Biomedical subjects

E J Stanek

Publications and source records attributed to E J Stanek.

At least 19 recordsLinked to original sources

PubMed2006

Low doses of dietary lead are associated with a profound reduction in the time to the onset of puberty in female mice.

We report results from a replication in second and third generation female mice of accelerated time to puberty associated with low Pb exposure levels . Mice in the 2nd generation study are offspring of mice from the initial study; the 3rd generation mice are offspring from mice in the 2nd generation study. For each generation the time to puberty onset was markedly influenced by exposure to dietary lead. Modest increases in blood lead concentration from a normal background of 2-3 to 8-13 micro g/dl delayed the onset of puberty by 10-20% from a normal of 33-35 days to about 40-43 days; reducing blood lead from 2-3 to 0.7 micro g/dl was associated with profound acceleration of puberty to 21 days, an enhancement by over 30%. This dose-response relationship, which replicates previous novel findings, has possible ecological as well as public health significance and indicates that lead is able to induce biologically significant changes at blood lead levels previously thought to be without effect.

Administration, Oral↗

PubMed2006

Improved control of niacin-induced flushing using an optimized once-daily, extended-release niacin formulation.

INTRODUCTION: Niacin is a recognized treatment for dyslipidemia due to its favorable effects on all lipid parameters. However, the clinical use of niacin has been limited by its adverse effects, particularly cutaneous flushing. A newly reformulated 1,000 mg niacin ER tablet has been designed to reduce flushing relative to the original commercial niacin ER formulation. The aim of this study is to compare the incidence, intensity and duration of flushing between the 1,000 mg reformulated niacin ER and the 1,000 mg commercially available formulation, when administered as a single 2,000 mg dose to healthy male volunteers. METHODS: This was a double-blind, double-dummy, placebo-controlled, 3-way crossover, flush provocation study conducted at a single center. To increase the probability of flushing, subjects were administered niacin ER at the upper limit of the approved dosage range (2,000 mg), and were precluded from using aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) during the study. Subjects received reformulated niacin ER, commercial niacin ER or placebo in a 3-way crossover fashion. The primary flushing variable was the occurrence of a flushing event. Secondary flushing variables included the number of flushing episodes, intensity and duration of flushing for both overall flushing events and for individual symptoms of flushing (redness, warmth, tingling and itching). RESULTS: A total of 156 subjects were enrolled in the study. Of 133 subjects who received at least 1 dose of study medication in at least 2 study periods, 89% of subjects experienced flushing during treatment with reformulated niacin ER, and 98% of subjects experienced flushing during treatment with commercial niacin ER. This difference was statistically significant (p - 0.0027). Reformulated niacin ER resulted in a 42% reduction in median flush intensity (p < 0.0001) and a 43% reduction in median flush duration (p < 0.0001) relative to commercial niacin ER. The duration of first flushing event was more than 1 hour shorter with reformulated niacin ER. During the study, 29% of subjects (45/156) experienced treatment-emergent adverse events, which were mostly mild in intensity and considered to be remotely related or unrelated to the study drug. CONCLUSION: The 1,000 mg reformulated niacin ER tablet substantially decreases the incidence, intensity and duration of flushing relative to the commercially available 1,000 mg niacin ER tablet, and represents an improved niacin therapy option.

Administration, Oral↗

PubMed2005

Below background levels of blood lead impact cytokine levels in male and female mice.

A number of studies have documented that Pb exerts immunotoxic effects on T lymphocytes. In studies designed to explore this general response over a broad dose range, female Swiss mice were administered six different diets containing Pb acetate 1 day after mating. During lactation, the mothers received the same feed given during pregnancy, and the same diets were administered to the offspring for 9 months after weaning. At the end of exposure, blood Pb level in the offspring was determined, and possible changes in two type 1 cytokines (IL-2, INF-gamma) and one type 2 cytokine (IL-4) in the serum were measured. At higher dietary Pb levels (40 and 400 ppm), a significant increase in IL-4 production was associated with a profound decrease in INF-gamma and IL-2 production. At the lowest Pb diet level (0.02 ppm), which resulted in a blood lead level of (0.8 microg/dL), which is below background (2-3 microg/dL) values in humans, increases in INF-gamma and IL-2 production along with a significant decrease in IL-4 production were observed. The findings provide evidence of a reversal of lead-induced cytokine skewing depending on the blood lead concentration. As blood lead concentration increases, there is a notable skewing toward Th2, while the pattern is reversed favoring Th1 development at lower blood lead values. The present findings are also notable since they indicate the potential for dietary Pb to have significant biological effects below normal background concentrations.

Administration, Oral↗

PubMed2004

Effects of low doses of dietary lead on puberty onset in female mice.

Female Swiss mice typically display signs of puberty at about 33-37 days of age. In the present investigation (96 female mice tested in 8 Pb exposure levels, n=12 per exposure level), the time to puberty onset was markedly influenced by exposure to dietary lead. While modest increases in blood lead concentrations from a normal background of 2-3 to 13.2 microg/dl delayed the onset of puberty by 15-20% to about 40-43 days, reducing blood lead from 2-3 to 0.7 microg/dl was associated with an acceleration of puberty to 21 days, an enhancement by over 30%. This dose-response relationship represents novel findings of possible ecological as well as public health significance and indicates that lead is able to induce biologically significant changes at blood lead levels previously thought to be without effect.

Administration, Oral↗

PubMed2003

Effects of low doses of dietary lead on red blood cell production in male and female mice.

The effect of lead (Pb) ingestion on hematological parameters in male and female Swiss mice was assessed. Eight different doses of Pb were administered through preparation of different feeds. The levels of Pb in the diet were designed to provide exposure below (0.6 to <2.0 microg/dl) and above (>2.0-13 microg/dl) normal background. One litter of mice was exposed to each Pb dose, with the mother given the feed 1 day after mating, and the mother and offspring continuing to receive the feed until the litter was 90 days old. Male and female mice receiving below normal background levels of dietary Pb displayed enhanced red blood cell (RBC) production as measured by increased numbers of RBC and increased hemoglobin and hematocrit values. However, as the blood Pb levels approached 10 microg/dl there was a marked decrease in RBC production. These findings are significant since Pb was biologically active in a stimulating manner below typical background levels (2.0 microg/dl) while adversely effecting red cell synthesis at above background levels (7.0-13 microg/dl) encountered in the environment by humans.

Air Pollutants↗

PubMed2002

Effects of per os lead acetate administration on mouse hepatocyte survival.

Previously published studies indicate that hepatotoxicity is associated with high blood lead (Pb) levels in animal models and humans. The present investigation evaluated the effects of in vivo Pb exposure via drinking water on mouse hepatocyte survival in vitro when blood Pb concentrations reflected those seen in children in urban and rural settings (2-15 microg/dl). The findings indicated a biphasic dose-response with low concentrations associated with a modest decrease in hepatocyte survival, while at the highest concentration, survival was significantly enhanced (60%). Since these responses were associated with concentrations normally encountered by children, follow-up investigations are warranted.

Animals↗

PubMed2001

Sources of variance in daily physical activity levels in the seasonal variation of blood cholesterol study.

The authors examined sources of variance in self-reported physical activity in a cohort of healthy adults (n = 580) from Worcester, Massachusetts (the Seasonal Variation of Blood Cholesterol Study, 1994-1998). Fifteen 24-hour physical activity recalls of total, occupational, and nonoccupational activity (metabolic equivalent-hours/day) were obtained over 12 months. Random effects models were employed to estimate variance components for subject, season, day of the week, and residual error, from which the number of days of assessment required to achieve 80% reliability was estimated. The largest proportional source of variance in total and nonoccupational activity was within-subject variance (50-60% of the total). Differences between subjects accounted for 20-30% of the overall variance in total activity, and seasonal and day-of-the-week effects accounted for 6% and 15%, respectively. For total activity, 7-10 days of assessment in men and 14-21 days of assessment in women were required to achieve 80% reliability. For nonoccupational activity, 21-28 days of assessment were required. This study is among the first to have examined the sources of variance in daily physical activity levels in a large population of adults using 24-hour physical activity recall. These findings provide insight for understanding the strengths and limitations of short term and long term physical activity assessments employed in epidemiologic studies.

Activities of Daily Living↗

PubMed2001

Seasonal variation in household, occupational, and leisure time physical activity: longitudinal analyses from the seasonal variation of blood cholesterol study.

The authors examined seasonal variation in physical activity in longitudinal analyses of 580 healthy adults from Worcester, Massachusetts (the Seasonal Variation of Blood Cholesterol Study, 1994-1998). Three 24-hour physical activity recalls administered five times during 12 months of follow-up were used to estimate household, occupational, leisure time, and total physical activity levels in metabolic equivalent (MET)-hours/day. Trigonometric models were used to estimate the peak-to-trough amplitude and phase of the peaks in activity during the year. Total activity increased by 1.4 MET-hours/day (121 kcal/day) in men and 1.0 MET-hours/day (70 kcal/day) in women during the summer in comparison with winter. Moderate intensity nonoccupational activity increased by 2.0-2.4 MET-hours/day in the summer. During the summer, objectively measured mean physical activity increased by 51 minutes/day (95% confidence interval: 20, 82) in men and by 16 minutes/day (95% confidence interval: -12, 45) in women. The authors observed complex patterns of seasonal change that varied in amplitude and phase by type and intensity of activity and by subject characteristics (i.e., age, obesity, and exercise). These findings have important implications for clinical research studies examining the health effects of physical activity and for health promotion efforts designed to increase population levels of physical activity.

Adult↗

PubMed2000

Children's emotional and behavioral disorders: attributions of parental responsibility by professionals.

In the wake of the neurobiological "revolution," do mental health professionals still assign etiological responsibility for emotional and behavioral disorders to deficient or harmful parenting? This study investigated differences in attributions of causality by theoretical orientation, professional discipline, areas of practice, familiarity with parent support groups, and demographic characteristics. Implications for policy, research, and practice are discussed.

Affective Symptoms↗

PubMed2000

Preferences for treatment outcomes in patients with heart failure: symptoms versus survival.

BACKGROUND: Patient preferences for congestive heart failure therapy outcomes may vary depending on the goals of improving symptoms versus survival, but this has not been extensively investigated. Our objective was to analyze patient preferences for congestive heart failure therapy outcomes based on the goals of symptom versus survival improvement. METHODS AND RESULTS: This was a prospective, full-profile conjoint analysis study of individual preferences for congestive heart failure treatment outcomes. Conjoint analysis was based on ratings of 16 treatment-outcome profiles, each consisting of 4 attributes (tiredness, shortness of breath, depression, and survival) varied across 4 severity levels. Part-worths (utilities) and importance weights were calculated for each attribute to determine their relative contribution to the full-profile rating decision using standard full-profile conjoint analysis techniques. Fifty-one patients with congestive heart failure from our medical center (University of Pennsylvania Medical Center, Philadelphia, PA) and 47 age-, gender-, and race-matched control subjects were studied. Part-worths and importance weights were significantly different for shortness of breath and depression between patients and control subjects. Symptom-sensitive (n = 33) and survival-sensitive (n = 17) treatment outcome preference segments were identified within the patient group. Importance weights for symptom-sensitive versus survival-sensitive patients were as follows: tiredness 0.30+/-0.10 versus 0.16+/-0.09 (P < .01); shortness of breath 0.26+/-0.08 versus 0.21+/-0.08 (P = .07); depression 0.26+/-0.09 versus 0.19+/-0.09 (P = .01); and survival 0.18+/-0.07 versus 0.43+/-0.11 (P < .01). There were no significant predictors of which treatment outcome preference segment a patient belonged. Control subjects did not display similar preference segmentation. CONCLUSIONS: Symptomatic congestive heart-failure patients were clustered into symptom-sensitive and survival-sensitive segments in a manner suggesting that treatment outcomes of improved symptoms were of greater importance to the majority than longer survival. A full understanding of these individual preferences may have important implications for the design of therapy for heart-failure patients.

Adult↗

PubMed2000

Sequence and seasonal effects of salivary cortisol.

Assessments of cortisol levels in saliva have been widely used by both researchers and clinicians as an index of adrenal functioning. Quarterly measurements of morning and evening cortisol levels were determined in a longitudinal study of 147 participants (72 women and 75 men) followed for 1 year each. The analysis of salivary cortisol revealed no significant gender or age differences in the sample. There was a sequence effect in quarterly cortisol values with a progressive decrease in serial measurements, especially notable in the morning values; as well as a seasonal variation in cortisol levels with significantly higher levels found in winter and fall, compared with spring and summer. The findings in this study suggest that repeated saliva sampling and seasonal variation in cortisol levels may independently affect adrenal response and, therefore, need to be accounted for in longitudinal studies.

Adult↗

PubMed2000

Comparing physical activity assessment methods in the Seasonal Variation of Blood Cholesterol Study.

PURPOSE: This paper evaluated three measures of physical activity employed in the Seasonal Variation of Blood Cholesterol Study (Seasons), and it had two objectives: 1) To examine the laboratory validity of the Actillume activity monitor, and 2) To examine the relative validity of three 24-h physical activity recalls (24HR) in quantifying short-term physical activity behaviors. METHODS: Nineteen healthy middle-age adults completed seven activity trials (reading, typing, box moving, stepping, and walking (3.5, 4.25, 5.0 km x h(-1))) while oxygen consumption and Actillume measures were obtained. ANOVA, linear regression, and a scatter plot were employed to examine the validity of the Actillume. In relative validity analyses of the 24HR in the Seasons study, participants (N = 481) completed two or three 24HR (MET-h x d(-1)) and a modified Baecke Questionnaire. A subset of the cohort (N = 41) wore the Actillume for 3-8 d (counts x min(-1) x d(-1)). The relative validity of the 24HR method was examined by comparison to these criterion measures. RESULTS: In laboratory validation analyses, the monitor was found to discriminate between sedentary and moderate intensity activities, changes in walking speed, and to account for 79% of the variance in oxygen consumption across sedentary and walking trials. In relative validity analyses, correlations between the 24HR and the modified Baecke ranged from 0.29 to 0.52 (P < 0.01) across total, household, occupational, and leisure-time activities. CONCLUSIONS: In laboratory testing, the Actillume monitor discriminated between sedentary and moderate intensity activities and was highly correlated with oxygen consumption. Three 24HR of physical activity were observed to have a relative validity that was comparable to published data from other short-term activity assessments that also employed the Baecke Questionnaire and activity monitors as criterion measures.

Adult↗

PubMed2000

Daily soil ingestion estimates for children at a Superfund site.

Ingestion of contaminated soil by children may result in significant exposure to toxic substances at contaminated sites. Estimates of such exposure are based on extrapolation of short-term-exposure estimates to longer time periods. This article provides daily estimates of soil ingestion on 64 children between the ages of 1 and 4 residing at a Superfund site; these values are employed to estimate the distribution of 7-day average soil ingestion exposures (mean, 31 mg/day; median, 17 mg/day) at a contaminated site over different time periods. Best linear unbiased predictors of the 95th-percentile of soil ingestion over 7 days, 30 days, 90 days, and 365 days are 133 mg/day, 112 mg/day, 108 mg/day and 106 mg/day, respectively. Variance components estimates (excluding titanium and outliers, based on Tukey's far-out criteria) are given for soil ingestion between subjects (59 mg/day)2, between days on a subject (95 mg/day)2, and for uncertainty on a subject-day (132 mg/day)2. These results expand knowledge of potential exposure to contaminants among young children from soil ingestion at contaminated sites. They also provide basic distributions that serve as a starting point for use in Monte Carlo risk assessments.

Child, Preschool↗

PubMed1999

Why not routinely use best linear unbiased predictors (BLUPs) as estimates of cholesterol, per cent fat from kcal and physical activity?

Measures of biologic and behavioural variables on a patient often estimate longer term latent values, with the two connected by a simple response error model. For example, a subject's measured total cholesterol is an estimate (equal to the best linear unbiased estimate (BLUE)) of a subject's latent total cholesterol. With known (or estimated) variances, an alternative estimate is the best linear unbiased predictor (BLUP). We illustrate and discuss when the BLUE or BLUP will be a better estimate of a subject's latent value given a single measure on a subject, concluding that the BLUP estimator should be routinely used for total cholesterol and per cent kcal from fat, with a modified BLUP estimator used for large observed values of leisure time activity. Data from a large longitudinal study of seasonal variation in serum cholesterol forms the backdrop for the illustrations. Simulations which mimic the empirical and response error distributions are used to guide choice of an estimator. We use the simulations to describe criteria for estimator choice, to identify parameter ranges where BLUE or BLUP estimates are superior, and discuss key ideas that underlie the results.

Adult↗

PubMed1997

Gender differences in social desirability and social approval bias in dietary self-report.

Social desirability (the tendency to respond in such a way as to avoid criticism) and social approval (the tendency to seek praise) are two prominent response set biases evident in answers on structured questionnaires. These biases were tested by comparing nutrient intakes as estimated from a single 24-hour diet recall interview (24 HR) and a 7-day dietary recall (7DDR). Data were collected as part of the Worcester Area Trial for Counseling in Hyperlipidemia, a randomized, physician-delivered nutrition intervention trial for hypercholesterolemic patients conducted in Worcester, Massachusetts, from 1991 to 1995. Of the 1,278 total study subjects, 759 had complete data for analysis. Men overestimated their fat and energy intakes on the 7DDR as compared with the 24HR according to social approval: One unit increase in the social approval score was associated with an overestimate of 21.5 kcal/day in total energy intake and 1.2 g/day in total fat intake. Women, however, underestimated their dietary intakes on the 7DDR relative to the 24HR according to social desirability: One unit increase in the social desirability score was associated with an underestimate of 19.2 kcal/day in energy intake and 0.8 g/day in total fat. The results from the present study indicate that social desirability and social approval biases appear to vary by gender. Such biases may lead to misclassification of dietary exposure estimates resulting in a distortion in the perceived relation between health-related outcomes and exposure to specific foods or nutrients. Because these biases may vary according to the perceived demands of research subjects, it is important that they be assessed in a variety of potential research study populations.

Adult↗

PubMed1997

Soil ingestion in adults--results of a second pilot study.

Soil ingestion was evaluated in 10 adults as part of a larger study to evaluate soil ingestion in children. Each adult was followed for 4 weeks in a mass-balance study that was designed to evaluate the detection limit for soil ingestion in a similarly designed, concurrent children's study. After a baseline week, during Weeks 2 through 4, adults received daily soil capsules containing 20, 100, and 500 mg of soil, respectively. A 1-week period separated each study week. Based on the first 3 weeks of observation after subtracting the capsule ingestion amounts, the median, 75th percentile, and 95th percentile soil ingestion estimates were 1, 49, and 331 mg/day, with estimates calculated as the median of the three trace elements Al, Si, and Y. The average estimate of soil ingestion was 10 mg/day (SD = 94 mg/day). These findings augment sparse empirical data on adult soil ingestion, and suggest lower levels of soil ingestion in adults than previous studies.

Adult↗

PubMed1997

Soil ingestion estimates for children residing on a superfund site.

Soil ingestion estimates were obtained from a stratified, simple random sample of 64 children aged 1-4 years residing on a superfund site in Montana. The study was conducted during the month of September for 7 consecutive days. The study utilized a mass-balance methodology in which eight naturally occurring soil tracers (Al, Si, Ti, Ce, Nd, La, Y, and Zr) believed to be poorly absorbed by the gastrointestinal tract were employed to provide soil ingestion estimates. Food and fecal samples were analyzed on a daily basis. Soil/dust samples representative of where the children played during the study period were obtained. Very high compliance among the participants was maintained throughout the study. The identical methodology employed in the childrens' study was used in an adult study of tracer recovery in 10 subjects over 28 days of observation to provide validation that soil ingestion over the range of 20 to 500 mg/day could be detected. Soil ingestion was estimated by each soil tracer via traditional methods as well as by an improved approach using five trace elements (Al, Si, Ti, Y, and Zr), called the Best Tracer Method (BTM), which substantially corrects for error due to misalignment of tracer input and output as well as error occurring from ingestion of tracers from nonfood, nonsoil sources, while being insensitive to the particle size of the soil/dust ingested. According to the BTM, the median soil ingestion was less than 1 mg/day while the upper 95% was 160 mg/day. No significant age (1 year vs 2, vs 3) or sex-related differences in soil ingestion were observed. These estimates are lower than estimates observed in another study in Massachusetts during September and October. Significant methodological improvements in this study as compared to previously conducted soil ingestion studies include the selection of a representative sample of children, longer study duration, inclusion of dietary recommendations to reduce food tracer input and variability, use of the BTM, and a stronger adult validation study with respect to number of subjects, and duration and range of possible soil ingestion rates. Despite these methodological improvements, evidence exists that this study displays a net residual negative error, suggesting that the above estimates are below the true soil ingestion. The magnitude of this residual negative error cannot be quantified with the BTM but is likely to not affect the median by more than 40 mg/day, while the impact of such an error on the upper end of the distribution is more uncertain.

Adult↗

PubMed1997

Soil ingestion: a concern for acute toxicity in children.

Several soil ingestion studies have indicated that some children ingest substantial amounts of soil on given days. Although the EPA has assumed that 95% of children ingest 200 mg soil/day or less for exposure assessment purposes, some children have been observed to ingest up to 25-60 g soil during a single day. In light of the potential for children to ingest such large amounts of soil, an assessment was made of the possibility for soil pica episodes to result in acute intoxication from contaminant concentrations the EPA regards as representing conservative screening values (i.e., EPA soil screening levels and EPA Region III risk-based concentrations for residential soils). For a set of 13 chemicals included in the analysis, contaminant doses resulting from a one-time soil pica episode (5-50 g of soil ingested) were compared with acute dosages shown to produce toxicity in humans in clinical studies or case reports. For four of these chemicals, a soil pica episode was found to result in a contaminant dose approximating or exceeding the acute human lethal dose. For five of the remaining chemicals, the contaminant dose from a soil pica episode was well within the reported dose range in humans for toxicity other than lethality. Because both the exposure episodes and the toxicological response information are derived from observations in humans, these findings are regarded as particularly relevant for human health risk assessment. They suggest that, for some chemicals, ostensibly conservative soil criteria based on chronic exposure using current EPA methodology may not be protective of children during acute soil pica episodes.

Child↗