Dissertations / Theses on the topic 'Uterus'

Bei Frauen verursacht der schnelle Abfall des Östradiolspiegels während des Klimakteriums oft unangenehme Beschwerden, wie Depressionen, Hitzewallungen und Schlafstörungen. Darüber hinaus löst der reduzierte Hormonspiegel auch chronische Effekte aus, wie z.B. eine Abnahme der Knochendichte und -masse sowie eine starke Zunahme kardiovaskulärer Risiken. Zur Behandlung von klimakterischen Symptomen wird seit vielen Jahren die Hormonersatztherapie (HRT) verschrieben. In letzter Zeit konnte allerdings in mehreren Studien gezeigt werden, dass die HRT neben den positiven Effekten, wie Linderung bzw. Prävention von klimakterischen Symptomen, auch adverse Effekte induzieren kann. So besteht ein erhöhtes Risiko an Endometrium- oder Mammakarzinomen zu erkranken. Aufgrund dieser Ergebnisse besteht ein wachsendes Interesse an effektiven aber auch sicheren Alternativen zu der klassischen HRT als Behandlungsmaßnahme klimakterischer Symptome. Aus diesem Grund hat die Behandlung mit pflanzlichen Präparaten als Alternative zur HRT in den letzten Jahren zunehmend an Bedeutung gewonnen. Der in dieser Arbeit untersuchte Extrakt ERr 731® ist Bestandteil eines solchen Präparates, welches seit 1993 zur Behandlung von prämenopausalen Frauen mit Ameno- bzw. Oligomenorrhö und klimakterischen Symptomen angewendet wird. Die klinische Wirksamkeit bzw. der grundsätzliche Nachweis der biologischen Aktivität des Extraktes wurde in klinischen Studien untersucht, in denen gezeigt werden konnte, dass dieser eine Reduzierung klimakterischer Symptome bewirkte und dabei keine unerwünschten Nebenwirkungen aufwies. Die klinischen Beobachtungen deuteten auf eine Hormon- bzw. Östrogen-ähnliche Wirkungsweise von ERr 731® hin. Daher wurde im Vorfeld dieser Arbeit zur Untersuchung potentiell östrogener Effekte von ERr 731® und seiner Bestandteile in vitro-Untersuchungen durchgeführt, deren Ergebnisse zeigten, dass der Extrakt und seine Bestandteile Östrogenrezeptor β (ERβ)-selektiv in endometrialen Zellen und nur schwach Östrogenrezeptor α (ERα)-selektiv in Knochenzellen wirkten. Darauf aufbauend war das Ziel dieser Arbeit den pflanzlichen Extrakt ERr 731® hinsichtlich seiner Wirksamkeit und Sicherheit bezüglich Uterus und Knochen zu charakterisieren. Dazu wurden tierexperimentelle in vivo-Experimente durchgeführt, in denen untersucht wurde, ob der subkutan (s.c.) applizierte Extrakt östrogene bzw. potentiell ERα-antagonisierende Wirkung im Uterus ovariektomierter (ovx) Ratten besitzt. Zusätzlich wurde ermittelt, ob eine länger anhaltende orale Behandlung mit dem Extrakt sicher hinsichtlich proliferativer Veränderungen im Uterus ist und der Extrakt knochenprotektive Eigenschaften aufweist. In dieser Arbeit konnte gezeigt werden, dass sowohl der s.c. als auch der oral verabreichte Extrakt weder einen uterotrophen Effekt, noch auf mRNA-Ebene die grundlegenden Mechanismen, welche in der Regulation der Zellproliferation oder Wachstumskontrolle involviert sind, induziert. Die Wirkung des Extraktes wird dabei vermutlich hauptsächlich über die Aktivierung des ERβ vermittelt, der keine Stimulation der Proliferation induziert. Zusätzlich übte der Extrakt so keine östrogenen Effekte auf die untersuchten Östrogen-responsiven Gene aus. Die in dieser Arbeit durchgeführten in vivo-Untersuchungen lieferten Hinweise, dass die in vitro festgestellte ERβ-Selektivität des Extraktes auch in vivo zum Tragen kommt. Als funktionelle Auswirkung dieser ERβ-Aktivierung führte die ERr 731®-Behandlung zu einem ERα-antagonistischen Wirkprofil auf die uterinen Funktionen in Gegenwart einer niedrigen Östradioldosis. Somit konnte in dieser Arbeit die in den klinischen Studien erwähnte Anwendungssicherheit des Extraktes bezüglich des Uterus bestätigt werden. Für den Extrakt konnte allerdings, trotz der in vitro beobachteten schwachen Aktivierung des ERα in den U2OS-Karzinomazellen, in vivo keine knochenprotektive Wirkung nach 90-tägiger oraler Behandlung gezeigt werden. Die Ergebnisse dieser Arbeit und der klinischen Studien deuten darauf hin, dass der Extrakt als ein selektiver Östrogenrezeptor-Modulator (SERM) bezeichnet werden kann. Zur genaueren Beurteilung des SERM-Charakters des Extraktes sind allerdings noch weiterführende Untersuchungen hinsichtlich seiner Wirkung im Gefäßsystem, im Zentralen Nervensystem und in der Brustdrüse notwendig. Zur Untersuchung der molekularen Mechanismen, durch die der Extrakt seine Effekte ausübt, muss eine geeignete Zelllinie gefunden werden. In dieser sollten dann Untersuchungen mit einem ERβ-selektiven Agonisten als Positivkontrolle und kombinierte Behandlung mit einem ERβ-selektiven Antagonisten, der ERβ-vermittelte Effekte inhibiert, durchgeführt werden, um eine eindeutige Aussagen bezüglich der möglichen ERβ-selektiven Wirkung des Extraktes treffen zu können.

Thesis (Ph. D.)--West Virginia University, 2001.
Title from document title page. Document formatted into pages; contains xiv, 150 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 104-120).

The carcinoembryonic antigen-related adhesion molecules (CEACAM) play a significant role in numerous physiological processes, such as cell-cell and cell-ECMadhesion, angiogenesis, proliferation, etc. The objective is characterization of the CEACAM1 expression pattern in normal tissues of rat uterus.

During early pregnancy in ruminants, progesterone (P4) from the corpus luteum (CL) and interferon tau (IFNT) from the conceptus act on the endometrium to regulate genes including interferon stimulated genes (ISGs) that are hypothesized to be important for uterine receptivity and conceptus growth. Previous custom ovine cDNA array analyses identified candidate genes that were regulated by pregnancy, P4 and/or IFNT in the ovine uterus. The first study validated pregnancy, P4 and/or IFNT regulated genes identified by previous custom ovine cDNA microarray analyses. ACTA2, COL3A1, POSTN, SPARC, S100A2, STAT5A and TAGLN were examined. POSTN was upregulated by P4 and S100A2 was downregulated by IFNT. Moreover, functional studies showed that POSTN stimulated attachment of ovine trophectoderm cells. However, neither COL3A1, SPARC, ACTA2 nor TAGLN was regulated by pregnancy, P4 or IFNT in the ovine endometrium. Collectively, these results confirmed that POSTN and S100A2 are P4 and IFNT regulated, respectively, and likely involved in uterine receptivity to conceptus implantation during early pregnancy. The second study determined expression of ISGs in the CL of pregnant ewes. MX1, MX2, ISG15, OAS1, and RSAD2 mRNAs were increased on Day 14 of pregnancy and maintained to Day 18, indicating that IFNT induced expression of ISGs in the CL. These results confirmed that locally produced IFNT has paracrine effects and also endocrine effects on reproductive organs other than the uterine endometrium and maternal immune system.

RESUMO Os trabalhos de investigação, conducentes à elaboração do presente estudo morfofuncional, subordinado ao tema da "VASCULARIZAÇÃO ARTERIAL DO ÚTERO",fundamenta-se em conceitos da anatomia descritiva clássica, complementados por técnicas de estudo mais modernas, permitindo-nos observações originais. O principal objectivo é de definir um padrão descritivo da vascularização uterina e de estabelecer uma correlação anatomo-fisiológica e anatomo-clínica na descrição da angiomorfologia uterina, actualizando as descrições clássicas da artéria com dados de observação originais, segundo as técnicas de estudo angiomorfológicas correntemente empregues no Departamento de Anatomia da Faculdade de Ciências Médicas da Universidade Nova de Lisboa. Correlacionam-se as observações com os mais recentes dados publicados, no âmbito da imuno-histoquímica e da moderna bioquímica endocrinológica, uma vez que os conceitos modernos de fisiologia uterina e ginecológica praticamente dominam a vasta literatura científica mundial. Como objectivos particulares, ou linhas orientadoras da tese, escolhemos: - A definição de parâmetros descritivos do padrão genérico da vascularização uterina, actualizando a nomenclatura descritiva de acordo com a moderna Nomina Anatomica mundialmente debatida, desde o XIV Congresso Internacional da Federação Internacional das Associações de Anatomistas, sob a presidência do Prof. Doutor J.A. Esperança Pina (1994) e publicada em 1999-2001. - A comparação do caso humano com o do animal de experiência, por observação meticulosa do maior número de casos possíveis, realizando um estudo comparativo que nos permita extrapolar dados de experimentação animal para o caso humano; - O estabelecimento de uma correlação anatomo-fisiológica, por análise do comportamento da vascularização uterina, ao longo da vida, desde o nascimento até à menopausa, e perante as influências hormonais a que se encontra exposta. A tese constrói-se em torno de três núcleos fundamentais: 1. Um capítulo introdutório, de contextualização teórica, por enquadramento histórico dos estudos dos órgãos genitais femininos e da evolução das técnicas de diagnóstico e terapêutica do útero, focando as primeiras referências à técnica da histerotomia (Cesariana) (com a lenda persa do nascimento do herói Rostam, ou do nascimento do deus Asclepius), as primeiras representações da vascularização uterina (por LEONARDO e iii VESÁLIO), ou as primeiras descrições anatómicas do útero, da autoria de Portugueses (RODRIGO DE CASTRO, 1516 e AMATO LUSITANO, 1551). Prossegue a contextualização teórica com breve referência à recente evolução das técnicas de diagnóstico e terapêutica dos fibromiomas uterinos, mencionando de modo particular a evolução das técnicas de embolização arterial uterina, por nos parecer corresponder a um campo de aplicação imediata dos estudos da vascularização do útero. Termina este capítulo com breve referência aos trabalhos do Prof. Doutor J. MARTINS PISCO que tem actualmente, no nosso País uma das mais extensas listas de trabalhos efectuados com sucesso a nível mundial, no campo da embolização arterial de fibromiomas uterinos. 2. O segundo núcleo fundamental, intitulado "Angiomorfologia uterina" corresponde a extensa revisão bibliográfica dos estudos descritivos da vascularização uterina, desde logo ilustrando a resenha teórica com algumas imagens fotográficas de úteros humanos, seleccionadas da nossa colecção. A descrição da vascularização uterina, fundamentada em 1500 citações bibliográficas, organiza-se, de acordo com o paralelismo entre a estratificação histológica e angiológica do órgão, e a hierarquia funcional, regulada pelas cíclicas variações hormonais. Descreve-se a camada serosa e correspondente vascularização; a camada muscular e vascularização do miométrio; e, por fim, a camada mucosa e os vasos endometriais. Verifica-se, perante os dados colhidos da literatura mundial, o interesse do aprofundamento dos estudos morfológicos da microvascularização endometrial e da adaptação das descrições aos resultados dos modernos estudos funcionais obtidos por técnicas da imuno-histoquímica. 3. Fundamentados nos dados colhidos das revisões bibliográficas, elaborámos um projecto de investigação original, visando o estabelecimento da relação morfo-funcional resultante do aprofundamento dos estudos descritivos da angiomorfologia e da microvascularização do útero. O capítulo de trabalho experimental organiza-se em três principais passos: – No capítulo de Materiais e métodos, procede-se à escolha, por um lado do animal de experiência mais adequado para os estudos da vascularização uterina (por estudo comparativo ao longo da escala animal) e, por outro lado, à escolha de três das técnicas disponíveis no Laboratório de Anatomia Experimental e aplicáveis à investigação angiomorfológica do útero; iv - No capítulo de Resultados, procedemos à exposição das nossas observações de 25 úteros humanos e de 154 úteros de animais de experiência, segundo as três técnicas seleccionadas (dissecção, Injecção-corrosão-fluorescência, Injecção-diafanização e injecção-corrosão paraobservação de moldes vasculares em microscopia electrónica de varrimento), organizando aselecção da vasta iconografia coleccionada em três novos subcapítulos: o útero humano, oútero do animal de experiência e um estudo comparativo, essencial para validar osresultados do trabalho experimental. - O capítulo de trabalho experimental, inteiramente efectuado por estudos na artéria uterina do rato Wistar, abrange primeiramente a tentativa de definição macroscópica de territórios de vascularização, seguido das observações microscópicas conducentes à definição dos parâmetros angiomorfológicos característicos de cada uma das etapas da grande variabilidade a que se sujeita a vascularização uterina, ao longo da vida, incluindo a infância, a gravidez, a paridade e o envelhecimento, e consoante as fases do ciclo hormonal ovárico. Aperfeiçoámos essa tarefa com a elaboração de três experiências distintas, para análise dos efeitos microvasculares uterinos da administração exógena de preparados comerciais hormonais, por observação em microscopia electrónica de varrimento. De acordo com as leituras da literatura clássica sobre a metodologia do trabalho científico, completamos os trabalhos por um capítulo de síntese e critica dos resultados, sequencialmente organizado consoante cada um dos passos experimentais atrás referidos. SUMMARY The aim of the present thesis is the description of the uterine arterial network, complementing the classical concepts of descriptive Anatomy with modern techniques of anatomical research, thus achieving original final results and observations. One of the main objectives of the research is to establish physiological and clinical correlations in the description of the uterine angiomorphology, with the techniques currently available for angiomorphological research in the Department of Anatomy of Faculty of Medical Sciences of the New University of Lisbon. As guidelines to our research, we established the following specific objectives: - defining the descriptive parameters of the standard pattern of the uterine vasculature, according to the modern Nomina Anatomica, as underlined in the latest Federative Congresses of the International Federation of the Associations of Anatomists, one of which took place in Lisbon, in 1994, under the presidency of Professor J.A. Esperança Pina, the supervisor of the present works; - comparing the human uterus with the uterus of the experimental animal, to extrapolate the experimental observations in animals to the particular case of the human uterus; - establishing a correlation between the physiology and the anatomical observations of the uterine vasculature throughout life, from childhood to menopause and in relation to the hormonal influences to which the uterus is exposed. The thesis is built around three main chapters: 1) The introduction chapter defines the historical framework of the studies of the female genital anatomy and the historical evolution of the clinical management of common uterine diseases, focusing on the first historical references to the Caesarean section (such as the Persian legend of the birth of the hero ROSTAM, or that of the birth of ASCLEPIUS, the Greek god of Medicine); the first depictions of the uterine vasculature (by LEONARDO and VESALIUS) or the first anatomical descriptions of the uterus, by Portuguese authors (RODRIGO DE CASTRO, 1517, or AMATUS LUSITANUS, 1551). The theoretical context proceeds, with reference to the recent evolution of the clinical and surgical management of uterine fibroids, and a particular mention to the modern techniques of Uterine Fibroid Embolisation, which corresponds to one of the fields of interest of the anatomic studies of uterine arterial vascularization. 2) The second chapter, devoted to the anatomical description of the Uterine Angiomorphology, is based on an extensive review of the available Medical literature,illustrated by a selection of our own research observations of the human uterine vasculature. The description is organized in view of the parallelism between histological and angiological stratification and the functional hierarchy, under the control of the cyclic hormonal variations. Each layer of the uterine wall is depicted with photographs of the human uterus and descriptions of its specific vascular network: the serosa, the muscular Myometrium, and the mucosa, or endometrium. This classical description, based on extensive quotations of the international scientific literature, enhances our interest for the research of a more detailed knowledge of the endometrial microvascular network, accordingly to the modern physiologic results obtained through immunohistochemical studies. 3) The results of our experimental research, aiming to establish the intimate relationship between the anatomical and functional studies of uterine vasculature, are organized in three main steps: - The chapter of Materials and Methods debates the choice of the experimental animal, based on a short review of the comparative anatomy of the uterus, and uterine physiology, throughout the animal scale. The selection of three fundamental techniques of anatomic research is made from the current variety available in the Laboratory of Experimental Anatomy of the Lisbon School of Medical Sciences. - The Results of our personal research and observations of 25 human and 154 animal uteri,after dissection, and the techniques of arterial injection for the preparation of fluorescent corrosion casts, of vascular injection and clearing, and of arterial injection and preparation of corrosion casts for Scanning Electron Microscopy are rganized in terms of human or animal macroscopic anatomy and microvascular network, followed by a summary of the comparative anatomy of human and rat uteri, which is essential to validate the resultant experimental observations of the rat endometrial microvasculature. - The experimental research is entirely devoted to the uterine artery of the Wistar rat. The first step consists of the attempt to define macroscopic territories of vascularization, followed by microscopic observations for the definition of the angiomorphological pattern that is characteristic of each stage of the extreme variations to which the uterus is subject throughout life, from childhood to sexual maturity, throughout the hormonal cycle, in pregnancy, according to parity, and through ageing. We complete these observations with the experimental exposure of the Wistar rat uterus to pharmacologic preparations of hormones, currently available in clinical practice, and observations of the vascular uterine changes in Scanning Electron Microscopy. The outcome results of our anatomical observations are followed by a critical synthesis of the results.

Thesis (MTech (Radiography))--Cape Peninsula University of Technology, 2012
Introduction: Brachytherapy plays an essential role in the management of patients with cervical cancer. The high cervical cancer burden in Africa presents challenges with regard to provision and sustainability of these services. This study analysed treatment outcomes of two brachytherapy modalities, high dose rate (HDR) and low dose rate (LDR) intracavitary treatment for patients with cervical cancer, and evaluated the problems and challenges of the provision of these services within the African context. Methodology: The study was conducted using a case study approach with mixed methods at two sites in Africa, one in South Africa (Centre I) and the other in Kenya (Centre II). The study explored factors and issues affecting definitive radiotherapy of the patient with cervical cancer at the two sites with a focus on the brachytherapy treatment. The case study provided an opportunity to collect in-depth data consisting of quantitative and qualitative components that generated numeric and textual data. Treatment outcomes of one site treating with HDR and the other LDR intracavitary brachytherapy were retrospectively analysed for a maximum sample size of 193 (91%) patients in the HDR group and 49 (100%) patients in the LDR group. All patients were treated with external beam radiation therapy (EBRT) using parallel opposed beams (POP) for the patients that received LDR brachytherapy, and four field box technique or POP for those that received HDR brachytherapy. The linear quadratic formula was used to calculate the equivalent dose in 2 Gy fractions (EQD2) between the two groups.

Ninety six women, average age 47, who had a hysterectomy between October 1997 and June 1999 were initially interviewed in hospital and followed up for four months after discharge. The findings of the study indicate that adequate support was needed in early recovery period and discharge programs should take into consideration the needs of women with small children and those who have no onsite home support. Strategies used by the women to assist convalescence included support from family and friends but little in the way of health professional or community support. The majority of women returned to normal activities by four months. Communication between women and health professionals was also considered by the women to be important following discharge, especially in terms of information and reassurance about their progress during recovery.
Master of Science (Hons) (Health)

Background: Endometrial polyps are common in women at reproductive ages, and found in more than 11% of infertile women. Hysteroscopic polypectomy is recommended to alleviating symptoms in patients with abnormal uterine bleeding. While the relationship between an endometrial polyp and subfertility is not clearly established, there is some evidence that hysteroscopic polypectomy may improve fertility outcome in IVF patients. Accumulating evidence suggested that elevated levels of activated mast cells as well as elevated matrix MMPs and cytokines levels in the patients who suffer from endometrial polyps. Moreover, significant increases in glycodelin levels were found in patients’ plasma and uterine. And there was a significant negative relationship between plasma glycodelin and progesterone levels in patients with endometrial polyps. To further understand whether hysteroscopic polypectomy affects endometrial microenvironment that is conductive to embryo implantation, we recruited 9 IVF patients and use microarray to compare their endometrial gene expressions before and after polypectomy. Methods: We investigated the change of endometrial gene expression patterns before and after polypectomy. Three out of 9 samples were subjected to microarray study. Quantitative-PCR (qPCR) was used to confirm the expression in all 9 samples, and compared with endometrial samples taken from patients underwent natural (LH+7 days, n = 8) and stimulated (hCG+7 days, n = 8) IVF cycles but without polyps. The outcome of subsequent IVF cycle was obtained to correlate the change of gene expression patterns. Results: Microarray analysis demonstrated that no genes are commonly differentially expressed in all 3 samples. One of the samples has shown very heterogeneous result. Sixteen genes (hERα, hERβ, OLFM1, OLFM2, IL15, CXCL14, GPX3, CCL4, UPKIB, PAEP, MMP26, SLC1A1, MUC15, MUC16, TM4SF4 and TFPI2) that are differentially expressed in any 2 of the samples and genes related to endometrial receptivity (OLFM1, IL15, CXCL14, GPX3, PAEP, MMP26, SLC1A1, MUC16) were selected for further analysis. We found that 3 samples have a gene expression pattern similar to natural cycle (LH+7 days) after polypectomy; while the other samples have a gene expression similar to the stimulated cycle (hCG+7 days). Clinical findings of the treated patients did not have strong correlation with pregnancy outcome. One out of two patients who had gene expression patterns similar to natural cycle got pregnant; while one out of seven patients who has gene expression patterns similar to stimulated cycle get pregnant after polypectomy. Conclusion: Polypectomy modulates endometrial gene expression patterns in some patients similar to those in natural cycles. However, our data did not support endometrial polypectomy significantly improved pregnancy outcome in the limited number of patient subjects (n=9) in this study.
published_or_final_version
Obstetrics and Gynaecology
Master
Master of Medical Sciences

While premature birth is still one of the major clinical problems worldwide, the exact physiological mechanisms underlying myometrium activity during pregnancy remain unclear. In this thesis, a novel biophysically detailed model was constructed using available experimental data to simulate chemical, electrical and mechanical activity in a late pregnant rat uterine myocycte. The developed model has been used to elucidate the ionic mechanism underlying myometrium functionality, providing better insights in the function of the uterus during pregnancy. The model consisted of 15 membrane currents, intracellular calcium handling process coupled with a sliding actin-myosin filament mechanical model to describe uterine behaviour and contractile activity at the single myocyte level. Each of the ionic currents were modelled using Hodgkin-Huxley-type equations. The simulated current traces and current-voltage curves were validated with experimental recordings and the model was further validated by the ability to produce a bursting action potential (AP) during an external stimulus. The model replicated the effects of estradiol during pregnancy, modulating the amplitude and activation properties of individual Ca2+ and K+ currents, therefore altering the AP configuration to a tonic-like plateau. The model also reproduced the actions of drugs to inhibit certain channels to investigate their roles in myometrium. Sensitivity analysis was performed to examine the model's behaviour to changing parameters. A simple 1-D study was conducted to investigate how electrical signals propagate along strand of cells. Although the model successfully replicated results similar to recordings seen in the experiments, limitations have to be addressed and more studies have to be carried out to further improve the model.