GLA Nonsense Mutation (c.485G>A) in a Three-Generation Family with Fabry’s Disease.

Background: GLA nonsense mutations seem to be associated with more severe clinical phenotype. Aims: Main aims were to identify the disease-causing mutation, to screen high risk family members and to predict the severity of clinical phenotype and age of onset based on genotype-phenotype analysis. Methods: Seven family members were clinically assessed and enzyme activity levels were evaluated as well. Genomic DNA was isolated from blood samples and analyzed for GLA gene mutation. Results: The proband, a 34-year-old man, was misdiagnosed for years. At 25 years of age he was diagnosed with Fabry’s disease. He had a less severe phenotype failing to express cardiac, cerebral or renal symptoms. In addition, the patient presented a ventricular septal defect as an incidental finding which has not been reported previously in Fabry’s disease. His maternal uncle had a severe classic form and, in addition, osteonecrosis of femoral head rarely reported as associated findings. All females were heterozygous; 3 of them were asymptomatic and 2 developed milder symptoms, skin and heart predominantly affected. Fabry’s disease was caused by the presence of GLA nonsense mutation c.485G>A. All close relatives of proband had one copy of the mutation. Conclusion: The family nonsense mutation c.485G>A known to predict the classic phenotype showed a wide range of clinical manifestations from severe to asymptomatic forms both in males and females supporting the intrafamilial phenotypic variability for Fabry’s disease.

Combination hyperbaric oxygen and temozolomide therapy in c6 rat glioma model / Terapia combinada de oxigênio hiperbárico e temozomida no modelo C6 de glioma em ratos

PURPOSE: Temozolomide (TMZ) has anti-tumor activity in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are limited because of the hypoxic tumor microenvironment. We examined the combined effects of TMZ-HBO in a rat glioma model. METHODS: After stereotactic injection of C6/LacZ rat glioma cells into the Wistar rats brain, the rats were randomly assigned to three treatment groups [group 1, control treatment; group 2, TMZ alone; group 3, a combination of TMZ and HBO]. Rats were sacrificed 18 days after treatment, and number of intra-/peri-tumoral vessels, microendothelial proliferations, immunohistochemistry and necrotic area were evaluated. RESULTS: Tumoral tissue was stained only sparsely with GFAP. Temozolomide treatment was significantly decreased in tumor tissue intratumoral vessel number / total tumor area level. The level of Ki67 was significantly decreased in the tumor tissue of the group 3. Additionally, the total necrotic area / total tumor volume (%) was decreased significantly in tumor tissue of the group 3 rats compared to group1 and 2. CONCLUSION: The combination of hyperbaric oxygen with temozolomide produced an important reduction in glioma growth and effective approach to the treatment of glioblastoma.

OBJETIVO: A temozolomida (TMZ) tem atividade anti-tumoral em pacientes com glioma maligno. Oxigênio hiperbárico (HBO) pode aumentar a eficácia de terapias que são limitadas devido a um microambiente do tumor hipóxico. Foram examinados os efeitos combinados de TMZ-HBO em um modelo de glioma em rato. MÉTODOS: Após a injeção estereotáxica de células de glioma de rato C6/LacZ no cérebro de ratos Wistar, os ratos foram distribuídos aleatoriamente em três grupos de tratamento: Grupo 1: tratamento de controle. Grupo 2: TMZ sozinho. Grupo 3: uma combinação de TMZ e HBO. Os ratos foram sacrificados 18 dias após o tratamento. Foram avaliados o número de vasos intra-/peri-tumoral, proliferação microendotelial, imunohistoquímica e área necrótica . RESULTADOS: O tecido tumoral foi marcado apenas esparsamente com GFAP. O tratamento com temozolomida diminuiu significativamente o tecido intratumoral e a área total do tumor. O nível de Ki67 foi significativamente diminuído no tecido do tumor do grupo 3. Além disso, a superfície necrótica total / volume total do tumor (%) diminuiu significativamente no tecido do tumor do grupo 3 em comparação com grupo 1 e 2. CONCLUSÃO: A combinação de oxigênio hiperbárico com temozolomida produziu uma redução importante no crescimento do glioma podendo ser abordagem eficaz para o tratamento do glioblastoma.

Multiple Indicator Cluster Survey 2003 in Afghanistan: Outdated Sampling Frame and the Effect of Sampling Weights on Estimates of Maternal and Child Health Coverage.

Due to an urgent need for information on the coverage of health service for women and children after the fall of Taliban regime in Afghanistan, a multiple indicator cluster survey (MICS) was conducted in 2003 using the outdated 1979 census as the sampling frame. When 2004 pre-census data became available, population- sampling weights were generated based on the survey-sampling scheme. Using these weights, the population estimates for seven maternal and child healthcare-coverage indicators were generated and compared with the unweighted MICS 2003 estimates. The use of sample weights provided unbiased estimates of population parameters. Results of the comparison of weighted and unweighted estimates showed some wide differences for individual provincial estimates and confidence intervals. However, the mean, median and absolute mean of the differences between weighted and unweighted estimates and their confidence intervals were close to zero for all indicators at the national level. Ranking of the five highest and the five lowest provinces on weighted and unweighted estimates also yielded similar results. The general consistency of results suggests that outdated sampling frames can be appropriate for use in similar situations to obtain initial estimates from household surveys to guide policy and programming directions. However, the power to detect change from these estimates is lower than originally planned, requiring a greater tolerance for error when the data are used as a baseline for evaluation. The generalizability of using outdated sampling frames in similar settings is qualified by the specific characteristics of the MICS 2003—low replacement rate of clusters and zero probability of inclusion of clusters created after the 1979 census.

An integrated program to train local health care providers to meet post-disaster mental health needs / Programa integrado para entrenar a proveedores de servicios sanitarios locales a satisfacer las necesidades de salud mental después de un desastre

En el presente trabajo se describe un programa de entrenamiento para la atención de la salud mental después de desastres, desarrollado por la Sección Internacional del Departamento de Psiquiatría de la Universidad de Dalhousie (Halifax, Canadá) y llevado a cabo en la isla de Granada después de que el huracán Iván azotó ese país en septiembre de 2004. Este programa de entrenamiento para entrenadores utilizó un modelo integrado de salud comunitaria para ayudar a los proveedores de los servicios sanitarios locales a desarrollar las habilidades necesarias para identificar los trastornos mentales frecuentes después de un desastre natural y aplicar tratamientos basados en pruebas científicas. Este programa también favorece el enfoque actual de atención sostenible de salud mental en la comunidad, promovido por la Organización Mundial de la Salud y la Organización Panamericana de la Salud. Además, se contrapone a las actividades verticales de consejería psicosocial dirigidas a toda la población, en su mayoría ineficaces y costosas, que se han venido empleando en el Caribe después de desastres naturales.

This paper describes a post-disaster mental health training program developed by the International Section of the Department of Psychiatry at Dalhousie University (Halifax, Canada) and delivered in Grenada after Hurricane Ivan struck the country in September 2004. This trainthe-trainer program used an integrated community health model to help local health care providers develop the necessary skills for the identification and evidenced-based treatment of mental disorders occurring after a natural disaster. The approach also provided for ongoing, sustainable mental health care delivered in the community setting, as advocated by the World Health Organization and the Pan American Health Organization. This approach is in contrast to the largely ineffective and costly vertical whole-population psychosocial counseling activities that have often been used in the Caribbean following natural disasters

Influence of HIV positive status on sexual behavior among males

Compara homens HIV soronegativos (HIV-) e HIV soropositivos (HIV+) em termos de comportamento sexual com parceiras e parceiros regulares ou casuais. De agosto de 1994 a fevereiro de 1995, uma amostra de 236 participantes (150 HIV- e 86 HIV+) foi recrutada de serviços públicos do Estado de Säo Paulo, Brasil, para atendimento e testagem de HIV/AIDS. Foi aplicado aos participantes questionário contendo questöes sobre aspectos demográficos, conhecimento sobre HIV e AIDS, orientaçäo sexual, uso de álcool e outras drogas, percepçäo de risco para HIV e comportamento sexual com parceiros e parceiras regulares e casuais (investigado nos últimos meses). A comparaçäo entre os indivíduos HIV+ e HIV- indicou que uma menor percentagem de HIV+ teve contato sexual com parceiras regulares (p<.01), praticou sexo vaginal com este tipo de parceira (p<.01) e praticou todo tipo de atividade sexual (p<.001). Os indivíduos HIV+ relataram uma freqüência menor de práticas sexuais penetrativas (p<0.5). Identificou-se um nível elevado de uso de preservativo com parceiras e parceiros sexuais e näo foi observada diferença significativa entre os dois grupos neste aspecto. Identificou-se algum comportamento de risco, especialmente com parceiros/parceiras regulares. O nível elevado de uso de preservativo sugere que têm sido adotadas recomendaçöes em relaçäo a sexo seguro. O uso de preservativo näo foi universal, sugerindo que alguns homens continuam a praticar sexo desprotegido. A efetiva prevençäo da transmissäo do vírus ocorrerá com programas de prevençäo que estimulem práticas de sexo seguro entre indivíduos HIV- e HIV+