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Biomedical subjects

William C Heird

Publications and source records attributed to William C Heird.

At least 19 recordsLinked to original sources

Body-composition assessment in infancy: air-displacement plethysmography compared with a reference 4-compartment model.

BACKGROUND: A better understanding of the associations of early infant nutrition and growth with adult health requires accurate assessment of body composition in infancy. OBJECTIVE: This study evaluated the performance of an infant-sized air-displacement plethysmograph (PEA POD Infant Body Composition System) for the measurement of body composition in infants. DESIGN: Healthy infants (n = 49; age: 1.7-23.0 wk; weight: 2.7-7.1 kg) were examined with the PEA POD system. Reference values for percentage body fat (%BF) were obtained from a 4-compartment (4-C) body-composition model, which was based on measurements of total body water, bone mineral content, and total body potassium. RESULTS: Mean (+/- SD) reproducibility of %BF values obtained with the PEA POD system was 0.4 +/- 1.3%. Mean %BF obtained with the PEA POD system (16.9 +/- 6.5%) did not differ significantly from that obtained with the 4-C model (16.3 +/- 7.2%), and the regression between %BF for the 4-C model and that for the PEA POD system (R2 = 0.73, SEE = 3.7%BF) did not deviate significantly from the line of identity (y = x). CONCLUSIONS: The PEA POD system provided a reliable, accurate, and immediate assessment of %BF in infants. Because of its ease of use, good precision, minimum safety concerns, and bedside accessibility, the PEA POD system is highly suitable for monitoring changes in body composition during infant growth in both the research and clinical settings.

Absorptiometry, Photon↗

Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis.

In animals, liver and white adipose are the main sites for the de novo fatty acid synthesis. Deletion of fatty acid synthase or acetyl-CoA carboxylase (ACC) 1 in mice resulted in embryonic lethality, indicating that the de novo fatty acid synthesis is essential for embryonic development. To understand the importance of de novo fatty acid synthesis and the role of ACC1-produced malonyl-CoA in adult mouse tissues, we generated liver-specific ACC1 knockout (LACC1KO) mice. LACC1KO mice have no obvious health problem under normal feeding conditions. Total ACC activity and malonyl-CoA levels were approximately 70-75% lower in liver of LACC1KO mice compared with that of the WT mice. In addition, the livers of LACC1KO mice accumulated 40-70% less triglycerides. Unexpectedly, when fed fat-free diet for 10 days, there was significant up-regulation of PPARgamma and several enzymes in the lipogenic pathway in the liver of LACC1KO mice compared with the WT mice. Despite the significant up-regulation of the lipogenic enzymes, including a >2-fold increase in fatty acid synthase mRNA, protein, and activity, there was significant decrease in the de novo fatty acid synthesis and triglyceride accumulation in the liver. However, there were no significant changes in blood glucose and fasting ketone body levels. Hence, reducing cytosolic malonyl-CoA and, therefore, the de novo fatty acid synthesis in the liver, does not affect fatty acid oxidation and glucose homeostasis under lipogenic conditions.

Acetyl-CoA Carboxylase↗

Current electrolyte intakes of infants and toddlers.

OBJECTIVE: To determine how sodium, chloride, and potassium intakes of today's infants and toddlers compare with the Dietary Reference Intakes (DRIs) of these nutrients established recently by the Food and Nutrition Board of the Institute of Medicine. STUDY DESIGN: Population estimates of usual intake distributions of sodium, chloride (assumed to be equamolar to sodium), and potassium of 4- to 5-, 6- to 11-, and 12- to 24-month-old infants and toddlers were calculated and compared with DRIs of these nutrients by 0- to 6-month-old, 7- to 12-month-old, and 1- to 3-year-old children. SUBJECTS: Infants and toddlers (n=3,022) who participated in the 2002 Feeding Infants and Toddlers Study. STATISTICAL ANALYSES: Means and distributions (percentiles) of the usual intakes of sodium, chloride, and potassium were calculated using Institute of Medicine-recommended procedures and compared with the DRIs (ie, Adequate Intake [AI] and tolerable upper intake level [UL]). RESULTS: Mean sodium and chloride intakes of 4- to 5-month-old infants (188 mg/day and 290 mg/day, respectively) were 57% greater than the AIs (120 mg/day and 180 mg/day) and mean potassium intake (730 mg/day) was 83% higher than the AI (400 mg/day). Mean sodium, chloride, and potassium intakes of 6- to 11-month-old infants were 493 mg/day, 761 mg/day, and 1,225 mg/day, respectively-33%, 33%, and 75% higher than the AIs of these nutrients for this age group (sodium, 370 mg/day; chloride, 570 mg/day; potassium, 700 mg/day). Even the 10th percentile of potassium intake of this age group was greater than the AI. The usual mean sodium and chloride intakes of 12- to 24-month-old toddlers (1,638 mg/day and 2,528 mg/day, respectively) were 64% higher than the AIs (1,000 mg/day and 1,540 mg/day, respectively) and the usual mean sodium and chloride intakes of 58% of this age group were above the ULs. In contrast, mean potassium intake of 12- to 24-month-old toddlers (1,971 mg/day) was only 66% of the AI (3,000 mg/day). At all ages, sources of sodium, chloride, and potassium intakes reflected current feeding guidelines, primarily human milk and formula prior to 6 months of age and primarily cow's milk and table foods after 1 year of age. CONCLUSIONS: Mean sodium and chloride intakes of infants and toddlers who participated in the 2002 Feeding Infants and Toddlers Study exceeded the recently established AIs of these nutrients and the mean intake of 58% of toddlers exceeded the ULs. Mean potassium intake of infants also exceeded the AI of potassium, but the mean potassium intake of toddlers was only 66% of the AI. Whether current intakes of sodium, chloride, and potassium by infants and toddlers are problematical is not clear. Nonetheless, it seems desirable to bring these intakes closer to AIs. This can be accomplished by continuing breast- or formula-feeding and delaying the introduction of cow's milk; limiting the amount of salt added to home-prepared foods; limiting the intake of high-sodium foods, such as processed meats and salty snacks; and increasing the intake of fruits (high potassium and low sodium content) and vegetables (moderate potassium and sodium content).

Bottle Feeding↗

Performance on a visual sustained attention and discrimination task is associated with urinary excretion of norepineprhine metabolite in children with attention-deficit/hyperactivity disorder (AD/HD).

The degree of association between performance on a sustained attention task requiring visual discrimination and urinary excretion of catecholamine metabolites was examined in a cohort of 6- to 12-year-old children (n = 31) strictly selected and diagnosed with attention-deficit/hyperactivity disorder (AD/HD) according to DSM-IV and other strict criteria. Sustained visual attention and discrimination were measured using the Test of Variables of Attention (T.O.V.A.). Urinary excretion of dopamine (DA) and norepinephrine (NE) metabolites was measured by reversed high-pressure liquid chromatography (HPLC). Pearson product-moment correlations were used to investigate the relationship between T.O.V.A. errors of omission (OMM), errors of commission (COM), response time (RT), and response time variability (RTV) and catecholamine metabolites of DA and NE. All T.O.V.A. indexes under investigation were significantly correlated with urinary excretion of NE metabolites, but correlations were low-to-moderate in magnitude (.37-.50). In contrast, there were no statistically significant correlations between T.O.V.A. indices and DA metabolites. These findings and their concordance with past research in human adults and animals, as well as theoretical issues associated with the present results, are discussed.

Attention↗

Protection against fatty liver but normal adipogenesis in mice lacking adipose differentiation-related protein.

Adipose differentiation-related protein (ADFP; also known as ADRP or adipophilin), is a lipid droplet (LD) protein found in most cells and tissues. ADFP expression is strongly induced in cells with increased lipid load. We have inactivated the Adfp gene in mice to better understand its role in lipid accumulation. The Adfp-deficient mice have unaltered adipose differentiation or lipolysis in vitro or in vivo. Importantly, they display a 60% reduction in hepatic triglyceride (TG) and are resistant to diet-induced fatty liver. To determine the mechanism for the reduced hepatic TG content, we measured hepatic lipogenesis, very-low-density lipoprotein (VLDL) secretion, and lipid uptake and utilization, all of which parameters were shown to be similar between mutant and wild-type mice. The finding of similar VLDL output in the presence of a reduction in total TG in the Adfp-deficient liver is explained by the retention of TG in the microsomes where VLDL is assembled. Given that lipid droplets are thought to form from the outer leaflet of the microsomal membrane, the reduction of TG in the cytosol with concomitant accumulation of TG in the microsome of Adfp-/- cells suggests that ADFP may facilitate the formation of new LDs. In the absence of ADFP, impairment of LD formation is associated with the accumulation of microsomal TG but a reduction in TG in other subcellular compartments.

Adipocytes↗

Biochemical homeostasis and body growth are reliable end points in clinical nutrition trials.

Studies of biochemical homeostasis and/or body growth have been included as outcome variables in most nutrition trials in paediatric patients. Moreover, these outcome variables have provided important insights into the nutrient requirements of infants and children, and continue to do so. Examples of the value of such studies in improving parenteral nutrition, in defining essential fatty acid metabolism and requirements of infants and in defining the protein and energy needs of low-birth-weight infants are discussed. Data from such studies have helped to define the mechanism of metabolic acidosis and hyperammonaemia associated with the use of early crystalline amino acid mixture and, hence, how to prevent these disorders. Such studies have allowed the development of parenteral amino acid mixtures that circumvent grossly abnormal plasma concentrations of most amino acids and appear to be utilized more efficiently. These studies have also helped define micronutrient requirements, including requirements for several such nutrients that had not been previously recognized as essential (e.g. Cr, Se, Mo, alpha-linolenic acid). Studies of body growth have been particularly valuable in defining the nutritional requirements of low-birth-weight infants. Finally, studies of metabolic homeostasis coupled with more sophisticated metabolic studies have provided considerable insight into the metabolism of the essential fatty acids, linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3). Although such studies have not defined the amount of the longer-chain PUFA synthesized from each of these essential fatty acids, i.e. arachidonic acid (20:4n-6) and DHA (22:6n-3), they have shown that the rates of conversion are extremely variable from infant to infant, suggesting a possible explanation of why some studies show developmental advantages from intake of these fatty acids while others do not.

Energy Metabolism↗

Effects of maternal docosahexaenoic acid intake on visual function and neurodevelopment in breastfed term infants.

BACKGROUND: Normal brain and visual development is thought to require exogenous docosahexaenoic acid (DHA; 22:6n-3) intake, but the amount needed is debatable. Because the supplementation of breastfeeding mothers with DHA increases the DHA content of their infants' plasma lipids, we hypothesized that it might also improve brain or visual function in the infants. OBJECTIVE: The objective was to determine the effect of DHA supplementation of breastfeeding mothers on neurodevelopmental status and visual function in the recipient infant. DESIGN: Breastfeeding women received capsules containing either a high-DHA algal oil ( approximately 200 mg DHA/d) or a vegetable oil (no DHA) for 4 mo after delivery. Outcome variables included the fatty acid pattern of maternal plasma phospholipid and milk lipids 4 mo postpartum, the fatty acid pattern of plasma phospholipids and visual function in infants at 4 and 8 mo of age, and neurodevelopmental indexes of the infants at 12 and 30 mo of age. RESULTS: Milk lipid and infant plasma phospholipid DHA contents of the supplemented and control groups were approximately 75% and approximately 35% higher, respectively, at 4 mo postpartum. However, neither the neurodevelopmental indexes of the infants at 12 mo of age nor the visual function at 4 or 8 mo of age differed significantly between groups. In contrast, the Bayley Psychomotor Development Index, but not the Mental Development Index, of the supplemented group was higher (P < 0.01) at 30 mo of age. CONCLUSION: DHA supplementation of breastfeeding mothers results in higher infant plasma phospholipid DHA contents during supplementation and a higher Bayley Psychomotor Development Index at 30 mo of age but results in no other advantages either at or before this age.

Adult↗

The role of essential fatty acids in development.

The presence of docosahexaenoic acid (DHA) and arachidonic acid (ARA) in human milk but not in infant formula, coupled with lower plasma and brain lipid contents of DHA in formula-fed than in breast-fed infants and reports of higher IQ in individuals who were breast-fed versus formula-fed as infants, suggest that exogenous DHA (and ARA) may be essential for optimal development. Thus, since 1990, several studies have examined the impact of formulas containing DHA or DHA plus ARA on visual function and neurodevelopmental outcome. Some of these studies have shown benefits but others have not. These results leave largely unanswered the question of whether these fatty acids are beneficial for either the term or preterm infant. However, evidence that preterm infants might benefit is somewhat more convincing than that for term infants. Despite the limited evidence for efficacy, formulas supplemented with DHA and ARA are now available and appear to be safe.

Arachidonic Acid↗

Supplementation with aromatic amino acids improves leucine kinetics but not aromatic amino acid kinetics in infants with infection, severe malnutrition, and edema.

We investigated whether supplementation with an aromatic amino acid (AAA) cocktail consisting of 0.5 mmol each of phenylalanine, tryptophan, and tyrosine compared with isonitrogenous amounts of alanine (Ala) would improve measures of protein kinetics in 14 (8 with AAA, 6 Ala) children with edematous malnutrition (aged 6-24 mo) during the infected acute malnourished state. Supplementation started immediately after the baseline experiment, 2 d postadmission and continued to the end of the acute phase of treatment. The second (postsupplementation) experiment was done approximately 12 d postadmission. We measured leucine kinetics, phenylalanine and tyrosine fluxes, using an i.g. 8-h prime continuous infusion of (2)H(3)-leucine, and an i.v. 6-h prime continuous infusion of (13)C-leucine, (2)H(2)-tyrosine, and (2)H(5)-phenylalanine in the fed state. Leucine flux tended to be faster (P = 0.06) in the AAA group compared with Ala group after supplementation (mean difference +/- SEM): 22.6 +/- 10.9 micromol/(kg . h). The rate of leucine appearance from protein breakdown [28.1 +/- 9.4 micromol/(kg . h)] and the nonoxidative disposal of leucine [i.e., leucine to protein synthesis; 35.4 +/- 12.9 micromol/(kg . h)] were faster (P < 0.02) in the AAA group than in the Ala group. There was no significant effect of supplementation on leucine splanchnic metabolism, phenylalanine, and tyrosine fluxes. These findings are consistent with the hypothesis that the blunting of the protein catabolic response to infection in children with edematous malnutrition syndrome is due to limited availability of aromatic amino acids.

Alanine↗

Polyunsaturated fatty acids and gene expression.

PURPOSE OF REVIEW: This review focuses on the effect(s) of n-3 polyunsaturated fatty acids on gene transcription as determined by data generated using cDNA microarrays. Introduced within the past decade, this methodology allows detection of the expression of thousands of genes simultaneously and, hence, is a potentially powerful tool for studying the regulation of physiological mechanisms that are triggered or inhibited by nutrients. RECENT FINDINGS: Recent data generated with cDNA microarrays not only confirm the effects of n-3 polyunsaturated fatty acids on regulation of lipolytic and lipogenic gene expression as determined by more traditional methods but also emphasize the tissue specificity of this regulation. cDNA microarray experiments also have expanded our understanding of the role of n-3 polyunsaturated fatty acids in regulation of expression of genes involved in many other pathways. These include: oxidative stress response and antioxidant capacity; cell proliferation; cell growth and apoptosis; cell signaling and cell transduction. SUMMARY: The cDNA microarray studies published to date show clearly that n-3 polyunsaturated fatty acids, usually provided as fish oil, modulate expression of a number of genes with such broad functions as DNA binding, transcriptional regulation, transport, cell adhesion, cell proliferation, and membrane localization. These effects, in turn, may significantly modify cell function, development and/or maturation.

Animals↗

Monounsaturated fatty acid intake by children and adults: temporal trends and demographic differences.

Epidemiologic evidence suggests that dietary monounsaturated fatty acids (MUFA) may have a beneficial health effect. Twenty-four-hour dietary intake data collected on 10-year-olds from 1978 to 1994 and on children and adults (ages 0-30 years) were examined for time, age, gender, ethnic, and geographic location differences in MUFA intake. Children's percent energy from MUFA decreased significantly from 1978 (14.1%) to 1994 (11.9%) with intake of oleic acid decreasing from 33.9 g/day (1973) to 25.7 g/day (1994). In 1994-96, percent energy from MUFA was 13% for children and adults aged 12 to 30 years, with 5% from palmitoleic acid and 93% from oleic acid. Males and blacks had significantly higher MUFA intake across all age groups than females and whites. Intakes of MUFA increased from 0 to 11 years of age to young adulthood (12-19 years), with no further increase at 20 to 30 years of age. Intakes of MUFA were lowest in the Northeast and highest in the Midwest. There were differences in food sources of MUFA by age group. For children 0 to 5 years of age, major sources were whole milk, peanut butter, 2% milk, and French fries; for children 6 to 11 years of age, major sources were whole milk, peanut butter, French fries, and 2% milk; for children 12 to 19 years of age, French fries, salt snacks, whole milk, and meat pizza were the major sources; for adults, French fries, whole milk, potato chips, and ground beef were the most common sources of MUFA. U.S. children and adults displayed temporal trends and demographic differences in intakes and food sources of MUFA. The implications of these changes and differences on biologic risk factors for specific chronic diseases warrant further investigation.

Adolescent↗

Effect of maternal docosahexaenoic acid supplementation on postpartum depression and information processing.

OBJECTIVE: The purpose of this study was to determine the effect of docosahexaenoic acid supplementation on plasma phospholipid docosahexaenoic acid content and indices of depression and information processing for women who breast-feed. STUDY DESIGN: Mothers who planned to breast-feed their infants were assigned randomly in a double-masked fashion to receive either docosahexaenoic acid (approximately 200 mg/d) or placebo for the first 4 months after the delivery. Major outcome variables included plasma phospholipid fatty acid patterns and scores on a self-rating questionnaire of current depression symptoms. A structured clinical interview of depression, scores on another self-rating questionnaire of depression symptoms, and a laboratory measure of information processing were obtained in subgroups of the total population. RESULTS: Plasma phospholipid contents of docosahexaenoic acid at baseline were 3.15 +/- 0.78 and 3.31 +/- 0.70 (mg/dL of total fatty acids) in the docosahexaenoic acid and placebo groups, respectively. After 4 months, the plasma phospholipid docosahexaenoic acid content of the docosahexaenoic acid group was 8% higher (3.40 +/- 0.97 mg/dL), whereas that of the placebo group was 31% lower (2.27 +/- 0.87 mg/dL). Despite the higher plasma phospholipid docosahexaenoic acid content of the supplemented group after 4 months, there was no difference between groups in either self-rating or diagnostic measures of depression; information processing scores of the two groups also did not differ. CONCLUSION: Docosahexaenoic acid supplementation ( approximately 200 mg/d) for 4 months after the delivery prevented the usual decline in plasma phospholipid docosahexaenoic acid content of women who breastfeed but did not influence self-ratings of depression, diagnostic measures of depression, or information processing.

Adult↗

Plausible mechanisms for effects of long-chain polyunsaturated fatty acids on growth.

A few studies conducted over the past decade suggest that formulas supplemented with long-chain polyunsaturated n-3 fatty acids may adversely affect growth of preterm infants. Others suggest that a high intake of alpha-linolenic acid (ALA; 18:3 n-3), the precursor of the long-chain polyunsaturated n-3 fatty acids, also may limit growth. The majority of studies, however, have not shown an effect of either long-chain polyunsaturated n-3 fatty acids or their precursor on growth. Nonetheless, the importance of growth during infancy and the possibility that these fatty acids may inhibit growth under some circumstances makes the issue worthy of further consideration. At the very least, plausible mechanisms for such an effect of n-3 PUFA on growth should be considered. These include (1) altered nutrient intake, absorption, and/or utilization; (2) low plasma and tissue contents of arachidonic acid (ARA;20:4 n-6); (3) an imbalance between n-6 and n-3 LCPUFA eicosanoid precursors and, hence, the eicosanoids produced from each; (4) altered membrane characteristics; and (5) effects on gene expression. Each of these is discussed. It is concluded that any or all are feasible but that none can be specifically implicated. Moreover, since few studies were designed specifically to assess growth, the reported effects of n-3 PUFA on growth could represent chance findings secondary to the suboptimal design. Furthermore, although additional data are needed for a definitive conclusion, the observed effects on growth, regardless of mechanism, does not appear to be biologically significant.

Animals↗

The protein metabolic response to HIV infection in young children.

BACKGROUND: Growth failure often precedes secondary infections in HIV-infected infants and children, suggesting that inadequate protein deposition may be an early manifestation of infection by the virus. However, the protein metabolic response elicited by the virus in young children is unknown. OBJECTIVE: We compared children with HIV infection and age-matched children without HIV infection with regard to whole-body and splanchnic protein kinetics and synthesis of acute phase proteins (APPs). DESIGN: Whole-body and splanchnic leucine kinetics and fractional and absolute synthesis rates of 2 positive and 4 negative APPs were measured in 6 asymptomatic, HIV-infected children (4 males and 2 females) aged 6-17 mo and 4 uninfected children (3 females and 1 male) aged 7-9 mo who were in the fed state. RESULTS: Compared with the control children, the HIV-infected children had significantly lower dietary energy and protein intakes and leucine balance and significantly faster leucine flux and fractional splanchnic leucine extraction; there was no significant difference between the groups in leucine oxidation rates. The HIV-infected children also had significantly higher plasma concentrations and absolute synthesis rates of the positive APPs and a significantly higher fractional synthesis rate of fibrinogen. The concentrations of 2 of the 4 negative APPs, albumin and HDL apolipoprotein A-I, were significantly lower in the HIV-infected children but were not associated with slower synthesis rates. CONCLUSIONS: Children with HIV infection but without secondary infection have reduced protein balance because of an inability to down-regulate protein catabolism. Furthermore, the acute phase protein response elicited by HIV infection is characterized by higher concentrations and synthesis rates of positive APPs without lower concentrations of some negative APPs.

Acute-Phase Proteins↗

Concurrent and predictive validity of the cognitive adaptive test/clinical linguistic and auditory milestone scale (CAT/CLAMS) and the Mental Developmental Index of the Bayley Scales of Infant Development.

The Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) was designed for use by primary pediatric health care providers to identify children with developmental delays. This study assesses the concurrent and predictive validity of CAT/CLAMS developmental quotient (DQ) scores and the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development in healthy children without risk factors for developmental delay. Overall CAT/CLAMS DQ scores correlated significantly with Bayley MDI scores at both 12 (r = 0.393; p = 0.008) and 30 months (r = 0.742; p = 0.0001) of age. Overall CAT/CLAMS DQ scores at 12 months of age also correlated modestly with Bayley MDI scores at 30 months of age (r = 0.181; p = 0.036). Despite its modest predictive validity at 12 months, its satisfactory concurrent validity plus its ease and speed of administration make the CAT/CLAMS a reasonable choice for assessment of early development by primary pediatric health care providers.

Child Development↗

Lipids with an emphasis on long-chain polyunsaturated fatty acids.

In addition to their role as a source of energy, several fatty acids are important components of cell membranes and/or precursors of biologically important eicosanoids. The long-chain polyunsaturated fatty acids, docosahexaenoic acid (DHA) and arachidonic acid (AA), are important for optimal visual function and neurodevelopment. These fatty acids are present in human milk but, until recently, have not been included in formulas marketed in the United States. Although the results of clinical trials assessing the effect of DHA and AA intakes on visual and cognitive development have been inconsistent, some studies suggest benefits. Adequate intake of these fatty acids may be especially important for the preterm infant.

Animals↗