Estudo transversal, descritivo e exploratório, com abordagem metodológica qualitativa, cujo objetivo foi identificar e avaliar a percepção da vulnerabilidade à doença, entre mulheres com diagnóstico avançado do câncer do colo do útero, tendo como referencial teórico, a vulnerabilidade, baseada no conceito proposto por Ayres et al. (2003). Os sujeitos do estudo foram doze mulheres que estavam em atendimento no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, para tratamento do câncer do colo do útero avançado, entre 08 de abril e 28 de maio de 2009. Os dados foram coletados por entrevistas. A análise dos dados se deu segundo os pressupostos da análise de conteúdo, proposta por Bardin (2006). Os resultados revelaram-se em 2 categorias centrais: Percebendo-se vulnerável e Enfrentando a doença e o tratamento. A vulnerabilidade se apresentou para as participantes deste estudo a partir do aparecimento dos primeiros sinais e sintomas da doença, crescendo à medida que o diagnóstico foi descoberto e o tratamento se fez necessário, trazendo dificuldades e sofrimento. Ao mesmo tempo, proporcionou a oportunidade de as mulheres encontrarem formas de enfrentamento e superação dos problemas, à medida do possível. Os componentes individual, social e programático da vulnerabilidade, contidos no conceito proposto por Ayres et al. (2003), mostraram-se nos fatores relacionados à cliente, aos profissionais, aos serviços, entre outros, e tornaram a mulher suscetível aos problemas e danos de sua saúde, relativos ao câncer cérvico-uterino, exacerbando sua vulnerabilidade à doença. Ficou clara a necessidade de se superar algumas deficiências no modelo de assistência e na humanização do atendimento, no grau de compromisso e na qualidade das instituições, dos recursos, do gerenciamento e do monitoramento dos programas de prevenção e detecção do câncer do colo do útero, nos diferentes níveis de atenção. / This cross-sectional, descriptive, exploratory and qualitative study aimed to identify and evaluate the perception of the vulnerability to the disease among women with delayed diagnosis of uterine cervical cancer. The theoretical framework used was the vulnerability, based in the concept proposed by Ayres et al. (2003). The subjects of the study were twelve women who were under follow-up at the Hospital das Clínicas of the University of São Paulo at Ribeirão Preto Medical School, for treatment of advanced uterine cervical cancer, between April 08th and May 28th 2009. Data were collected by interviews. The data analysis was done according to the presuppositions of content analysis, proposed by Bardin (2006). Two central categories emerged from the results: Perceiving yourself vulnerable and Facing the disease and the treatment. The vulnerability arose to the participants of this study through the emergence of the first signs and symptoms of the disease, increasing as the diagnosis was determined and treatment was needed, bringing difficulties and suffering. At the same time, women had the opportunity to find ways to face and overcome problems, to the extent possible. The individual, social and programmatic compounds of the vulnerability, included in the concept proposed by Ayres et al. (2003), were shown in the factors related to clients, professionals and services, among others, and made the women susceptible to the problems and damages of their health, related to the uterine cervical cancer, aggravating their vulnerability to the disease. The need to overcome some deficiencies in the model of care and in the humanization of care was evidenced, as well as in the level of commitment and in the quality of the institutions, resources, management, and monitoring of the programs of prevention and detection of uterine cervical cancer, in the different levels of care.

Background: O câncer de colo uterino é um grande problema de saúde pública no Brasil e no mundo. Atinge cerca de meio milhão de mulheres, sendo que 50 % destas morrem. Os métodos visuais, alternativos á citologia e viáveis para países em desenvolvimento, têm sido avaliados mais intensamente na última década. Objetivos: Avaliar o desempenho da Fotografia Cervical Digital (FCD) na detecção do câncer do colo de útero e de suas lesões precursoras. Métodos: 176 mulheres foram avaliadas pelos métodos de Inspeção Visual com ácido acético (VIA), Inspeção Visual com lugol (VILI), Fotografia Cervical Digital com ácido acético (FCDA) e Fotografia Cervical Digital com lugol (FCDL). Destas, 36 foram classificadas pela histologia. Resultados: A concordância entre avaliadores observou valores de Kappa: Fotografia Cervical Digital com ácido acético, K=0,441, e Fotografia Cervical Digital com lugol, K=0,533. A concordância entre as inspeções a olho nu e as fotografias cervicais digitais após a utilização de ácido acético no colo uterino, K=0,559, e a concordância após a utilização da solução de lugol, K=0,507, considerada como concordância moderada em ambos os casos. Das 36 pacientes com avaliações histológicas, 20 dos 25 casos positivos foram corretamente avaliados tanto pela FCDA, como pela FCDL, demonstrando resultados similares aos descritos anteriormente. Conclusão: A FCD é um método promissor para o rastreamento do câncer de colo de útero e suas lesões precursoras, para países em desenvolvimento. / Background: Uterine cervix cancer is a major public health problem in Brazil and in the world. It affects half a million women with a death rate of 50%. The visual, alternative methods to cytology, considered viable for developing countries, are being assessed more intensively in the last decade. Objective: To evaluate the performance of Cervical Digital Photography (CDP) in detecting cervical cancer and its precursory lesions. Methods: A total of 176 women were evaluated by the following methods: Visual Inspection with Acetic Acid (VIA), Visual Inspection with Lugol’s Iodine (VILI), Cervical Digital Photography with Acetic Acid (CDPA) and Cervical Digital Photography with Lugol’s Iodine (CDPL). Among these, 36 were classified by histology. Results: The correlation between evaluators observed Kappa values: Cervical Digital Photography with acetic acid, K = 0.441, and Cervical Digital Photography with Lugol's Iodine, K = 0.533. The correlation between the naked eye and cervical digital photography inspection after using acetic acid in the uterine cervix, K = 0.559, and the correlation after using Lugol's Iodine solution, K = 0.507, were regarded as moderate in both cases. Of the 36 patients with histological evaluation, 20 of the 25 positive cases were correctly assessed both by the CDPA as well as by CDPL, showing similar results than those described previously. Conclusion: CDP is considered a more promising method for screening the uterine cervix cancer and its precursory lesions in developing countries.

Leung, Winnie. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 155-164). / Abstracts in English and Chinese. / Abstract --- p.i / 摘要 --- p.iii / Acknowledgements --- p.v / Table of Contents --- p.vi / List of Figures --- p.x / Abbreviations --- p.xii / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Clinical management of Cancer --- p.2 / Chapter 1.2 --- Multidrug resistance --- p.8 / Chapter 1.3 --- Aim of study --- p.14 / Chapter Chapter 2 --- Identification of gene contributing to multidrug resistance in human uterine sarcoma cells --- p.16 / Chapter 2.1 --- Introduction --- p.17 / Chapter 2.2 --- Material and Methods / Chapter 2.2.1 --- Materials / Chapter 2.2.1.1 --- Cell lines --- p.20 / Chapter 2.2.1.2 --- "Cell culture medium, supplements and buffers" --- p.20 / Chapter 2.2.1.3 --- Gene expression assay reagents --- p.22 / Chapter 2.2.1.4 --- Western blotting reagents --- p.24 / Chapter 2.2.1.5 --- MTT assay reagents --- p.29 / Chapter 2.2.1.6 --- Apoptosis analysis by flow cytometry reagents --- p.29 / Chapter 2.2.2 --- Metho --- p.ds / Chapter 2.2.2.1 --- Cell Culture --- p.31 / Chapter 2.2.2.2 --- MTT assay --- p.32 / Chapter 2.2.2.3 --- Gene expression essay (RT-PCR) --- p.33 / Chapter 2.2.2.4 --- Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of protein lysate and Western blotting --- p.37 / Chapter 2.2.2.5 --- Quantification of doxorubicin uptake by flow cytometry --- p.40 / Chapter 2.2.2.6 --- Apoptosis analysis by flow cytometry --- p.41 / Chapter 2.3 --- Results --- p.4 / Chapter 2.3.1 --- Cytotoxicity of doxorubicin on SA and DX5 cells --- p.43 / Chapter 2.3.2 --- mRNA expression of multidrug resistance related genes in SA and DX5 cells --- p.46 / Chapter 2.3.3 --- P-glycoprotein expression in SA and DX5 cells --- p.49 / Chapter 2.3.4 --- Doxorubicin (Dox) uptake by SA and DX5 cells --- p.51 / Chapter 2.3.5 --- Doxorubicin induced Apoptosis in SA and DX5 cells --- p.54 / Chapter 2.4 --- Discussion --- p.61 / Chapter 2.5 --- Conclusion --- p.65 / Chapter Chapter 3 --- Alternation in P-glycoprotein expression in DX5_Ninjl cells --- p.66 / Chapter 3.1 --- Introduction --- p.67 / Chapter 3.2 --- Materials and Methods / Chapter 3.2.1 --- Materials / Chapter 3.2.1.1 --- Cell lines --- p.70 / Chapter 3.2.1.2 --- "Cell culture medium, supplements and buffers" --- p.70 / Chapter 3.2.1.3 --- Gene expression assay reagents --- p.70 / Chapter 3.2.1.4 --- Western blotting reagents --- p.72 / Chapter 3.2.1.5 --- Plasmid DNA extraction --- p.75 / Chapter 3.2.1.6 --- Transient transfection --- p.76 / Chapter 3.2.1.7 --- MTT reagents --- p.76 / Chapter 3.2.2 --- Methods / Chapter 3.2.2.1 --- Cell culture --- p.78 / Chapter 3.2.2.2 --- Gene expression essay (RT-PCR) --- p.79 / Chapter 3.2.2.3 --- Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of protein lysate and Western blotting --- p.81 / Chapter 3.2.2.4 --- DNA plasmid extraction --- p.83 / Chapter 3.2.2.5 --- Transient transfection --- p.84 / Chapter 3.2.2.6 --- MTT assay --- p.85 / Chapter 3.2.2.7 --- Quantification of doxorubicin (Dox) uptake by flow cytometry --- p.86 / Chapter 3.3 --- Results / Chapter 3.3.1 --- mRNA expression of Ninjurinl (Ninj1) in SA and DX5 cells --- p.87 / Chapter 3.3.2 --- The protein expression of Ninjurinl (Ninj1) in SA and DX5 cells --- p.89 / Chapter 3.3.3 --- Ninjurin1 (Ninj1) cDNA transfection in DX5 cells --- p.91 / Chapter 3.3.4 --- mRNA expression of MDR1 in Ninjurin1-transfected DX5 cells (DX5_Ninjl) --- p.93 / Chapter 3.3.5 --- P-glycoprotein expression in Ninjurin1-transfected DX5 cells --- p.95 / Chapter 3.3.6 --- "Cytotoxicity of doxorubicin (Dox) on DX5 control, DX5 vector control and DX5_Ninjl cells" --- p.97 / Chapter 3.3.7 --- "Doxorubicin (Dox) uptake by SA control, DX5 control and DX5_Ninjl cells" --- p.99 / Chapter 3.4 --- Discussion --- p.102 / Chapter 3.5 --- Conclusion --- p.105 / Chapter Chapter 4 --- Alternation in MDR1 expression in DX5一THBS1 cells --- p.106 / Chapter 4.1 --- Introduction --- p.107 / Chapter 4.2 --- Materials and Methods / Chapter 4.2.1 --- Materials / Chapter 4.2.1.1 --- Cell lines --- p.109 / Chapter 4.2.1.2 --- Cell culture medium； supplements and buffers --- p.109 / Chapter 4.2.1.3 --- Gene expression assay reagents --- p.109 / Chapter 4.2.1.4 --- Western blotting reagents --- p.111 / Chapter 4.2.1.5 --- Plasmid DNA extraction --- p.114 / Chapter 4.2.1.6 --- Transient transfection --- p.115 / Chapter 4.2.1.7 --- MTT reagents --- p.115 / Chapter 4.2.2 --- Methods / Chapter 4.2.2.1 --- Cell culture --- p.117 / Chapter 4.2.2.2 --- Gene expression essay (RT-PCR) --- p.118 / Chapter 4.2.2.3 --- Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of protein lysate and Western blotting --- p.120 / Chapter 4.2.2.4 --- DNA plasmid extraction --- p.123 / Chapter 4.2.2.5 --- Transient transfection --- p.123 / Chapter 4.2.2.6 --- MTT assay --- p.124 / Chapter 4.2.2.7 --- Quantification of doxorubicin (Dox) uptake by flow cytometry --- p.125 / Chapter 4.3 --- Results / Chapter 4.3.1 --- mRNA expression of Thrombospondinl (THBS1) in SA and DX5 cells --- p.126 / Chapter 4.3.2 --- The protein expression of Thrombospondinl (THBS1) in SA and DX5 cells --- p.128 / Chapter 4.3.3 --- Thrombospondinl (THBS1) cDNA transfection in DX5 cells --- p.130 / Chapter 4.3.4 --- mRNA expression of MDR1 in Thrombospondinl-transfected DX5 cells (DX5_THBS1) --- p.132 / Chapter 4.3.5 --- P-glycoprotein expression in Thrombospondinl-transfected DX5 cells --- p.134 / Chapter 4.3.6 --- "Cytotoxicity of doxorubicin (Dox) on DX5 control, DX5 vector control and DX5一THBS1 cells" --- p.136 / Chapter 4.3.7 --- "Doxorubicin (Dox) uptake by SA control, DX5 control and DX5_THBS1 cells" --- p.138 / Chapter 4.4 --- Discussion --- p.141 / Chapter 4.5 --- Conclusion --- p.145 / Chapter Chapter 5 --- General discussion --- p.146 / Chapter 5.1 --- Doxorubicin induced multidrug resistance in human uterin sarcoma cells via upregulation of P-glycoprotein --- p.147 / Chapter 5.2 --- The down-regulation of Ninjurin1 in human uterine sarcoma cells contributed to multidrug resistance --- p.148 / Chapter 5.3 --- The down-regulation of Thrombospondin1 in human uterine sarcoma cells contributed to multidrug resistance --- p.150 / Chapter 5.4 --- Conclusion and Future Perspective --- p.153 / Reference --- p.155

Em vacas de corte, folículos pré-ovulatórios (FPO) maiores, maiores concentrações de estradiol (E2) no proestro/estro e progesterona (P4) no diestro favorecem o crescimento do concepto e a fertilidade. Porém, os mecanismos mediados pelos esteroides femininos que influenciam a receptividade uterina ao embrião precisam ser esclarecidos. Os aminoácidos (AA) são componentes das secreções uterinas que são cruciais para a sobrevivência do embrião antes da implantação. A hipótese deste trabalho é que o tamanho do FPO e as concentrações de E2 e P4 modulam a abundância de transcritos relacionados ao transporte e metabolismo de AA no endométrio e afetam a concentração luminal de AA. Para isso, o crescimento folicular de vacas Nelore foi manipulado com o objetivo de formar dois grupos: FPO grande e CL grande (FG-CLG) e FPO pequeno e CL pequeno (FP-CLP). No Dia 4 (D4; Exp 1) e Dia 7 (D7; Exp 2) após a injeção de GnRH para indução da ovulação, foram coletados tecido endometrial e lavado uterino post-mortem. A abundância de transcritos foi avaliada por qRT-PCR e as concentrações de AA nos lavados foram quantificadas por HPLC. No Exp 1, o tamanho do FPO, concentrações plasmáticas de E2 no D-1 e de P4 no D4 foram 15,70mm±0,43 vs. 11,31mm±0,23 (p<0,01), 2,44pg/ml±0,19 vs. 0,65pg/ml (p<0,01) e 1,40ng/ml±0,23 vs. 0,80ng/ml±0,10 (p<0,01) para os grupos FG-CLG vs. FP-CLP, respectivamente. No Exp 2, o tamanho do FPO, concentrações plasmáticas de E2 no D-1 e de P4 no D7 foram 13,18mm±0,44 vs. 10,63mm±0,30 (p<0,01), 2,30pg/ml±0,57 vs. 0,50pg/ml±0,13 (p<0,01) e 3,68ng/ml±0,38 vs. 2,49ng/ml±0,43 (p=0,04) para os grupos FG-CLG vs. FP-CLP, respectivamente. No D4 a abundância de SLC1A4, SLC38A1, SLC6A6, SLC7A4 e SLCY e no D7, SLC1A4, SLC6A1, SLC6A14, SLC7A4, SLC7A8, SLC38A1, SLC38A7, SLC43A2 e DDO foi maior no endométrio dos animais do grupo FG-CLG (p<0,05). No D4, maiores concentrações de taurina, alanina e ácido α-aminobutírico foram observadas no grupo FP-CLP (p<0,05). Em contraste, menores concentrações de valina e cistationina foram encontradas nos lavados uterinos do D7 dos animais do grupo FP-CLP (p<0,05). No D4, os animais do grupo FG-CLG, associado a maior fertilidade, apresentaram menor quantidade de AA nas secreções uterinas, porém, a abundância dos transportadores de AA foi compatível com maior transporte em comparação aos animais do grupo FP-CLP. Esses resultados sugerem que antes do embrião se mover do oviduto ao útero, o transporte e metabolismo dos AA prioriza a preparação das células endometriais para receber o embrião e não o acúmulo nas secreções uterinas. Porém, no D7, quando o embrião está em contato direto com as secreções uterinas, os genes relacionados ao transporte de AA no endométrio e a concentração de AA no histotrofo são estimulados nas vacas do grupo FG-CLG. Portanto o metabolismo e transporte de AA no sentido das células endometriais ou das secreções uterinas pode ser um mecanismo importante para a receptividade materna. / In beef cattle, a large size of the pre-ovulatory follicle (POF) and resulting elevated proestrus/estrus estradiol (E2) and diestrus progesterone (P4) concentrations positively affect conceptus growth and fertility. However, sex-steroid-mediated mechanisms that influence uterine receptivity to the embryo need to be elucidated. Amino acids are important components of maternally-derived secretions that are crucial for embryo survival before implantation. The hypothesis is that the size of the POF, E2 and P4 concentrations modulate endometrial abundance of solute carrier proteins (SLC) transcripts related to AA transport and metabolism and subsequently affect lumenal amino acids concentrations. Therefore, follicle growth of Nelore cows was manipulated to produce two experimental groups: large POF and CL (LF-LCL group) and small POF and CL (SF-SCL group). On Day 4 (D4; Experiment 1) and Day 7 (D7; Experiment 2) post GnRH injection to induce ovulation, endometrial tissue and uterine washings were collected post-mortem. Transcript abundance was evaluated by qRT-PCR and amino acid concentrations were quantified in washings by HPLC. On Experiment 1, POF size, plasma E2 concentration on D-1, and plasma concentration of P4 on D4 were 15.70mm±0.43 vs. 11.31mm±0.23 (p<0.01), 2.44pg/ml±0.19 vs. 0.65pg/ml (p<0.01) and 1.40ng/ml±0.23 vs. 0.80ng/ml±0.10 (p<0.01) for the LF-LCL vs. SF-SCL groups, respectively. For Experiment 2, POF size, plasma E2 concentration on D-1 and plasma P4 concentration on D7 were 13.18mm±0.44 vs. 10.63mm±0.30 (p<0.01), 2.30pg/ml±0.57 vs. 0.50pg/ml±0.13 (p<0.01) and 3.68ng/ml±0.38 vs. 2.49ng/ml±0.43 (p=0.04) for the LF-LCL vs. SF-SCL groups, respectively. On D4, abundance of SLC6A6, SLC7A4, SLC17A5, SLC38A1, SLC38A7 and SLCY and on D7, SLC1A4, SLC6A1, SLC6A14, SLC7A4, SLC7A7, SLC7A8, SLC17A5, SLC38A1, SLC38A7, SLC43A2 and DDO was greater in the endometrium of cows from the LF-LCL group (p<0.05). On D4, higher concentrations of taurine, alanine and α-aminobutiric acid were observed in SF-SCL (p<0.05). In contrast, lower concentrations of valine and cystathionine were quantified in D7 uterine washings from SF-SCL cows (p<0.05). On D4, animals from LF-LCL group, associated with greater fertility, presented less amino acid content in uterine secretion but abundance of transporters was compatible to greater transport in comparison to animals from SF-SCL group. This suggests that before embryo moves from oviduct to uterus, amino acids transport and metabolism pathways prioritizes endometrium cells preparation for receiving the embryo but not accumulation in uterine secretions. However, on D7, when the embryo is in direct contact with uterine secretions, genes related to amino acids transport in endometrium and amino acids concentration in histotroph are up-regulated in LF-LCL cows. The latter insights indicate that amino acids metabolism and transport, towards endometrial cells or uterine secretions, might be mechanisms contributing to maternal receptivity.

Foram estudados, prospectivamente, por um período médio de 4,9 anos, os resultados do tratamento de 31 mulheres com incontinência urinária e afecção benigna do útero que foram submetidas à cirurgia de sling fascial associada à histerectomia vaginal, atendidas na Clínica Ginecológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de fevereiro de 2000 a outubro de 2006. O objetivo foi avaliar os resultados do tratamento comparando-se os diagnósticos urodinâmicos pré- e pós-tratamento. As mulheres foram submetidas à cirurgia de histerectomia vaginal, para tratamento da afecção benigna do útero e sling fascial para correção da incontinência urinária. Realizou-se estudo urodinâmico no pré- e pós-tratamento, para avaliação da taxa de cura da incontinência urinária e do comportamento vesical nas fases de enchimento e esvaziamento, os quais foram avaliados por meio dos parâmetros urodinâmicos de fluxometria e cistometria. Na fluxometria avaliou-se o fluxo urinário máximo, fluxo urinário médio e volume de urina residual e na cistometria, determinou-se a capacidade vesical no 1° desejo miccional, capacidade vesical máxima e a pressão vesical necessária para ocorrer ou não a perda de urina. Os resultados mostraram, em relação á fluxometria diminuição significante do fluxo máximo, tendência à diminuição do fluxo médio e redução significante do volume de urina residual. Em relação à cistometria, houve aumento estatisticamente significante da capacidade vesical no 1° desejo miccional, da capacidade vesical máxima e valor da pressão vesical necessária para avaliar a presença ou não de perda urinária. Com relação ao diagnóstico urodinâmico, foi demonstrada a cura da incontinência urinária em 96,8% dos casos. Avaliando-se os parâmetros de cura objetiva da incontinência urinária, em seguimento de 4,9 anos, podemos inferir que o tratamento da incontinência urinária de esforço pode ser realizado simultaneamente, quando houver também, a indicação de histerectomia vaginal / We studied, prospectively, for a 4.9 years period the results of the treatment of 31 women with urinary incontinence and benign uterine disease that were submitted the surgery fascial sling associated to vaginal hysterectomy, the patients were all treated in the Gynecology Department of the Clinic Hospital of the University of Sao Paulo, in the period between February 2000 to October 2006. The objective was evaluate the results of the treatment comparing the urodinamic diagnosis pre and post treatment. All women were submitted to vaginal hysterectomy for treatment of benign uterine disorders and to facial sling to treat the urinary incontinence. An urodinamic study was performed pre and post treatment to define the rate of cure of the urinary incontinence and vesical behaviour in the filling and emptying fases, witch will evaluate through urodinamic parameters of flowmetry and cystometry, In the flowmetry were evaluated maximum urinary flow, medium urinary flow and residual urinary volume; and in the cystometry were determinated the bowel capacity in the first urinary desire, maximum bowel capacity in the first urinary desire, maximum bowel capacity and the needed bowel pressure to occur or not the urinary loss. The results showed in relation to the flowmetry significant reduction of the maximum flow, medium flow and urinary residual volume. In relation to cystometry we demonstrated an increase statistically significant in the vesical capacity in the first miccional desire, in the maximum bowel capacity and the value of the bowel pressure to evaluate the presence or not of urinary lost. In relation to the urodimanic diagnosis we could demonstrate the cure of urinary incontinence in 96.8% of cases. Evaluating the parameters of objective cure of urinary incontinence, in a follow up of 4.9 years, we can affirm that the treatment of urinary incontinence should be always be together with the vaginal hysterectomy when it is needed

L’accouchement prématuré est l’un des problèmes majeurs en obstétrique. Par suite, il a été un sujet d'intérêt pour de nombreux chercheurs. Parmi les nombreuses méthodes utilisées pour enregistrer la contractilité utérine, le plus utilisé est l'EHG abdominal, comme étant un outil facile à utiliser et non invasif. De nombreuses études ont indiqué que l'utilisation de ce signal pourrait être un outil très puissant pour surveiller la grossesse et pour détecter le travail. Il permet en effet d'accéder à l'utérus ainsi que la synchronisation de l'activité utérine, en utilisant des signaux multiples. Il a été démontré que l'analyse de connectivité des signaux EHG a donné des résultats prometteurs en application clinique, comme la classification des contractions de travail et de grossesse. Cependant, dans presque toutes les études antérieures, les matrices de corrélation EHG étaient souvent réduites en ne gardant que leur moyenne et les écarts-types, ce qui a peut aboutir à perdre des informations pertinentes en raison de ce moyennage, ce qui peut induire le taux de classification relativement faible jusqu'à présent. Pour caractériser précisément la matrice de corrélation et quantifier la connectivité associée, nous avons proposé dans cette thèse d'utiliser une technique de mesure de réseau basée sur la théorie des graphes. Selon cette approche, la matrice de corrélation obtenue peut être représentée sous forme de graphiques constitués d'un ensemble de nœuds (électrodes) interconnectés par des arêtes (valeurs de connectivité / corrélation entre électrodes). La nouvelle procédure de l'analyse des signaux EHG enregistrés pendant la grossesse et le travail se base sur la caractérisation de la corrélation entre les activités électriques utérines et sur sa quantification précise en utilisant l'approche de la théorie des graphes. Le pipeline de traitement inclut i) l'estimation des dépendances statistiques entre les différents signaux EHG enregistrés, ii) la quantification des matrices de connectivité obtenues à l'aide de l'analyse théorique des graphes et iii) l'utilisation clinique des mesures de réseau pour la surveillance de la grossesse ainsi que la classification entre les éclosions d'EHG de grossesse et de travail. Une comparaison avec les paramètres déjà existants utilisés pour la détection du travail et la détection d’accouchement prématuré sera également effectuée. Nous étudions également une nouvelle méthode pour étudier la connectivité source EHG, afin de surmonter le problème du calcul de la connectivité au niveau de la surface abdominale. Les résultats de cette thèse montrent que cette approche basée sur la théorie de graphe est un outil très prometteur pour quantifier la synchronisation utérine, lorsqu'elle est appliquée à l'abdomen, pour une meilleure surveillance de la grossesse. Nous espérons que cette approche soit utilisée pour le suivi de la grossesse et contribuerait ainsi à la prédiction précoce de l’accouchement prématuré. / Preterm birth remains a major problem in obstetrics. Therefore, it has been a topic of interest for many researchers. Among the many methods used to record the uterine contractility, the most used is the abdominal EHG, as being an easy to use and a non-invasive tool. Many studies have reported that the use of this signal could be a very powerful tool to monitor pregnancy and to detect labor. It indeed permits to access the uterine as well as the synchronization of the uterine activity, by using multiple signals. It has been shown that the connectivity analysis gave promising results when using EHG recordings in clinical application, such as the classification labor/pregnancy contractions. However, in almost all previous studies EHG correlation matrices were often reduced keeping only their mean and standard deviations thus relevant information may have been missed due to this averaging, which may induce the relatively low classification rate reported so far. To characterize precisely the correlation matrix and quantify the associated connectivity, we proposed in this thesis to use a network measure technique based on graph theory. According to this approach, the obtained correlation matrix can be represented as graphs consisting of a set of nodes (electrodes) interconnected by edges (connectivity/correlation values between electrodes). The new framework, to analyze the EHG signals recorded during pregnancy and labor, is based on the characterization of the correlation between the uterine electrical activities and on its precise quantification by using graph theory approach. The processing pipeline includes i) the estimation of the statistical dependencies between the different recorded EHG signals, ii) the quantification of the obtained connectivity matrices using graph theory-based analysis and iii) the clinical use of network measures for pregnancy monitoring as well as for the classification between pregnancy and labor EHG bursts. A comparison with the already existing parameters used in the state of the art for labor detection and preterm labor prediction will also be performed. We also investigate a new method to study the EHG source connectivity, to overcome the problem of computing the connectivity at the abdominal surface level. The results of this thesis showed that this network-based approach is a very promising tool to quantify uterine synchronization, when applied at the abdominal level, for a better pregnancy monitoring. We expect this approach to be further used for the monitoring of pregnancy and would thus help for the early prediction of preterm labor.

Luk, Chun Shui. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 174-189). / Abstract also in Chinese. / Declaration --- p.I / Acknowledgements --- p.II / Funding Support --- p.IV / Abstract of thesis entitled --- p.V / 論文摘要 --- p.VII / Abbreviations --- p.IX / Table of Contents --- p.XIII / List of Figures --- p.XVIII / List of Tables --- p.XX / List of Appendix --- p.XXI / Chapter Chapter One - --- Literature Review --- p.1 / Chapter 1.1 --- History of Knowledge on Human Papillomavirus --- p.1 / Chapter 1.2 --- Virology of Human Papillomavirus --- p.2 / Chapter 1.2.1 --- Taxonomic Classification of Human Papillomavirus --- p.2 / Chapter 1.2.2 --- Morphology of Human Papillomavirus --- p.3 / Chapter 1.2.3 --- The Viral Genome --- p.3 / Chapter 1.2.4 --- The Viral Gene Products --- p.5 / Chapter 1.2.4.1 --- E1 and E2 Proteins --- p.5 / Chapter 1.2.4.2 --- E4 Protein --- p.6 / Chapter 1.2.4.3 --- "E5，E6, E7 Proteins" --- p.7 / Chapter 1.2.4.4 --- L1 and L2 Proteins --- p.8 / Chapter 1.3 --- Evolution of Human Papillomavirus --- p.9 / Chapter 1.3.1 --- Rates of Evolution --- p.11 / Chapter 1.3.2 --- Co-evolution Between Human Papillomavirus and Human --- p.11 / Chapter 1.4 --- Human Papillomavirus Infection and Disease --- p.13 / Chapter 1.4.1 --- Human Papillomavirus and Cervical Cancer --- p.13 / Chapter 1.4.1.1 --- Disease Burden of Cervical Cancer --- p.13 / Chapter 1.4.1.2 --- Epidemiology of Cervical Cancer --- p.14 / Chapter 1.4.1.3 --- Distribution of HPV types in Cervical Precancerous Lesions --- p.14 / Chapter 1.4.2 --- Human Papillomavirus and Non-cervical Diseases --- p.15 / Chapter 1.5 --- Human Papillomavirus Type 58 --- p.15 / Chapter 1.5.1 --- Biology of Human Papillomavirus Type 58 --- p.15 / Chapter 1.5.2 --- Epidemiology of Human Papillomavirus Type 58 Infections --- p.16 / Chapter Chapter Two - --- Background and Objectives of Study --- p.17 / Chapter 2.1 --- Background of study --- p.17 / Chapter 2.1.1 --- The Need for Research on HPV58 --- p.17 / Chapter 2.1.2 --- Intratypic Classification System for HPV --- p.17 / Chapter 2.2 --- Implication and Impact of Study --- p.19 / Chapter 2.2.1 --- Implication on HPV Virology --- p.19 / Chapter 2.2.2 --- HPV58 Classification --- p.19 / Chapter 2.2.3 --- Improvement on in the Detection of HPV58 --- p.20 / Chapter 2.2.4 --- Implication on Vaccine Development --- p.20 / Chapter 2.3 --- Objectives of Study --- p.21 / Chapter 2.3.1 --- To Generate a Database for Intratypic Variation of Different Gene Regions of HPV58 --- p.21 / Chapter 2.3.2 --- To Study the Variability of Seven Gene Regions of HPV58 --- p.21 / Chapter 2.3.3 --- To Study the Geographical Distribution of HPV58 Variants --- p.22 / Chapter 2.3.4 --- To Study the Phylogeny of HPV58 --- p.22 / Chapter 2.3.5 --- To Develop an Intratypic Classification System for HPV58 --- p.22 / Chapter 2.3.6 --- To Predict the Effectiveness of Commonly Used Primers on the Detection of HPV58 --- p.22 / Chapter Chapter Three - --- Materials and Methods --- p.24 / Chapter 3.1 --- Overall Study Design --- p.24 / Chapter 3.2 --- Study Population --- p.25 / Chapter 3.3 --- Sample Processing and Storage --- p.25 / Chapter 3.4 --- Primer Design --- p.26 / Chapter 3.5 --- Specimen Quality Assessment and Sample Selection --- p.30 / Chapter 3.6 --- Amplification of Gene Region --- p.30 / Chapter 3.7 --- Agarose Gel Electrophoresis --- p.34 / Chapter 3.8 --- Sequencing Reaction --- p.34 / Chapter 3.8.1 --- Purification of PCR Product --- p.34 / Chapter 3.8.2 --- Sequencing Reaction --- p.35 / Chapter 3.8.3 --- Purification of Fluorescence-labelled Product --- p.35 / Chapter 3.8.4 --- Sequence Identification --- p.35 / Chapter 3.9 --- Sequence Analysis --- p.36 / Chapter 3.9.1 --- Sequence Editing --- p.36 / Chapter 3.9.2 --- Criteria for Confirming the identity of HPV58 --- p.36 / Chapter 3.9.3 --- Identification of Variants --- p.38 / Chapter 3.9.4 --- Identification of Conserved and Variable Regions --- p.39 / Chapter 3.9.5 --- Phylogenetic Analysis --- p.40 / Chapter 3.9.5.1 --- Construction of Maximum Likelihood Tree --- p.40 / Chapter 3.9.5.2 --- Bootstrap Analysis --- p.41 / Chapter 3.9.5.3 --- Bayesian Phylogenetic Analysis --- p.42 / Chapter 3.9.5.4 --- Non-synonymous to Synonymous Substitution Rate Ratio (dN/dS) --- p.42 / Chapter 3.9.6 --- Evaluation of Performance of Commonly Used Primers --- p.43 / Chapter Chapter Four - --- Results --- p.44 / Chapter 4.1 --- Specimen Quality Assessment and HPV58 Confirmation --- p.44 / Chapter 4.2 --- HPV58 Genome Variability --- p.44 / Chapter 4.2.1 --- E6 Open Reading Frame --- p.45 / Chapter 4.2.2 --- E7 Open Reading Frame --- p.51 / Chapter 4.2.3 --- E2 Open Reading Frame --- p.56 / Chapter 4.2.4 --- E4 Open Reading Frame --- p.61 / Chapter 4.2.5 --- E5 Open Reading Frame --- p.66 / Chapter 4.2.6 --- L1 Open Reading Frame --- p.71 / Chapter 4.2.7 --- Long Control Region --- p.88 / Chapter 4.2.8 --- Whole HPV genome --- p.94 / Chapter 4.3 --- Evaluation of Commonly Used Primers --- p.99 / Chapter 4.3.1 --- PGMY09/11 Primers --- p.99 / Chapter 4.3.2 --- MY09/11 Primers --- p.99 / Chapter 4.3.3 --- GP5+/6+ Primers --- p.100 / Chapter 4.3.4 --- SPF Primers --- p.100 / Chapter 4.3.5 --- L1F/L1R Primers --- p.101 / Chapter Chapter Five - --- Discussion --- p.111 / Chapter 5.1 --- Overall Variation of HPV58 Genome --- p.111 / Chapter 5.2 --- Variability of Each Gene Region --- p.114 / Chapter 5.2.1 --- E6 Open Reading Frame --- p.115 / Chapter 5.2.2 --- E7 Open Reading Frame --- p.116 / Chapter 5.2.3 --- E2 Open Reading Frame --- p.117 / Chapter 5.2.4 --- E4 Open Reading Frame --- p.118 / Chapter 5.2.5 --- E5 Open Reading Frame --- p.119 / Chapter 5.2.6 --- L1 Open Reading Frame --- p.120 / Chapter 5.2.7 --- Long Control Region --- p.121 / Chapter 5.3 --- Phylogenetics of HPV58 --- p.122 / Chapter 5.3.1 --- Natural Selection Pressure --- p.122 / Chapter 5.3.2 --- HPV58 Lineage Using the L1 Gene --- p.124 / Chapter 5.3.3 --- Methods for Lineage Identification --- p.125 / Chapter 5.3.4 --- Geographical Distribution of the Four Lineages --- p.126 / Chapter 5.3.5 --- Recombination --- p.127 / Chapter 5.4 --- Evaluation of Commonly Used Primers --- p.128 / Chapter 5.5 --- Limitations of the Current Study --- p.129 / Chapter 5.6 --- Future Studies --- p.130 / Appendix --- p.133 / References --- p.174

Avaliar a associação entre as infecções genito-urinárias, o comprimento do colo uterino e a prematuridade é importante para determinar quais podem ser os fatores preditivos para o parto pré-termo. Foi realizado estudo tipo coorte de conveniência, prospectivo, avaliando 1370 gestantes na cidade de Ribeirão Preto, com idade gestacional entre 20 e 25 semanas. Aplicou-se questionário sócio demográfico com história reprodutiva para a identificação do histórico obstétrico, idade materna, paridade, tabagismo e antecedente de parto pré-termo. Foi realizada ultrassonografia endovaginal para a avaliação do comprimento do colo uterino segundo as diretrizes da Fetal Medicine Foundation (FMF). Foram coletadas amostras de urina e conteúdo vaginal para avaliar a presença de infecção urinária e vaginose bacteriana respectivamente. A associação entre infecções, comprimento do colo uterino e parto pré-termo (PPT) foi realizada mediante teste não paramétrico e o cálculo do Risco Relativo das diferentes variáveis, por meio do ajuste de modelos log-binomiais. Das 1370 mulheres grávidas avaliadas, 132(9,63%) cursaram com parto pré-termo (<37 semanas), sendo que 19 (14,4%) dos partos pré-termo ocorreram em mulheres com colo <= 2,5 cm. O estudo microbiológico determinou que no grupo das mulheres que cursaram com parto pré-termo, 15 apresentaram ITU, 19 apresentaram vaginose bacteriana (VB) e uma apresentou ITU e VB. Avaliando as 75 pacientes com PPT espontâneos, 10 apresentaram ITU e 14, VB. Após a análise destes dados, foi possível concluir que o colo uterino curto entre 20 e 25 semanas de gestação está associado ao PPT e que ITU e VB rastreadas nesta idade não se associaram ao encurtamento do colo nem ao PPT. No entanto a ITU, mesmo assintomática apresentou relação com o PPT espontâneo. / To evaluate the association between the genito-urinary infections, cervical length and preterm birth is important to determine which can be predictive factors for preterm birth. It was conducted cohort study of convenience, prospective, evaluating 1370 pregnant women in the city of Ribeirão Preto, with gestational age between 20 and 25 weeks. Applied socio-demographic questionnaire with reproductive history to identify the obstetric history, maternal age, parity, smoking and preterm birth (PTB) history. Transvaginal ultrasonography was performed for evaluation of cervical length in the guidelines of the Fetal Medicine Foundation (FMF). Urine and vaginal discharge samples were collected to evaluate the presence of urinary tract infection (UTI) and bacterial vaginosis (BV) respectively. The association between infections, cervical length and preterm delivery was performed using non-parametric test and calculate the relative risk of different variables, by adjusting log-binomial model. Of the 1370 evaluated pregnant women, 132 (9.63%) presenting with preterm delivery (<37 weeks), and 19 (14.4%) of preterm deliveries occurred in women with cervix <=2.5 cm. The microbiological study found that the group of women presenting with preterm birth(PTB), 15 had UTI, 19 had BV and one presented UTI and VB. Evaluating 75 patients with spontaneous PTB, 10 had UTI and 14, BV. After the analysis of these data, it was concluded that the short cervix between 20 and 25 weeks of gestation is associated with the PTB and UTI and VB screened at this age not associated to the shortening of the cervix or the PTB. However, the UTI even asymptomatic were related to the spontaneous PTB.

L’accouchement prématuré est un problème de santé publique dans le monde et notamment dans les pays économiquement développés avec un taux variant entre 7 et 12 % des naissances. Le diagnostic du risque d’accouchement prématuré est difficile à faire et les outils à notre disposition ont peu évolué ces dernières années. La contraction utérine est la conséquence directe de l’activité électrique au niveau du myomètre. Le type de contraction est lié à l’importance de l’excitabilité cellulaire et de sa diffusion à l’ensemble du myomètre. Le recueil et l’analyse de cette activité électrique par des électrodes de surface est aujourd’hui le seul moyen non invasif d’étudier, pendant la grossesse, les mécanismes qui sont à l’origine de la contraction. L’enregistrement de l’électromyogramme utérin ou électrohystérogramme (EHG) est donc prometteur pour réaliser un diagnostic et une surveillance des femmes à risque d’accouchement prématuré. Dans ce travail de thèse 3 études cliniques ont été réalisées. Dans la première, j’ai étudié différentes électrodes de surface permettant d’enregistrer les signaux électriques. Je propose à la fin de cette première partie un système d’électrodes pour permettre à la fois un enregistrement de qualité et une pose aisée compatible avec une application clinique. Dans la deuxième étude j’ai étudié la détection automatique des contractions par l’EHG avec des résultats encourageants pour l’application clinique et notamment en ambulatoire. Enfin dans la troisième étude j’ai étudié la prédiction du risque d’accouchement prématuré par l’analyse de paramètres électriques issus de l’EHG. Les résultats obtenus permettent d’améliorer la prédiction du risque d’accouchement prématuré par rapport aux outils utilisés en routine. / Premature birth is a public health problem in the world, particularly in economically developed countries with a rate varying between 7% and 12% of births. The diagnosis of the risk of premature labor is difficult to make and the tools at our disposal have changed little in recent years. Uterine contraction is a direct consequence of electrical activity at the level of the myometrium. The type of contraction is related to the importance of cell excitability and its diffusion to the entire myometrium. The analysis of this electrical activity by surface electrodes is currently the only non-invasive way to study the mechanisms that are at the origin of the contraction. The recording of the uterine electromyogram or electrohysterogram (EHG) is therefore promising for the diagnosis and surveillance of women at risk of preterm birth. In this thesis work 3 clinical studies have been carried out. In the first clinical study, different surface electrodes to record electrical signals were tested. I propose at the end of this first part a system of electrodes to allow at the same time a recording of quality and an easy pose compatible with a clinical application. In the second study , the automatic detection of contractions by the El-IG was studied with encouraging results for the clinical application and especially in ambulatory. Finally, in the third clinical experiment, I studied the prediction of the risk of premature delivery by the analysis of electrical parameters extracted from the EHG. The results obtained make it possible to improve the prediction of the risk of premature delivery compared to the tools used routinely.

A disproportionate number of African American women are at increased risk for uterine fibroid tumors (UF) compared to their Caucasian, Asian, and Hispanic counterparts. Researchers have indicated that women diagnosed with UF can have a poorer health-related quality of life (HRQOL) when compared to women who do not have a diagnosis of UF. The overall aim of this study was to explore the impact of UF symptoms on the HRQOL of African American women. A quantitative, cross-sectional design was employed utilizing the revised version of Wilson and Cleary's model of HRQOL. A sample was gathered of 80 participants who were African American women between age 30 and 45 years with a current diagnosis of UF. Linear and multiple hierarchical regressions were performed to determine the relationship among UF symptom severity and HRQOL based on 6 subscales of HRQOL (as measured by the UFS-QOL). There was a statistically significant association between symptom severity, the 6 subscale variables of HRQOL, and employment. No significant associations were observed with age, family history (hx) of UF diagnosis, body mass index, general health perception, overall quality of life, and symptom severity. The social change implication for this study is to provide information that can direct health care providers in the development of health maintenance programs that are sensitive to the needs of African American women diagnosed with UF. In addition it will promote the need for public health professionals and medical organizations to increase the availability of information related to UF symptoms and the impact of UF symptoms on HRQOL among women.