Fc receptor-mediated phagocytosis in tissues as a potent mechanism for preventive and therapeutic HIV vaccine strategies.

Although the development of a fully protective HIV vaccine is the ultimate goal of HIV research, to date only one HIV vaccine trial, the RV144, has successfully induced a weakly protective response. The 31% protection from infection achieved in the RV144 trial was linked to the induction of nonneutralizing antibodies, able to mediate antibody-dependent cell-mediated cytotoxicity (ADCC), suggestive of an important role of Fc-mediated functions in protection. Similarly, Fc-mediated antiviral activity was recently shown to play a critical role in actively suppressing the viral reservoir, but the Fc effector mechanisms within tissues that provide protection from or after infection are largely unknown. Here we aimed to define the landscape of effector cells and Fc receptors present within vulnerable tissues. We found negligible Fc receptor-expressing natural killer cells in the female reproductive and gastrointestinal mucosa. Conversely, Fc receptor-expressing macrophages were highly enriched in most tissues, but neutrophils mediated superior antibody-mediated phagocytosis. Modifications in Fc domain of VRC01 antibody increased phagocytic responses in both phagocytes. These data suggest that non-ADCC-mediated mechanisms, such as phagocytosis and neutrophil activation, are more likely to play a role in preventative vaccine or reservoir-eliminating therapeutic approaches.

The continuing epidemics of obesity and diabetes in the United States.

CONTEXT: Recent reports show that obesity and diabetes have increased in the United States in the past decade. OBJECTIVE: To estimate the prevalence of obesity, diabetes, and use of weight control strategies among US adults in 2000. DESIGN, SETTING, AND PARTICIPANTS: The Behavioral Risk Factor Surveillance System, a random-digit telephone survey conducted in all states in 2000, with 184 450 adults aged 18 years or older. MAIN OUTCOME MEASURES: Body mass index (BMI), calculated from self-reported weight and height; self-reported diabetes; prevalence of weight loss or maintenance attempts; and weight control strategies used. RESULTS: In 2000, the prevalence of obesity (BMI >/=30 kg/m(2)) was 19.8%, the prevalence of diabetes was 7.3%, and the prevalence of both combined was 2.9%. Mississippi had the highest rates of obesity (24.3%) and of diabetes (8.8%); Colorado had the lowest rate of obesity (13.8%); and Alaska had the lowest rate of diabetes (4.4%). Twenty-seven percent of US adults did not engage in any physical activity, and another 28.2% were not regularly active. Only 24.4% of US adults consumed fruits and vegetables 5 or more times daily. Among obese participants who had had a routine checkup during the past year, 42.8% had been advised by a health care professional to lose weight. Among participants trying to lose or maintain weight, 17.5% were following recommendations to eat fewer calories and increase physical activity to more than 150 min/wk. CONCLUSIONS: The prevalence of obesity and diabetes continues to increase among US adults. Interventions are needed to improve physical activity and diet in communities nationwide.

What are preschool children eating? A review of dietary assessment.

Accurate assessment of dietary intake among preschool-aged children is important for clinical care and research, for nutrition monitoring and evaluating nutrition interventions, and for epidemiologic research. We identified 25 studies published between January 1976 and August 2000 that evaluated the validity of food recalls (n = 12), food frequency questionnaires (n = 9), food records (n = 2), or other methods (n = 2). We identified four studies that evaluated the reproducibility of food frequency questionnaires. Validity studies varied in validation standard and study design, making comparisons between studies difficult. In general, food frequency questionnaires overestimated total energy intake and were better at ranking, than quantifying, nutrient intake. Compared with the validation standard, food recalls both overestimated and underestimated energy intake. When choosing a method to estimate diet, both purpose of the assessment and practicality of the method must be considered, in addition to the validity and reproducibility reported in the scientific literature.

Serum retinyl esters are not associated with biochemical markers of liver dysfunction in adult participants in the third National Health and Nutrition Examination Survey (NHANES III), 1988--1994.

BACKGROUND: Serum retinyl ester concentrations are elevated in hypervitaminosis A. It was suggested that retinyl esters >10% of total serum vitamin A indicate potential hypervitaminosis, but this cutoff was derived from small clinical samples that may not be representative of the general population. OBJECTIVE: We sought to examine the distribution of serum retinyl ester concentrations and associations between retinyl ester concentrations and biochemical markers of liver dysfunction in a nationally representative sample. DESIGN: We assessed the associations between serum retinyl ester concentrations and 5 biochemical indexes of liver dysfunction by using multivariate linear and multiple logistic regression techniques and controlling for age, sex, use of supplements containing vitamin A, alcohol consumption, smoking status, and use of exogenous estrogens in 6547 adults aged > or =18 y in the third National Health and Nutrition Examination Survey (NHANES III), 1988--1994. RESULTS: Thirty-seven percent of the sample had serum retinyl ester concentrations >10% of total serum vitamin A and 10% of the sample had serum retinyl esters >15% of total vitamin A. We found no associations between serum retinyl ester concentrations and 1) concentrations of any biochemical variable (multiple linear regression) or 2) risk of having biochemical variables above the reference range (multiple logistic regression). We did not find a serum retinyl ester value with statistically significant sensitivity and specificity for predicting increases in biochemical indexes of liver dysfunction. CONCLUSIONS: The prevalence of serum retinyl ester concentrations >10% of the total vitamin A concentration in the NHANES III sample was substantially higher than expected but elevated retinyl ester concentrations were not associated with abnormal liver function.

Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States.

CONTEXT: Population-based estimates of the prevalence of disease-associated mutations, such as hemochromatosis (HFE) gene mutations, are needed to determine the usefulness of genetic screening. OBJECTIVE: To estimate the prevalence of the HFE mutations C282Y and H63D in the US population. DESIGN: Cross-sectional population-based study of samples in the DNA bank from phase 2 of the Third National Health and Nutrition Examination Survey conducted from 1992 to 1994. SETTING AND PARTICIPANTS: Genotyped samples of cells from a total of 5171 participants, cross-classified by sex, age, and race/ethnicity in the analysis. MAIN OUTCOME MEASURES: Estimates of the prevalence of C282Y and H63D mutations. RESULTS: The prevalence of C282Y homozygosity is estimated to be 0.26% (95% confidence interval [CI], 0.12%-0.49%); 1.89% (95% CI, 1.48%-2.43%) for H63D homozygosity; and 1.97% (95% CI, 1.54%-2.49%) for compound heterozygosity. The prevalence estimates for C282Y heterozygosity (C282Y/wild type) are 9.54% among non-Hispanic whites, 2.33% among non-Hispanic blacks, and 2.75% among Mexican-Americans. The prevalence estimates of the C282Y mutation in the US population are 5.4% (95% CI, 4.7%-6.2%) and 13.5% (95% CI, 12.5%-14.8%) for the H63D mutation. CONCLUSIONS: Estimates of prevalence of HFE mutations are within the expected range for non-Hispanic whites and blacks but the estimated prevalence of the C282Y mutation among Mexican-Americans is less than expected. Mutation data now need to be linked to clinically relevant indices, such as transferrin saturation level.

Distribution and correlates of high-density lipoprotein subclasses among children and adolescents.

Levels of high-density lipoprotein (HDL) cholesterol among children vary by sex and race/ethnicity and are correlated with age, obesity, and other characteristics. Several studies of adults have indicated that atherogenicity of HDL particles may vary by size, but there is little information on the distribution and correlates of HDL subfractions in early life. We used nuclear magnetic resonance (NMR) spectroscopy to determine the mean HDL particle size and levels of 3 HDL subclasses among 10- to 17-year-olds (n = 918). We found the mean HDL particle size to be (1) inversely associated with age among boys, (2) larger among girls than boys, and (3) larger among black children than among white children. These associations with particle size reflected contrasting associations with various HDL subclasses; among boys, for example, levels of large HDL decreased with age, whereas levels of small HDL remained constant (black boys) or tended to increase (white boys). Furthermore, relative weight and levels of both triglycerides and low-density lipoprotein (LDL) cholesterol were associated inversely with levels of large HDL, but positively with levels of small HDL. These contrasting associations suggest that the role of HDLC in coronary heart disease (CHD) may be more complex than previously thought, and that the analysis of HDL subclasses may improve the accuracy of CHD prediction.

Serum retinol distributions in residents of the United States: third National Health and Nutrition Examination Survey, 1988-1994.

BACKGROUND: Inadequate vitamin A status has been a potential nutritional problem for some segments of the US population, particularly children and the poor. OBJECTIVE: We evaluated serum retinol concentration by using population-representative data from 16058 participants aged 4 to >/=90 y in the third National Health and Nutrition Examination Survey, 1988-1994. DESIGN: We used multivariate regression to examine the simultaneous associations of sociodemographic, biologic, and behavioral factors with serum retinol concentration. RESULTS: In children, serum retinol concentrations were greater with greater age, body mass index, serum lipids, and the use of supplements containing vitamin A. In adults, male sex, serum lipids, alcohol consumption, and age were positively associated with serum retinol concentration in most racial/ethnic strata. Household income was not associated with serum retinol concentration in children; associations were inconsistent in adults. The prevalence of serum retinol <0.70 micromol/L was very low in all strata; the prevalence of serum retinol <1.05 micromol/L was 16.7-33.9% in children aged 4-8 y and 3.6-14.2% in children aged 9-13 y, depending on sex and racial/ethnic group. The prevalence of serum retinol<1.05 micromol/L was higher in non-Hispanic black and Mexican American children than in non-Hispanic white children; these differences remained significant (P < 0.0001) after covariates were controlled for. Among adults, nonwhite women were significantly (P < 0.0001) more likely than white women to have serum retinol <1.05 micromol/L after covariates were controlled for. CONCLUSIONS: Clinically low serum retinol concentration is uncommon in US residents aged > or = 4 y, although racial/ethnic and socioeconomic differences in serum retinol concentration still exist.

Use of prescription weight loss pills among U.S. adults in 1996-1998.

BACKGROUND: Pharmacotherapy is recommended for the treatment of obese persons with a body mass index of 30 kg/m(2) or higher or a body mass index of at least 27 kg/m(2) plus an obesity-related comorbid condition. OBJECTIVE: To estimate the prevalence of use of prescription weight loss pills in the United States in 1996-1998. DESIGN: 1998 Behavioral Risk Factor Surveillance System, a nationally representative telephone survey. SETTING: United States. PARTICIPANTS: 139 779 adults 18 years of age and older. MEASUREMENTS: Self-reported pill use for 1996-1998, body mass index (current and before pill use), age, sex, and race or ethnicity. RESULTS: The 2-year prevalence of pill use was 2.5% (95% CI, 2.1% to 2.9%), or 4.6 million U.S. adults. Use was higher in women than in men (4.0% vs. 0.9%, respectively) and highest among Hispanic respondents (3.2%). Of pill users, 25% were not overweight (body mass index < 27 kg/m(2) before using pills. CONCLUSIONS: Nearly 5 million U.S. adults used prescription weight loss pills in 1996-1998. However, one quarter of users were not overweight, suggesting that weight loss pills may be inappropriately used, especially among women, white persons, and Hispanic persons.

Serum total homocysteine concentration is related to self-reported heart attack or stroke history among men and women in the NHANES III.

High circulating total homocysteine (tHcy) concentration, which is influenced by folate and vitamin B-12 status, is a suspected cause of cardiovascular events. This relation has been investigated in both case-control and prospective studies but has not been evaluated for different sex x age subgroups of the general U.S. population. We used data on adult (i.e., aged > or =40 y) male (n = 1097) and female (n = 1107) participants in the third National Health and Nutrition Examination Survey, excluding diabetics and those supplemented with estrogen, vitamins or minerals, to evaluate the association between serum tHcy concentration and self-report of heart attack or stroke. After adjustment for age, race-ethnicity, smoking, blood pressure, blood pressure medication, body mass index and serum concentrations of creatinine and cholesterol, past events were reported 2.4 (95% confidence interval 1.0-5.5) times as often by men with tHcy concentration of >12 micromol/L as by men with lower values. The odds ratio for women was 2.6 (95% confidence interval 1.1-6.6) after adjustment for the same factors plus menopausal status. A stronger relation in men aged < or =60 y compared with older men may help reconcile conflicting results of earlier studies.

Analysis of factors influencing the comparison of homocysteine values between the Third National Health and Nutrition Examination Survey (NHANES) and NHANES 1999+.

Two important changes occurred in the time between the Third National Health and Nutrition Examination Survey (NHANES III) (1991-1994) and the later survey (NHANES 1999+) regarding total homocysteine (tHcy), i.e., a change in matrix from serum to plasma and a change in analytical methods. The goals of this study were to determine the magnitude of potential differences between plasma and serum with regard to tHcy concentrations, and between the two analytical methods used in these surveys. Optimally prepared plasma, serum allowed to clot for 30 and 60 min at room temperature and serum allowed to clot for 30 and 60 min and subjected to four freeze-thaw cycles, prepared from blood samples collected from 30 healthy people, were analyzed by both methods. Serum samples had significantly higher tHcy concentrations than plasma samples, and the difference increased with longer clotting time. Freeze-thaw cycles had little or no effect on the variability or bias in the serum sample results. The tHcy results produced by the two analytical methods were significantly different, but consistent across sample types. On average, the results of the method used in NHANES III were lower by 0.64 micromol/L; however, the relative bias varied with tHcy concentration. The tHcy results determined in surplus serum from NHANES III overestimated tHcy concentrations by approximately 10% compared with optimally prepared plasma. The average method bias was 6% between the two analytical methods. On the basis of changes in matrix and methodology, direct comparison of tHcy results between the two surveys is inappropriate.

Diabetes trends in the U.S.: 1990-1998.

OBJECTIVE: To examine trends in diabetes prevalence in the U.S. RESEARCH DESIGN AND METHODS: This study was conducted via telephone surveys in states that participated in the Behavioral Risk Factor Surveillance System between 1990 and 1998. The participants consisted of noninstitutionalized adults aged 18 years or older. The main outcome measure was self-reported diabetes. RESULTS: The prevalence of diabetes rose from 4.9% in 1990 to 6.5% in 1998--an increase of 33%. Increases were observed in both sexes, all ages, all ethnic groups, all education levels, and nearly all states. Changes in prevalence varied by state. The prevalence of diabetes was highly correlated with the prevalence of obesity (r = 0.64, P<0.001). CONCLUSIONS: The prevalence of diabetes continues to increase rapidly in the U.S. Because the prevalence of obesity is also rising, diabetes will become even more common. Major efforts are needed to alter these trends.

Levels and correlates of LDL and VLDL particle sizes among children: the Bogalusa heart study.

Levels of lipids and lipoproteins among children vary by sex and race/ethnicity, and are correlated with age, obesity, and other characteristics. There is, however, little information on the distribution and correlates of low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) subclasses in early life. We used nuclear magnetic resonance (NMR) spectroscopy to determine mean LDL and VLDL particle sizes among 10- to 17-year-olds (n=918) who participated in the 1992-94 examination of the Bogalusa heart study. As compared with girls, boys had a smaller (0.1 nm) mean LDL particle size and a larger (0.9 nm) mean VLDL size; furthermore, the average size of VLDL particles increased with age among white boys but not among other children. Although there were also black/white differences in particle sizes, with black children having larger LDL and smaller VLDL particles, these racial contrasts could be attributed to differences in lipid levels. Levels of triglycerides, insulin, and relative weight were associated with the size of VLDL (positive) and LDL (negative) particles. These results suggest that the analysis of lipoprotein subclasses may provide a better understanding of the role of various risk factors in the development of coronary heart disease

The spread of the obesity epidemic in the United States, 1991-1998.

CONTEXT: The increasing prevalence of obesity is a major public health concern, since obesity is associated with several chronic diseases. OBJECTIVE: To monitor trends in state-specific data and to examine changes in the prevalence of obesity among adults. DESIGN: Cross-sectional random-digit telephone survey (Behavioral Risk Factor Surveillance System) of noninstitutionalized adults aged 18 years or older conducted by the Centers for Disease Control and Prevention and state health departments from 1991 to 1998. SETTING: States that participated in the Behavioral Risk Factor Surveillance System. MAIN OUTCOME MEASURES: Body mass index calculated from self-reported weight and height. RESULTS: The prevalence of obesity (defined as a body mass index > or =30 kg/m2) increased from 12.0% in 1991 to 17.9% in 1998. A steady increase was observed in all states; in both sexes; across age groups, races, educational levels; and occurred regardless of smoking status. The greatest magnitude of increase was found in the following groups: 18- to 29-year-olds (7.1% to 12.1%), those with some college education (10.6% to 17.8%), and those of Hispanic ethnicity (11.6% to 20.8%). The magnitude of the increased prevalence varied by region (ranging from 31.9% for mid Atlantic to 67.2% for South Atlantic, the area with the greatest increases) and by state (ranging from 11.3% for Delaware to 101.8% for Georgia, the state with the greatest increases). CONCLUSIONS: Obesity continues to increase rapidly in the United States. To alter this trend, strategies and programs for weight maintenance as well as weight reduction must become a higher public health priority.

Dose-effect of fenfluramine use on the severity of valvular heart disease among fen-phen patients with valvulopathy.

OBJECTIVE: To determine whether the severity of valvulopathy was associated with the dosage of fenfluramine taken by fenfluramine-phentermine users with valvulopathy. DESIGN: Out of 105 suspected valvulopathy case reports received by the US Food and Drug Administration (FDA) among fenfluramine-phentermine users, 74 patients meeting FDA case definition for valvulopathy were included in this study. Patients with severe valvulopathy were classified as those either undergoing valve replacement surgery or having severe aortic or mitral regurgitation; all other patients were considered to have less severe valvulopathy. RESULTS: The proportion with severe valvulopathy increased from 20-66% with increasing fenfluramine dosage from /=60 mg/d. Compared with patients taking<40 mg/d fenfluramine, patients taking >/=60 mg/d had an adjusted odds ratio of 9.2 (95% confidence interval=2.1-40.8) for severe valvulopathy. CONCLUSION: Compared to patients with less severe valvulopathy, those with severe valvulopathy were substantially more likely to have taken >/=60 mg/d fenfluramine.

Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1991-1994): population reference ranges and contribution of vitamin status to high serum concentrations.

BACKGROUND: The concentration of circulating total homocysteine is a sensitive marker of inadequate folate and vitamin B12 status. Elevated homocysteine concentrations are associated with an increased risk for vascular disease. OBJECTIVE: To identify reference ranges for serum total homocysteine concentration in U.S. residents and quantify the contribution of circulating vitamin concentrations to high homocysteine concentrations. DESIGN: Cross-sectional prevalence study. SETTING: United States. PATIENTS: A nationally representative sample of 3563 male participants and 4523 female participants 12 years of age or older who participated in the third National Health and Nutrition Examination Survey. MEASUREMENTS: Reference ranges (5th and 95th percentiles) for the total homocysteine concentration were defined among participants who were folate- and vitamin B12-replete and had normal creatinine concentrations. A high total homocysteine concentration was defined as one that exceeded the sex-specific 95th percentile for the reference sample (participants 20 to 39 years of age). The population attributable risk percentage was calculated to determine the contribution of low folate (<11 nmol/L) and vitamin B12 (<185 pmol/L) concentrations to a high homocysteine concentration. RESULTS: Reference ranges for serum total homocysteine concentration increased with age; these ranges were 4.3 to 9.9 micromol/L for male participants and 3.3 to 7.2 micromol/L for female participants 12 to 19 years of age and from 5.9 to 15.3 micromol/L for men and 4.9 to 11.6 micromol/L for women 60 years of age or older. A high homocysteine concentration was defined as at least 11.4 micromol/L for male participants and at least 10.4 micromol/L for female participants. Approximately two thirds of the cases of high homocysteine concentrations were associated with low vitamin concentrations. CONCLUSIONS: Upper reference limits for the serum total homocysteine concentration increased with age and were higher for male participants than for female participants at all ages. In most cases, high homocysteine concentrations were associated with low serum vitamin concentrations.