Orientador: Luiz Carlos Zeferino / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-22T21:06:24Z (GMT). No. of bitstreams: 1 Vale_DiamaBhadraAndradePeixotodo_D.pdf: 2458866 bytes, checksum: 5cf40849bf3e978225063c3bfedc7aea (MD5) Previous issue date: 2013 / Resumo: INTRODUÇÃO: O exame citológico ainda é o método de rastreamento mais utilizado para a prevenção do câncer do colo do útero. Apesar da sua alta eficiência na prevenção do carcinoma escamoso invasivo, esses benefícios não são tão claros para as lesões escamosas em mulheres jovens e para o adenocarcinoma invasivo. Além disso, esse efeito protetor varia de acordo com o intervalo de realização dos controles. Uma vez que o teste de HPV não é recomendado para mulheres com menos de 30 anos de idade, a avaliação cuidadosa do desempenho do rastreamento neste grupo etário pode auxiliar os médicos a selecionar criteriosamente aquelas que irão ser encaminhadas para prosseguimento diagnóstico. OBJETIVO: Avaliar o impacto do rastreamento do câncer do colo do útero na prevalência dos resultados citológicos em função da idade da mulher e do intervalo entre os controles. MÉTODOS: Foi analisado o banco de dados de um laboratório central de citopatologia. O estudo incluiu 2.002.472 testes obtidos de mulheres previamente rastreadas e 217.826 testes obtidos de mulheres não previamente rastreadas. A Razão de Prevalência (RP) com um intervalo de confiança de 95% foi calculada para os resultados de testes de mulheres rastreadas em relação aos testes de mulheres não rastreadas, em função da idade. O laboratório utiliza o Sistema de Bethesda desde 1998, mas ainda subdivide o resultado Lesão Intraepitelial de Alto Grau (HSIL) em dois níveis: HSIL-CIN 2 e HSIL-CIN 3. RESULTADOS Para HSIL, a RP dos testes de mulheres rastreadas em relação aos testes de mulheres não rastreadas foi de 0,97 (0,83-1,13) em mulheres abaixo de 20 anos e 0,99 (0,86-1,14) para mulheres entre 20 e 24 anos, diminuindo significativamente em mulheres entre 25 e 29 anos (RP 0,63, 0,52-0,76). As RP para o carcinoma espinocelular (SCC), adenocarcinoma in situ (AIS) e adenocarcinoma invasivo apresentaram uma redução significativa em todos os grupos etários acima de 30 anos. Para o grupo etário 30 a 59 anos, a proteção conferida pelo rastreamento para SCC, AIS e adenocarcinoma invasivo foi de 83% ou mais, para intervalos de realização dos exames entre 1 e 5 anos. Para mais de cinco anos de intervalo, o efeito protetor oferecido para SCC foi de 50%. Nas mulheres não previamente rastreadas, a prevalência de lesões intraepiteliais de baixo grau (LSIL) e HSIL-CIN 2 diminuíram com a idade, enquanto que para HSIL-CIN 3 a prevalência aumentou. Ainda nesse grupo de testes, a prevalência de HSIL-CIN 2 foi maior do que a de HSIL-CIN 3 para mulheres de até 29 anos (RP = 4,73, 3,90-5,75) e mais baixa para os grupos de 30 a 49 anos (RP = 0,66, 0,50-0,87) e 50 anos ou mais (RP = 0.21,0.12-0.36). No grupo de testes de mulheres rastreadas, a prevalência de HSIL-CIN 2 foi maior nas faixas etárias até 29 anos (RP = 2,72, 2,49-2,97). CONCLUSÕES O rastreamento citológico reduziu a prevalência dos diagnósticos citológicos de HSIL, CEC, AIS e adenocarcinoma invasivo. Um intervalo de 3 anos para a realização dos controles foi apropriado para reduzir os resultados citológicos. O perfil da prevalência de HSIL-CIN 2 se assemelha ao padrão de prevalência de LSIL e foi mais prevalente do que HSIL-CIN 3 em mulheres jovens. O impacto do rastreamento foi menos evidente quando HSIL foi sugestivo de CIN 2. O rastreamento citológico em mulheres abaixo de 25 anos deve ser criteriosamente avaliado / Abstract: BACKGROUND Cervical cytology still is the cervical cancer screening test for women more used. Even though there is no doubt about the impact of cytology screening on invasive squamous cervical cancer, this issue is not as clear for squamous lesions on young women and for invasive adenocarcinoma. Moreover this protective effect varies according to interval tests. HPV testing is not recommended for women under age 30, and the carefully analysis of the performance of screening on this age group can help physicians to qualify their approach. OBJECTIVE To evaluate the impact of cervical cytology screening on the prevalence of cervical cytological results in women, as a function of age and the interval between tests. METHODS A central cytopathology laboratory database for cervical screening was analyzed. It included cytology screening data of 2.002.472 tests obtained from previously screened women and 217.826 tests from unscreened women. A prevalence ratio (PR) with a 95% confidence interval for screened women was calculated, in relation to unscreened women, as a function of age. The laboratory has been using the Bethesda System since 1998, but maintain the sub-categorization of HSIL in two levels: HSIL-CIN 2 and HSIL-CIN 3. RESULTS For high-grade squamous intraepithelial lesion (HSIL), the PR was 0.97 (0.83-1.13) for women aged 20 or younger and 0.99 (0.86-1.14) for women aged 20-24 years, decreasing significantly in women aged 25-29 years (PR 0.63, 0.52-0.76). The PR for squamous cell carcinoma (SCC), adenocarcinoma in situ (AIS) and invasive adenocarcinoma showed a significant reduction in all age groups over 30 years. For the age group ranging from 30-59 years, protection conferred by screening for SCC, AIS and invasive adenocarcinoma was 83% or higher for screening intervals ranging from 1-5 years. For 5-year intervals or longer, the protective effect offered for SCC was 50%. For unscreened women, the prevalence of Low Grade Intraepithelial Lesions (LSIL) and HSIL-CIN 2 decreased with age, whereas HSIL-CIN 3 prevalence increased. The prevalence of HSIL-CIN 2 was higher than that of HSIL-CIN 3 for women up to 29 years (PR=4.73, 3.90-5.75) and lower for age groups 30-49 years (PR=0.66, 0.50-0.87) and 50 years or more (PR=0.21,0.12-0.36). For screened women, the prevalence of HSIL-CIN 2 was also higher in age groups up to 29 years (PR=2.72, 2.49-2.97). CONCLUSIONS Cytology screening reduced the prevalence of HSIL, SCC, AIS and invasive adenocarcinoma cytological results. A three-year interval was appropriate for the reduction of these lesions. HSIL-CIN 2 resembles the prevalence pattern of LSIL and was more prevalent than HSIL-CIN 3 in younger women. The impact of screening was less evident when HSIL is suggestive of CIN 2. Cervical cytology screening in women 25 or younger should be critically evaluated / Doutorado / Oncologia Ginecológica e Mamária / Doutora em Ciências da Saúde

Orientador: Pablo Agustin Vargas / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-18T23:49:50Z (GMT). No. of bitstreams: 1 Ribeiro_AnaCarolinaPrado_D.pdf: 3258651 bytes, checksum: 970c0be7e5e81418de0473e4d576d304 (MD5) Previous issue date: 2011 / Resumo: A displasia fibrosa (DF) e o fibroma ossificante central (FOC) fazem parte de um grupo de lesões conhecido como fibro-ósseas benignas (LFOB) e afetam principalmente a maxila, a mandíbula e ossos da região craniofacial. Caracterizam-se pela substituição do tecido ósseo normal por uma matriz de tecido conjuntivo fibroso com níveis variados de material mineralizado. As DFs e os FOCs costumam apresentar características clínicas e histopatológicas similares, entretanto, possuem padrões distintos de progressão e comportamento biológico. Portanto é muito importante fazer a distinção diagnóstica entre estas lesões. Este trabalho teve como objetivos analisar e comparar as características demográficas, clínicas, imaginológicas e histopatológicas de pacientes diagnosticados com DFs e FOCs. Foi realizada uma análise retrospectiva internacional e multi-institucional que selecionou 68 casos de DF e 37 casos de FOC e permitiu o estudo de características clinicopatológicas. As DFs (n=41; 60,2%) e os FOCs (n=24; 64,9%) foram mais comuns em pacientes do gênero feminino na segunda e terceira década de vida. As DFs acometeram preferencialmente a maxila (n=38; 56%) e os FOCs a mandíbula (n=23; 62,2%). Com relação aos aspectos imaginológicos, as DFs apresentaram-se predominantemente como lesões radiopacas com limites mal definidos e os FOCs como lesões radiolúcidas bem delimitadas. Microscopicamente, foi possível evidenciar continuidade do osso lesional com a cortical óssea de revestimento nas DFs e, interessantemente, um fenômeno de separação entre as trabéculas ósseas lesionais e o estroma adjacente também foi evidente nas DFs. Nos FOCs, foi possível evidenciar a descontinuidade da lesão com a cortical óssea de revestimento externo e a presença de estruturas semelhante ao cemento. Em conclusão, o diagnóstico de DF e FOC deve ser realizado a partir da correlação das características clínicas, imaginológicas e histopatológicas. No entanto, foi possível observar algumas características peculiares em cada uma das lesões, o que poderá auxiliar o diagnóstico e consequentemente favorecer o tratamento dos pacientes acometidos por estas patologias ósseas / Abstract: Fibrous dysplasia (FD) and ossifying fibroma (OF) comprehend a group of benign fibro-osseous lesions (BFOL) which mainly affects the maxilla, mandible and craniofacial bones. They are characterized by the replacement of normal bone tissue by a matrix of fibrous connective tissue with varying degrees of mineralization. Both lesions frequently share clinical and microscopic features and the final diagnose require a combined analysis of clinical, radiologic and histological data. There might be significant cosmetic and functional impairment despite having a distinct pattern of progression and biological behavior, therefore, it is important to distinguish them from each other at the final diagnose. This research focused on the study and comparison of the demographic, clinical, imaging and microscopic aspects of patients with FD and OF, at the moment of the diagnostics. A retrospective multiinstitucional research was conducted in which there were 68 FD cases and 37 of OF. Characteristics such as gender, age and anatomic site of the tumor samples were obtained from the medical records. FDs (n=41; 60,2%) and OFs (n=24; 64,9%) were more frequently detected in female patients who were at the second or third decade of life. The maxilla was more prominently affected among the FD cases (n=38; 56%) contrasting to the prevalence of the mandible in the OF cases (n=23 62.2%). According to the radiographic aspects, FDs frequently presented as radiopaque lesions, with ill-defined limits, and OFs had well defined margins and were radiolucid. Microscopically, a continuity of the lesion with the bone cortical was evident in the FDs, as well as a separation phenomenon between the bone trabeculae and the surrounding connective tissue of the adjacent stroma. In OFs, the discontinuity of the lesion with the bone cortical was noticed, so were the presence of cement-like structures. In conclusion, the diagnose of FD and OF must be done based on the sum of the clinical, radiographic and microscopic features, although it was possible to observe a few peculiar characteristics in each one of them, which might serve as a diagnostic tool and therefore improve the treatment of the patients / Doutorado / Patologia / Doutor em Estomatopatologia

A displasia coxo-femoral tem sido descrita como moléstia de origem genética, caracterizada por incongruência articular, com alterações dos tecidos conectivos da articulação. Podendo afetar qualquer raça, é particularmente prevalente em raças grandes e gigantes e está apontada como a principal causa do desenvolvimento de osteoartrite em cães. Muitas técnicas são apontadas para o tratamento destes quadros, e novas pesquisas têm sido desenvolvidas no intuito de se obter técnicas mais eficazes e menos cruentas, diminuindo também o tempo de recuperação. Destas, a denervação da articulação coxo-femoral surge como técnica simples e eficaz que recupera a atividade funcional dos membros afetados em tempo significativamente menor em relação às demais. Esta técnica consiste em remoção do periósteo acetabular, eliminando as fibras nervosas sensitivas da região com conseqüente promoção da analgesia. Este estudo visou quantificar as fibras nervosas presentes na região descrita, relacionando a densidade encontrada com a técnica cirúrgica, na intenção de torná-la mais precisa e eficaz. Foram utilizados 30 acetábulos, provenientes de 15 cães, machos e fêmeas, com peso variando entre 22,0 Kg e 62,0 Kg. A dissecção macroscópica revelou simetria bilateral com variação individual da enervação regional, com ramos originados dos nervos glúteo cranial, isquiático e femoral. A enervação do periósteo acetabular foi estudada por método de impregnação pela prata e os resultados obtidos apontam uma diferença estatística significativa entre a densidade (fibras/mm2) da região crânio-lateral em relação à região caudo-lateral do acetábulo. Demonstraram ainda haver simetria entre os antímeros estudados. As fibras nervosas apresentam disposição quase vertical no periósteo acetabular, em direção à cápsual articular, o que sugere a densidade nervosa também presente na região. / Hip dysplasia has been described as a genetic disease, caracterized by articular incongruence with alterations in the articular connective tissues. It may affect all breeds, prevailing in large and very large ones and it is supposedly the main cause in the development of osteoarthrites in dogs. Many techniques are indicated for the treatment of this disease, and new researches are being developed in the meaning of obtaining more efficient and less traumatic techniques, keeping the post operative time as short as possible. Among these, the denervation of the hip joint capsule comes as a simple and effective technique, that recovers the functional activity of the affected limbs in significantly less time then the others. This surgical procedure consists in removing the acetabular periosteum, eliminating the nervous fibers with consequent analgesy This study tried to quantify the nervous fibers present in the mentioned region, relating the density found with the surgical technique, intending to make it more efficient. Thirty acetabular fragments, from 15 dogs, both male and female, weighting between 22,0 and 62,0 Kg, were used. Macroscopic dissection showed bilateral symmetry, with individual variation of regional innervation, and branches from the cranial gluteal, ischiaticus and femoral nerves. The acetabular periosteal innervation was studied by silver staining and the results showed a significatn difference between the nervous fiber density (fibers/mm2) of the cranial lateral portion and caudal lateral portions of the acetabulum. They also showed both antimeres are symmetric. Nervous fibers are positioned almost in a vertical position in the acetabular periosteum, running directed to the joint capsule, suggesting nervous density also in that region.

O letrozol é usado como terapêutico em desordens reprodutivas provocadas pelos altos níveis de estrógenos. A enzima citocromo P450 aromatase biossintetiza estrógenos a partir dos andrógenos em tecidos com capacidade esteroidogênica, como o cérebro, testículo e ovário. O objetivo do nosso estudo foi avaliar se o letrozol afeta o desenvolvimento das principais vias de controle reprodutivo de preás machos e fêmeas. Para tanto, consideramos o ganho de peso corporal, do testículo, do ovário e do cérebro, a progressão morfológica da espermatogênese e da foliculogênese, bem como a atividade enzimática da citocromo P450 aromatase nesses tecidos, comparado-os entre os grupos experimentais de machos e fêmeas. Os preás receberam 0,01 g/kg-1 de letrozol diluído, via oral, semanalmente, até as idades de 30, 45, 90 e 120 dias. O letrozol aumentou o ganho de peso corporal, das gônadas e do cérebro. Também, prejudicou a formação do epitélio germinativo testicular e estratificou o epitélio de revestimento do ovário. Ainda, o inibidor pode alterar os campos neurais relacionados às zonas de aromatização. E alterou os sítios de atuação da aromatase nas gônadas. Concluímos que o uso prolongado do letrozol pode ocasionar efeito anabólico, infertilidade de machos, induzir a displasia ovariana em fêmeas e alterar os sítios de atuação da aromatase. / Letrozole is used as a therapeutic in reproductive disorders caused by high estrogen levels. The enzyme cytochrome P450 aromatase biosynthesizes estrogens from androgens on tissues with steroidogenic capacity such as brain, testis and ovary. The objective of our study was to evaluate whether letrozole affects the development of the main reproductive control pathway of male and female spixs yellow-toothed cavy. For this, we considered body weight, testis, ovary and brain gain, spermatogenesis and folliculogenesis, as well as the enzymatic activity of cytochrome P450 aromatase in these tissues compared to experimental groups of males and females. The cavies received dilute letrozole orally (0,01 g/kg-1), once a week, until 30, 45, 90 and 120 days. Letrozole increased body weight, gonad and brain gain. Also, it impaired the formation of the testicular germinal epithelium and epithelium of ovary. Furthermore, the inhibitor may alter the neural fields related to the aromatization zones and changed the sites of aromatase in the gonads. We concluded that prolonged use of letrozole may result in an anabolic effect, male infertility, induce ovarian dysplasia in females, and alter the sites of aromatase activity.

The initiating events of ovarian cancer remain unknown, but an established risk factor is use of estrogen therapy by post-menopausal women where there is a positive correlation between duration of use and risk for disease. Mouse models of ovarian cancer have shown that exposure to exogenous 17β-estradiol (E2) accelerates tumour onset so this study aims to investigate the E2 signalling mechanisms responsible for sensitizing ovarian epithelial cells to transformation. By developing model systems that are responsive to E2 manipulation, we showed that E2 induces the formation of epithelial dysplasias both in vitro and in vivo. microRNA microarray was used to discover that E2 up-regulates microRNA-378 via the ESR1 pathway, resulting in the down-regulation of a tumour suppressor gene called Disabled-2 (Dab2). E2 suppression of Dab2 was found to result in increased proliferation, loss of contact inhibition, epithelial dysplasia, and increased sensitivity to transformation. This mechanism was also found to be active in mouse fallopian tube epithelium and human ovarian cancer cells. Single-cell RNA sequencing and trajectory analysis was subsequently used to explore additional signalling mechanisms that might contribute to the emergence of dysplastic lesions induced by E2. Multiple molecular signalling pathways dysregulated by E2 were identified and this revealed several possible biomarkers to be investigated for early detection of ovarian cancer. In the context of a current lack of strategies for ovarian cancer prevention or early detection, this work represents a significant advance in our understanding of how E2 promotes ovarian cancer initiation.

Diploma thesis "Interaction in multisystemic problems of bronchopulmonary dysplasia - effects of physiotherapy upon lung functions of immature infants" deals with relevant questions about care of immature newborns both during hospitalization at NICU and after discharge, inclusive of examination at Center for comprehensive care for risk newborns. Especially deals with possibilities of physiotherapy of newborns with bronchopulmonary dysplasia pathology and demonstrates the necessity of tight cooperation among physiotherapists, nurses and doctors during daily care of these children. Powered by TCPDF (www.tcpdf.org)

Introduction: Infants with Bronchopulmonary Dysplasia (BPD) are at higher risk of developing severe RSV Bronchiolitis requiring hospitalisation. Palivizumab Immunoprophylaxis (PIP) was shown to reduce the severity of illness and hence the need for hospitalisation. Currently PIP is recommended for all infants with BPD, but there is little evidence on which infants with BPD would most benefit from PIP. Aim: This study aims to identify the clinical benefit of administering PIP to infants with BPD of different severities and to determine which infants would benefit most from PIP. In order to achieve this, the study also identifies the incidence of BPD, categorised into mild, moderate and severe in infants, in the Greater Manchester Region (GMR).Methods: This is a multi-centre, prospective, observational cohort study, involving 11 hospitals across GMR. Patients were recruited over 2 years, from 1st April 2009 to 31st March 2011. The infants with BPD were recruited and further categorised in various severities, based on Jobe’s BPD classification [Jobe et al 2001]. Patients were followed up for a minimum of one year. Results: The incidence of BPD in the GMR was 5.9 infants per 1000 live births. On categorisation by level of severity, the study found 31% of these to have mild BPD, 39% moderate and 30% severe BPD. Around 60% of infants received PIP in our cohort: one third of mild group, two thirds of moderate and three quarters of severe BPD. The overall proportion of hospitalisation for all the respiratory illnesses in infants with BPD was 44%. The overall incidence of hospitalization secondary to RSV infection was 7.6% of the cohort, and 14.8% due to other respiratory viruses. PIP was most beneficial in infants with moderate BPD (p = 0.016). Infants hospitalised with RSV infection required more admissions to HDU, required a longer duration of supplemental oxygen as well as a longer hospital stay compared to infants hospitalised due to other respiratory viruses and all other respiratory illnesses. Conclusion: This is the first study identifying the incidence of BPD in the GMR, which was lower than expected based on estimates from the JCVI. Both, the distribution of BPD into the various severity categories, as well as the requirement of hospital admission secondary to respiratory illness, were in keeping with published evidence from the USA and UK. PIP practices across North West of England were varied and not compliant with JCVI guidelines. Infants with moderate BPD showed the largest benefit from receiving PIP. This is a novel finding that highlights the need for further research, to determine whether a subgroup of infants might benefit from PIP.

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京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18644号 / 医博第3943号 / 新制||医||1006(附属図書館) / 31558 / 京都大学大学院医学研究科医学専攻 / (主査)教授 河野 憲二, 教授 福山 秀直, 教授 渡邉 大 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Minority women groups in the United States have the highest incidence and mortality rates of cervical cancer. Hispanic women have the highest incidence rate and the second highest mortality rate of the disease. Researchers have examined the lower rates of cervical cancer screening among Hispanic women, as compared to other groups of U.S. women, but researchers have not examined the extent to which socioeconomic status, acculturation, and sexual activity impact Hispanic women's compliance with screening. The purpose of this study was to examine the association between compliance with cervical cancer screening and acculturation, socioeconomic status, and sexual activity among U.S. Hispanic women. The framework for investigating the extent of association between these identified barriers and willingness to comply with screening was the behavioral model for vulnerable populations. Chi-square tests and logistic regression were used to analyze data from the National Health Interview Survey for 2011, 2012, and 2013, focusing on U.S. Hispanic women ages 21 - 65 (N = 739). The findings from this study revealed that educational level was significantly associated with U.S. Hispanic women's cervical cancer screening; however, no statistically significant associations were found for socioeconomic status, acculturation, and sexual activity and screening rates for this group. Findings from this study can better inform researchers and others of the lower rate of screening for cervical cancer among U.S. Hispanic women. The findings will also promote positive social change by targeting U.S. Hispanic women and other minority women groups for programs that promote cervical cancer screening.