RESUMEN
O Programa de Monitoramento da Qualidade da Água Tratada para Diálise integra a agenda de saúde do estado de São Paulo e tem como objetivo avaliar,sistematicamente, a qualidade da água necessária ao tratamento dialítico, uma vez que a Insuficiência Renal Crônica representa um dos maiores problemas de Saúde Pública da atualidade. Dados preliminares sobre as análises das amostras de água para diálise, coletadas no último trimestre de 2007, revelaram que os resultadosnão foram satisfatórios em 100% dos serviços. Atualmente, o Programa, encontrase implantado em todoo Estado e aponta resultados, que embora não representem100% do universo dos serviços dialíticos, retrata, de maneira significativa, a melhoria do padrão de qualidade da água em conformidade aos parâmetros preconizados pela Resolução RDC nº 154/2004. No ano 2007, foram colhidas amostras de água tratada em 69 serviços sediados na Capital e Grande São Paulo,sendo que 49% estavam em desacordo. No ano 2008, o foco de atenção foi o Interior do Estado e Grande São Paulo, onde foram colhidas amostras em 104 serviços, cujosresultados favoráveis foram da ordem de 68%. Esses resultados refletem osesforços dos técnicos das vigilâncias sanitárias, estadual e municipais, que em conjunt com o trabalho desenvolvido pelo Instituto Adolfo Lutz (IAL) vem atendendo as expectativas do Programa, sinalizando que é possível e factível minimizar os riscos potenciais no tratamento dialítico
Asunto(s)
Enfermedades Renales , Enfermedades Renales/terapia , Calidad del AguaRESUMEN
O Programa de Terapia Renal Substitutiva (TRS) integra a agenda de saúde do Estado de São Paulo por tratar-se de área prioritária dentre as políticas de saúde, face ao aumento progressivo da incidência e da prevalência da doença renal crônica, a cada ano. O custo elevado para manter pacientes em TRS tem sido motivo de grande preocupação por parte de órgãos governamentais. Práticas baseadas em evidências científicas mostram um número relevante de complicações agudas decorrentes do tratamento dialítico que utiliza água, fundamental para a terapia, com padrões bacteriológicos e físico-quimicos inadequados, que levam a intoxicações por metais e reações adversas. O Programa de Monitoramento da Qualidade da Água Tratada para Diálise teve início no Estado de São Paulo em dezembro de 1999. Dados preliminares sobre as análises das amostras de água para diálise, coletadas no último trimestre de 2007, revelaram que os resultados não foram satisfatórios em 100% dos serviços, o que reforça a necessidade de implementação de medidas de controle de riscos para salvaguardar o padrão de qualidade da água seja ela proveniente do abastecimento público ou de fontes alternativas , em conformidade com a legislação vigente. No último trimestre de 2007, foram treinados 47 técnicos de vigilância sanitária dos âmbitos estadual e municipal, que atuam diretamente no segmento de diálise. Esses técnicos coletaram 156 amostras de água para análise dos 52 serviços cadastrados na VS da Capital e Grande São Paulo.
Asunto(s)
Microbiología del Agua , Insuficiencia Renal Crónica , Calidad del AguaRESUMEN
A common goal of microarray experiments is to detect genes that are differentially expressed under distinct experimental conditions. Several statistical tests have been proposed to determine whether the observed changes in gene expression are significant. The t-test assigns a score to each gene on the basis of changes in its expression relative to its estimated variability, in such a way that genes with a higher score (in absolute values) are more likely to be significant. Most variants of the t-test use the complete set of genes to influence the variance estimate for each single gene. However, no inference is made in terms of the variability itself. Here, we highlight the problem of low observed variances in the t-test, when genes with relatively small changes are declared differentially expressed. Alternatively, the z-test could be used although, unlike the t-test, it can declare differentially expressed genes with high observed variances. To overcome this, we propose to combine the z-test, which focuses on large changes, with a chi(2) test to evaluate variability. We call this procedure CLEAR-test and we provide a combined p-value that offers a compromise between both aspects. Analysis of three publicly available microarray datasets reveals the greater performance of the CLEAR-test relative to the t-test and alternative methods. Finally, empirical and simulated data analyses demonstrate the greater reproducibility and statistical power of the CLEAR-test and z-test with respect to current alternative methods. In addition, the CLEAR-test improves the z-test by capturing reproducible genes with high variability.
Asunto(s)
Algoritmos , Interpretación Estadística de Datos , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica/fisiología , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Proteoma/metabolismo , Transducción de Señal/fisiología , Inteligencia ArtificialRESUMEN
The advent of various 'omic' technologies has increased expectations in the field of biomarkers. In an attempt to clarify how different strategies may contribute to improving prognostic classification and to identify new predictors of patient outcome we analyzed genomic and transcriptomic profiles in a series of R0 Dukes B and C colorectal carcinomas. We have compared the predictive capability of each approach against conventional clinicopathological and molecular parameters. At a genomic level, gains at 11q including amplification at 11q13 were an indicator of poorer outcome. In transcriptomic analyses we identified 68 genes whose expression levels correlated with survival (p<0.01) and included overexpression of WASF1, NFE2L2, and MMP9, and underexpression of ITGAL, TSC2, and SDF2. Gene expression levels paralleled chromosomal changes only in 56% of the genes, suggesting that, as a general trend, the direct effect of chromosomal copy number changes on gene expression levels is minimal. Classification of tumors by genomic and transcriptomic signatures resulted in non-overlapping subgroups and was not of prognostic value. We conclude that genomic and transcriptomic profiling of colorectal carcinomas may contribute as novel prognostic markers, but it does not improve outcome prediction when global profiles or signatures are considered.
Asunto(s)
Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Genoma Humano , Proteoma , Transcripción Genética , Mapeo Cromosómico , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Genoma , Humanos , Masculino , Hibridación de Ácido Nucleico , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: The applicability of microarray-based transcriptome massive analysis is often limited by the need for large amounts of high-quality RNA. RNA arbitrarily primed PCR (RAP-PCR) is an unbiased fingerprinting PCR technique that reduces both the amount of initial material needed and the complexity of the transcriptome. The aim of this study was to evaluate the feasibility of using hybridization of RAP-PCR products as transcriptome representations to analyze differential gene expression in a microarray platform. METHODS: RAP-PCR products obtained from samples with limited availability of biological material, such as experimental metastases, were hybridized to conventional cDNA microarrays. We performed replicates of self-self hybridizations of RAP-PCR products and mathematical modeling to assess reproducibility and sources of variation. RESULTS: Gene/slide interaction (47.3%) and the PCR reaction (33.8%) accounted for the majority of the variability. From these observations, we designed a protocol using two pools of three independent RAP-PCR reactions coming from two independent reverse transcription reactions hybridized in duplicate and evaluated them in the analyses of paired xenograft-metastases samples. Using this approach, we found that HER2 and MMP7 may be down-regulated during distal dissemination of colorectal tumors. CONCLUSION: RAP-PCR glass array hybridization can be used for transcriptome analysis of small samples.
Asunto(s)
ADN Complementario/química , Perfilación de la Expresión Génica/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Sondas ARN/química , Acetiltransferasas/biosíntesis , Acetiltransferasas/genética , Animales , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Estudios de Factibilidad , Vidrio , Histona Acetiltransferasas , Humanos , Metaloproteinasa 7 de la Matriz , Metaloendopeptidasas/biosíntesis , Metaloendopeptidasas/genética , Ratones , Ratones Desnudos , Modelos Químicos , Metástasis de la Neoplasia , Hibridación de Ácido Nucleico , Receptor ErbB-2/biosíntesis , Receptor ErbB-2/genética , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trasplante HeterólogoRESUMEN
Cancer cells progress through the accumulation of genetic alterations. Familial adenomatous polyposis (FAP) tumors provide an excellent model to unravel the molecular steps underlying malignant transformation. Global genomic damage was assessed in 56 adenomas and 3 carcinomas from six FAP patients and compared with that of sporadic adenomas and carcinomas. Evolutive trees were traced after application of maximum likelihood clustering and split decomposition methods to the analysis of comprehensive genetic profiles generated by diverse molecular approaches: arbitrarily primed PCR, comparative genomic hybridization, and flow cytometry. Overall, genomic damage as assessed by arbitrarily primed PCR was lower in familial adenomas than in sporadic adenomas and carcinomas. Comparative genomic hybridization data also show a low number of alterations in the majority of FAP adenomas. Tumors of the same patient were likely to share specific genetic alterations and may be grouped into one or two clusters. Putative common pathways were also identified, which included tumors of up to three different patients. According to our data, FAP tumors accumulate specific genetic alterations and in a preferred order that is characteristic of each individual. Moreover, the particular genetic background and environmental conditions of a FAP patient restrain the molecular evolution portrait of synchronous tumors.