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Biomedical subjects

S E Nelson

Publications and source records attributed to S E Nelson.

At least 55 records · Page 3Linked to original sources

Cow milk feeding in infancy: further observations on blood loss from the gastrointestinal tract.

Because feeding of cow milk causes normal infants to lose increased amounts of occult blood from the gastrointestinal tract, we conducted a prospective trial to measure intestinal blood loss quantitatively and to monitor iron nutritional status. Fifty-two infants entered the trial at 168 days of age and were assigned at random to receive either cow milk or a milk-based formula. Initially, 31 infants had been breast-fed and 21 had been fed formulas. With the feeding of cow milk, the proportion of guaiac-positive stools increased from 3.0% at baseline to 30.3% during the first 28 days of the trial (p less than 0.01), whereas the proportion of positive stools remained low (5.0%) with the feeding of formula. The proportion of guaiac-positive stools among cow milk-fed infants declined later, but for the entire trial it remained significantly (p less than 0.01) elevated. Stool hemoglobin concentration increased markedly with the introduction of cow milk, rising from a mean (+/- SD) of 622 +/- 527 micrograms/gm dry stool at baseline to 3598 +/- 10,479 micrograms/gm dry stool during the first 28 days of ingestion of cow milk. Among infants fed formula, stool hemoglobin did not increase and was significantly (p less than 0.01) less than in the cow milk group. Among infants fed cow milk, the increase in hemoglobin concentration tended to be greater for those who had initially been fed human milk than for those who had initially been fed formulas. Iron nutritional status was not significantly different between the two feeding groups. However, one infant became iron deficient after 4 weeks of ingesting cow milk. We conclude that cow milk feeding leads to increased intestinal tract blood loss in a large proportion of normal infants and that the amount of iron lost is nutritionally important.

Animals↗

Role of carnitine in utilization of dietary medium-chain triglycerides by term infants.

The role of carnitine in oxidation of dietary medium-chain fatty acids (as medium-chain triglycerides) was studied in term human infants. Infants were fed, alternately, formulas with fat content that was predominantly long-chain triglycerides, or 40% medium-chain triglycerides. Urinary acylcarnitine excretion was significantly higher and the ratio of free to total carnitine was significantly lower when infants were fed the formula with medium-chain triglycerides. Two groups of 10 infants were fed a commercial soy-protein-based formula modified to contain 40% of fat calories as medium-chain triglycerides and with or without added L-carnitine. By 56 d, infants fed the formula without added L-carnitine excreted significantly more medium-chain dicarboxylic acids than did the same infants at 28 d and significantly more than infants consuming the carnitine-supplemented formula at either 28 or 56 d. Results are consistent with a role for carnitine in metabolism of dietary medium-chain triglycerides in infants.

Animals↗

Feasibility of using the stable isotope 25Mg to study Mg metabolism in infants.

The feasibility of using isotopic techniques to study Mg absorption and metabolism was explored in three full-term human infants. 25Mg (98.8 atom %) was administered orally as an in vivo tracer. Fractional 25Mg absorption, isotope retention, endogenous fecal Mg losses, and apparent Mg exchangeable pool size were then determined under three conditions of isotope administration: 1) 20 mg 25Mg, with single feeding; 2) 20 mg 25Mg, distributed over a 24-h period; and 3) 60 mg 25Mg, over a 24-h period. Mg isotope ratios were determined by inductively coupled plasma mass spectrometry. Fractional absorption was increased in all three infants after distributed versus bolus administration at the 20 mg dose; mean (+/- SD) fractional absorption was 64.0 +/- 3.9 versus 54.3 +/- 5.9%, respectively. 25Mg retention was also more in all three infants after distributed administration (55.8 +/- 3.0 versus 44.3 +/- 1.3% of dose). At the 60-mg 25Mg dose, compared to 20 mg, fractional absorption was reduced but absolute isotope absorption more than doubled in all infants; urine isotope losses represented a similar fraction of the absorbed dose, thus, 25Mg retention also more than doubled. Compared to the results of the isotope studies, net Mg absorption and balance were uninfluenced by total Mg intake. Isotope retention with distributed isotope administration resulted in measurable isotopic enrichment of plasma and erythrocytes at 72 h (i.e. plasma isotope enrichment was 6.3-10.2 and 19.2-23.5% for the 20- and 60-mg dose, respectively). With these doses, apparent Mg exchangeable pool size ranged from 5.5 to 7.6 mmol/kg body wt; these values showed a decrease with age both within and between infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Feasibility Studies↗

Gain in weight and length during early infancy.

Although rate of growth is generally recognized as a valuable indicator of health status, few reference data are available for gain in weight or length during the period of most growth in infancy. We have therefore summarized our data concerning gains in length and weight of 203 breast-fed males, 216 breast-fed females, 380 formula-fed males, and 340 formula-fed females. Seven sets of measurements (at ages 8, 14, 28, 42, 56, 84 and 112 days) were made with each infant. The 5th, 10th, 25th, 50th, 75th, 90th and 95th centile values together with the means and standard deviations are presented for selected age intervals on a feeding-specific (i.e. breast-fed or formula-fed) and sex-specific basis. We believe that these data will be useful as a reference for interpreting results of infant studies.

Aging↗

Low carnitine intake and altered lipid metabolism in infants.

We examined the effect of dietary carnitine on variables of lipid metabolism in human infants. Normal male full-term infants were fed an isolated soy-protein-based formula with or without added carnitine from age 6-9 d to age 112 d. Growth and food intake were measured throughout the study. At ages 56 and 112 d serum concentrations of carnitine, free fatty acids, and triglycerides and urinary excretion of carnitine and medium-chain dicarboxylic acids were measured. Serum carnitine concentrations were lower in all infants fed unsupplemented formula. There was no difference in growth or food intake between the two groups of infants. Serum free fatty acid concentrations were significantly higher in the infants not receiving dietary carnitine. Moreover, excretion of all three medium-chain dicarboxylic acids was significantly higher in infants not receiving dietary carnitine. We conclude that lack of dietary carnitine affects lipid metabolism of infants during the first 4 mo of life.

Carnitine↗

Carnitine status of lactoovovegetarians and strict vegetarian adults and children.

Because carnitine is contained primarily in meats and dairy products, vegetarian diets provide a model for assessing the impact of prolonged low carnitine intake on carnitine status. Plasma carnitine concentrations and urinary carnitine excretion were measured in adults and children consuming a strict vegetarian, lactoovovegetarian, or mixed diet. In adults plasma carnitine concentration and urinary carnitine excretion of strict vegetarians and lactoovovegetarians were significantly lower than those in the mixed-diet group but were not different from each other. In children significant differences were found between all three diet groups for both plasma carnitine concentration and urinary carnitine excretion. The differences in plasma carnitine concentrations were greater in children than in adults, possibly reflecting the effects of growth and tissue deposition. Small differences between diet groups in adults do not suggest a nutritionally significant difference in carnitine status. Whether vegetarian children are at greater risk for overt deficiency is not answered.

Adolescent↗

Effect of low zinc intake on absorption and excretion of zinc by infants studied with 70Zn as extrinsic tag.

The effect of low dietary intake of zinc was studied in six normal infants with the use of 70Zn as an extrinsic tag. Of the two study formulas, one provided a zinc intake similar to that of customary infant formulas ("high" intake), whereas the other provided a "low" zinc intake. Two zinc absorption studies were performed with each formula (sequence: high-low-low-high). Extrinsically labeled formula was fed for 24 h and excreta were collected for 72 h. Zinc isotope ratios were determined by inductively coupled plasma mass spectrometry (ICP/MS). When zinc intake was high, net zinc absorption was 9.1 +/- 8.7% (mean +/- SD) of intake and net zinc retention was 74 +/- 91 micrograms/(kg.d). True zinc (70Zn) absorption was 16.8 +/- 5.8% of intake and fecal excretion of endogenous zinc was 78 +/- 56 micrograms/(kg.d). When zinc intake was low, net absorption of zinc increased significantly (P less than 0.001) to 26.0 +/- 13.0% of intake, but net retention was not significantly different at 42 +/- 33 micrograms/(kg.d). True absorption of zinc also increased significantly (P less than 0.001) to 41.1 +/- 7.8% of intake, whereas fecal endogenous zinc decreased (P less than 0.05) to 34 +/- 16 micrograms/(kg.d) during low zinc intake. Thus, infants maintain zinc balance in the face of low zinc intake through increased efficiency of absorption and decreased excretion of endogenous zinc.

Adaptation, Physiological↗

Utilization of dietary precursors for carnitine synthesis in human adults.

Endogenous synthetic pathways are presumed to be sufficient to provide adequate amounts of carnitine to meet the needs of the body. However, circulating carnitine levels of strict vegetarian adults and children, and particularly of infants fed carnitine-free formulas, are significantly lower than normal. Therefore, we investigated loci at which rates of carnitine synthesis may be restricted in human adults. Excess amounts of the carnitine precursors lysine plus methionine, epsilon-N-trimethyllysine or gamma-butyrobetaine were fed as supplements to a low carnitine diet for 10 d. Rate of carnitine synthesis was estimated by changes in carnitine excretion and changes in serum and muscle carnitine levels. Dietary gamma-butyrobetaine dramatically increased carnitine production, epsilon-N-trimethyllysine had a somewhat smaller effect, and lysine plus methionine had even less effect on carnitine synthesis. We conclude that carnitine synthesis is not limited by the activity of gamma-butyrobetaine hydroxylase. Carnitine synthesis from exogenous epsilon-N-trimethyllysine is limited either by enzymatic processes that lead to the final intermediate, gamma-butyrobetaine, or by the ability of this substrate to enter tissues capable of carrying out these transformations.

Adult↗

Iron absorption from infant foods.

To determine the bioavailability of iron from iron-fortified infant foods, we have determined erythrocyte incorporation of the stable isotope, 58Fe, after feeding the following foods extrinsically labeled with 58Fe: 1) rice cereal with apples and bananas ("cereal-fruit product"), 2) Mead Johnson Enriched Baby Food (MJEBF), a vitamin, mineral, and protein-enriched rice cereal, 3) vegetables and beef ("vegetable-beef product"), 4) grape-juice, and 5) MJEBF. Foods 1-4 were fortified with ferrous sulfate, and food 5 was fortified with ferrous fumarate. Blood was obtained at ages 140, 168, and 196 d of age, and the test meal was fed under standardized conditions at 154 d of age. Erythrocyte incorporation of the 58Fe label was determined from the increase in the mass isotope ratio, 58Fe/57Fe, from the baseline value (at 140 d of age) to the follow-up values. The mass isotope ratio was determined by inductively coupled mass spectrometry. Geometric mean total iron incorporation into erythrocytes from the test meal of MJEBF fortified with ferrous sulfate (food 2) was 0.05 mg, and from the vegetable-beef product test meal (food 3) was 0.08 mg. The low value for MJEBF is presumably explained by the low level of iron fortification. The low value for the vegetable-beef product may reflect the presence of inhibitors of iron absorption. Geometric mean erythrocyte incorporations of iron from the test meals with foods 1, 4 and 5 were 0.15, 0.14, and 0.18 mg, respectively. These erythrocyte incorporation values are 20 to 26% of the estimated 0.7 mg requirement for absorbed iron, and therefore seem nutritionally important.

Biological Availability↗

Erythrocyte incorporation of ingested 58-iron by infants.

The least abundant stable isotope of iron, 58Fe (natural abundance 0.322 weight %), was administered orally to infants to explore the feasibility of using a stable rather than a radioisotope in studies of iron absorption. The dose of 58Fe was given between feedings at age 126 days. The mass isotope ratio, 58Fe/57Fe, was determined in blood by inductively coupled plasma mass spectroscopy and at ages 140, 168, and 196 days. The percentage of the 58Fe dose entering the circulation (3.2 to 16.0%) was inversely correlated with serum ferritin concentration (r = -0.867, p less than 0.01). For individual infants the SD of the percentage of administered dose of iron appearing in the circulation ranged from 0.22 to 1.28. We conclude that the method is likely to be suitable for within-subject comparisons of iron availability from foods. Because of the large between-subject variation, we are pessimistic for this age group about the usefulness of study designs based on group comparisons.

Absorption↗

Lack of adverse reactions to iron-fortified formula.

Some physicians are reluctant to recommend feeding of iron-fortified formulas to infants because of a fear of adverse reactions. In crossover studies, parents' records were compared with regard to their infant's behavior (fussiness, cramps, regurgitation, flatus, colic) and stool characteristics during periods when iron-fortified formulas were fed and periods when non-iron-fortified formulas were fed. No statistically significant feeding-related difference was noted except for stool color.

Double-Blind Method↗

Bioavailability of dietary urea nitrogen in the infant.

Because the human body has no enzymes capable of hydrolyzing urea, nitrogen from this source becomes bioavailable only by release of ammonia from urea by bacterial hydrolysis in the intestines, with subsequent absorption and utilization of ammonia. To explore extent to which urea ingested in milk becomes bioavailable, we fed di-15N-urea (both nitrogen atoms in the form of the stable isotope 15N) and determined urinary excretion of di-15N-urea (excreted without having become bioavailable) and mono-15N-urea (urea containing only one atom of 15N and therefore reflecting excretion of absorbed ammonia). The largest percentage of the ingested di-15N-urea was excreted promptly in the urine still in the form of di-15N-urea. We conclude that most of the urea ingested by a normal infant is not bioavailable.

Animals↗

RNA complementary to alfalfa mosaic virus RNA 4 is not translated in vitro.

cDNA of the subgenomic messenger RNA (RNA 4) of alfalfa mosaic virus was ligated in both orientations into plasmids containing the bacteriophage SP 6 promoter. Upon transcription in vitro these plasmids yielded synthetic full-length complementary RNA and messenger-sense RNA. The complementary RNA contained an open reading frame of 417 nucleotides; the messenger-sense RNA encodes the virus coat protein. No translation products from the complementary RNA were detected in a wheat germ translation system, a reticulocyte lysate translation system, or Xenopus oocytes, whereas the messenger sense RNA was very active in these translation systems.

Autoradiography↗

Progesterone secretion by primary cultures of rat luteal cells.

Primary cultures were prepared from ovaries of immature rats that had been superovulated. The dispersed luteal cells attached to growth surfaces, formed monolayers and secreted progesterone. Progesterone accumulation in the medium was most pronounced in the first week of culturing. Removal of serum from the medium resulted in a progressive decline in progesterone concentration in the culture medium which reached basal levels by 5 hours. In medium without serum, the addition of hCG, FSH or prolactin stimulated an increase in progesterone secretion within 1 hour. Also cholera toxin stimulated a significant increase in progesterone levels in the medium. Prior exposure of cultures to estradiol for 3 days did not augment the response to hCG and inhibited the ability of cholera toxin to stimulate progesterone secretion. These results indicate that the steroidogenic function of rat luteal cells can be studied in culture and that a number of hormones rapidly stimulate the secretion of progesterone from these cells.

Animals↗

Requirement for sulfur-containing amino acids in infancy.

A series of studies designed to define the requirement of normal infants for sulfur-containing amino acids (methionine, cystine) was conducted with formulas providing 3.0, 2.8, 2.6, 2.2 or 1.8 g of isolated soy protein per 100 kcal. The formulas were fed with or without a methionine supplement. Adequacy of the diet was determined by measurement of growth, serum chemical indices and nitrogen balance. Nitrogen balance demonstrated a beneficial effect of methionine supplementation only at the lowest protein concentration (1.8 g/100 kcal). However, measurement of weight gain and/or serum concentrations of urea nitrogen and albumin clearly showed a beneficial effect of methionine supplementation at protein concentrations of 2.2 and 2.6 g/100 kcal. Intakes of sulfur-containing amino acids of 435 and 495 mumol/100 kcal therefore appear inadequate. At higher intakes of protein (2.8 and 3.0 g/100 kcal) there was no beneficial effect of methionine supplementation. Possible exceptions were male infants provided with 3.0 g protein per 100 kcal, in whom weight gain between 8 and 56 d of age was significantly (P less than 0.05) greater with than without a methionine supplement. Based on intakes of sulfur-containing amino acids from the formula providing 2.8 g of isolated soy protein per 100 kcal without methionine supplementation, we conclude that for male infants older than 56 d the requirement for sulfur-containing amino acids is no more than 588 mumol/100 kcal when intake of methionine is 264 mumol/100 kcal. However, it seems possible that such intake fails to meet the requirement in male infants less than 56 d of age. For female infants, regardless of age, 533 mumol/100 of sulfur-containing amino acids per 100 kcal meet the requirement when intake of methionine is 239 mumol/100 kcal.

Amino Acids, Sulfur↗

Effect of dietary calcium on metabolic balance of normal infants.

Metabolic balance studies were performed with six normal infants fed in a balanced cross-over design three formulas differing only in calcium concentration: 389, 659, and 1024 mg/liter. Absorption of phosphorus was significantly affected by increasing calcium intake decreasing from 68 to 63 to 52% of intake. However, since urinary excretion of phosphorus also decreased, there was no significant effect on retention of phosphorus. Absorption of fat was slightly (but significantly) depressed by calcium, decreasing from 97.5 to 95.5 to 92.1% as calcium intake increased. The level of dietary calcium had no significant effect on absorption or retention of nitrogen, magnesium, copper, and zinc. One of the subjects had consistently lower absorption of calcium and fat than the other subjects, suggesting an absorptive defect. The decrease in fractional absorption of calcium (57 to 47 to 39% of intake) with increasing intake of calcium is compatible with adaptive regulation. On the other hand, the observation that absorbed calcium (mg/kg/day) was linearly related to intake of calcium with a slope of 0.373 suggests an alternative explanation: constant passive, concentration-dependent (slope), and constant active (y-intercept) transport of calcium over the range of calcium intakes. Thus, the findings are explainable in more than one way and do not necessarily demonstrate regulatory changes.

Calcium↗