John A. Kerner

Improved growth and disease activity after intermittent administration of a defined formula diet in children with Crohn's disease.

Growth failure is the most common extraintestinal manifestation of Crohns disease in childhood, occurring in up to 50% to 88% of affected patients. Previous studies have shown malnutrition to be the most likely cause of the decrease in height and weight velocities in these children. The purpose of this study was to determine the effect of an intermittent defined formula diet on growth and disease activity in children with Crohns disease and growth failure. Six Tanner stage I-II patients, mean age 13.6 years with height less than the 5th percentile or height velocity less than the 3rd percentile were enrolled in a 1-year prospective study. An isotonic, hydrolyzed whey, medium-chain triglyceride formula was given by nocturnal nasogastric infusion at a caloric equivalent of 50th percentile for age, as the exclusive nutrient source 1 out of 4 months during a 1-year period. A 2-week exclusion diet and a 2-week low-residue diet followed the defined formula diet before resuming the regular diet for 2 months. Patients served as their individual control based on observations of at least 1 year before the study. Height and weight velocity significantly increased. Prednisone intake significantly decreased, and significant improvement was seen in disease activity, albumin, and somatomedin C. The results indicate that an intermittent defined formula diet can improve growth failure and significantly decrease disease activity in children with Crohns disease.

Treatment of catheter occlusion in pediatric patients.

A proper initial assessment of catheter occlusion is the key to successful management. The assessment screens are for both thrombotic and nonthrombotic causes (including mechanical occlusion). If mechanical occlusion is excluded, thrombotic occlusion is treated with alteplase. Nonthrombotic occlusions are treated according to their primary etiologies: lipid occlusion is treated with 70% ethanol, mineral precipitates are treated with 0.1-N hydrochloric acid (HCl), drug precipitates are treated according to their pH-acidic drugs can be cleared with 0.1-N HCl, basic medications can be cleared with sodium bicarbonate or 0.1-N sodium hydroxide (NaOH). Prevention of occlusion of central venous access devices is also critical. To date, no data conclusively show heparin flushes to be superior to saline flushes. No prophylactic regimen, including low-dose warfarin, low-molecular-weight heparin, or 1 unit heparin/mL of parenteral nutrition has been endorsed by any major medical, nursing, or pharmacy group due to lack of scientific evidence. The most encouraging information on decreasing occlusion rate comes from experience with positive-pressure devices that attach to the hub of most catheter lumens and prevent retrograde blood flow and, consequently, decrease the risk of thrombus formation in the catheter lumen.

Copper Deficiency During Parenteral Nutrition: A Report of Four Pediatric Cases:

The standard of care for patients with cholestasis (direct bilirubin >or=2 mg/dL) while receiving parenteral nutrition (PN) solutions is to reduce or discontinue the copper and manganese. The repercussions of this action have not been studied. Two adult case reports document low serum copper levels associated with clinical symptoms of copper deficiency after the removal of copper from their PN solutions. We now describe the first known series of pediatric patients to develop copper deficiency after copper was removed from their PN solutions.

Increased Number of Regulatory T Cells in Children With Eosinophilic Esophagitis

Objectives: There are limited data on the role of regulatory T cells (Treg) in the disease pathology of eosinophilic esophagitis (EoE). We tested the differences in Treg in subjects with EoE compared with those with gastroesophageal reflux disease (GERD) and healthy controls (HC). Patients and Methods: Pediatric patients evaluated by endoscopy were recruited for our study. Participants were categorized into 3 groups: EoE, GERD, and HC. RNA purified from esophageal biopsies were used for real-time quantitative polymerase chain reaction assays and tested for forkhead box P3 (FoxP3) mRNA expression. Treg were identified as CD4+CD25hiCD127lo cells in peripheral blood and as CD3+/FoxP3+cells in esophageal tissue. Results: Forty-eight subjects were analyzed by real-time quantitative polymerase chain reaction: EoE (n = 33), GERD (n = 7), and HC (n = 8). FoxP3 expression was higher by up to 1.5-fold in the EoE group compared with the GERD and HC groups (P < 0.05). Protein levels of FoxP3 in blood and tissue were then investigated in 21 subjects: EoE (n = 10), GERD (n = 6), and HC (n = 5). The percentage of Treg and their subsets in peripheral blood were not significant between groups (P > 0.05). The amount of Treg in esophageal tissue was significantly greater in the EoE group (mean 10.7 CD3+/FoxP3+cells/high power field [HPF]) compared with the other groups (GERD, mean 1.7 CD3+/FoxP3+cells/HPF and HC, mean 1.6 CD3+/FoxP3+cells/HPF) (P < 0.05). Conclusions: We show that Treg are increased in esophageal tissue of EoE subjects compared with GERD and HC subjects. The present study illustrates another possible mechanism involved in EoE that implicates impairment of immune homeostasis.

Microvillous inclusion disease. The importance of electron microscopy for diagnosis.

We report two cases of microvillous inclusion disease (MID) occurring in a set of siblings. Although it is a rare disorder, MID appears to be a common cause of familial intractable secretory diarrhea. Diagnosis rests on the ultrastructural finding of intracytoplasmic inclusions that are lined by intact microvilli. These inclusions are present in the absorptive surface epithelial cells of the small and large intestine and are associated with poorly developed surface brush border microvilli. The prognosis of MID is poor and curative therapy is not currently available. Because MID appears to be a hereditary disorder, genetic counseling of affected families is essential.

The Effect of Nutritional Additives on Anti-Infective Factors in Human Milk

It has become a common practice to supplement human milk with a variety of additives to improve the nutritive content of the feeding for the premature infant. Twenty-two freshly frozen human milk samples were measured for lysozyme activity, total IgA, and specific IgA to Escherichia coli serotypes 01, 04, and 06. One mL aliquots were mixed with the following: 1 mL of Similac, Similac Special Care, Enfamil, Enfamil Premature Formula, and sterile water; 33 mL of Poly-Vi-Sol, 33 mg of Moducal, and 38 mg of breast-milk fortifier, and then reanalyzed. Significant decreases (41 % to 74%) in lysozyme activity were seen with the addition of all formulas; breast-milk fortifier reduced activity by 19%, while no differences were seen with Moducal, sterile water, or Poly-Vi-Sol. No differences were seen in total IgA content, but some decreases were seen in specific IgA to E. coli serotypes 04 and 06. E. coli growth was determined after 3 1/2 hours of incubation at 37°C after mixing. All cow-milk formulas enhanced E. coli growth; soy formulas and other additives preserved inhibition of bacterial growth. Nutritional additives can impair anti-infective properties of human milk, and such interplay should be considered in the decision on the feeding regimen of premature infants.

Growth in human milk-Fed very low birth weight infants receiving a new human milk fortifier.

Background/Aims: Human milk fortification has been advocated to enhance premature infants’ growth. We, therefore, undertook this study of a new human milk fortifier containing more protein than a reference one. Methods: Open, randomized, controlled, multiclinic trial, with weekly growth parameters and safety evaluations in premature infants <1,500 g. Results: The 2 groups did not differ in demographic and baseline characteristics. The adjusted daily milk intake was significantly higher in the infants fed reference human milk fortifier (n = 29; 154.2 ± 2.1 vs. 144.4 ± 2.5 ml/kg/day, mean ± SE; p < 0.05). Both human milk fortifiers produced increases over baseline in weight, length, and head circumference, with greater gains observed in the new human milk fortifier-fed infants for the former two parameters (weight gain 26.8 ± 1.3 and 20.4 ± 1.2 g/day, p < 0.05; head circumference 1.0 ± 0.1 and 0.8 ± 0.1 cm/week; length 0.9 ± 0.1 and 0.8 ± 0.1 cm/week, respectively). Serum chemistries were normal and acceptable for age. Study events were typical for premature infants and similar in both groups. Conclusions: This new human milk fortifier had comparable safety to the reference human milk fortifier and promoted faster weight gain and head circumference growth.

Hepatic failure following ingestion of multiple doses of acetaminophen in a young child.

A 7-month-old male developed hepatic failure following the mistaken administration of multiple excessive doses of acetaminophen. Hepatic toxicity following multiple dose ingestion has been reported infrequently. Risk factors for hepatic toxicity following multiple dose ingestion are discussed.

Eotaxin and FGF enhance signaling through an Extracellular signal-related kinase (ERK)-dependent pathway in the pathogenesis of Eosinophilic Esophagitis

BackgroundEosinophilic esophagitis (EoE) is characterized by the inflammation of the esophagus and the infiltration of eosinophils into the esophagus, leading to symptoms such as dysphagia and stricture formation. Systemic immune indicators like eotaxin and fibroblast growth factor were evaluated for possible synergistic pathological effects. Moreover, blood cells, local tissue, and plasma from EoE and control subjects were studied to determine if the localized disease was associated with a systemic effect that correlated with presence of EoE disease.MethodReal-time polymerase chain reaction from peripheral blood mononuclear cells (PBMC), immunohistochemistry from local esophageal biopsies, fluid assays on plasma, and fluorescence-activated cell sorting on peripheral blood cells from subjects were used to study the systemic immune indicators in newly diagnosed EoE (n = 35), treated EoE (n = 9), Gastroesophageal reflux disease (GERD) (n = 8), ulcerative colitis (n = 5), Crohns disease (n = 5), and healthy controls (n = 8).ResultOf the transcripts tested for possible immune indicators, we found extracellular signal-regulated kinase (ERK), Bcl-2, bFGF (basic fibroblast growth factor), and eotaxin levels were highly upregulated in PBMC and associated with disease presence of EoE. Increased FGF detected by immunohistochemistry in esophageal tissues and in PBMC was correlated with low levels of pro-apoptotic factors (Fas, Caspase 8) in PBMC from EoE subjects. Plasma-derived bFGF was shown to be the most elevated and most specific in EoE subjects in comparison to healthy controls and disease control subjects.ConclusionWe describe for the first time a possible mechanism by which increased FGF is associated with inhibiting apoptosis in local esophageal tissues of EoE subjects as compared to controls. Eotaxin and FGF signaling pathways share activation through the ERK pathway; together, they could act to increase eosinophil activation and prolong the half-life of eosinophils in local tissues of the esophagus in EoE subjects.

The Use of IV Fat in Neonates

IV fat emulsion (IVFE) is an integral part of the parenteral nutrition (PN) regimen in neonates. It provides a concentrated isotonic source of calories and prevents or reverses essential fatty acid deficiency. Continuous administration of IV fat with PN regimens prolongs the viability of peripheral IV lines in infants who might have limited venous access. IVFE must be administered separately from the PN solution in neonates. The acidic pH of a PN solution is necessary for maximum solubility of calcium and phosphorus. If fat emulsion is added to the PN solution, as is done in 3-in-1 (total nutrient admixture) solutions, the high amount of calcium and phosphorus needed by these infants may result in an unseen precipitate with serious consequences. Continuous fat infusion over 24 hours is the preferred method in neonates. The administration rate of 0.15 g/kg/hour for IVFE in the neonate should not be exceeded. Essential fatty acid deficiency can be prevented in neonates by providing IVFE in a dose of 0.5-1.0 g/kg/day. Carnitine is not routinely required to metabolize IVFE in the neonate. Infants should receive 20% lipid emulsion to improve clearance of triglycerides and cholesterol. Serum triglyceride levels should be maintained at <150-200 mg/dL in neonates. There are concerns about potential adverse effects of early administration of IV fat in very-low-birth-weight infants weighing <800 g. We hold the IV fat dose at 1.0-1.5 g/kg/day until the second week of life in infants <30 weeks gestation.