Hematological alterations in protein malnutrition.

Protein malnutrition is one of the most serious nutritional problems worldwide, affecting 794 million people and costing up to $3.5 trillion annually in the global economy. Protein malnutrition primarily affects children, the elderly, and hospitalized patients. Different degrees of protein deficiency lead to a broad spectrum of signs and symptoms of protein malnutrition, especially in organs in which the hematopoietic system is characterized by a high rate of protein turnover and, consequently, a high rate of protein renewal and cellular proliferation. Here, the current scientific information about protein malnutrition and its effects on the hematopoietic process is reviewed. The production of hematopoietic cells is described, with special attention given to the hematopoietic microenvironment and the development of stem cells. Advances in the study of hematopoiesis in protein malnutrition are also summarized. Studies of protein malnutrition in vitro, in animal models, and in humans demonstrate several alterations that impair hematopoiesis, such as structural changes in the extracellular matrix, the hematopoietic stem cell niche, the spleen, the thymus, and bone marrow stromal cells; changes in mesenchymal and hematopoietic stem cells; increased autophagy; G0/G1 cell-cycle arrest of progenitor hematopoietic cells; and functional alterations in leukocytes. Structural and cellular changes of the hematopoietic microenvironment in protein malnutrition contribute to bone marrow atrophy and nonestablishment of hematopoietic stem cells, resulting in impaired homeostasis and an impaired immune response.

High Frequency of Bone Marrow Depression During Congenital Toxoplasmosis Therapy in a Cohort of Children Identified by Neonatal Screening in Minas Gerais, Brazil.

BACKGROUND: There are few studies reporting frequency and control of adverse events associated with congenital toxoplasmosis treatment. The objective of this study is to describe treatment adherence and adverse hematologic events in a cohort of children identified with congenital toxoplasmosis in Minas Gerais, Brazil. METHODS: Children were treated with sulfadiazine, pyrimethamine and folinic acid and were evaluated clinically and by laboratory tests at regular intervals. RESULTS: Of 146,307 live newborns who participated in the Neonatal Screening Program in Minas Gerais in 2006-2007, 190 had congenital toxoplasmosis. Among the 171 children whose treatment data were available, 73.1% completely adhered to antiparasitic therapy. Hematologic adverse events (macrocytic anemia and/or neutropenia and/or thrombocytopenia) were diagnosed in 44% of them. The most common adverse event was neutropenia (31%). In most cases, it was not severe and reversed after increase in folinic acid dosage (25.7%) or temporary treatment suspension (1.8%). No infections were observed in association with neutropenic events. Significant associations were detected between macrocytic anemia and lower weight Z score at first medical appointment (P = 0.03), and between severe neutropenia (<500/mm) and lower weight Z score toward the end of treatment (P = 0.04). CONCLUSIONS: The high frequency of hematologic adverse events found, especially in malnourished children, highlight the importance of careful monitoring of these children throughout treatment, as well as considering nutritional aspects and the need for higher doses of folinic acid. With adequate monitoring, antiparasitic treatment was feasible and relatively safe in the setting of this large screening program for congenital toxoplasmosis.

[Bone marrow microenvironment in chronic myeloid leukemia: implications for disease physiopathology and response to treatment]. / Microambiente medular en la leucemia mieloide crónica: su relación con la enfermedad y la respuesta al tratamiento.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm related to the presence of the BCR-ABL1 fusion gene, linked to t (9;22) (q34;q11). It is originated from an abnormal hematopoietic stem cell, which is characterized as its normal counterparts by long-term self-renewal and multi-lineage differentiation. Both leukemic and quiescent normal hematopoietic stem cells preferentially reside in the osteoblastic niche. Mesenchymal stromal cells (MSC) are located near them, playing a critical role in their regulation. Currently, with tyrosine kinase inhibitor (TKI) therapy, long term clinical responses are achieved in most CML cases. However, late treatment failures may be observed related to the persistence of leukemic stem cells. The interactions between the leukemic stem cell and the microenvironment may be responsible in part for these events. We review the interactions between the leukemic stem cell and BM stroma and its potential clinical and therapeutic implications.

Microambiente medular en la leucemia mieloide crónica: su relación con la enfermedad y la respuesta al tratamiento / Bone marrow microenvironment in chronic myeloid leukemia: Implications for disease physiopathology and response to treatment

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm related to the presence of the BCR-ABL1 fusion gene, linked to t (9;22) (q34;q11). It is originated from an abnormal hematopoietic stem cell, which is characterized as its normal counterparts by long-term self-renewal and multi-lineage differentiation. Both leukemic and quiescent normal hematopoietic stem cells preferentially reside in the osteoblastic niche. Mesenchymal stromal cells (MSC) are located near them, playing a critical role in their regulation. Currently, with tyrosine kinase inhibitor (TKI) therapy, long term clinical responses are achieved in most CML cases. However, late treatment failures may be observed related to the persistence of leukemic stem cells. The interactions between the leukemic stem cell and the microenvironment may be responsible in part for these events. We review the interactions between the leukemic stem cell and BM stroma and its potential clinical and therapeutic implications.

Intoxicação aguda por Pteridium arachnoideum e Pteridium caudatum em bovinos e distribuição das plantas em Mato Grosso / Acute poisoning by Pteridium arachnoideum and Pteridium caudatum in cattle and distribution of the plants in Mato Grosso

São descritos os aspectos epidemiológicos, clínicos e patológicos de um surto de intoxicação por Pteridium arachnoideum e Pteridium caudatum em bovinos no Estado de Mato Grosso. A distribuição dessas plantas no Estado, a intensidade de invasão de pastagens e alguns fatores associados à invasão das pastagens por Pteridium spp. são também descritos. Pteridium spp. foi observada em 83 propriedades de nove municípios de Mato Grosso e deste total, amostras de 22 propriedades foram coletadas para identificação taxonômica. Em 22 propriedades identifica-se P. arachnoideum e em duas dessas havia também P. caudatum. O desmatamento e a realização de queimadas parecem estar relacionados com a invasão de Pteridium spp. nas pastagens. Na propriedade em que ocorreu a doença, 306 bovinos foram introduzidos em uma pastagem formada por Brachiaria brizantha intensamente invadida por P. arachnoideum e P. caudatum e desses 22 bovinos adoeceram e morreram. Os principais sinais clínicos foram febre alta, apatia, fadiga, fraqueza e decúbito. Na necropsia havia graus variáveis de hemorragias em vários órgãos e cavidades e infartos ocasionais. Microscopicamente, a alteração mais importante consistiu em aplasia severa da medula óssea vermelha. Os achados epidemiológicos, clínicos e patológicos associados à identoificação taxonômica da planta fundamentam o diagnóstico de intoxicação aguda por P. arachnoideum e P. caudatum em bovinos. O crescente desmatamento e a frequente utilização de queimadas em Mato Grosso podem contribuir para que esta doença venha a ser uma importante fonte de prejuízos para a pecuária do Estado.

Epidemiological features, clinical signs and pathological findings of a spontaneous acute poisoning by Pteridium arachnoideum and Pteridium caudatum in cattle in the State of Mato Grosso, Brazil, are described. The plant distribution, magnitude and some aspects about the pasture invasion by P. arachnoideum and P. caudatum in the State are also described. Pteridium spp. were found in 83 farms from nine counties and 22 of them were submitted to taxonomic identification. P. arachnoideum was found in 22 farms and in two farms also P. caudatum. Deforestation and burning appear to be associated with pasture invasion by Pteridium spp. On the farm where the poisoning occurred 306 cattle were introduced into a pasture of Brachiaria brizantha intensely invaded by P. arachnoideum and P. caudatum. Twenty two cattle were poisoned by the plants and died. The main clinical signs were hemorrhages, high fever, apathy, fatigue, weakness and recumbency. Gross findings included variable degrees of hemorrhages in several organs and cavities with occasional infarcts. The most consistent histological finding was marked bone marrow aplasia. Epidemiological, clinical and pathological findings associated with the taxonomic identofication of the plant support the diagnosis of acute poisoning by P. arachnoideum and P. caudatum in cattle. The increasing rate of deforestation and frequent burning in Mato Grosso can contribute to this disease which becomes a major cause of economic losses to livestock production in the State.

Intoxicação aguda por Pteridium arachnoideum e Pteridium caudatum em bovinos e distribuição das plantas em Mato Grosso / Acute poisoning by Pteridium arachnoideum and Pteridium caudatum in cattle and distribution of the plants in Mato Grosso

São descritos os aspectos epidemiológicos, clínicos e patológicos de um surto de intoxicação por Pteridium arachnoideum e Pteridium caudatum em bovinos no Estado de Mato Grosso. A distribuição dessas plantas no Estado, a intensidade de invasão de pastagens e alguns fatores associados à invasão das pastagens por Pteridium spp. são também descritos. Pteridium spp. foi observada em 83 propriedades de nove municípios de Mato Grosso e deste total, amostras de 22 propriedades foram coletadas para identificação taxonômica. Em 22 propriedades identifica-se P. arachnoideum e em duas dessas havia também P. caudatum. O desmatamento e a realização de queimadas parecem estar relacionados com a invasão de Pteridium spp. nas pastagens. Na propriedade em que ocorreu a doença, 306 bovinos foram introduzidos em uma pastagem formada por Brachiaria brizantha intensamente invadida por P. arachnoideum e P. caudatum e desses 22 bovinos adoeceram e morreram. Os principais sinais clínicos foram febre alta, apatia, fadiga, fraqueza e decúbito. Na necropsia havia graus variáveis de hemorragias em vários órgãos e cavidades e infartos ocasionais. Microscopicamente, a alteração mais importante consistiu em aplasia severa da medula óssea vermelha. Os achados epidemiológicos, clínicos e patológicos associados à identoificação taxonômica da planta fundamentam o diagnóstico de intoxicação aguda por P. arachnoideum e P. caudatum em bovinos. O crescente desmatamento e a frequente utilização de queimadas em Mato Grosso podem contribuir para que esta doença venha a ser uma importante fonte de prejuízos para a pecuária do Estado.(AU)

Epidemiological features, clinical signs and pathological findings of a spontaneous acute poisoning by Pteridium arachnoideum and Pteridium caudatum in cattle in the State of Mato Grosso, Brazil, are described. The plant distribution, magnitude and some aspects about the pasture invasion by P. arachnoideum and P. caudatum in the State are also described. Pteridium spp. were found in 83 farms from nine counties and 22 of them were submitted to taxonomic identification. P. arachnoideum was found in 22 farms and in two farms also P. caudatum. Deforestation and burning appear to be associated with pasture invasion by Pteridium spp. On the farm where the poisoning occurred 306 cattle were introduced into a pasture of Brachiaria brizantha intensely invaded by P. arachnoideum and P. caudatum. Twenty two cattle were poisoned by the plants and died. The main clinical signs were hemorrhages, high fever, apathy, fatigue, weakness and recumbency. Gross findings included variable degrees of hemorrhages in several organs and cavities with occasional infarcts. The most consistent histological finding was marked bone marrow aplasia. Epidemiological, clinical and pathological findings associated with the taxonomic identofication of the plant support the diagnosis of acute poisoning by P. arachnoideum and P. caudatum in cattle. The increasing rate of deforestation and frequent burning in Mato Grosso can contribute to this disease which becomes a major cause of economic losses to livestock production in the State.(AU)

Evaluation of (anti)genotoxic activities of Phyllanthus niruri L. in rat bone marrow using the micronucleus test

Phyllanthus niruri L. (Euphorbiaceae), known as "quebra-pedra" (Portuguese for "stonebreaker"), is an herb used for kidney disorders. In light of its frequent use by the population, the present study aimed to investigate the genotoxic, antigenotoxic and cytotoxic activities of a standardized P. niruri extract in bone marrow rats. Three groups of 12 animals were treated daily by gavage over a period of 30 days, with 50, 150 or 250 mg/kg of P. niruri extract aqueous solution. The control group (n = 12) received tap water. At the end of treatment (day 31), groups were divided into two minor subgroups (n=6/group) and received cyclophosphamide (50 mg/kg, i.p.) or saline 0.9% (i.p.). After 24 hours, we evaluated the frequency of micronucleated polychromatic erythrocytes for each animal (MNPCE) at 1000 PCE. Cytotoxicity was evaluated with the PCE/NCE ratio (NEC = normochromatic erythrocytes). General toxicity was assessed during treatment using the parameters of body weight gain, ration and water consumption. The dry extract did not provoke changes in body weight, weight gain, ration and water intake or changes in the frequency of MNPCE or cytotoxicity in bone marrow. We propose that the P. niruri extract used here showed no genotoxic, antigenotoxic and cytotoxic activities under the experimental conditions.

Phyllanthus niruri L. (Euphorbiaceae), conhecida como "quebra-pedra", é uma planta medicinal utilizada frequentemente pela população no tratamento de problemas renais. Foram avaliadas as atividades genotóxicas, antigenotóxicas e citotóxicas de um extrato padronizado dessa espécie em ratos. Três grupos de doze animais foram tratados durante trinta dias, por gavagem, com 50, 150 ou 250 mg/kg/dia de solução aquosa do extrato de P. niruri e um grupo controle (n=12) recebeu água destilada pela mesma via. No final do tratamento os grupos foram divididos em dois subgrupos (6 animais/grupo) e receberam uma dose única de ciclofosfamida (50 mg/kg, i.p.) ou de solução salina 0,9% (i.p.). Após 24 horas, a frequência de eritrócitos policromáticos micronucleados (EPCMN) foi avaliada em 1000 EPC. A citotoxicidade foi avaliada pela relação entre eritrócitos policromáticos e normocromáticos (EPC/ENC) e a toxicidade geral foi avaliada através dos parâmetros de ganho de peso corporal, consumo de ração e ingestão hídrica. O extrato seco não provocou alterações significativas no peso corporal, ganho de peso e consumo de ração em relação ao grupo controle, nem alterações na frequência de EPCMN ou citotoxicidade em medula óssea. Dessa maneira, pode-se concluir que P. niruri não apresentou atividades genotóxica, antigenotóxica e/ou citotóxica nas condições experimentais executadas.

Resposta osteogênica sistêmica no estímulo medular ósseo / Osteogenic systemic response at bone marrow stimulation

OBJETIVO: Avaliar a influência da resposta osteogênica sistêmica, causada pelo estímulo da medula óssea à distância, na consolidação de falha óssea. MÉTODO: 36 coelhos adultos jovens foram divididos aleatoriamente em três grupos (A, B, C) e submetidos à ostectomia do rádio direito, com retirada de 4mm de fragmento ósseo. Os animais do grupo A foram submetidos ao estímulo da medula óssea pela sua ablação do fêmur esquerdo. Os animais do grupo B foram submetidos ao estímulo da medula óssea pela introdução de fio de Kirschner com 1,5mm de espessura, no interior do canal medular femoral esquerdo. Os animais do grupo C foram utilizados como grupo controle. Foram realizadas radiografias semanais até a 4ª semana pós-operatória, quando os animais foram sacrificados. Foi realizado estudo histomorfométrico do calo ósseo formado no local da ostectomia. As radiografias foram avaliadas para análise da evolução da consolidação óssea. RESULTADOS: Os grupos que sofreram estímulo medular à distância tiveram menor número de células ósseas, comparativamente ao grupo controle. No estudo radiográfico não houve diferença na evolução da consolidação entre os grupos. CONCLUSÃO: O estímulo da medula óssea à distância influenciou desfavoravelmente a consolidação de falha óssea em coelhos.

OBJECTIVE: To assess the influence of systemic osteogenic response caused by remote stimulation of bone marrow in a bone gap union. METHOD: 36 young adult rabbits were employed. The animals were randomly divided into 3 groups (A, B, C) and submitted to ostectomy of the right radius, removing 4mm of bone. The animals on Group A had their bone marrow stimulated by ablation on the left femur. Animals on Group B had their bone marrow stimulated by introducing a 1.5mm-thick Kirschner wire into the shaft of the left femur. The animals on Group C served as controls. X-ray images were taken on a weekly basis until the 4th post-surgical week, when the animals were sacrificed. Histomorphometric study of the bony callus formed at the ostectomy site was conducted. The x-ray images were evaluated in order to analyze the evolution of bone union at the ostectomy site. RESULTS: The groups with remote bone marrow stimulation had a smaller number of bone cells as compared to the control group. On radiographic studies, no difference in terms of evolution of union was evident between the groups. CONCLUSION: Remote stimulation of bone marrow had an unfavorable influence on bone gap union in rabbits.

Efeitos da lidocaína hiperbárica em concentrações crescentes, administrada no espaço subaracnóideo, sobre a medula e meninges: estudo experimental no cão / Effect of the hyperbaric lidocaína in increasing concentrations, managed in the subaracnóideo space, on the marrow and meninges: experimental study in the dog

Em estudo experimental em ratos, a injeçao de lidocaina subaracnoidea a partir da concentraçao de 7,5 porcento, resultou em mudanças neurofuncionais e histopatologicas. O proposito deste estudo foi investigar, em animais vivos as possiveis alteraçoes clinicas e histologicas desencadeadas por injeçoes de lidocaina hiperbarica nas concentraçoes de 5 porcento, 7,5 porcento e 10 porcento, administradasno espaço subaracnoideo de caes. Quarenta animais foram randomizados em quatro grupos que receberam por via subaracnoidea: G1 glicose a 7,5 porcento e 10 porcento, administradas no espaço subaracnoideo de caes. Quarenta animais foram randomizados em quatro grupos que receberam por via subaracnoidea: G1 glioce a 7,5 porcento, G2 lidocaina hiperbarica a 5 porcento, G3 lidocaina hiperbarica a 7,5porcento e G4 lidocaina hiperbarica a 10 porcento. A punçao subaracnoidea foi realizada no espaço intervetebral L6-L7. O volume da solução injetada foi de 1 ml. Os animais foram sacrificados apos sete dias de observaçao em cativeiro.As porçoes lombar e sacral da medula foram removidas para exame histologico, por microscopia optica. Os caes pertencentes aos grupos G1 e G2, ao apresentaram alteraçoes clinicas e histologicas na medula e meninges. Foi observado tres casos em G3, de necrose em focosno tecido medular mas, necrose abrangendo toda a superficie da medula em somente um dos animais e, a despeito dos achados histologicos, um destes caes permaneceu clinicamente normal. No G4, sete caes apresentaram alteraçoes clinicas e histologicas. As mudanças histologicas encontradas variaram de areas de necrose restritas a algumas regioes da medula a necrose em faixa abrangendo toda a superficie medular. Observamos diminuiçao de força muscular nas patas posteriores em seis animais, sendo que em tres deles houve associação em relaxamento de esfincter anal, e em um dos animais, a diminiçao do tonus esfincteriano foi a unica alteraçao clinica obervada. A neurotoxicidade da lidocaina hiperbarica espinhal em concentraçoes supra-clinicas determinou alteraçoes histopatologicas, restritas ao tecido nervoso da medula espinhal. A extensão e gravidade das lesoes foram intimamente relacionadas com a concentração da lidocaina. Lesoes brandas causadas por concentraçoes mais baixas de lidocaina podem nao manifestar alteraçoes clinicas.

Hyperfibrotic myelodysplasia: case report with response to steroid therapy / Mielodisplasia hiperfibrótica: relato de caso com resposta à terapia com corticoesteróides

A fibrose de medula óssea é encontrada em algumas doenças hematológicas clonais, incluindo síndromes mieloproliferativas, leucemias agudas e síndromes mielodisplásicas. Nas síndromes mielodisplásicas, uma nova entidade clinicopatológica com acentuado aumento das fibras de reticulina tem sido sugerida, e o termo "síndrome mielodisplásica hiperfibrótica" é usado para sua definiçäo. A biópsia de medula óssea mostra aumento das fibras de reticulina e hiperplasia megacariocítica com displasia. O diagnóstico diferencial com mielofibrose primária é difícil, e casos híbridos podem ocorrer. Pacientes com síndromes mielodisplásicas hiperfibróticas que respondem à terapia com corticosteróide têm sido descritos. Na maioria dos casos a remissäo é apenas hematológica, mas resoluçäo da fibrose de medula óssea já ocorreu em um paciente. Planejamento: Relato de caso. Relato: Paciente do sexo masculino, 62 anos de idade, apresentouðse, em junho de 1995, com história de seis meses de letargia e dispnéia. Ao exame, mostrouðse pálido, sem hepatoesplenomegalia. A concentraçäo de hemoglobina foi de 3g/dl, com acentuada anisocitose, mas sem "células em lágrimas". Os aspirados de medula óssea mostraramðse "secos", enquanto a biópsia revelou hipercelularidade e fibrose grau IV, obliterando a arquitetura habitual. Os megacariócitos estavam em número aumentado, com morfologia anômala, reagindo com anticorpos antifator VIII e CD31. Com a introduçäo de prednisona 1mg/kg em junho de 1996, os sintomas reduziram, a hemoglobina elevouðse a fibrose cedeu para grau II, tornandoðse independente de transfusões até janeiro de 1999. Entäo, a hemoglobina caiu para 6g/kl e, com a introduçäo de prednisona, houve pronta elevaçäo da hemoglobina

Factores predictivos de infiltración a médula ósea en niños con enfermedad de Hodking del Instituto Nacional de Pediatría / Predictive factors if bone marrow infiltration in children with Hodgkin's disease of the Instituto Nacional de Pediatría. Mexico

La biopsia de médula ósea ha sido esencial para la estadificación de pacientes con enfermedad de Hodgkin (EH). El presente estudio tiene como objetivo conocer si existen factores predictivos, clínicos, radiológicos y de laboratorio que permitan al oncólogo pediatra decidir de manera objetiva en qué pacientes debe o no realizar biopsia de médula ósea o debe de seguir siendo aparte del abordaje diagnóstico básico. Se incluyeron a los pacientes de uno u otro sexo con diagnóstico histopatológico de enfermedad de Hodgkin. Se consideraron como factores predictivos la variedad histológica, la presencia o ausencia de síntomas B, el estadio al momento del diagnóstico sin tomar en cuenta la infiltración a la médula ósea según la estadificación de Ann Arbor. Se realizó biometría hem tica completa, DHL y fosfatasa alcalina. Como variable dependiente se realizó biopsia de médula ósea bilateral a todos los pacientes posterior a la estadificación inicial, la médula ósea fue evaluada en el departamento de patología. Se formaron dos grupos de correlación entre la afección o no a la médula ósea y los factores predictivos estableciendo la significancia estadística de estas últimas tomando en cuenta el error alfa de .05. Para las variables continuas se realizó el Análisis con prueba de t y para las variables ordinales y nominales prueba exacta de Fisher. Se analizaron 109 pacientes. Los síntomas B, el estadio avanzado, variedad histología, depleción linfocítica, los niveles Hb al momento del diagnóstico y los niveles de fosfatasa alcalina mostraron tener una fuerte asociación con el resultado positivo de la biopsia de médula ósea. El estadio clínico se modificó en 12 pacientes posterior a las biopsias, del estadio III se estatificaron como IV sin embargo no hubo un caso en que un estadio temprano I o II se modificara, esto no tuvo repercusión en el tratamiento ya que el manejo para ambos estadios avanzados es el mismo. No se encontró asociación con género, cuenta leucocitaria o plaquetaria. De acuerdo a lo reportado y en estudios previos, la biopsia de MO podría estar limitada a pacientes con determinadas características clínicas como estadios clínicos III y IV así como en los pacientes con presencia de síntomas B, o con variedad histológica de depleción linfocítica, niveles bajos de Hb o fosfatasa alcalina elevada, lo que podría asegurar evitar realizar un procedimiento invasivo doloroso al paciente con EH que no tenga estas características

Long-term outcome of 25 children and adolescents with severe aplastic anemia treated with antithymocyte globulin

Severe aplastic anemia (SAA) is probably an immune-mediated disorder, and immunosuppressive therapy is recommended for patients with no available donor for bone marrow transplant. Between October 1984 and November 1987, 25 consecutive children and adolescents with SAA with no HLA-compatible marrow donor received equine antithymocyte globulin (ATG) (15 mg kg-1 day-1) for 10 days. The patients were evaluated 6 weeks, 6 months, and 12 months after starting ATG treatment. Thereafter, patients were evaluated yearly until July 1998. Median age was 10 years (range, 1.5-20 years), granulocyte counts on referral ranged from 0.032 to 1.4 x 10(9)/l (median 0.256 x 10(9)/l), and 12 patients had granulocyte counts < 0.2 x 10(9)/l. At a median follow-up of 9.6 years (range, 8.6-11.8 years), 10 patients (40 percent) remained alive with good marrow function. No morphologic evidence of hematological clonal disorders has been observed, although two patients probably have acquired clonal chromosomal abnormalities (trisomy 8 and del(6)q21, respectively). Responses to ATG were observed between 6 weeks and 6 months from the start of treatment in 60 percent of evaluable patients. The response rate was not different in patients whose granulocyte count at diagnosis was < 0.2 x 10(9)/l, or in those who were < 10 years of age. This study supports the view that, when compared with supportive measures, ATG is an effective treatment for children or adolescents with SAA. Although these results are inferior to those reported for marrow transplantation or more intensive immunosuppressive regimens, these patients who responded to ATG are long-term survivors with stable peripheral blood counts and a low rate of relapse.

Long-term outcome of 25 children and adolescents with severe aplastic anemia treated with antithymocyte globulin.

Severe aplastic anemia (SAA) is probably an immune-mediated disorder, and immunosuppressive therapy is recommended for patients with no available donor for bone marrow transplant. Between October 1984 and November 1987, 25 consecutive children and adolescents with SAA with no HLA-compatible marrow donor received equine antithymocyte globulin (ATG) (15 mg kg-1 day-1) for 10 days. The patients were evaluated 6 weeks, 6 months, and 12 months after starting ATG treatment. Thereafter, patients were evaluated yearly until July 1998. Median age was 10 years (range, 1.5-20 years), granulocyte counts on referral ranged from 0.032 to 1.4 x 10(9)/l (median 0.256 x 10(9)/l), and 12 patients had granulocyte counts <0.2 x 10(9)/l. At a median follow-up of 9.6 years (range, 8.6-11.8 years), 10 patients (40%) remained alive with good marrow function. No morphologic evidence of hematological clonal disorders has been observed, although two patients probably have acquired clonal chromosomal abnormalities (trisomy 8 and del(6)q21, respectively). Responses to ATG were observed between 6 weeks and 6 months from the start of treatment in 60% of evaluable patients. The response rate was not different in patients whose granulocyte count at diagnosis was <0.2 x 10(9)/l, or in those who were <10 years of age. This study supports the view that, when compared with supportive measures, ATG is an effective treatment for children or adolescents with SAA. Although these results are inferior to those reported for marrow transplantation or more intensive immunosuppressive regimens, these patients who responded to ATG are long-term survivors with stable peripheral blood counts and a low rate of relapse.

Estudio de la incidencia de tumores raquimedulares tratados en el Servicio de Neurocirugía Hospital San Juan de Dios set. 1994 - mar. 1998 y revisión del tema / Study is a retrospective review of spinal cord tumors, it`s incidence and treatment at San Juan de Dios Hospital, that underwent surgery betwen september 94 to march 98

El presente trabajo es un estudio retrospectivo sobre la incidencia de presentación de tumores raquimedulares en pacientes tratados en el servicio de Neurocirugía del Hospital San Juan de Dios durante cuarenta y dos meses (8 setiembre de 1994 a marzo de 1998). Se incluyeron veintiséis pacientes: dieciocho (18) de sexo masculino y ocho (8) femeninas, se logró determinar los tipos de tumores más frecuentes y si eran de origen primario o metastásico, su histopatología; en relación con su localización a nivel raquídeo 46,1 por ciento fueron extraudrals y 53,9 intradurales. Se logró conocer las manifestaciones clínicas y síndromes clínicos al igual que los tratamientos realizados para cada caso en particular y los métodos de diagnósticos disponibles y empleados en estos pacientes y así obtener un modelo de tratamiento integral para que los futuros pacientes de nuestro servicio sean manejados en forma ideal

Development of basophils in Mongolian gerbils: formation of basophilic cell clusters in the bone marrow after Nippostrongylus brasiliensis infection.

Development of basophilic leukocytes was studied in the Mongolian gerbil, Meriones unguiculatus, after infection with the nematode Nippostrongylus brasiliensis. After infection, peripheral blood basophilia developed and peaked at 2 weeks. In bone marrow sections, numbers of alcian blue+/safranine- basophilic cells were increased. These cells did not bind berberine sulfate and were clearly distinguishable from the bone marrow-resident mast cells, safranine+ and berberine sulfate+. Alcian blue+/safranine- cells were identified by electron microscopy as basophilic myelocytes in various stages of maturation. In the early period of infection, these cells had round-to-oval granules with a homogenous electron-dense matrix, a well-developed Golgi apparatus and rough endoplasmic reticulum, and a nonsegmented nucleus. By enzyme cytochemical analysis, intense peroxidase activity was demonstrated in all of the specific granules as well as in the rough endoplasmic reticulum and Golgi apparatus. Two weeks after infection, the number of bone marrow basophilic cells further increased, forming distinct clusters or islands composed of up to 100 cells each. On electron micrographs, the basophilic cells in these clusters appeared to be late-stage basophilic myelocytes, ie, having an increased number of granules, a less-conspicuous Golgi apparatus and rough endoplasmic reticulum, a horseshoe-shaped-to-lobulated nucleus, and reduced peroxidase activity. Eosinophils and mast cells were rarely found in the basophilic cell clusters. Four weeks after infection, the clusters had disappeared. These results show that gerbil basophilic myelocytes tend to form cell clusters in the bone marrow during their active proliferation. The comparative paucity of other cell lineages in basophilic cell clusters suggests that basophilia is generated from differentiation/proliferation of precommitted basophil progenitors independently from cells of other lineages.

Síndrome de Shwachman / Shwachman syndrome

Antecedentes: El síndrome de Shwachman es considerado como la segunda causa de insuficiencia pancreática en niños, se acompaña de disfunción de la médula ósea así como de alteraciones esqueléticas. Objetivo: Conocer e identificar las manifestaciones clínicas, de laboratorio y gabinete en los pacientes con síndrome de Shwachman. Material y métodos: Se estudió a paciente femenino de un año cuatro meses realizándole historia clínica tomándose para el estudio peso y talla, percentilas y examen físico. Exámenes de laboratorio: biometría hemática, hemoglobina fetal, ferrocinética, de terminación de vitamina B12 y folatos, aspirado de médula ósea, pruebas de absorción intestinal, coproparasitoscópicos y coprocultivos, coproantígeno para Giardia, transaminasas séricas, perfíl viral para hepatitis, electrólitos en sudor. Gabinete: Radiografía de huesos largos, cadera, ultrasonido abdominal y tomografía axial computarizada pancreática. Biopsia hepática e intestinal. Resultados: En la paciente se corroboró la presencia de insuficiencia pancreática, alteración de la médula ósea, alteraciones óseas compatibles con el síndrome de Shwachman.

Cell cycle phase duration in bone marrow cells from malnourished rats during suckling.

The generation time and duration of the different phases of the cell cycle were estimated in cultured bone marrow cells from malnourished and well-nourished rats during the lactation period by the percentage labeled mitosis (PLM) technique after a short pulse treatment with tritiated thymidine. The PLM were obtained in sequential analysis after every 3 h from removing labeled thymidine to 27 h of incubation. Results have shown a longer cell cycle time in cells from malnourished rats. The G1 + 1/2M phases are sensitive to experimental severe protein malnutrition (PCM), while S and G2 + 1/2 M phases did not show any differences in duration between malnourished and well-nourished rats.

Composition and function of the hemopoietic microenvironment in human myeloid leukemia.

In normal adult mammals, blood cell production, hemopoiesis, takes place within the medullary cavity. There, hemopoietic cell proliferation and differentiation are regulated by a network of stromal/accessory cells and their products (ie cytokines and extracellular matrix molecules), known as the hemopoietic microenvironment. Recent in vitro studies indicate that both cell composition and functional abnormalities of the hemopoletic microenvironment are present in a proportion of patients with myeloid leukemia, both chronic (CML) and acute (AML). Cell composition abnormalities have been primarily observed in a subset of patients with AML; these abnormalities include reduced numbers of fibroblast progenitors and, in some cases, reduced numbers of macrophages and adipocytes. In terms of function, it has been shown that the marrow stromal cells from a significant number of both CML and AML patients, possess a deficient hemopoletic supportive capacity in vitro. This seems to be related to the presence of functionally abnormal, malignant macrophages. The mechanisms by which these macrophages alter the hemopoietic function of the marrow stroma, as a whole, are still not fully understood. Whereas in AML, a macrophage-derived soluble inhibitory activity (containing tumor necrosis factor alpha) has been described; in CML, a direct, macrophage-mediated cell-to-cell contact mechanism for hemopoietic inhibition seems to be involved. To date, however, it is not clear whether the abnormalities in the hemopoietic microenvironment are secondary to myeloid leukemia or if they precede clinical CML/AML. Furthermore, it is not known to what extent the functional abnormalities observed in vitro contribute to the hematologic dysfunction that characterizes myeloid leukemia and to the in vivo progression of the disease.