http://hdl.handle.net/10171/3456 2013-05-22T22:50:44Z http://hdl.handle.net/10171/27505 Title: Maintained effectiveness of an electronic alert system to prevent venous thromboembolism among hospitalized patients Author(s) : Lecumberri, R. (Ramón); Marques, M. (Margarita); Diaz-Navarlaz, M.T. (María Teresa); Panizo, E. (Elena); Toledo, J. (Jon); Garcia-Mouriz, A. (Alberto); Paramo, J.A. (José Antonio) Abstract: Despite current guidelines, venous thromboembolism (VTE) prophylaxis is underused. Computerized programs to encourage physicians to apply thromboprophylaxis have been shown to be effective in selected populations. Our aim was to analyze the impact of the implementation of a computer-alert system for VTE risk in all hospitalized patients of a teaching hospital. A computer program linked to the clinical record database was developed to assess all hospitalized patients' VTE risk daily. The physician responsible for patients at high risk was alerted, but remained free to order or withhold prophylaxis. Over 19,000 hospitalized, medical and surgical, adult patients between January to June 2005 (pre-intervention phase), January to June 2006 and January to June 2007 (post-intervention phase), were included. During the first semesters of 2006 and 2007, an electronic alert was sent to 32.8% and 32.2% of all hospitalized patients, respectively. Appropriate prophylaxis among alerted patients was ordered in 89.7% (2006) and 88.5% (2007) of surgical patients, and in 49.2% (2006) and 64.4% (2007) of medical patients. A sustained reduction of VTE during hospitalization was achieved, Odds ratio (OR): 0.53, 95% confidence interval (CI) (0.25-1.10) and OR: 0.51, 95%CI (0.24-1.05) during the first semesters of 2006 and 2007 respectively, the impact being significant (p < 0.05) among medical patients in 2007, OR: 0.36, 95%CI (0.12-0.98). The implementation of a computer-alert program helps physicians to assess each patient's thrombotic risk, leading to a better use of thromboprophylaxis, and a reduction in the incidence of VTE among hospitalized patients. For the first time, an intervention aimed to improve VTE prophylaxis shows maintained effectiveness over time. 2008-12-31T23:00:00Z http://hdl.handle.net/10171/23058 Title: Respuestas del miocardio al estrés biomecánico Author(s) : Diez, J. (Javier); Lopez, B. (Begoña); Gonzalez, A. (Arantxa); Ardanaz, N. (Noelia); Fortuño, M.A. (María Antonia) Abstract: El estrés biomecánico del miocardio hace referencia a la situación que se genera cuando, debido a la hipertensión, la hipoxia u otras formas de daño miocárdico, están aumentadas las demandas de trabajo cardíaco y/o se ha perdido miocardio funcionante. Como consecuencia del estrés biomecánico se producen diversas respuestas que afectan a todas las células miocárdicas, en particular a los cardiomiocitos. El resultado final de las mismas son distintas modificaciones fenotípicas que inicialmente son compensadoras (p. ej., hipertrofia), pero que si persiste el estrés pueden mediar la transición de la hipertrofia a la insuficiencia cardíaca (p. ej., apoptosis y fibrosis). Esta revisión se centra en la descripción de las distintas fases de las respuestas miocárdicas al estrés, así como en la consideración de los hallazgos más recientes sobre los mecanismos moleculares implicados en el desarrollo de insuficiencia cardíaca. 2000-12-31T23:00:00Z http://hdl.handle.net/10171/22929 Title: A new favourable effect of cocoa on atherosclerosis? Author(s) : Paramo, J.A. (José Antonio) 2007-12-31T23:00:00Z http://hdl.handle.net/10171/22928 Title: Hemorragia, hemostasia y trombosis en cirugía Author(s) : Paramo, J.A. (José Antonio) Abstract: Surgery is a leading cause of major hemorrhage as well as of thrombosis unless patients are administered appropriate antithrombotic prophylaxis after their thrombo-hemorrhagic risk has been stratified. Therefore, thorough preoperative evaluation is essential to minimize surgical complications. In cases of incoercible bleeding, drugs such as desmopressin, synthetic antifibrinolytics or recombinant factor VII can be administered. To prevent postoperative thrombosis, low molecular weight heparins or pentasaccharide have been shown to significantly reduce the incidence of thromboembolism. 2008-12-31T23:00:00Z http://hdl.handle.net/10171/22927 Title: Atherosclerosis: Is it time for a new name? Author(s) : Paramo, J.A. (José Antonio); Beloqui, O. (Óscar); Diez, J. (Javier) 2000-12-31T23:00:00Z http://hdl.handle.net/10171/22926 Title: The hemostatic system as a modulator of atherosclerosis Author(s) : Paramo, J.A. (José Antonio) 2010-12-31T23:00:00Z http://hdl.handle.net/10171/22925 Title: Inherited haemorrhagic disease with abnormal prothrombin consumption Author(s) : Rocha, E. (Eduardo); Paramo, J.A. (José Antonio); Cuesta, B. (Braulia); Fernandez, J. (Javier) Abstract: The propositus is a 4-year-old boy who presented with a history of excessive bleeding after surgical procedures as well as haematomas and epistaxis. The defect in haemostasis consisted in an anomaly of the prothrombin consumption tests as the only abnormality while all the other conventional coagulation and fibrinolysis tests as well as platelet function tests were normal. The father of the propositus had no previous history of excessive bleeding but was found to have an abnormal prothrombin consumption index. The reaction to prothrombin conversion, normal at onset, slowed down to less than normal and did not reach completion until 24 h. The in vivo studies suggest that the effect does not act on the interaction between platelet phospholipid and plasma. The factor II dosage and the electrophoretic mobility of prothrombin of the plasma were normal; nevertheless when studying the purified prothrombin by means of crossed immunoelectrofocusing there appeared an anomaly of pI. This result suggests the possible existence of an abnormal prothrombin molecule responsible for a slow prothrombin conversion. 1984-12-31T23:00:00Z http://hdl.handle.net/10171/22924 Title: Influence of the fast-acting inhibitor of plasminogen activator on in vivo thrombolysis induced by tissue-type plasminogen activator in rabbits. Interference of tissue-derived components Author(s) : Colucci, M. (M.); Paramo, J.A. (José Antonio); Stassen, J.M. (J.M.); Collen, D. (D.) Abstract: The influence of endotoxin-induced elevated plasma levels of the fast-acting inhibitor of plasminogen activator (PA-inhibitor) on thrombolysis was investigated in rabbits with a jugular vein thrombus. Infusion of human tissue-type plasminogen activator (t-PA) produced similar degrees of thrombolysis in control and endotoxin-treated rabbits, although no free t-PA could be demonstrated in plasma of endotoxin-treated animals. Infusion of t-PA in an extracorporeal arteriovenous shunt resulted in loss of thrombolytic activity in endotoxin-treated animals but not in control animals. Blood clots superfused in vitro with mixtures of t-PA and normal plasma lysed in contrast to clots superfused with t-PA and PA-inhibitor-rich plasma. However, addition of rabbit lung slices to the plasma surrounding the blood clot, reversed the inhibition of thrombolysis by PA-inhibitor-rich plasma. This indicates that tissue-derived factor(s) are involved in the regulation of in vivo thrombolysis. These hypothetical factor(s) are, however, very unstable in plasma, which has thus far precluded their further characterization. 1985-12-31T23:00:00Z http://hdl.handle.net/10171/22923 Title: Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo Author(s) : Colucci, M. (M.); Paramo, J.A. (José Antonio); Collen, D. (D.) Abstract: The inhibition of one-chain and two-chain molecular forms of human tissue-type plasminogen activator (t-PA) by the fast-acting inhibitor of plasminogen activator (PA-inhibitor) present in plasma was studied in vitro and in vivo in rabbits. In vitro, both one-chain and two-chain forms of t-PA were neutralized very rapidly in rabbit plasma with high levels of PA-inhibitor. The rate constant of the interaction between two-chain t-PA and PA-inhibitor was estimated to be 3.10(7) L/mol/sec. The presence of CNBr-digested fibrinogen, which mimics the effect of fibrin on the activation of plasminogen by t-PA, did not influence the rate constant. Moreover, PA-inhibitor-rich plasma inhibited in a very similar way in vitro thrombolysis by one-chain or two-chain t-PA incorporated into the clot. Injection of one-chain or two-chain t-PA into rabbits with increased levels of PA-inhibitor, induced by endotoxin, resulted in very rapid inhibition of t-PA activity. Within 30 seconds after injection, no residual free t-PA could be demonstrated. Gel filtration analysis showed that the disappearance of t-PA activity was associated with the generation of t-PA-PA-inhibitor complex with an apparent Mr of 100,000. This enzyme-inhibitor complex, like free t-PA, was cleared from the circulation with a half-life of approximately 2 minutes, mainly via the liver. It is concluded that PA-inhibitor neutralizes one-chain and two-chain molecular forms of t-PA in plasma at very similar rates, both in vitro and in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) 1985-12-31T23:00:00Z http://hdl.handle.net/10171/22922 Title: Trombosis arterial y polimorfismos genéticos: demasiados actores, escenario complejo Author(s) : Paramo, J.A. (José Antonio); Lecumberri, R. (Ramón); Orbe, J. (Josune) Abstract: La trombosis arterial es una enfermedad compleja y multifactorial, resultado de interacciones entre factores genéticos y ambientales. La tríada de Virchow, clásicamente empleada para definir la trombosis venosa, también se aplica a la trombosis arterial: alteraciones reológicas, disfunción endotelial y alteraciones hemostáticas que producen hipercoagulabilidad sanguínea. Algunos estudios llevados a cabo en la última década han identificado numerosos polimorfismos en genes involucrados en diversos componentes de esta tríada, entre los que destacan polimorfismos en factores de coagulación, fibrinólisis y receptors plaquetarios, en el metabolismo de la homocisteína, en la enzima óxido nítrico sintetasa, polimorfismos asociados con alteraciones reológicas y, finalmente, los relacionados con el estrés oxidativo.En conjunto, la contribución individual de estos polimorfismos a la trombosis arterial es modesta, mientras que interacciones gen-gen y gen-factores de riesgo parecen ser más relevantes en el desarrollo de la trombosis arterial. 2004-12-31T23:00:00Z http://hdl.handle.net/10171/22910 Title: Randomized study of aprotinin and DDAVP to reduce postoperative bleeding after cardiopulmonary bypass surgery Author(s) : Rocha, E. (Eduardo); Hidalgo, F. (Francisco); Llorens, R. (Rafael); Melero, J.M. (José María); Arroyo, J.L. (José L.); Paramo, J.A. (José Antonio) Abstract: BACKGROUND: Patients on cardiopulmonary bypass (CPB) have an increased susceptibility to postoperative bleeding. Previous reports using desmopressin acetate (DDAVP) for the prevention of postoperative bleeding have given contradictory results, whereas the protease inhibitor aprotinin has been shown to reduce blood loss after this type of surgery. This randomized study was performed to assess the efficacy of DDAVP versus aprotinin in the prevention of bleeding after CPB. METHODS AND RESULTS: One hundred nine of 122 eligible patients were randomized to four different groups: Group A (n = 28) received aprotinin starting with a bolus of 2 x 10(6) KIU followed by a continuous infusion of 0.5 x 10(6) KIU/h until the end of surgery; group B (n = 25) received of DDAVP 0.3 micrograms/kg i.v. on completion of CPB; group C (n = 28) received two doses of DDAVP, the first as in group B and an additional dose 6 hours after surgery; group D (n = 28) received no treatment. There was a marked reduction of postoperative blood loss either at 12 hours (P < .01) or 72 hours (P < .02) in the aprotinin group compared with all other groups, whereas no significant effect was observed in either of the two DDAVP regimens. A significant reduction in the amount of blood used was observed only in the aprotinin group (P < .01). Of the plasma fibrinolytic components assayed, there was a significant reduction of the fibrin degradation product generation in the aprotinin group (P < .001), whereas a significant systemic hyperfibrinolysis was observed in both DDAVP-treated groups and the control group. No side effects related to the study drugs were observed in any patient. CONCLUSIONS: Aprotinin inhibited fibrinolysis; this correlated with a significant reduction of postoperative blood loss and need for blood replacement after CPB. Neither one nor two doses of DDAVP had a beneficial effect. Aprotinin offers a better alternative than DDAVP in the prevention of bleeding after CPB. 1993-12-31T23:00:00Z http://hdl.handle.net/10171/22892 Title: Activador tisular del plasminógeno. Mecanismo de acción y propiedades trombolíticas Author(s) : Paramo, J.A. (José Antonio); Collen, D. (D.) 1983-12-31T23:00:00Z http://hdl.handle.net/10171/22882 Title: Enfermedad tromboembólica y modificaciones de la coagulación tras artroplastia total de cadera. Acción de la profilaxis con ácido acetilsalicílico o heparina-dihidroergotamina Author(s) : Alfaro, M.J. (M.J.); Paramo, J.A. (José Antonio); Pablos, J. (Julio) de; Cañadell, J.M. (J. M.); Rocha, E. (Eduardo) 1985-12-31T23:00:00Z http://hdl.handle.net/10171/22876 Title: Alteraciones de la fibrinoformación en la cirrosis hepática Author(s) : Fernandez, J. (Javier); Narvaiza, M.J. (M.J.); Cuesta, B. (Braulia); Paramo, J.A. (José Antonio); Lopez-Fernandez, A. (A.); Febres, R. (R.); Rocha, E. (Eduardo) 1981-12-31T23:00:00Z http://hdl.handle.net/10171/22872 Title: Development and clinical application of a new ELISA assay to determine plasmin-alpha2-antiplasmin complexes in plasma Author(s) : Montes, R. (Ramón); Paramo, J.A. (José Antonio); Angles-Cano, E. (Eduardo); Rocha, E. (Eduardo) Abstract: Plasmin-alpha2-antiplasmin complexes (PAP) are considered good markers of fibrinolytic activation in vivo. The presence of neoantigens in these complexes offers the possibility to develop specific immunoassays to determine PAP levels. We have developed a sensitive PAP purification method in vitro by adding urokinase to fresh plasma followed by affinity chromatography to lysine-sepharose and elution with epsilon-aminocaproic acid. This material, characterized by SDS-PAGE and Western blotting, was used to raise monoclonal antibodies (MoAbs). We describe a new enzyme linked immunosorbent assay (ELISA) to quantify PAP complexes in plasma. The assay follows the sandwich principle and is based on two MoAbs, CPL12 and CPL15, that bind to the modified alpha2-antiplasmin moiety and the plasmin moiety of the complex respectively. The calibration curve was constructed with definite concentrations of purified PAP. The lower limit of the assay is 75 ng/ml and the variation coefficients are 3.5% (intra-assay) and 10-6% (interassay). A mean value of 573.5+/-131.4 ng/ml was obtained from PAP concentration in a healthy population (n = 30). Significantly higher PAP levels were observed under diverse clinical conditions in which fibrinolysis is activated: clinical sepsis, acute myocardial infarction (AMI), malignancy, diabetes, pregnancy, elderly people and thrombolytic therapy. From our results we conclude that this ELISA is suitable to measure in vivo plasma PAP levels. 1995-12-31T23:00:00Z