Serum ferritin and transferrin saturation levels in ß° and ß(+) thalassemia patients.

There have been few studies on the mutations that cause heterozygous beta-thalassemia and how they affect the iron profile. One hundred and thirty-eight individuals were analyzed, 90 thalasemic ß° and 48 thalasemic ß(+), identified by classical and molecular methods. Mutations in the hemochromatosis (HFE) gene, detected using PCR-RFLP, were found in 30.4% of these beta-thalassemic patients; heterozygosity for H63D (20.3%) was the most frequent. Ferritin levels and transferrin saturation were similar in beta-thalassemics with and without mutations in the HFE gene. Ferritin concentrations were significantly higher in men and in individuals over 40 years of age. Transferrin saturation also was significantly higher in men, but only in those without HFE gene mutations. There was no significant difference in the iron profile among the ß° and ß(+) thalassemics, with and without HFE gene mutations. The frequency of ferritin values above 200 ng/mL in women and 300 ng/mL in men was also similar in ß° and ß(+) thalassemics (P > 0.72). Our conclusion is that ferritin levels are variable in the beta-thalassemia, trait regardless of the type of beta-globin mutation. Furthermore, HFE gene polymorphisms do not change the iron profile in these individuals.

HFE gene mutations in Brazilian thalassemic patients.

Hereditary hemochromatosis is a disorder of iron metabolism characterized by increased iron intake and progressive storage and is related to mutations in the HFE gene. Interactions between thalassemia and hemochromatosis may further increase iron overload. The ethnic background of the Brazilian population is heterogeneous and studies analyzing the simultaneous presence of HFE and thalassemia-related mutations have not been carried out. The aim of this study was to evaluate the prevalence of the H63D, S65C and C282Y mutations in the HFE gene among 102 individuals with alpha-thalassemia and 168 beta-thalassemia heterozygotes and to compare them with 173 control individuals without hemoglobinopathies. The allelic frequencies found in these three groups were 0.98, 2.38, and 0.29% for the C282Y mutation, 13.72, 13.70, and 9.54% for the H63D mutation, and 0, 0.60, and 0.87% for the S65C mutation, respectively. The chi-square test for multiple independent individuals indicated a significant difference among groups for the C282Y mutation, which was shown to be significant between the beta-thalassemia heterozygote and the control group by the Fisher exact test (P value = 0.009). The higher frequency of inheritance of the C282Y mutation in the HFE gene among beta-thalassemic patients may contribute to worsen the clinical picture of these individuals. In view of the characteristics of the Brazilian population, the present results emphasize the need to screen for HFE mutations in beta-thalassemia carriers.

HFE gene mutations in Brazilian thalassemic patients

Hereditary hemochromatosis is a disorder of iron metabolism characterized by increased iron intake and progressive storage and is related to mutations in the HFE gene. Interactions between thalassemia and hemochromatosis may further increase iron overload. The ethnic background of the Brazilian population is heterogeneous and studies analyzing the simultaneous presence of HFE and thalassemia-related mutations have not been carried out. The aim of this study was to evaluate the prevalence of the H63D, S65C and C282Y mutations in the HFE gene among 102 individuals with alpha-thalassemia and 168 beta-thalassemia heterozygotes and to compare them with 173 control individuals without hemoglobinopathies. The allelic frequencies found in these three groups were 0.98, 2.38, and 0.29 percent for the C282Y mutation, 13.72, 13.70, and 9.54 percent for the H63D mutation, and 0, 0.60, and 0.87 percent for the S65C mutation, respectively. The chi-square test for multiple independent individuals indicated a significant difference among groups for the C282Y mutation, which was shown to be significant between the beta-thalassemia heterozygote and the control group by the Fisher exact test (P value = 0.009). The higher frequency of inheritance of the C282Y mutation in the HFE gene among beta-thalassemic patients may contribute to worsen the clinical picture of these individuals. In view of the characteristics of the Brazilian population, the present results emphasize the need to screen for HFE mutations in beta-thalassemia carriers.

Clozapina no Brasil: avaliação da aplicabilidade do sistema de farmacovigilância e resultados terapêuticos preliminares / Clozapine in Brazil: evaluation of the feasibility of the drug surveillance system and preliminary therapeutic results

É apresentado o resultado de um estudo multicêntrico brasileiro cujos objetivos foram: aplicar em condições reais o modelo de farmacovigilância da clozapina no país (Sistema de Farmacovigilância de Leponex ð SFL) para detectar e corrigir eventuais falhas e proporcionar a diversos psiquiatras a experiência com o medicamento dentro das normas de segurança do SFL. Foram estudados 34 pacientes com diagnóstico de esquizofrenia crônica, refratários e/ou intolerantes ao tratamento com neurolépticos, que apresentavam exames hematológicos dentro dos parâmetros exigidos pelo SFL. A avaliação da eficácia antipsicótica da CZP foi feita pela BPRS e pela CGI e a tolerabilidade geral foi avalidada pela escala UKU, ao lado da avaliação hematológica semanal nas primeiras 18 semanas e mensal nos meses subseqüentes. O tratamento com a CZP incluiu doses crescentes e variáveis, tendo sido observado, ao final dos seis meses de tratamento, que a dose de manutenção se situava entre 75 e 700mg (mediana de 400mg). A análise da média dos escores da BPRS mostrou que houve melhora estatisticamente significante dos sintomas (ANOVA F = 112,24; p < 0,001), e essa diferença estatística ocorreu a partir do primeiro mês de tratamento. A avaliação préðtratamento, mostrou que houve redução significante da gravidade da doença, com remissão em 14,7 por cento (5/34) e melhora parcial em 70 por cento (24/34). Com relação à tolerabilidade, destacaðse a ausência de reações extrapiramidais bem como a boa adesão à rotina de controles hematológicos; um paciente apresentou trombocitopenia, que levou à interrupção da CZP, e outro interrompeu o tratamento devido a efeitos colaterais nãoðhematológicos. Os autores concluem que o efeito terapêutico da CZP foi promissor e ressaltam o bom resultado obtido com a operacionalização do SFL no Brasil

Clozapina no Brasil: avaliacao da aplicabilidade do sistema de farmacovigilancia e resultado terapeuticos preliminares

E apresentado o resultado de um estudo multicentrico brasileiro cujos objetivos foram: aplicar em condicoes reais o modelo da farmacovigilancia da clozapina no pais (Sistema de Farmacovigilancia de Leponex - SFL) para detectar e corrigir eventuais falhas e proporcionar a diversas psiquiatras a experiencia com o medicamento dentro das normas de seguranca do SFL. Foram estudados 34 pacientes com diagnostico de esquizofrenia cronica, refratarios e/ou intolerantes ao tratamento com neurolepticos, que apresentavam exames hermatologicos dentro dos parametros exigidos pelo SFL. A avaliacao da eficacia antipsicotica da CZP foi feita pela BPRS e pela CGI e a tolerabilidade geral foi avaliada pela escala UKU, ao lado da avaliacao hematologica semanal nas primeiras 18 semanas e mensal nos meses subsequentes. O tratamento com a CZP incluiu doses crescentes e variaveis, tendo sido observado, ao final dos seis meses de tratamento, que a dose de manutencao se situava entre 75 e 700mg (mediana de 400mg). A analise da media dos escores da BPRS mostrou que houve melhora estatisticamente significante dos sintomas (ANOVA F=112,24; p<0,001), e essa diferenca estatistica ocorreu a partir do primeiro mes de tratamento. A avaliacao final dos pacientes, em comparacao a avaliacao pre-tratamento, mostrou que houve reducao significante da gravidade da doenca, com remissao em 14,7 por cento (5/34) e melhora parcial em 70 por cento (24/34). Com relacao a tolerabilidade, detaca-se a ausencia de reacoes extrapiramidais bem como a boa adesao a rotina de controles hematologicos; um paciente apresentou trombocitopenia, que levou a interrupcao da CZP, e outro interrompeu o tratamento devido a efeitos colaterais nao-hematologicos. Os autores concluem que o efeito terapeutico da CZP foi promissor e ressaltam o bom resultado obtido com a operacionalizacao do SFL no Brasil.