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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
31

Avaliação toxicológica pré-clínica com extrato bruto seco das folhas de Vitex agnus castus Linn

Diniz Barros, Jussara 31 January 2008 (has links)
Made available in DSpace on 2014-06-12T16:26:25Z (GMT). No. of bitstreams: 2 arquivo1155_1.pdf: 1441766 bytes, checksum: 3090e50673db4f8353bc6516c2af26b5 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2008 / Inúmeros estudos científicos vêm sendo realizados no sentido de validar as informações populares referentes ao uso de plantas medicinais. É comum no estado de Pernambuco, assim como em todo o Brasil, a existência de feiras livres que comercializam produtos feitos com ervas e extratos naturais (com composição não padronizada), que associada à suscetibilidade do indivíduo agrava o quadro de acidentes por plantas tóxicas. Estes ensaios tiveram como objetivo a verificação da toxicidade do Extrato Bruto Seco e do Extrato aquoso mimetizando o seu uso popular (na forma de infusão), da folha da planta Vitex agnus castus Linn. popularmente conhecida por erva-de-caboclo e Liamba (PE), alecrim-de-planta (PA) e pau-de-angola (PA e MA). Este projeto visou esclarecer possíveis alterações provocadas pelo Extrato Bruto Seco (EBS) das folhas da Vitex agnus castus Linn no Sistema Nervoso Central e determinar sua toxicidade. A avaliação toxicológica pré clínica aguda (CL50) usando metanáuplios de Artemia salina Leach deu um valor de 801,266 μg/mL para Vitex agnus castus Linn. Os valores obtidos são próximos a 1000 μg/mL, indicando uma baixa toxicidade para esta planta. O extrato aquoso de V. agnus-castus não apresentou DL50 inferior a dose de 4g/kg, indicando baixa toxicidade aguda em ratos. Já o estudo toxicológico pré clínico crônico dos ratos por 90 dias com o EBS das folhas da Vitex anus castus Linn com doses de 2,18 mg/kg (uso popular), 10,9 mg/kg (dose 5x) e 54,5 mg/kg (dose 25x) nas doses usual , 5x a usual, 25x a usual mostrou uma pequena alteração já esperadas das transaminases hepáticas não apresentando nenhuma alteração histopatológica considerável
32

Exenteração pélvica e preservação dos esfíncteres: análise de 96 casos / Pelvic exenteration and sphincter preservation: an analysis of 96 cases

Antonio Henrique Oliveira Poletto 15 April 2005 (has links)
A exenteração pélvica é método efetivo no tratamento de tumores pélvicos localmente avançados. As cirurgias mais conservadoras, com preservação funcional dos esfíncteres e reconstrução continente dos tratos intestinal e urinário podem melhorar a qualidade de vida e estimular os pacientes a aceitar a cirurgia. O objetivo deste estudo foi avaliar os resultados da exenteração pélvica no tratamento dos tumores pélvicos localmente avançados em relação à preservação dos esfíncteres e fatores associados ao prognóstico. Analisou-se retrospectivamente os fatores relacionados à preservação dos esfíncteres bem como os fatores associados ao prognóstico em pacientes submetidos à exenteração pélvica. Dos 96 pacientes submetidos à exenteração pélvica, preservou-se pelo menos um dos esfíncteres em 36 (37,5%). Na década de 1990 a taxa de preservação esfincteriana foi significativamente maior do que na década de 1980 (47,6 versus 18,2%) (p = 0,005). As variáveis independentemente relacionadas à preservação de esfíncter foram tratamento realizado na década de 1990 e tumor de origem coloproctológica. A taxa de complicação pós-operatória não foi influenciada pela preservação dos esfíncteres (p = 0,276). Não se observou diferença estatisticamente significativa nas taxas de morbidade entre as décadas de 1990 e 1980 (55,6% versus 75,8%; p = 0,075). Na década de 1990 houve redução da taxa de mortalidade pós-operatória em relação à década de 1980 (9,5% versus 27,3%; p = 0,023). Em nove pacientes, as margens de ressecção estavam microscopicamente comprometidas (R1) e, em cinco macroscopicamente comprometidas (R2). As margens de ressecção não foram influenciadas pelo tipo de cirurgia (p = 0,104), nem pela preservação dos esfíncteres (p = 0,881). A taxa de sobrevida livre de doença em cinco anos foi de 40,5%. Observou-se associação da recorrência com perda de peso (p = 0,006), índice de Karnofsky (p = 0,035) e a topografia do tumor (p = 0,027). No modelo multivariado, a perda de peso e os tumores de origem ginecológica foram as variáveis independentes para recorrência. Pacientes portadores de tumores ginecológicos ou com perda de peso foram considerados de alto risco para recorrência e os pacientes portadores de tumores não ginecológicos e sem perda de peso, de baixo risco. O grupo de alto risco apresentou chance de recorrência cerca de sete vezes maior do que o de baixo risco. A sobrevida livre de doença em 5 anos para os grupos de baixo e de alto risco foram, respectivamente, de 78,0% e 21,2%. As variáveis associadas ao óbito foram a idade superior a 60 anos (p = 0,007), a perda de peso (p = 0,004), radioterapia pré-operatória (p = 0,043), década de trata mento (p = 0,050) e preservação de esfíncter (p=0,026). No modelo multivariado as variáveis associadas ao óbito foram tratamento realizado na década de 1980, a idade superior a 60 anos e a perda de peso. Com os resultados deste estudo podemos concluir que houve aumento significante da preservação dos esfíncteres na década de 1990 sem aumento da freqüência de margens cirúrgicas comprometidas nem prejuízo na sobrevida dos pacientes submetidos à exenteração pélvica com preservação dos esfíncteres / Pelvic exenteration (PE) is an effective method for treating locally advanced pelvic tumors. More conservative surgeries, preserving sphincters and continent reconstruction of the intestinal and urinary tract, which could contribute to a better quality of life and encourage patients to accept this procedure. The objective of this study was to evaluate the results of PE in the treatment of locally advanced pelvic tumors, mainly considering sphincter preservation and factors associated to the prognosis. Between 1980 and 2000, 96 PE were performed. Factors related to sphincter preservation as well as factors associated to prognosis were respectively analyzed. Of the 96 patients treated with pelvic exenteration, at least one sphincter in 36 patients was preserved (37.5%). In the 1990\'s, the sphincter preservation rate was significantly higher than in the 1980\'s (47.6 vs. 18.2 %) (p = 0.005). Independent variables related to the sphincter preservation were decades from the realization of surgery 1990\'s and coloproctological tumors. The postoperative complication rate was not influenced by sphincter preservation (p = 0.276). Statistically, there was no differentiation between the morbidity rates during the 1980\'s and 1990\'s (55.6% versus 75.8%, p = 0.075). In the 1990\'s, there was a reduction in the post-operative mortality rate compared to the 1980s\' rate (9.5% versus 27.3%; p = 0.023). In nine patients, the resection margins were compromised microscopically (R1) and in five patients, macroscopically compromised (R2). The resection margins were not influenced by the type of surgery (p = 0.104), nor by the preservation of sphincters (p = 0.881). Disease free survival at five years was 40.5%. Among the clinical variables, there was an association between recurrence and weight loss (p = 0.006) and the Karnofsky index (p = 0.035). The topography of the tumor showed links with recurrence (p = 0.027). In the multivariable model, the independent variables related to recurrence were weight loss and gynecological tumors. Patients with gynecological tumors or with weight loss were considered high risk for recurrence, while patients with no gynecological tumors and without weight loss were considered low risk. The high risk group showed 7 times more chance of recurrence than the low risk group. Survival rates of patients, who remained disease-free, after 5 years, for the low and high risk group were 78.0% and 21.2% respectively. Death was linked to ages over 60 (p = 0.007), weight loss (p = 0.004), pre-surgery radiotherapy (p = 0.043), decades from the realization of surgery (p = 0.050) and the sphincter preservation (p = 0.026). The independent variables related to death were treatments in the 1980\'s, ages over 60 and weight loss. Taking into account the results in this research, we conclude that there was a significant increase of sphincter preservation during the 1990\'s and neither the type of surgery nor sphincter preservation were associated to a higher number of surgeries with compromised margins allows pelvic exenteration to be performed with sphincter preservation, without harming survival rates
33

Tissue Specific <em>Porcupine</em> Deletion Reveals a Novel Role for Ectodermal <em>Wnts</em> in Musculotendon Development

Smith, Aaron P. 05 July 2012 (has links) (PDF)
The Wnt family of secreted proteins consists of 19 family members (in the mouse) and is known to signal through multiple pathways that regulate crucial processes in the development of almost all tissues. Dissecting the roles of individual Wnts has been hampered due to functional redundancy that exists between family members. We made use of a conditional allele of the acyltransferase, Porcupine (Porcn), that is required for the secretion of all Wnt ligands, and the Msx2Cre deleter to eliminate the secretion of all Wnt ligands from the ventral limb ectoderm, ventral abdominal ectoderm, and urogenital ectoderm. Phenotypically the limbs of these mice have several similarities with En1 mutant mice which have a double-dorsal phenotype. however, we show that appropriate dorsoventral limb pattern is maintained at the molecular level and that the observed defects are due to a failure to appropriately execute ventral pattern. Additionally, newborn mice lack ventral digital tendons and the most superficial musculature in the regions of strongest and earliest deletion. Molecular analysis indicates that tendons are lost downstream of the absent musculature and are initially patterned correctly. Thus we show a role for ectodermal Wnts in the development of underlying musculature. We additionally examine the role of limb mesenchymal Wnts in the development of deeper limb musculature utilizing the Prx1Cre deleter. The deep musculature of the autopod and zeugopod is reduced or absent in mutants and the development of superficial musculature appears to proceed normally. Hence we show that superficial muscles require only ectodermal Wnts and deeper muscles require only mesenchymal Wnts.
34

Estudo de fase II de substituição do 5-FU por capecitabina no esquema de quimio-radioterapia em pacientes com carcinoma de células escamosas do canal anal / Phase II study of capecitabine in substitution of 5-FU in the chemoradiotherapy regimen for patients with squamous cell carcinoma of the anal canal

Oliveira, Suilane Coelho Ribeiro 30 January 2015 (has links)
Introdução: O carcinoma de células escamosas (CEC) do canal anal é uma neoplasia pouco frequente, correspondendo a 1-5% dos tumores intestinais. Entretanto, o risco de CEC do canal anal vem crescendo. O tratamento padrão do CEC de canal anal nos estádios II-III consiste em 5-fluorouracil infusional associado a mitomicina-C e radioterapia, desde 1974. Estudos clínicos com o objetivo de identificar novos esquemas terapêuticos mais convenientes para câncer do canal anal devem continuar. Métodos: Pacientes com CEC de canal anal T2-4N0M0 ou T (qualquer) N1-3M0, com bom performance clínico, função renal e hematológica normais foram tratados com capecitabina 825 mg/m2 12/12 horas durante a radioterapia associada a dose única de mitomicina-C 15 mg/m2 no Dia 1. O objetivo primário do estudo foi determinar a taxa de controle local em 6 meses da associação de capecitabina, mitomicina-C e radioterapia em pacientes com câncer do canal anal. Os objetivos secundários foram determinar a taxa de toxicidade aguda graus 3-4, conforme os critérios da CTCaev4.0, taxa de resposta completa 6 semanas após término da quimio-radioterapia, sobrevida global e livre de progressão e taxa de colostomia em 1 ano. O tamanho da amostra foi calculado usando a ferramenta \"estágio único de Fleming\". Considerando 85% de eventos esperados (taxa de controle local em 6 meses), 1 desvio padrão e 5% de erro alfa, o tamanho ideal da amostra foi de 51 pacientes. Resultados: De novembro/2010 a fevereiro/2014, 51 pacientes foram incluídos, sendo avaliados 43 pacientes. Dezessete pacientes (39,5%) tinham estádio II, 11 (25,6%) estádio IIIA e 15 (34,9%) estádio IIIB. O seguimento mediano foi de 23,1 meses. Entre os pacientes que foram avaliados em 6 meses, 3 (7%) apresentaram resposta clínica parcial, 37 (86%) tiveram resposta clínica completa e 3 (7%) apresentaram progressão de doença. O controle loco-regional em 6 meses foi de 86%. Em relação às toxicidades graus 3-4, observaram-se diarreia grau 3, em 4,6% dos pacientes, radiodermite grau 3, em 23,2%, vômitos grau 3, em 2,3%, plaquetopenia graus 3-4, em 6,9%, leucopenia grau 3, em 6,9%, e linfopenia grau 3, em 11,6%. Um paciente HIV positivo (2,3%) apresentou choque séptico grau 4, pneumonia grau 4, meningoencefalite herpética grau 4 e síndrome de ativação macrofágica grau 4. A taxa de colostomia foi de 18,6%. Conclusão: Capecitabina e mitomicina-C são um tratamento bem tolerado em pacientes com carcinoma de canal anal, com controle loco-regional em 6 meses em 86% dos pacientes. Palavras-chave: carcinoma de células escamosas, câncer anal, capecitabina, radioterapia, mitomicina-c / Background: Squamous cell carcinoma (SCC) of the anal canal is an uncommon malignancy accounting for 1-5% of intestinal tumors; however, its incidence has been increasing. Treatment for stage II and III anal canal SCC is infusional 5-fluorouracil associated with mitomycin and radiotherapy, since 1974. More convenient treatments for patients are needed. Methods: Patients with SCC of anal cancer T2-4N0M0 or T (any) N1-3M0, with good performance status, normal blood, and renal function were treated with capecitabine 825 mg/m2 bid during radiotherapy associated with a single dose of mitomycin 15 mg/m2 on day 1. Primary objective was local control rate at 6 months determined by clinical examination and radiological assessment. Sample size was calculated using Fleming single stage design. Results: From november/2010 to february/2014 51 patients were initially included, however 43 patients were assessed. Seventeen patients (39.5%) were stage II, 11 patients (25.6%) stage IIIA, and 15 patients (34.9%) stage IIIB. Four patients (9.3%) were HIV-positive, while 39 (90.7%) were HIV-negative. Median follow-up was 23.1 months. Among patients who finished the treatment and were reevaluated at 6 months 3 patients (7%) presented partial response, 37 patients (86%) had complete response, and 3 patients developed progression of the disease (7%). Regarding grade 3-4 toxicities, 10 patients (23.2%) had grade 3 radiodermitis, 3 patients (6.9%) had grade 3-4 thrombocytopenia, 5 (11.6%) had grade 3 lymphopenia, 1 patient (2.3%) had grade 3 vomiting, 2 patients (4.6%) had grade 3 diarrhea and 3 patients (6.9%) had grade 3 leukopenia. One HIV+ patient had septic shock, pneumonia, herpetic encephalitis and macrophage activation syndrome. Colostomy rate was 18.6%. Conclusions: Capecitabine and mitomycin with radiotherapy seem to be a safe treatment for SCC of the anal cancer, with a complete response rate in 6 months of 86%
35

Estudo de fase II de substituição do 5-FU por capecitabina no esquema de quimio-radioterapia em pacientes com carcinoma de células escamosas do canal anal / Phase II study of capecitabine in substitution of 5-FU in the chemoradiotherapy regimen for patients with squamous cell carcinoma of the anal canal

Suilane Coelho Ribeiro Oliveira 30 January 2015 (has links)
Introdução: O carcinoma de células escamosas (CEC) do canal anal é uma neoplasia pouco frequente, correspondendo a 1-5% dos tumores intestinais. Entretanto, o risco de CEC do canal anal vem crescendo. O tratamento padrão do CEC de canal anal nos estádios II-III consiste em 5-fluorouracil infusional associado a mitomicina-C e radioterapia, desde 1974. Estudos clínicos com o objetivo de identificar novos esquemas terapêuticos mais convenientes para câncer do canal anal devem continuar. Métodos: Pacientes com CEC de canal anal T2-4N0M0 ou T (qualquer) N1-3M0, com bom performance clínico, função renal e hematológica normais foram tratados com capecitabina 825 mg/m2 12/12 horas durante a radioterapia associada a dose única de mitomicina-C 15 mg/m2 no Dia 1. O objetivo primário do estudo foi determinar a taxa de controle local em 6 meses da associação de capecitabina, mitomicina-C e radioterapia em pacientes com câncer do canal anal. Os objetivos secundários foram determinar a taxa de toxicidade aguda graus 3-4, conforme os critérios da CTCaev4.0, taxa de resposta completa 6 semanas após término da quimio-radioterapia, sobrevida global e livre de progressão e taxa de colostomia em 1 ano. O tamanho da amostra foi calculado usando a ferramenta \"estágio único de Fleming\". Considerando 85% de eventos esperados (taxa de controle local em 6 meses), 1 desvio padrão e 5% de erro alfa, o tamanho ideal da amostra foi de 51 pacientes. Resultados: De novembro/2010 a fevereiro/2014, 51 pacientes foram incluídos, sendo avaliados 43 pacientes. Dezessete pacientes (39,5%) tinham estádio II, 11 (25,6%) estádio IIIA e 15 (34,9%) estádio IIIB. O seguimento mediano foi de 23,1 meses. Entre os pacientes que foram avaliados em 6 meses, 3 (7%) apresentaram resposta clínica parcial, 37 (86%) tiveram resposta clínica completa e 3 (7%) apresentaram progressão de doença. O controle loco-regional em 6 meses foi de 86%. Em relação às toxicidades graus 3-4, observaram-se diarreia grau 3, em 4,6% dos pacientes, radiodermite grau 3, em 23,2%, vômitos grau 3, em 2,3%, plaquetopenia graus 3-4, em 6,9%, leucopenia grau 3, em 6,9%, e linfopenia grau 3, em 11,6%. Um paciente HIV positivo (2,3%) apresentou choque séptico grau 4, pneumonia grau 4, meningoencefalite herpética grau 4 e síndrome de ativação macrofágica grau 4. A taxa de colostomia foi de 18,6%. Conclusão: Capecitabina e mitomicina-C são um tratamento bem tolerado em pacientes com carcinoma de canal anal, com controle loco-regional em 6 meses em 86% dos pacientes. Palavras-chave: carcinoma de células escamosas, câncer anal, capecitabina, radioterapia, mitomicina-c / Background: Squamous cell carcinoma (SCC) of the anal canal is an uncommon malignancy accounting for 1-5% of intestinal tumors; however, its incidence has been increasing. Treatment for stage II and III anal canal SCC is infusional 5-fluorouracil associated with mitomycin and radiotherapy, since 1974. More convenient treatments for patients are needed. Methods: Patients with SCC of anal cancer T2-4N0M0 or T (any) N1-3M0, with good performance status, normal blood, and renal function were treated with capecitabine 825 mg/m2 bid during radiotherapy associated with a single dose of mitomycin 15 mg/m2 on day 1. Primary objective was local control rate at 6 months determined by clinical examination and radiological assessment. Sample size was calculated using Fleming single stage design. Results: From november/2010 to february/2014 51 patients were initially included, however 43 patients were assessed. Seventeen patients (39.5%) were stage II, 11 patients (25.6%) stage IIIA, and 15 patients (34.9%) stage IIIB. Four patients (9.3%) were HIV-positive, while 39 (90.7%) were HIV-negative. Median follow-up was 23.1 months. Among patients who finished the treatment and were reevaluated at 6 months 3 patients (7%) presented partial response, 37 patients (86%) had complete response, and 3 patients developed progression of the disease (7%). Regarding grade 3-4 toxicities, 10 patients (23.2%) had grade 3 radiodermitis, 3 patients (6.9%) had grade 3-4 thrombocytopenia, 5 (11.6%) had grade 3 lymphopenia, 1 patient (2.3%) had grade 3 vomiting, 2 patients (4.6%) had grade 3 diarrhea and 3 patients (6.9%) had grade 3 leukopenia. One HIV+ patient had septic shock, pneumonia, herpetic encephalitis and macrophage activation syndrome. Colostomy rate was 18.6%. Conclusions: Capecitabine and mitomycin with radiotherapy seem to be a safe treatment for SCC of the anal cancer, with a complete response rate in 6 months of 86%
36

Perfil de expressão de biomarcadores no carcinoma de canal anal e correlação com falha ao tratamento com quimio-radioterapia / Prospective study of biomarkers in squamous cell carcinoma of the anal canal and their influence on treatment outcomes

Moniz, Camila Motta Venchiarutti 16 October 2017 (has links)
Introdução: O tumor de canal anal é raro, sendo a histologia epidermóide a mais frequente. A quimio-radioterapia é capaz de curar a maioria dos casos de câncer de canal anal localizado, entretanto, um grupo de pacientes apresenta resistência primária ao tratamento multimodal. Métodos: Estudo de coorte prospectivo desenhado para avaliar a influência de biomarcadores (HIV, Ki-67, PD-L1, HPV e mutações no DNA tumoral) na resposta do câncer de canal anal ao tratamento com quimio-radioterapia. Resposta completa aos 6 meses após tratamento foi o desfecho primário. O DNA tumoral foi avaliado por sequenciamento genético, através do painel TruSight Tumor 26®. HPV foi testado pelo teste PapilloCheck®. Ki-67 e PD-L1 foram avaliados por imunoistoquímica. Sorologia para HIV foi realizada em todos os pacientes antes do início do tratamento. Resultados: Os pacientes foram recrutados de outubro/2011 a dezembro/2015 e 75 foram avaliados para resposta após o tratamento. A idade mediana foi de 57 anos, a maioria dos pacientes apresentou estadio III ao diagnóstico 65% (n=49) e 12% (n=9) tinha sorologia positiva para HIV. Aos 6 meses após término da quimio-radioterapia 62,7% (n=47) dos pacientes apresentou resposta completa, 24% (n=18) resposta parcial e 13,3% (n=10) progressão de doença. HPV foi avaliado em 67 amostras e encontrado em 70,1%, sendo o HPV 16 o tipo mais frequente. A pesquisa de PD-L1 foi realizada em 61 amostras e 16,4% (n=10) apresentou expressão > 1%. Idade, estadio clínico, HIV, expressão de Ki-67, presença de HPV, expressão de PD-L1 e interrupção de tratamento foram avaliados como preditores de resposta, aos 6 meses após o término do tratamento, por meio de regressão logística multivariada. Pacientes com estadio II apresentaram 4,7 vezes mais chance de resposta completa que pacientes com estadio III (OR=4,70; IC95%=1,36-16,30; p=0,015). Quando considerada resposta completa e/ou parcial, a presença do vírus HIV foi associada a pior resposta: pacientes HIV negativo apresentaram 5,7 vezes mais chance de resposta completa e/ou parcial que pacientes HIV positivo (OR=5,72; IC95%=2,5-13,0; p < 0,001). Foi possível a realização de sequenciamento do DNA tumoral em 25 pacientes avaliáveis para resposta, sendo as mutações mais frequentes encontradas nos genes PIK3CA (n=6) e MET (n=6). Não houve diferença em resposta de acordo com presença dessas mutações. Conclusões: Aos 6 meses após término do tratamento com quimio-radioterapia a expressão de Ki-67, PD-L1, presença de HPV e mutações em PIK3CA e MET não foram associadas com resposta ao tratamento. Pacientes com estadio III e pacientes portadores do vírus HIV apresentaram pior resposta ao tratamento / Background: While chemoradiation is the curative treatment for squamous cell carcinoma of the anal canal, some patients present primary resistance. As a rare tumor, predictors of response remain unknown. Patients and Methods: Prospective cohort study aimed at evaluating biomarkers (Ki-67, PD-L1, Human papillomavirus (HPV), tumor mutations and HIV) possibly associated with tumor response to chemoradiation. Complete response at 6 months was the primary endpoint. Tumor DNA was analyzed by next-generation sequencing (TruSight Tumor 26 ®). HPV was tested by PapilloCheck®. KI-67 and PD-L1 were evaluated by immunohistochemistry. Results: Seventyeight patients were recruited from October/2011 to December/2015, and 75 were evaluable for response. Median age was 57 years, 65% (n=49) were stage III, and 12% (n=9) were HIV positive (HIV+). At 6 months 62.7% (n=47) presented complete response, 24% (n=18) partial response and 13.3% (n=10) disease progression. HPV was evaluated in 67 and found in 70.1%, the majority being HPV 16. PD-L1 was tested in 61 being 16.4% (n=10) positive. Age, clinical stage, HIV status, KI-67, HPV, PD-L1 and treatment interruption were tested as predictive factors for complete response at 6 months by logistic regression. On multivariate analyses, stage II patients were 4.7 more likely to achieve complete response than stage III (OR=4.70; IC95%=1.36-16.30; p=0.015). When we considered patients with complete and partial response, HIV+ was associated with a worse response (OR=5.72; IC95%=2.5-13.0; p < 0.001). Twenty-five patients had samples proper for NGS and 17 had at least one mutation, with PIK3CA (n=6) and MET (n=6) being the most common mutated genes. There were no differences in response according to MET or PIK3CA status. Conclusions: At 6 months after chemoradiation Ki-67, PD-L1, HPV and mutations in PIK3CA and MET were not associated with response. Patients with stage III disease and patients HIV+ had a significantly poor response
37

O intempestivo BATAILLE: êxtase orgiástico, experiência interior, erotismo e ânus solar / The untimely BATAILLE: orgiastic ecstasy, inner experience, eroticism and solar anus

Barros, Lindinês Gomes de 03 June 2013 (has links)
Made available in DSpace on 2016-04-25T20:21:00Z (GMT). No. of bitstreams: 1 Lindines Gomes de Barros.pdf: 1639739 bytes, checksum: abb8e1a179cc0baeb81d0e0a8e966ae8 (MD5) Previous issue date: 2013-06-03 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / This thesis provides a reading through the fields of social sciences, of the philosophical concepts that compose the subject erotic and orgiastic in the thought and the narrative work - out with the paradigm of civilization of Georges Bataille: eroticism, ecstasy, inner experience, excess, transgression, and solar anus. This thinker, whose works deal with an erotic intention stigmatized as both pornographic and disconcerting because it subverts the concepts of reality and normality, constituted our main theoretical and literary "corpus". Bataille proposes a decomposition of the paradigm of civilizing rationality thanks to the idiosyncratic and obscure rhythms that form his erotic subject, with impure and imperfect subjectivities. In this discussion, we address his vision that consists in eroticism recognized as an inner experience, not subdued to regulation or discipline. This type of experience causes a kind of not-knowing, which reproduces the configuration of wild singularities proposed by Foucault and related to what cannot be assimilated by institutions and cultures. The characters in his literary narrative allow us to observe and define the erotic subject at the intersection between ecstasy and inner experience. They are convulsive bodies emerging from vertigo. Impregnated with this problem, they bring Eros sovereignty with elements of tragic eroticism and of horror that plunge the subject into the unknowable and the rationalizing inapprehensible. What we question in his mind is the challenge of thinking the abject and the excremental, that escape deterministic reasoning and release the vision of contemplative ecstasy by dispelling the significant determinants and the pedagogization that intertwine the social fabric.. The thesis will present his position deliberately at the fringe, which aimed to upset the established order in theology and science. It will reveal the orgiastic itinerary created by Bataille and characterized by economy of outlay, excess, anguish, ecstasy, eroticism, inner experience and concerns. Such a philosophical intent proposes a thought of waste, consumption and reasoning that release from the human condition / Esta tese estabelece uma leitura, no campo das ciências sociais, dos conceitos filosóficos: erotismo, êxtase, experiência interior, excesso, transgressão e ânus solar, que compõem o orgiástico sujeito erótico no pensamento e na narrativa romanescas do pensador Georges Bataille, que rompe com o paradigma civilizatório. O autor constitui nosso principal corpus teórico e literário, cujas obras, estão envolvidas numa concepção erótica estigmatizada como pornográfica e desconcertante, por subverter os conceitos de normalidade e realidade. Ele propõe uma decomposição do paradigma da racionalidade civilizatória, aos ritmos idiossincráticos e obscuros que compõem o sujeito erótico batailliano, com subjetividades impuras e imperfeitas . Nessa discussão conferimos o seu olhar constituinte de uma eroticidade, reconhecida enquanto experiência interior, não submetida à normatização e ao disciplinamento. Tal natureza de experiência, provoca uma espécie de não-saber, refletindo a configuração das singularidades selvagens, propostas em Foucault, relacionadas com aquilo ainda inassimilável pelas instituições e pelas culturas. Em sua narrativa literária, os personagens nos permitem observar e margear o sujeito erótico constituído no cruzamento entre o êxtase com a experiência interior. São corpos convulsivos que emergem da vertigem. Impregnados nessa problematicidade, trazem a soberania de Eros com elementos de um erotismo trágico e de horror, que mergulham o sujeito batailliano no incognoscível e no desentendimento racionalizante. O que interrogamos em seu pensamento é o desafio de pensar o que é abjeto e excremental, que escapa da razão determinista e liberta a visão da estaticidade contemplativa, dissipando significados determinantes e a pedagogização dos sentidos que entretece os tecidos sociais. A tese apresentará a sua posição nas margens, de modo a provocar desacomodações teológicas e cientifizantes. Revelará o itinerário orgiástico concebido por Bataille, tomado pela economia do dispêndio, excesso, angústias, êxtases, erotismos, experiência interior e inquietações. Tal concepção filosófica propõe um pensar do desperdício, da consumação e do raciocínio obsessivo que instaura uma libertação da condição humana
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O intempestivo BATAILLE: êxtase orgiástico, experiência interior, erotismo e ânus solar / The untimely BATAILLE: orgiastic ecstasy, inner experience, eroticism and solar anus

Barros, Lindinês Gomes de 03 June 2013 (has links)
Made available in DSpace on 2016-04-26T14:54:18Z (GMT). No. of bitstreams: 1 Lindines Gomes de Barros.pdf: 1639739 bytes, checksum: abb8e1a179cc0baeb81d0e0a8e966ae8 (MD5) Previous issue date: 2013-06-03 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / This thesis provides a reading through the fields of social sciences, of the philosophical concepts that compose the subject erotic and orgiastic in the thought and the narrative work - out with the paradigm of civilization of Georges Bataille: eroticism, ecstasy, inner experience, excess, transgression, and solar anus. This thinker, whose works deal with an erotic intention stigmatized as both pornographic and disconcerting because it subverts the concepts of reality and normality, constituted our main theoretical and literary "corpus". Bataille proposes a decomposition of the paradigm of civilizing rationality thanks to the idiosyncratic and obscure rhythms that form his erotic subject, with impure and imperfect subjectivities. In this discussion, we address his vision that consists in eroticism recognized as an inner experience, not subdued to regulation or discipline. This type of experience causes a kind of not-knowing, which reproduces the configuration of wild singularities proposed by Foucault and related to what cannot be assimilated by institutions and cultures. The characters in his literary narrative allow us to observe and define the erotic subject at the intersection between ecstasy and inner experience. They are convulsive bodies emerging from vertigo. Impregnated with this problem, they bring Eros sovereignty with elements of tragic eroticism and of horror that plunge the subject into the unknowable and the rationalizing inapprehensible. What we question in his mind is the challenge of thinking the abject and the excremental, that escape deterministic reasoning and release the vision of contemplative ecstasy by dispelling the significant determinants and the pedagogization that intertwine the social fabric.. The thesis will present his position deliberately at the fringe, which aimed to upset the established order in theology and science. It will reveal the orgiastic itinerary created by Bataille and characterized by economy of outlay, excess, anguish, ecstasy, eroticism, inner experience and concerns. Such a philosophical intent proposes a thought of waste, consumption and reasoning that release from the human condition / Esta tese estabelece uma leitura, no campo das ciências sociais, dos conceitos filosóficos: erotismo, êxtase, experiência interior, excesso, transgressão e ânus solar, que compõem o orgiástico sujeito erótico no pensamento e na narrativa romanescas do pensador Georges Bataille, que rompe com o paradigma civilizatório. O autor constitui nosso principal corpus teórico e literário, cujas obras, estão envolvidas numa concepção erótica estigmatizada como pornográfica e desconcertante, por subverter os conceitos de normalidade e realidade. Ele propõe uma decomposição do paradigma da racionalidade civilizatória, aos ritmos idiossincráticos e obscuros que compõem o sujeito erótico batailliano, com subjetividades impuras e imperfeitas . Nessa discussão conferimos o seu olhar constituinte de uma eroticidade, reconhecida enquanto experiência interior, não submetida à normatização e ao disciplinamento. Tal natureza de experiência, provoca uma espécie de não-saber, refletindo a configuração das singularidades selvagens, propostas em Foucault, relacionadas com aquilo ainda inassimilável pelas instituições e pelas culturas. Em sua narrativa literária, os personagens nos permitem observar e margear o sujeito erótico constituído no cruzamento entre o êxtase com a experiência interior. São corpos convulsivos que emergem da vertigem. Impregnados nessa problematicidade, trazem a soberania de Eros com elementos de um erotismo trágico e de horror, que mergulham o sujeito batailliano no incognoscível e no desentendimento racionalizante. O que interrogamos em seu pensamento é o desafio de pensar o que é abjeto e excremental, que escapa da razão determinista e liberta a visão da estaticidade contemplativa, dissipando significados determinantes e a pedagogização dos sentidos que entretece os tecidos sociais. A tese apresentará a sua posição nas margens, de modo a provocar desacomodações teológicas e cientifizantes. Revelará o itinerário orgiástico concebido por Bataille, tomado pela economia do dispêndio, excesso, angústias, êxtases, erotismos, experiência interior e inquietações. Tal concepção filosófica propõe um pensar do desperdício, da consumação e do raciocínio obsessivo que instaura uma libertação da condição humana
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Routine Anal Cytology Screening for Anal Squamous Intraepithelial Lesions in an Ethnically Diverse Urban HIV Clinic

Scott, Hyman 15 November 2006 (has links)
Anal cancer, like cervical cancer, is associated with Human Papillomavirus (HPV) infection. HIV+ patients have 38-60 fold increased risk of anal cancer compared to HIV- patients prompting many to suggest routine screening given the success of cervical Pap screening. Our goal is to describe our experience with routine anal Pap screening, determine which patients are most likely to have abnormal results, if anal disease on physical exam is predictive of cytology, and correlate cytology with histology findings. Charts of all patients with an anal Pap followed at the Hospital of Saint Raphael HIV Clinic were reviewed. Demographics, immune status, sexually transmitted disease history, cytology and histology data was extracted from medical charts. Patients with an anal Pap between November 1, 2002-November 30, 2004 were included. Those with an insufficient sample were excluded. Analysis was done using ÷2 for comparison of proportions and student t-test for continuous variables. Overall, 265/560 HIV+ patients had at least one anal Pap. Seventy-four of these 265 patients had an abnormal anal Pap. Mean age was 44 yrs, and 68% were men. Fifty-nine percent were African American, 34% White, and 17% Hispanic. Those with an abnormal Pap were more likely to be White (p=.03), and be gay or bisexual men (p=.02). They were also more likely to have lower CD4+ nadir (142 vs 223, p=.005) and CD4+ at time of anal Pap (353 vs 497, p<.001). Those with an abnormal anal Pap also had more anal disease (30% vs 9%, p<.001), history of warts (23% vs 12%, p=.02) and herpes (35% vs 22%, p=.02). Anal disease on physical exam had a sensitivity of 56% and specificity of 77% for abnormal cytology findings. On histology two patients had Anal Intraepithelial Neoplasia (AIN ) I, 2 AIN II, 3 AIN III, and 2 Squamous Cell Carcinoma In Situ. There was no correlation between cytology and histology. Routine anal cytology screening is a feasible tool to incorporate into an ethnically diverse HIV clinic for identifying precancerous anal lesions, a group which has been largely overlooked. Anal disease on physical exam is a poor predictor of abnormal cytology and there was no correlation between severity of disease on cytology and histology. However, further follow-up study is required to determine the impact on morbidity and mortality.
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Physiological Effects and Biotransformation of Paralytic Shellfish Toxins in New Zealand Marine Bivalves

Contreras Garces, Andrea Maud January 2010 (has links)
Although there are no authenticated records of human illness due to PSP in New Zealand, nationwide phytoplankton and shellfish toxicity monitoring programmes have revealed that the incidence of PSP contamination and the occurrence of the toxic Alexandrium species are more common than previously realised (Mackenzie et al., 2004). A full understanding of the mechanism of uptake, accumulation and toxin dynamics of bivalves feeding on toxic algae is fundamental for improving future regulations in the shellfish toxicity monitoring program across the country. This thesis examines the effects of toxic dinoflagellates and PSP toxins on the physiology and behaviour of bivalve molluscs. This focus arose because these aspects have not been widely studied before in New Zealand. The basic hypothesis tested was that bivalve molluscs differ in their ability to metabolise PSP toxins produced by Alexandrium tamarense and are able to transform toxins and may have special mechanisms to avoid toxin uptake. To test this hypothesis, different physiological/behavioural experiments and quantification of PSP toxins in bivalves tissues were carried out on mussels (Perna canaliculus), clams (Paphies donacina and Dosinia anus), scallops (Pecten novaezelandiae) and oysters (Ostrea chilensis) from the South Island of New Zealand. Measurements of clearance rate were used to test the sensitivity of the bivalves to PSP toxins. Other studies that involved intoxication and detoxification periods were carried out on three species of bivalves (P. canaliculus, P. donacina, P. novaezelandiae), using physiological responses (clearance and excretion rate) and analysis of PSP toxins in the tissues over these periods. Complementary experiments that investigated other responses in bivalves fed with the toxic cells were also carried out. These included byssus production, and the presence of toxic cells in the faeces of mussels, the siphon activity and burrowing depth in clams and the oxygen consumption in scallops. The most resistant species to PSP toxins were the mussel, Perna canaliculus and the clam, Dosinia anus. Both species fed actively on toxic dinoflagellates and accumulated toxins. The intoxication and detoxication rate of the mussel was faster than the other species of bivalve studied (P. donacina and P. novaezelandiae) which confirm mussels as a good sentinel species for early warning of toxic algal blooms. The clearance rate of the clam, Paphies donacina decreased when fed on Alexandrium species but the effect of the PSP toxins on this physiological response was not confirmed. Over the detoxification period of 8 days, this clam did not detoxify which suggests that its ability to retain high level of toxins for an extensive period may be critical for public health management. The scallop, Pecten novaezelandiae was clearly the most sensitive species to the PSP toxins and the clearance rate was significantly lower in the presence of the toxic dinoflagellate A. tamarense. Although the clearance rate was low, the scallops still fed on the toxic dinoflagellate and accumulated PSP toxins in the tissues. The scallops detoxified slowly which would affect the market for this bivalve in the presence of a toxic algal bloom. This bivalve would retain PSP toxins for longer period of time than other species such as mussels. The oyster, Ostrea chilensis, had erratic clearance rate and did not respond clearly to any of the variables tested over the time. Oysters accumulated more toxins than the sensitive species, but they had been exposed to two more days of feeding with A. tamarense; therefore this species may actually have a similar intoxication responses to P. novaezalandiae and P. donacina. The results from this thesis suggest further directions for the aquaculture sector and ongoing research in this field, which in future will lead to a better selection of suitable species for culture as well as species for monitoring of PSP toxins. In the future, research that integrates field and controlled laboratory studies will expand to other species of interest and a more complete record will in time be available in order to manage more efficiently the negative effects that harmful algal blooms may have in New Zealand.

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