Vigilância de fatores de risco para doenças não transmissíveis entre adolescentes: a experiência da cidade do Rio de Janeiro, Brasil

Este trabalho apresenta métodos e resultados da implantação de sistema de vigilância de fatores de risco para doenças não transmissíveis entre adolescentes. Uma amostra (n = 1.699) probabilística de alunos de oitava série do ensino fundamental da rede pública municipal de ensino do Rio de Janeiro, Brasil, respondeu a questionário autopreenchido anônimo sobre consumo alimentar, atividade física, atividades sedentárias de lazer e consumo de cigarro. Estimativas de prevalência dos fatores de risco foram calculadas para o total da amostra e segundo sexo. Taxas de não resposta variaram de 0,2% a 13,4%. Foram observados: baixo consumo de frutas (45,8%) e hortaliças (20% e 16,5% para saladas e legumes cozidos), consumo freqüente de refrigerantes (36,7%), balas e doces (46,7%), grande quantidade de horas alocadas em frente à TV, computador ou videogame (71,7% alocam pelo menos 4h/dia nestas atividades), baixa freqüência de prática regular de atividade física (40%) e prevalência de 6,4% de fumantes. Meninas apresentaram menores índices de atividade física e maiores de consumo de cigarro. O sistema testado mostrou-se factível e indicou prevalências relevantes de fatores de risco para doenças não transmissíveis.

Rastreamento anterior para câncer de colo uterino em mulheres com alterações citológicas ou histológicas

OBJETIVO: Analisar a história de rastreamento citológico anterior em mulheres que apresentaram alterações citológicas e confirmação histológica para câncer cervical. MÉTODOS: Estudo transversal com 5.485 mulheres (15-65 anos) que se submeteram a rastreamento para o câncer cervical entre fevereiro de 2002 a março de 2003, em São Paulo e Campinas, SP. Aplicou-se questionário comportamental e foi feita a coleta da citologia oncológica convencional ou em base líquida. Para as participantes com alterações citológicas indicou-se colposcopia e, nos casos anormais, procedeu-se à biópsia cervical. Para investigar a associação entre as variáveis qualitativas e o resultado da citologia, utilizou-se o teste de qui-quadrado de Pearson com nível de significância de 5%. RESULTADOS: Dentre os resultados citológicos, 354 (6,4%) foram anormais, detectando-se 41 lesões intra-epitelial escamosa de alto grau e três carcinomas; em 92,6% revelaram-se normais. De 289 colposcopias realizadas, 145 (50,2%) apresentaram alterações. Dentre as biópsias cervicais foram encontrados 14 casos de neoplasia intra-epitelial cervical grau 3 e quatro carcinomas. Referiram ter realizado exame citológico prévio: 100% das mulheres com citologia compatível com carcinoma, 97,6% das que apresentaram lesões intra-epiteliais de alto grau, 100% daquelas com confirmação histológica de carcinoma cervical, e 92,9% das mulheres com neoplasia intra-epitelial cervical grau 3. A realização de citologia anterior em período inferior a três anos foi referida, respectivamente, por 86,5% e 92,8% dessas participantes com alterações citológicas e histológicas. CONCLUSÕES: Entre as mulheres que apresentaram confirmação histológica de neoplasia intra-epitelial cervical grau 3 ou carcinoma e aquelas que não apresentaram alterações histológicas não houve diferença estatisticamente significante do número de exames citológicos realizados, bem como o tempo do último exame citológico anterior.

Irrompimento do primeiro molar permanente em crianças de 5 e 6 anos de idade: implicações da análise longitudinal para prevenção da cárie oclusal

O tempo de irrompimento dentário é essencial para o planejamento de medidas de prevenção da cárie oclusal. Com a ampliação do ensino fundamental de oito para nove anos de duração, um número maior de crianças entre cinco e seis anos de idade é incluído na primeira série do ensino fundamental. OBJETIVO: O objetivo foi estimar as tendências do irrompimento dos primeiros molares permanentes em meninos e meninas de 5 e 6 anos de idade. MÉTODOS: Em estudo longitudinal, espaços dentários de 497 crianças de 60 meses e mais de idade foram examinados quatro vezes por um dentista calibrado (kappa > 0,97) durante 18 meses. O primeiro molar permanente foi considerado irrompido quando qualquer parte de sua superfície podia ser tocada por uma sonda de ponta esférica. A idade dos participantes foi medida em meses. Intervalos para 95% de confiança dos valores de prevalência e incidência foram apurados conforme o sexo para três coortes etárias: 60,0 a 65,9; 66,0 a 71,9; 72,0 a 77,9 meses. A razão entre as taxas de incidência foi estimada por meio de análise de regressão de Poisson. RESULTADOS: A maioria das crianças entre 66,0 e 71,9 meses e entre 72,0 e 77,9 meses tem pelo menos um molar permanente irrompido. No grupo de 66,0 a 71,9 meses, de cada três crianças pelo menos uma apresentou os quatro primeiros molares permanentes irrompidos. CONCLUSÃO. As tendências de irrompimento observadas justificam a necessidade da adoção de medidas de vigilância e de proteção específica em relação à lesão de cárie oclusal.

Consumo e comportamento alimentar entre adolescentes brasileiros: Pesquisa Nacional de Saúde do Escolar (PeNSE), 2009

O objetivo deste artigo é descrever características de consumo e comportamento alimentar de adolescentes brasileiros e sua associação com fatores sociodemográficos. Estudou-se, em 2009, amostra representativa de alunos do 9º ano do ensino fundamental de escolas públicas e privadas das 26 capitais brasileiras e do Distrito Federal. Utilizou-se questionário autoaplicável sobre atributos sociodemográficos, consumo e comportamento alimentar, entre outros. Estimativas dos indicadores construídos foram apresentadas para o total da população e por sexo. A associação de cada um dos indicadores com variáveis sociodemográficas foi examinada por meio de regressão logística. A maioria dos adolescentes consumia regularmente feijão (62,6%), leite (53,6%) e guloseimas (50,9%), realizava pelo menos o almoço ou o jantar com a mãe ou responsável (62,6%) e comia assistindo televisão ou estudando (50,9%). Em geral, as meninas estavam mais expostas a práticas alimentares não desejáveis, e o melhor nível socioeconômico associou-se a maiores prevalências dos indicadores estudados. Os resultados revelaram consumo regular dos marcadores de alimentação não saudável e consumo inferior ao recomendado dos de alimentação saudável, apontando a necessidade de ações de promoção de saúde dirigidas a jovens.

Prevalência e fatores associados ao tabagismo em escolares da Região Sul do Brasil

OBJETIVO: Estimar a prevalência do tabagismo em estudantes e os fatores associados.MÉTODOS: Foram utilizados dados secundários, provenientes do inquérito Vigescola realizado em Curitiba (PR), Florianópolis (SC) e Porto Alegre (RS) em 2002 e 2004. A amostra compreendeu 3.690 escolares de 13 a 15 anos, cursando as sétima e oitava séries do ensino fundamental e primeira do ensino médio, em escolas públicas e privadas. Para a análise dos resultados foram estimadas proporções ponderadas, odds ratio (OR), e utilizada a técnica de regressão logística múltipla.RESULTADOS: As taxas de prevalência de tabagismo corresponderam a 10,7 por cento (IC 95 por cento: 10,2;11,3) em Florianópolis, 12,6 por cento (IC 95 por cento: 12,4;12,9) em Curitiba e 17,7 por cento (IC 95 por cento: 17,4;18,0) em Porto Alegre. Os fatores associados ao tabagismo em escolares em Curitiba foram: sexo feminino (OR=1,49), pai fumante (OR=1,59), amigos fumantes (OR=3,46), exposição à fumaça do tabaco fora de casa (OR=3,26) e possuir algum objeto com logotipo de marca de cigarro (OR=3,29). Em Florianópolis, as variáveis associadas ao tabagismo foram escolares do sexo feminino (OR=1,26), ter amigos fumantes (OR=9,31), exposição à fumaça do tabaco em casa (OR=2,03) e fora de casa (OR=1,45) e ter visto propaganda em cartazes (OR=1,82). Em Porto Alegre, as variáveis que estiveram associadas com o uso de tabaco pelos escolares foram sexo feminino (OR=1,57), idade entre 14 anos (OR=1,77) e 15 anos (OR=2,89), amigos fumantes (OR=9,12), exposição à fumaça do tabaco em casa (OR=1,87) e fora de casa (OR=1,77) e possuir algo com logotipo de marca de cigarro (OR=2,83).CONCLUSÕES: Há elevada prevalência de tabagismo entre escolares de 13 a 15 anos, cujos fatores significativamente associados comuns às três capitais são: ter amigos fumantes e estar exposto à fumaça ambiental fora de casa

Prevalência do HPV em mulheres rastreadas para o câncer cervical

OBJETIVO: Analisar a prevalência da infecção genital por papilomavírus humano (HPV) de alto risco por faixa etária e fatores associados. MÉTODOS: Estudo transversal com amostra de 2.300 mulheres (15-65 anos) que buscaram rastreamento para o câncer cervical entre fevereiro de 2002 e março de 2003 em São Paulo e Campinas, estado de São Paulo. Aplicou-se questionário epidemiológico e realizou-se coleta cervical para citologia oncológica e teste de captura híbrida II. As análises estatísticas empregadas foram teste de qui-quadrado de Pearson e análise multivariada pelo método forward likelihood ratio. RESULTADOS: A prevalência total da infecção genital por HPV de alto risco foi de 17,8%, distribuída nas faixas etárias: 27,1% (<25 anos), 21,3% (25-34 anos), 12,1% (35-44 anos), 12,0% (45-54 anos) e de 13,9% (55-65 anos). Participantes com maior número de parceiros sexuais durante a vida apresentaram maior freqüência da infecção. Relacionamento estável, idade de 35 a 44 anos e ex-fumantes foram associados à proteção da infecção. A infecção genital por HPV de alto risco ocorreu em 14,3% das citologias normais, em 77,8% das lesões escamosas de alto grau e nos dois (100%) casos de carcinoma. CONCLUSÕES: A prevalência da infecção genital por HPV de alto risco na amostra estudada foi alta. Houve predomínio de casos abaixo dos 25 anos e tendência a um novo aumento após os 55 anos, com maior freqüência naqueles com maior número de parceiros sexuais durante a vida

Gene expression relationship between prostate cancer cells of Gleason 3, 4 and normal epithelial cells as revealed by cell type-specific transcriptomes

Background: Prostate cancer cells in primary tumors have been typed CD10(-)/CD13(-)/CD24(hi)/CD26(+)/CD38(lo)/CD44(-)/CD104(-). This CD phenotype suggests a lineage relationship between cancer cells and luminal cells. The Gleason grade of tumors is a descriptive of tumor glandular differentiation. Higher Gleason scores are associated with treatment failure. Methods: CD26(+) cancer cells were isolated from Gleason 3+3 (G3) and Gleason 4+4 (G4) tumors by cell sorting, and their gene expression or transcriptome was determined by Affymetrix DNA array analysis. Dataset analysis was used to determine gene expression similarities and differences between G3 and G4 as well as to prostate cancer cell lines and histologically normal prostate luminal cells. Results: The G3 and G4 transcriptomes were compared to those of prostatic cell types of non-cancer, which included luminal, basal, stromal fibromuscular, and endothelial. A principal components analysis of the various transcriptome datasets indicated a closer relationship between luminal and G3 than luminal and G4. Dataset comparison also showed that the cancer transcriptomes differed substantially from those of prostate cancer cell lines. Conclusions: Genes differentially expressed in cancer are potential biomarkers for cancer detection, and those differentially expressed between G3 and G4 are potential biomarkers for disease stratification given that G4 cancer is associated with poor outcomes. Differentially expressed genes likely contribute to the prostate cancer phenotype and constitute the signatures of these particular cancer cell types.

Evaluation of the Incidence of Bladder Perforation After Transurethral Bladder Tumor Resection in a Residency Setting

Purpose: To evaluate prospectively the actual bladder perforation incidence during transurethral resection of bladder tumor (TURB) performed by residents and to identify possible predisposing factors to such condition. Patients and Methods: Thirty-four patients with bladder tumor were submitted to TURB in our academic institution in April 2006, and were prospectively studied. Procedures were all done by senior residents under an attending direct supervision. All patients had a cystograms performed after the procedure by the injection of 400 mL of saline-diluted contrast solution with low-pressure infusion through the Foley catheter. The cystograms were evaluated blindly by a single radiologist. All patients were examined by cystoscopy and/or CT every 3 months for the first 2 years postoperatively. Results: The cystogram showed contrast leaking compatible with bladder perforation in 17 (50%) cases. None of the perforations were recognized intraoperatively by the surgeon. All perforations were extraperitoneal and managed conservatively. There was no significant correlation between the incidence of bladder perforation and the patient age (p = 0.508), the tumor stage (p = 0.998), the tumor grade (p = 0.833), the number of lesions (p = 0.394), and the tumor size (p = 0.651). The only factor that had impact on the development of bladder perforation was tumor localization at the bottom of the bladder (p = 0.035; OR, 6750; 95% CI, 1.14, 39.8). Conclusion: Asymptomatic perforations of the bladder wall occur very frequently after a TURB procedure performed by residents in training and, most of the time, are not noticed by the surgeon. Localization of the tumor at bladder dome was the only factor that negatively influenced perforation rates.

Five-year follow-up of angiographic disease progression after medicine, angioplasty, or surgery

Background: Progression of atherosclerosis in coronary artery disease is observed through consecutive angiograms. Prognosis of this progression in patients randomized to different treatments has not been established. This study compared progression of coronary artery disease in native coronary arteries in patients undergoing surgery, angioplasty, or medical treatment. Methods: Patients (611) with stable multivessel coronary artery disease and preserved ventricular function were randomly assigned to CABG, PCI, or medical treatment alone (MT). After 5-year follow-up, 392 patients (64%) underwent new angiography. Progression was considered a new stenosis of >= 50% in an arterial segment previously considered normal or an increased grade of previous stenosis > 20% in nontreated vessels. Results: Of the 392 patients, 136 underwent CABG, 146 PCI, and 110 MT. Baseline characteristics were similar among treatment groups, except for more smokers and statin users in the MT group, more hypertensives and lower LDL-cholesterol levels in the CABG group, and more angina in the PCI group at study entry. Analysis showed greater progression in at least one native vessel in PCI patients (84%) compared with CABG (57%) and MT (74%) patients (p < 0.001). LAD coronary territory had higher progression compared with LCX and RCA (P < 0.001). PCI treatment, hypertension, male sex, and previous MI were independent risk factors for progression. No statistical difference existed between coronary events and the development of progression. Conclusion: The angioplasty treatment conferred greater progression in native coronary arteries, especially in the left anterior descending territories and treated vessels. The progression was independently associated with hypertension, male sex, and previous myocardial infarction.

The Ultrastructural Study of Tumorigenic Cells Using Nanobiomarkers

Despite recent advances, patients with malignant brain tumors still have a poor prognosis. Glioblastoma (WHO grade 4 astrocytoma), the most malignant brain tumor, represents 50% of all astrocytomas, with a median survival rate of <1 year. It is, therefore, extremely important to search for new diagnostic and therapeutic approaches for patients with glioblastoma. This study describes the application of superparamagnetic nano-particles of iron oxide, as well as monoclonal antibodies, of immunophenotypic significance, conjoined to quantum dots for the ultrastructural assessment of glioblastoma cells. For this proposal, an immunophenotypic study by flow cytometry was carried out, followed by transmission electron microscopy analysis. The process of tumor cell labeling using nanoparticles can successfully contribute to the identification of tumorigenic cells and consequently for better understanding of glioblastoma genesis and recurrence. In addition, this method may help further studies in tumor imaging, diagnosis, and prognostic markers detection.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and high plasma homocysteine in chronic hepatitis C (CHC) infected patients from the Northeast of Brazil

Background/Aim: Hyperhomocysteinemia due to Methylenetetrahydrofolate Reductase (MTHFR) gene, in particular the C677T (Ala222Val) polymorphism were recently associated to steatosis and fibrosis. We analyzed the frequency of MTHFR gene in a cross-sectional study of patients affected by Chronic Hepatitis C (CHC) from Northeast of Brazil. Method: One hundred seven-four untreated patients with CHC were genotyped for the C677T MTHFR. Genomic DNA was extracted from peripheral blood cells and the C677T MTHFR polymorphism was identified by PCR-RFLP. The homocysteine (Hcy) levels were determined by chemiluminescence method. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and have current and past daily alcohol intake less than 100 g/week. Results: Among subjects infected with CHC genotype non-1 the frequency of MTHFR genotypes TT was 9.8% versus 4.4% genotype 1 (p = 0.01). Nevertheless, association was found between the MTHFR genotype TT x CT/CC polymorphism and the degree of steatosis and fibrosis in both hepatitis C genotype (p < 0.05). A significant difference was found on plasma Hcy levels in patients with steatosis regardless of HCV genotype (p = 0.03). Conclusion: Our results indicate that plasma Hcy levels is highly prevalent in subjects with chronic hepatits C with steatosis regardless of HCV genotype and vitamin deficiency. The presence of genotype TT of MTHFR C677T polymorphism was more common in CHC genotype non-1 infected patient regardless of histopathological classification and genotype TT+CT frequencies were significant in the presence of fibrosis grade 1+2 and of steatosis in CHC infected patients from the northeast of Brazil regardless of HCV genotype. The genetic susceptibility of MTHFR C677T polymorphism should be confirmed in a large population.

Mucin pattern reflects the origin of the adenocarcinoma in Barrett's esophagus: a retrospective clinical and laboratorial study

Background: Mucin immunoexpression in adenocarcinoma arising in Barrett's esophagus (BE) may indicate the carcinogenesis pathway. The aim of this study was to evaluate resected specimens of adenocarcinoma in BE for the pattern of mucins and to correlate to the histologic classification. Methods: Specimens were retrospectively collected from thirteen patients who underwent esophageal resection due to adenocarcinoma in BE. Sections were scored for the grade of intestinal metaplasia. The tissues were examined by immunohistochemistry for MUC2 and MUC5AC antibodies. Results: Eleven patients were men. The mean age was 61 years old (varied from 40 to 75 years old). The tumor size had a mean of 4.7 +/- 2.3 cm, and the extension of BE had a mean of 7.7 +/- 1.5 cm. Specialized epithelium with intestinal metaplasia was present in all adjacent mucosas. Immunohistochemistry for MUC2 showed immunoreactivity in goblet cells, while MUC5AC was extensively expressed in the columnar gastric cells, localizing to the surface epithelium and extending to a variable degree into the glandular structures in BE. Tumors were classified according to the mucins in gastric type in 7/13 (MUC5AC positive) and intestinal type in 4/13 (MUC2 positive). Two tumors did not express MUC2 or MUC5AC proteins. The pattern of mucin predominantly expressed in the adjacent epithelium was associated to the mucin expression profile in the tumors, p = 0.047. Conclusion: Barrett's esophagus adenocarcinoma shows either gastric or intestinal type pattern of mucin expression. The two types of tumors developed in Barrett's esophagus may reflect the original cell type involved in the malignant transformation.

Activation of Neural and Pluripotent Stem Cell Signatures Correlates with Increased Malignancy in Human Glioma

The presence of stem cell characteristics in glioma cells raises the possibility that mechanisms promoting the maintenance and self-renewal of tissue specific stem cells have a similar function in tumor cells. Here we characterized human gliomas of various malignancy grades for the expression of stem cell regulatory proteins. We show that cells in high grade glioma co-express an array of markers defining neural stem cells (NSCs) and that these proteins can fulfill similar functions in tumor cells as in NSCs. However, in contrast to NSCs glioma cells co-express neural proteins together with pluripotent stem cell markers, including the transcription factors Oct4, Sox2, Nanog and Klf4. In line with this finding, in high grade gliomas mesodermal-and endodermal-specific transcription factors were detected together with neural proteins, a combination of lineage markers not normally present in the central nervous system. Persistent presence of pluripotent stem cell traits could only be detected in solid tumors, and observations based on in vitro studies and xenograft transplantations in mice imply that this presence is dependent on the combined activity of intrinsic and extrinsic regulatory cues. Together these results demonstrate a general deregulated expression of neural and pluripotent stem cell traits in malignant human gliomas, and indicate that stem cell regulatory factors may provide significant targets for therapeutic strategies.

Interleukin-10 production by tumor infiltrating macrophages plays a role in Human Papillomavirus 16 tumor growth

Background: Human Papillomavirus, HPV, is the main etiological factor for cervical cancer. Different studies show that in women infected with HPV there is a positive correlation between lesion grade and number of infiltrating macrophages, as well as with IL-10 higher expression. Using a HPV16 associated tumor model in mice, TC-1, our laboratory has demonstrated that tumor infiltrating macrophages are M2-like, induce T cell regulatory phenotype and play an important role in tumor growth. M2 macrophages secrete several cytokines, among them IL-10, which has been shown to play a role in T cell suppression by tumor macrophages in other tumor models. In this work, we sought to establish if IL-10 is part of the mechanism by which HPV tumor associated macrophages induce T cell regulatory phenotype, inhibiting anti-tumor activity and facilitating tumor growth. Results: TC-1 tumor cells do not express or respond to IL-10, but recruit leukocytes which, within the tumor environment, produce this cytokine. Using IL-10 deficient mice or blocking IL-10 signaling with neutralizing antibodies, we observed a significant reduction in tumor growth, an increase in tumor infiltration by HPV16 E7 specific CD8 lymphocytes, including a population positive for Granzyme B and Perforin expression, and a decrease in the percentage of HPV specific regulatory T cells in the lymph nodes. Conclusions: Our data shows that in the HPV16 TC-1 tumor mouse model, IL-10 produced by tumor macrophages induce regulatory phenotype on T cells, an immune escape mechanism that facilitates tumor growth. Our results point to a possible mechanism behind the epidemiologic data that correlates higher IL-10 expression with risk of cervical cancer development in HPV infected women.

Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas

Background: Glioblastoma is the most lethal primary malignant brain tumor. Although considerable progress has been made in the treatment of this aggressive tumor, the clinical outcome for patients remains poor. Histone deacetylases (HDACs) are recognized as promising targets for cancer treatment. In the past several years, HDAC inhibitors (HDACis) have been used as radiosensitizers in glioblastoma treatment. However, no study has demonstrated the status of global HDAC expression in gliomas and its possible correlation to the use of HDACis. The purpose of this study was to evaluate and compare mRNA and protein levels of class I, II and IV of HDACs in low grade and high grade astrocytomas and normal brain tissue and to correlate the findings with the malignancy in astrocytomas. Methods: Forty-three microdissected patient tumor samples were evaluated. The histopathologic diagnoses were 20 low-grade gliomas (13 grade I and 7 grade II) and 23 high-grade gliomas (5 grade III and 18 glioblastomas). Eleven normal cerebral tissue samples were also analyzed (54 total samples analyzed). mRNA expression of class I, II, and IV HDACs was studied by quantitative real-time polymerase chain reaction and normalized to the housekeeping gene beta-glucuronidase. Protein levels were evaluated by western blotting. Results: We found that mRNA levels of class II and IV HDACs were downregulated in glioblastomas compared to low-grade astrocytomas and normal brain tissue (7 in 8 genes, p < 0.05). The protein levels of class II HDAC9 were also lower in high-grade astrocytomas than in low-grade astrocytomas and normal brain tissue. Additionally, we found that histone H3 (but not histone H4) was more acetylated in glioblastomas than normal brain tissue. Conclusion: Our study establishes a negative correlation between HDAC gene expression and the glioma grade suggesting that class II and IV HDACs might play an important role in glioma malignancy. Evaluation of histone acetylation levels showed that histone H3 is more acetylated in glioblastomas than normal brain tissue confirming the downregulation of HDAC mRNA in glioblastomas.