published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Anatomy / Master / Master of Philosophy

Chronic inflammation stimulates mammary tumourigenesis by disrupting signalling interactions between the epithelial ducts and the surrounding stromal microenvironment. Adipocyte enhancer-binding protein 1 (AEBP1) promotes mammary epithelial cell hyperplasia as a stromal factor that enhances activity of the proinflammatory transcription factor Nuclear Factor-?B (NF-?B) in macrophages. Aberrant NF-?B activity in macrophages elevates production of proinflammatory signals and the ligand sonic hedgehog (Shh), a significant contributor to tumourigenesis. In this study, Shh expression was elevated in macrophages isolated from transgenic mice (AEBP1TG) that overexpress AEBP1. Transient overexpression of AEBP1 in a macrophage cell line resulted in increased Shh expression. Furthermore, hedgehog target genes Gli1 and Bmi1 were up-regulated in mammary epithelium of AEBP1TG mice and HC11 mammary epithelial cells co-cultured with AEBP1TG macrophages. Growth of HC11 cells and mammary tumours was enhanced in response to AEBP1TG macrophages. These findings suggest that macrophage AEBP1 overexpression contributes to mammary hyperplasia through enhanced hedgehog signalling.

No description available.

Thesis (M.Med.Sc.)--University of Hong Kong, 1982. / Also available in print.

Thesis (Ph. D.)--University of North Carolina at Greensboro, 2006. / Title from PDF title page screen. Advisor: Ron Morrison; submitted to the School of Human Environmental Sciences. Includes bibliographical references.

Thesis (M.S.)--University of Delaware, 2005. / Principal faculty advisor: Mary C. Farach-Carson, Dept. of Biological Sciences. Includes bibliographical references.

Made available in DSpace on 2014-06-11T19:28:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2002-02-25Bitstream added on 2014-06-13T18:32:31Z : No. of bitstreams: 1 sousa_cp_me_arafo.pdf: 282394 bytes, checksum: da271e59dd6d66efadb106512dc6504c (MD5) / O objetivo deste trabalho foi avaliar a prevalência e severidade do crescimento gengival em pacientes brasileiros sob terapia com nifedipina, por meio do uso do Novo Índice Clínico para Crescimento Gengival Induzido por Drogas(Índice DIGO). O estudo foi realizado em 35 pacientes sob terapia com nifedipina (grupo teste ) e em um grupo controle de 35 pacientes. Foram feitos os registros das variáveis demográficas (idade e sexo do paciente), farmacológicas (dose e tempo de uso da nifedipina) e das variáveis periodontais (índice de placa, índice gengival, profundidade de sondagem, nível de inserção clínico, sangramento à sondagem) e do crescimento gengival. O teste Z (nível de significância a 5% e p<0.05) e a correlação de Spearman foram usados para a comparação dos resultados entre os grupos teste e controle. Os resultados mostraram que o crescimento gengival foi observado em 68% dos pacientes e que não houve associação entre o crescimento gengival e as variáveis demográficas e as variáveis farmacológicas. No entanto, houve associação entre o crescimento gengival e as variáveis periodontais, exceto para o índice de placa. Podemos concluir que a inflamação gengival apresentou influência no crescimento gengival associado à nifedipina. / The aim of this study was to evaluate the occurrence of nifedipine induced GO in patients and the risk factors associated using a New Clinical Index for Drug Induced Gingival Overgrowth (DIGO) and the relation between The study was carried out with 35 patients under treatment with nifedipine (test group) and 35 patients without treatment (control group). There was assessed the characteristics of demographic (age, gender), pharmacological (dose, time of use), periodontal variables (plaque index, gingival index, probing depth, attachment level, bleeding on probing) and gingival overgrowth of the sample. The test Z (significance level at 5% - p< 0.05) and the Spearman correlation were used to compare data in test and control groups. Gingival overgrowth was noticed in 68% of patients. The statistical analyses showed no association between the gingival overgrowth and demographic and pharmacological variables, except for the plaque index. However, there was an association between the gingival overgrowth and periodontal variables. Further, it is possible to conclude that the presence of gingival inflammation was the main factor of risk to promote nifedipine-induced gingival overgrowth.

We present a case of a woman with a history of Congenital Adrenal Hyperplasia (CAH) diagnosed at the age of 12, who was referred to our unit for surgical treatment. Despite the initial diagnosis was an indirect inguinal hernia, it was a misdiagnosis. Once in our service, this was corrected into clitoromegaly secondary to CAH. Physical examination and imaging test discarded other abnormalities, such as secondary effects androgenization. Regarding surgical treatment, the techniques used were Spencer and Allen combined with Kumar, which are the most used for clitoroplasty but also less used in Peru.

Angioplasty, or the use of rapidly deploying stents, is a common treatment for reopening narrowed vasculature often caused by atherosclerotic plaque. However, in-stent restenosis (ISR) induced by intimal hyperplasia is a common challenge to angioplasty. High impact stresses from current stent deployment processes have been linked to intimal hyperplasia; thus a stent that is gradually deployed over a longer period of time holds potential to mitigate these stresses. This work hypothesizes that resorbable polymeric links can be used as a triggering mechanism to enable repeatably controlled deployment of a compliant nitinol stent design with the eventual goal of reducing intimal hyperplasia. The aims of this work include the structured design process and design validation of a stent intended to meet this challenge. A structured design process was used to develop a multi-stage, gradually deploying nitinol stent in which PDLG (DL-lactide/Glycolide copolymer) bioresorbable links constrained specific mechanical cells within the stent geometry, thus limiting initial deployment to an intermediate diameter and allowing for secondary gradual deployment as the PDLG degraded via a combination of bioresorption and creep. A finite element analysis was carried out to design the link geometry to hold the stent at an intermediate stage (90% of final diameter) upon initial deployment, and enable a gradual secondary deployment phase lasting several minutes. Prototypes were then manufactured and the design was validated in a flow chamber mimicking the conditions of human blood flow and temperature. Using a camera and image processing methods, the diameter increase of the stents was tracked over time to characterize the secondary gradual deployment process of the stents. Results showed the links constrained the stents to an initial ~90% diameter upon initial deployment, followed by a gradual, secondary deployment with an average 63.2% rise time of 16.2 minutes. Creep was observed to be the primary driver of the gradual deployment, followed by subsequent bioresorption of the material. All prototypes exhibited gradual secondary deployment without any visible delamination of the bioresorbable links from the stent struts. Based on these findings it can be concluded our hypothesis has been demonstrated, and that a feasible gradually deploying stent design has been mechanically validated, preparatory to pre-clinical studies of its efficacy. Prior to clinical application, future in vivo work is needed to compare actual ISR rates with this stent design to other commonly used stent designs in preclinical trials. In addition, further preclinical work is needed to compare ISR rates through several stent design parameters such as initial deployment diameter, gradual deployment rate, final deployment diameter, and stent sizes to give insights into the optimal stent design. We anticipate that this gradually expanding stent design could reduce in-stent restenosis and improve clinical outcomes.