Comparison between two surgical techniques for prenatal correction of meningomyelocele in sheep

OBJECTIVE: To compare the classical neurosurgical technique with a new simplified technique for prenatal repair of a myelomeningocelelike defect in sheep. METHODS: A myelomeningocele-like defect (laminectomy and dural excision) was created in the lumbar region on day 90 of gestation in 9 pregnant sheep. Correction technique was randomized. In Group 1 the defect was corrected using the classic neurosurgical technique of three-layer suture (dura mater, muscle and skin closure) performed by a neurosurgeon. In Group 2, a fetal medicine specialist used a biosynthetic cellulose patch to protect the spinal cord and only the skin was sutured above it. Near term (day 132 of gestation) fetuses were sacrificed for pathological analysis. RESULTS: There were two miscarriages and one maternal death. In total, six cases were available for pathological analysis, three in each group. In Group 1, there were adherence of the spinal cord to the scar (meningo-neural adhesion) and spinal cord architecture loss with posterior funiculus destruction and no visualization of grey matter. In Group 2, we observed in all cases formation of a neo-dura mater, separating the nervous tissue from adjacent muscles, and preserving the posterior funiculus and grey matter. CONCLUSION: The new simplified technique was better than the classic neurosurgical technique. It preserved the nervous tissue and prevented the adherence of the spinal cord to the scar. This suggests the current technique used for the correction of spina bifida in humans may need to be reassessed.

Conhecimento médico sobre as imunodeficiências primárias na cidade de São Paulo, Brasil

OBJETIVO: Avaliar o conhecimento médico sobre as imunodeficiências primárias na cidade de São Paulo (SP). MÉTODOS: Um questionário de 14 questões sobre as imunodeficiências primárias foi aplicado a médicos que trabalhavam em hospitais gerais. Uma das questões apresentava 25 situações clínicas que poderiam ou não estar associadas às imunodeficiências primárias, e a porcentagem de respostas apropriadas gerou um indicador de conhecimento. RESULTADOS: Participaram do estudo 746 médicos, dentre os quais 215 pediatras (28,8%), 244 cirurgiões (32,7%) e 287 clínicos (38,5%). Cerca de 70% dos médicos responderam ter aprendido sobre as imunodeficiências primárias na graduação ou na residência médica. O atendimento a pacientes que usam antibióticos com frequência foi relatado por 75% dos médicos, mas apenas 34,1% já haviam investigado algum paciente e 77,8% não conheciam os dez sinais de alerta para as imunodeficiências primárias. O indicador de conhecimento obtido apresentou uma média de 45,72% (±17,87). Apenas 26,6% dos pediatras e 6,6% tanto dos clínicos quanto dos cirurgiões apresentaram indicador de conhecimento de pelo menos 67% (equivalente à resposta apropriada em dois terços das situações clínicas). CONCLUSÃO: Há uma deficiência no conhecimento médico das imunodeficiências primárias na cidade de São Paulo, mesmo entre os pediatras, a despeito do maior contato com o tema nos últimos anos. A melhora da informação sobre as imunodeficiências primárias entre a comunidade médica é um importante passo para o diagnóstico e o tratamento precoces dessas doenças.

Brazilian psychiatric brain bank: a new contribution tool to network studies

There is an urgent need for expanding the number of brain banks serving psychiatric research. We describe here the Psychiatric Disorders arm of the Brain Bank of the Brazilian Aging Brain Study Group (Psy-BBBABSG), which is focused in bipolar disorder (BD) and obsessive compulsive disorder (OCD). Our protocol was designed to minimize limitations faced by previous initiatives, and to enable design-based neurostereological analyses. The Psy-BBBABSG first milestone is the collection of 10 brains each of BD and OCD patients, and matched controls. The brains are sourced from a population-based autopsy service. The clinical and psychiatric assessments were done by an expert team including psychiatrists, through an informant. One hemisphere was perfused-fixed to render an optimal fixation for conducting neurostereological studies. The other hemisphere was comprehensively dissected and frozen for molecular studies. In 20 months, we collected 36 brains. A final report was completed for 14 cases: 3 BDs, 4 major depressive disorders, 1 substance use disorder, 1 mood disorder NOS, 3 obsessive compulsive spectrum symptoms, 1 OCD and 1 schizophrenia. The majority were male (64%), and the average age at death was 67.2 +/- 9.0 years. The average postmortem interval was 16 h. Three matched controls were collected. The pilot stage confirmed that the protocols are well fitted to reach our goals. Our unique autopsy source makes possible to collect a fairly number of high quality cases in a short time. Such a collection offers an additional to the international research community to advance the understanding on neuropsychiatric diseases.

Vascular dementia: Different forms of vessel disorders contribute to the development of dementia in the elderly brain

The diagnosis of vascular dementia (VaD) describes a group of various vessel disorders with different types of vascular lesions that finally contribute to the development of dementia. Most common forms of VaD in the elderly brain are subcortical vascular encephalopathy, strategic infarct dementia, and the multi infarct encephalopathy. Hereditary forms of VaD are rare. Most common is the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Sporadic forms of VaD are caused by degenerative vessel disorders such as atherosclerosis, small vessel disease (SVD) including small vessel arteriosclerosis, arteriolosclerosis, and lipohyalinosis, and cerebral amyloid angiopathy (CAA). Less frequently inflammatory vessel disorders and tumor-associated vessel lesions (e. g. angiocentric T-cell or angiotropic large cell lymphoma) can cause symptoms of dementia. Here, we review and discuss the impact of vessel disorders to distinct vascular brain tissue lesions and to the development of dementia in elderly individuals. The impact of coexisting neurodegenerative pathology in the elderly brain to VaD as well as the correlation between SVD and CAA expansion in the brain parenchyma with that of Alzheimer's disease (AD)-related pathology is highlighted. We conclude that "pure" VaD is rare and most frequently caused by infarctions. However, there is a significant contribution of vascular lesions and vessel pathology to the development of dementia that may go beyond tissue damage due to vascular lesions. Insufficient blood blow and alterations of the perivascular drainage mechanisms of the brain may also lead to a reduced protein clearance from extracellular space and subsequent increase of proteins in the brain parenchyma, such as the amyloid beta-protein, and foster, thereby, the development of AD-related neurodegeneration. As such, it seems to be important for clinical practice to consider treatment of potentially coexisting AD pathology in cognitively impaired patients with vascular lesions. (C) 2012 Elsevier Inc. All rights reserved.

Cerebral amyloid angiopathy impact on endothelium

Cerebral amyloid angiopathy (CAA) is an age-associated disease characterized by amyloid deposition in cerebral and meningeal vessel walls. CAA is detected in the majority of the individuals with dementia and also in a large number of non-demented elderly individuals. In addition, CAA is strongly associated with Alzheimer's disease (AD) pathology. Mechanical consequences including intra-cerebral or subarachnoid hemorrhage remains CAA most feared complication, but only a small fraction of CAA results in severe bleeding. On the hand the non-mechanical consequences in cerebrovascular regulation are prevalent and may be even more deleterious. Studies of animal models have provided strong evidence linking the vasoactive A beta 1-40, the main species found in CAA, to disturbances in endothelial-dependent factors, disrupting cerebrovascular regulation Here, we aimed to review experimental findings regarding the non-mechanical consequences of CAA for cerebrovascular regulation and discuss the implications of these results to clinical practice. (C) 2012 Elsevier Inc. All rights reserved.

MicroRNA expression profile in head and neck cancer: HOX-cluster embedded microRNA-196a and microRNA-10b dysregulation implicated in cell proliferation

Abstract Background Current evidence implicates aberrant microRNA expression patterns in human malignancies; measurement of microRNA expression may have diagnostic and prognostic applications. Roles for microRNAs in head and neck squamous cell carcinomas (HNSCC) are largely unknown. HNSCC, a smoking-related cancer, is one of the most common malignancies worldwide but reliable diagnostic and prognostic markers have not been discovered so far. Some studies have evaluated the potential use of microRNA as biomarkers with clinical application in HNSCC. Methods MicroRNA expression profile of oral squamous cell carcinoma samples was determined by means of DNA microarrays. We also performed gain-of-function assays for two differentially expressed microRNA using two squamous cell carcinoma cell lines and normal oral keratinocytes. The effect of the over-expression of these molecules was evaluated by means of global gene expression profiling and cell proliferation assessment. Results Altered microRNA expression was detected for a total of 72 microRNAs. Among these we found well studied molecules, such as the miR-17-92 cluster, comprising potent oncogenic microRNA, and miR-34, recently found to interact with p53. HOX-cluster embedded miR-196a/b and miR-10b were up- and down-regulated, respectively, in tumor samples. Since validated HOX gene targets for these microRNAs are not consistently deregulated in HNSCC, we performed gain-of-function experiments, in an attempt to outline their possible role. Our results suggest that both molecules interfere in cell proliferation through distinct processes, possibly targeting a small set of genes involved in cell cycle progression. Conclusions Functional data on miRNAs in HNSCC is still scarce. Our data corroborate current literature and brings new insights into the role of microRNAs in HNSCC. We also show that miR-196a and miR-10b, not previously associated with HNSCC, may play an oncogenic role in this disease through the deregulation of cell proliferation. The study of microRNA alterations in HNSCC is an essential step to the mechanistic understanding of tumor formation and could lead to the discovery of clinically relevant biomarkers.