RESUMEN
Acute leukemias are oncohematological diseases that compromise the bone marrow and have a complex diagnostic definition, leading to a high mortality when diagnosed late. This study proposed to determine the spectral differences between whole blood and plasma samples of healthy and leukemic subjects based on Raman spectroscopy (RS), correlating these differences with their resulting biochemical alterations and performing discriminant analysis of the samples (n = 38 whole blood and n = 40 plasma samples). Raman spectra were obtained using a dispersive Raman spectrometer (830-nm wavelength, 280-mW laser power, 30-s exposure time) with a Raman probe. The exploratory analysis based on principal component analysis (PCA) of the blood and plasma sample's spectra showed loading vectors with peaks related to amino acids, proteins, carbohydrates, lipids, and carotenoids, being the spectral differences related to amino acids and proteins for whole blood samples, and mainly carotenoids for plasma samples. Discriminant models based on partial least squares (PLS) and PCA were developed and classified the spectra as healthy or leukemic, with sensitivity of 91.9% (PLS) and 83.9% (PCA), specificity of 100% (both PLS and PCA), and overall accuracy of 96.5% (PLS) and 93.0% (PCA) for the whole blood spectra. In plasma, the sensitivity was 95.7% (PLS) and 11.6% (PCA), specificity of 98% (PLS) and 100% (PCA), and overall accuracy of 97.1% (PLS) and 64.1% (PCA). The study demonstrated that RS is a technique with potential to be applied in the diagnosis of acute leukemias in whole blood samples.
Asunto(s)
Análisis Químico de la Sangre/métodos , Leucemia/sangre , Leucemia/diagnóstico , Espectrometría Raman/métodos , Proteínas Sanguíneas/análisis , Carbohidratos/sangre , Carotenoides/sangre , Estudios de Casos y Controles , Análisis Discriminante , Humanos , Análisis de los Mínimos Cuadrados , Lípidos/sangre , Análisis de Componente Principal , Sensibilidad y EspecificidadRESUMEN
We have previously reported the cytotoxic effects of chalcone A1, derived from 1-naphthaldehyde, in leukemia cell lines. On the basis of these findings, the main aim of this study was to elucidate some of the molecular mechanisms involved in apoptosis induced by chalcone A1 toward K562 and Jurkat cells. In both cell lines, chalcone A1 decreased the mitochondrial membrane potential, increased the expression of Bax proapoptotic protein, and decreased the expression of Bcl-2 antiapoptotic protein (resulting in the inversion of the Bcl-2/Bax ratio), which indicates the involvement of the intrinsic pathway. In addition, chalcone A1 increased the expression of FasR in Jurkat cells, which also indicates the involvement of the extrinsic pathway in this cell line. The results also showed an increased expression of effector caspase-3 and cleaved PARP-1 and a decreased expression of IAP protein survivin, which are consistent with apoptotic cell death. The decreased expression of Ki67 suggests that the mechanism involved in cell death induced by chalcone A1 also involves a decrease in cell proliferation. In ex-vivo experiments, chalcone A1 reduced the cell viability of blast cells collected from eight patients with different types of acute leukemia, confirming the cytotoxicity results found in vitro. The results obtained so far are very promising and further studies need to be carried out so that chalcone A1 can be used as a prototype for the development of new antileukemia agents.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Chalconas/farmacología , Leucemia/sangre , Antineoplásicos/química , Factor Inductor de la Apoptosis/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Células Jurkat , Células K562 , Leucemia/tratamiento farmacológico , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Survivin , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by systemic intravascular activation of coagulation, leading to deposition of fibrin in the bloodstream. It may occur in patients with acute and chronic leukemia and is particularly associated with acute promyelocytic leukemia (a subtype of acute myeloid leukemia). OBJECTIVES: To assess the clinical benefits and harms of any pharmacological intervention for treating DIC in patients with acute or chronic leukemia. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2015, Issue 05), MEDLINE (1946 to 7 May 2015), LILACS (1982 to 7 May 2015) and African Index Medicus (7 May 2015). There was no language restrictions. We sought additional randomized controlled trials (RCTs) from the World Health Organization International Clinical Trials Registry Platform and the reference lists of primary studies identified. SELECTION CRITERIA: RCTs assessing the clinical benefits and harms of interventions for treating DIC in patients with acute and chronic leukemia. DATA COLLECTION AND ANALYSIS: Two review authors independently performed trial selection, 'Risk of bias' assessment and data extraction. Primary outcomes were overall mortality, in-hospital mortality from any cause (15-day and 30-day) and adverse events. MAIN RESULTS: In this Cochrane Review update we did not include any new RCT compared with the first review version. Accordingly, four RCTs (388 participants) met the inclusion criteria. These trials evaluated the human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate. Included trials reported data on mortality and bleeding. The studies were conducted in Japan, Italy and the Netherlands. We classified the included trials as: 1) including patients with or without leukemia which did not report data for the leukemia subgroup (366 participants); and 2) only including patients with leukemia (22 participants). Overall, the risk of bias of the included trials was high, since the trial authors did not provide a detailed description about trial design and execution.According to the GRADE recommendations, we judged the overall quality of the body of evidence for all prefixed outcomes as 'very low', due to methodological limitations and very small sample size.One trial, including 10 participants with leukemia and comparing dermatan sulphate with heparin, reported no deaths during trial treatment.In terms of bleeding data, we were unable to pool results from two studies that were only conducted with leukemia patients due to the inconsistency in the measurement and reporting of this outcome. One trial, including 12 participants with leukemia, found very low quality evidence that tranexamic acid can reduce the cumulative hemorrhagic score in participants compared with those assigned to placebo (P = 0.0015, very low quality evidence). On the contrary, there is no evidence that dermatan sulphate compared with placebo reduces new events of hemorrhagic diathesis (1/5 (20%) versus 2/5 (40%); RR 0.50; 95% CI 0.06 to 3.91; P = 0.51, very low quality evidence).No thromboembolic complications were reported in either trial that included patients with leukemia only (very low quality evidence). The safety profile was inconclusive.The included trials did not assess overall mortality, resolution of respiratory failure, renal failure or shock. AUTHORS' CONCLUSIONS: Due to a lack of new RCTs, our conclusions in this Cochrane Review update are the same as the previous review version. We included four RCTs which reported mortality and bleeding data. It is not possible to determine whether human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate are effective or harmful for patients presenting with DIC related to acute or chronic leukemia. The quality of the evidence was low to very low. Therefore, prescription of these interventions for treating DIC in patients with acute and chronic leukemia can neither be supported nor rejected, unless new evidence from a large high-quality trial alters this conclusion.
Asunto(s)
Anticoagulantes/uso terapéutico , Coagulación Intravascular Diseminada/tratamiento farmacológico , Leucemia/complicaciones , Enfermedad Aguda , Enfermedad Crónica , Dermatán Sulfato/uso terapéutico , Humanos , Leucemia/sangre , Proteína C/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Trombomodulina/uso terapéutico , Ácido Tranexámico/uso terapéuticoRESUMEN
OBJECTIVE: The acute lymphocytic leukemia is a hematopoietic cancer that occurs predominantly in children. Methotrexate is one of the most useful drugs in cancer chemotherapy. The aim of the study was to develop and validate the methodology of high performance liquid chromatography (HPLC) with ultraviolet detection for methotrexate dosage and to determine its concentration in plasma samples from children with leukemia. PATIENTS AND METHODS: The study included patients from the outpatient care of pediatric oncology at the Faculty of Medicine of ABC carriers in treatment of leukemia. The study was conducted in chromatographic model Agilent 1100 with UV detector at 302 nm and by the method of ELISA microplate reader capable of reading absorbance at 450 nm. RESULTS: We obtained satisfactory results of selectivity, accuracy, linearity, limit of quantification (LOQ), limit of detection (LOD), precision and robustness and apply the basic criteria for validation as RE No. 899, of May 29, 2003 Guide validation of analytical and bioanalytical National Agency Health Surveillance (ANVISA). CONCLUSIONS: We conclude that results for linearity/concentration range, precision, robustness, limit of quantification and detection limits are within the acceptance criteria defined by ANVISA and that the developed analytical method is valid and feasible to be used as a tool in monitoring therapy of methotrexate.
Asunto(s)
Antimetabolitos Antineoplásicos/sangre , Cromatografía Líquida de Alta Presión/normas , Leucemia/sangre , Metotrexato/sangre , Antimetabolitos Antineoplásicos/uso terapéutico , Niño , Cromatografía Líquida de Alta Presión/tendencias , Humanos , Leucemia/tratamiento farmacológico , Límite de Detección , Metotrexato/uso terapéutico , Reproducibilidad de los ResultadosRESUMEN
INTRODUCTION: Early lymphocyte recovery after allogeneic hematopoietic stem cell transplantation (HSCT) is related to the prevention of serious infections and the clearing of residual tumor cells. METHODS: We analyzed the absolute lymphocyte count at 20 (D+20) and 30 (D+30) days after HSCT in 100 patients with malignant hematologic diseases and correlated with the risk of transplant-related mortality, overall survival (OS), disease-free survival (DFS), nonrelapsed mortality (NRM), and risk of infection. RESULTS: Patients presenting with lymphocyte counts of <300 × 103/µL on D+30 have a 3.76 times greater risk of death in <100 days. Over a medium follow-up of 20 months OS, DFS, and NRM were similar between the groups. CONCLUSION: In our group of patients delayed lymphocyte recovery after HSCT was a predictor of early death post-HSCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia/sangre , Leucemia/terapia , Recuento de Linfocitos , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/terapia , Adolescente , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia/mortalidad , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
The current study is conducted to observe the differences in the level of low molecular weight proteins in the sera of patients with leukaemia in comparison to healthy subjects (control group). The sera of patients with leukaemia showed 15 peaks in the densitometric curve in comparison to the seven peaks of the controls. The peaks in the experimental samples that coincide with those in the control were of 134.14, 113.15, 76.06, 63.25, 48.07, 22.85 and 16.47 kDa molecular weights, respectively. Most of the new peaks appeared between the proteins of molecular weight 36-29 kDa in the experimental groups. Mean density of the 134.14 kDa protein band showed an increase in the protein in experimental groups I and II only whereas 113.15 and 22.85 kDa protein were increased in all experimental groups of patients with leukaemia. The expression of 76.06 and 63.25 kDa protein fraction was downregulated in the patients with leukaemia. A decline in the level of the protein of 48.07 kDa was observed in patients with leukaemia except in group I. Unlike the other protein fractions, the level of the protein of 16.47 kDa was significantly (p < 0.05) increased with a maximum density in group II. Intergroup experimental) comparison revealed an increasing pattern of 95.44 and 89.21 kDa with maximum level in group III sera. However the protein fractions of 38.07 and 34.94 kDa varied in the serum with maximum density in Group IV Protein fractions of 32.92 and 31.24 kDa were expressed in all age groups of patients with leukaemia with a maximum density in group III whereas the percentage densities of 14.42 and 13.56 kDa protein were quite different. This preliminary study will provide a basis to study the role of different proteins in patients with leukaemia.
Asunto(s)
Proteínas Sanguíneas/análisis , Leucemia/sangre , Adolescente , Adulto , Niño , Preescolar , Densitometría , Electroforesis en Gel de Poliacrilamida , Humanos , Lactante , Persona de Mediana Edad , Peso Molecular , Adulto JovenRESUMEN
The current study is conducted to observe the differences in the level of low molecular weight proteins in the sera of patients with leukaemia in comparison to healthy subjects (control group). The sera of patients with leukaemia showed 15 peaks in the densitometric curve in comparison to the seven peaks of the controls. The peaks in the experimental samples that coincide with those in the control were of 134.14, 113.15, 76.06, 63.25, 48.07, 22.85 and 16.47 kDa molecular weights, respectively. Most of the new peaks appeared between the proteins of molecular weight 36-29 kDa in the experimental groups. Mean density of the 134.14 kDa protein band showed an increase in the protein in experimental groups I and II only whereas 113.15 and 22.85 kDa protein were increased in all experimental groups of patients with leukaemia. The expression of 76.06 and 63.25 kDa protein fraction was downregulated in the patients with leukaemia. A decline in the level of the protein of 48.07 kDa was observed in patients with leukaemia except in Group I. Unlike the other protein fractions, the level of the protein of 16.47 kDa was significantly (p < 0.05) increased with a maximum density in Group II. Intergroup (experimental) comparison revealed an increasing pattern of95.44 and 89.21 kDa with maximum level in Group III sera. However, the protein fractions of 38.07 and 34.94 kDa varied in the serum with maximum density in Group IV Protein fractions of 32.92 and 31.24 kDa were expressed in all age groups of patients with leukaemia with a maximum density in Group III whereas the percentage densities of 14.42 and 13.56 kDa protein were quite different. This preliminary study will provide a basis to study the role of different proteins in patients with leukaemia.
El presente estudio se realiza con elfin de observar las diferencias en el nivel de proteínas de bajo peso molecular en los sueros de pacientes con leucemia, en comparación con pacientes sanos (grupo control). Los sueros de los pacientes con leucemia mostraron 15 picos en la curva densitométrica en comparación con los siete picos de los controles. Los picos en las muestras experimentales que coincidieron con aquéllos en los controles fueron de 134.14, 113.15, 76.06, 63.25, 48.07, 22.85y 16.47 kDa de peso molecular, respectivamente. La mayoría de estos nuevos picos aparecían entre las proteínas de peso molecular 36-29 kDa en los grupos experimentales. La densidad promedio de la banda proteica de 134.14 kDa sólo mostró un aumento en los grupos experimentales I y II, mientras que las proteínas de 113.15 y 22.85 kDa experimentaron un aumento en todos los grupos experimentales de pacientes con leucemia. La expresión de las fracciones de proteína de 76.06 y 63.25 kDa experimentó una reducción negativa (downregulation) en los pacientes con leucemia. Se observó una disminución en el nivel de la proteína de 48.07 kDa en los pacientes con leucemia, excepto en el Grupo I. A diferencia de las otras fracciones proteicas, el nivel de la proteína de 16.47 kDa aumentó significativamente (p < 0.05) con una densidad máxima en el Grupo II. La comparación intergrupal (experimental) puso de manifiesto un patrón de aumento de 95.44 y 89.21 kDa con un nivel máximo en los sueros del Grupo III. Sin embargo, las fracciones proteicas de 38.07 y 34.94 kDa variaron en el suero con densidad máxima en el Grupo IV Las fracciones proteicas de 32.92 y 31.24 kDa se expresaron en todos los grupos etarios de los pacientes con leucemia con una densidad máxima en el Grupo III, mientras que las densidades porcentuales del porcentaje de las proteínas de 14.42 y 13.56 kDa fueron bastante diferentes. Este estudio preliminar proporcionará la base para estudiar el papel de las diferentes proteínas en los pacientes con leucemia.
Asunto(s)
Adolescente , Adulto , Niño , Preescolar , Humanos , Lactante , Persona de Mediana Edad , Adulto Joven , Proteínas Sanguíneas/análisis , Leucemia/sangre , Densitometría , Electroforesis en Gel de Poliacrilamida , Peso MolecularRESUMEN
Leukemia has been associated with oral manifestations. However, the available literature on this topic consists of mostly reports of cases, without data about the periodontal parameters that may be under the influence of hematologic factors. The aim of this cross-sectional study was to assess the correlation between the Gingival Index and Bleeding on Probing with the platelet count in patients with leukemia. Patients with diagnosis of any kind of leukemia, at any stage of treatment, having a minimum age of 14 years, treated at the Department of Hematology-Oncology of the University Hospital of Santa Maria, Brazil, between December 2009 and March 2010, were assessed. Excluded patients were: edentulous, with orthodontic appliances, with psychomotor disturbances, requiring antibiotic prophylaxis for the examinations, or those using medications associated with gingival swelling. Two trained and calibrated examiners evaluated the Plaque Index, Gingival Index (GI), Probing depth, Bleeding on Probing (BOP), and Clinical Attachment Loss. Hematologic data were collected from a blood test performed on the same day as the periodontal examination. Thirty-seven patients (26 males), aged between 15 and 80 years (mean age 41.7 ± 18.31) were evaluated. Correlation between platelet count and BOP (p > 0.05), or between platelet count and GI (p > 0.05), were both weak (Pearson's correlation coefficient r = 0.171 and r = -0.003, respectively) and not statistically significant. It can be concluded from the preliminary results that the low platelet count was not correlated with the higher prevalence of gingival and periodontal bleeding in patients with leukemia.
Asunto(s)
Gingivitis/sangre , Leucemia/sangre , Índice Periodontal , Adolescente , Adulto , Anciano , Estudios Transversales , Índice de Placa Dental , Femenino , Humanos , Leucemia/complicaciones , Masculino , Persona de Mediana Edad , Pérdida de la Inserción Periodontal/sangre , Recuento de Plaquetas , Adulto JovenRESUMEN
Leukemia has been associated with oral manifestations. However, the available literature on this topic consists of mostly reports of cases, without data about the periodontal parameters that may be under the influence of hematologic factors. The aim of this cross-sectional study was to assess the correlation between the Gingival Index and Bleeding on Probing with the platelet count in patients with leukemia. Patients with diagnosis of any kind of leukemia, at any stage of treatment, having a minimum age of 14 years, treated at the Department of Hematology-Oncology of the University Hospital of Santa Maria, Brazil, between December 2009 and March 2010, were assessed. Excluded patients were: edentulous, with orthodontic appliances, with psychomotor disturbances, requiring antibiotic prophylaxis for the examinations, or those using medications associated with gingival swelling. Two trained and calibrated examiners evaluated the Plaque Index, Gingival Index (GI), Probing depth, Bleeding on Probing (BOP), and Clinical Attachment Loss. Hematologic data were collected from a blood test performed on the same day as the periodontal examination. Thirty-seven patients (26 males), aged between 15 and 80 years (mean age 41.7 ± 18.31) were evaluated. Correlation between platelet count and BOP (p > 0.05), or between platelet count and GI (p > 0.05), were both weak (Pearson's correlation coefficient r = 0.171 and r = -0.003, respectively) and not statistically significant. It can be concluded from the preliminary results that the low platelet count was not correlated with the higher prevalence of gingival and periodontal bleeding in patients with leukemia.
Asunto(s)
Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Gingivitis/sangre , Leucemia/sangre , Índice Periodontal , Estudios Transversales , Índice de Placa Dental , Leucemia/complicaciones , Recuento de Plaquetas , Pérdida de la Inserción Periodontal/sangreRESUMEN
BACKGROUND: Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by systemic intravascular activation of coagulation, leading to deposition of fibrin in the bloodstream, that may occur in patients with acute and chronic leukemia. OBJECTIVES: To assess the clinical effectiveness and safety of any pharmacological intervention for treating DIC in acute or chronic leukemia. SEARCH STRATEGY: The search strategy included the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 12), MEDLINE (1950 to 28 October 2010), EMBASE (1980 to 10 October 2010), LILACS (1982 to 19 August 2010) and African Index Medicus (1993 to 19 August 2010). There was no language restriction. We sought additional randomized controlled trials (RCTs) from the World Health Organization (WHO) Clinical Trials Registry Platform and by using the reference lists of primary studies found. SELECTION CRITERIA: RCTs assessing the effectiveness of interventions for treating disseminated intravascular coagulation (DIC) in patients with acute and chronic leukemia. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment and data extraction. MAIN RESULTS: Four RCTs (126 participants) met the inclusion criteria. These trials evaluated the human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate. Included RCTs reported data on mortality and bleeding. The included RCTs were classified as: 1) including patients with or without leukemia, and 2) only including patients with leukemia. However, data were not reported for the leukemia subgroup. We were not able to pool results from studies due to the inconsistency in the measurement and reporting of mortality and bleeding data. The included studies were at high risk of bias. AUTHORS' CONCLUSIONS: We found four RCTs which reported mortality and bleeding data. It is not possible to determine whether human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate are effective or harmful for patients presenting with DIC related to acute or chronic leukemia. The effects of these interventions need to be tested in sufficiently powered RCTs. Outcome measures should include in-hospital mortality from any cause, overall mortality, incidence of resolution of respiratory failure, renal failure, shock and safety. The definition of bleeding should be standardized in these patients.
Asunto(s)
Anticoagulantes/uso terapéutico , Coagulación Intravascular Diseminada/tratamiento farmacológico , Leucemia/complicaciones , Enfermedad Aguda , Enfermedad Crónica , Dermatán Sulfato/uso terapéutico , Humanos , Leucemia/sangre , Proteína C/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Trombomodulina/uso terapéutico , Ácido Tranexámico/uso terapéuticoRESUMEN
The ABO blood group is the most important blood group system in transfusion medicine and organ transplantation. To date, more than 160 ABO alleles have been identified by molecular investigation. Almost all ABO genotyping studies have been performed in blood donors and families and for investigation of ABO subgroups detected serologically. The aim of the present study was to perform ABO genotyping in patients with leukemia. Blood samples were collected from 108 Brazilian patients with chronic myeloid leukemia (N = 69), chronic lymphoid leukemia (N = 13), acute myeloid leukemia (N = 15), and acute lymphoid leukemia (N = 11). ABO genotyping was carried out using allele specific primer polymerase chain reaction followed by DNA sequencing. ABO*O01 was the most common allele found, followed by ABO*O22 and by ABO*A103. We identified 22 new ABO*variants in the coding region of the ABO gene in 25 individuals with leukemia (23.2%). The majority of ABO variants was detected in O alleles (15/60.0%). In 5 of 51 samples typed as blood group O (9.8%), we found non-deletional ABO*O alleles. Elucidation of the diversity of this gene in leukemia and in other diseases is important for the determination of the effect of changes in an amino acid residue on the specificity and activity of ABO glycosyltransferases and their function. In conclusion, this is the first report of a large number of patients with leukemia genotyped for ABO. The findings of this study indicate that there is a high level of recombinant activity in the ABO gene in leukemia patients, revealing new ABO variants.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/genética , Alelos , Variación Genética , Leucemia/sangre , Sistema del Grupo Sanguíneo ABO/clasificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , ADN/genética , ADN/aislamiento & purificación , Análisis Mutacional de ADN , Femenino , Genotipo , Humanos , Leucemia/clasificación , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo GenéticoRESUMEN
The ABO blood group is the most important blood group system in transfusion medicine and organ transplantation. To date, more than 160 ABO alleles have been identified by molecular investigation. Almost all ABO genotyping studies have been performed in blood donors and families and for investigation of ABO subgroups detected serologically. The aim of the present study was to perform ABO genotyping in patients with leukemia. Blood samples were collected from 108 Brazilian patients with chronic myeloid leukemia (N = 69), chronic lymphoid leukemia (N = 13), acute myeloid leukemia (N = 15), and acute lymphoid leukemia (N = 11). ABO genotyping was carried out using allele specific primer polymerase chain reaction followed by DNA sequencing. ABO*O01 was the most common allele found, followed by ABO*O22 and by ABO*A103. We identified 22 new ABO* variants in the coding region of the ABO gene in 25 individuals with leukemia (23.2%). The majority of ABO variants was detected in O alleles (15/60.0%). In 5 of 51 samples typed as blood group O (9.8%), we found non-deletional ABO*O alleles. Elucidation of the diversity of this gene in leukemia and in other diseases is important for the determination of the effect of changes in an amino acid residue on the specificity and activity of ABO glycosyltransferases and their function. In conclusion, this is the first report of a large number of patients with leukemia genotyped for ABO. The findings of this study indicate that there is a high level of recombinant activity in the ABO gene in leukemia patients, revealing new ABO variants.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano de 80 o más Años , Alelos , Variación Genética , Leucemia/sangre , Sistema del Grupo Sanguíneo ABO/genética , ADN , Análisis Mutacional de ADN , Genotipo , Leucemia/clasificación , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Sistema del Grupo Sanguíneo ABO/clasificaciónRESUMEN
Leukemia-associated antigens such as proteins encoded by MAGE genes might provide tools for immunotherapy of leukemia. Positive and negative results of MAGE-A gene expression in hematological malignancies have been reported. This led us to study MAGE-A gene expression in human leukemias using RT-PCR. Among 115 leukemias from various subtypes, 14/34 (41.17%) AML were positive for one of the three genes analyzed (MAGE-A1 1/32; MAGE-A3 10/32; MAGE-B2 3/12). Expression was also detected in 23/76 (30.26%) B-cell ALL patients (MAGE-A1 2/53; MAGE-A3 20/53; MAGE-B2 1/32). One of these patients expressed both MAGE-A1 (weak signal) and -A3 (strong signal) genes. Other patient with CML were positive for MAGE-B2 (1/5, 20%). MAGE-A3 expression data were corroborated by real time RT-PCR through determination of MAGE-A3 transcript levels. We concluded that the MAGE-A3 gene is expressed at the mRNA level in a proportion of human leukemias.
Asunto(s)
Antígenos de Neoplasias/genética , Leucemia/genética , Proteínas de Neoplasias/genética , ARN Mensajero/genética , Transcripción Genética , Adulto , Antígenos de Neoplasias/sangre , Secuencia de Bases , Cartilla de ADN , Femenino , Amplificación de Genes , Humanos , Leucemia/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
We compared the functional status of the hypothalamic dopaminergic tone in patients given an allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chronic graft-versus-host disease (GVHD) with that observed in patients with allo-HSCT without chronic GVHD and in healthy controls. The effect of acute dopaminergic blockade with intravenous metoclopramide on serum prolactin (PRL) concentrations was evaluated. Twenty volunteers, 20 to 52 years of age, seronegative for both hepatitis C virus and the human immunodeficiency virus, were studied: (1) 10 clinically healthy men (group 1), and (2) 9 patients with leukemia, and 1 patient with refractory aplastic anemia who underwent allo-HSCT, 5 of whom (3 men and 2 women) developed chronic GVHD (group 2), and 5 (3 men and 2 women) who did not develop chronic GVHD (group 3). Serum PRL concentrations were measured both fasting and after intravenous administration of metoclopramide (10-mg bolus). The area under the PRL curve was calculated. Patients in group 2 were older than those in groups 1 and 3 (P<.018), but their body mass index was similar. Fasting serum PRL concentrations were similar among the 3 groups; however, group 2 had higher PRL concentrations throughout the test (P<.001) and a greater area under the PRL curve than groups 1 and 3 (P<.001), without differences between the last 2 groups. The differences remained significant after adjustment for age (P<.01). Our results in a small group of patients with chronic GVHD after allo-HSCT suggest the existence of an increased functional level of their hypothalamic dopamine tone, which would favor a tendency toward a diminished endogenous production, release of pituitary PRL, or both. This could represent an adaptive mechanism aiming to maintain circulating PRL concentrations within a physiological range.
Asunto(s)
Dopamina/metabolismo , Enfermedad Injerto contra Huésped/fisiopatología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Sistema Hipotálamo-Hipofisario/fisiopatología , Hipotálamo/metabolismo , Prolactina/sangre , Adulto , Factores de Edad , Anemia Aplásica/sangre , Anemia Aplásica/fisiopatología , Anemia Aplásica/cirugía , Área Bajo la Curva , Índice de Masa Corporal , Enfermedad Crónica , Antagonistas de Dopamina/farmacología , Femenino , Enfermedad Injerto contra Huésped/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Leucemia/sangre , Leucemia/fisiopatología , Leucemia/cirugía , Masculino , Metoclopramida/farmacología , Persona de Mediana Edad , Proyectos Piloto , Adenohipófisis/metabolismo , Prolactina/metabolismo , Estudios Prospectivos , Trasplante Homólogo/efectos adversosAsunto(s)
Humanos , Masculino , Femenino , Enfermedades Hematológicas , Hematología , Eritrocitos/citología , Eritrocitos/clasificación , Eritrocitos/fisiología , Eritrocitos/patología , Anemia/clasificación , Anemia/diagnóstico , Anemia/epidemiología , Anemia/etiología , Anemia/fisiopatología , Anemia/terapia , Neutrófilos/clasificación , Neutrófilos/patología , Macrófagos/clasificación , Macrófagos/patología , Macrófagos/fisiología , Linfocitos/clasificación , Linfocitos/fisiología , Linfocitos/parasitología , Leucemia/clasificación , Leucemia/complicaciones , Leucemia/diagnóstico , Leucemia/etiología , Leucemia/fisiopatología , Leucemia/patología , Leucemia/sangre , Leucemia/terapia , Linfoma/clasificación , Linfoma/complicaciones , Linfoma/diagnóstico , Linfoma/etiología , Linfoma/fisiopatología , Linfoma/patología , Linfoma/terapia , Trombosis/clasificación , Trombosis/diagnóstico , Trombosis/fisiopatología , Transfusión Sanguínea/clasificación , Transfusión Sanguínea , Transfusión Sanguínea/efectos adversosAsunto(s)
Humanos , Masculino , Femenino , Enfermedades Hematológicas , Hematología , Eritrocitos/citología , Eritrocitos/clasificación , Eritrocitos/fisiología , Eritrocitos/patología , Anemia/clasificación , Anemia/diagnóstico , Anemia/epidemiología , Anemia/etiología , Anemia/fisiopatología , Anemia/terapia , Neutrófilos/clasificación , Neutrófilos/patología , Macrófagos/clasificación , Macrófagos/patología , Macrófagos/fisiología , Linfocitos/clasificación , Linfocitos/fisiología , Linfocitos/parasitología , Leucemia/clasificación , Leucemia/complicaciones , Leucemia/diagnóstico , Leucemia/etiología , Leucemia/fisiopatología , Leucemia/patología , Leucemia/sangre , Leucemia/terapia , Linfoma/clasificación , Linfoma/complicaciones , Linfoma/diagnóstico , Linfoma/etiología , Linfoma/fisiopatología , Linfoma/patología , Linfoma/terapia , Trombosis/clasificación , Trombosis/diagnóstico , Trombosis/fisiopatología , Transfusión Sanguínea/clasificación , Transfusión Sanguínea , Transfusión Sanguínea/efectos adversosRESUMEN
As leucemias são neoplasias hematológicas decorrentes do desequilíbrio entre as taxas de proliferação, maturação e apoptose das células hematopoéticas, comumente associadas com polimorfismos gênicos. Polimorfismos nos genes do TNFa e da enzima MTHFR têm sido associados como fatores de susceptibilidade para diversas patologias, inclusive neoplasias hematológicas. O presente estudo investigou a freqüência do polimorfismo -308 da região promotora no gene do TNFa, cuja variante genotipica AA está associada a níveis de transcrição elevados da citocina, e dos polimorfismos C677T e A1298C no gene da MTHFR, que estão associados com atividade enzimática reduzida. Para investigação dos polimorfismos foi utilizada a técnica de PCR-RFLP. Foram estudados 94 pacientes leucêmicos, sendo 66 portadores de LMC e 28 de LMA-M3, além de 100 indivíduos da população de Salvador. Dos 66 pacientes com LMC, cinco (7,6%) foram homozigotos para a variante genotipica menos comum (AA) do polimorfismo -308 do TNF. Essa freqüência foi de 3,7% entre os 28 portadores de LMA-M3 e de 3,0% entre os indivíduos do grupo populacional. Dentre os portadores de 66 LMC, dois (3,0%) foram homozigotos para a variante TT do polimorfismo C677T da MTHFR, sendo que foi encontrada frequência de 7,1% entre os portadores de LMA- M3 e de 6,0% para o grupo populacional. Para o polimorfismo A1298C da MTHFR, as freqüências encontradas para a variante CC foram de 4,5% entre os 66 portadores de LMC, 3,6% entre os 28 portadores de LMA-M3 e 5,0% entre os indivíduos do grupo populacional. Diante dos resultados obtidos, concluímos que os polimorfismos -308 (TNFa), bem como C677T e A1298 (MTHFR) parecem não interferir diretamente com os mecanismos de patogênese da LMC e LMA-M3.
Asunto(s)
Humanos , Genes/genética , Genes/inmunología , Leucemia/inmunología , Leucemia/mortalidad , Leucemia/patología , Leucemia/prevención & control , Leucemia/sangre , Leucemia/tratamiento farmacológicoRESUMEN
The purpose of this work was to compare the efficacy of blood culture conventional method vs. a modified lysis/centrifugation technique. Out of 450 blood specimens received in one year, 100 where chosen for this comparative study: 60 from patients with AIDS, 15 from leukemic patients, ten from febrile neutropenic patients, five from patients with respiratory infections, five from diabetics and five from septicemic patients. The specimens were processed, simultaneously, according to the above mentioned methodologies with daily inspections searching for fungal growth in order to obtain the final identification of the causative agent. The number (40) of isolates recovered was the same using both methods, which included; 18 Candida albicans (45%), ten Candida spp. (25%), ten Histoplasma capsulatum (25%), and two Cryptococcus neoformans (5%). When the fungal growth time was compared by both methods, growth was more rapid when using the modified lysis/centrifugation technique than when using the conventional method. Statistical analysis revealed a significant difference (p<0.05) between them. The modified lysis/centrifugation technique showed to be more efficacious than the conventional one, and therefore the implementation of this methodology is highly recommended for the isolation of fungi from blood.
Asunto(s)
Sangre/microbiología , Fungemia/microbiología , Hongos/aislamiento & purificación , Micología/métodos , Manejo de Especímenes/métodos , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Células Sanguíneas/efectos de los fármacos , Candida/crecimiento & desarrollo , Candida/aislamiento & purificación , Candidiasis/sangre , Candidiasis/complicaciones , Candidiasis/diagnóstico , Candidiasis/microbiología , Centrifugación , Criptococosis/sangre , Criptococosis/complicaciones , Criptococosis/diagnóstico , Criptococosis/microbiología , Cryptococcus neoformans/crecimiento & desarrollo , Cryptococcus neoformans/aislamiento & purificación , Complicaciones de la Diabetes/sangre , Fungemia/complicaciones , Fungemia/diagnóstico , Hongos/crecimiento & desarrollo , Histoplasma/crecimiento & desarrollo , Histoplasma/aislamiento & purificación , Histoplasmosis/sangre , Histoplasmosis/complicaciones , Histoplasmosis/diagnóstico , Histoplasmosis/microbiología , Humanos , Leucemia/sangre , Leucemia/complicaciones , Neutropenia/sangre , Neutropenia/complicaciones , Infecciones del Sistema Respiratorio/sangre , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/microbiología , Saponinas/farmacologíaRESUMEN
We propose a class of longitudinal data models with random effects that generalizes currently used models in two important ways. First, the random-effects model is a flexible mixture of multivariate normals, accommodating population heterogeneity, outliers, and nonlinearity in the regression on subject-specific covariates. Second, the model includes a hierarchical extension to allow for meta-analysis over related studies. The random-effects distributions are decomposed into one part that is common across all related studies (common measure), and one part that is specific to each study and that captures the variability intrinsic between patients within the same study. Both the common measure and the study-specific measures are parameterized as mixture-of-normals models. We carry out inference using reversible jump posterior simulation to allow a random number of terms in the mixtures. The sampler takes advantage of the small number of entertained models. The motivating application is the analysis of two studies carried out by the Cancer and Leukemia Group B (CALGB). In both studies, we record for each patient white blood cell counts (WBC) over time to characterize the toxic effects of treatment. The WBCs are modeled through a nonlinear hierarchical model that gathers the information from both studies.
Asunto(s)
Teorema de Bayes , Metaanálisis como Asunto , Modelos Biológicos , Humanos , Leucemia/sangre , Leucemia/tratamiento farmacológico , Recuento de Leucocitos , Funciones de Verosimilitud , Estudios Longitudinales , Análisis Multivariante , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricosRESUMEN
The risk of acquiring both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in patients with hematological-oncological disorders has been documented. However, the impact and risk factors for such infections from different geographical areas vary, and the use of both immunological and molecular assays to determine HCV infections has been our approach. Children from a hematology-oncology unit (HOU) in Nicaragua were studied for both HBV and HCV serological markers; studies for the latter used both immunological (anti-HCV) and molecular (HCV RNA) assays. The children from the HOU included patients with leukemia, lymphoma, other neoplasias, and anemia and a smaller group with other hematological diseases. As a control group, children from other units at the same hospital were enrolled, as well as health care workers attending both patient populations. Pertinent clinical and personal data for each child at the HOU were obtained for statistical analysis. Of the 625 children from the HOU enrolled in this study 53.3% were infected with HCV and 29.4% had a prior or present HBV infection. In the child patient control group 3.2% had HBV markers and all were negative for HCV. The group of children with leukemia had the highest infection rate for both HBV and HCV. However, the determination of anti-HCV was found to have an overall low sensitivity in children from HOU, and a retest consisting of a molecular assay to determine HCV RNA was performed to better establish the total number of HCV-infected subjects in this group. The highest independent risk factor for infection was hospitalization. The very high prevalence rates for both HBV and HCV infection in this patient group indicate an urgent need to implement better control of known risk factors and to consider the use of both immunological and molecular assays for HCV diagnostic purposes.