Orientador: Agnaldo Lopes da Silva Filho / Resumo: O câncer do colo uterino mantém altas taxas de incidência e mortalidade no Brasil, apesar do Programa Viva Mulher ter ampliado muito o acesso ao teste de Papanicolaou. O rastreamento desta neoplasia através do exame citológico foi responsável por redução significativa da sua ocorrência em países desenvolvidos, que monitoram a qualidade deste método em todos os passos que envolvem sua realização. Entretanto, essa realidade não é observada regularmente nos países em desenvolvimento. Partindo desta constatação, esse trabalho tem como foco as análises da visão do patologista brasileiro sobre o exame citológico e de critérios médicos necessários para melhorar a qualidade do rastreamento. Para tanto, foi realizado estudo descritivo observacional constituído por uma análise qualitativa reunindo entrevistas com patologistas, e pela aplicação de um questionário aos patologistas brasileiros, com perguntas sobre a estrutura de serviços que realizam exames citológicos no país. Os resultados evidenciaram claramente a preocupação deste profissional com seu afastamento do programa de rastreamento e com a necessidade de um controle de qualidade mais criterioso. Também foi observada uma crítica relação entre as falhas do rastreamento citológico, a atuação do patologista e a estrutura dos serviços responsáveis por este exame. Assim, o estudo identificou a imperativa necessidade de educação continuada dos profissionais responsáveis pelo exame citológico do colo uterino, além da implementação de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The uterine cervix's cancer maintains high rates of incidence and mortality in Brazil, despite of the fact that the Programa Viva Mulher have expanded the access to the Papanicolaou’s test. The screening of this neoplasm by the cytological test was responsible for a significant reduction of events in developed countries, which have well stablished quality control systems. However, this reality cannot be seen in developing countries. Therefore, this study focuses on the analysis of the Brazilian pathologist's view of the cytological test and the medical criteria needed to improve the quality of screening. For this reason, a descriptive observational study was conducted, including a qualitative analysis with interviews with pathologists and the application of a questionnaire, about the structure of services that perform cytological examinations in the country. The results clearly showed the concern of this professional with your gradative removal from the screening program, and the need for a more careful quality control. A critical relationship was also observed between the failures of cytological screening, the performance of the pathologist and the structure of the services responsible for this exam. In this way, the study identified the imperative need for continued education of the professionals responsible for cervical cytological examination, in addition to the implementation of a comprehensive and judicious external quality control. / Doutor

Aim The burden of cervical cancer in Sri Lanka is high and research is limited. The objective was to describe the knowledge of Human Papilloma Virus (HPV), cervical cancer and its cytological screening, as well as worry of HPV and attitudes towards and practices of screening among undergraduate students at Rajarata University of Sri Lanka, Mihintale. Methods A cross-sectional study was conducted in January 2015 at Rajarata University, using a self-administrated questionnaire containing socio-demographics, knowledge, attitudes and practices (KAP). Male and female undergraduates, 18-30 years, were eligible. Knowledge was assessed by a numerical sum score ranging from 0 to 13, with 13 as maximum. Analyses were performed using ANOVA or Kruskal-Wallis tests. Results 326 students answered the questionnaire that revealed limited knowledge on cervical cancer, HPV and screening, with a mean score of 5.34 (SD 3.33). Knowledge was higher among older, medical students in the fifth year, however there was a high correlation between these variables. Knowledge was lower among management students. Most students were uncertain about the questions in the attitude section. A majority of students would be worried if they got infected with HPV. Screening practices were low (0.45 %). Approximately half of the women would consider cytological screening in the future. Conclusion The limited knowledge, low screening practices and high worry imply a need for information and awareness programs. Further research is needed in order to fully understand the delicacy of this public health threat for Sri Lankan women.

Hund, bakterieller/ zytologischer Konjunktivalstatus, Konjunktivitis, Klinikaufenthalt

Made available in DSpace on 2014-10-09T12:52:55Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:03:50Z (GMT). No. of bitstreams: 0 / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Made available in DSpace on 2014-12-17T14:10:17Z (GMT). No. of bitstreams: 1 ErmetonDN.pdf: 732618 bytes, checksum: 6b2f580e4b65ea3ec17c1996913b4a02 (MD5) Previous issue date: 2008-12-05 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The Human Papillomavirus (HPV) infection is the major sexually transmitted disease all over the world. There are many factors associated to infection and the virus persistency in the organism. This study aims to evaluate the women's knowledge, attitudes and practice about the Papanicolaou test (Pap), as well as analyze the HPV and Chlamydia trachomatis infections prevalences in sexually active women from the city of S?o Jos? do Mipibu/RN/Brazil. This research was divided in two steps (step I and step II), using different methodologies and samples each. The samples collected in each step, even socio-demographic or from uterus cervix, are from different patients e were analyzed separated. In step I was evaluated 267 rural and urban zone women s knowledge, attitudes and practices about the Pap by home interview. In the step II were included 605 women with age ranged from 15 to 71 years old, with mean of 33,5 years old and from each one were collected two cervical samples, one for Pap and other for molecular biology, beside the epidemiological interview to investigate the correlation between prevalence of HPV infection and risk factors. To molecular analyses, the samples were processed using a mammal rapid DNA extraction technique protocol. For C. trachomatis DNA detection were used the CP24/27 primers, and GP5+/GP6+ to HPV. PCR products were analyzed by electrophoresis on 8% polyacrylamide gels, followed by silver staining. The results of the step I showed that, in spite of only 46,1% of the interviewed women they have demonstrated to possess appropriate knowledge on the Pap test, the attitude and practice proportions were significantly larger, 63,3% and 64,4% respectively. The largest education degree presented association with adaptation of the knowledge, attitudes and practice, while neglect, lack of solicitation of the exam for the doctor and shame, came as main barriers for the accomplishment of the exam. In the stage II the HPV general prevalence was 28,9%, being 26,7% in the women with normal cytology or benign alterations, 26,7% in the ones that had atypical squamous cells of undetermined significance (ASC-US) and 80% in those with Low grade squamous intraepithelial lesion (LSIL). the HPV infection prevalence was larger in the patients with up to 30 years of age and in the unmarried women, and those that had more than one sexual partner presented larger infection risk. The results show that the sexual relationship with multiple partners increased the infection risk for HPV and consequently the possibility of the occurrence of lesions uterine cervix / O v?rus do papiloma humano (HPV) representa um dos principais agentes sexualmente transmiss?veis entre as popula??es humanas de todo o mundo. V?rios fatores est?o associados ? infec??o e a persist?ncia desse v?rus no organismo. A infec??o produtiva pelo HPV resulta em altera??es no epit?lio da c?rvice uterina que podem evoluir para les?es de diferentes graus inclusive as malignas. Tais les?es podem ser visualizadas atrav?s do exame citol?gico de Papanicolaou (Pap), que apesar de simples, tem alto valor como teste de triagem na preven??o do c?ncer de colo do ?tero. Este estudo constou de duas etapas, com metodologias e abordagens distintas. O material coletado em cada etapa, sejam dados s?cio-demogr?ficos ou esp?cimes da c?rvice uterina para an?lise, foram obtidas de pacientes diferentes e foram analisados separadamente. Na etapa I, avaliou-se o conhecimento, a atitude e a pr?tica das mulheres em rela??o ao Pap por meio de entrevistas domiciliares de 267 mulheres das zonas rural e urbana do munic?pio de S?o Jos? do Mipibu, utilizando question?rio estruturado. Na etapa II, foram inclu?das 605 mulheres com idade variando de 15 a 71 anos, media de 33,5 anos das quais foram coletados dois esp?cimes cervicais, sendo um para o exame citol?gico e o outro para an?lise molecular. Um question?rio epidemiol?gico foi utilizado para obter informa??es, visando identificar fatores de risco associados ? infec??o. Para a an?lise molecular as amostras foram processadas utilizando protocolo de extra??o r?pida de DNA de mam?feros. Para detec??o do DNA da C. trachomatis e do HPV foi utilizada a t?cnica de PCR com os iniciadores CP24/27, e GP5+/GP6+ respectivamente. Os produtos de PCR foram submetidos ? eletroforese em gel de poliacrilamida e corados pela prata. Do total de mulheres analisadas na etapa I apenas 46,1% demonstram possuir conhecimento adequado sobre o teste de Pap. As propor??es de atitude e pr?tica adequadas foram significativamente maiores, 63,3% e 64,4% respectivamente. As mulheres com maior grau de escolaridade apresentaram melhores ?ndices de adequa??o dos conhecimentos, atitudes e pr?tica. O descuido, a falta de solicita??o do exame pelo m?dico e a vergonha, se apresentaram como principais barreiras para a realiza??o do exame. Na etapa II encontrou-se uma preval?ncia geral do HPV de 28,9%, sendo 26,7% nas mulheres com citologia normal ou altera??es benignas, sendo 26,7% as que tinham atipia de c?lula escamosa de significado indeterminado (ASC-US) e 80% naquelas com les?o intraepitelial escamosa de baixo grau (LSIL). A preval?ncia da infec??o pelo HPV foi maior nas pacientes com at? 30 anos de idade, nas solteiras, e naquelas que tiveram mais de um parceiro sexual e estas apresentaram maior risco de aquisi??o da infec??o pelo HPV e para o desenvolvimento de les?es da c?rvice uterina

Made available in DSpace on 2014-10-09T12:52:55Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:03:50Z (GMT). No. of bitstreams: 0 / Um dos objetivos da pesquisa em Biomateriais é o desenvolvimento de dispositivos que auxiliem a regeneração óssea. Duas cerâmicas sintéticas têm sido largamente utilizadas: a hidroxiapatita (HAp) e o beta fosfato tricálcico (b- TCP). Em muitas situações é desejável que a velocidade de absorção desses materiais pelo organismo seja compatível com a velocidade de crescimento ósseo, e nesses casos, o emprego da mistura dessas duas fases mostra-se vantajoso. A absorção e o crescimento ósseo são processos fisiológicos complexos, afetados, entre outras coisas, pela resposta inflamatória da região cirúrgica. Assim, uma resposta inflamatória exacerbada é potencialmente danosa, já que pode induzir a um aumento no estresse oxidativo devido à produção de radicais livres. O ataque dos radicais livres causa, entre outros efeitos danosos, a degeneração da membrana celular, que pode acarretar necrose e/ou apoptose das células da região cirúrgica. Neste trabalho, duas cerâmicas foram implantadas em fêmures de ratos: b-TCP ou a mistura bifásica 60:40% em massa de HAp:b-TCP. O crescimento ósseo foi avaliado por microscopia ótica e de fluorescência, utilizando marcadores ósseos fluorescentes. Além disso, avaliou-se o efeito da presença de um complexo vitamínico, moderador do processo inflamatório. Concluiu-se que o b-TCP puro foi mais absorvido quando comparado a mistura b-TCP-HAp, e encontram-se indícios de que a presença do composto vitamínico mediou de forma favorável a neoformação óssea. / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

O presente estudo teve como objetivos avaliar a sensibilidade, a especificidade e a acurácia da Punção Aspirativa por Agulha Fina (PAAF) em nódulos submucosos da cavidade bucal e da região de cabeça e pescoço como ferramenta auxiliar de diagnóstico. Foram selecionados 50 pacientes consecutivamente que procuraram a Clínica da Disciplina de Estomatologia Clínica da FOUSP, portadores de lesões em boca e em região de cabeça e pescoço. O material obtido pela PAAF foi enviado a um mesmo patologista apenas com o diagnóstico clínico e após a emissão do laudo da PAAF o laudo do anátomo patológico era emitido servindo como padrão ouro. Após os cálculos, o resultado da sensibilidade foi de 75%, a especificidade foi de 96%, a acurácia foi de 58,8%, o valor preditivo positivo foi de 86% e o valor preditivo negativo foi de 93%. A significância foi estabelecida para 5% e o teste usado foi o teste de Kappa com valor de P<0,001 e um teste qui-quadrado, com valor de P=0,788. Pela análise dos resultados a PAAF teve uma alta sensibilidade para identificar lesões malignas, uma alta especificidade para identificar lesões benignas e uma baixa acurácia para se obter um diagnóstico definitivo. / The objectives of this present study are to evaluate the sensitivity, specificity and accuracy of Fine Needle Aspiration Biopsy (FNAB) in submucous nodules of oral cavity and nodules of head and neck region as an auxiliary tool of diagnoses. 50 patients that looked for the Clinic of the Discipline of Oral Stomatology of FOUSP were consecutively selected, carrying lesions in the oral cavity and the head and neck region. The material obtained by FNA was sent to only one pathologist with the clinical diagnosis and after the emission of FNAB report the biopsy report was emitted serving as the gold standard. After the calculation, the results of sensibility was 75%, the specificity was 96%, the accuracy was 58,8%, the positive predict value was 86% and the negative predict value was 93%. The significance was established for 5% and the tests used was Kappa with P<0,001 and a Chi-square with a P value of 0,778.With the results analysis the FNAB had a high sensibility to identify malignant lesions, a high specificity to identify benign lesions and a low accuracy to obtain final diagnoses.

A conservative strategy for women with a low-grade abnormal cervical smear is continued cytological surveillance by repeat Papinacolaou testing, but there is surprisingly little information on the management of such follow-up. Our objectives were to investigate such management pathways, their determinants, and psychological implications using data from the cytological surveillance arm of the Trial of Management of Borderline and Other Low-grade Abnormal cervical smears. A substantial proportion of participants had ongoing unresolved cytology at last follow-up (42.7%); a policy of following women solely though cytological surveillance to manage these women may be inefficient. A high-risk human papillomavirus test, smoking and age were significantly associated with the management pathways (p-value <0.05). While there were some limitations, our results were reassuring with respect to this group of women with ongoing unresolved cytology, since there were no differences in anxiety and depression scores across the management pathways after thirty months of follow-up.

The natural resources offer a unique opportunity for the discovery of active compounds, due to the complexity and biodiversity of their chemical structures. Natural resources have been used as medicines throughout human history. Saudi Arabia’s natural resources, for instance its terrestrial medicinal plants and the Red Sea sponges, have not been extensively investigated with regard to their biological activities. To better identify the diversity of compounds with bioactive potential, new techniques are also necessary in order to improve the drug discovery path. This study comprises three sections. The first section examines Juniperus phoenicea (Arar), Anastatica hierochuntica (Kaff Maryam) and Citrullus colocynthis (Hanzal); these herbal plants were screened for potential bioactivity using a newly developed pipeline based on a high-content screening technique. We report a new cell-based high-throughput phenotypic screening for the bio-prospecting of unknown natural products from Saudi Arabian plants, in order to reveal their biological activities. The second section investigates Avicennia marina plants, screened for reverse transcriptase anti-HIV bioactivity using biochemical assay. Image-based high-content screening with a set of cellular stains was used to investigate the phenotypic results of toxicity and cell cycle arrest. The third section considers the isolation of Actinomycetes from Red Sea Sponges. Actinomycetes bacterial isolates were tested for bioactivity against West Nile Virus NS3 Protease. Analytical chemical techniques such as liquid chromatography–mass spectrometry (LC-MS), gas chromatography–mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) were used to gain more understanding of the possible chemical compounds responsible for this bioactivity. Overall, the aim of this work is to investigate the potential bioactive effect of several Saudi Arabian plants and Red Sea sponges against cancer cells and viral infections. Our study demonstrates the efficiency of the newly developed pipeline using cell-based phenotypic screening. Anti-cancer potential activity was detected in Juniperus phoenicea. Bioactive potential against the reverse transcriptase enzyme of HIV virus was confirmed in Avicennia marina leaves. The organic extracts of Actinomycetes bacterial isolates were found active against West Nile Virus NS3 Protease. Here, promising starting point for the potential of drug discovery of plants and marine organism of Saudi Arabia.

Anthracycline-based chemotherapy is the mainstay neoadjuvant therapy for breast cancer. However, it is efficacious in only 60% of patients while carrying substantial toxicity. The application of a predictive marker of response may spare predicted ‘poor responders’ from the toxicity. Previously, we demonstrated a gene expression signature that predicts chemotherapy resistance which is linked to TP53 integrity. Further investigation showed that p53 signatures predict response in only ER+ tumors. We hypothesized that the loss of p53 confers an elevated chemotherapy sensitivity in ER+ breast tumors. We engineered isogenic p53 mutant ER+ breast cancer cell lines and assayed their cell cycle kinetics and chemotherapy sensitivity. Our results demonstrated that the loss of p53 is necessary to abrogate p53-mediated cell cycle arrest and produce an increase in apoptosis. Therefore, p53 signatures may be utilized as a predictive marker of response for patients with ER+ breast tumor and spare ‘poor responders’ from toxicity. Since ER+ p53 wild-type breast tumors are associated with anthracycline resistance, new anticancer drugs against that subgroup of tumors are needed. Phenotypic drug screening approach, which do not focus on isolated targets but instead classify compounds by their impact on cell physiology, is highly suitable for this purpose. Current cell-based phenotypic assays require fixation and staining for phenotypic markers, which reduce screen throughput and introduce potential variations and artifacts. Here we describe a high-content live-cell phenotypic assay, which streamlines the process of cytological profiling and provides a consistent platform for empirically evaluating drug action. Importantly, when combined with chemical similarity clustering, the phenotypic assay provided an inference of structure-activity relationships. Finally, a small-scale phenotypic screen of natural products enabled classification of unknown compounds against the cytological profiles of commercial compounds. Hence, the phenotypic screen provides a new and robust opportunity for accelerating the evaluation of compound activity during high-throughput drug screens. / Thesis / Master of Science (MSc)