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Orientador: Aarão Mendes Pinto-Neto / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-08T02:23:48Z (GMT). No. of bitstreams: 1 Costa_AurelioAntonioRibeiroda_D.pdf: 582824 bytes, checksum: b130d3e6304e9d014c75b64794caae29 (MD5) Previous issue date: 2006 / Resumo: a histeroscopia é um dos procedimentos mais realizados em ginecologia. Muitos ensaios controlados sugerem vantagens no uso prévio de misoprostol para diminuir a resistência da cérvix uterina; entretanto este tipo de estudo ainda é escasso quando se compara o uso do misoprostol prévio à histeroscopia diagnóstica em mulheres na pós-menopausa. avaliar os efeitos intra e pós-operatórios em mulheres na pós-menopausa, submetidas à histeroscopia diagnóstica, sem anestesia, com uso prévio de misoprostol para amadurecimento do colo uterino. Sujeitos e métodos: foi realizado um estudo tipo ensaio clínico, duplamente mascarado, randomizado, em pós-menopausadas que se submeteram à histeroscopia diagnóstica sem anestesia no IMIP e no hospital Barão de Lucena, em Recife, Pernambuco. Foram incluídas 120 pacientes alocadas aleatoriamente em dois grupos, sendo 60 com uso de 200µg de misoprostol via vaginal e 60 com uso de 200µg de placebo. Foram estudadas as seguintes variáveis: tempo do procedimento, freqüência e intensidade da dor durante o exame, necessidade de dilatação cervical adicional, efeitos colaterais (sangramento genital, náuseas, vômitos, diarréia, hipertermia) e complicações (perfuração uterina, falso pertuito, laceração cervical, infecções, dor no pós-operatório imediato). Para análise estatística, utilizaram-se os testes de qui-quadrado de associação, testes exato de Fisher e Mann-Whitney para comparação dos grupos, considerando-se significativo um erro alfa menor que 5%. Resultados: os grupos foram semelhantes em relação à média de idade (61,3 e 59,2, p=0,09), paridade (04 e 04, p=0,88), IMC (27 e 27,5, p=0,55) e tempo de menopausa (12,5 versus 9,6, p=0,52), intervalo entre medicação e exame (8,4 e 8,2, p=0,4), meio distensor com CO2 (39% versus 32%, p=0,44) e indicações por mioma, espessamento ou sangramento genital (p=0,52; 0,37; 0,62, respectivamente). O grupo do misoprostol apresentou menor intensidade da dor durante o procedimento, tanto na comparação das medianas (05 versus 07, p=0,02) quanto nos escores acima de cinco (44,6% versus 66,7%, p=0,01). Não houve diferenças entre os grupos com relação à duração do procedimento (2,4 versus 2,0 min, p=0,3), presença de dor ao exame ou na biópsia (p=0,74 e p=0,19, respectivamente). Não ocorreu diferença na necessidade de dilatação (17,2 versus 20,3, p=0,66) nem na presença de efeitos colaterais ou complicações. Também não se observaram diferenças significativas na presença e intensidade da dor após o procedimento. Conclusão: o uso prévio de misoprostol parece diminuir a intensidade da dor durante a histeroscopia diagnóstica em pós-menopausadas; entretanto não demonstrou diferenças significativas em relação à diminuição do tempo para o procedimento e nem da necessidade de dilatação cervical entre os grupos, sugerindo não utilizá-lo rotineiramente e sim em alguns casos selecionados / Abstract: hysteroscopy is one of the most useful procedure to study uterine cavity and widely used in gynecologic clinic. Although many controlled clinical trials have shown advantages in the use of misoprostol in realeasing cérvix uterine resistanse, there are few evidence regarding its use before office hysteroscopy in postmenopausal women. Objective: to compare the trans and postoperative results of postmenopausal women underwent office hysteroscopy without anesthesia that used misoprostol or placebo previouslly to the procedure to mature the uterine cérvix in two teaching hospitals in Recife. Patients and methods: a randomized, double masked, clinical trial was conducted enrolling 120 postmenopausal women who had been submitted to office hysteroscopy without anesthesia at IMIP and Barão de Lucena teaching hospital. Among those patients 60 were randomized allocated in the study group using 200µg of vaginal misoprostol and 60 took part in the placebo group using 200µg of a vaginal placebo.The following variable were studied: duration of the procedure, frequency and intensity of pain during the exame, necessity of additional dilatation, side effect as (genital bleeding, nauseas, vomits, diarrhea, and hyperthermia) and complications (uterine perforation, false way, cervical laceration, infections and pain in the imediate postoperatory period). For analysis statistics we used the tests of association qui-square, accurate test of Fisher and Mann-Whitney for comparison of the groups, considering itself significant with lesser alpha error that 5%. Results: We found no significant statistic difference between the groups regarding age (61,3 e 59,2, p=0,09), parity (04 e 04, p=0,88), IMC (27 e 27,5, p=0,55) ,time since menopause (12,5 versus 9,6, p=0,52), time between medication and hysteroscopy (8,4 e 8,2, p=0,4), distensor fluid with CO2 (39% versus 32%, p=0,44) and the indication of the exam (myoma, endometrial thickness and postmenopausal bleeding (p=0,52; 0,37; 0,62, respectively).There was no differences between the groups with regard to duration of the procedure, presence of pain to the examination or hystopathologic findings. No differences in the necessity of extra cervical dilatation nor in the presence of side effects or complications was observed. We also didn't find any statistic difference regarding the presence and intensity of pain after the procedure. The misoprostol group had less pain during hysteroscopy than placebo group (p= 0,02). Conclusions: Although the previous use of misoprostol seems to decrease the intensity of pain during the hysteroscopy in postmenopausal women when compared with those who had used placebo, there were no significant difference in duration of procedure and necessity of extra cervical dilataion. Therefore we do not suggest its routinely use, but only in selected cases / Doutorado / Doutor em Tocoginecologia

Breast cancer is a disease that afflicts a significant proportion of women globally. 5-10% of breast cancer cases are linked to inherited polymorphisms in critical genes such as BRCA1, a tumour suppressor essential for genomic stability. A dysfunctional BRCA1 gene can increase breast cancer risk by 60-80%. Previous microarray analysis established that differential gene expression in unperturbed Epstein-Barr virus transformed lymphocyte cell lines (EBV-LCL) was able to distinguish BRCA1 mutation carriers from controls with a high degree of accuracy. A 43-gene radiation-independent classifier for BRCA1 status was constructed. We hypothesize that this differential gene expression can be observed in a subset of these genes using quantitative PCR (qPCR) in both EBV-LCL and B-lymphocytes isolated from patients with known BRCA1 mutation carrier status. The 43-gene classifier was analyzed using gene ontology analysis and 4 target genes selected based on predictive value, expression intensity and gene ontology similarity. Genes selected were CXCR3, TBX21, MX2, and IFIT1, with GusB as an endogenous reference gene. EBV-LCL established from known BRCA1 mutation carriers and from BRCA1 wildtype individuals were obtained and RT-qPCR (reverse transcriptase qPCR) performed on isolated RNA. Our results showed significant downregulation of CXCR3 and TBX21 in BRCA1 mutation carriers (p=0.018 and p=0.003, respectively), as expected from previous microarray results. IFIT1, while showing a non-significant upregulation (p=0.183), agreed with the expected trend. MX2 did not show significant differential expression. These results indicate that differential gene expression has the potential to accurately distinguish pathogenic variants, even if it may require EBV immortalization of B-lymphocytes. To determine whether the assay could be extended to fresh blood samples, B-lymphocytes were isolated from patients with known BRCA1 mutation carrier status from North York General Hospital in Toronto, ON. An optimized protocol to enrich the B-lymphocyte population using magnetic separation was developed for this purpose. RT-qPCR using RNA isolated from these lymphocytes showed no significant differential gene expression in CXCR3 and TBX21. However, a low sample size, use of non-sequenced controls and a need for further qPCR optimization may call these results into question. In addition, problems with blood sample transportation from off-site sources resulted in an unacceptable drop in RNA integrity. While this gene expression assay may be limited to screening a small number of blood samples, results indicate that may still have clinical relevance that can be explored. This would necessitate further optimization of the qPCR methodology and resolution of the issues surrounding RNA integrity and sample transport. / Thesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2013-09-26 13:13:50.809

A novel clinical assay for the assessment and subsequent treatment of Haemonchus infection in sheep to slow down the development of anthelmintic resistance – the FAMACHA / Dissertation (MSc)--University of Pretoria, 2001. / Veterinary Tropical Diseases / unrestricted