labelled Glu-plasminogen (residues 1-790) and urokinase. The plasma was kept at 37 degrees C for 0.5 and 10 times the lysis time of the clotted plasma, the clotted plasma until lysis. The plasmin heavy chain from the plasmin-inhibitor complexes was subsequently prepared. Only in one case could a low-grade proteolytic conversion of Glu- forms into Lys/Met/Val-forms (residues 77-790, 68-790 and 78-790 respectively) during the preparations be detected. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and N-terminal sequence analysis of the purified plasminogen and plasmin heavy chain showed the following. The plasminogen in plasma was on the Glu- form. Glu-plasmin constituted 0.74 and 0.58 of the plasmin bound to the alpha 2-plasmin inhibitor in plasma after brief and prolonged activation respectively. The rest was Lys/Met/Val-plasmin. The clotted plasma contained about equal amounts of Glu-plasminogen and Lys/Met/Val-plasminogen, and predominantly Lys/Met/Val-plasmin complexed to alpha 2-plasmin inhibitor and alpha 2-macroglobulin. The results of the analysis of the purified material substantiated the identity of radioactive protein bands in the gel after acetic acid/urea/polyacrylamide-gel electrophoresis. PMID: 6208893 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 43: Angiology. 1984 Jul;35(7):427-35. Studies of the clinical pharmacology and therapeutic efficacy of pentoxifylline in peripheral obstructive arterial disease. Di Perri T, Carandente O, Vittoria A, Guerrini M, Messa GL. Studies were carried out to investigate the effects of pentoxifylline on various hemorheological (whole blood, plasma and serum viscosity, erythrocyte filtrability, hematocrit), hemostasiological (blood coagulation and fibrinolysis: euglobulin lysis time, fibrinogen, plasminogen, alpha-2-macroglobulin, alpha-1-antitrypsin, antiplasmin; platelet function: beta-thromboglobulin), and hemodynamic factors (limb perfusion: rest and peak flow, time to peak flow; systemic blood pressure, heart rate). In addition, clinical efficacy was monitored in patients with claudication by assessing walking capacity under placebo controlled double blind cross over conditions. The investigations disclosed the positive influence of acute and chronic pentoxifylline administration on hemorheological, hemostasiological and perfusion parameters, most of the changes recorded being statistically significant. The clinical benefit of pentoxifylline (Trental 400) treatment was demonstrated by the significantly superior increase in walking capacity in comparison to placebo in the controlled study. PMID: 6540539 [PubMed - indexed for MEDLINE] ---------------------------------------------------------------