Diffusion tensor MR imaging in neurofibromatosis type 1: expanding the knowledge of microstructural brain abnormalities.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a hereditary disease with a dominant autosomal pattern. In children and adolescents, it is frequently associated with the appearance of T2-weighted hyperintensities in the brain's white matter. MRI with diffusion tensor imaging (DTI) is used to detect white matter abnormalities by measuring fractional anisotropy (FA). OBJECTIVE: This study employed DTI to evaluate the relationship between FA patterns and the findings of T2 sequences, with the aim of improving our understanding of anatomical changes and microstructural brain abnormalities in individuals with NF1. MATERIALS AND METHODS: Forty-four individuals with NF1 and 20 control subjects were evaluated. The comparative analysis of FA between NF1 and control groups was based on four predetermined anatomical regions of the brain hemispheres (basal ganglia, cerebellum, pons, thalamus) and related the presence or absence of T2-weighted hyperintensities in the brain, which are called unidentified bright objects (UBOs). RESULTS: The FA values between the groups demonstrated statistically significant differences (P ≤ 0.05) for the cerebellum and thalamus in patients with NF1, independent of the occurrence of UBOs. CONCLUSIONS: Diffusion tensor MR imaging confirms the influence of UBOs in the decrease of FA values in this series of patients with NF1. Additionally, this technique allows the characterization of microstructural abnormalities even in some brain regions that appear normal in conventional MR sequences.

The association between CBS 844ins68 polymorphism and head and neck squamous cell carcinoma risk - a case-control analysis.

INTRODUCTION: Susceptibility to head and neck squamous cell carcinoma may be modified by functional polymorphisms in genes involved in the folate pathway, such as cystathionine beta-synthase (CBS). The CBS 844ins68 polymorphism is associated with DNA methylation changes and cancer development. MATERIAL AND METHODS: A case-control retrospective study was conducted in 322 patients with head and neck squamous cell carcinoma and in 531 control subjects without cancer. The polymerase chain reaction-restriction fragment length polymorphism technique was used to genotype the polymorphism. For statistical analysis, χ(2) test was conducted to examine whether the genotypic frequency of CBS 844ins68 was in Hardy-Weinberg equilibrium and multiple logistic regression was used for comparisons between groups, and for interactions between the polymorphism and risk factors and clinical histopathological parameters. RESULTS: No significant difference in CBS 844ins68 genotypic distribution was observed between the groups. Age > 50 years, male gender and tobacco consumption were predictors of the disease with increased risk of 7.89 (95% CI: 5.56-11.21), 2.49 (95% CI: 1.72-3.62), 6.44 (95% CI: 4.63-8.96) and 2.29 times (95% CI: 1.71-3.06) respectively. There was no association between the distribution of the CBS 844ins68 genotype and risk factors for this disease. According to clinical histopathological parameters, CBS 884ins68 polymorphism presented high frequency in oral cavity (p < 0.05) and patients with the polymorphism presented less survival time (p < 0.05). CONCLUSIONS: We concluded that the CBS 844ins68 polymorphism is not associated with HNSCC risk and there is increased risk of this disease in male gender individuals smokers aged over 50 years. In adittion, the polymorphism is more frequent in patients with oral cavity as primary site and in patients with less survival time.

The maspin expression in canine mammary tumors: an immunohistochemical and molecular study / A expressão do maspin nos tumores mamários caninos: um estudo imuno-histoquímico e molecular

The serpin maspin, a tumor suppressor in breast cancer was described as an inhibitor of cell migration and inducer of cell adhesion between the basement membrane and extracellular matrix resulting in inhibition of tumor metastasis. In contrast, overexpression of maspin is correlated with poor prognosis in other types of cancer. Little is known about expression, regulation and function of maspin in canine mammary tumors. It was demonstrated in this study, a loss of maspin expression in malignant canine mammary cells compared with a pool of normal canine mammary tissue, analyzed by quantitative real-time PCR; weak maspin expression in malignant canine mammary tumors were observed by immunohistochemistry. It was also demonstrated that a correlation with nuclear maspin expression and a good prognosis. It is suggested that maspin could be used as a prognostic marker in canine mammary neoplasia.

O serpin maspin, um supressor tumoral no câncer de mama foi descrito como inibidor de migração celular e indutor de adesão celular entre a membrana basal e a matriz extracelular resultando na inibição da metástase tumoral. Por outro lado, a alta expressão do maspin está relacionada com um mau prognóstico em outros tipos de câncer. Pouco se sabe sobre a expressão, regulação e função do maspin nos tumores mamários caninos. Neste estudo, foi demonstrada uma perda da expressão de maspin nas células mamárias malignas de cães quando comparadas com um pool de tecido mamário normal de cães, analisado por PCR quantitativa em tempo real. Houve uma expressão fraca maspin em preparações de tumores mamários malignos observadas por imuno-histoquímica. Também foi verificado que a expressão nuclear do maspin em tumores mamários caninos está relacionada a um bom prognóstico. Assim, o maspin pode ser utilizado como um marcador prognóstico nas neoplasias mamárias em cães.

Associação do polimorfismo 936C>T do gene do Fator de Crescimento Endotelial Vascular (VEGF) com a Doença Arterial Coronariana / Association between VEGF 936C>T Polymorphism and Vascular Endothelial Growth Factor (VEGF) with Coronary Artery Disease

Introdução: O gene que codifica o fator de crescimento endotelial vascular (VEGF) tem sido investigado no desenvolvimento de doenças coronárias. Estudos apontam para um efeito protetor do VEGF no desenvolvimento da placa aterosclerótica, atuando como regulador da integridade endotelial vascular. O polimorfismo 936C>T do gene VEGF está associado com redução da síntese da proteína e parece desempenhar um importante papel no desenvolvimento da doença arterial coronariana (DAC). Objetivo: Investigar a relação entre o polimorfismo VEGF e presença, extensão e gravidade da DAC. Casuística e Métodos: Foram incluídos no estudo 50 pacientes com DAC confirmada por angiografia coronária e 50 indivíduos controles sem sinais angiográficos da doença. A genotipagem do polimorfismo VEGF 936C>T foi realizada por Reação em cadeia da polimerase, seguida de digestão enzimática. As análises estatísticas foram feitas por meio de teste Qui-quadrado, Teste exato de Fisher, Teste t e Regressão logística. Resultados: Tabagismo e Diabetes Mellitus (DM) foram mais freqüentes nos pacientes em relação aos controles (P = 0,015 e P = 0,013,respectivamente). As freqüências do alelo polimórfico foram 0,11 no grupo de pacientes e 0,17 no grupo controle (P = 0,308). A distribuição genotípica não diferiu significantemente entre os grupos (P = 0,397). Os genótipos VEGF 936C>T não foram associados ao número de vasos obstruídos (P = 0,452) ou grau deobstrução arterial (P = 0,681). Conclusão: O polimorfismo 936C>T do gene VEGF não apresentou associação com a DAC ou com a severidade da obstrução coronariana.

Introduction: The gene encoding vascular endothelial growth factor (VEGF) has been investigated in coronary artery disease progression. Studies point out protector effect of VEGF on atherosclerotic plaque development, playing regulating role of vascular endothelial integrity. The polymorphism VEGF 936C>T is associated with reduction of the protein synthesis, and could have an important role in coronary artery disease (CAD)development. Objective: To investigate the relationship between the VEGF 936C>T polymorphism and the presence, extension, and severity of CAD. Casuistics and Methods: Fifty patients with CAD confirme dangiographically, and 50 individuals without angiographic signs of the disease were included in the study. The genotyping of the VEGF 936C>T polymorphism was conducted by Polymerase chain reaction followed by enzyme digestion. Statistical analyses were performed by Chi-square, Exact Fisher test, Test t and Logistic regression. Results: Smoking and Diabetes Mellitus (DM) were frequent in patients compared to the controls(P = 0.015 and P = 0.013, respectively). The frequencies of the polymorphic allele were 0.11 in the CAD group and 0.17 in the control group (P = 0.308). Genotype distribution did not differ significantly between the groups (P = 0.397). The genotypes VEGF 936C>T were not associated to the number of blocked vessels (P= 0.452), or degree of arterial obstruction (P = 0.681). Conclusion: The polymorphism 936C>T of the VEGF gene did not present association with CAD or with severity of the coronary obstruction.

Identification of dysregulated genes in lymphocytes from children with Down syndrome.

The molecular mechanisms by which trisomy of human chromosome 21 disrupts normal development are not well understood. Global transcriptome studies attempting to analyze the consequences of trisomy in Down syndrome (DS) tissues have reported conflicting results, which have led to the suggestion that the analysis of specific tissues or cell types may be more productive. In the present study, we set out to analyze global changes of gene expression in lymphocytes from children with trisomy 21 by means of the serial analysis of gene expression (SAGE) methodology. Two SAGE libraries were constructed using pooled RNA of normal and Down syndrome children. Comparison between DS and normal profiles revealed that most of the transcripts were expressed at similar levels and functional classes of abundant genes were equally represented. Among the 242 significantly differentially expressed SAGE tags, several transcripts downregulated in DS code for proteins involved in T-cell and B-cell receptor signaling (e.g., PI3Kdelta, RGS2, LY6E, FOS, TAGAP, CD46). The SAGE data and interindividual variability were validated by real-time quantitative PCR. Our results indicate that trisomy 21 induces a modest dysregulation of disomic genes that may be related to the immunological perturbations seen in DS.

Estresse oxidativo e disfunção crônica do enxerto renal / Oxidative stress and renal cChronic aAllograft dDysfunction

A doença renal crônica (DRC) pode ser considerada um problema mundial de saúde pública e o transplante(Tx) renal é a melhor opção terapêutica e de reabilitação para pacientes com DRC em estágio terminal.Entretanto, a perda progressiva da função do Tx em conseqüência da disfunção crônica do enxerto (DCE) ainda constitui um sério problema sem terapêutica específica, constituindo a principal causa de falência desses Tx. Na presente revisão visamos mostrar o papel do estresse oxidativo (formação de Espécies Reativasde Oxigênio - EROs) na DCE, bem como o papel e a possível correlação entre as enzimas do grupo das glutationas.

Análise imunocitoquímica do padrão celular de neurofibromas em neurofibromatose tipo 1 (NF1) / Immunocytochemistry analysis of neurofibroma cell patterns in neurofibromatosis type 1 (NF1)

Neurofibromas múltiplos são as mais importantes características da NF1, uma das desordens genéticas autos-sômicas dominantes mais freqüentes no ser humano. Analisaram-se biópsias de 25 pacientes acometidos porNF1, investigando-se as variações no padrão celular dos diferentes neurofibromas, por meio de marcadores imunocitoquímicos para células de origem neuroectodérmica: S-100, GFAP e Ck35. As células dos neurofibro-mas mostraram-se positivas para S-100 (++++), GFAP (++) e Ck35 (+). Não houve diferenças no padrão de imunopositividade entre os diferentes tipos de neurofibromas do mesmo paciente (diferença focal heterotópica), assim como no mesmo tipo de neurofibroma entre os diferentes pacientes (variação individual)

Avaliação e características do erro médico na região de São José do Rio Preto / Evaluation and characteristics of medical errors in the region of São José do Rio Preto

O erro médico é o resultado adverso decorrente de ação inadequada ou omissão do profissional médico e pode ocorrer de três maneiras principais: imprudência, imperícia e negligência. Estudos epidemiológicos sobre o erro médico são escassos em todo o mundo, especialmente no Brasil e o assunto ainda é pouco abordado no currículo das escolas de medicina, embora amplamente divulgado pela mídia. o objetivo deste trabalho foi avaliar as características dos processos referentes a erro médico instaurados no Conselho Regional de Medicina do Estado de São Paulo - Delegacia Regional de São José do Preto (CREMESP-RP) e dos profissionais médicos a eles relacionados, no período de 1995 a 2000. A pesquisa foi elaborada usando-se uma planilha com os seguintes dados: tipo e resolução do processo, idade, sexo e especialidade do profissinal. Foram instaurados 41 processos no CREMESP-RP, envolvendo 61 médicos, 47 homens e 14 mulheres, com idade entre 40 e 65 anos. As razões mais frequentes dos processos foram relacionadas às condutas ético profissional (n=15) e negligência, imperícia, imprudência (n=6). As principais especialidades envolvidas foram Ortopedia e Traumatologia (n=14) e Cirurgia Geral (n=7). Conclui-se que os processos de erro médico foram mais frequentes nas especialidades cirúrgicas