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Biomedical subjects

R J Shulman

Publications and source records attributed to R J Shulman.

At least 19 recordsLinked to original sources

Absorption of lactose, glucose polymers, or combination in premature infants.

STUDY OBJECTIVE: To determine the digestion and absorption of lactose, a combination of lactose and glucose polymers, and glucose polymers alone in infants born at 28 to 42 weeks of gestation. DESIGN: Each infant received the three carbohydrate solutions (85 gm/L concentration) in random order. SETTING: Tertiary care urban children's hospital. INTERVENTIONS: A double-lumen perfusion catheter was placed in the duodenum-jejunum. Absorption was defined as the disappearance of the carbohydrate and all its components (e.g., for lactose: galactose, glucose). MEASUREMENTS AND MAIN RESULTS: Absorption of lactose was less than that of the lactose-glucose polymer combination and the glucose polymers alone. There was no relationship between lactose absorption and postnatal age, whereas absorption of the lactose-glucose polymer combination and the glucose polymers alone correlated with age. Lactose absorption was not related to the number of days that the infants received full-strength feedings or the total number of days of feeding before the study, whereas absorption of both the lactose-glucose polymer combination and the glucose polymers alone was related to both. Absorption of the three solutions was not related to gestational age or to the number of days before the initial feeding. Lactose absorption was greater in infants who received formula alone than in infants fed formula together with human milk. CONCLUSIONS: Premature infants do not digest and absorb lactose as well as glucose polymers. However, lactose does not impair the absorption of glucose polymers. Lactose assimilation is not affected by maturation, but the type of diet may affect lactose digestion and absorption. In contrast, digestion and absorption of glucose polymers are related to both postnatal age and diet.

Absorption

Cereal feeding and its impact on the nitrogen economy of the infant.

To quantify the effect of rice cereal on nitrogen balance and fecal nitrogen excretion, and the contribution of endogenous nitrogen sources to fecal nitrogen output, nine infants aged 3-5 mo received [15N]glycine in all feedings. Samples of urine and feces were obtained daily and analyzed for nitrogen and 15N. On days 1-7 the infants received only formula, and a complete urine and fecal collection was made on days 6-7. From days 8 to 12 the formula was supplemented with rice cereal (133.3 g/L, or 4 g/30 mL formula) and a second complete urine and fecal collection was made on days 11-12. Cereal did not alter fecal nitrogen output or the calculated contribution (45%) of endogenous nitrogen to fecal nitrogen. Cereal did increase nitrogen retention and lower the urinary excretion of the 15N dose (24% of dose). The calculated true digestibility of the rice cereal protein was > 95%. Our results indicate that infants aged 4 mo, in contrast with younger infants, are able to digest and absorb cereal. The addition of cereal to the diet does not lead to increased fecal protein losses.

Bacteria

Parenteral nutrient needs of very low birth weight infants.

OBJECTIVE: To determine nitrogen and mineral needs in parenterally nourished very low birth weight infants. DESIGN: Prospective observational study. SETTING: Neonatal intensive care unit. PATIENTS: Twenty-four very low birth weight infants (< 1.2 kg) expected to receive parenteral nutrition (PN) exclusively for 3 weeks beginning 3 days after birth. INTERVENTIONS: Infants received PN solutions according to nursery protocol. Serial 24-hour balance studies were conducted twice weekly. Clinical therapies were tabulated. MAIN OUTCOME MEASURES: Intake, urinary excretion, and apparent retention of nitrogen, sodium, potassium, zinc, copper, calcium, phosphorus, and magnesium after initiation of PN. RESULTS: Although urinary K, Zn, Ca, P, and Mg excretion (but not N, Na, and Cu excretion) increased after PN therapy was begun, net nutrient retention increased significantly above baseline for all nutrients. Average weekly nutrient retention was significantly below intrauterine estimates of nutrient accretion for N, Na, Ca, P, and Cu; closely approximated estimates for Zn; and significantly exceeded those for K and Mg. Regression analysis was used to predict parenteral nutrient intakes that would support postnatal nutrient retentions equivalent to the intrauterine estimates. Postnatal therapy with dexamethasone affected N, P, and K excretion and retention. CONCLUSIONS: Soon after PN administration is begun, positive nutrient balance may be achieved early in the neonatal period. The magnitude of this effect remains uniform during PN administration. Adjustments in parenteral nutrient intake are needed to provide nutrient intakes sufficient to support postnatal retention at rates similar to those of intrauterine accretion. These data should be considered in the design of future studies to determine optimal PN needs of very low birth weight infants.

Calcium

Controversies in the composition of infant formulas.

Available infant formulas contain a vast assortment of carbohydrate, protein, and fat sources in an effort to emulate the composition of human milk. Although infants receiving commercial formulas thrive, physicians should be cognizant of differences in formula composition and the research that has resulted in the differences. Such awareness permits rational and scientific recommendations both in prescription of formulas and in direction of research on the optimal formula composition for infants.

Dietary Carbohydrates

Molecular epidemiology of coagulase-negative Staphylococcus blood isolates from neonates with persistent bacteremia and children with central venous catheter infections.

Multilocus enzyme electrophoresis was used to genetically characterize sequential isolates of coagulase-negative staphylococci (CONS) from 3 neonates with persistent bacteremia and organisms cultured from several sites in 23 children with presumed catheter-related sepsis (CRS). For 2 of 3 neonates and 21 (91%) of 23 of the patients with presumed CRS, the same CONS clone was isolated from multiple consecutive blood cultures (mean, 7.3 isolates; range, 3-19). For the 23 children with presumed CRS, 7 (30%) had catheter hub (CH) and 7 (30%) had catheter exist site (CES) cultures positive for CONS; cultures from 3 of these patients (from both CH and CES) grew CONS. Genetic analysis of isolates recovered from the CH and peripheral and central venous catheter blood cultures of all 7 patients revealed clonal identity of the strain grown from all sites. In contrast, only 4 (57%) of 7 of the CONS isolates from the CES were the same clone as that isolated from the blood. These data suggest that repetitive isolation of CONS during the course of CRS is due to ongoing bacteremia, not culture contamination with distinct CONS isolates. The results also are consistent with the hypothesis that the CH is a more likely site of initial colonization by CONS than the exist site in patients with CRS.

Bacteremia

Jejunal brush border hydrolase activity is higher in tallow-fed pigs than in corn oil-fed pigs.

We tested the effect of dietary fat on the lipid composition and hydrolase activity of jejunal brush border membranes in piglets. Eighteen 5-wk-old piglets were divided into three groups and for 4 wk fed either an unsaturated low fat diet (3.2% corn oil), an unsaturated high fat diet (17.2% corn oil) or a saturated high fat diet (2.2% corn oil + 15% tallow). Brush border membranes were prepared from the jejunal mucosa and analyzed for cholesterol, phospholipid and fatty acids. The activities of sucrase-isomaltase, lactase-phlorizin hydrolase, maltase-glucoamylase, aminopeptidase and alkaline phosphatase were measured. Lactase-phlorizin hydrolase isoforms were immunopurified and separated by SDS-PAGE, and their relative proportions were measured by densitometry. The activities of the disaccharidases and alkaline phosphatase, but not aminopeptidase, were greater in animals fed the saturated high fat diet than in animals fed the unsaturated high fat diet. The fatty acid composition of the membranes generally reflected the composition of the diet. Correlation analysis demonstrated that the phospholipid, fatty acid and cholesterol compositions of the membranes were associated with the differences in brush border hydrolase activity.

Animals

Bolus versus continuous feedings stimulate small-intestinal growth and development in the newborn pig.

Although bolus and continuous tube feedings are common, little is known about their effect on the developing small intestine. To compare their effect on small-intestinal growth and differentiation, six pairs of 3-day-old piglet littermates were randomized to receive similar volumes of sow milk replacer, either by bolus (four times daily, group B) or continuous feedings (over 24 h, group C) for 7 days. The piglets were then killed and small-intestinal length, weight, protein mass, and disaccharidase activities were determined. Small-intestinal mucosal weight and ileal protein mass were greater in group B than in group C (p = 0.0024 and 0.019, respectively). No differences were noted between groups in jejunal mucosal protein mass. Ileal maltase activity also was greater in group B than group C (p = 0.02). Although ileal lactase activity in group B was twice that in group C, the differences did not quite reach statistical significance (p = 0.11). No differences between groups were noted in ileal or jejunal sucrase activity. Our study demonstrated that bolus feedings increased mucosal mass, protein mass, and maltase activity to a greater degree than continuous feedings. These results may have clinical significance for infants receiving long-term tube feedings.

Animals

Porcine colostrum and milk stimulate visceral organ and skeletal muscle protein synthesis in neonatal piglets.

Our objective was to determine the relative contributions of protein synthesis and protein absorption in the rapid accretion of gastrointestinal protein in suckling piglets during the early neonatal period. We measured the rates of tissue protein synthesis using a flooding dose of L-[4-3H]phenylalanine in various visceral and peripheral tissues of neonatal piglets fed water, mature milk or colostrum for 6 h. The jejunal and ileal protein synthesis rates in piglets fed either colostrum or milk were three- to fourfold higher than in piglets fed water. The increased jejunal and ileal protein synthesis could not, however, account for the differences in protein mass between the colostrum-fed and water-fed groups. The relative abundance of IgG, a major porcine colostral protein, in jejunal tissue was markedly higher in piglets fed colostrum than in piglets fed either milk or water. The fractional protein synthesis rates in liver, kidney, spleen and skeletal muscle and the absolute protein synthesis rates in liver and spleen were also greater in piglets fed colostrum than in those fed milk or water. Increased endogenous protein synthesis made only a minor contribution to the increased intestinal protein accretion in neonatal piglets fed colostrum. A much larger proportion of this increase seemed to be a result of absorption and retention of ingested immunoglobulins.

Animals

Effect of oral insulin on lactase activity, mRNA, and posttranscriptional processing in the newborn pig.

Insulin, found in human and pig colostrum and mature milk, appears to influence small intestinal growth and development. Ileal lactase activity is increased when porcine insulin is added to feedings administered to newborn piglets. We studied 2-day-old miniature piglets to determine whether the increase in lactase activity is accompanied by changes in enterocyte expression of lactase activity, steady-state levels of lactase mRNA, and/or posttranscriptional changes in lactase processing. We randomized the piglets to receive bottle feedings of a swine-weaning milk formula with (group F + I) or without (group F) the addition of 85 mU/ml of regular porcine insulin. The piglets were fed for 6 days (to 8 days of age), after which they were killed and the small intestine removed for analysis. Despite large differences between groups in enterocyte expression of lactase activity in the ileum, no differences were noted in the level of ileal lactase mRNA. The relative proportions of the 207, 210, and 230 kDa precursors of the 160 kDa mature lactase protein were similar between groups. These data indicate that the insulin-induced increased expression of ileal lactase activity is not regulated at the level of its mRNA or at the level of processing of the polypeptide.

Administration, Oral

Developmental changes in lactase-phlorizin hydrolase precursor isoforms in the rat.

The purpose of this study was to determine whether the developmental decline in lactase specific activity (mumol/min/g protein) in the rat was associated with (a) changes in the relative quantities of immunoisolated precursor and mature forms of the enzyme purified by SDS-PAGE and/or (b) immunohistologic changes in the jejunal mucosa. We studied 10- and 16-day-old suckling rat pups, 22-day-old weaned rat pups, and adult female rats (nongravid, pregnant, and lactating). Lactase activity was three- to fourfold higher in 10-day-old pups than in adult rats. Lactase activity was 27% greater in lactating compared with nongravid or pregnant rats. Three molecular forms of the enzyme that migrated identically in all animals were observed on SDS-polyacrylamide gels stained with Coomassie blue: 140-kDa (mature brush border form), 200-kDa, and 220-kDa (apparent precursor forms). There was a striking difference in the proportions of the three polypeptides at different ages that was unrelated to animal status, i.e., pregnant or lactating. As the animals aged, the relative amount of the 140-kDa band declined from 86 +/- 1.1% of the total immunoprecipitated lactase in 10-day old suckling pups to 68 +/- 0.7% in adults. Simultaneously, the relative concentration of the 200-kDa band rose from 1.7 +/- 0.4% in the 10-day-old to 19 +/- 0.6% in adults. The relative concentration of the 220-kDa polypeptide did not change as a function of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Effect of pancreatic secretions upon ileal disaccharidase activities of neonatal miniature pigs.

Mechanisms by which pancreatic secretions influence disaccharidase activities in the distal small intestine have been investigated in 1-week-old miniature pigs. Using a combination of biochemical, cytochemical and morphological techniques it has been found that the decrease in lactase specific activity is due solely to a reduction in villus surface area. By contrast, the increased sucrase-isomaltase activities, which occur despite the reduction in villus surface area, are due entirely to increased enzyme expression during enterocyte differentiation.

Animals

Impact of dietary cereal on nutrient absorption and fecal nitrogen loss in formula-fed infants.

STUDY OBJECTIVE: To determine the capacity of infants to digest and absorb rice cereal and to determine the effect of cereal feeding on total energy and nitrogen absorption. SETTING: Subject's residences and the Texas Children's Hospital Clinical Research Center, Houston. PATIENTS: Eight healthy 1-month-old bottle-fed infants. INTERVENTIONS: Infants were fed their usual formula for 3 days. For the subsequent 6 days, they received 4 gm of rice cereal, labeled with carbon 13, per 30 ml of the formula. MEASUREMENTS AND MAIN RESULTS: Fecal balance studies were performed for a 72-hour period while the infants received only formula and again during the last 3 days of cereal feeding. Breath samples for hydrogen measurement were collected before and after the cereal feeding. Nutrient intake was measured and stools were analyzed for 13C abundance, energy, nitrogen, fiber content, and bacterial mass. Cereal absorption was 88 +/- 9% (mean +/- SD). Despite a significant increase in energy and nitrogen intake from cereal feeding, the coefficient of absorption fell (energy: 97% to 90%, p = 0.048; nitrogen: 94% to 74%, p = 0.009). Fecal dry weight increased after the cereal feeding (p = 0.004), primarily as a result of a sevenfold increase in fecal bacterial mass (p = 0.002). Fecal nitrogen increased primarily because of incorporation of nitrogen into bacteria. No differences were detected in breath hydrogen as a consequence of formula feeding versus formula-cereal feeding. CONCLUSIONS: Although cereal was relatively well-absorbed in this group of infants and increased their intakes of energy and nitrogen, it did not increase the coefficients of energy and nitrogen absorption. Cereal feeding increased fecal bacterial mass and bacterial nitrogen.

Bacteria

Cysteine usage increases the need for acetate in neonates who receive total parenteral nutrition.

The addition of cysteine (as cysteine HCl) to a total parenteral nutrition (TPN) solution enhances calcium and phosphate solubility because cysteine lowers the pH of the solution. To determine whether adding cysteine to TPN solutions affected the acid-base homeostasis of infants and increased their need for acetate to obviate acidosis, we studied two groups of neonates--those receiving TPN before (group C) and after (group NC) the addition of cysteine. Measurements were made before and during the first 2 wk of TPN administration. We measured the pH of our standard TPN solution with and without the addition of cysteine. Serum carbon dioxide was significantly lower in group C despite a significantly greater intake of acetate in group NC. In the in vitro study the addition of cysteine to the TPN solution lowered the pH from 5.5 to 5.1. Newborns who received TPN solutions to which cysteine was added had lower serum carbon dioxide values and a greater need to receive acetate than did newborns who received TPN solutions without cysteine.

Acetates

Histologic findings are not correlated with disaccharidase activities in infants with protracted diarrhea.

Histologic assessment as well as information about the disaccharidase activity of the small intestinal mucosa can be useful in the management of patients with small intestinal mucosal damage. In an effort to determine whether the degree of small intestinal mucosal damage would be reflected in a corresponding reduction in disaccharidase activity, we compared small intestinal mucosal histology with the results of disaccharidase activity measured in per oral suction small intestinal biopsies obtained from 21 infants with protracted diarrhea. The degree of small intestinal mucosal damage was graded using a subjective score (i.e., 0 to 4+ damage) by a pathologist (P) and by a computer-assisted digitizing system (to assess villus surface area, VSA, and villus/crypt ratio, V/C) in a blinded fashion. The mean (+/- SD) age of the infants was 2.5 +/- 1.5 months, and the duration of diarrhea was 25.2 +/- 11.5 days. There was good correlation between the results obtained from the digitizing system and from the pathologist: VSA versus P, r = 0.695; V/C versus P, r = 0.791; p = 0.0004. All infants demonstrated some degree of small intestinal mucosal damage. The mean (+/- SD) values for P, VSA, and V/C were 2.2 +/- 1.3, 2.9 +/- 0.9, and 0.9 +/- 0.5, respectively. The mean values for lactase, sucrase, and maltase were 17.1 +/- 17.0, 71.1 +/- 54.0, and 224.3 +/- 233 mumol/min/g protein, respectively. No correlation was observed between the histologic scoring results and lactase, sucrase, or maltase measurements. Expressing the disaccharidase activities per unit wet weight of tissue did not improve the correlations. Log transformation of the data also failed to improve the correlations.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy