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Biomedical subjects

R J Shulman

Publications and source records attributed to R J Shulman.

At least 55 records · Page 3Linked to original sources

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↗

Nutritional therapy for infants with diarrhea.

The appropriate choice of treatment for infants with diarrhea has long provoked debate. Growth of infants with diarrhea is adversely affected by associated diseases including anorexia, malabsorption, catabolic response to infection, and iatrogenic starvation. To prevent the negative effects of diarrhea on the nutrition of infants, continued feeding during the active and early convalescent phases has been recommended. Although this concept is not new, until recently it has been little used in the treatment of diarrhea. In this article we examine the current knowledge about, and trends in, feeding infants with diarrhea. We will discuss treatments for the well-nourished infant with acute diarrhea, the infant with prolonged diarrhea, and the malnourished infant. Information regarding the use of local staples will also be provided.

Acute Disease↗

Oral insulin increases small intestinal mass and disaccharidase activity in the newborn miniature pig.

Factors, such as insulin, found in human and pig colostrum and mature milk likely influence small intestinal growth and development. Although pharmacologic doses of insulin injected parenterally may accelerate small intestinal development in altricial animals such as the rodent, the effects of oral insulin on intestinal development have not been studied. In the first of two studies, we randomized 2-d-old miniature piglets to receive bottle-feedings of a swine weaning milk formula with (group F + I) or without (group F) the addition of insulin. Serum glucose, insulin, and cortisol were measured before and 1 h after the first feeding the piglets received at our facility. In the second study, piglets were randomized (groups F and F + I) and fed for 6 d, after which blood samples were obtained as in the first experiment. The piglets were then killed and the small intestine removed for analysis. We found no differences between groups in serum glucose, insulin, and cortisol at both 2 and 8 d of age, both before and after feeding. In the second experiment, small intestinal weight was greater in the F + I than in the F group. Although no differences were noted between groups in the jejunum, values were greater for group F + I versus group F for ileal mucosal weight, protein, RNA, lactase, and maltase activities. No differences were found between groups in ileal DNA or sucrase activity. We conclude that the administration of oral insulin stimulated an increase in ileal mass and disaccharidase activity in the newborn miniature pig without apparent concomitant changes in serum glucose, insulin, or cortisol.

Administration, Oral↗

An educational booklet diminishes anxiety in parents whose children receive total parenteral nutrition.

A major cause of anxiety in parents of hospitalized children is insufficient information about hospital procedures. In an effort to determine the extent to which parental anxiety could be diminished and knowledge and satisfaction enhanced in regard to total parenteral nutrition (TPN), we developed a booklet that describes the mechanics of TPN administration and related procedures. When informal discussions were held between parents and members of the nutritional support team during four alternating periods (every five to six months), parents of first-time recipients of TPN either did not receive the booklet (period 1, n = 20; period 3, n = 30) or received it (period 2, n = 23; period 4, n = 27). Within one week of TPN initiation, parents in both groups completed the Spielberger State-Trait anxiety scale, an attitude questionnaire, and a quiz on TPN. No differences between groups were found in ethnic background, socioeconomic status, severity of illness, age of children, or route of TPN administration. Predisposition to anxiety was also similar between the groups. In contrast, acute situational anxiety was significantly greater in the group with no booklet than in the booklet group. Parents in the no-booklet group demonstrated less comfort in the care of their children and less knowledge about TPN than did the booklet group. Written information provided to parents decreased their anxiety and increased satisfaction with patient care more successfully than did verbal communication. Such a booklet may reduce parentally induced anxiety in the child and facilitate parent-hospital staff interactions.

Anxiety↗

Colonic interposition after esophagogastrectomy in a child with Zollinger-Ellison syndrome.

Zollinger-Ellison syndrome is a rare childhood entity that usually presents with peptic ulcer disease and is resistant to medical management. In contrast to the treatment of the disease in adults, total gastrectomy is the procedure of choice for pediatric patients. We report on a child with Zollinger-Ellison syndrome complicated by esophageal stricture in whom we performed a new operative procedure using a colonic interposition. The use of the procedure has obviated the side effects commonly associated with gastrectomy.

Child↗

Human milk and the rate of small intestinal mucosal recovery in protracted diarrhea.

STUDY OBJECTIVE: To determine whether human milk accelerates the recovery rate of injured small intestinal mucosa. DESIGN: Randomized, controlled trial. SETTING: County and nonprofit, private urban hospitals. PATIENTS: Moderately to severely malnourished infants less than 6 months of age who required parenteral nutrition for treatment of protracted diarrhea. INTERVENTIONS: Either a human milk preparation (n = 7) or sterile water (n = 9) was administered by continuous nasogastric feeding (14 mL/kg/d) over a 2-week study period while the infants received parenteral nutrition. MEASUREMENTS AND MAIN RESULTS: Small intestine perfusion studies and biopsies were performed at the beginning and end of the study. Age, duration of prior illness, severity of malnutrition, glucose and water absorption, disaccharidase activities, atrophy of villi, and nutritional intake were comparable in both groups of infants. At the end of the 2-week study, improvement toward normal sucrase activity and intraepithelial lymphocytes was found in significantly fewer infants in the milk group than in the water group. No differences were noted in glucose and water absorption or in lactase and maltase activities as a function of the milk versus water treatment. CONCLUSIONS: Human milk did not accelerate functional recovery of the small intestinal mucosa.

Clinical Trials as Topic↗

Zinc and copper balance studies in infants receiving total parenteral nutrition.

To determine the adequacy of zinc and copper supplementation for infants receiving total parenteral nutrition (TPN), we performed 24-h balance studies in infants with diarrhea and infants who had recently undergone surgery. Measurements were made at base line, 1, and 2 wk. Mean serum Zn and Cu levels of the diarrhea group remained normal and were low in the postoperative group but normalized over the study period. Mean 24-h Zn and Cu balances were positive in infants with diarrhea and negative in postoperative infants. The high Zn and Cu content in the gastrointestinal fluid loss associated with surgery may have accounted in part for this finding. Normal serum levels of Zn and Cu did not guarantee positive balance. No significant changes were found in serum albumin, alkaline phosphatase, or ceruloplasmin. The current Zn and Cu recommendations may be appropriate only for hospitalized infants who have no excessive gastrointestinal fluid losses.

Chronic Disease↗

Comparison of the D-xylose and polyethylene glycol absorption tests as indicators of mucosal damage in infants with chronic diarrhea.

The determination of serum levels of D-xylose and the urinary excretion of an orally administered mixture of low-molecular-weight polyethylene glycol were compared to assess their sensitivity to predict small-bowel mucosal damage. Eighteen infants with severe diarrhea and villus atrophy were observed. Results of the D-xylose and polyethylene glycol tests were compared with the villus-to-crypt ratios that were determined from biopsy specimens. The D-xylose test predicted accurately 12 (67%) of the 18 small-bowel biopsy results, while the polyethylene glycol test predicted 14 (78%). However, the McNemar test indicated that the two tests did not differ significantly in their ability to predict an abnormal small-bowel biopsy. We conclude that neither the D-xylose nor the polyethylene glycol test is a reliable indicator of small intestinal mucosal damage in infants with chronic diarrhea.

Atrophy↗

Single- vs double-lumen central venous catheters in pediatric oncology patients.

Double-lumen central venous catheters (CVCs) have been introduced recently for use in pediatric patients. The objective of our study was to determine if double-lumen CVC usage increased the possibility of infectious and mechanical complications compared with that of traditional single-lumen CVCs in a population at high risk for infection (oncology patients). Thirty pediatric patients (2.5 +/- 3.0 years old; mean +/- SD) who received single-lumen CVCs were compared with 31 patients (5.9 +/- 4.7 years old) who received double-lumen CVCs. The incidence of infectious complications was compared while controlling for potential confounding variables. Fifty-seven percent (17/30) of patients in the single-lumen group experienced bacteremia or cellulitis that required removal of six catheters compared with a rate of 52% (16/31) and nine catheter removals in the double-lumen group. Fewer manipulations occurred in the single-lumen group compared with the double-lumen group, but the incidence of mechanical complications tended to be greater. When managed carefully, double-lumen CVCs were not associated with a greater risk of infection than single-lumen CVCs.

Bacterial Infections↗

Effects of changes in infusion rate versus glucose concentration on absorption in infant miniature pig small intestine.

The effect of changes in the rate of infusion versus glucose concentration on glucose, water, and sodium absorption was studied in 20 infant miniature pigs using the single-pass small intestinal perfusion technique. During infusions of glucose loads of up to 75.0 mumol/min, glucose absorption increased similarly whether rate of infusion or glucose concentration was increased. Beyond 75.0 mumol/min, glucose absorption was not altered by changes in infusion rate, but was enhanced by increases in glucose concentration (slope of rate vs. concentration, p less than 0.0001). Net water and sodium absorption were similar in the two groups except for a decrease at the highest glucose concentration (rate vs. concentration at 187.5 mumol/min, p less than 0.05). A glucose concentration of 112.5 mM resulted in maximal glucose, water, and sodium absorption.

Animals↗

Effect of different total parenteral nutrition fuel mixes on small intestinal growth and differentiation in the infant miniature pig.

Insulin has been proposed as an important factor in the regulation of growth and differentiation of the small intestine. In the newborn miniature pig, we induced significant physiologic increases in serum insulin and the insulin/glucagon ratio without altering serum glucose, beta-hydroxybutyrate, glucagon, cortisol, T3, and T4 using glucose-based total parenteral nutrition (TPN) in one group (group G) compared with a combination of glucose and fat in another group (group G/F). Control animals were sham-operated and fed a pelleted diet (group OC). Duodenal villus surface area and mucosal height were significantly greater in group G/F compared with group G. No other differences between the TPN groups were found in small intestinal growth, mucosal protein, deoxyribonucleic acid and ribonucleic acid content, and disaccharidase activities. As anticipated, group OC demonstrated increased intestinal length, weight, and villous surface area compared with the TPN groups. Ileal sucrase and jejunal and ileal maltase activities were greater in the TPN groups compared with those in group OC. Physiologic changes in serum insulin and the insulin/glucagon ratio induced by the TPN fuel mix do not appear to have altered small intestinal growth, composition, and differentiation in the healthy small intestine.

Age Factors↗

The miniature pig as an animal model for the study of intestinal enzyme development.

Studies of intestinal enzyme development and regulation relevant to the human infant require an animal model with a rate of maturation similar to that of the human infant. Hanford miniature pigs were weaned at 3 days of age to a standard swine weaning formula. At 1, 2, 3, 4, 5, and 6 wk of age, duodenal jejunal, and ileal segments were analyzed for protein content and lactase, sucrase, maltase, glucoamylase, and acid beta-galactosidase activities. Protein content of the small intestine changed significantly with age only in the ileum (p less than 0.05). Lactase activity fell significantly with age in all segments of the small intestine (p less than 0.001); activity was highest in the jejunum. Sucrase and maltase activities were present in all segments of the small intestine at 1 wk of age. Sucrase increased significantly (2-fold, p less than 0.02) with age only in the ileum and maltase increased significantly with age in the jejunum (by 50%, p less than 0.05) and the ileum (3-fold, p less than 0.001). Activities were highest in the jejunum. Glucoamylase activity was present at 1 wk of age and showed a small but significant increase with age only in the duodenum (p less than 0.005). Acid beta-galactosidase activity demonstrated small but significant decreases with age in all small intestinal segments. Glucoamylase and acid beta-galactosidase activities were similar in all segments. In the 6-wk-old pigs, activities of all the enzymes tested were similar to those found in young human infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A totally implanted venous access system used in pediatric patients with cancer.

A safe and effective method of venous access is important in the care and treatment of patients with malignancies. A recently available totally implantable venous access system offers advantages over traditional central vein catheters (Broviac and Hickman, Houston). We report our experience with the implanted venous access system used in 31 pediatric patients with malignancies. The mean age of the patients was 7 years (range, 6 months to 17 years), and the mean indwelling time of the catheters was 232 days (range, 14 to 607 days; total patient days, 7,198). The catheters were used to administer chemotherapy, drugs, blood products, and parenteral nutrition, as well as to draw blood. Clotting occurred in the catheters on four occasions, requiring removal of two catheters. Fever occurred in eight patients; one developed a local infection at the site of implantation and four developed bacteremia. Our use of the implanted venous access system in children resulted in a lower rate of infection compared with that when the traditional Broviac and Hickman catheters were used, and simplified patient management.

Adolescent↗

Pulmonary vascular lipid deposition after administration of intravenous fat to infants.

The incidence of pulmonary vascular lipid deposits in infants who did or did not receive intravenous lipid emulsion was determined through a review of the pulmonary histopathology and clinical course of 39 neonates who died during a two-year period. The relationship between pulmonary vascular lipid deposits and the duration and amount of administered intravenous fat emulsion was assessed. In addition, the effect of monitored serum triglyceride levels on the development of pulmonary vascular lipid deposits was evaluated. The incidence of pulmonary vascular lipid deposits was greater in the group that received intravenous fat emulsion (P less than .02). Both the amount (grams per kilogram per day) and duration (days) of intravenous fat emulsion infusion were correlated positively with severity (P less than .05) in infants who had pulmonary vascular lipid deposits. No relationship was seen between peak serum triglyceride levels, the frequency of elevated triglycerides, and pulmonary vascular lipid deposits. Although administered fat emulsion was a risk factor for the development of pulmonary vascular deposits, two of 13 infants who had not received intravenous fat emulsion had such deposits.

Fat Emulsions, Intravenous↗

The effects of different total parenteral nutrition fuel mixes on skeletal muscle composition of infant miniature pigs.

Two groups of 10-day-old miniature pigs were maintained on isocaloric and isonitrogenous total parenteral nutrition (TPN) regimens for nine days. One group received nonprotein energy as glucose, whereas the second group received a mixture of fat and glucose. The administration of the amino acid/glucose fuel mix resulted in higher plasma insulin but lower glucagon concentrations compared to the amino acid/glucose/fat mix. Differences also were observed in the composition of skeletal muscle, which contained higher concentrations of alkali-soluble (AS) proteins (chiefly cellular protein) and DNA, when glucose was the only source of nonprotein energy. Intracellular sodium and water content and nonalkali-soluble proteins (largely extracellular proteins) were lower in the skeletal muscle of the amino acid/glucose group than in that of the group receiving the fat regimen. No differences in RNA concentration, RNA/AS protein, or AS protein/DNA ratios were observed. These data suggest that conditions of high insulin production in the postnatal growth period favored increased DNA replication and accretion of AS protein. The differences in water and electrolyte composition indicate that the rate of chemical maturation of skeletal muscle was slower in the piglets receiving amino acids/glucose/fat than in those on the glucose regimen. This study has demonstrated that the source of nonprotein energy can influence skeletal muscle maturation in the postnatal period.

Animals↗

Comparison of percutaneous and surgical placement of central venous catheters in neonates.

A comparison of randomized placement of percutaneous and surgical central venous catheters was made in 53 low birthweight infants. Twenty-eight infants received percutaneous central venous lines, and 21 infants underwent surgical placement of catheters. The incidence of complications did not differ between the groups. The mean length of time the catheter was in place also was similar. Percutaneous placement of central venous catheters appears to compare favorably with the traditional surgical approach.

Catheterization↗