958 resultados para Työlahti, Nina
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Purpose Dasatinib is a BCR-ABL inhibitor, 325-fold more potent than imatinib against unmutated BCR-ABL in vitro. Phase II studies have demonstrated efficacy and safety with dasatinib 70 mg twice daily in chronic-phase (CP) chronic myelogenous leukemia (CML) after imatinib treatment failure. In phase I, responses occurred with once-daily administration despite only intermittent BCR-ABL inhibition. Once-daily treatment resulted in less toxicity, suggesting that toxicity results from continuous inhibition of unintended targets. Here, a dose-and schedule-optimization study is reported. Patients and Methods In this open-label phase III trial, 670 patients with imatinib-resistant or -intolerant CP-CML were randomly assigned 1: 1: 1: 1 between four dasatinib treatment groups: 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. Results With minimum follow-up of 6 months (median treatment duration, 8 months; range, = 1 to 15 months), marked and comparable hematologic (complete, 86% to 92%) and cytogenetic (major, 54% to 59%; complete, 41% to 45%) response rates were observed across the four groups. Time to and duration of cytogenetic response were similar, as was progression-free survival (8% to 11% of patients experienced disease progression or died). Compared with the approved 70-mg twice-daily regimen, dasatinib 100 mg once daily resulted in significantly lower rates of pleural effusion (all grades, 7% v 16%; P = .024) and grade 3 to 4 thrombocytopenia (22% v 37%; P = .004), and fewer patients required dose interruption (51% v 68%), reduction (30% v 55%), or discontinuation (16% v 23%). Conclusion Dasatinib 100 mg once daily retains the efficacy of 70 mg twice daily with less toxicity. Intermittent target inhibition with tyrosine kinase inhibitors may preserve efficacy and reduce adverse events.
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In the early postoperative period of Cushing`s disease patients, desmopressin may stimulate ACTH secretion in the remnant corticotrophic tumour, but not in nontumour suppressed cells. Objective The aim of this study is to evaluate the serum cortisol responses to desmopressin after pituitary surgery, establishing an optimal cut-off for absolute increment (Delta) of serum cortisol (F) suitable to predict recurrence risk. Design Retrospective case record study. Patients Fifty-seven Cushing`s disease patients submitted to pituitary surgery and desmopressin stimulation in the early postoperative with a long-term follow-up (20-161 months) were studied. Methods and measurements Serum cortisol levels after desmopressin test (10 mu g IV) 15-30 days after adenomectomy were used to determine Delta F (absolute increment of F: F peak - F baseline). Sensitivity and specificity of Delta F were calculated and a ROC curve was performed to establish an optimal cut-off for Delta F to predict recurrence risk. Results Fifteen patients had immediate postoperative failure (basal F > 165 nmol/l; 6 mu g/dl) and one patient was lost during the follow-up. Forty-one patients achieved initial remission and were followed-up. Five of 11 patients who recurred had Delta F > 193 nmol/l (7 mu g/dl), but none of 30 patients who remained in prolonged remission showed Delta F > 193 nmol/l after postoperative desmopressin stimulation. Conclusions Persistence of cortisol response (Delta F > 193 nmol/l) to desmopressin in the early postoperative period can help to identify Cushing`s disease patients with initial remission who present risk for later recurrence.
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About one-third of acromegalics are resistant to the clinically available somatostatin analogs (SA). The resistance is related to density reduction or different expression of somatostatin receptor subtypes (SSTR). This study analyzes SSTR`s expression in somatotrophinomas, comparing to SA response, hormonal levels, and tumor volume. We analyzed 39 somatotrophinomas; 49% were treated with SA. The most expressed SSTR was SSTR5, SSTR3, SSTR2, SSTR1, and SSTR4, respectively. SSTR1 and SSTR2 had higher expression in patients that had normalized GH and IGF-I. SSTR3 was more expressed in patients with tumor reduction. There was a positive correlation between the percentage of tumor reduction and SSTR1, SSTR2 and SSTR3 expression. Also, a positive correlation between SSTR2 mRNA expression and the immunohistochemical reactivity of SSTR2 was found. Our study confirmed the association between the SA response to GH and IGF-I and the SSTR2. Additionally, this finding was also demonstrated in relation to SSTR1.
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Dopamine agonists are the treatment of choice for prolactinomas. However, there are still controversies concerning dose, treatment duration and criteria for drug withdrawal in different clinical situations. The aim of this study was to assess diagnostic and therapeutic approaches to prolactinomas among members of the Brazilian Society of Endocrinology and Metabolism (SBEM). SBEM members answered a questionnaire sent by e-mail that included 18 questions related to controversial issues about the management of prolactinomas. Among SBEM members, 721 (approximately 24% of total) answered the questionnaire. Concerning the diagnosis, 38% of the respondents stated that prolactin levels < 100 ng/ml would exclude the presence of a prolactinoma. Most of them favored the screening for macroprolactin in asymptomatic individuals instead of a routine screening (74% vs. 26%). Regarding the treatment, 70% of the respondents chose cabergoline as the drug of choice to treat macroprolactinomas whereas similar proportions advised cabergoline or bromocriptine as the best treatment for microprolactinomas (52% vs. 48%). Only 20% and 34% of respondents favored treatment withdrawal 2-3 years after prolactin normalization in patients with macroprolactinomas and microprolactinomas, respectively. In case of pregnancy, only 58 and 70% of respondents advocated discontinuation of treatment with dopamine agonists in patients with macroprolactinomas and microprolactinomas, respectively. Finally, only 36% would allow breast-feeding without restriction, 44% would restrict it to patients with microprolactinomas and 20% would not recommend it for women with prolactinomas There are several points of disagreement among SBEM members regarding the management of prolactinomas.
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Posttraumatic stress disorder (PTSD) is a prevalent, disabling anxiety disorder marked by behavioral and physiologic alterations which commonly follows a chronic course. Exposure to a traumatic event constitutes a necessary, but not sufficient, factor. There is evidence from twin studies supporting a significant genetic predisposition to PTSD. However, the precise genetic loci still remain unclear. The objective of the present study was to identify, in a case-control study, whether the brain-derived neurotrophic factor (BDNF) val66met polymorphism (rs6265), the dopamine transporter (DAT1) three prime untranslated region (3`UTR) variable number of tandem repeats (VNTR), and the serotonin transporter (5-HTTPRL) short/long variants are associated with the development of PTSD in a group of victims of urban violence. All polymorphisms were genotyped in 65 PTSD patients as well as in 34 victims of violence without PTSD and in a community control group (n = 335). We did not find a statistical significant difference between the BDNF val66met and 5-HTTPRL polymorphism and the traumatic phenotype. However, a statistical association was found between DAT1 3`UTR VNTR nine repeats and PTSD (OR = 1.82; 95% CI, 1.20-2.76). This preliminary result confirms previous reports supporting a susceptibility role for allele 9 and PTSD.
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Background/Aims: These studies investigated the role of apoptosis following ischaemia/reperfusion (I/R) injury to the liver and the effect of pretreatment with Cyclosporin A. Methods: Male Sprague-Dawley rats received 30 min of warm ischaemia followed by a period of reperfusion of 6 h. Rats were given olive oil or Cyclosporin A (30 mg/kg p.o.) the day before surgery. Neutrophil numbers were assessed in haematoxylin-eosin-stained sections of liver. In situ staining of sections using TdT-mediated dUTP-fluoreseein nick-end labelling was carried out to determine the extent of apoptosis, followed by electron microscopy. Semi-quantitative polymerase chain reaction (PCR) analysis of the transcript for Fas antigen was performed. Results and Conclusions: High levels of apoptosis were observed in I/R injury, which were greatly ameliorated in Cyclosporin A-pretreated groups. PCR analysis indicated a reduction in the level of expression of Fas transcript in Cyclosporin A-treated rats. Histological analysis showed a significant increase in the number of neutrophils infiltrating I/R-injured tissue (62 +/- 10.69, it = 16), which was markedly reduced by Cyclosporin A pretreatment (16 +/- 7, n = 6, P < 0.05). These results indicate a role of parenchymal apoptosis in the pathogenesis of I/R injury, which occurs in association with neutrophil infiltration, both of which can be significantly reduced by Cyclosporin A pretreatment. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.
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The light-evoked release of acetylcholine (ACh) affects the responses of many retinal ganglion cells, in part via nicotinic acetylcholine receptors (nAChRs). nAChRs that contain beta2alpha3 neuronal nicotinic acetylcholine receptors have been identified and localized in the rabbit retina; these nAChRs are recognized by the monoclonal antibody mAb210. We have examined the expression of beta2alpha3 nAChRs by glycinergic amacrine cells in the rabbit retina and have identified different subpopulations of nicotinic cholinoceptive glycinergic cells using double and triple immunohistochemistry with quantitative analysis. Here we demonstrate that about 70% of the cholinoceptive amacrine cells in rabbit retina are glycinergic cells. At least three nonoverlapping subpopulations of mAb210 glycine-immunoreactive cells can be distinguished with antibodies against calretinin, calbindin, and gamma-aminobutyric acid (GABA)(A) receptors. The cholinergic cells in rabbit retina are thought to synapse only on other cholinergic cells and ganglion cells. Thus, the expression of beta2alpha3 nAChRs on diverse populations of glycinergic cells is puzzling. To explore this finding, the subcellular localization of beta2alpha3 was studied at the electron microscopic level. mAb210 immunoreactivity was localized on the dendrites of amacrines and ganglion cells throughout the inner plexiform layer, and much of the labeling was not associated with recognizable synapses. Thus, our findings indicate that ACh in the mammalian retina may modulate glycinergic circuits via extrasynaptic beta2alpha3 nAChRs. (C) 2002 Wiley-Liss, Inc.
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A reorganiza????o do modelo de gest??o de recursos humanos do governo federal ???acompanhada da recomposi????o de sal??rios e revitaliza????o das carreiras e cargos ??? e o impacto fiscal dos reajustes dos servidores p??blicos foram as quest??es que movimentaram essa edi????o do Caf?? com Debate. O evento teve a participa????o do secret??rio e da secret??ria-adjunta de Recursos Humanos do Minist??rio do Planejamento, Or??amento e Gest??o, Duvanier Paiva Ferreira e Nina Gomes, da presidente da Enap, Helena Kerr do Amaral, e da jornalista M??nica Izaguirre, rep??rter especial do Valor Econ??mico
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O objetivo deste artigo ?? apresentar um modelo alternativo de an??lise da efici??ncia dos programas de p??s-gradua????o acad??micos em Administra????o, Contabilidade e Turismo, vinculados ??s institui????es de ensino superior p??blicas e privadas. O estudo tem como base te??rica a efici??ncia e a otimiza????o de recursos, tomando como refer??ncia a maximiza????o do retorno, sujeito ??s limita????es de recursos. Como modelo anal??tico foi utilizada a An??lise Envolt??ria de Dados (DEA), enquanto t??cnica n??o param??trica de an??lise da efici??ncia relativa. Os resultados apontaram que os programas de p??s-gradua????o foram mais eficientes em 2006, seguido por 2004 e 2005, respectivamente. Notou- se ainda que, em m??dia, os programas vinculados ??s institui????es privadas de ensino foram mais eficientes que os da rede p??blica no tri??nio 2004/2006. Os gestores desses programas podem utilizar a an??lise da efici??ncia relativa como estrat??gia de benchmarking, adotando as melhores pr??ticas observadas nos programas eficientes, visando ?? maximiza????o da efici??ncia em sua gest??o.
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This study was carried out to investigate the effects of light spectra, additional UV-A, and different growth regulators on the in vitro germination of Senecio cineraria DC. Seeds were surface-sterilized and inoculated in MS medium to evaluate the following light spectra: white, white plus UV-A, blue, green, red or darkness. The maximum germinability was obtained using MS0 medium under white light (30%) and MS + 0.3 mg L-1 GA3 in the absence of light (30.5%). S. cineraria seeds were indifferent to light. Blue and green lights inhibited germination. Different concentrations of gibberellic acid (GA3) (0.1; 0.4; 0.6; 0.8; 1.0 and 2.0 mg L-1) and indole-3-acetic acid IAA (0.1; 0.3 and 1.0 mg L-1) were evaluated under white light and darkness. No concentration of GA3 enhanced seed germination percentage under white light. However, when the seeds were maintained in darkness, GA3 improved germination responses in all tested concentrations, except at 1.0 mg L-1. Under white light, these concentrations also increased the germination time and reduced germination rate. Germination rate, under light or darkness, was lower using IAA compared with GA3.
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Desde a década de 1990, o setor público brasileiro tem buscado modificar sua atuação perante a sociedade. Em um contexto de reformas, a área de recursos humanos tornase essencial, pois são as pessoas que colocam em prática tais mudanças. Uma política de recursos humanos imprescindível para o êxito das reformas é o treinamento, que possibilita a capacitação do funcionário para um melhor desempenho na prestação de serviços aos cidadãos. Este artigo identifica o modo como o treinamento dos servidores técnico-administrativos (STAs) influencia a realização das atividades na Universidade Federal de Viçosa (UFV), na percepção dos treinados e dos dirigentes da instituição. As informações foram obtidas por meio de uma revisão da literatura, de visita à diretoria de recursos humanos da UFV, e de entrevistas com alguns treinados e dirigentes da instituição. De acordo com os resultados, existem diversos fatores que interferem positiva e negativamente no processo de treinamento. A falta de uma política de aperfeiçoamento formalizada e a legislação contribuem para essa realidade. Como o processo não é bem estruturado, não existe um planejamento para as atividades de treinamento, nem mesmo uma avaliação do STA que o fez.
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Desde a segunda metade do século XIX e até a década de 1940, as práticas e doutrinas espíritas mobilizaram o pensamento médico, num duplo empreendimento intelectual e de intervenção social. O artigo aborda vários textos elaborados, neste período, por médicos (tais como Nina Rodrigues e Leonídio Ribeiro), explorando como neles é definido e analisado o espiritismo, e localizando, entre as diversas épocas, continuidades e rupturas. Na década de 1930, o espiritismo e os cultos de possessão em geral começam a ser tratados por referência a categorias sociológicas e antropológicas, sinalizando uma transformação importante no seu estatuto (Arthur Ramos é um nome chave). No artigo, esta transição é problematizada a partir da análise da categoria "higiene mental", utilizada por intelectuais durante as décadas de 1920 e 1930 e associada às discussões sobre a constituição e destinos do Brasil enquanto nação.
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As artes culinárias, os seus intervenientes e a envolvente associada às mesmas, assumem hoje um interesse crescente por parte dos consumidores, podendo funcionar como uma ferramenta de educação, tornando os consumidores mais recetivos à influência da alimentação na saúde. Por outro lado, o entretenimento direcionado para alimentação poderá conduzir o consumidor a um desvio das suas práticas alimentares saudáveis, envolvendo os espetadores numa fantasia e glamour, de cenários encenados que parecem reais em particular para pessoas sem qualificações em artes culinárias. Esta investigação pretende aferir a perceção dos Chefs sobre o conceito de alimentação saudável e a sua influência no bem-estar das pessoas na região da grande Lisboa. Metodologicamente, realizaram-se entrevistas a Chefs, privilegiando o método qualitativo. A informação recolhida foi tratada recorrendo-se à análise de conteúdo, utilizando-se o software QSR Nvivo 10®. As entrevistas seguiram um guião pré-estabelecido, incidindo sobre os seguintes temas: i) hábitos alimentares dos Chefs em casa; ii) perceção sobre alimentação saudável; iii) práticas em contexto de trabalho. Os Chefs percecionaram corretamente o conceito de alimentação saudável e associaram o bem-estar como o principal benefício associado à sua prática. Porém, nos seus locais de trabalho, os Chefs referem que se sentem pressionados pelas questões economicistas aquando da elaboração das suas receitas. Importa pois promover uma oferta alimentar atrativa e simultaneamente saudável, contribuindo para o bem-estar das pessoas.
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OBJECTIVE: To evaluate possible adverse reproductive outcomes in an area adjacent to a petrochemical plant in southern Brazil. METHODS: A review of 17,113 birth records of the main hospital of the municipality of Montenegro, southern Brazil, from 1983 to 1998 was carried out. Three groups of cases were selected: (1) newborns with major congenital malformations; (2) newborns with low birth weight (<2,500 g); and (3) stillborns (>500 g). A control was assigned to each case. Controls were the first newborns weighing > or = 2,500 g without malformations and of case-matching sex. Mother's residence during pregnancy was used as an exposure parameter. Statistical analyses were performed using Chi-square test or Fisher test, odds ratio, 0.05 significance level, and 95% confidence interval. RESULTS: For unadjusted analysis, it was found a correlation between low birth weight and geographical proximity of mother's residence to the petrochemical plant (OR = 1.66; 95% CI = 1.01--2.72) or residence on the way of preferential wind direction (OR = 1.62; 95% CI = 1.03--2.56). When other covariates were added in the conditional logistic regression (maternal smoking habits, chronic disease and age), there was no association. CONCLUSIONS: Despite final results were negative, low birth weight could be a good parameter of environmental contamination and should be closely monitored in the studied area.
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Two distinct subsets of γδ T cells that produce interleukin 17 (IL-17) (CD27(-) γδ T cells) or interferon-γ (IFN-γ) (CD27(+) γδ T cells) develop in the mouse thymus, but the molecular determinants of their functional potential in the periphery remain unknown. Here we conducted a genome-wide characterization of the methylation patterns of histone H3, along with analysis of mRNA encoding transcription factors, to identify the regulatory networks of peripheral IFN-γ-producing or IL-17-producing γδ T cell subsets in vivo. We found that CD27(+) γδ T cells were committed to the expression of Ifng but not Il17, whereas CD27(-) γδ T cells displayed permissive chromatin configurations at loci encoding both cytokines and their regulatory transcription factors and differentiated into cells that produced both IL-17 and IFN-γ in a tumor microenvironment.