HLA CW3 and HLA CW4 have a protective effect on acquisition of chronic myeloid leukemia on Mexican patients.

INTRODUCTION: Chronic myeloid leukemia (CML) is characterized by a chromosomal translocation t(9; 22) resulting in the chimeric ber-abl oncogene that encode for the p210 protein which has an increased tyrosine kinase activity. The fusion part of this protein contains a novel aminoacid sequence. If peptides derived from this leukemia-specific part of p210 are expressed in the context of HLA molecules on malignant cells this may elicit immunologically specific responses. Recent studies using synthetic peptides identical to the bcr-abl fusion region revealed that breakpoint specific peptides are capable of binding to the class I molecules HLA-A3, -A11 and -B8. It has been shown that individuals expressing HLA-A3 or HLA-B8 have a diminished risk for development of CML in Caucasoid populations. Other authors have reported a statistically significant increase in the frequency of Cw3 and Cw4 antigens in Causcasoids and European CML patients. These data suggested that Cw3 and Cw4 may be markers for CML susceptibility on these populations. OBJECTIVE: To asses a possible susceptibility effect of these HLA molecules we studied 63 CML Mexican Mestizo patients and 746 healthy subjects for the distribution of HLA class I and class II molecules. RESULTS: The gene products that showed statistically significant differences between CML patients and controls were DR14, DR3, Cw3 and Cw4. DR14 and DR3 were significantly increased in the patients group with respect to the controls group (DR14 antigen frequency: 3.17% vs. 0.29%; p = 0.03; DR3 20.63% vs. 8.33%; p = 0.0001). Cw3 and Cw4 were significantly decreased in the patient group (Cw3 26.9% vs. 49.11%; p = 0.03; Cw4 antigen frequency 23.8% vs. 86.28%; p = 0.0000001). The relative risk for DR14 was 10.48 (95% CI 1.52-79.29) and for DR3 was 3.96 (95% CI 2.05-7.71). The relative risk for Cw3 was 0.38 (95% CI 0.08-1.79) and for Cw4 was 0.11 (95% CI 0.048-0.81). CONCLUSION: These results suggest that the development of CML is apparently associated with HLA phenotypes specific to each population, and indicate that Cw3 and Cw4 expression may result in a protective effect on the CML acquisition on Mexican Mestizo population probably by bcr-abl breakpoint peptides presentation through these HLA molecules.

Changes on hemostatic parameters induced by 17beta-estradiol, ethinylestradiol, and the 17beta-aminoestrogen pentolame in the male Wistar rat.

Oral contraceptives containing estrogens increases the incidence of thromboembolic events. In contrast, administration of 17beta-aminoestrogens prolonged blood clotting time (BCT) in rodents. We studied the effect of estradiol (E(2)), ethinylestradiol (EE) and pentolame on some screening hemostatic tests. BCT was evaluated 24, 48, 72 and 96 h post-treatment. Rats received subcutaneously (s.c.) for five consecutive days E(2) (0.1-1000 microg), EE (1-1000 microg), pentolame (0.1-1000 microg), or vehicle (propyleneglycol 0.3 ml). At 48 h post-treatment E(2) (1000 microg) diminished BCT (32%, P<0.01), in contrast pentolame (1000 microg) augmented BCT by 41% (P<0.01). After 72 h, E(2) showed procoagulant effects with 10, 100 and 1000 microg doses (-45, -30, and -21%, respectively). Significant effects on BCT of EE were observed 72 h after with 1000 microg (-12%, P<0.05). Animals were treated s.c. for two consecutive days with E(2) (3mg/100g), pentolame (4 mg), or vehicle (0.1 ml). BCT, bleeding time (BT), platelet aggregation (PA), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen concentration were determined. E(2) produced a significant diminution on BCT (-20%) after 72 h whereas pentolame increased BCT from 24 to 96 h (62%, maximal response at 48 h). APTT and PT coagulation times of the groups treated with E(2) and pentolame were lengthened (33 and 29%; 16 and 24%, respectively; P<0.05). Fibrinogen concentration increased (115%, P<0.01) only in the pentolame-treated group. Pentolame and E(2) produced any effects on BT and PA compared with control groups, indicating that platelet function was not modified. Our results indicate that E(2), EE and pentolame affects the plasmatic phase of the hemostatic mechanism.

Increased incidence of anxiety and depression during bone marrow transplantation.

BACKGROUND: Since the first organ transplantation in the 1950s, there have been reports that patients who underwent organ transplantation had a poor prognosis if they were depressed and/or anxious prior to transplantation. Our objective in this study was to determine the prevalence of anxiety and depression in the different stages of bone marrow transplantation (BMT). METHODS: Mood disorders (MD), anxiety disorders (AD), and adjustment disorders (ADD) were measured five times with DSM IV. The Beck Inventory of Depression (BID) and Hamilton Rating Scale of Anxiety (HRSA) were used to measure levels of depression and anxiety, respectively, at registration and at days -1, +21 +/- 7, +30 +/- 10, and 90 +/- 10 days from BMT. Analysis between diverse periods was made for allogeneic BMT (allo-BMT) with chi square test, while Fisher exact test was used for the autologous BMT (auto-BMT). RESULTS: We report on 26 patients, including 18 with allo-BMT, and eight with auto-BMT. The allo-BMT was associated with depression during post BMT period (chi(2) = 11.924; p = 0.01). Slight anxiety without statistical significance was found in all stages. There was a high prevalence of anxiety and adjustment disorder in the immediate posttransplantation stage. Anxiety and adjustment disorders were more frequently found in all posttransplantation stages, particularly in the immediate stage (chi(2) =11.104, p = 0.02). After 3 months, no survivor received a psychiatric diagnosis. We did not find any differences in MD. There were five deaths. CONCLUSIONS: The auto-BMT group did not show significant associations between different stages and psychiatric variables studied. One death occurred at 1 month. This patient had severe depression. We recommend that the depressive syndrome be intentionally researched during the different stages of BMT, specifically in the immediate transplantation stage.

Cytogenetic findings in 303 mexican patients with de novo acute myeloblastic leukemia

In this report we show the chromosomal changes seen in a group of 303 Mexican patients with de novo Acute myeloblastic Leukemia (AML). Two hundred forty-two patients were diagnosed and treated at two hospitals affiliated with the Instituto Mexicano del Seguro Social (IMSS). These are the Centro Medico Nacional Siglo XXI and Centro Medico La Raza Hospitals; the remaining 61 patients were diagnosed and treated at the Hospital General de Mexico (HGM). Clonal abnormalities were detected in 75.6 percent of the patients; this result agrees with what has been reported in other large series of AML studies. The incidence of changes per hospital was similar in patients from the IMSS hospitals (72-75 percent), while an increase was seen in patients from the HGM (85.2 percent). The cromosomal changes seen in this study in order of frequency were: t(15;17)[18.8 percent], t(9;22)[9.2 percent], miscellaneous chromosomal changes (mainly rearrangementa of chromosomes 1,2,3,12 y 17) [8.2 percent], abnormalities of 16q22 [7.3 percent], t(8;21)[6.3 percent], -7/del(7q)[5.6 percent], t(6;9)[5.3 percent), and abnormalities of 11q23 [4.6 percent]. We reported an increase in the indicidence of certain types of chromosomal changes seen in cases of AML, in comparison with reports from other countries. These differences must not be disregarded. We support this finding when comparing distribution of changes in the population of patients seen in the IMSS hospitals with those from the HGM; the main difference lies in the socioeconomic level

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

Objetivo. Evaluar si el interferón-alfa humano recombinante (IFN), combinado con quimioterapia, suprime la clona portadora del cromosoma Filadelfia en pacientes con leucemia mieloide crónica (LMC). Material y métodos. Se estudiaron 53 pacientes con LMC en fase crónica de novo. Los pacientes recibieron uno de tres esquemas de tratamiento: a) inducción a la remisión con daunorrubicina, vincristina, arabinósido de citosina y prednisona (DOAP) y mantenimiento con IFN (n = 12); b) inducción con busulfán (BUS) o hidroxiurea (HIDX) siguiendo el mantenimiento con IFN (n = 26); c) inducción con DOAP y mantenimiento con BUS (n = 15). Resultados. La remisión hematológica se observó dos a seis meses después del inicio de tratamiento: 10 tuvieron remisión completa, seis parcial, 14 menor y 23 nula. Los 16 con respuesta completa o parcial recibieron IFN. Ninguno de los 15 casos mantenidos con BUS tuvo respuesta parcial o completa. La proporción de casos con respuesta citogenética completa (3/12) fue ligeramante menor en los tratados con quimioterapia intensiva (DOAP/IFN) que en aquéllos (7/26) de quimioterapia convencional (BUS/HIDX/IFN). Conclusiones. Nuestros resultados muestran que: a) el IFN en combinación con quimioterapia contribuyó a lograr respuesta citogenética parcial o completa en 30 por ciento de los casos; y b) la quimioterapia (DOAP) combinada con IFN no fue superior, en términos de respuesta citogenética, al tratamiento combinado de monodrogas (Bus/Hidx) con IFN

Plasmaferesis o infusión de plasma fresco en el tratamiento de la púrpura trombocitopénica: informe preliminar / Fresh frozen plasma or plasmapheresis in the treatment of thrombotic trombocytopenic purpura: preliminary communication

Cinco pacientes con púrpura trombótica trombocitopénica (PTT) fueron seleccionados al azar para ser tratados con infusión de plasma fresco (dos pacientes) o plasmaféresis (tres pacientes). En todos los casos se observó una remisión completa 2 a 4 días después de que se inició el tratamiento. Estos resultados preliminares muestran que tanto la infusión de plasma fresco como la plasmaféresis son procedimientos terapéuticos adecuados en la PTT, por lo que consideramos que la infusión de plasma fresco se podría considerar como la primera opción terapéutica, ya que es de menos costo por no requerir de equipos especiales

Síndrome mielodisplasicos: un análisis retrospectivo de 72 casos; I. Semología clínica y evolución / Myelodysplastic syndrome: a retrospective analysis of 72 cases; I. Clinical semiology and course

Se analizan la semiología clínica y la evolución de 72 casos con síndrome mielodisplásico primario (SMP). El diagnóstico fue de anemia refractaria (AR) en 20, anemia sideroblástica (AS) en 7; anemia refractaria con exceso de blastos (ARCEB) en 26; anemia refractaria con exceso de blastos en transformación (ARCEB-t) en 14 y los cinco pacientes restantes tuvieron leucemia mielomonocítica crónica (LMMC). Ma mediana de edad fue de 64 años, con un discreto predominio del sexo masculino. La anemia fue el dato clínico más frecuente (94%), pero la infección y la hemorragias fueron las complicaciones evolutivas más frecuentes, así como la causa de muerte de estos pacientes. Doce de los mismos (18%) tuvieron una transformación a leucemia aguda. La mediana de la sobrevida fue mejor en pacientes con AR (34 meses) y AS (32 meses) que en pacientes con ARCEB (11 meses), ARCEB-t (8 meses) y LMMC (13 meses) p < 0.01. El diagnóstico se pudo sospechar en la citología hemática en el 83% de los casos y se confirmó en el aspirado de la médula ósea. Los intentos terapéuticos han sido infructuosos y el 80% de los pacientes requirieron de transfusiones de glóbulos rojos en forma periódica

Púrpura trombocitopénica inmunológica y embarazo (experiencia de 10 casos / Immunologic thromboccytopenic purpura and pregnancy (the experience with 10 cases)

Se estudiaron diez pacientes con púrpura trombocitopénica inmunológica (P.T.I.) y embarazo, atendidas en el Hospital de Ginecología y Obstetricía No.3 del Centro Médico "La Raza" durante un periodo de dos años; se analizaron los procedimientos diagnósticos e igualmente, la valoración de las condiciones fetales, la vía de resolución del embarazo y el estado de los productos al nacimiento. Finalmente se compararon los resultados obtenidos con lo informado en la literatura revisada

Ferritin and malignant hemopathies.I.Ferritin in cerebrospinal fluid as an indicator of central nervous system leukemic involment.

La infiltracion del sistema nervioso central (SNC) por celulas leucemicas es una complicacion que se presenta cada vez con mayor frecuencia. El diagnostico de infiltracion leucemica se confirma por la observacion de celulas malignas en el liquido cefalorraquideo (LCR). No obstante, la evaluacion morfologica de las celulas resulta dificil, ya que estas pierden frecuentemente su morfologia debido a las caracteristicas fisicas del LCR y porque en ocasiones la celulas leucemicas se encuentran confinadas unicamente al parenquima cerebral. Para demonstrar la infiltracion leucemica del SNC se midieron los niveles de ferritina en el LCR mediante una tecnica inmunorradiometrica. Los pacientes con infiltracion del SNC tuvieron niveles mas altos de ferritina en el LCR (11.2 +/- 1.4 ug/l) que los enfermos con leucemia aguda que no presentaban esta complicacion (p = 0.001). Los niveles de ferritina en LCR en el grupo control y en los enfermos con leucemia aguda sin infiltracion leucemica fueron casi identicos 4.4 +/- 0.6 y 4.5 +/- 0.7 ug/l respectivamente.Estos hallazgos sugieren que la dosificacion de ferritina en el LCR puede ser de utilidad en el diagnostico de esta grave complicacion

Granulopoyesis normal y patologica.Una revision. / Normal and pathologic granulopoiesis. A review

En este trabajo se revisan brevemente los conceptos recientes y mas relevantes, relacionados con el origen, maduracion y diferenciacion de los granulocitos, asi como los mecanismos que regulan la granulopoyesis en condiciones normales y patologicas.De las ultimas, se revisan la leucemia aplastica, las neutropenias y las leucocitosis