Andrée Weber

Chronic intermittent elemental diet improves growth failure in children with Crohn's disease

Growth failure often complicates Crohns disease in pediatric patients and is principally due to inadequate caloric intake. To assess whether intermittent courses of an elemental diet could reestablish growth, 8 children (aged 9.8-14.2 yr) with Crohns disease and growth failure entered into a prospective trial. Each patient was studied during an observation year on standard therapy, then for an experimental year during which they received enteral elemental diet 1 out of 4 mo. An age- and disease-matched control group of 4 patients was treated by conventional medical therapy during both years. Elemental diet therapy was administered nocturnally, at home, by continuous nasogastric infusion and increased the daily caloric intake by 25% (p less than 0.01). Anthropometric measurements demonstrated significant height and weight gains in the elemental diet group vs. controls (p less than 0.01). Crohns disease activity index and prednisone intake decreased significantly in patients receiving elemental diet therapy when compared with themselves and with controls on conventional medical therapy (p less than 0.05). In contrast, the rate of pubertal development was similar in both groups irrespective of the treatment modality. This study demonstrates that chronic intermittent elemental diet effectively reverses growth arrest, while decreasing prednisone requirements and Crohns disease activity index in pediatric Crohns disease patients prior to puberty.

One-hour blood-xylose test in diagnosis of cow's milk protein intolerance.

In this prospective study, 18 consecutive children suspected of cows milk protein intolerance (C.M.P.I.) on clinical grounds were investigated before and after challenge with cows milk. One-hour blood-xylose, serum-IgE, eosinophil count, serum-complement (C3) and a jejunal biopsy specimen for histology and disaccharidase activity were obtained from all patients before challenge. Serum-complement was measured again 24 h after the beginning of the challenge and the first three tests were repeated on the fifth day. A second jejunal biopsy was obtained in 9 of the first 10 children. 15 of the 18 children were considered to have C.M.P.I. The one-hour blood-xylose test emerged as a simple and valuable test in the diagnosis of C.M.P.I. A significant drop (51--81%) in the one-hour blood-xylose level was observed in all 15 patients. In all patients but one it dropped below 25 mg/dl. Mean value (+/- S.D.) for the group was 47.5 +/- 11.1 mg/dl before and 17.2 +/- 4.2 mg/dl after cows milk ingestion.

Neurologic Crises in Hereditary Tyrosinemia

Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. The disease is known to cause acute and chronic liver failure, renal Fanconis syndrome, and hepatocellular carcinoma. Neurologic manifestations have been reported but not emphasized as a common problem. In this paper, we describe neurologic crises that occurred among children identified as having tyrosinemia on neonatal screening since 1970. Of the 48 children with tyrosinemia, 20 (42 percent) had neurologic crises that began at a mean age of one year and led to 104 hospital admissions. These abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (in 75 percent), vomiting or paralytic ileus (69 percent), muscle weakness (29 percent), and self-mutilation (8 percent). Eight children required mechanical ventilation because of paralysis, and 14 of the 20 children have died. Between crises, most survivors regained normal function. We found no reliable biochemical marker for the crises (those we evaluated included blood levels of tyrosine, succinylacetone, and hepatic aminotransferases). Urinary excretion of delta-aminolevulinic acid, a neurotoxic intermediate of porphyrin biosynthesis, was elevated during crises but also during the asymptomatic periods. Electrophysiologic studies in seven patients and neuromuscular biopsies in three patients showed axonal degeneration and secondary demyelination. We conclude that episodes of acute, severe peripheral neuropathy are common in hereditary tyrosinemia and resemble the crises of the neuropathic porphyrias.

Malabsorption of Bile Acids in Children with Cystic Fibrosis

Abstract Quantitative fecal bile acids (in milligrams per 24 hours per square meter of body-surface area) in 24 children with untreated pancreatic insufficiency secondary to cystic fibrosis were increased (743.2 ± 55.3 — mean ± S.E.) whereas those in 12 cases of celiac disease and in seven with chronic nonspecific diarrhea did not differ from values in 18 controls (110.0 ± 11.0). Bile acid loss in cystic fibrosis was comparable to that of six infants after ileal resection (957.7 ± 195.1). A large increase (p<0.01) in fecal bile acids occurred when pancreatic enzyme therapy was withdrawn in five patients with cystic fibrosis. These data and the good correlation (r = 0.78) found in cystic fibrosis and not in celiac disease between fecal fat and bile acids suggest that unhydrolyzed fat or other products of maldigestion may interfere with bile acid absorption. The daily fecal bile acid sequestration of 1.9 g and 3.7 g found in two cases of cystic fibrosis studied during pancreatic supplementation indicates th...

Hirschsprung's Disease in a Family with Multiple Endocrine Neoplasia Type 2

SummaryGastrointestinal symptoms are known to occur in association with multiple endocrine neoplasia (MEN) type 2. Patients with the variant 2b are at special risk and show diffuse intestinal ganglioneuromatosis. Megacolon is frequently an early X-ray finding and is associated with hyperplastic gang

Abnormal biliary lipid composition in cystic fibrosis. Effect of pancreatic enzymes.

Because of the increased incidence of gallstones in cystic fibrosis we compared biliary lipid composition in 26 patients with cystic fibrosis, seven children with cholelithiasis but no cystic-fibrosis and 13 controls. Eighteen of the cystic fibrosis group had cholecystograms, and only one had gallstones. In 14 patients with cystic fibrosis who had stopped taking pancreatic enzymes for one week molar percentage of lipid composition accounted for by cholesterol (mean +/- S.E., 16.3 +/- 2.9) and saturation index (2.0 +/- 0.3) were comparable to values of the cholelithiasis group and higher (P less than 0.01) than those of controls. In 12 patients with cystic fibrosis taking pancreatic enzymes, molar percentage of cholesterol (8.6 +/- 1.7) and saturation index (1.0 +/- 0.1) did not differ from those of controls; in cystic fibrosis there was a preponderance of cholic over chenodeoxycholic acid both off (1.7 +/- 0.2) and on (1.9 +/- 0.3) therapy as compared to the cholelithiasis (0.7 +/- 0.1) and control (0.8 +/- 0.0) groups. The glycine/taurine ratio of conjugated bile acids were lower in enzyme-treated patients with cystic fibrosis (3.7 +/- 0.6) than in patients off treatment (6.4 +/- 1.0), but was higher (P less than 0.01) than in controls (1.8 +/- 0.2). Bile is lithogenic in untreated cystic fibrosis and responds to pancreatic enzymes.

Correction of the malabsorption of the preterm infant with a medium-chain triglyceride formula

After receiving milk-based formula for one week, 16 preterm infants, weighing 1,300 to 1,800 gm, were fed two isocaloric formulas containing either medium-chain or long-chain triglycerides for 15 days; the alternate formula was given for a second period of identical duration. While receiving MCT, the infants had greater (P smaller than 0.01) percent fat absorption (83.4 leads to 97.1%) and weight gain (7.5 leads to 11.5 gm/kg/100 calories). Because metabolic acidosis occurred with the LCT formula, the chloride content was adjusted to that of the MCT were confirmed and, in addition, there was a higher (P smaller than .01) percent retention of nitrogen (67.3 leads to 82.1).

Hepatobiliary disease in cystic fibrosis: a survey of current issues and concepts.

The incidence of hepatobiliary complications of cystic fibrosis (CF) has been increasing in parallel with the rate of survival. Detection of hepatic involvement remains a problem, as liver function tests, serum bile acid determinations, and ultrasonography do not permit an early diagnosis. The pathogenesis of cholelithiasis has been elucidated in the past few years. However, the mechanism leading to the pathognomonic CF lesion, focal biliary cirrhosis, is still unknown. There are indications that mucus plugging may be the ancestral lesion and the triggering factor. The possibility that correction of the abnormalities of bile acid metabolism could slow the progress or prevent CF cirrhosis is discussed in light of recent experimental data.

Malabsorption, hypocholesterolemia, and fat-filled enterocytes with increased intestinal apoprotein B

Eight infants presented with a malabsorption syndrome, normal fasting triglycerides, hypocholesterolemia (64.3 +/- 10.0 mg/dl), and deficiency of vitamins A and E. Plasma low-density lipoprotein, apolipoprotein B, and apolipoprotein A-I were decreased. After a fatty meal, plasma triglycerides did not increase and chylomicrons could not be identified. Lipoprotein composition was characterized by normal apoproteins, high phospholipids, and low cholesterol. Increased triglycerides were present in low-density lipoproteins. Immunoperoxidase localization of apolipoprotein B on fasting biopsy specimens showed increased staining of the lipid-laden intestinal epithelial cells compared to normals. On electron microscopy after a fat load, the enterocytes contained large numbers of fat particles vesiculating the endoplasmic reticulum. These particles, morphologically similar to chylomicrons, were also present as aggregates of well-individualized lipid droplets within dilated vesicles in the Golgi zone, but were not seen in the intercellular spaces and lacteals. This recessively transmitted condition differs from abetalipoproteinemia and from the homozygous form of hypobetalipoproteinemia and may be caused by a defect in the final assembly of chylomicrons or in the mechanism of their exocytosis.

Total parenteral nutrition-associated cholestasis in rats: comparison of different amino acid mixtures

It has been suggested that the quantity of amino acids perfused is a pathogenetic factor in total parenteral nutrition (TPN)-associated hepatotoxicity. However, the effect of the qualitative pattern of amino acid solutions has not been studied. Rats on parenteral nutrition for 5 days received 10.2 g of dextrose and 3.4 g of amino acids daily. Bile flow (microliter/min/g liver protein) after administration of Vamin was 16.2 +/- 0.8, which was similar to that in controls given chow and dextrose iv, but it was significantly higher (p less than 0.001) than those on Travasol (12.3 +/- 0.8). The decrease in bile flow was not related to the large concentrations of alanine and glycine present in Travasol. However, the addition to Travasol of serine present only in Vamin increased bile flow significantly. Bile acid secretion rate, biliary lipid constituents, calcium, sodium, and glucose showed little change. In contrast, alpha-amino nitrogen was increased (p less than 0.05) in Vamin-perfused animals. Steatosis was noted in only a few animals in the Travasol group, and was not associated with an increase in the triglycerides content of the liver. Glycogen and protein content of the livers did not differ. The data show that the composition of amino acid solutions may be a determinant of TPN-induced cholestasis and suggest that the presence of methyl donor amino acids may have a protective effect.