Benjamin Torun

Epidemiology of altered intestinal permeability to lactulose and mannitol in Guatemalan infants

BACKGROUND Subclinical alterations of small intestinal function have been reported frequently in tropical countries. Studies of small intestinal permeability to lactulose and mannitol were therefore completed in Guatemalan infants from a low-income, periurban community to assess the prevalence of altered intestinal function and the factors associated with this condition. METHODS Two hundred studies were successfully completed in 158 infants who had been free of diarrhea for at least 1 week before the day of study. Urinary concentrations of lactulose and mannitol during the 5-hour period after ingestion of 400 mg/kg body weight of lactulose and 100 mg/kg body weight of mannitol were measured by gas-liquid chromatography and compared by age group, feeding practices, anthropometric indexes, and serum iron and zinc concentrations. RESULTS The overall prevalence of altered intestinal permeability (defined as a ratio of urinary recovery of lactulose to mannitol [L/M] > or =0.07) was 30%. The urinary L/M recovery ratio was positively associated with age; low weight for age; and, in infants less than 6 months of age, non-breast-feeding. Children with serum iron concentrations less than 7.16 microM/l (40 [microg/dl) had higher median L/M ratios (L/M = 0.068; 95% confidence interval [CI], 0.054, 0.085) than those with iron levels higher than this cutoff (L/M = 0.052; CI = 0.046, 0.058; p = 0.038). The median urinary L/M recovery ratio in 10 currently asymptomatic infants who had diarrhea during the week before testing (0.087; CI = 0.49, 0.154) was higher than that in children who had been free from diarrhea for at least 1 week (0.052; CI = 0.048, 0.056; p = 0.01). CONCLUSION Age, feeding practices, low weight-for-age, low serum iron concentration, and recent diarrhea were all associated with altered intestinal function in this group of Guatemalan infants.

Energy costs of activities of preschool children

Abstract Energy expenditures were measured in 47 children, 17–45 months old, under basal metabolic conditions (mean±SD: 38±5 cal/kg/min) and while resting supine (44±5), sitting (47±6), walking leisurely on level ground (71±8), walking rapidly at a grade (98±11), climbing and descending ramps (87±7), climbing stairs (94±8) and riding on a tricycle (73±5). These values are greater than those reported in adults per unit of body weight. Consequently, the energy costs of activities determined in adults should not be applied to preschool children. Our results support the following recommendations to calculate the energy expanditure of preschool children in time-and-motion studies: a)use the energy costs of activities that have been measured in children, whenever available; and b) use 1.2, 2 and 2.5 times the childs basal metabolism, respectively, for sedentary, light and moderately heavy activities, or use the values determined in adults per unit of body weight multiplied by 2 for sedentary activities, and by 1.2 for all other activities.

Immature circulating lymphocytes in severely malnourished Guatemalan children.

The percentage of peripheral blood lymphocytes forming rosettes with sheep erythrocytes (E-rosettes) was determined in 33 severely malnourished Guatemalan children, and in two groups of clinically well but mildly growth retarded children from the same environment. Mean E-rosettes in the acutely ill patients was lower than the value observed in the mildly malnourished children, although there was considerable overlap between groups. These data differ from previously published studies of severely malnourished children from other parts of the world in that not all patients had decreased values for E-rosettes, in contrast to the uniform depression reported by others. As all patients were clinically similar, the results suggest that there may be specific nutrient defects associated with protein-energy malnutrition that particularly affect immune function. In addition, in vitro incubation of lymphocytes from the acutely malnourished children with the thymic factor, thymosin fraction 5, increased the percentage of E-rosettes in a dose-dependent fashion. These data suggest that immature, thymosin-responsive T cells are present in circulation. It is possible that in vivo thymosin administration may be beneficial for malnourished individuals.

3. Practical approaches towards dietary management of acute diarrhoea in developing communities

Diarrhoeal diseases are a major cause of malnutrition, partly due to poor dietary practices. Misconceptions among the general population and medical personnel lead to withholding of food or avoiding the use of nutritious, locally available and affordable foods. Breast-feeding should not be interrupted during diarrhoea. Many recent studies have shown that when cows milk is used, full-strength milk should be fed throughout the disease and in convalescence. The concept of diluting milk with water should be altogether avoided. If necessary, full-strength milk should be mixed with equal amounts of other foods. Other recent studies have shown that several diets based on local staples are excellent choices for the dietary management of diarrhoea. An all-vegetable diet commonly eaten in Guatemala produced a sharp decrease in the duration of acute diarrhoea (median duration after feeding began: 1.8 d) and its macronutrients were reasonably well absorbed. Practical recommendations are given, including nutritional, physiological, cultural and economic considerations.

Absorption of Selenium From Milk Protein and Isolated Soy Protein Formulas in Preschool Children: Studies Using Stable Isotope Tracer 74se

Summary Absorption of selenium as the stable isotopic tracer [74Se]selenite was measured in four preschool children who were receiving liquid formula diets based on casein, isolated soy protein, and a 50:50 combination of the two protein sources. The children were in continuous ambulatory balance studies within the Clinical Research Center during three consecutive 11-day collection periods. The enrichment of the 74Se/76Se ratio in feces was measured by radiochemical neutron activation analysis, with fractional absorption estimated therefrom. Mean fractional absorption of selenium (± SD) from the formulas based on milk, isolated soy protein, and milk-soy were 64.2 ± 14.6, 73.4 ± 19.0, and 45.0 ± 10.9%, respectively, with the combined formula having a significantly lower intestinal uptake for added selenite than the casein formula. Stable isotopes of selenium are safe and potentially useful tools for examining its bioavailability in the diets of young children.

Oral gentamicin is not effective treatment for persistent diarrhea

We conducted a randomized, double‐blind, placebo controlled clinical trial of oral gentamicin (10 milligrams/kilogram body weight/day for five days) in treatment of unselected cases of persistent diarrhea (duration 14‐18 days at initiation of treatment) among 3‐36‐month‐old children in a rural Guatemalan community. Following random assignment of each child to a treatment group, the appropriate dose of gentamicin or placebo was administered to the child three times daily by a study nurse; this nurse also identified the presence or absence of diarrhea on each day of treatment and for the next two days. Cure was defined as cessation of diarrhea during the five‐day treatment period, sustained through at least the two days after completion of treatment. Among 92 evaluable cases who entered the clinical trial, there was essentially no difference in cure rate between gentamicin and placebo treatment groups (42% versus 43%). Enteroadherent strains of Escherichia coli were identified in 46% of children tested in this trial; no significant difference existed between treatment groups in frequency of isolation of this or any other enteropathogen. Among 40 children having successful duodenal cultures immediately prior to beginning treatment, 104 aerobic organisms per milliliter of fluid were identified in 12 (30%); treatment groups did not differ substantially with respect to proportion of children identified with this level of duodenal microbial colonization. Failure of gentamicin treatment did not appear to be explained by emergence of resistance, although a small number of resistant enteropathogens were identified near the end of the study. We conclude that in this population and in the dose used, oral gentamicin has no value in the treatment of persistent diarrhea.

Diarrhea and Nutrient Requirements

The high prevalence rates, particularly among young children in most developing countries, make the influence of diarrhea on nutritional requirements of major concern. The multiple mechanisms whereby diarrhea of infectious origin can affect dietary requirements for calories and protein are listed in Table I. Estimation of the consequences for nutritional requirements is complicated by large quantitative and qualitative variations in the disease burden among different population and age groups. The effects depend on the type of diarrhea as well as on its frequency, severity, and duration. Moreover, available quantitative data are extremely limited. Those available under each of the categories indicated are examined separately in the text that follows.

Absorption of carbon 13-labeled rice in milk by infants during acute gastroenteritis

To determine whether rice cereal could be used to complement a cow milk-based diet in the nutritional management of infants with acute diarrhea, we assessed its digestion and absorption in eight affected male infants, 69 to 131 days of age. They received cow milk formula with 5.4% lactose (diluted 1:1 with water and precooked rice cereal) 5 to 22 hours after admission and rehydration. The first feeding consisted of milk diluted with carbon 13-enriched rice cereal. A 48-hour fecal collection and balance study was performed. Rice cereal was reasonably well absorbed (84.0% to 95.8%) by seven of the eight infants. The study was repeated in seven of the infants after they had recovered. Our results indicated that rice cereal is well absorbed by young infants with acute diarrhea and that it is an adequate nutrient supplement for this patient population.

Fecal reducing substances and breath hydrogen excretion as indicators of carbohydrate malabsorption.

Summary: Data from serial determinations of fecal volume, characteristics, pH, and reducing substances, and postprandial breath hydrogen (H2) concentrations in severely malnourished children receiving milk‐based recovery diets were used to evaluate the quality of the correspondence among diagnostic indices for carbohydrate malabsorption, with specific emphasis on the comparison of breath H2 excretion and fecal reducing substances. Only postprandial breath H2 results for subjects with a proven capacity to mount an H2 response to the nonabsorbable disaccharide, lactulose, were included. There was a poor correlation between the diagnostic indication provided by the breath test and fecal reducing sugars. Biological considerations about the metabolism of unabsorbed carbohydrates in relation to colonic transit time and fecal flora may explain the poor degree of correlation. The two indices should not be considered interchangeable, but should be used selectively in accordance with the clinical situation.

Effects of nutritional recuperation on E-rosetting lymphocytes and in vitro response to thymosin in malnourished children.

The percentage of peripheral blood lymphocytes forming rosettes with sheep erythrocytes (E-rosettes) was determined at admission to the INCAP Clinical Center in eight acutely malnourished Guatemalan children, and again after 14 and 28–30 days of nutritional therapy. While the mean percentage of E-rosettes increased during therapy, the change (from 35.6 ± 10% to 43.3 ± 19%) did not reach statistical significance because of the variable response of different subjects. At each time period, however, in vitro incubation with the thymic factor, thymosin fraction 5, significantly increased the percentage of E-rosetting lymphocytes. The presence of thymosin responsive cells in circulation after 1 month of optimal nutritional support indicates that immature T-lymphocytes can persist in circulation in patients with severe malnutrition, even after clinical improvement. Thus, neither the percentage of E-rosettes in peripheral blood nor their response to in vitro incubation with thymosin correlated with anthropometric measures of nutritional status in individual patients. This suggests that other nutritional or nonnutritional factors may be important modulating influences on T-lymphocytes, and that prospective studies with thymic factor administration are warranted.