In vivo effects of an inhibitor of nuclear factor-kappa B on thrombogenic properties of antiphospholipid antibodies.

It has been shown that endothelial cell (EC) activation and tissue factor (TF) upregulation in EC and monocytes by antiphospholipid antibodies (aPL Abs) leads to a prothrombotic state and involves translocation of nuclear factor-kappa B (NF-kappaB). Here we examined the effects of an NF-kappaB inhibitor on aPL-induced thrombosis, TF activity, and EC in vivo. We treated CD1 mice with IgG from a patient with antiphospholipid syndrome (IgG-APS) or with control IgG (IgG-NHS). The adhesion of leukocytes (number of white blood cells) to EC in cremaster muscle (as an indication of EC activation) as well as the size of an induced thrombus in the femoral vein of the mice were examined. Some mice in each group were infused with 10 microM MG132 (an inhibitor of NF-kappaB). TF activity was determined using a chromogenic assay in homogenates of carotid arteries and in peritoneal cells of mice. In vivo, IgG-APS increased significantly the number of white blood cells adhering to ECs (4.7 +/- 2.2) when compared to control mice (1.5 +/- 0.8), and these effects were significantly reduced when mice were pretreated with MG132 (0.8 +/- 0.2). IgG-APS increased significantly the thrombus size and MG132 inhibited that effect (93%). Treatment of the mice with IgG-APS also induced significantly increased TF function in peritoneal cells and in homogenates of carotid arteries. Pretreatment of the mice with MG132 abrogated those effects significantly. Mice injected with IgG-APS or with IgM-APS with or without the inhibitor had medium-high titers of anticardiolipin antibodies in serum at the time of the surgical procedures. The data show that prothrombotic and proinflammatory properties of IgG-APS and IgM-APS are downregulated in vivo by an NF-kappaB inhibitor. These findings may be important in designing new modalities of targeted therapies to treat thrombosis in patients with APS.

[Interferon in the eradication of the Philadelphia chromosome in chronic myeloid leukemia]. / El interferón en la erradicación del cromosoma Filadelfia de la leucemia mieloide crónica.

OBJECTIVE: To evaluate if human recombinant interferon alpha (IFN) combined with chemotherapy is able to suppress the Philadelphia chromosome clone in patients with chronic myeloid leukemia (CML). MATERIAL AND METHODS: The cytogenetic evolution in 53 patients with CML in chronic phase de novo was studied. They received one of three treatment schemes: a) induction of remission with daunorubicin, vincristine, cytosine arabinose and prednisone (DOAP) and maintenance with IFN (n = 12); b) induction with busulfan (BUS) or hydroxyurea (HYDX) and maintenance with IFN (n = 26); c) induction with DOAP and maintenance with BUS (n = 15). RESULTS: The remission was seen two to six months after the start of treatment: 10 had complete remission, six a partial one, 14 a minor remission and 23 none. The 16 with complete or partial response received treatment with IFN. None of the 15 cases maintained with BUS had complete or partial response. The proportion of cases with complete response (3/12) was slightly lower in patients treated with intensive chemotherapy (BUS/HIDX/IFN) than in those receiving conventional treatment (7/26). CONCLUSIONS: Our results showed that: a) IFN in combination with chemotherapy induced partial or complete response in 30% of our cases; and b) intensive chemotherapy combined with IFN was not superior in terms of a cytogenetic response to treatment with monodrugs (BUS/HIDX) and IFN.

[Evaluation of undesirable effects of low-molecular-weight heparin during prevention of thromboembolic disease in abdominal surgery patients]. / Valoración de los efectos indeseables de una heparina de bajo peso molecular, durante la profilaxia de enfermedad tromboembólica en pacientes de cirugía abdominal.

The objective of the present study was to determine the type, frequency and severity of the side effects of a low-molecular-weight heparin (LMWH) during the prophylaxis of thromboembolic disease (TED) after abdominal surgery. The study was prospective, comparative, longitudinal, and open. The setting was at the surgical and hematology services of a teaching hospital. There were 57 patients (27 males, 30 females) with risk factors for TED, including gastrointestinal malignancies. Seventeen patients (Group A) received LMWH, 20 mg/day; 20 (Group B) standard heparin (SH), 5,000 U/12 h, and 20 (Group C) formed the control group. LMWH or SH were administered 2 h before surgery and then, when patients assumed complete ambulatory status, at the end of their hospital stay or for a maximum of ten days. There were no significant differences among the groups in relation with age, anthropometric variables, type and duration of surgery, nor in the extent of the surgical bleeding, days to full ambulatory status nor length of postoperative hospital stay. A similar number of erythrocyte transfusions were used on the three groups. Eighty-three percent of the patients were 50 years of age or older. None developed TED. Postoperatively in group "A" a significant increase in platelets (p = 0.01) was found, as was the shortening of the activated partial thromboplastin time (P = 0.007); other adverse effects did not occur during the administration of LMWH. These findings allowed us to conclude that LMWH constitutes a safe, reliable and comfortable alternative for prophylaxis of TED in this type of surgical patients.

[Results of the treatment of chronic idiopathic thrombocytopenic purpura with ascorbic acid]. / Resultado del tratamiento de la púrpura trombocitopénica idiopática crónica con ácido ascórbico.

The main objective of the present work is to describe the results of the treatment with ascorbic acid in thirteen patients with refractory chronic idiopathic thrombocytopenic purpura (CITP) and to compare its results with those informed in the literature. The patients received ascorbic acid 2 g/day, orally, in the morning during at least eight weeks. At the end of the period of control there were only four partial responses (30%); the remaining patients did not experience any kind of favorable reaction. Previous publications informed mean partial and complete responses of 11 and 19% respectively. According to such results and those of the present work, and taking into account the generally transitory duration of the response it is concluded that ascorbic acid is of no use in the treatment of CITP.

[The therapeutic advances in adult acute nonlymphoblastic leukemia. The experience at the Hospital de Especialidades of the Centro Médico Nacional Siglo XXI]. / Avances terapéuticos en la leucemia aguda no linfoblástica del adulto. Experiencia en el Hospital de Especialidades del Centro Médico Nacional Siglo XXI.

Acute adult nonlymphoblastic leukemia (ANLL) involves a large group of diseases which originate in an abnormal process of differentiation of the hematopoietic stem cell. This paper analyses the historical background of such a group of malignant hemopathies, current criteria to perform the diagnosis and also the most important therapies used in both the stage of remission induction and the period following this stage (post-remission status). In this context, the therapeutic achievements that have had place during the last two decades at the Hospital de Especialidades del Centro Medico Nacional Siglo XXI are analyzed.

[Treatment of intracranial hemorrhage in chronic idiopathic thrombocytopenic purpura]. / Tratamiento de la hemorragia intracraneana en la púrpura trombocitopénica idiopática crónica.

Conventional treatment of two patients with chronic idiopathic thrombocytopenic purpura (CITP) and petechial intracranial hemorrhage was ineffectual. However, after a treatment with vincristine, the neurological manifestations disappeared and platelet counts improved; clinical recovery was complete. This success contrast with results informed in similar patients treated with corticosteroids or splenectomy, among whom the mortality is as high as 100%. The favorable reaction may be related to the various mechanisms of the action of vincristine, which usually lead to control of CITP. The use of this drug is proposed in association of conventional therapy of this severe complication, especially in patients in whom splenectomy is contraindicated.