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D B Allison

Publications and source records attributed to D B Allison.

At least 37 records · Page 2Linked to original sources
PubMed2004

A randomized double-blind placebo-controlled clinical trial of a product containing ephedrine, caffeine, and other ingredients from herbal sources for treatment of overweight and obesity in the absence of lifestyle treatment.

OBJECTIVE: To evaluate the efficacy and side effects of an herbal formulation to promote weight loss, as compared to placebo. DESIGN: 12-week multicenter double-blind, placebo-controlled, randomized parallel groups design. Study conducted at three clinical sites in New York State. Subjects were randomized to receive either the 'active' product or a 'placebo' supplement for 12 weeks. Minimal steps were taken to influence lifestyle changes with regard to diet or exercise. SUBJECTS: 102 overweight/obese (30<BMI</=39.9 kg/m(2)) volunteers between the ages of 18 and 65 y. MAIN OUTCOME MEASURES: Weight, percent body fat, fat mass, waist circumference, BMI, blood pressure, and pulse measured at 2 days, 1 week, 2 weeks, 4 weeks, 8 weeks, and 12 weeks postrandomization. RESULTS: Subjects receiving the 'active' treatment experienced, on average, an additional 1.5 kg of weight loss compared with subjects receiving the placebo. In addition, subjects receiving the 'active' treatment experienced greater reductions in BMI and waist circumference over the 12-week period. No differences were observed with respect to percent body fat, fat mass, diastolic or systolic blood pressure, pulse, the occurrence of any adverse event, or the occurrence of any presumed treatment-related adverse event. Testing of the study product by two independent laboratories indicated that it had only approximately half of the intended amount of ephedrine alkaloids and caffeine. CONCLUSIONS: Over the 12-week trial, subjects on the active treatment experienced significantly greater weight loss than subjects on placebo, without an increase in blood pressure, pulse, or the rate of adverse events. These benefits were achieved in the absence of any lifestyle treatment to change dietary or exercise behavior and with lower doses of ephedrine alkaloids and caffeine than those commonly utilized.

Adult↗
PubMed2004

Changes in blood chemistry and hematology variables during aging in captive rhesus macaques (Macaca mulatta). J Med Primatol 30:161-173, 2001.

The Primate Aging Database (PAD) is being developed to assist research using nonhuman primate models for various gerontological applications. We provide now an update of an earlier report providing data on hematological and blood chemistry values for rhesus monkeys across the adult lifespan. These data were collected from several research colonies and have been submitted to rigorous statistical analyses to identify relationships with chronological age.

Aging↗
PubMed2003

A novel soy-based meal replacement formula for weight loss among obese individuals: a randomized controlled clinical trial.

OBJECTIVE: To assess the efficacy and safety of a low calorie soy-based meal replacement program for the treatment of obesity. DESIGN: A 12-week prospective randomized controlled clinical trial. SETTING: Outpatient weight control research unit. SUBJECTS: One hundred obese (28<BMI<or=41 kg/m(2)) volunteers between the ages of 35 and 65 y. Seventy-four participants completed the trial. INTERVENTION: Participants were randomized to either the meal replacement treatment group (n=50; 240 g/day, 1200 kcal/day) or control group (n=50). Both groups at baseline received a single dietary counseling session and a pamphlet describing weight loss practices. MAIN OUTCOME MEASURES: Weight, body fat, serum lipid concentrations. RESULTS: : By intent-to-treat analysis, the treatment group lost significantly more weight than the control group (7.00 vs 2.90 kg; P<0.001) and had a greater change in total (22.5 vs 6.8 mg/dl; P=0.013) and LDL cholesterol (21.2 vs 7.1 mg/dl; P<0.009). Among completers only, the treatment group again lost more weight (7.1 kg; n=37 vs 2.9 kg; n=37; P=0.0001) and had a greater reduction in total cholesterol (26.1 mg/dl; n=37 vs 6.7 mg/dl; P=0.0012) and a greater change in LDL cholesterol (21.6 vs 5.5 mg/dl; P=0.0025). (For any given degree of weight loss, the reduction in LDL cholesterol was significantly greater in the treatment group.) Treatment was well tolerated and no serious side effects were detected. CONCLUSIONS: Use of this soy-based meal replacement formula was effective in lowering body weight, fat mass and in reducing LDL cholesterol beyond what could be expected given the weight lost.

Adult↗
PubMed2003

Age-related thymic involution in C57BL/6J x DBA/2J recombinant-inbred mice maps to mouse chromosomes 9 and 10.

A comprehensive analysis of initial thymus size and involution rate has not been quantitated for different genetic backgrounds of mice, thus genetic linkage analysis of thymic involution has not been possible. Here, we have used a mathematical method to analyze the age-related decline in thymocyte count in C57BL/6 and DBA/2 mice and have observed that thymic involution could be best fit with a negative exponential curve N(t)=beta(0) x exp(-beta(1)t), where t represents the age (day). This regression model was applied to C57BL/6 x DBA/2 (B x D) recombinant inbred strains of mice to identify the genetic loci influencing age-related thymic involution. There was a dramatic genetic effect of B and D alleles on thymocyte count at young age and the age-related thymic involution rate. The strongest quantitative trait loci (QTL) influencing the rate of thymic involution were mapped to mouse chromosome (Chr) 9 (D9Mit20 at 62 cM) and Chr 10 (D10Mit61 at 32 cM). The strongest QTLs influencing the initial thymocyte count were mapped to ChrX (DXMit324 at 26.5 cM) and Chr 3 (D3Mit127 at 70.3 cM). The present study suggests that the initial thymus size and the rate of thymic involution may be influenced by a relatively small number of genetic loci.

Aging↗
PubMed2003

Effects of outcome-driven insurance reimbursement on short-term weight control.

CONTEXT: Although most health insurers exclude coverage of weight control therapy, one local insurer offered partial reimbursement of the cost of a weight control program, using an incentive plan. OBJECTIVE: To determine whether outcome-driven insurer-based reimbursement improves participation in a weight control program and short-term weight loss outcomes. DESIGN: Cohort follow-up study between January 1998 and February 2001. SETTING: Community weight management program operated by an academic medical center. SUBJECTS: Obese participants who had the potential for reimbursement (Group A, n=25) and participants in the same program classes (Group B, n=100) who had no possibility for reimbursement. Subjects in Group B were selected from among 206 potential participants using a propensity score to match them with subjects in Group A on age, gender, ethnicity, starting BMI, starting weight, and educational, economic, and demographic variables. INTERVENTION: Group lifestyle-based weight management program. The insurer reimbursed half the cost of the program to obese participants who met minimum weight criteria, paid the program fee at enrollment, attended > or =10 of the 12 classes, and lost > or =6% of initial body weight after 12 weeks. MAIN OUTCOME MEASURES: Participation rates and weight loss outcomes. RESULTS: Group A subjects attended significantly more classes (mean+/-s.d.: 10.1+/-1.8 vs 8.2+/-2.5, P<0.001) and lost more weight than Group B subjects (6.1+/-3.1 vs 3.7+/-3.6%, P=0.002). While 84% of Group A subjects attended > or =10 classes, only 37% of Group B subjects did so (P<0.001); 56% of Group A subjects lost > or =6% of body weight, but only 20% of Group B subjects did so (P<0.001); 56% of Group A subjects achieved both the class attendance and weight loss goals, but only 14% of Group B subjects did so (P<0.001). Logistic regression estimated that Group A subjects had 8.2 times the odds of attending > or =10 classes and 4.5 times the odds of losing > or =6% of body weight of Group B subjects, after controlling for class attendance. CONCLUSIONS: Insurer-based reimbursement that is contingent upon initial financial commitment on the part of the patient, consistent program participation, and successful weight loss is associated with significantly better short-term weight control outcomes.

Adult↗
PubMed2003

Weight loss causes increased mortality: cons.

Short-term studies indicate that intentional weight loss (IWL) among obese persons significantly improves health variables that are often precursors or markers of chronic diseases (e.g. heart diseases, type-2 diabetes). Hence, it is logical to assume that IWL among obese persons would lead to increased longevity. On the whole, epidemiological studies, including recent ones that use conservative analytic approaches such as distinguishing between apparently IWL and unintentional weight loss (UWL), adjusting for potential confounders and excluding apparently unhealthy subjects, indicate that apparently IWL appears to neither increase nor decrease mortality rate. However, it is important to note that none of the existing studies were designed specifically to test the hypothesis that IWL reduces mortality rate, and given methodological problems, these studies do not provide a satisfactory way to address the body mass index (BMI)-mortality question. Several controlled clinical trials suggest that IWL may reduce mortality rate. However, even in these studies, it is important to acknowledge that subjects are randomized to conditions that produce more or less weight loss and not to distinct levels of weight loss per se. Nevertheless, while we await additional data from better designed studies, given our incomplete knowledge, we conclude that it seems more likely than not that IWL achieved by medically recommended methods does not increase and probably decreases mortality rate.

Animals↗
PubMed2003

Modern statistical methods for handling missing repeated measurements in obesity trial data: beyond LOCF.

This paper brings together some modern statistical methods to address the problem of missing data in obesity trials with repeated measurements. Such missing data occur when subjects miss one or more follow-up visits, or drop out early from an obesity trial. A common approach to dealing with missing data because of dropout is 'last observation carried forward' (LOCF). This method, although intuitively appealing, requires restrictive assumptions to produce valid statistical conclusions. We review the need for obesity trials, the assumptions that must be made regarding missing data in such trials, and some modern statistical methods for analysing data containing missing repeated measurements. These modern methods have fewer limitations and less restrictive assumptions than required for LOCF. Moreover, their recent introduction into current releases of statistical software and textbooks makes them more readily available to the applied data analyses.

Clinical Trials as Topic↗
PubMed2003

Effect of Box-Cox transformation on power of Haseman-Elston and maximum-likelihood variance components tests to detect quantitative trait Loci.

Non-normality of the phenotypic distribution can affect power to detect quantitative trait loci in sib pair studies. Previously, we observed that Winsorizing the sib pair phenotypes increased the power of quantitative trait locus (QTL) detection for both Haseman-Elston (HE) least-squares tests [Hum Hered 2002;53:59-67] and maximum likelihood-based variance components (MLVC) analysis [Behav Genet (in press)]. Winsorizing the phenotypes led to a slight increase in type 1 error in H-E tests and a slight decrease in type I error for MLVC analysis. Herein, we considered transforming the sib pair phenotypes using the Box-Cox family of transformations. Data were simulated for normal and non-normal (skewed and kurtic) distributions. Phenotypic values were replaced by Box-Cox transformed values. Twenty thousand replications were performed for three H-E tests of linkage and the likelihood ratio test (LRT), the Wald test and other robust versions based on the MLVC method. We calculated the relative nominal inflation rate as the ratio of observed empirical type 1 error divided by the set alpha level (5, 1 and 0.1% alpha levels). MLVC tests applied to non-normal data had inflated type I errors (rate ratio greater than 1.0), which were controlled best by Box-Cox transformation and to a lesser degree by Winsorizing. For example, for non-transformed, skewed phenotypes (derived from a chi2 distribution with 2 degrees of freedom), the rates of empirical type 1 error with respect to set alpha level=0.01 were 0.80, 4.35 and 7.33 for the original H-E test, LRT and Wald test, respectively. For the same alpha level=0.01, these rates were 1.12, 3.095 and 4.088 after Winsorizing and 0.723, 1.195 and 1.905 after Box-Cox transformation. Winsorizing reduced inflated error rates for the leptokurtic distribution (derived from a Laplace distribution with mean 0 and variance 8). Further, power (adjusted for empirical type 1 error) at the 0.01 alpha level ranged from 4.7 to 17.3% across all tests using the non-transformed, skewed phenotypes, from 7.5 to 20.1% after Winsorizing and from 12.6 to 33.2% after Box-Cox transformation. Likewise, power (adjusted for empirical type 1 error) using leptokurtic phenotypes at the 0.01 alpha level ranged from 4.4 to 12.5% across all tests with no transformation, from 7 to 19.2% after Winsorizing and from 4.5 to 13.8% after Box-Cox transformation. Thus the Box-Cox transformation apparently provided the best type 1 error control and maximal power among the procedures we considered for analyzing a non-normal, skewed distribution (chi2) while Winzorizing worked best for the non-normal, kurtic distribution (Laplace). We repeated the same simulations using a larger sample size (200 sib pairs) and found similar results.

Chromosome Mapping↗
PubMed2002

Differential associations of body mass index and adiposity with all-cause mortality among men in the first and second National Health and Nutrition Examination Surveys (NHANES I and NHANES II) follow-up studies.

OBJECTIVE: The frequently observed U-shaped relationship between body mass index (BMI; kg/m(2)) and mortality rate may be due to the opposing effects of fat mass (FM) and fat-free mass (FFM) components of BMI on mortality rate. The purpose is to test the hypothesis stated above. DESIGN: Longitudinal prospective cohort studies. The mortality follow-up of the first and second National Health and Nutrition Examination Surveys (NHANES I and NHANES II). SUBJECTS: A total of 10 169 male subjects aged 25-75 who participated in NHANES I and II were selected for analyses. Follow-up continued until 1992. The mean follow-up time was 14.6 y for NHANES I and 12.9 y for NHANES II. Ninety-eight percent of the participants were successfully followed representing a total of 3722 deaths. MEASUREMENTS: Subscapular and triceps skinfolds thickness were used as FM indicators, whereas upper arm circumference was used as a FFM indicator. The Cox proportional hazards model tested the relationships of BMI, FM and FFM with all-cause mortality adjusting for age, smoking status, race and education levels. RESULTS: BMI had a U-shaped relationship with mortality, with a nadir of approximately 27 kg/m(2). However, when indicators of FM and FFM were added to the model, the relationship between BMI and mortality became more nearly monotonic increasing. Moreover, the relationship between FM indicator and mortality was monotonic increasing and the relationship between FFM indicator and mortality was monotonic decreasing. CONCLUSION: These results support the hypothesis that the apparently deleterious effects of marked thinness may be due to low FFM and that, over the observed range of the data, marked leanness (as opposed to thinness) has beneficial effects.

Adipose Tissue↗
PubMed2002

Twins and virtual twins: bases of relative body weight revisited.

OBJECTIVE: Application of a new investigative strategy to assess genetic and environmental influences on relative body weight. DESIGN: Covariance structure analysis of body mass index (BMI) using genetically informative samples. SUBJECTS: One-hundred and fourteen monozygotic (MZ) twin pairs (age 5.04-22.93 y), 81 dizygotic (DZ) twin pairs (age 6.05-16.52 y), and 98 virtual twin (VT) pairs, ie same-age unrelated siblings (3.68-54.75 y). MEASUREMENTS: Height, weight, BMI variously obtained by direct measurement and self-report. RESULTS: In contrast with most previous studies, significant common environmental influence on BMI was observed. CONCLUSION: Much past research may have underestimated common environmental effects on BMI because the designs lacked the power or ability to detect them.

Adoption↗
PubMed2002

A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference.

METHODS: We analyzed data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R and K656N) of LEPR with body mass index (BMI; kg/m(2)) and waist circumference (WC). A total of 3263 related and unrelated subjects from diverse ethnic backgrounds including African-American, Caucasian, Danish, Finnish, French Canadian and Nigerian were studied. We tested effects of individual alleles, joint effects of alleles at multiple loci, epistatic effects among alleles at different loci, effect modification by age, sex, diabetes and ethnicity, and pleiotropic genotype effects on BMI and WC. RESULTS: We found that none of the effects were significant at the 0.05 level. Heterogeneity tests showed that the variations of the non-significant effects are within the range of sampling variation. CONCLUSIONS: We conclude that, although certain genotypic effects could be population-specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or WC in the overall population.

Alleles↗
PubMed2002

Sexual dimorphism in the energy content of weight change.

BACKGROUND: The energy content of weight change is assumed to be sex- and age-neutral at 3,500 kcal/pound or 32.2 MJ/kg. OBJECTIVES: As sexual dimorphism in body composition generally exists in mammals, the primary hypothesis advanced and tested was that the energy content of weight change differs between men and women. DESIGN: The energy content of 129 adult men and 287 women was measured by neutron activation analysis. Cross-sectional energy content prediction models were developed and then evaluated in two longitudinal samples: one that used the same methods in 26 obese women losing weight; and the other a compilation of 18 previously reported weight change-body composition studies. RESULTS: Multiple regression modeling identified weight, sex, age and height as total energy content predictor variables with significant sex x weight (P<0.001) and age x weight (P<0.001) interactions; total model r(2) and s.e.e. were 0.89 and 107.3 MJ, respectively. The model's predictive value was supported in both longitudinal evaluation samples. Model calculations using characteristics of representative adults gaining or losing weight suggested that the energy content of weight change in women (approximately 30.1-32.2 MJ/kg) is near to the classical value of 32.2 MJ/kg and that in men the value is substantially lower, approximately 21.8-23.8 MJ/kg. The predicted energy content of weight change increases by about 10% in older (age approximately 70 y) vs younger (approximately 35 y) men and women. CONCLUSIONS: Sexual dimorphism and age-dependency appears to exist in the estimated energy content of weight change and these observations have important clinical and research implications.

Adult↗
PubMed2001

Influences of aging and caloric restriction on the transcriptional profile of skeletal muscle from rhesus monkeys.

In laboratory rodents, caloric restriction (CR) retards several age-dependent physiological and biochemical changes in skeletal muscle, including increased steady-state levels of oxidative damage to lipids, DNA, and proteins. We have previously used high-density oligonucleotide arrays to show that CR can prevent or delay most of the major age-related transcriptional alterations in the gastrocnemius muscle of C57BL/6 mice. Here we report the effects of aging and adult-onset CR on the gene expression profile of 7,070 genes in the vastus lateralis muscle from rhesus monkeys. Gene expression analysis of aged rhesus monkeys (mean age of 26 years) was compared with that of young animals (mean age of 8 years). Aging resulted in a selective up-regulation of transcripts involved in inflammation and oxidative stress, and a down-regulation of genes involved in mitochondrial electron transport and oxidative phosphorylation. Middle-aged monkeys (mean age of 20 years) subjected to CR since early adulthood (mean age of 11 years) were studied to determine the gene expression profile induced by CR. CR resulted in an up-regulation of cytoskeletal protein-encoding genes, and also a decrease in the expression of genes involved in mitochondrial bioenergetics. Surprisingly, we did not observe any evidence for an inhibitory effect of adult-onset CR on age-related changes in gene expression. These results indicate that the induction of an oxidative stress-induced transcriptional response may be a common feature of aging in skeletal muscle of rodents and primates, but the extent to which CR modifies these responses may be species-specific.

Aging↗
PubMed2001

Estimating the consequences of anti-psychotic induced weight gain on health and mortality rate.

Many anti-psychotic medications produce marked weight gain. In this study, we estimate the expected impact of degrees of antipsychotic-induced weight gain on selected mortality rate and incidence rates of impaired glucose tolerance (IGT) and hypertension (HTN) among US adults. Using raw data from 5209 respondents from the Framingham Heart Study's public use data set and national statistics on population demographics, we estimated the expected effect of weight gain on number of deaths and incident cases of IGT and HTN for a 10-year period commencing in 1999. Results indicated that the estimated deleterious effects of weight gain were greater for people with higher BMIs at baseline, for greater degrees of weight gain, for men than women, and for older than younger persons. Because there is a 'U-shaped' relation between BMI and mortality rate, small to moderate weight gains among people with baseline BMIs less than 23 were predicted to decrease mortality rates, whereas weight gains among people with baseline BMIs above that level were expected to increase mortality rates. However, the relations of IGT and HTN with BMI are monotonically increasing. Thus, the anticipated effect of weight gain on IGT and HTN is deleterious regardless of baseline BMI. Because it is unclear whether the beneficial effects of the atypical agents on, for example, reducing suicide mortality, outweigh the putative increase in mortality due to weight gain, we estimate the beneficial effects due to decreased death from suicide with the potential deleterious effects due to a 10-kg weight gain. We found that 492 suicide deaths per 100,000 schizophrenic patients would be prevented over 10 years with the use of clozapine compared to 416 additional deaths due to antipsychotic induced weight gain. Although this estimate is rather crude and should be seen only as offering a sense of the likely situation, results suggest that the lives saved via clozapine may essentially be offset by the deaths due to weight gain. As we discuss, it is not possible to provide definitive estimates of the effect of antipsychotic-induced weight gain on health and mortality, but our findings suggest that the magnitude of weight gains induced by many antipsychotic agents is likely to have important deleterious effects on mortality and health.

Antipsychotic Agents↗
PubMed2001

Joint tests of linkage and association for quantitative traits.

In this paper we describe various study designs and analytic techniques for testing the joint hypothesis that a genetic marker is both linked to and associated with a quantitative phenotype. Issues of power and sampling are addressed. The distinction between methods that explicitly examine association and those that infer association by examining the distribution of allelic transmissions from a heterozygous parent is examined. Extensions to multivariate, multiallelic, and multilocus situations are addressed. Recent approaches that combine variance-components-based linkage analyses with joint tests of linkage in the presence of association for disentanglement of the linkage and association and the application of such methods to fine mapping are discussed. Finally, new classes of joint tests of linkage and association that do not require samples of related individuals are described.

Alleles↗
PubMed2001

Does intentional weight loss affect mortality rate?

Short-term studies indicate that intentional weight loss among obese persons significantly improves physiologic variables. Hence, it is logical to conjecture that intentional weight loss would lead to long-term benefits and increased longevity. Herein, we review recent epidemiologic studies that investigate the weight loss-mortality association using a conservative analytic approach that included distinguishing between intentional and unintentional weight loss, adjusting for potential confounders, and excluding unhealthy subjects. On balance, results indicate that intentional weight loss appears to neither increase nor decrease mortality rate. Discussion focuses on the problems of addressing this important public health question with observational data.

Journal Article↗
PubMed2001

Larger amounts of visceral adipose tissue in Asian Americans.

OBJECTIVE: Excess visceral adipose tissue (VAT) is recognized as an important risk factor for the development of coronary heart disease and type 2 diabetes. Several studies have reported less VAT in African Americans compared with whites. As little is known about the levels of VAT in Asians, we compared whole-body VAT in Asian Americans with European Americans. RESEARCH METHODS AND PROCEDURES: VAT was measured using whole-body multislice magnetic resonance imaging in 54 women (18 Asian Americans, 36 European Americans) and 53 men (19 Asian Americans, 34 European Americans) with body mass index (measured in kilograms per square meter) < 30. Data were analyzed by multiple regression modeling. RESULTS: Asian American women had higher log-transformed VAT compared with European American women (p < 0.05), after adjusting for age and total body fat. There was a significant age by race interaction such that race differences in VAT were most evident over the age of 30 years. No differences in VAT could be detected between Asian American and European American men, even after adjusting for potential covariates, including total adiposity. DISCUSSION: These data are the first to demonstrate higher amounts of VAT in healthy Asian Americans, a finding that suggests normative VAT values or standards derived from whites may not be applicable to Asians.

Absorptiometry, Photon↗