Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2018-03-21T11:50:05Z No. of bitstreams: 1 AndreiaFerreiraDoCarmo_TESE.pdf: 2170675 bytes, checksum: 49a8001d1651a77b1ebea9cb5d0cc766 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-03-23T11:55:44Z (GMT) No. of bitstreams: 1 AndreiaFerreiraDoCarmo_TESE.pdf: 2170675 bytes, checksum: 49a8001d1651a77b1ebea9cb5d0cc766 (MD5) / Made available in DSpace on 2018-03-23T11:55:44Z (GMT). No. of bitstreams: 1 AndreiaFerreiraDoCarmo_TESE.pdf: 2170675 bytes, checksum: 49a8001d1651a77b1ebea9cb5d0cc766 (MD5) Previous issue date: 2017-12-15 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O horm?nio glicoproteico estaniocalcina 2 (STC2) est? envolvido na carcinog?nese e progress?o de muitos tipos de c?ncer. No entanto, seu significado cl?nico e mecanismos moleculares no carcinoma de c?lulas escamosas oral (CCEO) foram pouco estudados e permanecem incertos. O presente estudo investigou associa??es da express?o da STC2 com par?metros clinicopatol?gicos e de sobrevida em pacientes com CCEO. Al?m disso, foram avaliados os efeitos biol?gicos causados pela redu??o dos n?veis de STC2 em linhagens celulares de CCEO e fibroblastos associados ao c?ncer (do ingl?s CAF ? carcinoma associated fibroblasts). A an?lise imunoistoqu?mica em 100 casos de CCEOs prim?rios indicou que a superexpress?o da STC2 foi associada com o par?metro N do sistema TNM e foi um fator de risco independente para sobrevida espec?fica da doen?a e sobrevida livre de doen?a em pacientes com CCEO. Usando ensaios in vitro, foi demonstrado que o silenciamento da STC2 em linhagens de CCEO promoveu a apoptose e reduziu a prolifera??o celular, migra??o, invas?o e transi??o epit?lio-mesenquimal. An?lises adicionais revelaram que o CAF expressa maiores n?veis de STC2 do que as c?lulas de CCEO. O silenciamento da STC2 no CAF reduziu a invas?o celular do CCEO, sugerindo que a STC2 liberada por CAFs contribui para um fen?tipo mais invasivo no CCEO. Esses resultados sugerem que a STC2 modula eventos importantes para a tumorig?nese oral e pode ser um biomarcador progn?stico para pacientes com CCEO. / The glycoprotein hormone stanniocalcin 2 (STC2) is involved in carcinogenesis and progression of several cancer types. However, its clinical significance and molecular mechanisms in oral squamous cell carcinoma (OSCC) have been partially studied and remain uncertain. In the present study, we investigated associations of STC2 expression with clinicopathological and survival parameters of OSCCs patients. We also determined the biological effects caused by STC2 downregulation in OSCC and cancer associated fibroblasts (CAF) cell lines. Immunohistochemical analysis in 100 cases of primary OSCC indicated that STC2 overexpression was associated with N stage (TNM staging) and was an independent risk factor for disease-specific survival and disease-free survival in patients with OSCC. Using in vitro assays, we demonstrated that STC2 knockdown in OSCC cell lines promoted apoptosis, and reduced cell proliferation, migration, invasion and epithelial-mesenchymal transition. Further analysis revealed that CAF expresses higher levels of STC2 than OSCC cells. Knockdown of STC2 in CAF reduced OSCC cell invasion, suggesting that STC2 released by CAF contributes to a more invasive phenotype in OSCC. These results suggest that STC2 modulates important events for oral tumorigenesis and can be a prognostic biomarker for OSCC.

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-05-04T19:26:50Z No. of bitstreams: 1 DANIELE_CRISTOV?O_ESCOUTO.pdf: 3899595 bytes, checksum: 60af701fccf65168e901b103c704e2fe (MD5) / Rejected by Sheila Dias (sheila.dias@pucrs.br), reason: Devolvido devido ao t?tulo da capa (em ingl?s) estar diferente do t?tulo da folha de rosto e ficha catalogr?fica (em portugu?s). on 2018-05-16T19:01:31Z (GMT) / Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-05-17T11:39:29Z No. of bitstreams: 1 DANIELE_CRISTOV?O_ESCOUTO.pdf: 3899595 bytes, checksum: 60af701fccf65168e901b103c704e2fe (MD5) / Rejected by Caroline Xavier (caroline.xavier@pucrs.br), reason: Devolvido devido ao t?tulo da capa (em ingl?s) estar diferente do t?tulo da folha de rosto e ficha catalogr?fica (em portugu?s). on 2018-05-28T18:04:10Z (GMT) / Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-09-03T19:01:37Z No. of bitstreams: 1 DANIELE_CRIST?V?O_ESCOUTO.pdf: 2805745 bytes, checksum: c76c0d3c115aae92a7015f9312fd9604 (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-09-05T13:05:03Z (GMT) No. of bitstreams: 1 DANIELE_CRIST?V?O_ESCOUTO.pdf: 2805745 bytes, checksum: c76c0d3c115aae92a7015f9312fd9604 (MD5) / Made available in DSpace on 2018-09-05T13:40:27Z (GMT). No. of bitstreams: 1 DANIELE_CRIST?V?O_ESCOUTO.pdf: 2805745 bytes, checksum: c76c0d3c115aae92a7015f9312fd9604 (MD5) Previous issue date: 2018-03-19 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Introdu??o ? A distin??o adequada dos casos de alto risco para eventos graves nas doen?as hipertensivas gestacionais, n?o apenas pr?-ecl?mpsia, ? um desafio cl?nico. O modelo fullPIERS ? uma ferramenta simples e de baixo custo que utiliza vari?veis cl?nicas para estratificar a probabilidade de eventos adversos em gestantes com pr?-ecl?mpsia. O fator de crescimento placent?rio (PlGF) ? um biomarcador com concentra??es reduzidas no plasma de mulheres com pr?-ecl?mpsia e com crescente emprego na avalia??o de gestantes com suspeita de pr?-ecl?mpsia. Objetivos ? O objetivo deste estudo ? estimar a acur?cia do modelo fullPIERS e do biomarcador PlGF como preditores de desfechos adversos maternos em gestantes com doen?a hipertensiva gestacional. M?todos ? Estudo de coorte prospectiva em um hospital terci?rio em Porto Alegre, Brasil, que incluiu gestantes admitidas com press?o arterial sist?lica ? 140 e/ou press?o arterial diast?lica ? 90 mmHg a partir da 20? semana de gesta??o. Os piores valores de vari?veis cl?nicas e laboratoriais dentro das primeiras 48 horas de admiss?o foram coletados. Desenvolvimento de eventos adversos foi acompanhado por um per?odo de 14 dias. Concentra??es plasm?ticas maternas de PlGF do momento da admiss?o foram mensuradas. Resultados ? 405 gestantes foram inclu?das no estudo. Entre as 351 mulheres inclu?das na an?lise do modelo fullPIERS, 20 (5%) desenvolveram pelo menos um evento adverso materno dentro de 14 dias de interna??o. O modelo fullPIERS teve pouca capacidade discriminativa para prever desfechos em 48 horas [AUC 0,639 (95% CI 0,458-0,819)]. A acur?cia do modelo foi ainda mais baixa dentro de sete semanas da admiss?o [AUC 0,612 (95% CI 0,440-0,783)]; a capacidade discriminativa manteve-se similar dentro de 14 dias da admiss?o [AUC 0,637 (95% CI 0,491-0,783)]. A calibra??o do modelo fullPIERS tamb?m foi ruim: inclina??o 0,35 (95% CI 0,08-0,62) e intercepto 1,13 (95%CI -2,4-0,14). A an?lise do PlGF incluiu 392 gestantes. PlGF <5? percentil esteve associados a eventos adversos maternos dentro de 48 horas em gestantes inclu?das antes de 35 semanas com sensibilidade de 0,80 (0,4-0,96), valor preditivo negativo (VPN) de 0,98 (0,9-0,99) e AUC ROC de 0,672 (IC 95% 0,5-0,9). PlGF <100 pg/mL apresentaram sensibilidade de 0,8 (0,4-0,96), especificidade de 0,6 (0,5-0,7) e VPN de 0,99 (0,94-0,99) em mulheres ap?s 37 semanas de gravidez. PlGF apresentou bom desempenho para prever parto at? 14 dias em gestantes inclu?das antes de 35 semanas. PlGF <5? percentil esteve associado a rec?m-nascido pequeno para idade gestacional (PIG) com sensibilidade de 0,75 (0,6-0,9), especificidade 0,65 (0,5-0,7), NPV de 0,87 (0,79-0,94) e AUC ROC 0,698 (0,6-0,79), em gestantes com <35 semanas, a acur?cia diminuiu com o aumento das idades gestacionais. Conclus?es ? O modelo fullPIERS e a concentra??o de PLGF mostraram baixa acur?cia na predi??o de desfechos adversos maternos em mulheres com doen?a hipertensiva gestacional, incluindo pr?-ecl?mpsia. O modelo fullPIERS teve desempenho inferior na nossa amostra quando comparado com o estudo que validou este teste. O PLGF parece ser um biomarcador para uso como ferramenta adicional na predi??o de parto dentro de 14 dias e rec?m-nascidos PIG, especialmente em gestantes antes da 35? semana gestacional. / Introduction - Singling out high-risk patients from the diverse hypertensive disorders of pregnancy, and not only preeclampsia, is a challenge for clinicians. The fullPIERS model is a simple and low-cost evaluation instrument using clinical variables to stratify the adverse outcomes probability of pregnant women with high-risk preeclampsia. Placental growth factor (PlGF) levels are reduced in preeclampsia and are increasingly being used as a biomarker in the assessment of this disease. Objectives - The aim of the study is to evaluate the performance of the fullPIERS model and PlGF to predict adverse outcomes in women with hypertensive disorders of pregnancy. Methods - A prospective cohort study carried out at a teaching hospital in Porto Alegre, Brazil enrolling pregnant women admitted with a systolic blood pressure ? 140 mmHg and/or a diastolic blood pressure ? 90 mmHg from the 20th week of gestation. First 48 hours of admission worst clinical and laboratory data were recorded and the development of adverse maternal and perinatal outcomes scrutinised up to 14 days. Admission maternal plasma PlGF concentrations were measured. Results ? A total of 405 women were enrolled. From the 351 women included in the fullPIERS model analysis, 20 (5%) developed at least one of the combined maternal adverse outcomes. The fullPIERS model had poor outcomes discrimination at 48h [AUC 0.639 (95% CI 0.458-0.819)]. At the seventh admission day, the model?s accuracy was even lower [AUC 0.612 (95% CI 0.440-0.783)]; the model?s discriminative ability remained similar [AUC 0.637 (95% CI 0.491-0.783)] at 14 days. Calibration of the fullPIERS model was poor: slope - 0.35 (95% CI 0.08-0.62), intercept -1.13 (95%CI -2.4-0.14). PlGF analysis included 392 women. PlGF < 5th percentile predicted maternal adverse outcomes within 48h in women with gestation < 35 weeks with sensitivity of 0.80, NPV of 0.98 and AUC ROC of 0.672 (CI 95%0.5-0.9). The threshold of <100 pg/mL, had best accuracy in women after 37 weeks of pregnancy, sensitivity of 0.8, specificity of 0.6, negative predictive value of 0.99 and PPV of 0.04. PlGF had good performance to predict delivery within 14 days in women presenting before 35 weeks. PlGF <5th percentile predicted delivery of a SGA infant with sensitivity of 0.75, specificity 0.65, PPV of 0.45, NPV of 0.87, and AUC ROC 0.698, in women with gestation < 35 weeks, accuracy decreased at later gestational ages. Conclusion - In conclusion, in our sample the fullPIERS model and PlGF were limited predictors of maternal adverse outcomes in pregnant women with hypertensive disorders of pregnancy, including preeclampsia. The performance of the fullPIERS model in our sample was inferior to that of the original cohort. PlGF as a biomarker appears to be an additional tool to predict delivery within 14 days and SGA newborn in women before 35 weeks gestation.

Made available in DSpace on 2015-04-14T13:32:37Z (GMT). No. of bitstreams: 1 408203.pdf: 902552 bytes, checksum: 43eeacb29fa587011c5d5f9705597d22 (MD5) Previous issue date: 2008-12-01 / Objetivo: analisar o comportamento do ?ndice de respira??o superficial, press?o inspirat?ria m?xima e volume corrente no per?odo pr?-extuba??o de crian?as submetidas ? ventila??o mec?nica. Delineamento: estudo transversal observacional prospectivo. M?todos: entre Agosto de 2007 e agosto de 2008, foram avaliadas todas as crian?as aptas para a retirada da ventila??o mec?nica, de acordo com a equipe m?dica do Hospital S?o Lucas da PUCRS. Foram mensuradas vari?veis ventilat?rias (volume minuto expirat?rio, freq??ncia respirat?ria, press?o inspirat?ria e expirat?ria m?ximas). A partir destas vari?veis, calculou-se o volume corrente e o ?ndice de respira??o superficial. O sucesso de extuba??o foi considerado quando n?o houve reintuba??o em at? 48 horas ap?s a retirada do tubo endo-traqueal. Resultados: foram inclu?das no estudo 100 crian?as, com idade m?dia de 2,1 anos. Treze crian?as necessitaram de reintuba??o (13%). O peso m?dio foi de 9,6Kg e o tempo m?dio de ventila??o mec?nica foi de 6,5 dias. A maioria dos pacientes era do sexo masculino (63%) e apresentava diagn?stico de bronquiolite viral aguda (47%). As crian?as menores de um ano (61) apresentaram 18% de falha de extuba??o. A press?o inspirat?ria m?xima apresentou diferen?a significativa entre o grupo sucesso e falha de extuba??o (- 62,6 ? 29 cmH2O vs -42,7 ? 20,2 cmH2O; p=0,03). Atrav?s da curva ROC identificou-se 82% de sensibilidade e 55% de especificidade no ponto de corte da press?o inspirat?ria m?xima de -37cmH2O (?rea de 0,7). Conclus?es: a press?o inspirat?ria m?xima parece ser a melhor vari?vel para identificar crian?as com potencial para sucesso de extuba??o, mas com um poder preditivo considerado baixo. As vari?veis ventilat?rias analisadas apresentaram uma dispers?o muito grande, tanto na amostra geral, quanto na subdivis?o por doen?a e faixa et?ria.

Made available in DSpace on 2014-12-17T14:13:34Z (GMT). No. of bitstreams: 1 AnaMCS.pdf: 1887892 bytes, checksum: 05f9c6bffc3d95915a924712e4e7b5c7 (MD5) Previous issue date: 2007-12-19 / The purpose of this paper was to study patients with congenital and acquired hemiparesis, their clinical aspects, the presence or not of epileptic seizures, and electroencephalographic (EEG) and Magnetic Resonance Imaging (MRI) findings. We analyzed the interrelation between etiology, the presence and seriousness of epileptic seizures (ES) and the possible causes of refractoriness. This is a prospective study using the clinical diagnosis of a child neurologist, who attested to the presence of unilateral motor lesions. We compared the electroencephalographic findings in patients with or without epileptic seizures, and investigated if among the former, these seizures were controlled or not, their likely etiology and risks of refractoriness. EEG background activity on the lesion and contralateral side was analyzed, in addition to the presence of concomitant epileptiform activity. Encephalon MRIs of all the patients were studied to correlate etiology and the control or not of epileptic seizures. The disorganization of bilateral EEG activity correlated with the difficult-to-control epileptic seizures. Suitably organized background activity contralateral to the lesion is a good prognosis in relation to epileptic seizures. Focal epileptogenic activity does not necessarily predispose to epileptic manifestation. The MRI is more important in determining etiology than in prognosing epileptic seizures. This study used a multidisciplinary approach involving child neurologists, a physical therapist and a neuroradiologist. This meets the criteria of multidisciplinarity of the Postgraduate Program in Health Sciences / O objetivo do nosso trabalho foi estudar pacientes com hemiparesia, cong?nitas e adquiridas, seus aspectos cl?nicos e epidemiol?gicos, a presen?a ou n?o de crises epil?pticas e os achados eletrencefalogr?ficos e de neuroimagem por Resson?ncia Nuclear Magn?tica. Tentando relacionar a etiologia ? presen?a e gravidade de crises epil?pticas e as poss?veis causas de refratariedade. Trata-se de um estudo prospectivo a partir do diagn?stico cl?nico por um neurologista infantil que atestou a presen?a de les?o motora unilateral. Compararam-se os achados eletrencefalogr?ficos em pacientes sem ou com crises epil?pticas, e dentre esses ?ltimos, se h? ou n?o controle das crises, sua prov?vel etiologia e riscos de refratariedade. Analisou-se a atividade de base do EEG do lado da les?o e contra lateral a esta, al?m da presen?a de atividade epileptiforme concomitante. Estudaram-se as RNM do enc?falo realizadas em todos os pacientes, tentando relacionar a etiologia e controle ou n?o de crises epil?pticas. A desorganiza??o da atividade de base bilateral no EEG correlacionou-se com crises epil?pticas de dif?cil controle. A atividade de base adequadamente organizada contra lateral a les?o ? de bom prognostico em rela??o ?s crises epil?pticas. A atividade epileptog?nica focal n?o necessariamente predisp?e a manifesta??o epil?ptica. A RNM ? mais importante na determina??o da etiologia do que no progn?stico das crises epil?pticas. A realiza??o deste estudo foi concretizada pela abordagem multidisciplinar, envolvendo neurologistas infantis, fisioterapeuta e neurorradiologista. Este aspecto preenche os requisitos de multidisciplinaridade do programa de p?s-gradua??o em Ci?ncias da Sa?de

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-06-03T23:19:48Z No. of bitstreams: 1 GeorgeAlexandreLira_DISSERT.pdf: 12487121 bytes, checksum: e5befba62b31cf9c0849235dd847b32c (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-06-06T23:43:09Z (GMT) No. of bitstreams: 1 GeorgeAlexandreLira_DISSERT.pdf: 12487121 bytes, checksum: e5befba62b31cf9c0849235dd847b32c (MD5) / Made available in DSpace on 2016-06-06T23:43:09Z (GMT). No. of bitstreams: 1 GeorgeAlexandreLira_DISSERT.pdf: 12487121 bytes, checksum: e5befba62b31cf9c0849235dd847b32c (MD5) Previous issue date: 2015-08-31 / Excluindo-se os tumores de pele n?o-melanoma, o c?ncer colorretal ? o segundo mais comum no sudeste do Brasil; o terceiro na regi?o sul e na regi?o Centro-Oeste. J? no norte do Brasil, ? o quarto e, na regi?o Nordeste, o quinto. Avaliar vari?veis clinico-patol?gicos do c?ncer colorretal ? de fundamental import?ncia para se conhecer poss?veis desfechos na sobrevida dos pacientes portadores e pontuar caracter?sticas na progress?o tumoral como o perfil da invas?o tumoral e angiog?nese. O objetivo desse trabalho ? estudar as caracter?sticas cl?nico-patol?gicas dos pacientes portadores do c?ncer colorretal (CCR) na Liga Norte Riograndense contra o c?ncer em Natal-RN/BR, analisando as vari?veis cl?nicas e patol?gicas como par?metros de progn?stico e determinando o n?vel de express?o de prote?nas, tais sejam: E-caderina (E-cad), Beta-catenina (?-cat), Galectina-3 (Gal-3), Metaloproteinases de matriz (MMP) 2 e 9 e o Fator alfa de crescimento v?sculo-endotelial (VEGF-?) nos tecidos tumorais. Foi realizado um estudo retrospectivo dos casos de c?ncer colorretal da Liga Norte-Riograndense contra o C?ncer no per?odo de 1995 a 2005 em Natal-RN / Brasil. As vari?veis cl?nico-patol?gicas, tais como: idade, sexo, etnia, h?bitos de vida, hist?ria familiar, local do tumor prim?rio, grau de diferencia??o, estadiamento TNM, Dukes? modificado, tratamento e sobrevida foram analisadas. Os dados cl?nico-patol?gicos foram coletados dos prontu?rios m?dicos atrav?s de um formul?rio espec?fico e os dados foram armazenados em uma planilha do Excel. Um total de 534 pacientes foi selecionado do arquivo do setor da patologia dessa institui??o, mas 176 pacientes foram exclu?dos. 358 pacientes foram inclu?dos para an?lise epidemiol?gica e suas correla??es cl?nico-patol?gicas foram realizadas. 180 pacientes foram selecionados para estudos histol?gicos e imunohistoqu?micos. Prote?nas participantes da progress?o tumoral E-caderina, Beta-catenina, Galectina-3, Metaloproteinases 2 e 9 e o Fator alfa de crescimento endotelial vascular foram analisadas. Os blocos de parafina dessas amostras foram tratados pela t?cnica de Tissue Microarray e suas l?minas submetidas a imunohistoqu?mica para avaliar a intensidade de marca??o dessas prote?nas nos tecidos tumorais. Os resultados dessa an?lise foram correlacionados ?s vari?veis cl?nico-patol?gicas dos pacientes. An?lise estat?stica pelo Teste de qui-quadro de Pearson e an?lise de sobrevida pela Curva de Kaplan-Meier foram utilizados. Valores de p<0,05 foram considerados estatisticamente significativos. A m?dia de idade da nossa amostra foi de 58,8 anos e 51,7% foram do sexo feminino. O consumo de ?lcool aumentou em 1,71 vezes o risco de morte pelo CCR (p=0,034). J? o tabaco aumentou 2,7 vezes a chance de desenvolver tumores de alto est?gio TNM (p=0,001). Os pacientes com hist?rico familiar de c?ncer teve 3,833 vezes a chance de desenvolver o CCR (p=0,002). A express?o da MMP-2 mostrou uma associa??o significativa com os tumores de alto est?gio TNM (p<0,046) e mortalidade (p=0,041). A express?o do ? VEGF teve correla??o estatisticamente significante com o alto est?gio TNM (p<0,009), grau de indiferencia??o celular (p<0,025) e mortalidade (p<0,035). As express?es da E-caderina e Beta-catetina mostraram associa??o do tumor com alto est?gio TNM (p=0,0001) e Dukes? modificado (p=0,05), les?o em reto (p=0,03 e p=0,007, respectivamente), tabaco (p=0,05) e indiferencia??o (p=0,001). A express?o das Gal-3 apresentou relev?ncia estat?stica com pacientes de alto est?gio TNM (p=0,01), fumantes (p=0,01), etilista (p=0,03), indiferencia??o (p=0,0001) e mortalidade (p=0,0001). Frente aos resultados, pode-se perceber que o estilo de vida e hist?rico familiar teve correla??o no progn?stico do CCR, assim como a express?o de MMP-2, MMP-9, VEGF alfa, E-caderina, Beta-catenina e Galectina-3 foram importantes marcadores de progn?stico na progress?o tumoral no c?ncer colorretal. / Except the non-melanoma skin tumors, colorectal cancer is the second most common in the Southeastern Region of Brazil, the third most common in the Southern and Central Regions. It is also the forth most common in the Northern Region and it is the fifth one in the Northeastern. To assess pathological and clinical variables of colorectal Cancer is crucial to know the possible conclusions for the survival of patients and point out the characteristics in the progress of tumor, such as the profile of tumor invasion and its angiogenesis. This work focuses on analyzing clinically and pathologically some settings in colorectal cancer patients (CRC) in the city of Natal and its countryside through those variables as parameters of prognosis and determine the level of protein expression, for instance: E-cadherin (E-cad), beta- -catenin (?-cat), galectin-3 (gal-3), matrix metalloproteinases (MMP) 2 and 9 and vascular-endothelial growth factor alpha (? VEGF) in the tumor tissues. A retrospective study was done in colorectal cancer cases in the regions of Rio Grande do Norte state from 1995 to 2005, specifically in Natal city/RN/Brazil. The pathological and clinical variables, such as: age, gender, ethnicity, lifestyle, family history, the location of the primary tumor, level of differentiation, TDM staging, modified Dukes?, treatment and survival were analyzed. The pathological and clinical data were collected from medical records through a specific form and were filed on Excel. A total of 534 patients were selected from the Pathology Department file in this institution, however, 176 patients were excluded. 358 patients were included for Epidemiological analysis and its clinical and pathological correlations were selected. 180 patients were also selected for histological and immunohistochemical studies. The tumor progression of these selected proteins mentioned before were analyzed. The Paraffin blocks of these samples were treated by Microarray Tissue technique and its blades subjected to immunohistochemistry to test the intensity of these proteins in tumor tissues. The results of this analysis were correlated with clinicopathologic variables of patients. Statistical analysis using the chi-frame Pearson test and analysis of midlife by Kaplan-Meier curve was also utilized. P values < 0.05 were considered statistically significant. The average age of our sample was 58.8 years and 51.7 % were female. Alcohol consumption has increased by 1.71 time the risk of death by CCR (p = 0.034) and tobacco consumption increased 2.7 times the chance of developing tumors of high TNM stage (p = 0.001). Cancer patients had a family history of 3,833 times the chance of developing the CCR (p = 0.002). The expression of MMP-2 showed a significant association with tumors of high TNM stage (p <0.046) and mortality (p = 0.041). The ? VEGF expression had statistically significant correlation with high TNM stage (p <0.009), degree of cell indifferentiation (p <0.025) and mortality (p <0.035). Expressions of E-cadherin and beta-catetina demonstrated tumor linked to high TNM stage (p = 0.0001) and Dukes? modified (p = 0.05), lesions in the rectum (p = 0.03 and p = 0.007, respectively), smoking (p = 0.05) and indifferentiation (p = 0.001). The expression of Gal-3 showed statistical significance with high TNM stage of patients (p = 0.01), smokers (p = 0.01), alcohol drinking (p = 0.03), indifferentiation (p = 0.0001) and mortality (p = 0.0001). Based on the results, therefore, we could realize that lifestyle and family history had correlation in the CCR prognosis, as well as MMP-2 expression, MMP-9, VEGF alpha, E-cadherin, Beta-catenin and Galectin-3 were important prognostic markers in tumor progression in colorectal cancer.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-07-11T17:13:30Z No. of bitstreams: 1 LuizArthurBarbosaDaSilva_DISSERT.pdf: 4460566 bytes, checksum: 2c38f38ad7f85e1ed2fa49de5dcf3fe9 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-07-15T17:09:15Z (GMT) No. of bitstreams: 1 LuizArthurBarbosaDaSilva_DISSERT.pdf: 4460566 bytes, checksum: 2c38f38ad7f85e1ed2fa49de5dcf3fe9 (MD5) / Made available in DSpace on 2016-07-15T17:09:16Z (GMT). No. of bitstreams: 1 LuizArthurBarbosaDaSilva_DISSERT.pdf: 4460566 bytes, checksum: 2c38f38ad7f85e1ed2fa49de5dcf3fe9 (MD5) Previous issue date: 2016-02-26 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / O carcinoma de c?lulas escamosas oral apresenta altas taxas de morbidade e mortalidade na popula??o, com isso, enormes esfor?os est?o sendo feitos para categorizar altera??es morfol?gicas e identificar biomarcadores que tenham valor progn?stico, bem como que estratifiquem os pacientes em op??es terap?uticas individualizadas. Nessa perspectiva, destaca-se o fator do choque t?rmico 1 (HSF1), o qual ? um fator de transcri??o de prote?nas do choque t?rmico (HSPs) que permite ao c?ncer lidar com estressores associados ? malignidade, atuando de diferentes formas na progress?o tumoral. Esta pesquisa objetivou realizar a an?lise clinicopatol?gica de 70 casos de carcinoma de c?lulas escamosas de l?ngua oral (CCELO) e o estudo imunoistoqu?mico dos n?veis de express?o da prote?na HSF1 em CCELO em compara??o com 30 esp?cimes de mucosa oral normal (MON), correlacionando-se, ainda, esta imunoexpress?o com aspectos clinicopatol?gicos do CCELO. Quanto aos casos de CCELO, 57,1% exibiram estadiamento cl?nico III ou IV, 82,9% foram gradados como de alto grau segundo Bryne (1998) e 47,1% como de alto risco de malignidade segundo Brandwein-Gensler et al., (2005). Foi observada uma taxa de sobrevida livre de doen?a de 47,84% e taxa de sobrevida global de 68,20% nos casos analisados e que o alto grau de malignidade segundo a Grada??o de Bryne (1998) (p= 0,05) e tamanho do tumor T3 ou T4 (p= 0,04), recidiva local (p= 0,02) e invas?o perineural (p= 0,02) determinaram impactos negativos nesses tempos de sobrevida. Estes resultados corroboram as informa??es consolidadas na literatura quanto ? influ?ncia negativa de alguns indicadores clinicopatol?gicos na sobrevida dos pacientes com CCELO. Encontrou-se resultado estatisticamente significativo (p<0,01) quando comparou-se a imunoexpress?o de HSF1 entre a MON e o CCELO. Esta significativa maior express?o de HSF1 nos casos de CCELO sugere que esta prote?na atue, de fato, no processo de patog?nese desta les?o. Entretanto, n?o foram encontradas associa??es estatisticamente significativas entre esta superexpress?o com os par?metros cl?nicopatol?gicos analisados. Esse achado pode refletir a influ?ncia de eventos epigen?ticos sobre o gene HSF1 ou uma poss?vel estabilidade da express?o desta prote?na ao longo da progress?o da doen?a. / Squamous cell carcinoma of oral tongue shows high rates of morbidity and mortality in the population, therefore, great efforts are being made to classify morphological changes and identify biomarkers that have prognostic value and that are able to group patients in individualized therapeutic options. From this perspective, there is the heat shock factor 1 (HSF1), which is a heat shock factor transcription protein (HSPs) that allows the cancer to deal with stressors associated with malignancy, acting differently in tumor progression. This research aimed to perform a clinico-pathological analysis of 70 cases of oral tongue squamous cell carcinoma (OTSCC) and immunohistochemical study of the expression of HSF1 protein in OTSCC, comparing it with 30 specimens of normal oral mucosa (NOM), and correlating this immunostaining with clinico-pathological aspects of OTSCC. To analyze the association between immunoexpression of HSF1 and clinicophatoloical aspects, the cases were categorized in minor and major overexpression, based in the median immunostaining score. Regarding the cases of OTSCC, 57.1% showed clinical stage III or IV, 82.9% were graded as high grade according to Bryne (1998) and 47.1% as high risk of malignancy according to Brandwein-Gensler et al., (2005). A disease free survival rate of 47.84% and overall survival rate of 68.20% was observed in the analyzed cases, and the high degree of malignancy according to Bryne?s system (1998) (p=0.05), tumor size T3 or T4 (p=0.04), local recurrence (p=0.02), and perineural invasion (p=0.02) determined negative impacts in survival time. We observed also a statistically significant result (p<0.01) when comparing the immunoreactivity of HSF1 between NOM and OTSCC. This significantly increased expression of HSF1 in cases of OTSCC suggests that this protein acts, indeed, in the pathogenesis of this disease. However, there were no statistically significant associations between this overexpression and the clinico-pathological parameters analyzed. This finding may reflect the influence of epigenetic events on HSF1 gene or a possible stability of this protein expression throughout disease progression.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-02-10T16:52:35Z No. of bitstreams: 1 JavierJerezRoig_TESE.pdf: 3511641 bytes, checksum: 4ae07f46d035d68bf8ef148cfa29afe2 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-02-10T22:20:22Z (GMT) No. of bitstreams: 1 JavierJerezRoig_TESE.pdf: 3511641 bytes, checksum: 4ae07f46d035d68bf8ef148cfa29afe2 (MD5) / Made available in DSpace on 2017-02-10T22:20:22Z (GMT). No. of bitstreams: 1 JavierJerezRoig_TESE.pdf: 3511641 bytes, checksum: 4ae07f46d035d68bf8ef148cfa29afe2 (MD5) Previous issue date: 2016-08-23 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O presente trabalho teve como objetivos principais: verificar a preval?ncia de incapacidade funcional (IF) para as atividades b?sicas da vida di?ria (ABVD) e os fatores associados (Estudo 1), assim como verificar a incid?ncia de decl?nio funcional e os fatores progn?sticos de decl?nio funcional (Estudo 2) em idosos institucionalizados. A amostra do trabalho foi formada por indiv?duos de 60 anos ou mais pertencentes a 10 institui??es de longa perman?ncia para idosos (ILPI) da cidade do Natal/RN, sendo exclu?dos os hospitalizados ou em processo de cuidados paliativos. O Estudo 1 ? de tipo transversal (Outubro e Dezembro de 2013) e foi avaliada a IF mediante a escala de Katz e caracterizada quando houve limita??o em uma ou mais ABVD (alimenta??o, controle de esf?ncteres, transfer?ncias posturais, higiene pessoal, capacidade para se vestir e tomar banho). Como vari?veis independentes foram consideradas as sociodemogr?ficas, as relacionadas ? institui??o e ?s condi??es de sa?de. Usaram-se o teste qui-quadrado, teste de Fisher ou teste qui-quadrado de tend?ncia linear para a an?lise bivariada, assim como a regress?o log?stica para a multivariada. A amostra foi de 321 idosos e a preval?ncia de IF de 72,9% (IC 95%: 67,8-77,5%). A tarefa mais afetada foi o ?banho?, seguido por ?vestir-se? e ?ir ao banheiro?. O modelo final constatou associa??o com a institui??o de tipo privado (RP=1,33, p<0,001), idade igual ou superior a 83 anos (RP=1,26, p=0,003), ser institucionalizado por n?o ter cuidador (RP=1,17, p=0,033) e osteoporose (OR=1,23, p=0,045), ajustado por sexo. O Estudo 2 ? longitudinal de 24 meses de acompanhamento com intervalos de follow-up de 6 meses (5 ondas). Al?m dos crit?rios aplicados no Estudo 1, foram exclu?dos aqueles que apresentavam IF para todas as ABVD (banho, higiene pessoal, vestir-se, ir ao banheiro, caminhar, transfer?ncias posturais e comer) no in?cio do estudo. Foi considerada a presen?a de decl?nio funcional quando houve redu??o na pontua??o total das ABVD, as quais foram avaliadas mediante uma escala tipo Likert de 5 pontos. Foram analisadas todas as vari?veis independentes do Estudo 1, mais o estado de mobilidade, cognitivo (teste de Pfeiffer), h?bitos t?xicos e atividade f?sica, al?m de vari?veis dependentes do tempo. Para a an?lise estat?stica, foi utilizado o m?todo atuarial, o teste log-rank, a an?lise univariada de Cox e a regress?o de Cox. A coorte esteve composta por 280 idosos: 140, 50,0% (IC 95%: 44,2-55,8%), sofreram decl?nio funcional, 94, 33,6% (IC 95%: 28,3-39,3%) mantiveram a capacidade funcional, e 40, 14,3% (IC 95%: 10,7-18,9%), apresentaram melhora funcional em uma ou mais avalia??es. A probabilidade acumulada de manuten??o funcional foi de 44,0% (IC 95%: 37,7-50,2%) aos 24 meses. A capacidade de se alimentar foi a que apresentou maior decl?nio durante o per?odo (-0,54 pontos), seguido por deambula??o (-0,43), vestir-se (-0,35), transfer?ncias posturais (-0,31), banho (-0,29), higiene pessoal (-0,24) e ir ao banheiro (-0,22). O modelo multivariado mostrou que os fatores predictores de decl?nio funcional foram a incapacidade cognitiva grave (HR=1,98; p=0,003), decl?nio da contin?ncia (HR=1,70; p=0,013) e incid?ncia de hospitaliza??es (HR=1,65; p=0,023). / The main objectives of this work were: to verify the prevalence of functionaldisability (FD) inthe basic activities of daily living (BADL) and its associated factors (Study 1) and verify the incidence of functional decline and predictor factors of functional decline (Study 2) in institutionalized older people. The sample of the study was formed by individuals aged 60 years and over belonging to 10 nursing homes (NH) in Natal/RN, being excluded hospitalized or palliative care residents. The Study 1 is a cross-sectional study (October-December 2013) and FD was evaluated by Katz scale and characterized when there was limitation in one or more BADL (eating, sphincter control, transferring, personal hygiene, dressing and bathing). As independent variables sociodemographic, instituition-related health-related variables were considered. The Chi-square test, Fisher's exact test or the linear Chi-square test for the bivariate analysis and logistic regression for multivariate analysis were applied. The sample consisted of 321 individuals and the prevalence of FD was 72.9% (95% CI: 67.8-77.5%). The most affected task was 'bathing', followed by 'dressing' and 'toileting.' The final model found association with private NH (PR=1.33, p<0.001), age 83 and over (RP=1.26, p=0.003), reason for institutionalization ?lack of caregiver? (RP=1.17, p=0.033) and osteoporosis (RP=1.23, p=0.045), adjusted by sex. The Study 2 is a 24-months longitudinal study with follow-up every 6 months (5 waves). Apart from the criteria considered in the Study 1, residents with FD for all BADL (bathing, personal hygiene, dressing, toileting, walking, transferring and eating) at baseline were excluded. The presence of functional decline was defined when there was a reduction the total score of BADL, which were assessed by a 5-point Likert scale. All independent variables of the Study 1 were considered, as well asthe mobility status, cognitive status (Pfeiffer test), toxic habits, physical activity and time-dependent variables. Statistical analysis was performed using the actuarial method, log-rank test, Cox univariate analysis and Cox regression. The cohort was composed of 280 individuals: 140, 50.0% (95% CI: 44.2-55.8%) experienced functional decline; 94, 33.6% (95% CI: 28.3-39.3%), maintained their functional capacity, and; 40, 14.3% (95% CI: 10.7-18.9%), showed functional improvement at one or more waves. The cumulative probability of functional maintenance was 44.0% (95% CI: 37.7-50.2%) at 24 months. The ability to eat showed the largest decline during the period (-0.54 points), followed by walking (-0.43), dressing (-0.35), transferring (-0.31), bathing (-0.29), personal hygiene (-0.24) and toileting (-0.22). The final model showed that the predictors factors of functional decline were severe cognitive impairment (HR=1.96, p=0.001), continence decline (HR=1.85, p=0.002) and incidence of hospitalizations (HR=1.62, p=0.020).

Submitted by PPG Pediatria e Sa?de da Crian?a (pediatria-pg@pucrs.br) on 2019-03-12T12:24:17Z No. of bitstreams: 1 DISSERTA??O MariaRita Celiny 18_07_2018.pdf: 820907 bytes, checksum: 09346c615fe9651922e9d8fa8ab20b27 (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2019-03-18T11:12:08Z (GMT) No. of bitstreams: 1 DISSERTA??O MariaRita Celiny 18_07_2018.pdf: 820907 bytes, checksum: 09346c615fe9651922e9d8fa8ab20b27 (MD5) / Made available in DSpace on 2019-03-18T11:17:03Z (GMT). No. of bitstreams: 1 DISSERTA??O MariaRita Celiny 18_07_2018.pdf: 820907 bytes, checksum: 09346c615fe9651922e9d8fa8ab20b27 (MD5) Previous issue date: 2018-04-23 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Aims and Objectives: To evaluate the predictive capacity of Pediatric Risk of Mortality Score IV (PRISM IV) in a Pediatric Intensive Care Unit (PICU) in Southern Brazil. Secondarily compare this research to two other scores, Pediatric Index of Mortality (PIM) 2 and PIM 3 Methods: Longitudinal retrospective study, during one year, from January 1 to December 31, 2016. Children admitted to a PICU at a University Hospital in Southern Brazil. Patients older than 20 years and dying patients with vital signs incompatible with life after 2 hours of PICU admission were not included. Only the first entry into PICU during hospitalization was considered. Discrimination, calibration and comparison tests with other indexes and a PRISMIV / PIM2 concordance test were performed. The study was approved by the institution's ethics committee Results: There were 411 admissions in the year 2016, 378 patients were included in the study. Of these 378, 13 died, generating a mortality rate of 3.44%. PRISM IV estimated mortality of 3.18% with Standardised Mortality Ratio (SMR) of 1.08, zflora= -0.3. For the same sample, the PIM2 predicted a mortality of 2.78% and the PIM 3 of 2.51. In the same way, PIM 2 and PIM 3 presented SMR of 1.24 and 1.37, respectively, with zflora=-0.91 and -1.40. The Hosmer-Lemeshow (HL) adjustment test obtained a X? = 4,472 (p = 0.484) for PRISM IV. Similarly, the PIM 2 presented a good calibration with X? = 8,359 and p = 0.138. However, PIM 3 presented X?=16.013 and p = 0.007. The discrimination test with the area under the curve (AUC / ROC ? Receiver Operating Charateristic) of PRISM IV was 0.811 (95% CI 0.695-0.928). Similarly, the area of the PIM 2 was 0.779 (95% CI 0.645-0.913) and the PIM 3 obtained 0.759 (IC 95% 0.621-0.898). Among the three prognostic scores there was no statistical difference. The disagreement between the results of PRISM IV and PIM 2 was small. Conlusion: PRISM IV presented good predictive capacity in the study population, demonstrating good calibration and discrimination. In the comparative analysis, a similar predictive capacity was observed between this PRISM IV and PIM 2, which was not confirmed with PIM 3. It is suggested that PRISM IV be a validated tool for this population. / Objetivo: Avaliar a capacidade de predi??o do Pediatric Risk of Mortality Score IV (PRISM IV) em uma Unidade de Terapia Intensiva Pedi?trica (UTIP) no Sul do Brasil. Secundariamente comparar esta investiga??o a outros dois escores, Pediatric Index of Mortality (PIM) 2 e PIM 3. M?todos: Estudo retrospectivo longitudinal, de 01? de janeiro a 31 de dezembro de 2016 com crian?as admitidas em uma UTIP de um Hospital Universit?rio do Sul do Brasil. N?o foram inclu?dos pacientes com idade maior que 20 anos e pacientes moribundos, com sinais vitais incompat?veis com a vida ap?s 2 horas de admiss?o em UTIP. Apenas a primeira interna??o em UTIP durante a hospitaliza??o foi considerada. Foram realizados testes de discrimina??o, calibra??o e de compara??o com outros ?ndices e um teste de concord?ncia PRISM IV / PIM 2. O estudo foi aprovado pelo comit? de ?tica da institui??o. Resultados: Houveram 411 admiss?es no ano de 2016, 378 pacientes foram inclu?dos no estudo. Destes 378, 13 foram a ?bito, gerando uma taxa de mortalidade de 3,44%. O PRISM IV estimou mortalidade de 3,18% com Indice de Mortalidade Pad?o - (SMR) de 1,08, zflora= -0,31. Para a mesma amostra, o PIM 2 previu uma mortalidade de 2,78% e o PIM 3 de 2,51% e apresentaram SMR de 1,24 e 1,37, respectivamente, com valores para o zflora=-0,91 e -1,40. O teste de ajuste de Hosmer-Lemeshow (HL) obteve um X?=4,472 (p=0,484) para o PRISM IV. De forma semelhante, o PIM 2 apresentou boa calibra??o com X2=8,359 e p=0,138. Contudo, o PIM 3 apresentou X2=16,013 e p=0,007. O teste de discrimina??o com a ?rea abaixo da curva (AUC/ROC), do PRISM IV foi de 0,811 (IC95% 0,695-0,928). Por sua vez, a ?rea do PIM 2 foi de 0,779 (IC95% 0,645-0,913) e o PIM 3 obteve 0,759 (IC95% 0,621-0,898). Considerando a curva ROC, entre os tr?s escores progn?sticos n?o houve diferen?a estat?stica. A discord?ncia entre os resultados do PRISM IV e o PIM2 foi pequena. Conlus?o: O PRISM IV apresentou adequada capacidade preditiva na popula??o do estudo, demonstrando boa calibra??o e discrimina??o. Na an?lise comparativa observou-se semelhante capacidade preditiva entre este PRISM IV e PIM 2, o que n?o se confirmou com o PIM 3. O PRISM IV mostrou-se uma ferramenta validada para utiliza??o em UTIP no presente estudo.

Made available in DSpace on 2016-01-26T12:51:19Z (GMT). No. of bitstreams: 1 jorgeadasdib_tese.pdf: 343099 bytes, checksum: ab3f9830cf7060129a9dcec26d66b83c (MD5) Previous issue date: 2008-06-06 / No previous study has addressed the question of prognostic determinants for patients with Chagas? cardiomyopathy at the terminal stage listed for heart transplantation. Casuistic and Method: All patients listed for heart transplantation at our institution from August, 2000 to March, 2005 were considered for the study. Patients removed from the waiting list for clinical status improvement were excluded from the investigation. Patients were followed until death, cardiac transplantation or the end of the study period. Cardiac transplant recipients were censored at the time of transplantation. No patient was lost to follow up. A Cox regression hazards model was used to establish independent predictors of all-cause mortality. Variables previously demonstrated to predict mortality in either Chagas or non-Chagas? disease heart failure were entered the univariate analysis. Separate analyses were performed for Chagas and non-Chagas? disease patients. Results: Median follow up was 32 (15,121) days in Chagas disease and 79 (14,151) days in non-Chagas? disease patients. In Chagas disease patients, the hemodynamic instability (p=0.01; hazard ratio=0,077, 95% confidence interval, 0.01 to 0.58) as well as the transpulmonary gradient (p=0.02; hazard ratio=1.15, 95% confidence interval, 1.02 to 1.30) were retained as independent predictors of all-cause mortality. Serum sodium levels (p=0.002; hazard ratio=0.81; 95% confidence interval, 0.71 to 0.93) was independent predictor of all-cause mortality for non-Chagas? disease patients. Conclusion: The hemodynamic instability and transpulmonary gradient were independent predictors of all-cause mortality for Chagas? disease patients listed for heart transplantation. A larger, prospective cohort study is needed to validate our findings. / At? agora nenhum estudo preocupou-se em estabelecer determinantes progn?sticos para pacientes com insufici?ncia card?aca cr?nica terminal secund?ria ? cardiomiopatia da doen?a de Chagas na fila de espera para transplante card?aco. Casu?stica e M?todo: Todos os pacientes alocados em fila de espera de transplante card?aco em nossa institui??o, de agosto de 2000 a mar?o de 2005, foram inicialmente considerados para o estudo. Os pacientes que foram removidos da lista de espera em virtude de melhora no estado cl?nico foram retirados do estudo. Os pacientes foram acompanhados at? a morte, transplante card?aco ou a data final estipulada para o estudo. Os pacientes receptores de transplante de cora??o foram retirados do estudo na data em que o ato operat?rio ocorreu. N?o se perdeu contato com os pacientes durante o acompanhamento cl?nico enquanto na fila de espera de transplante card?aco. O modelo de an?lise de riscos proporcionais de Cox foi utilizado para se estabelecer vari?veis de predi??o independentes de mortalidade geral. As vari?veis que eram capazes de predizer mortalidade geral em pacientes com insufici?ncia card?aca cr?nica secund?ria ? cardiomiopatia da doen?a de Chagas ou a outras cardiomiopatias foram utilizadas no modelo univariado. An?lises univariadas foram feitas nos pacientes chag?sicos e n?o chag?sicos separadamente. Resultados: A mediana do tempo de acompanhamento cl?nico foi 32 (15, 121) dias nos pacientes chag?sicos e 79 (14, 151) dias nos pacientes n?o chag?sicos. Nos pacientes chag?sicos, a instabilidade hemodin?mica (p=0,01; raz?o de risco=0,077, intervalo de confian?a de 95% entre 0,01 e 0,58) e o gradiente transpulmonar (p=0,02; raz?o de risco =1,15, intervalo de confian?a de 95% entre 1,02 e 1,30) foram as vari?veis de predi??o independentes de mortalidade geral. Os n?veis s?ricos de s?dio (p=0,002; raz?o de risco =0,81; intervalo de confian?a de 95% entre 0,71 e 0,93) foi a vari?vel de predi??o independente para os pacientes n?o chag?sicos na fila de espera para transplante card?aco. Conclus?es: A instabilidade hemodin?mica e o gradiente transpulmonar foram preditores independentes de mortalidade geral em pacientes com insufici?ncia card?aca cr?nica secund?ria ? cardiomiopatia da doen?a de Chagas na lista de espera para transplante card?aco. Um estudo prospectivo de coorte longitudinal ? necess?rio para validar os resultados obtidos nesta investiga??o.

Made available in DSpace on 2014-12-17T15:32:25Z (GMT). No. of bitstreams: 1 AndreaFS_tese.pdf: 610478 bytes, checksum: 22934e3fba7a401686d3b0057e0e7f35 (MD5) Previous issue date: 2007-07-11 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The expression of bone morphogenetic proteins (BMPs) is altered in a variety of human canceres. The BMP-2/4 and BMPR-IA were recently shown to be overexpressed in high-risk premalignant and malignant lesions of oral epithelium. The present study analysed the expression of BMP-2/4 and BMPR-IA in Oral Squamous Cell Carcinoma (OSCC) such as their implications in disease prognostic using munohistochemistry. Ten cases of Oral Fibroepithelial Hiperplasia were selected as a control group. The experimental group included 16 cases of OSCC without metastases and 7 cases of OSCC metastatic. The presence or absence of nodal metastases was used as parameter to evaluated the disease prognostic. The results demonstrated weak immunoreactivity for BMP-2/4 and BMPR-IA in every case of the control group. In the cases of OSCC with metastases an overexpression of BMP-2/4 (71,4%) was observed while the BMPR-IA showed weak expression (85,7%). In the cases of OSCC without metastases BMP-2/4 (62,5%) and BMPR-IA showed strong immunostaining standing out an overexpression of the receptor in all the specimens. Observed statistical significance for correlation between the oral cancer prognostic and the staining intensity of the BMP-2/4 (p=0,002). There wasn t statistical significance for association between the staining intensity of the BMPR-IA and the disease prognostic (p<0,001). In conclusion, this findings suggest that the overexpression of BMP-2/4 associated with the loss of expression of the BMPR-IA in OSCC metastatic has prognostic relevance, as the loss of sensitivity to BMPs can be an indicative of metastases development in OSCC / A express?o das prote?nas morfogen?ticas ?sseas (BMPs) est? alterada em v?rios c?nceres humanos. A BMP-2/4 e o BMPR-IA foram recentemente encontrados superexpressos em les?es malignas e pr?-malignas de alto risco em epit?lio oral. Este estudo analisou a express?o da BMP-2/4 e seu receptor BMPR-IA em 23 esp?cimes de Carcinoma Epiderm?ide Oral (CEO), utilizando a imuno-histoqu?mica. O grupo controle constou de 10 casos de Hiperplasia Fibro-epitelial da mucosa oral. O grupo experimental foi constitu?do por 16 casos de CEO n?o metast?tico e 7 casos de CEO metast?tico. Utilizou-se o par?metro presen?a ou aus?ncia de met?stase nodal para avaliar o progn?stico da doen?a. Os resultados demonstraram imunorreatividade fraca para a BMP-2/4 e o BMPR-IA em todos os esp?cimes do grupo controle. No grupo experimental com met?stase, a BMP-2/4 exibiu forte expressividade (71,4%), enquanto que o BMPR-IA mostrou fraca express?o (85,7%). No grupo experimental sem met?stase, evidenciou-se forte express?o para a BMP-2/4 (62,5%) e para o BMPR-IA (100%). Encontrou-se signific?ncia estat?stica para a associa??o entre o progn?stico do CEO e a intensidade de marca??o da BMP-2/4 (p=0,002). Para o BMPR-IA n?o houve signific?ncia estat?stica ? sua associa??o com o progn?stico da doen?a (p<0,001), em fun??o do tamanho da amostra. Portanto, os resultados sugerem que a fraca expressividade do BMPR-IA associada ? forte express?o da BMP-2/4, no grupo experimental com met?stase, tem relev?ncia progn?stica, j? que a perda de sensibilidade ?s BMPs, atrav?s da perda de express?o de seus receptores pode ser indicativo de desenvolvimento de met?stase em CEO