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Objective: To identify the physician-, patient- and health-system-related factors that influence gynecologists’ decision to recommend endometrial sampling in young women (less than 40 years) with abnormal uterine bleeding Study methods: A mail-based survey study was conducted using the Salant-Dillman method with 4 points of contact over 9 weeks. All Canadian obstetrician/gynecologists were initially surveyed (N=1746), receiving either French or English questionnaires. Eligible respondents were gynecologists practicing in Canada who treat these young women (N=834). Order response bias was taken into consideration by mailing two versions of the survey. Categorical data were analyzed using Pearson’s Chi-square statistics. A logistic regression with mixed effect model was performed to determine the odds of sampling the endometrium, using physician as random factor. Results: Overall response rate was 56.5%. The majority of respondents were generalists (83.6%). 70.3% of respondents have had young patients with malignant or pre-malignant endometrial conditions. Physicians ≤ 39 years have had less experience with these patients (59.6%, p=0.002) as have physicians practicing in communities without ob/gyn residents (35.2%, p=0.006). Sampling method was predominantly by office pipelle (79.7%), with younger physicians and female respondents employing this method most frequently (p=0.0001). In case scenarios which explored the importance of four patient-related risk factors (obesity, irregular cycles, nulliparity and older age), on the decision to sample, 98.8% of respondents would sample a young woman presenting with all four risk factors, as opposed to 8.8% who would sample if the patient did not have any of these characteristics. Obesity and irregular cycles was the next most important combination of risk factors prompting sampling in 87.3% of physicians. In the logistic regression, the odds ratio to proceed with endometrial sampling was 2.23 (95% CI 1.64-3.03) if a physician had previous experience with young women diagnosed with endometrial cancer or a pre-malignant condition, and was 1.45 (95% CI 1.05-2.01) if the physician was female. Conclusion: Patient and physician factors influenced the decision to proceed with sampling the endometrium of young women with abnormal uterine bleeding, whereas the health-system factors studied in this survey did not seem to play a strong role. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2010-07-14 15:06:07.786

Made available in DSpace on 2018-08-01T22:57:00Z (GMT). No. of bitstreams: 1 tese_9938_JACYMARA DUTRA SANTOS.pdf: 1451382 bytes, checksum: e8738baf40dde66da45878e0fe8a27d6 (MD5) Previous issue date: 2018-02-27 / Desordens metabólicas e reprodutivas afetam vacas leiteiras no pós-parto apresentando relevante importância econômica, pois reduzem a produção. Objetivou-se verificar a influência das alterações clínicas e reprodutivas, escore de condição corporal (ECC), perfil metabólico energético e enzimático hepático no retorno à ciclicidade ovariana e ocorrência de infecções uterinas pós-parto em fêmeas leiteiras. Foram utilizadas 53 fêmeas cruzadas Gir x Holandês, provenientes de propriedades do Sul do Espírito Santo, subdivididas em dois grupos: Primíparas, com 19 fêmeas de primeira cria e; Multíparas, com 34 fêmeas com mais de dois partos. Avaliou-se os seguintes momentos: 15 dias pré-parto e, 15, 30, 45 e 60 dias pós-parto. No exame físico avaliou-se as frequências cardíaca (FC) e respiratória (FR), temperatura retal (TºR), peso e ECC. Foram coletadas amostras sanguíneas por meio de venopunção da veia coccígea para avaliação das concentrações séricas de β-hidroxibutirato, colesterol total e lipoproteínas (perfil energético) e alanina aminotransferase (ALT), gama glutamiltransferase (GGT) e fosfatase alcalina (FA) (perfil enzimático hepático). O exame ginecológico foi realizado por meio de palpação e ultrassonografia transretal. O útero foi avaliado quanto ao tamanho, posição, consistência e simetria de cornos uterinos para acompanhamento do processo de involução uterina e os ovários, quanto ao tamanho e presença de estruturas ovarianas para determinação do retorno à atividade ovariana luteal cíclica. Realizou-se o exame de vaginoscopia para avaliação da presença e características das secreções vaginais. As infecções uterinas foram classificadas como metrite clínica e puerperal e endometrite clínica de acordo com a característica e tempo da secreção liberada e; endometrite subclínica quando diagnosticada por citologia endometrial. As variáveis paramétricas foram submetidas ao teste de Tukey e variáveis não paramétricas, ao teste de Kruskall-Wallis. Para correlação, utilizou-se o teste de correlação de Spearman; todos com nível de significância de 5%. Os parâmetros clínicos de FC, FR e TºR encontraram-se dentro dos limites de normalidade estabelecidos para a espécie. O ECC variou de 4 a 2,5 e o peso, de 273 a 315kg; observou-se diminuição nos dois parâmetros do momento D-15 para os demais, indicando a importância da adoção de estratégias que minimizem os efeitos da perda de condição corporal pós-parto.; sendo observadas diferenças entre os grupos em todos os momentos avaliados para o peso. Aos 60 dias pós-parto 33,96%(18/53) dos animais haviam retomado a atividade ovariana. Não observou-se diferença no tamanho dos ovários entre momentos e grupos. Em relação ao tamanho de útero e cérvix notou-se diminuição entre D-15 e os demais, entretanto, não observou-se diferenças entre grupos. A incidência de infecções uterinas foi de 33,96%(18/53), sendo que 27,78%(5/18) dos animais que cursaram a enfermidade eram primíparas. Dos animais que apresentaram infecção uterina, 50%(9/18) apresentaram metrite clínica, dos quais 33,33% eram primíparas e 50%(9/18) apresentaram endometrite clínica, sendo 22,22% primíparas. Nenhum animal apresentou endometrite subclínica. A perda de ECC pós-parto não influenciou na ocorrência de infecções uterinas e no retorno à ciclicidade. Não houve correlação entre a ocorrência de cetose e infecções uterinas nem com o tempo de retorno ao cio pós-parto. Não foram observadas alterações no perfil metabólico enzimático hepático.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 87-107).

Made available in DSpace on 2014-06-11T19:32:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-08-25Bitstream added on 2014-06-13T19:26:25Z : No. of bitstreams: 1 martins_amvc_dr_botfm_prot.pdf: 1428441 bytes, checksum: e687eeb3da2bd5d051917dea14402c3d (MD5) / Universidade Estadual Paulista (UNESP) / Fundação para o Desenvolvimento Médico e Hospitalar (Famesp) / O objetivo deste estudo foi determinar a importância do local de transferência embrionária (metade superior ou inferior da cavidade endometrial) nas taxas de implantação e gestação. Metodologia: Foram randomizadas 400 transferências embrionárias, guiadas por ultra-sonografia em dois grupos, de acordo com a distância entre a camada de basal de endométrio fúndico e a ponta do cateter de transferência, no ato do procedimento. O Grupo 1 (n200) correspondeu às transferências sendo realizadas a uma distância <50% do comprimento da cavidade endometrial, isto é, na metade superior da cavidade. O Grupo II (n=200) correspondeu às transferências realizadas a uma distância 50% do comprimento da cavidade endometrial, isto é, na metade inferior da cavidade. Os dados foram avaliados pelos testes t de Student, Mann-Whitney e exato de Fisher. Resultados: As características gerais da população estudada e das transferências tiveram distribuição igualitária (p>0,05) entre Grupos l e II. Não houve diferença estatística entre os grupos com relação às taxas de implantação embrionária (Grupo 1: 16,0%; Grupo II: 16,4% p=0,86) e gestação (Grupo 1: 35,0%; Grupo II: 29,5% p=0,28). Conclusão: As taxas de implantação e gestação são similares, quando os embriões são colocados na metade superior ou inferior da cavidade endometrial. / The objective of the present study was to determine the importance of the site of embryo transfer (upper or lower haif endometrial cavity) on implantation and clinical pregnancy rates. Methods: A total of 400 transfers guided by ultrasound were randomly assigned to two groups according to the distance between the basal layer of fundal endometrium and the catheter tip at the time of embryo placement. Group 1 (n=200) consísted of transfers corresponding to a distance of <50% of the endometrial cavity length, i.e. transfer in upper haif of the cavity; and group li (n=200) consisted of transfers corresponding to a distance of 50% of the endometrial cavity Iength, ie. transfer in lower haif of cavity. The Student's t-test, Mann-Whitney test and Fishers exact test were used where appropriate. Results: The general characteristics of the study population and the main transfer cycle characteristics had an equal distribution (p>0.05) between groups 1 and II. No significant difference in implantation (Group 1: 16.0%; Group II: 16.4% p=0.86) or pregnancy rates (Group 1: 35.0%; Group II: 29.5% p=0.28) was observed between groups 1 and II. Conclusion: The implantation or pregnancy rates were similar whether the embryos were deposited in the upper or lower half of the endometrial cavity.

Resumo: O objetivo deste estudo foi determinar a importância do local de transferência embrionária (metade superior ou inferior da cavidade endometrial) nas taxas de implantação e gestação. Metodologia: Foram randomizadas 400 transferências embrionárias, guiadas por ultra-sonografia em dois grupos, de acordo com a distância entre a camada de basal de endométrio fúndico e a ponta do cateter de transferência, no ato do procedimento. O Grupo 1 (n200) correspondeu às transferências sendo realizadas a uma distância <50% do comprimento da cavidade endometrial, isto é, na metade superior da cavidade. O Grupo II (n=200) correspondeu às transferências realizadas a uma distância 50% do comprimento da cavidade endometrial, isto é, na metade inferior da cavidade. Os dados foram avaliados pelos testes t de Student, Mann-Whitney e exato de Fisher. Resultados: As características gerais da população estudada e das transferências tiveram distribuição igualitária (p>0,05) entre Grupos l e II. Não houve diferença estatística entre os grupos com relação às taxas de implantação embrionária (Grupo 1: 16,0%; Grupo II: 16,4% p=0,86) e gestação (Grupo 1: 35,0%; Grupo II: 29,5% p=0,28). Conclusão: As taxas de implantação e gestação são similares, quando os embriões são colocados na metade superior ou inferior da cavidade endometrial. / Abstract: The objective of the present study was to determine the importance of the site of embryo transfer (upper or lower haif endometrial cavity) on implantation and clinical pregnancy rates. Methods: A total of 400 transfers guided by ultrasound were randomly assigned to two groups according to the distance between the basal layer of fundal endometrium and the catheter tip at the time of embryo placement. Group 1 (n=200) consísted of transfers corresponding to a distance of <50% of the endometrial cavity length, i.e. transfer in upper haif of the cavity; and group li (n=200) consisted of transfers corresponding to a distance of 50% of the endometrial cavity Iength, ie. transfer in lower haif of cavity. The Student's t-test, Mann-Whitney test and Fishers exact test were used where appropriate. Results: The general characteristics of the study population and the main transfer cycle characteristics had an equal distribution (p>0.05) between groups 1 and II. No significant difference in implantation (Group 1: 16.0%; Group II: 16.4% p=0.86) or pregnancy rates (Group 1: 35.0%; Group II: 29.5% p=0.28) was observed between groups 1 and II. Conclusion: The implantation or pregnancy rates were similar whether the embryos were deposited in the upper or lower half of the endometrial cavity. / Orientador: José Gonçalves Franco Júnior / Coorientador: Anaglória Pontes / Banca: Marilza Vieira Cunha Rudge / Banca: Eliana Milanesi Rubio / Banca: João Batista Alcântara Oliveira / Banca: Mário Cavagna / Doutor

Abstract Apoptosis is a genetically programmed mechanism for a multicellular organism to remove cells that are unnecessary, or potentially harmful. The female reproductive system is characterised by a high rate of cellular proliferation. At the same time, apoptosis is also abundant during the normal physiological function of the ovary and endometrium. More than half of the 7 million oocytes that are produced during human ovarian development are deleted before birth and only about 400 oocytes reach the stage of ovulation during the female fertile lifespan. The fate of the non-ovulatory follicles is atresia, occurring through the mechanism of apoptosis. The endometrium goes through radical renewal processes during each menstrual cycle. Apoptosis has been suggested to participate in the regulation of endometrial cellular homeostasis. Errors in this mechanism can result in endometrial diseases such as hyperplasia and cancer. In this work, apoptosis and its regulation were studied in the human fetal and adult ovary, normal endometrium and endometrial pathologies. In fetal ovaries, apoptosis was already abundantly present in oocytes at 13 weeks of gestation. The maximum rate of apoptosis was seen between the 14th and 20th weeks, after which apoptosis decreased towards term. Ovarian Bcl-2 expression was detected in early fetal life during weeks 13 and 14. Bax expression was observed throughout the studied period, from week 13 to 40. The expression of transcription factor GATA-4, which is linked to follicular survival, was localised to the granulosa cells and was high in early fetal life and decreased somewhat towards term. In adult life apoptosis was located in the granulosa cells of the growing follicles. In ovarian biopsies from women homozygous for the inactivating C566T mutation of the FSH receptor, apoptosis or GATA-4 expression was not detected. During corpus luteum regression a peak in apoptosis was detected 10 - 12 days after the LH surge, and was preceded by an increase in 17HSD type 1 and TNF-α expression. During normal menstrual cycles, the highest rate of apoptosis was observed in the menstrual endometrium. This increase in apoptosis was preceded by a decreased Bcl-2/Bax ratio. In endometrial hyperplasia, the rate of apoptosis was similar to that seen during normal proliferation of the endometrium, but an apparent increase was observed in grade II endometrial carcinoma. In grade III carcinoma, the rate of apoptosis was lower than in grade II carcinoma but higher than in hyperplasia. These results indicate that apoptosis is the mechanism behind the substantial oocyte demise during ovarian development. During adult life, apoptosis was mainly localised to the granulosa cells of the growing follicles which do not reach the stage of a dominant follicle. In ovaries where FSH action is abolished, folliculogenesis was impaired and ovarian apoptosis was negligible. Apoptosis is also the underlying mechanism of corpus luteum regression. In the endometrium, apoptosis has a role in rejuvenating the endometrium for growth during the next endometrial cycle and in regulating cellular homeostasis.

Endometrial adenocarcinoma is the most common gynaecological malignancy in Western countries, affecting mainly post-menopausal women with a frequency of 15-20 per 100 000 women per year. Over-expression of the cyclooxygenase (COX) enzymes and prostaglandin receptors has been demonstrated in endometrial adenocarcinoma as well as other gynaecological pathologies. Increased expression of the prostaglandin F2α (PGF2α) receptor (FP) has been previously demonstrated in endometrial adenocarcinoma. A role for the FP receptor in the promotion of endometrial adenocarcinoma has been shown, with evidence for elevated PGF2α-FP signalling up-regulating angiogenic and tumourigenic genes, and increasing proliferation and migration of neoplastic epithelial cells. This thesis examines signalling pathways regulated by and interacting with the FP receptor that influence chemokine expression and subsequent effects in endometrial adenocarcinoma. To investigate PGF2α-FP interactions in endometrial adenocarcinoma, an endometrial epithelial cell line of adenocarcinoma origin (Ishikawa cells) stably transfected with the FP receptor to levels seen in cancer was used (FPS cells). An antibody array identified the chemokine C-X-C motif Ligand 1 (CXCL1) as a target gene regulated by PGF2α-FP signalling in this cell line. Expression of CXCL1 and its receptor, CXCR2, were elevated in cancer tissue as compared to normal endometrium and localised to glandular epithelium, endothelium and stroma. The induction of CXCL1 expression in FPS cells and endometrial adenocarcinoma explants was determined to be by a signalling pathway involving Gq, the epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK). The infiltration of immune cells into endometrial adenocarcinoma as compared to normal endometrium was then investigated. Increased neutrophils were present in endometrial adenocarcinoma compared with normal endometrium, and the expression of CXCR2 was colocalised to neutrophils. In vitro chemotaxis assays demonstrated that conditioned media from PGF2α-treated FPS cells stimulated human neutrophil chemotaxis which could be abolished by CXCL1 protein immunoneutralisation from the conditioned media or antagonism of CXCR2 on neutrophils. Moreover, xenograft tumours in nude mice arising from inoculation with FPS cells had higher neutrophil infiltration compared to tumours arising from wild-type cells or following treatment of mice bearing FPS tumours with CXCL1-neutralising antibody. Therefore, the up-regulation of CXCL1 by PGF2α promoted neutrophil chemotaxis into endometrial adenocarcinoma. The expression of a further chemokine, CC motif Ligand 20 (CCL20) was determined to be regulated by PGF2α -FP signalling in endometrial adenocarcinoma, and expression of CCL20 and its receptor CCR6 was elevated in endometrial adenocarcinoma. The induction of CCL20 by PGF2α -FP signalling in FPS cells was dependent on the signalling molecules Gq, EGFR, ERK, calcineurin and nuclear factor of activated T-cells (NFAT). The treatment of endometrial epithelial cells with recombinant CCL20 caused a significant increase in proliferation. Finally interactions between the signalling pathway of another pro-inflammatory lipid, lysophosphatidic acid (LPA), and FP receptor signalling in endometrial adenocarcinoma were examined. LPA increased expression of the FP receptor and the FP target genes previously discussed in this thesis, CXCL1 and CCL20, in FPS cells. Expression of the LPA receptors (LPAR) 1, 2 and 3 was localised in endometrial tissue, and LPAR2 and 3 were found to be elevated in endometrial adenocarcinoma compared with normal endometrium, suggesting amplification of the PGF2α -FP signalling pathway by LPA was possible. Collectively, these data demonstrate that inflammatory cytokine signalling pathways regulated by PGF2α-FP activation can promote immune cell infiltration and proliferation of endometrial adenocarcinoma, and that interaction of LPA and PGF2α-FP signalling in endometrial adenocarcinoma may exacerbate the disease.

The purpose of this thesis is to explore the methodological and empirical issues relating to the economic evaluation of minimal access surgery (MAS). Given the likely increase in the utilisation of economic analysis in this area, it is crucial to explore whether the methods of economic evaluation have limitations in the face of the particular characteristics of MAS. The comparison of abdominal hysterectomy (AH) and transcervical endometrial resection (TCRE), for the treatment of menorrhagia, is used as a vehicle to develop methods in relation to MAS. Having reviewed the literature and issues relating to the economic analysis of this group of technologies, the empirical starting point of the thesis is the assessment of the limitations of economic evaluations alongside clinical trials, using a trial comparing AH and TCRE. Three major areas of weakness are identified, and alternative ways of addressing these weaknesses are explored in the remainder of the thesis. The first area of methodological development relates to the measure of benefit used in economic evaluation of MAS. In this clinical context, it is argued that the trade-offs that exist between MAS and conventional surgery, in terms of process characteristics and outcomes, should result in an important role for patients' preferences in the construction of a benefit measure. A cost-utility analysis using the standard quality-adjusted life year (GALY) is undertaken, using trial data augmented with valuation data from a further study. The lack of consistency between individual preferences and standard QALYs suggests a major weakness with this measure of benefit. The strengths and weaknesses of an alternative measure of benefit in cost-utility analysis - the ex ante healthy years equivalent (HYE) - are assessed based on a further valuation study. It is shown that it is feasible to elicit ex ante HYEs from patients and that this measure of benefit exhibits some consistency with other expressions of patients' preferences. However, the HYE is likely to impose a greater measurement burden than the standard QALY. The second area of methodological development in the thesis is the analysis of the generalisability of trial-based economic evaluation, given the limitations that often exist with the external validity of trials. A framework is developed within which trial and observational data can be synthesised. This facilitates the use of sensitivity analysis to explore the robustness of base-case (trial-generated) results to alternative sources of data, which may be more representative of routine practice. The third area of methodological development stems from the importance of patients' preferences in relation to MAS. This element relates to the use of methods to model and to evaluate management strategies which use patients' preferences to determine treatment allocation. It is concluded that preference-based decision making has the potential to be cost effective in relation to TCRE and AH, and MAS applications more generally. The thesis demonstrates the importance of continued development in the detailed methods of economic evaluation.