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W C Heird

Publications and source records attributed to W C Heird.

At least 37 records · Page 2Linked to original sources
PubMed1998

Parenteral nutrition selectively decreases protein synthesis in the small intestine.

We investigated the effects of an elemental diet fed parenterally or enterally on total mucosal protein and lactase phlorizin hydrolase (LPH) synthesis. Catheters were placed in the stomach, jugular vein, and carotid artery of 12 3-day-old pigs. Half of the animals were given an elemental regimen enterally and the other half parenterally. Six days later, animals were infused intravenously with [2H3]leucine for 6 h and killed, and the midjejunum of each animal was collected for analysis. The weight of the midjejunum was 8 +/- 1.5 and 17 +/- 1.6 g in parenterally fed and enterally fed piglets, respectively. LPH activities (mumol.min-1.g protein-1) were significantly higher in parenterally vs. enterally fed piglets. Total small intestinal LPH activities were lower in parenterally vs. enterally fed animals. The abundance of LPH mRNA relative to elongation factor-1 alpha mRNA was not different between groups. The fractional synthesis rate of total mucosal protein and LPH was significantly lower in parenterally fed animals (67 +/- 7 and 66 +/- 7%/day, respectively) than in enterally fed animals (96 +/- 7 and 90 +/- 6%/day, respectively). The absolute synthesis rate (the amount of protein synthesized per gram of mucosa) of total mucosal protein was significantly lower in parenterally fed than in enterally fed piglets. However, the absolute synthesis rate of LPH was unaffected by the route of nutrient administration. These results suggest that the small intestine partially compensates for the effects of parenteral feeding by maintaining the absolute synthesis rate of LPH at the same levels as in enterally fed animals.

Animals↗
PubMed1997

New insights into the metabolism of long chain polyunsaturated fatty acids during infancy.

Data obtained with stable isotope methodology have demonstrated that preterm and term infants can convert LA and ALA, respectively, to AA and DHA. In addition, they have clarified the pathways by which infants convert LA and ALA to LCPUFA and have demonstrated the importance of factors such as the dietary LA/ALA ratio and postnatal age on biosynthesis of AA and DHA. Further work is needed to clarify the role of other influential factors on endogenous synthesis of LCPUFA and to determine the absolute amounts of endogenous LCPUFA synthesis. Such data are necessary to define more precisely the LCPUFA requirements of growing infants.

Dietary Fats↗
PubMed1997

Effect of dietary linoleic/alpha-linolenic acid ratio on growth and visual function of term infants.

OBJECTIVES: To determine the effect of alpha-linolenic acid (ALA) intake (or the dietary linoleic acid [LA]/ALA ratio) on the growth and visual function of term infants. STUDY DESIGN: Normal term infants were assigned randomly and in masked fashion at birth to receive formulas with approximately 16% of total fatty acids as LA and 0.4%, 1.0%, 1.7%, or 3.2% of fatty acids as ALA (LA/ALA ratios of 44, 18.2, 9.7, and 4.8) for the first 4 months of life. The fatty acid pattern of plasma phospholipids was determined shortly after birth and at approximately 21, 60, and 120 days of age. Anthropometric data were obtained at the same times and also at approximately 240 days of age. Transient visual evoked responses (VERs) were measured at approximately 120 and 240 days of age. For comparisons, anthropometric and VER data also were obtained in infants who were exclusively breast-fed for the first 4 months of life. RESULTS: Infants who received the formula with 3.2% ALA (LA/ALA ratio, 4.8) had higher plasma concentrations of phospholipid docosahexaenoic acid (DHA) but lower concentrations of arachidonic acid at 21, 60, and 120 days of age. Mean weight of this group at 120 days of age was 760 gm less (p < 0.05) than the mean weight of the group that received the formula with 0.4% ALA (LA/ALA ratio, 44). Despite differences in plasma phospholipid DHA contents among groups, neither VER latency nor amplitude differed significantly among formula groups or between any formula group and age-matched, breast-fed infants. CONCLUSIONS: The highest versus the lowest ALA intake (or the lowest vs the highest LA/ALA ratio) resulted in higher plasma phospholipid DHA content from 21 to 120 days of age but was not associated with improved visual function as assessed by transient VER. Moreover, mean body weight of infants who received the highest versus lowest ALA intake was less at 120 days (p < 0.05). These data suggest that the lower LA/ALA ratios currently recommended for infant formulas should not be adopted until the effect of such ratios on growth are evaluated more completely.

Arachidonic Acids↗
PubMed1997

Nutrient accretion in preterm infants fed formula with different protein:energy ratios.

BACKGROUND: Although standard formulas for preterm infants promote intrauterine rates of weight gain, fat deposition in preterm infants fed these formulas has been reported to be considerably higher than that in the fetus. We hypothesized that a preterm infant formula with a higher protein:energy (P:E) ratio would promote accretion rates of fat, fat-free mass, and minerals closer to those of the fetus. METHODS: As part of a larger study to determine whether accretion rates of fat and fat-free mass closer to those of the fetus can be achieved with a higher P:E ratio, we present a descriptive analysis of 72-h nutrient balance studies performed on a subset (n = 15/30) of the infants randomly assigned to be fed formula with a P:E ratio of either 3.2 g/100 kcal or 2.6 g/100 kcal. RESULTS: Despite the higher intake and net absorption of nitrogen by infants fed the higher P:E formula, there was no statistically significant difference in net nitrogen retention between groups. There also were no statistically significant differences between groups in digestible energy, metabolizable energy, energy expenditure, or energy storage. Thus, partitioning of stored energy as protein and fat did not differ between groups. The retention of calcium, phosphorus, sodium, potassium, copper, and zinc also did not differ between groups, and nitrogen intake did not affect mineral retention. CONCLUSIONS: In this study, formula for preterm infants with a P:E ratio of 3.2 g/100 kcal vs. 2.6 g/100 kcal provided no apparent benefit in terms of the proportion of fat to lean tissue accretion as determined from nutrient balance data.

Calcium↗
PubMed1997

Intermediates in endogenous synthesis of C22:6 omega 3 and C20:4 omega 6 by term and preterm infants.

An alternative pathway of omega 3 and omega 6 fatty acid metabolism has been described in isolated rate hepatocytes and human fibroblasts. This alternative pathway, which is independent of delta 4 desaturation, involves elongation of C22 5 omega 3 and C22:4 omega 6 to C24 fatty acids, delta 6 desaturation of the C24 fatty acids and subsequent beta oxidation of the desaturated products to C22:6 omega 3 and C22:5 omega 6. To determine whether this alternative pathway is operative in the human infant and also to obtain additional information concerning endogenous conversion of C18:3 omega 3 and C18:2 omega 6 to longer chain more unsaturated fatty acids, presence of [M + 18] isotopomers of omega 3 and omega 6 fatty acids in the plasma phospholipid fraction of term and preterm infants after administration of [U-13C]18:3 omega 3 and [U-13C]18:2 omega 6 was determined by negative chemical ionization gas chromatography/mass spectrometry. [M + 18] isotopomers of the following omega 3 fatty acids were detected: C18:3, C18:4, C20:3, C20:4, C20:5, C22:4, C22:5, C22:6, C24:4 (two infants only), C24:5, and C24:6. [M + 18] isotopomers of omega 6 fatty acids detected included only C18:2, C18:3, C20:2, C20:3, and C20:4, but sensitivity was insufficient to detect [M + 18] isotopomers of C22 and C24 omega 6 fatty acids. Presence of [M + 18] isotopomers of C24:5 omega 3 and C24:6 omega 3 indicates that these fatty acids were synthesized endogenously from C18:3 omega 3. This plus the in vitro data strongly suggests that infants use the recently described alternative pathway in endogenous synthesis of C22:6 omega 3. However, involvement also of delta 4 desaturation cannot be excluded. Detection of [M + 18] isotopomers of C20:3 omega 3, C20:2 omega 6, and C22:4 omega 3 suggests that C18:3 omega 3, C18:2 omega 6, and C20:4 omega 3 are elongated as well as desaturated. The specific fate of these elongation products and their importance in endogenous synthesis of omega 3 and omega 6 long chain polyunsaturated fatty acids remain to be determined.

Arachidonic Acid↗
PubMed1996

Biochemical effects of dietary linoleic/alpha-linolenic acid ratio in term infants.

Recent statements concerning linoleic (LA) and alpha-linolenic acid (LNA) intakes for infants include a desirable range of LA/LNA ratios. To evaluate several dietary LA/LNA ratios, the fatty acid patterns of plasma and erythrocyte phospholipid fractions, as well as plasma total lipid fractions, were determined shortly after birth and at 21, 60, and 120 d of age in term infants fed formula with 16% of fat as LA and either 0.4, 0.95, 1.7, or 3.2% as LNA (LA/LNA ratios of approximately 44, 18, 10, and 5). The content of all n-3 fatty acids in both plasma fractions was higher at all times in infants who received the highest LNA intake; however, the docosahexaenoic acid (DHA) content was only half that shortly after birth or reported in breast-fed infants of comparable ages. The LA content of plasma lipids of all groups was higher at all times than shortly after birth but did not differ among groups. The arachidonic acid (AA) content was higher in infants who received the lowest LNA intake, but only half that at birth or reported in breast-fed infants. In contrast, the DHA content of the erythrocyte phospholipid fraction did not differ among groups until 120 d of age when it was higher in those who received the highest LNA intake and the AA content of this fraction did not differ among groups at any time. These data demonstrate that dietary LA/LNA ratios between 5 and 44 do not result in plasma or erythrocyte lipid levels of DHA or plasma lipid levels of AA similar to those at birth or reported by others in breast-fed infants. However, the data indicate that the LA/LNA ratio of the formula is an important determinant of the amounts of DHA and AA required to achieve plasma and erythrocyte levels of these fatty acids similar to those of breast-fed infants.

Dietary Fats↗
PubMed1996

Effect of dietary alpha-linolenic acid intake on incorporation of docosahexaenoic and arachidonic acids into plasma phospholipids of term infants.

The fractional conversion rates of plasma phospholipid alpha-linolenic acid (18:3n-3) and linoleic acid (18:2n-6) to docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6), respectively, and the fractional rates of incorporation of 22:6n-3 and 20:4n-6 into plasma phospholipids were determined in 27 healthy 3-wk-old term infants who had received formulas with approximately 16% of fat as 18:2n-6 and 0.4% (n = 6), 1.0% (n = 11), or 3.2% (n = 10) as 18:3n-3 from birth. The infants were given a single dose of both [U-13C] 18:2n-6 and [U-13C] 18:3n-3 with a feeding, and blood samples were collected 8, 12, and 24 h afterward for determination of the isotopic enrichments of the [M + 18] isotopomers of plasma phospholipid fatty acids by negative chemical ionization gas chromatography/mass spectrometry. A simple precursor/product compartmental model was used to estimate fractional rates of conversion and incorporation. All infants converted 18:3n-3 to 22:6n-3 and 18:2n-6 to 20:4n-6. Although the fractional rate of conversion of 18:3n-3 to 22:6n-3 did not differ among groups, the fractional rate of incorporation of 22:6n-3 into the plasma phospholipid fraction was greater in infants who received 3.2% vs. 0.4% or 1.0% 18:3n-3 (4.1 +/- 2.2 vs. 1.6 +/- 1.5 or 2.0 +/- 1.0% of the plasma phospholipid 22:6n-3 pool daily). The fractional rate of conversion of 18:2n-6 to 20:4n-6 was less in infants who received the 3.2% 18:3n-3 intake (0.4 +/- 0.3% of the plasma phospholipid 18:2n-6 pool daily vs. 1.1 +/- 0.7% and 0.8 +/- 0.5% in those who received 0.4 and 1.0% 18:3n-3, respectively). The fractional rate of incorporation of 20:4n-6 into plasma phospholipid also was less in the 3.2% vs. the 0.4 and 1.0% 18:3n-3 groups (2.7 +/- 1.4% vs. 5.9 +/- 2.6 and 4.4 +/- 1.7%, respectively, of the plasma phospholipid 20:4n-6 pool daily).

Arachidonic Acid↗
PubMed1996

Parenteral nutrition in low-birth-weight infants.

Parenteral nutrition has been used in the nutritional management of low-birth-weight infants for the past 25 years. Nonetheless, many aspects of the technique still are not completely understood. Further, Other aspects that are reasonably well understood frequently are not applied in clinical practice. As a result, infants requiring this therapy frequently do not benefit maximally from it. Some of the important issues concerning this technique are discussed, and some of the important questions that need to be addressed are identified. Answers to many of these important questions are necessary to further enhance the benefits and diminish the undesired consequences of this therapy for infants who require it.

Amino Acids↗
PubMed1995

A new stable isotope tracer technique to assess human neonatal amino acid synthesis.

The amino acid (AA) synthetic ability and requirements of human infants are undefined. A stable isotope tracer technique was employed in neonates to assess conversion of uniformly labeled 13C glucose into biochemically nonessential AA (NEAA). Ten neonates (5 males, 5 females) were studied at a mean age of 7 +/- 2.0 (SEM) days. The mean gestational age was 35.5 +/- 1.1 weeks, and the mean weight at time of study was 2,191 +/- 181 g. Six infants were fed enterally, and four received only intravenous 10% dextrose (D10W). Blood samples were obtained before, and 30, 60, and 120 minutes after an orogastric bolus of D-[U-13C]glucose (100 mg/kg). The conversion of glucose carbon into seven NEAA was assessed by measuring their isotopic enrichments in plasma, using gas chromatography/mass spectrometry (GC/MS), and was expressed as mole percent excess (MPE), with detectable MPE defined as > or = 0.2. The isotopic enrichment of plasma glucose also was measured using GC/MS. Free plasma AA concentrations were assayed using an automated AA analyzer and expressed in micromoles per liter. The mean glucose enrichment was 9.33 +/- 1.8 MPE (range, 5.82 to 13.48). Detectable 13C-labeling of the NEAA was observed as follows: Glu in 100% of infants; Gly, 100%; Ala, 90%; Ser, 80%; Asp, 70%; Cys, 60%; and Pro, 60%. Detectable Pro enrichment was observed in none of three premature infants on D10W. Free plasma Cys concentration was markedly lower than normal (19.8 v 86 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1995

Amino acid and energy needs of pediatric patients receiving parenteral nutrition.

The technique of parenteral nutrition has become such an established part of modern pediatric care that it is difficult to imagine how pediatricians, as recently as 25 years ago, managed a large group of very difficult patients; however, despite its obvious nutritional advantages, the technique is not without problems. Many of these can be circumvented or controlled by careful attention to all aspects of the technique. Certainly the incidence of these problems can be maintained at a level sufficiently low that the benefits of the technique far outweigh its risks; however, the technique clearly can be further improved. One requirement for doing so is to recognize that the technique is deceptively simple and that it should not be used indiscriminantly without careful consideration of indications and alternative strategies for nutritional management. Additional research also is required. As discussed earlier, the available parenteral amino acid mixtures and lipid emulsions, although considerably improved over earlier versions, remain far from optimal. Some of the actual and theoretic problems that should be addressed in the near future are discussed in the preceding sections; there also are many others.

Amino Acids↗
PubMed1994

Attenuation of acetaminophen hepatotoxicity in mice as evidence for the bioavailability of the cysteine in D-glucose-L-cysteine in vivo.

A substantial fraction of the cysteine added to total parenteral nutrition (TPN) solutions is converted to the corresponding thiazolidine derivative, while in solution with relatively large concentrations of glucose typical of TPN (700 mM and higher). It was recently reported (Roberts et al. (1987) J. Med. Chem. 30, 1891-1896) that this thiazolidine, D-glucose-L-cysteine (DGC), offered no significant protection against the hepatic injury caused by 5 mmol/kg of acetaminophen in mice, suggesting that the cysteine present as DGC is poorly bioavailable in vivo. In the present study, fasted male ICR mice given 1.6 or 2.6 mmol/kg of acetaminophen sustained hepatic injury, estimated by elevations in plasma alanine aminotransferase (ALT) activities. Administration of 2.5 mmol/kg of N-acetylcysteine (NAC) 1 h before acetaminophen given i.p. prevented the rise in plasma ALT activities, apparently through support of glutathione (GSH) synthesis. Administration of 2.5 mmol/kg of DGC prior to acetaminophen resulted in slightly lower mean plasma ALT activities than were observed in animals given saline before acetaminophen, but the effect was not statistically significant. When DGC was given 1 h before p.o. administration of 1.6 or 2.6 mmol/kg of acetaminophen, the protective effects of DGC were statistically significant (P < 0.01, 0.025, respectively), although NAC afforded significantly greater protection than did DGC at the higher dose of acetaminophen. Given 4 h before acetaminophen, DGC attenuated acetaminophen-induced increases in plasma ALT activities significantly, whereas NAC was without effect. These results indicate that the cysteine in DGC is at least partially bioavailable in vivo and, further, that DGC may function as a slow release formulation of cysteine.

Acetaminophen↗
PubMed1994

Effects of feeding on the small intestinal mucosa of beagle pups during the first 5 d of life.

To further define the effects of feeding on small intestinal ontogeny, naturally suckled and formula-fed beagle pups were studied over the first 120 h of life. In suckled animals, proximal jejunal and midintestinal mucosal weight and protein and DNA contents increased > 75% by 24 h (P < 0.005), with no further increases at 120 h. In formula-fed pups, no mucosal mass changes were found between 0 and 72 h of life. At 120 h, proximal jejunal mucosal weight and protein and DNA contents were significantly greater than in newborns (P < 0.005) and were similar to values for suckled animals at the same time. No significant mid-intestinal or terminal ileal growth was noted in formula-fed pups at any time. Specific and total activities of proximal jejunal brush border lactase, sucrase, and alkaline phosphatase were significantly greater in suckled vs formula-fed animals at 120 h. In a parallel study to assess postnatal effects of mature milk vs colostrum, significant mucosal growth at 24 h of life was demonstrated in pups suckled by surrogate dams who had whelped 21 d previously. These data indicate that both natural suckling (colostrum or milk) and formula feeding support enteric mucosal growth in newborn dogs; however, the two feeding regimens are characterized by unique ontogenic patterns of intestinal mucosal growth and function.

Alkaline Phosphatase↗
PubMed1994

Evaluation of a mathematical model for predicting the relationship between protein and energy intakes of low-birth-weight infants and the rate and composition of weight gain.

A model for predicting the relationship between protein and energy intakes of low-birth-weight (LBW) infants and the rate and composition of weight gain is described. It is based on linear multiple regression equations summarizing the rates of weight gain, nitrogen retention, and energy retention of 101 previously studied LBW infants fed protein intakes ranging from 2.25 to 3.9 g.kg-1.d-1 and concomitant energy intakes ranging from 115 to 147 kcal.kg-1.d-1 plus current theory concerning nutrient retention and body composition. To test the validity of the model, three combinations of protein and energy intake predicted by the model to result in specific rates and compositions of weight gain were fed to 44 LBW infants, and the observed rates of weight gain, protein accretion, and fat accretion were compared with the rates predicted by the model. Differences in these and other outcome variables between two of the groups, the intakes of which differed only in energy, also were compared to provide additional insight into the effect of concomitant energy intake on protein utilization. Across groups, actual outcomes correlated closely with predicted outcomes, supporting the validity of the model for the total population. However, outcomes of individual infants deviated as much as 30% from predicted outcomes; the magnitude of the deviation was independent of birth weight, gestational age, or size for gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition↗
PubMed1994

Total parenteral nutrition in necrotizing enterocolitis.

Total parenteral nutrition (TPN) is used both to prevent necrotizing enterocolitis (NEC) and to treat infants who develop the disease. Evidence for the efficacy of the technique in both settings is discussed. Several practical aspects of TPN also are discussed, as are a variety of theoretical considerations relevant to use of TPN either to prevent NEC or as an adjunct to treatment of the infant with the disease.

Enterocolitis, Pseudomembranous↗
PubMed1992

Practical aspects of achieving positive energy balance in low birth weight infants.

For the low birth weight (LBW) infant, energy balance during the first several days of life usually is equated to absorption of sufficient energy to match energy expenditure. Most studies show that energy expenditure of nongrowing LBW infants is 45 to 55 kcal/kg/day. Hence, for energy equilibrium, energy intake minus energy losses (i.e., metabolizable energy intake) must be at least 50 kcal/kg/day. Intakes above this amount result in energy storage or positive energy balance, whereas lesser intakes necessitate mobilization of endogenous energy stores (negative energy balance). Some of the problems of achieving positive energy balance in LBW infants (e.g., feeding intolerance and fear of necrotizing enterocolitis) can be circumvented by use of parenterally delivered nutrients. On balance, virtually all LBW infants will tolerate parenteral amino acid, glucose, and lipid intakes, respectively, of 2, 5, and 1 gm/kg/day or an energy intake of about 40 kcal/kg/day. It usually is possible to increase energy intake of most infants by an additional 10 kcal/kg/day. Whether this is achieved with enterally delivered nutrients or additional parenteral glucose or lipid intake, including the necessary modifications to enhance tolerance (e.g., insulin, 20% vs 10% lipid emulsions, and lipid emulsions containing medium-chain fatty acids), must be decided for each infant based on his or her underlying condition, likelihood of tolerating either substrate, and the impact of intolerance on the underlying condition. The consequences of not providing an essential nutrient during the immediate postnatal period also must be considered. The fact that essential fatty acid deficiency develops more rapidly in infants receiving isocaloric (60 kcal/kg/day) parenteral intakes with versus without amino acids, the likelihood that brain growth continues despite negative energy balance, and the possibility that LBW infants may not be able to desaturate/elongate linoleic and linolenic acids to the more unsaturated, longer-chain fatty acids that are deposited in the developing brain suggest that these infants may require exogenous intakes of specific fatty acids.

Energy Intake↗