RESUMO
While the genetic and environmental contributions to developmental dyslexia (DD) have been studied extensively, the effects of identified genetic risk susceptibility and of specified environmental hazardous factors have usually been investigated separately. We assessed potential gene-by-environment (GxE) interactions on DD-related reading, spelling and memory phenotypes. The presence of GxE effects were investigated for the DYX1C1, DCDC2, KIAA0319 and ROBO1 genes, and for seven specified environmental moderators in 165 nuclear families in which at least one member had DD, by implementing a general test for GxE interaction in sib-pair-based association analysis of quantitative traits. Our results support a diathesis-stress model for both reading and memory composites: GxE effects were found between some specified environmental moderators (i.e. maternal smoke during pregnancy, birth weight and socio-economic status) and the DYX1C1-1259C/G marker. We have provided initial evidence that the joint analysis of identified genetic risk susceptibility and measured putative risk factors can be exploited in the study of the etiology of DD and reading-related neuropsychological phenotypes, and may assist in identifying/preventing the occurrence of DD.
Assuntos
Dislexia/genética , Interação Gene-Ambiente , Fenótipo , Estudos de Casos e Controles , Criança , Proteínas do Citoesqueleto , Dislexia/etiologia , Feminino , Estudos de Associação Genética , Humanos , Masculino , Memória , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/genética , Característica Quantitativa Herdável , Fatores Socioeconômicos , Estresse Psicológico/complicações , Poluição por Fumaça de Tabaco/efeitos adversosRESUMO
The relevance of high-dose chemotherapy followed by auto-SCT in CLL remains to be defined. The aim of the prospective, randomized, GOELAMS LLC 98 trial was to compare two strategies in previously untreated CLL patients aged <60 years. Conventional chemotherapy (Arm A) consisted of six monthly courses of CHOP followed by six CHOP courses in every 3 months in those achieving a complete or PR. Arm A was compared with high-dose therapy with auto-SCT (Arm B), used as consolidation after three CHOP courses in case of CR or very good PR. A total of 86 patients were enrolled, of which 39 and 43 patients were evaluable in arm A and arm B, respectively. The primary endpoint was PFS. On an intent-to-treat basis and with a median follow-up time of 77.1 (range 1-135.5) months, the median PFS was 22 months in Arm A and 53 months in Arm B (P<0.0001). Median survival time was 104.7 months in arm A and 107.4 months in arm B. This trial demonstrates that frontline high-dose therapy with auto-SCT prolongs PFS but does not translate into a survival advantage in advanced CLL patients in the pre-rituximab era.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Crônica de Células B/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , Taxa de Sobrevida , Transplante Autólogo , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
PURPOSE: We present the way to integrate gravimetric control (GC) in a centralized preparation of cytotoxic drugs unit. Two different modalities are described. In the first strategy, the balance is located inside the isolator, whereas in the second, it is located outside in order to remove many technical and ergonomic constraints. These two modalities are compared in terms of benefits and limits. METHODS: GC consists in comparing the observed weight variation with the expected weight variation using a precision balance. According to the B-in strategy, this variation is directly attributable to the weight of the cytotoxic solution injected, whereas with the B-out strategy, the weight of various additional components must be taken into account. RESULTS: Five hundred and seventy-seven preparations have been weighed. For "B-in" strategy, the 95% confidence interval is [1.02-1.14%] and every preparation is below the threshold of 5%. For "B-out" strategy, the 95% confidence interval is [2.34-2.63%] and 94% of preparations are below the threshold of 5%. B-in strategy is distinctly more precise than B-out strategy and can be applied to all preparations. However, B-out strategy is a feasible option in practice and enables the detection of an important mistake. All in all, results obtained from B-out strategy can be considered as a quality indicator in the production line. CONCLUSION: Results of GC are helpful in the final step of release, which the pharmacist is responsible for. Many contributions in the quality assurance policy could justify using of GC in every unit.