Adib A. Moukarzel

BACKGROUND: Numerous animal studies have demonstrated intestinal villus atrophy occurs when luminal nutrition is withheld and total parenteral nutrition (TPN) is provided. Intestinal morphologic and functional changes have not been well studied in humans during TPN. METHODS: Eight normal volunteers were hospitalized in the Clinical Research Center for 3 weeks. The subjects received TPN as an exclusive means of nutritional support for 14 days followed by 5 days of enteral refeeding with either a standard or a glutamine and arginine-supplemented formula. Endoscopic jejunal biopsies were taken before and after TPN and after enteral refeeding. Intestinal morphology was examined by light and transmission electron microscopy. Mucosa DNA, RNA, and protein concentrations were measured. Lactose breath hydrogen and intestinal permeability testing (urinary lactulose and mannitol excretion after an oral dose) were performed before and after TPN and after enteral refeeding. RESULTS: Total mucosal thickness decreased after TPN (645 +/- 19 to 512 +/_ 19 microns, p = .003) and increased significantly towards baseline after enteral refeeding (575 +/- 19 microns, p = .04). The change was related solely to villus height; crypt depth was unaffected. Villus cell count decreased from 179 +/- 15 to 163 +/- 12 after TPN (p = .03) and increased after enteral refeeding to 176 +/- 21 (p = .06). Crypt cell count was unaffected by TPN or refeeding. A nonsignificant decrease in the mitotic index after TPN was seen. Intracellular edema developed during TPN and resolved with enteral refeeding. The urinary lactulose-mannitol ratio increased with TPN [0.06 +/- 0.03 to 0.11 +/- 0.05 after TPN and 0.14 +/_ 0.09 after short-term enteral refeeding (p = .05)], indicating increased intestinal permeability. The urinary lactulose-mannitol ratio was significantly greater after refeeding with standard formula than the free amino acid peptide formula with glutamine and arginine (0.20 +/- 0.05, vs 0.08 +/- 0.01, p = .05). No significant differences were noted in mucosal RNA, DNA, protein, DNA-protein or RNA-DNA rations or breath hydrogen after lactose ingestion after either TPN or enteral refeeding. No significant difference in plasma glutamine was found during TPN (462.7 +/ 38.7 vs 491.8 +/- 46.1 mumol/L) or after enteral refeeding (457.3 +/- 51.4 mumol/L). CONCLUSIONS: Intestinal morphologic and functional changes occur in human for whom TPN is the sole nutritional source, although the findings in humans are substantially less significant than observed in animal models. The loss of mucosal structure may be sufficient to cause increased intestinal permeability, the clinical significance of which remains to be defined. Enteral nutrition is important in restoring and probably preventing morphologic intestinal changes associated with TPN, and a peptide and free amino acid-based formula supplemented with glutamine and arginine may have some added role. Our findings also suggest sepsis is associated with gut adaptation rather than degradation.

Patients receiving long-term total parenteral nutrition (TPN) develop hepatic steatosis as a complication. Our previous studies have shown this to be caused, at least in part, by choline deficiency. We studied four patients (1 man, 3 women) aged 50 +/- 13 years who had low plasma-free choline concentrations 4.8 +/- 1.7 (normal, 11.4 +/- 3.7 nmol/mL). The patients had received TPN for 9.7 +/- 4.7 years. They received parenteral nutrition solutions containing choline chloride (1 to 4 g/d) for 6 weeks. Abdominal computed tomography (CT) was performed at baseline, biweekly during the choline supplementation, and 4 weeks after discontinuation of choline. During choline administration, the plasma-free choline concentration increased into the normal range within 1 week in all four patients and remained at or above the normal range for all 6 weeks, but decreased back to baseline when choline supplementation was discontinued. Hepatic steatosis resolved completely, as estimated by CT. Liver density increased from -14.2 +/- 22.3 Hounsfield units (HU) to 8.4 +/- 10.3 HU at week 2 (P = .002); 9.6 +/- 10.7 HU at week 4 and 13.1 +/- 7.3 HU at week 6, as determined by the liver-spleen CT number difference obtained by the subtraction of the average spleen CT number (in HU) from the average liver CT number. This improvement continued up to 4 weeks after choline supplementation (13.8 +/- 2.8 HU). Hepatic steatosis was shown to have recurred in one patient after 10 weeks of return to choline-free parenteral nutrition. The hepatic steatosis associated with parenteral nutrition can be ameliorated, and possibly prevented, with choline supplementation. Therefore, choline may be an essential nutrient for patients who require long-term parenteral nutrition.

One hundred and six patients were placed on a home parenteral nutrition program because of severe gastrointestinal tract lesions. In 41, sufficient improvement allowed the resumption of oral alimentation. Forty-eight remain on the program. Seventeen, including ten with malignant disease, died from causes not related to home parenteral nutrition. All patients achieved and maintained the appropriate weight for age and body build. In the pediatric patients, normal or accelerated linear growth occurred. Complications included sepsis, 18 episodes in 12 patients; local infection of the catheter, 14 in six; catheter thrombosis, six in five; ketoacidosis, one in one; contaminated solutions, one in one, and essential fatty acid deficiency, one in one. Home parenteral nutrition is a relatively safe and effective alternative for long term nutritional support.

OBJECTIVE(S): Advantages of prethickened formulas (AR) with regards to esophageal pH and gastric emptying were investigated in this study as compared with a regular formula (R). STUDY DESIGN: Seventy-four healthy infants, <6 months old, with gastroesophageal reflux were enrolled into the study. All infants underwent 24-hour esophageal pH monitoring while receiving R and AR, alternately. Electrogastrography was measured before and after feeding each study formula. Thereafter, the infants were randomly assigned to receive either R or AR for 1 month. Episodes of regurgitation, vomiting, coughing, crying, and bowel movements were recorded on a weekly interval. RESULTS: Reflux index (RI) of AR-fed infants were lower (5.64%) than the R-fed infants (7.77%) showing a significant difference (P<0.01) between the 2 groups, favoring AR. Eighty-seven percent of infants improved their RI while receiving the AR formula. Electrogastrography variables were not significantly different between the 2 study groups. A significant decrease (P<0.01) in the daily episodes of regurgitation and vomiting was observed in the AR-fed infants. No adverse events were reported during the study. CONCLUSIONS: Prethickened infant formula was effective in reducing clinical symptoms of uncomplicated gastroesophageal reflux and reducing RI. Prethickened formulas do not alter gastric emptying time and was very well tolerated.