El sistema monocito-macrófago en la enfermedad de Hodgkin. / [The monocyte-macrophage system in Hodgkins disease]

Hodgkins disease (HD) is considered as a tumor of the lymph nodes histologically characterized by a variety of cell types, resembling a nonspecific inflammatory reaction. The Reed-Sternberg cells present in the granuloma are considered neoplastic due to cytogenetic alterations, tissue culture properties and heterotransplantability. They originate from a macrophage-derived interdigitating reticulum cell. The lymph node is an immunologic organ and its alterations reveal qualitative and/or quantitative defects of the immune system. These are observed in HD at very early stages even with a minimum of lymph node involvement. Considering HD as a neoplasm of the monocyte-macrophage system, our objective was to investigate the functional capability of peripheral blood monocytes transformed into macrophages in vitro. The phagocytic and lytic activities were evaluated by the generation of toxic oxygen metabolites as due to an excessive production of PGE-2. This defect could be corrected by cyclo-oxygenase inhibitors. The defect was present at very early stages of HD and persisted even during prolonged continuous complete remissions. We also found a defect in the ingestion of candida which could not be modified by drug treatment, indicating the existence of a global dysfunction of the phagocyte. Presently, more than 90

of HD patients respond to specific therapy and remain in prolonged remission, being considered [quot ]cured[quot ]. This fact may contribute to the diminished number of reports in relation to the biology of the monocyte-macrophage system in this disease.

El sistema monocito-macrófago en la enfermedad de Hodgkin / The monocyte-macrophage system in Hodgkins disease

La enfermedad de Hodgkin (EH) se caracteriza por la aparición de un tumor en los ganglios linfáticos constituido por una gran variedad de células que se asemejan a una reacción inflamatoria inespecífica. Las células de Reed-Sternberg (R-S) presentes en la granuloma tienen características citogenéticas, de cultivo y de heterotransplantabilidad que parecen neoplásicas. Su origen más probable es en las células interdigitantes ganglionares derivadas de los macrófagos. Al ser el ganglio linfático un órgõo inmunológico, sus alteraciones se manifestan en defectos de la respuesta inmune, los cuales pueden deberse tanto a la expresión de la calidad de las mismas. En la EH la alteración de la respuesta inmune se observa en estadíos precoces, aún con una mínima extensión de compromiso ganglionar, lo que sugiere más una lesión cualitativa que cuantitativa. Teniendo en cuenta que el origen más probable de esta extraña neoplasia es la célula de R-S y que ésta deriva de los macrófagos, investigamos la capacidad funcional de los monocitos sanguíneos transformados in vitro en macrófagos. Se estudió su capacidad fagocítica y lítica a través de la generación de productos tóxicos del oxígeneo, medidos por quimioluminiscencia y citomorfologia. Se encontró un defecto en la generación de productos tóxicos del oxígeno, que se debía a un exceso en la producción de PGE2 y era corregido por inhibidores de la síntesis de prostaglandinas (ciclooxigenasas); este defecto aparece precozmente en la EH y continúa... (AU)

Interacciones de la ciclosporina en transplantados renales. / [Cyclosporin interactions in kidney transplants]

Treatment with Cyclosporine has resulted in improved allograft survival. Cyclosporine metabolism occurs in the liver via hepatic cytochrome P-450IIIA microsomal enzyme. Pharmacokinetic drug interactions usually involve drugs which induce or inhibit the cytochrome P-450 system. We reviewed the Medical Charts of 53 renal transplant recipients immunosuppressed with Cyclosporine between 1985 and 1991. We analysed the relationship between Cyclosporine concentration, its dose and the change induced by concomitant administration of different drugs. Until December 1988, Cyclosporine was measured by solid-phase radioimmunoassay (RIA) using a polyclonal antibody. This method measures Cyclosporine and some of its metabolites. Since January 1989, Cyclosporine was measured in whole blood by radioimmunoassay (RIA-Kit Sandimmun, Sandoz), which used a specific monoclonal antibody which binds Cyclosporine and a non-specific monoclonal antibody which binds Cyclosporine and its metabolites. The therapeutic range recommended by Sandoz in whole blood using the specific monoclonal antibody is 100 to 400 ng/ml. We present 3 cases of probable pharmacokinetic drug interactions with Cyclosporine. The first patient received concomitantly isoniazide (150 mg/day). Cyclosporine levels were between 600 and 2085 ng/ml despite the dose reduction from 10 to 1.5 mg/kg/day (Fig. 1). The dose reduction of isoniazide to 100 mg/day resulted in reduction of Cyclosporine levels. Until December 1988 with the polyclonal antibody the median was 320 ng/ml (range: 185 to 760 ng/ml; n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)

Interacciones de la ciclosporina en transplantados renales. / [Cyclosporin interactions in kidney transplants]

Treatment with Cyclosporine has resulted in improved allograft survival. Cyclosporine metabolism occurs in the liver via hepatic cytochrome P-450IIIA microsomal enzyme. Pharmacokinetic drug interactions usually involve drugs which induce or inhibit the cytochrome P-450 system. We reviewed the Medical Charts of 53 renal transplant recipients immunosuppressed with Cyclosporine between 1985 and 1991. We analysed the relationship between Cyclosporine concentration, its dose and the change induced by concomitant administration of different drugs. Until December 1988, Cyclosporine was measured by solid-phase radioimmunoassay (RIA) using a polyclonal antibody. This method measures Cyclosporine and some of its metabolites. Since January 1989, Cyclosporine was measured in whole blood by radioimmunoassay (RIA-Kit Sandimmun, Sandoz), which used a specific monoclonal antibody which binds Cyclosporine and a non-specific monoclonal antibody which binds Cyclosporine and its metabolites. The therapeutic range recommended by Sandoz in whole blood using the specific monoclonal antibody is 100 to 400 ng/ml. We present 3 cases of probable pharmacokinetic drug interactions with Cyclosporine. The first patient received concomitantly isoniazide (150 mg/day). Cyclosporine levels were between 600 and 2085 ng/ml despite the dose reduction from 10 to 1.5 mg/kg/day (Fig. 1). The dose reduction of isoniazide to 100 mg/day resulted in reduction of Cyclosporine levels. Until December 1988 with the polyclonal antibody the median was 320 ng/ml (range: 185 to 760 ng/ml; n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)

Estudios inmunológicos en talasemia mayor. / [Immunologic studies in thalassemia major]

It is accepted that the immune alterations in patients with thalassemia major (TM) are secondary to the continuous transfusion-related antigenic stimulation together with iron overload. We evaluated the immune status of TM patients and found quantitative alterations in the distribution of peripheral blood lymphocyte subpopulations as well as functional alterations in natural killer (NK) cytotoxicity, B-cell differentiation, T-cell immunoregulation and phagocyte functional activities. TM patients, 10 years old or younger, have a lymphocyte profile and phagocytic activity similar to normal controls. Non-splenectomized thalassemic patients, older than 10, present lymphocytosis due to an increase in B lymphocytes and with splenectomy the T-CD8+ lymphocytes increase. With respect to phagocytes, the capacity to ingest candida is preserved while the candidacidal activity and the generation of toxic oxygen metabolites during the respiratory burst are diminished, and are inversely proportional with age and serum ferritin concentration, that is, older in age and higher in iron overload, more profound are the phagocyte dysfunctions. The altered B-cell function, the dysfunction of T immunoregulatory cells and the defective NK activity observed in TM patients were independent of the age of the patients and they were observed even in children younger than 10 years old and in general are attributed to blood transfusions. Moreover, there are some alterations that thalassemic carriers can express such as a defect at the level of NK and at B-cell function regulations, suggesting a possible genetic origin. Although complex, TM constitutes a human model that allows the dissection of specific immune defects, involving multiple factors, and can provide a better comprehension of how this complex immunoregulatory system works.

Estudios inmunológicos en talasemia mayor / Immunologic studies in thalassemia major

Los pacientes con talasemia mayor (TM) presentan defectos inmunes secundarios la estimulación antigénica y sobrecarga de hierro que resultan de su contínuo tratamiento con alteraciones cuantitativas en las subpoblaciones linfocitarias sanguíneas, como defectos funcionales en la citotoxicidad natural (NE), en la diferenciación B, en la inmunorregulación por células T, y en la actividad efectora de los fagocitos. Los pacientes con TM de hasta 10 años de edad tienen una distribución linfocitaria similar a la de controles normales y lo mismo ocurre con la función de sus fagocitos. Los pacientes de más de 10 años presentan una linfocitosis, con aumento de linfocitos B y en los pacientes esplenectomizados, también de los linfocitos T-CD8 positivos. El defecto en los fagocitos consiste en una disminución en la generación de metabolitos tóxicos del O2 durante el estallido respiratorio, con menor capacidad candidicida, pero con capacidad fagocitica normal. Este defecto es proporcional a la edad y a la concentración de ferritina sérica o sea que a mayor edad y/o sobrecarga de hierro, mayor defecto en los fagocitos. Las disfunciones B, T y NK eran independientes de la edad de los pacientes, observándose incluso en pacientes de menos de años, aunque se las atribuye a las transfusiones de sangre. Algunos defectos se pueden encontrar incluso en los portadores de TM, específicamente en la función B y NK, lo que sugiere un componente genético. La TM constituye un modelo humano que se pese a su... (AU)

Impaired monocyte function in patients succesfully treated for Wipples disease

Peripheral blood mononuclear cells (monocytes) from patients with Whipples disease in long-term remission were tested for their ability to handle intracellular microorganisms. Phagocytosis and lysis of Candida tropicalis by monocytes of patients (n=12) andcontrols (n=8) were quantified after 30 min of incubation. Phagocytosis was similar in both groups but intracellular Killing of Candida tropicalis was significativily lower in patients (p<0.001). We concluded that our study showed an in vitro defect in the intracellular Killing function of monocytes in subjects in remission many years after diagnosis of Whipples disease. The defective function did not seem to be related to relapse or to the susceptibility to other infections. (AU)