Therapy of acute diarrhoea in children: re-evaluation.
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Biomedical subjects
Publications and source records attributed to E Lebenthal.
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UNLABELLED: Acetylated distarch phosphate (ADiSP) is a modified starch used in some baby foods. The bioavailability of ADiSP and a native (unmodified) starch was evaluated in 20 normal infants and 21 toddlers aged 8-24 mo with chronic non-specific diarrhea. Formulae contained 8% native or 8% modified waxy maize starch. No infant or toddler consuming Formula N (native starch) had elevated peak breath hydrogen levels (20 ppm or greater), stools clinically positive for reducing substances (0.75% or greater) or loose stools. Fourteen infants received formula M (modified starch): 2 had elevated breath hydrogen, 1 had positive stools and another had loose stools. Of the 21 toddlers fed formula M, 2 had elevated breath hydrogen, but none had positive stools or loose stools. Formula NS (native starch with 2% sorbitol) had little effect on breath hydrogen in the infants but significantly increased it in the toddlers. Formula NS produced loose stools in 2 toddlers but no clinically positive stools in any infant or toddler. Formula MS (modified starch with 2% sorbitol) elevated breath hydrogen in 3 infants and 8 toddlers, and produced positive stools in 2 infants and 2 toddlers, and loose stools in 4 infants and 7 toddlers. Formula MSF (modified starch with 2% sorbitol and 5% fructose) elevated breath hydrogen in 7 infants and 10 toddlers, positive stools in 7 infants and 6 toddlers, and loose stools or diarrhea in 7 infants and 11 toddlers. CONCLUSION: ADiSP modified starch can increase breath hydrogen and produce loose stools. Sorbitol and fructose aggravate the malabsorption, in some cases leading to frank diarrhea.
Modified food starches were developed as a stabilizer, suspending the food particles and providing a desirable consistency, texture, and storage ability. They are used primarily in strained and junior foods and to a minor extent in infant formulas. This review discusses modified food starches because of four principal concerns. The first relates to the bioavailability of the starch itself. The second is the potential that indigestible starch may have for producing diarrheal symptoms, malabsorption, and changes in gastrointestinal flora. The third is the possibility that modified food starches might be implicated in gastrointestinal disease like Crohn's ileocolitis. The fourth is the toxicological effect of the chemicals used to modify the starch and their possible mutagenic and carcinogenic properties.
Malnutrition is known to have adverse effects on the physiology and morphology of the liver. The aim of this investigation was to examine the effect of protein restriction on the content of plasma membrane proteins residing in the sinusoidal and bile canalicular domains of rat liver. Post-weanling rats maintained on low protein isocaloric diets showed marked growth retardation concomitant with reduced liver protein concentration compared to control animals. The content of leucine aminopeptidase, a bile canalicular enzyme, and asialoglycoprotein receptor, a sinusoidal receptor, in livers of protein-restricted rats was 66% and 50%, respectively, of control livers. In contrast, the relative concentrations of dipeptidyl peptidase IV and a cell adhesion molecule (GP 110), both canalicular proteins, were 160% and 121%, respectively, in rat livers upon protein restriction. After a 4-week rehabilitation period, the concentrations of all canalicular membrane proteins were similar to those in control livers, while the sinusoidal receptor was only 68% of control values. Protein restriction was found to adversely affect the concentrations of protein constituents, but not their localization in the hepatocyte plasma membrane. In general, altered concentrations of hepatocyte membrane proteins were reversed on the administration of a normal protein diet.
The main congenital anomalies of the exocrine pancreas are reviewed, and several generalized and isolated hereditary pancreatic diseases are discussed. In contrast with adults, the most frequent causes of acute pancreatitis are viral infection, drug induction, and trauma. The dissimilarities between pediatric and acute and chronic pancreatitis are emphasized.
Diarrhea is one of the major causes of infant morbidity and mortality worldwide. Major advances in understanding the pathophysiology of chronic diarrhea and malabsorption have taken place during the past three decades. Analysis of absorptive and secretory functions of the intestine has provided some insight into the possible causes of diarrhea. This article summarizes some of the specific causes of malabsorptive diarrhea in infancy and childhood, with emphasis on pathophysiology and approaches to therapy.
OBJECTIVE: The purpose of this study was to experimentally develop and clinically evaluate the safety and potential usefulness of a rice-based, short glucose polymer oral rehydration solution (ORS), Amylyte, in the treatment of acute diarrhea. Amylyte has a similar osmolality but a higher caloric density than the WHO ORS. METHODS: Different amounts of rice were cooked in 500 ml of water containing salts (1.5 g NaCl, 600 mg KCl, and 150 mg CaCl2) with varying amounts of thermophilic amylase (252,500 modified Wohlgemuth units). Amylase (25 mg) thinned the gluey rice water when 100 g of rice was cooked in 500 ml of water for 10 minutes. The volume of the resultant supernatant (Amylyte) was approximately 250 ml. A two-part, clinical case study was performed. In study 1, 12 children with diarrhea and mild dehydration were studied to determine the safety of Amylyte. In study 2, Amylyte and the WHO ORS were given to 24 and 31 male children with acute diarrhea and moderate to severe dehydration, respectively. RESULTS: 92-96% of the rice amylose and amylopectin were converted to short polymers of glucose (3-9 molecules of glucose). The osmolality of 7,994 packages used to make the Amylyte solution ranged between 277-340 mOsm/kg. The mean electrolyte composition was Na+ = 68 mEq/L, K+ = 20 mEq/L, Cl = 73 mEq/L, the caloric density 425 kcal/L and rice proteins 0.7 g/L. In study 1, 12 children with diarrhea and mild dehydration were rehydrated successfully with Amylyte ORS and the diarrhea ceased within 48 hours. None developed clinical features of carbohydrate intolerance. In study 2, an open-label clinical case study, children with acute diarrhea given Amylyte ORS had significantly less stool output than children given the WHO ORS. CONCLUSIONS: Amylyte ORS has the advantages of a higher caloric density than the WHO ORS and shares a simple preparation of appropriate osmolality and electrolyte composition. It can safely and effectively rehydrate children with acute diarrhea and dehydration.
In this study, we have compared the effects of the World Health Organization oral rehydration solution (WHO ORS) and an ORS containing short polymers of glucose (Amylyte ORS) at a high caloric density (five times) and comparable osmolality, on stool output, duration of diarrhea, weight gain and fluid and electrolyte balance, in randomized, open-labeled, controlled clinical trials in five centers. A total of 198 male children (4 months to 10 years) with acute diarrhea ( <72 h after onset) were assigned by random allocation to either WHO ORS or Amylyte ORS at five centers in Asia. Children were stratified according to grade of dehydration (mild, moderate or severe) and the initial purging rates during the first 6 h (low ( < 2 ml/kg/h), moderate (2-5 ml/kg/h) and high ( > 5 ml/kg/h) purgers). The clinical characteristics of the children in the two treatment groups were comparable. Amylyte ORS reduced stool volumes significantly in children with severe dehydration (285.4 +/- 74.2 versus 75.5 +/- 20.0 ml/kg; p < 0.05) and in children with a high initial purging rate (200.3 +/- 42.8 versus 130.5 +/- 9.1 ml/kg; p < 0.05). This was accompanied by a significant (276.4 +/- 14.6 versus 227.6 +/- 11.8 ml/kg; p < 0.01) reduction in ORS requirements in the Amylyte ORS treated group, the effect being greatest in children with severe dehydration (491.5 +/- 108.5 versus 155.7 +/- 27.3 ml/kg; p < 0.01) or high initial purging rates (394.2 +/- 66.2 versus 316.8 +/- 34.8 ml/kg; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To compare the efficacy of an oral rehydration solution (ORS) containing short polymers of glucose derived from rice (Amylyte-ORS) and five times the caloric density of current ORS to the standard glucose-ORS (World Health Organization [WHO] = ORS) in the treatment of acute diarrhea in children. METHODS: The rice ORS (Amylyte-ORS) was obtained by adding thermophilic amylase (252,500 MW units) and salts (1.5 g NaCl, 600 mg KCl, and 150 mg CaCl2) to 100 g rice and boiling for 10 minutes in 500 mL water. This yields 250 mL Amylyte-ORS, which contains 92% to 96% short-chain glucose polymers, three to nine molecules in length, and provides 425 kcal/L, compared to 80 kcal/L for the WHO-ORS. One hundred forty-four male children, 4 months to 3 years of age, presenting with acute diarrhea and mild, moderate, or severe dehydration, were assigned by random allocation to receive either WHO-ORS or Amylyte-ORS. Data from 127 children were analyzed (57 received the WHO-ORS and 70 the Amylyte-ORS). Two children given Amylyte-ORS and 15 given the WHO-ORS were not included in the analysis because of improperly collected data or lost urine or fecal specimens. None were given antibiotics during the study. Free water and feeding were allowed after the children were rehydrated. RESULTS: The clinical characteristics of the children in the two treatment groups were comparable. Five children who received the WHO-ORS and three children given Amylyte-ORS were treatment failures. Amylyte-ORS reduced diarrhea duration by 15% (41.4 +/- 2.5 vs 34.7 +/- 1.8 hours; P < .03) compared to the WHO-ORS, regardless of the severity of dehydration. In the Amylyte-treated group, ORS requirements were significantly less (234 +/- 15.2 vs 295 +/- 17.6 mL/kg; P < .01) and weight gain was significantly more (367.7 +/- 45.1 vs 199.2 +/- 38.2 g; P < .01) than in those given the WHO-ORS. The net intestinal fluid balance and total body fluid balance were similar in the two groups. CONCLUSIONS: Amylyte-ORS effectively rehydrates children with acute diarrhea, reduces diarrhea duration, decreases ORS requirements, and improves weight gain compared to the WHO-ORS.
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We investigated soluble interleukin-2 receptor (sIL-2R), soluble CD8 (sCD8) and soluble intercellular adhesion molecule-1 (sICAM-1) levels in the sera of patients with non-malignant diseases believed to have an autoimmune or immunosuppressive component, Crohn's disease, celiac disease, and systemic lupus erythematosus (SLE). Sera of healthy blood donors served as controls. All samples were analyzed by commercial ELISA kits for sIL-2R, sCD8, and sICAM-1. Our control level of sIL-2R (x +/- S.D) was 395 +/- 84 units/ml, sCD8 (x +/- S.D.) 263 +/- 90 units/ml and sICAM-1 405 +/- 118 ng/ml. The 8 Crohn's disease patients had an average sIL-2R level of 920 +/- 329 units/ml, and an average sCD8 level of 355 +/- 91 units/ml, and sICAM-1 952 +/- 329 ng/ml. The four celiac disease patients had an average sIL-2R concentration of 1740 +/- 1071 units/ml, a sCD8 level of 460 +/- 320 units/ml and sICAM-1 1221 +/- 720 ng/ml. The three systemic lupus erythematosus patients had an average sIL-2R of 1023 +/- 123 units/ml, and an average sCD8 of 395 +/- 69 units/ml, and sICAM-1 1153 +/- 219 ng/ml. Thus, sIL-2R and sICAM-1 were significantly elevated over control levels in all 3 patient groups, and sCD8 was mildly elevated. These results indicate enhanced immune activation which may be a common feature in the onset and/or progression of these idiopathic illnesses.
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This study was undertaken to assess the short-term effects of EGF on sodium and glucose uptake, glucose metabolism and Na+/K(+)-ATPase activity in isolated enterocytes of rats. Jejunal cells exposed to EGF had a significantly greater total uptake of sodium compared to controls after 6 min. Kinetic analysis of glucose transport across BBMV's demonstrated similar Km values but a significant increase of the Vmax in vesicles prepared from cells first exposed to EGF as compared to controls. EGF was also associated with a significant increase in glucose metabolism of jejunal enterocytes after 15 min. The activity of Na+/K(+)-ATPase increased in jejunal enterocytes exposed to EGF. The increase in Na+/K(+)-ATPase activity of the cells following EGF exposure was not accompanied by an increase in immunodetectable total or assembled Na+/K(+)-ATPase protein. EGF's effect on enzyme activity was abolished by removing NaCl from the incubation solution, and by preincubating the enterocytes with phlorizin prior to addition of EGF. Preincubation with amiloride did not inhibit the effect of EGF on Na+/K(+)-ATPase. The results confirm that EGF promotes uptake of both sodium and glucose by the jejunal mucosal cells, and suggest the effect of EGF on glucose and sodium is mediated through the brush-border membrane glucose-sodium transporter. The increase in Na+/K(+)-ATPase activity that occurs with EGF appears to be secondary to a rise in intracellular Na+ concentration. The short-term effects of EGF on glucose and sodium transport by the small intestine may have potential therapeutic implications.
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To determine the prevalence of short polymers of glucose and starch malabsorption caused by small intestinal glucoamylase deficiency in children with chronic diarrhea, we studied small bowel biopsy specimens from 511 children (aged 1 month to 9 years) with chronic diarrhea evaluated at 54 medical centers. Glucoamylase and disaccharidase (lactase, sucrase, maltase, and palatinase) enzyme assays were performed. Of the 511 children, 15 had glucoamylase deficiency. Six who had significant small intestinal mucosal injury and disaccharidase deficiencies were defined as having secondary glucoamylase deficiency; the other nine patients with normal mucosal morphologic features were defined as having primary glucoamylase deficiency. Secretin tests showed normal pancreatic amylase values for age in all seven children tested. Four of them had abnormal findings on tolerance tests for starch and short polymers of glucose (rise in blood glucose concentration: < 20 mg/dl) and reducing substances in stools, and three of these four had symptoms of intolerance (abdominal distention, flatulence, and diarrhea). All seven patients responded to a starch elimination diet. After reintroduction of a starch diet, diarrhea recurred in four patients; this was alleviated 48 hours after reelimination of starch. We conclude that intestinal glucoamylase deficiency is present in some patients with chronic diarrhea.
This study aims to determine the effect of glucose and glucose polymers (GP) from corn in oral rehydration solutions (ORS) on disaccharidases and morphometric measurements in small intestinal mucosa of rats. ORS containing standard composition of salts as in WHO ORS and 2, 5, or 10 per cent glucose or GP [initial glucose polymers, long chain (> 9 molecules) and short chain (2-9 molecules) glucose polymers] from corn were infused into the duodenum of 72 Sprague-Dawley rats (250-350 g). Six rats were sham operated as controls. The levels of lactase, sucrase, maltase, palatinase, and glucoamylase enzymes were higher in rats infused with ORS-containing glucose or GP than control rats. Villus height, villus width, and crypt height in corresponding segments of duodenum, jejunum, and ileum were not significantly different between rats perfused with ORS containing glucose polymers from corn and those with ORS containing glucose. ORS containing GP from corn have no adverse effects on small intestinal enzymes and morphometric measurements.
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Pancreatic enzyme extracts have been used for several decades to decrease maldigestion of macro- and micronutrients due to pancreatic insufficiency and to alleviate various abdominal symptoms, including the pain of alcohol-induced chronic pancreatitis and distal intestinal obstruction. Decreasing nutrient maldigestion and malabsorption in pancreatic insufficiency is of additional critical importance because improvement in nutritional status reduces morbidity and mortality. For example, pancreatic sufficient patients with cystic fibrosis (CF) demonstrate a slower decline in pulmonary function. In spite of the recognized importance of pancreatic enzymes, several problems exist with current preparations, and as newer enzyme preparations are marketed, proper evaluation becomes critical. There is a clear need to optimize the constituents of enzyme preparations, improve manufacturing processes, and find better sources of enzymes. Other issues that need addressing include standardization of the ratios of enzymes (lipase, amylase, protease) in these products; the stability of the enzymes at room temperature; the shelf life of the finished product; whether there are significant batch-to-batch differences; and the need for a USP reference standard.