PubMed Health⌕ Search

Biomedical subjects

Malka Gorfine

Publications and source records attributed to Malka Gorfine.

9 recordsLinked to original sources
PubMed2006

Feedback inhibition of gonadotropins by testosterone in men with hypogonadotropic hypogonadism: comparison to the intact pituitary-testicular axis in primary hypogonadism.

Men with hypogonadotropic hypogonadism (HH) due to hypothalamic-pituitary disease present with low serum testosterone levels combined with undetectable, low, or normal gonadotropin levels. Treatment consists of testosterone replacement to reverse the symptoms of androgen deficiency. The aim of this study was to examine the dynamics and feedback inhibition of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in relation to testosterone in 38 men with HH treated with testosterone. Findings were compared with 11 men with primary hypergonadism (PH). Testosterone replacement led to a suppression of FSH levels from 2.8 IU/L at baseline to 1.1 IU/L and to a suppression of LH levels from 2.3 to 0.8 IU/L. There was a linear correlation between levels of FSH and LH (after natural log transformation for both) and testosterone levels in both the HH and PH groups. However, the differences in intercepts and slopes between the groups were significant. To determine whether nonsuppressed FSH or LH during testosterone replacement reduces the probability of eugonadism, as reflected by normal testosterone levels, gonadotropin levels were measured and categorized as low (<0.5 IU/L), medium (0.5-2 IU/L), and high levels (>2 IU/L). The higher FSH or LH levels were found to significantly decrease the chance for achieving eugonadism. In conclusion, in men with HH due to hypothalamic-pituitary disease or injury, the pituitary-testicular hormonal axis maintains its physiological negative feedback between testosterone and gonadotropins. Thus, gonadotropin levels in men with HH might be useful, together with testosterone concentrations, for assessing the adequacy of androgen replacement.

Adolescent↗
PubMed2005

Multivariate survival analysis for case-control family data.

Multivariate survival data arise from case-control family studies in which the ages at disease onset for family members may be correlated. In this paper, we consider a multivariate survival model with the marginal hazard function following the proportional hazards model. We use a frailty-based approach in the spirit of Glidden and Self (1999) to account for the correlation of ages at onset among family members. Specifically, we first estimate the baseline hazard function nonparametrically by the innovation theorem, and then obtain maximum pseudolikelihood estimators for the regression and correlation parameters plugging in the baseline hazard function estimator. We establish a connection with a previously proposed generalized estimating equation-based approach. Simulation studies and an analysis of case-control family data of breast cancer illustrate the methodology's practical utility.

Age of Onset↗
PubMed2004

Germ-line ATM gene alterations are associated with susceptibility to sporadic T-cell acute lymphoblastic leukemia in children.

A major feature of ataxia-telangiectasia (A-T) is an increased risk of cancer, particularly of lymphoid malignancies. We studied ATM gene involvement in leukemic cells derived from 39 pediatric T-cell acute lymphoblastic leukemias (ALLs). Two types of sequence changes--truncating and missense--were identified in 8 T-cell ALL samples: 3 truncating changes, all previously identified in A-T (R35X, -30del215, 2284delCT), and 3 missense variants (V410A, F582L, F1463C) were found, none associated with loss of heterozygosity (LOH). In all patients studied, the mutation was present in the germ-line. A-T carriers, defined by the finding of truncating mutations, were found to be 12.9 times more frequent than in the normal population (P = 0.004). A normally ethnically matched population was screened for the 3 missense variants, and their frequency was significantly more prevalent (4.9-fold excess) than in the normal population (P = 0.03). Our data suggest there is some evidence of an association between missense alterations in the ATM gene and T-cell ALL. A significant difference in the mean age at diagnosis of T-cell ALL was noted between patients harboring an ATM sequence change and those with no change, 5.4 years and 9.7 years, respectively (P = 0.001). No ATM alterations were identified in relapse samples, indicating that ATM does not play a role in disease progression. The high prevalence of germ-line truncating and missense ATM gene alterations among children with sporadic T-cell ALL suggests an association with susceptibility to T-cell acute leukemia and supports the model of predisposition to cancer in A-T heterozygotes.

Ataxia Telangiectasia↗
PubMed2004

Nonparametric correction for covariate measurement error in a stratified Cox model.

Stratified Cox regression models with large number of strata and small stratum size are useful in many settings, including matched case-control family studies. In the presence of measurement error in covariates and a large number of strata, we show that extensions of existing methods fail either to reduce the bias or to correct the bias under nonsymmetric distributions of the true covariate or the error term. We propose a nonparametric correction method for the estimation of regression coefficients, and show that the estimators are asymptotically consistent for the true parameters. Small sample properties are evaluated in a simulation study. The method is illustrated with an analysis of Framingham data.

Adult↗
PubMed2004

Semiparametric estimation of marginal hazard function from case-control family studies.

Estimating marginal hazard function from the correlated failure time data arising from case-control family studies is complicated by noncohort study design and risk heterogeneity due to unmeasured, shared risk factors among the family members. Accounting for both factors in this article, we propose a two-stage estimation procedure. At the first stage, we estimate the dependence parameter in the distribution for the risk heterogeneity without obtaining the marginal distribution first or simultaneously. Assuming that the dependence parameter is known, at the second stage we estimate the marginal hazard function by iterating between estimation of the risk heterogeneity (frailty) for each family and maximization of the partial likelihood function with an offset to account for the risk heterogeneity. We also propose an iterative procedure to improve the efficiency of the dependence parameter estimate. The simulation study shows that both methods perform well under finite sample sizes. We illustrate the method with a case-control family study of early onset breast cancer.

Adult↗
PubMed2003

Maximum likelihood estimator and likelihood ratio test in complex models: an application to B lymphocyte development.

In this paper we introduce a simple framework which provides a basis for estimating parameters and testing statistical hypotheses in complex models. The only assumption that is made in the model describing the process under study, is that the deviations of the observations from the model have a multivariate normal distribution. The application of the statistical techniques presented in this paper may have considerable utility in the analysis of a wide variety of complex biological and epidemiological models. To our knowledge, the model and methods described here have not previously been published in the area of theoretical immunology.

Animals↗
PubMed2003

Differences between estimated caloric requirements and self-reported caloric intake in the women's health initiative.

PURPOSE: To compare energy intake derived from a food frequency questionnaire (FFQ) with estimated energy expenditure in postmenopausal women participating in a large clinical study. METHODS: A total of 161,856 women aged 50 to 79 years enrolled in the Women's Health Initiative (WHI) Observational Study (OS) or Clinical Trial (CT) [including the Diet Modification (DM) component] completed the WHI FFQ, from which energy intake (FFQEI) was derived. Population-adjusted total energy expenditure (PATEE) was calculated according to the Harris-Benedict equation weighted by caloric intakes derived from the National Health and Nutrition Examination Survey. Stepwise regression was used to examine the influence of independent variables (e.g., demographic, anthropometric) on FFQEI-PATEE. Race, region, and education were forced into the model; other variables were retained if they increased model explanatory ability by more than 1%. RESULTS: On average, FFQEI was approximately 25% lower than PATEE. Regression results (intercept=-799 kcal/d) indicated that body mass index (b=-23 kcal/day/kg.m(-2)); age (b=15 kcal/day/year of age); and study arm (relative to women in the OS, for DM women b=169 kcal/d, indicating better agreement with PATEE) increased model partial R(2)>.01. Results for CT women not eligible for DM were similar to those of women in the OS (b=14 kcal/d). There also were apparent differences by race (b=-152 kcal/d in Blacks) and education (b=-67 kcal/d in women with<high school). CONCLUSION: This large, carefully studied population confirms previous observations regarding underestimates in self-reported caloric intake relative to estimates of metabolic need in younger women, and those with higher weight, with less education, and in Blacks. These differences, along with effects related to intervention assignment, underline the need for additional research to enhance understanding of errors in dietary measurement.

Aged↗
PubMed2003

Survivor function estimators under group sequential monitoring based on the logrank statistic.

In this paper we investigate a group sequential analysis of censored survival data with staggered entry, in which the trial is monitored using the logrank test while comparisons of treatment and control Kaplan-Meier curves at various time points are performed at the end of the trial. We concentrate on two-sample tests under local alternatives. We describe the relationship of the asymptotic bias of Kaplan-Meier curves between the two groups. We show that even if the asymptotic bias of the Kaplan-Meier curve is negligible relative to the true survival, this is not the case for the difference between the curves of the two arms of the trial. A corrected estimator for the difference between the survival curves is presented and by simulations we show that the corrected estimator reduced the bias dramatically and has a smaller variance. The methods of estimation are applied to the Beta-Blocker Heart Attack Trial (1982), a well-known group sequential trial.

Adrenergic beta-Antagonists↗