Shorter CAG repeat length in the AR gene is associated with poor outcome in head and neck cancer

Objective: Alterations in the size of the [CAG](n) repeats of the AR gene have been described in several types tumors. The purpose of this study was to evaluate if there is an association between the AR [CAG](n) repeat alleles and the relative risk for head and neck cancer and to analyse microsatellite instability (MSI) and loss of heterozygosity (LOH) in these tumors.Design: Matched samples of blood and head and neck tumors were evaluated using two methodologies, silver-stained gels to perform the analyses of MSI and LOH, and automated analysis to confirm these results and for genotyping of the AR [CAG](n), repeat length. Sixty-nine individuals without cancer were used as a control group for both procedures. The Log-rank test was used to compare overall survival and disease-free survival curves. The Cox proportional hazards regression models were performed to determine the [CAG], repeats as an independent prognostic factor.Results: Patients with alleles <= 20 in the male group showed a correlation with lower disease-free survival (P = 0.0325) and with recurrence or metastasis (RR 2.52, CI 95%). in the female group, the allele 2 (longer allele) showed a significant lower mean of [CAG](n), repeat when compared to the control group. Microsatellite instability was detected in nine cases in both procedures. In six out of these nine cases, we observed a reduction of the AR [CAG](n) repeat length. LOH was detected in one out of 17 women informative for oral cancer in both procedures.Conclusion: These results suggest that short [CAG](n) repeat length (: 20) polymorphism is associated with poor prognosis in a subset of male patients with head and neck cancer and that AR gene microsatellite instability is uncommon in these tumors. (C) 2007 Elsevier Ltd. All rights reserved.

COX-2 Inhibitors for Cancer Treatment in Dogs

Cancer is one of the main causes of death in canines and felines, and this fact is probably related to the increase in the longevity of these species. The longer the animals live, the higher the exposure to carcinogenic agents will be. With the high incidence of cancer in companion animals, new studies are currently being performed with the aim of finding therapeutic options which make the complete inhibition of the development of neoplasms in animals possible in the future. The correlation of cyclooxygenase-2 (COX-2) whith the development of cancer opens the way for the use of new therapeutic approaches. This relationship has been suggested based on various studies which established an association between the chronic use of nonsteroidal anti-inflammatory drugs (NSAID) and a decrease in the incidence of colon carcinoma. As cancer progresses, COX-2 participates in the arachidonic acid metabolism by synthesizing prostaglandins which can mediate various mechanisms related to cancer development such as: increase in angiogenesis, inhibition of apoptosis, suppression of the immune response, acquisition of greater invasion capacity and metastasis. Accordingly, overexpression of this enzyme in tumors has been associated with the most aggressive, poor-prognosis cancer types, especially carcinomas. Therefore, treatments which use COX-2 inhibitors such as coxibs, whether administered as single agents or in combination with conventional antineoplastic chemotherapy, are an alternative for extending the survival of our cancer patients.

Canine corpus luteum regression: Apoptosis and caspase-3 activity

The present study evaluated the occurrence of apoptosis and caspase-3 activity in the canine corpus luteum during the period of luteal regression in eight pregnant and nine nonpregnant diestrus bitches. Intact luteal cells were obtained from corpora lutea in both peripartum pregnant bitches and nonpregnant diestrus bitches at approximately 65 d (range 63-68) after estrus, but not at days 75 and 85 in nonpregnant bitches. In all bitches, apoptotic cells were rarely detected and when present, those cells were more easily detected using the hematoxylin and eosin technique than using the critical electrolyte concentration technique. The luteal structures at 75 and 85 d of diestrus had histological characteristics similar to a corpus albicans. Caspase-3 activity was detected in morphologically normal corpora lutea from both pregnant and diestrus bitches around day 65, and also in the later structures considered corpus albicans tissue. These results suggested that apoptosis may not be the major mechanism involved in canine functional luteal regression, and that caspase-3 participated in both functional and morphological luteolysis and in the tissue reorganization involved in corpus albicans formation. (c) 2006 Published by Elsevier B.V.

Logistic regression analysis of potential prognostic factors for pulmonary thromboembolism

Objective: To identify potential prognostic factors for pulmonary thromboembolism (PTE), establishing a mathematical model to predict the risk for fatal PTE and nonfatal PTE.Method: the reports on 4,813 consecutive autopsies performed from 1979 to 1998 in a Brazilian tertiary referral medical school were reviewed for a retrospective study. From the medical records and autopsy reports of the 512 patients found with macroscopically and/or microscopically,documented PTE, data on demographics, underlying diseases, and probable PTE site of origin were gathered and studied by multiple logistic regression. Thereafter, the jackknife method, a statistical cross-validation technique that uses the original study patients to validate a clinical prediction rule, was performed.Results: the autopsy rate was 50.2%, and PTE prevalence was 10.6%. In 212 cases, PTE was the main cause of death (fatal PTE). The independent variables selected by the regression significance criteria that were more likely to be associated with fatal PTE were age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.00 to 1.03), trauma (OR, 8.5; 95% CI, 2.20 to 32.81), right-sided cardiac thrombi (OR, 1.96; 95% CI, 1.02 to 3.77), pelvic vein thrombi (OR, 3.46; 95% CI, 1.19 to 10.05); those most likely to be associated with nonfatal PTE were systemic arterial hypertension (OR, 0.51; 95% CI, 0.33 to 0.80), pneumonia (OR, 0.46; 95% CI, 0.30 to 0.71), and sepsis (OR, 0.16; 95% CI, 0.06 to 0.40). The results obtained from the application of the equation in the 512 cases studied using logistic regression analysis suggest the range in which logit p > 0.336 favors the occurrence of fatal PTE, logit p < - 1.142 favors nonfatal PTE, and logit P with intermediate values is not conclusive. The cross-validation prediction misclassification rate was 25.6%, meaning that the prediction equation correctly classified the majority of the cases (74.4%).Conclusions: Although the usefulness of this method in everyday medical practice needs to be confirmed by a prospective study, for the time being our results suggest that concerning prevention, diagnosis, and treatment of PTE, strict attention should be given to those patients presenting the variables that are significant in the logistic regression model.

Choosing between Cox proportional hazards and logistic models for interval-censored data via bootstrap

This work develops a new methodology in order to discriminate models for interval-censored data based on bootstrap residual simulation by observing the deviance difference from one model in relation to another, according to Hinde (1992). Generally, this sort of data can generate a large number of tied observations and, in this case, survival time can be regarded as discrete. Therefore, the Cox proportional hazards model for grouped data (Prentice & Gloeckler, 1978) and the logistic model (Lawless, 1982) can befitted by means of generalized linear models. Whitehead (1989) considered censoring to be an indicative variable with a binomial distribution and fitted the Cox proportional hazards model using complementary log-log as a link function. In addition, a logistic model can be fitted using logit as a link function. The proposed methodology arises as an alternative to the score tests developed by Colosimo et al. (2000), where such models can be obtained for discrete binary data as particular cases from the Aranda-Ordaz distribution asymmetric family. These tests are thus developed with a basis on link functions to generate such a fit. The example that motivates this study was the dataset from an experiment carried out on a flax cultivar planted on four substrata susceptible to the pathogen Fusarium oxysoprum. The response variable, which is the time until blighting, was observed in intervals during 52 days. The results were compared with the model fit and the AIC values.

Likelihood approximations and discrete models for tied survival data

Ties among event times are often recorded in survival studies. For example, in a two week laboratory study where event times are measured in days, ties are very likely to occur. The proportional hazards model might be used in this setting using an approximated partial likelihood function. This approximation works well when the number of ties is small. on the other hand, discrete regression models are suggested when the data are heavily tied. However, in many situations it is not clear which approach should be used in practice. In this work, empirical guidelines based on Monte Carlo simulations are provided. These recommendations are based on a measure of the amount of tied data present and the mean square error. An example illustrates the proposed criterion.

Some practical advice on polynomial regression analysis from blocked response surface designs

It is often necessary to run response surface designs in blocks. In this paper the analysis of data from such experiments, using polynomial regression models, is discussed. The definition and estimation of pure error in blocked designs are considered. It is recommended that pure error is estimated by assuming additive block and treatment effects, as this is more consistent with designs without blocking. The recovery of inter-block information using REML analysis is discussed, although it is shown that it has very little impact if thc design is nearly orthogonally blocked. Finally prediction from blocked designs is considered and it is shown that prediction of many quantities of interest is much simpler than prediction of the response itself.

Carbon Nuclear Magnetic Resonance Spectroscopic Profiles coupled to Partial Least-Squares Multivariate Regression for Prediction of Several Physicochemical Parameters of Brazilian Commercial Gasoline

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Logistic regression to estimate the welfare of broiler breeders in relation to environmental and behavioral variables

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bayesian binary regression model: an application to in-hospital death after AMI prediction

Um modelo bayesiano de regressão binária é desenvolvido para predizer óbito hospitalar em pacientes acometidos por infarto agudo do miocárdio. Métodos de Monte Carlo via Cadeias de Markov (MCMC) são usados para fazer inferência e validação. Uma estratégia para construção de modelos, baseada no uso do fator de Bayes, é proposta e aspectos de validação são extensivamente discutidos neste artigo, incluindo a distribuição a posteriori para o índice de concordância e análise de resíduos. A determinação de fatores de risco, baseados em variáveis disponíveis na chegada do paciente ao hospital, é muito importante para a tomada de decisão sobre o curso do tratamento. O modelo identificado se revela fortemente confiável e acurado, com uma taxa de classificação correta de 88% e um índice de concordância de 83%.

Occurrence and significance of ovarian and follicular regression in cachara Pseudoplatystoma fasciatum (Linnaeus, 1766): a histology approach

Estudaram-se os processos de regressão ovariana e atresia folicular em cachara, Pseudoplatystoma fasciatum, mantida em cativeiro, na reprodução não induzida por hormônios. As características macro e microscópicas (diâmetro dos ovócitos e histologia) dos ovários foram descritas a cada 20 dias, em quatro estádios: na regressão inicial (Rg I - os primeiros 20 dias), na regressão intermediária (Rg II - do 21º ao 40º dia), na regressão final (Rg III - do 41º ao 80º dia) e na fase de recuperação ou de repouso II (R II - do 81º ao 150º dia). O experimento foi realizado do final de janeiro (verão-dias longos) a maio (outono-dias curtos). No início do experimento, as amostras apresentaram ovócitos com diâmetros que variaram de 437,5 a 1.187,5mm, sugerindo encontrarem-se nas fases perinucleolar, de maturação final e atrésicos. Aos 150 dias, os diâmetros atingiram os menores valores e pôde-se visualizar a zona radiata rompida e o vitelo reabsorvido. Concomitantemente, houve diminuição abrupta dos valores médios do índice gonadossomático, da temperatura da água, das horas de luz e de chuva. A involução gradual do longo processo foi dinâmica e complexa, afetando o êxito da desova (taxas de fertilização, de eclosão e de sobrevivência de larvas) e, conseqüentemente, o sistema produtivo.

Determinação da idade fetal por meio da técnica ultra-sonográfica de fetometria e de morfologia fetal em cabras

Utilizaram-se 13 cabras gestantes da raça Saanen, para estudo das características da gestação a partir do 60º dia, segundo as técnicas de fetometria e avaliação morfológica fetal, utilizando-se ultra-sonografia em modo-B. Analisaram-se: diâmetro orbital (DO), diâmetro interorbital (DIO), diâmetro biorbital (DBO), diâmetro biparietal (DBP), comprimento do fêmur (CF), comprimento da tíbia (CT), comprimento do rádio (CR), diâmetro do tórax (DT), diâmetro abdominal transversal (DAT), diâmetro abdominal anteroposterior (DAP), diâmetro occípito-frontal (DOF), diâmetro transversal renal (RIMT), diâmetro longitudinal renal (RIML), comprimento da escápula (ESC), comprimento do metacarpo (MEC), medida da pelve (COX) e comprimento do úmero (CU). As médias dos valores achados foram correlacionadas com a idade fetal. As equações de regressão inversa foram criadas para cada parâmetro, sendo que DBP (R²=0,93), CF (R²=0,95), CU (R²=0,96), do (R²= 0,84) e DAT (R²= 0,91) foram as variáveis de melhor correlação estatística, cuja equação pode ser representada pela fórmula: idade fetal = 34,5 + 4,8DBP + 9,9 CF - 7,5 CU - 2,3 do + 6,1 DAT.

Late administration of a specific COX-2 inhibitor does not treat and/or prevent progression of gastric tumors in rats submitted to duodenogastric reflux procedure

PURPOSE:To assess whether late introduction of a specific COX-2 inhibitor (Meloxicam) can treat and/or prevent the progression of tumors in the stomach of rats submitted to duodenogastric reflux. METHODS: Seventy five male Wistar rats, weighing 150 grams, were submitted to the induction of duodenogastric reflux through the pylorus. At 36 weeks of follow-up were established three experimental groups: DGR36 sacrificed immediately, DGR54 and DGR54MLX both sacrificed at 54th week of follow-up . The animals of the latter group were fed with a rat chow premixed with Meloxicam (2.0 mg/ kg feed; 0.3 mg / kg bw / day) and the other two with standard rat chow. The lesions found in the pyloric mucosa and gastrojejunal anastomosis were analyzed macroscopically and histologically. For statistical analysis was adjusted a generalized linear model assuming a binomial distribution with LOGIT link function. RESULTS: No significant differences were found when comparing the incidences of benign tumor lesions (Adenomatous Hyperplasia), p=0.4915, or malignant (Mucinous Adenocarcinoma), p=0.2731, among groups. CONCLUSION: Late introduction of specific COX-2 inhibitor (Meloxicam) did not treat and was not able to prevent the progression of tumoral lesions induced by duodenogastric reflux in the rat stomachs.

Methods to verify parameter equality in nonlinear regression models

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)