Acute Ostracism-Related Pain Sensitization in the Context of Accumulated Lifetime Experiences of Ostracism.

Ostracism (ie, being ignored/excluded) is a form of social adversity that powerfully impacts health and well-being. While laboratory research indicates that experimentally manipulated experiences of ostracism impact pain, findings have been mixed. Prior investigations have not considered moderating or main effects of individual histories of ostracism, and have been limited in the scope of their pain testing. In this study, participants without current pain reported lifetime experiences of ostracism prior to a laboratory visit where they were randomized to experience either a single episode of ostracism (ie, acute ostracism) or control condition that was immediately followed by quantitative sensory testing. Results indicate that the experimental effect of a single episode of ostracism on pain ratings, after-sensations, and temporal summation of pain is moderated by lifetime ostracism; no main effects were found. For individuals with histories of more lifetime ostracism, encountering a single episode of ostracism led to greater pain sensitization relative to the control condition, whereas no experimental effect was observed for individuals with little lifetime exposure to ostracism. These findings indicate that acute experiences of ostracism may be accompanied by periods of hyperalgesia for people who are chronically ostracized, implicating ostracism as a potential social moderator of pain sensitization. People who are stigmatized may therefore experience enhanced pain burden with repeated and accumulating experiences of ostracism. PERSPECTIVE: Results suggest that in the context of accumulated lifetime experiences of ostracism, single experiences of ostracism evoke central sensitization. In this way, ostracism may function to trigger central sensitization and shape socially- and societally-determined patterns of pain burden and disparity.

Serum lycopene, other serum carotenoids, and risk of prostate cancer in US Blacks and Whites.

Epidemiologic studies investigating the relation between individual carotenoids and risk of prostate cancer have produced inconsistent results. To further explore these associations and to search for reasons prostate cancer incidence is over 50% higher in US Blacks than Whites, the authors analyzed the serum levels of individual carotenoids in 209 cases and 228 controls in a US multicenter, population-based case-control study (1986-1989) that included comparable numbers of Black men and White men aged 40-79 years. Lycopene was inversely associated with prostate cancer risk (comparing highest with lowest quartiles, odds ratio (OR) = 0.65, 95% confidence interval (CI): 0.36, 1.15; test for trend, p = 0.09), particularly for aggressive disease (comparing extreme quartiles, OR = 0.37, 95% CI: 0.15, 0.94; test for trend, p = 0.04). Other carotenoids were positively associated with risk. For all carotenoids, patterns were similar for Blacks and Whites. However, in both the controls and the Third National Health and Nutrition Examination Survey, serum lycopene concentrations were significantly lower in Blacks than in Whites, raising the possibility that differences in lycopene exposure may contribute to the racial disparity in incidence. In conclusion, the results, though not statistically significant, suggest that serum lycopene is inversely related to prostate cancer risk in US Blacks and Whites.

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.

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.

NIST micronutrients measurement quality assurance program: characterizing individual participant measurement performance over time.

The mission of the Micronutrients Measurement Quality Assurance Program (M2QAP) at the National Institute of Standards and Technology is enhanced interlaboratory measurement comparability for fat-soluble vitamin-related measurands in human serum. We recently described improved tools for evaluating individual participant measurement performance in single interlaboratory comparison exercises; we here apply and extend these tools to the evaluation of participant performance over the entire 15-year history of the M2QAP. We describe and illustrate a set of interconnected graphical reporting tools for identifying long-term trends and single-exercise events. We document and discuss recurrent patterns we observe in the measurement performance characteristics for M2QAP participants. The graphical analysis techniques utilized may be applicable to other interlaboratory comparison programs.

Serum alpha-tocopherol status in the United States population: findings from the Third National Health and Nutrition Examination Survey.

Despite the role vitamin E may have in protecting against various chronic conditions, little is known about vitamin E status in the US population. Using data from the Third National Health and Nutrition Examination Survey (1988-1994), the authors examined the distribution and correlates of serum alpha-tocopherol among 16,295 US adults aged 18 or more years. The mean concentration of alpha-tocopherol was 26.8 micromol/liter (geometric mean, 25.0 micromol/liter). The 25th, 50th, and 75th percentiles were 19.6, 24.1, and 30.4 micromol/liter, respectively. The mean alpha-tocopherol/cholesterol ratio was 5.1 (geometric mean, 4.9); the 25th, 50th, and 75th percentiles were 4.1, 4.7, and 5.5 (10(-3)), respectively. About 27% of the US population had a low alpha-tocopherol concentration (<20 micromol/liter). After age standardization, 29% of the men, 28% of the women, 26% of the Whites (men, 27%, and women, 26%), 41% of the African Americans (men, 42%, and women, 40%), 28% of the Mexican Americans (men, 29%, and women, 27%), and 32% of the other participants (men, 36%, and women, 29%) had this low concentration. For all participants, age, educational attainment, serum cholesterol, and several serum vitamins and carotenoids were directly related to and high density lipoprotein cholesterol was inversely related to serum alpha-tocopherol concentration in multiple linear regression analysis. Men had a higher concentration than did women, and African Americans had the lowest concentration of any racial or ethnic group. These results show that important proportions of US adults have a low serum alpha-tocopherol concentration, which may increase their risk for chronic diseases in which low dietary intake or blood concentration of alpha-tocopherol have been implicated.

Micronutrients Measurement Quality Assurance Program: helping participants use interlaboratory comparison exercise results to improve their long-term measurement performance.

Over the past decade, the Micronutrients Measurement Quality Assurance Program (M2QAP) at the National Institute of Standards and Technology (NIST) has administered nearly 40 interlaboratory comparison exercises devoted to fat-soluble vitamin-related analytes in human serum. While M2QAP studies have been used to help certify reference materials and to document the performance of analytical systems, the primary focus of the M2QAP has been, and remains, the improvement of among-participant measurement comparability for target analytes. Recent analysis of historical measurement performance indicated the most efficient mechanism for further improving measurement comparability among participants is the improvement of long-term (months to years) comparability within each laboratory. The summary reports for the M2QAP studies are being redesigned to provide more chemist-friendly analyses of participant performance, dissecting systematic and random components of measurement incomparability as functions of analyte level and time. This report documents the semantic and graphical tools developed to help interlaboratory-comparison-exercise participants interpret their own measurement performance.

Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States)

To evaluate relationships of serum carotenoids, alpha-tocopherol, selenium, and retinol with breast cancer prospectively, we conducted a case-control study nested in a cohort from the Breast Cancer Serum Bank in Columbia, Missouri (United States). Women free of cancer donated blood to this bank in 1977-87. During up to 9.5 years of follow-up (median = 2.7 years), 105 cases of histologically confirmed breast cancer were diagnosed. For each case, two women alive and free of cancer at the age of the case's diagnosis and matched on age and date of blood collection were selected as controls. A nonsignificant gradient of decreasing risk of breast cancer with increasing serum beta-cryptoxanthin was apparent for all women. Serum lycopene also was associated inversely with risk, and among women who donated blood at least two years before diagnosis, a significant gradient of decreasing breast cancer risk with increasing lycopene concentration was evident. A marginally significant gradient of decreasing risk with increasing serum lutein/zeaxanthin also was apparent among these women. We did not observe any evidence for protective effects of alpha- and beta-carotene, alpha-tocopherol, retinol, or selenium for breast cancer. Results of this study suggest that the carotenoids beta-cryptoxanthin, lycopene, and lutein/zeaxanthin may protect against breast cancer.

Effect of hemolysis on serum retinol as assessed by direct fluorometry.

To assess the effect of hemolysis on serum retinol concentrations determined by direct fluorometry, we assayed 196 blood samples from children 6-72-mo of age with various grades of hemolysis for serum retinol by both fluorescence and HPLC. Mean serum retinol concentrations determined by HPLC did not differ significantly according to hemolysis grade; however, fluorometric values did. Additionally, serum retinol concentrations obtained from HPLC and those obtained from direct fluorometry were significantly different in samples with severe hemolysis. Multivariate-regression analysis showed that hemolysis grade was a significant predictor of the difference in mean serum retinol values determined by the two methods. Although severe hemolysis interfered with determinations of serum retinol by direct fluorometry, this method is still a viable choice for field studies of vitamin A status.

Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: has the dose been too low? The NICHD Neonatal Research Network.

OBJECTIVE: Inconsistent effects of vitamin A supplementation on prevention of bronchopulmonary dysplasia have been reported. Meta-analysis of these reports resulted in a relative risk of 0.69-1.02 for death or bronchopulmonary dysplasia associated with vitamin A supplementation. Effective dosage regimens or serum retinol concentrations have not been determined in previous reports. The purpose of this pilot study was to define a vitamin A regimen that produces serum retinol concentrations of 25-55 micrograms/dl. STUDY DESIGN: In this three-phase study, 91 infants (mean birth weight 799-864 g) were enrolled. Vitamin A was administered three times/week for 4 weeks at an average daily dose of 986-2143 IU/day. Physical examinations were performed and serum retinol specimens were collected weekly to assess clinical signs of toxicity. RESULTS: The majority of serum retinol concentrations remained < 25 micrograms/dl until an intramuscular vitamin A dose of 5000 IU/dose three times/week was used. No clinical signs of toxicity were associated with the higher dosage and higher serum concentrations of vitamin A. CONCLUSION: A large clinical trial of vitamin A supplementation with 5000 IU/dose three times/week (25-114% more than the dose used in the three published clinical trials) is needed to assess whether vitamin A supplementation safely reduces the risk of bronchopulmonary dysplasia in very-low-birth-weight infants.

Miracle Village: a recovery community for addicted women and their children in public housing.

Miracle Village is a comprehensive substance-abuse treatment program for women and their children with a major goal of lasting sobriety for its clients. Recovery is built upon the principles of gender sensitive therapy and uses a family-centered perspective. Miracle Village offers an initial 3 months of intensive treatment followed by 21 months of continued comprehensive services. Located within a public housing complex, its secondary goal is the development of a core group of drug-free families to help revitalize the neighborhood. After 4 years of operation, 63% of the women who completed initial treatment are sober and living in the area.

Indexes of food and nutrient intakes as predictors of serum concentrations of nutrients: the problem of inadequate discriminant validity. The Polyp Prevention Trial Study Group.

Nutrient indexes derived from food-frequency questionnaires have generally been regarded as acceptably valid for epidemiologic purposes. Evaluations of these indexes, however, have considered only their convergent validity. We suggest that discriminant validity, or the ability to distinguish among exposures to different nutrients, is also important. Using baseline data from a large clinical trial, we tested the discriminant validity of indexes of intake of vitamin E, alpha-carotene, and beta-carotene. Our results suggest that the vitamin E index possesses neither convergent not discriminant validity, the alpha-carotene index adequate convergent and discriminant validity, and the beta-carotene index adequate convergent but no discriminant validity.

Serum carotenoid concentrations and their reproducibility in children in Belize.

Suggestions that carotenoid-containing foods are beneficial in maintaining health have led to several studies of circulating carotenoid concentrations of adults. Because few data are available for children, we report serum carotenoid concentrations of 493 children in Belize. Carotenoid concentrations were determined as part of a survey of vitamin A status of children, most between 65 and 89 mo of age. Reproducibility was tested by collecting a second blood sample 2 wk after the first collection from a subset of children (n = 23) who consumed their habitual diet with no treatment during the interim. Predominant serum carotenoids were lutein/zeaxanthin and beta-carotene, which accounted for 26% and 24% of median total carotenoids, respectively. The three provitamin A carotenoids, alpha- and beta-carotene and beta-cryptoxanthin, constituted 51% of median total carotenoid concentrations. Partial correlations of each carotenoid with fasting retinol concentration indicated that beta-carotene had the highest correlation. Concordance correlation coefficients (rc) for fasting carotenoid concentrations determined 2 wk apart were > or = 0.89 for lycopene, beta-cryptoxanthin, and alpha- and beta-carotene. The rc for lutein/zeaxanthin and total carotenoids was lower, 0.59 and 0.68, respectively, because of higher lutein/zeaxanthin concentrations at the second sampling than at the first. The reproducibility of the concentrations suggests both that individuals have characteristic profiles and that serum carotenoid concentrations can be measured randomly over > or = 2 wk without significant bias.

Serum carotenoid concentrations and their reproducibility in children in Belize

Suggestions that carotenoid-containing foods are beneficial in maintaining health have led to several studies of circulating carotenoid concentrations of adults. Because few data are available for children, we report serum carotenoid concentrations of 493 children in Belize. Carotenoid concentrations were determined as part of a survey of vitamin A status of children, most between 65 and 89 mo of age. Reproducibility was tested by collecting a second blood samples 2 wk after the first collection from a subset of children (n = 23) who consumed their habiitual diet with no treatment during the interim. Predominant serum carotenoids were lutein/zeaxanthin and beta-carotene, which accounted for 26 percent and 24 percent of median total carotenoids, respectively. The three provitamin A carotenoids, alpha- and beta-carotene and beta-cryptoaxnthin, constituted 51 percent od median total carotenoid concentrations. Partial correlations of each carotenoid with fasting retinol concentrations indicated that beta-carotene had the highest correlation. Concordance correlation coefficients (rc) for fasting carotenoid concentrati9ons determined 2 wk apart were > or = 0.89 for lycopene, beta-cryptoxanthin, and alpha- and beta-catotene. The rc for lutein/zeaxanthin and total carotenoids was lower, 0.59 and 0.68, respectively, because of higher lutein/zeaxanthin concentrations at the second sampling than at the first. The reproducibility of the concentrations suggest both that individuals have characteristic profiles and that serum carotenoid concentrations can be measured randomly over > or =2 wk without significant bias. (au)

Comparison of methods of assessing vitamin A status in children.

OBJECTIVE: A study of children (2-8 years; n = 613) in Belize, Central America, was conducted to determine what proportion of the children might be at risk of vitamin A (vit A) deficiency. The data provide an opportunity to compare results of three methods of assessing vit A status in a population which was not severely malnourished. Serum retinyl ester concentrations were also determined; their relevance to one of the tests, the relative dose response (RDR) test, is discussed. METHODS: The three methods of assessing vit A status were: RDR test, fasting serum retinol concentration, and conjunctival impression cytology (CIC). Retinol-binding protein (RBP), serum retinyl esters and serum zinc concentrations were also determined. RESULTS: Inadequate vit A status was indicated for 17% of subjects by the RDR test (14% cutoff), for 24% by fasting serum retinol concentration (< 0.87 mumol/L), and for 49% by "abnormal" CIC score. Retinyl esters constituted 24% of serum retinoids at the time (5 hours after a retinyl palmitate dose) at which the second blood sample is taken for the RDR test. Regression tree analyses (CART) indicated ethnicity was a predictor of RDR score; ethnicity, stunting and age were predictors of fasting serum retinol concentration; ethnicity and stunting were predictors of 0-hour retinyl ester concentration. CONCLUSION: The three indices of vit A status did not identify the same individuals nor indicate the same percentage of the population to be at risk for vit A deficiency. Increased concentrations of retinyl esters at 5 hours compared to those at 0 hours suggest that insufficient retinol may have been taken up by the liver at 5 hours to release all accumulated retinol-binding protein (RBP) in deficient individuals; prevalence of vit A deficiency might therefore be underestimated by the RDR test. The selection of ethnicity as a predictor of RDR score and of 0-hour retinol and retinyl ester concentrations suggests that factors other than vit A status affect vit A metabolism and may affect the RDR test.

Reproducibility of relative dose response (RDR) test and serum retinol and retinyl ester concentrations in children after a 2-week interval.

OBJECTIVE: Reproducibility of the relative dose response test (RDR), a test designed to measure vitamin A status, was tested in 23 Belizean children, 5-8 years after 2-week interval during which no treatment was given. METHODS: As required for the RDR test, serum retinol concentrations were determined before and 5 hours after an oral dose of vitamin A. An RDR score > 14% was used as the criterion of inadequate vitamin A status. The HPLC method used to measure serum retinol concentrations also determined the concentrations of four retinyl esters. RESULTS: The RDR test was reproducible for 17 of 23 subjects: 3 scored > 14% on both tests; 14, < 14% on both. Six subjects scored > 14% on only one test. The concordance correlation coefficient (rc) for the percent change in the two tests was 0.24; for fasting serum retinol concentration, rc = 0.81. For retinyl palmitate and stearate, the esters present in highest concentrations at 5 hours, concordance correlation coefficients were 0.75 and 0.59, respectively. CONCLUSION: The failure of the RDR test to classify 26% of the subjects reproducibly reduces the usefulness of the test. In addition, the reproducibility of the retinyl ester concentrations in serum 5 hours after the retinyl palmitate dose and the relatively high concentrations in some subjects suggests that some individuals may not metabolize sufficient retinol in 5 hours to cause a maximal increase in serum retinol, resulting in an underestimation of deficiency in a population in which the RDR test is used.

Comparison of methods of assessing vitamin A status in children

A study of children (2 - 8 years; n = 613) in Belize, Central America, was conducted to determine what proportion of the children might be at risk of vitamin A (vit A) deficiency. The data provide an opportunity to compare results of three methods of assessing vit A status in a population which was not severely malnourished. Serum retinyl ester concentrations were also determined; their relevance to one of the tests, the relative dose response (RDR) test, is discussed. METHODS: The three methods of assessing vit A status were: RDR test, fasting serum rintol concentration, and conjunctival impression cytology (CIC). Retinol-binding protein (RBP), serum retinyl esters and serum zinc concentrations were also determined. RESULTS: Inadequate vit A status was indicated for 17 percent of subjects by the RDR test (14 percent cutoff), for 24 percent by fasting serum retinol concentration (< 0.87 mumol/L), and for 49 prcent by abnormal. CIC score. Retinyl esters constituted 24 percent of serum retinoids at the time (5 hours after a retinyl palmitate dose) at which the second blood sample is taken for the RDR test. Regresssion trees analyses (CART) indicated ethnicity was a predictor of RDR score; ethnicity, stunting and age were predictors of fasting serum retinol concentration; ethnicity and stunting were predictors of O-hour retinyl ester concentration. CONCLUSION: The three indices of vit A status did not identify the same individuals nor indicate the same percentage of the population to be at risk for hours compared to those at O hours suggest that insufficient retinol may have been taken up by the liver at 5 hours to release all accumulated retinol-binding protein (RBP) in deficient individuals; prevalence of vit A deficiency might therefore be underestimated by the RDR test. The selection of ethnicity as a predictor of RDR score and of O-hour retinol and retinyl ester concentrations suggests that factors other than vit A status affect vit A metabolism and may affect the RDR test.(AU)

Vitamin A therapy for children with respiratory syncytial virus infection: a multicenter trial in the United States.

BACKGROUND: High dose vitamin A therapy is effective in reducing morbidity and mortality associated with measles infection. Children with acute respiratory syncytial virus (RSV) infection have low serum vitamin A concentrations. METHODS: We performed a multicenter, randomized, placebo-controlled trial of high dose vitamin A therapy among 239 children 1 month to 6 years of age to determine whether high dose vitamin A therapy would reduce morbidity associated with RSV infection. RESULTS: There were no differences between the vitamin A and placebo recipients for most clinical outcomes; however, vitamin A recipients had-longer hospital stays than placebo recipients (5.0 days vs. 4.4 days, P = 0.01) after enrollment. This effect was significant for children who were older than 1 year (who also had received the highest doses of vitamin A), particularly among those at low risk for complications of RSV infection and those enrolled during the second study season. Serum retinol levels at enrollment were inversely correlated with severity of illness. CONCLUSIONS: We found no evidence of a beneficial effect of vitamin A for the treatment of RSV infection in children in the United States. There may be groups of children for which vitamin A has an adverse effect, resulting in longer hospital stays.

Treatment of respiratory syncytial virus infection with vitamin A: a randomized, placebo-controlled trial in Santiago, Chile.

BACKGROUND: Treatment with high dose vitamin A reduces complications and duration of hospitalization for children with measles. In respiratory syncytial virus (RSV) infection, as with measles, low serum vitamin A concentrations correlate with increased severity of illness. METHODS: To determine whether high dose vitamin A treatment is also effective for treating RSV disease, we conducted a randomized, double blind, placebo-controlled trial among 180 RSV-infected children between 1 month and 6 years of age at three hospitals in Santiago, Chile. Children with nasal washes positive for RSV antigen were given oral vitamin A (50,000 to 200,000 IU of retinyl palmitate, doses according to age; n = 89) or placebo (n = 91) within 2 days of admission. RESULTS: There was no significant benefit from vitamin A treatment for the overall group in duration of hospitalization, need for supplemental oxygen or time to resolve hypoxemia. For the subgroup of children with significant hypoxemia on admission (room air oxygen saturation level < or = 90%), those given vitamin A had more rapid resolution of tachypnea (P = 0.01) and a shorter duration of hospitalization (5.5 vs. 9.3 days, P = 0.09). No toxicities were seen, including excess vomiting or bulging fontanel. CONCLUSIONS: If vitamin A has a beneficial effect on the course of RSV disease, it may be seen only in more severely ill children.