Steven M. Schwarz

Optimizing the diagnosis of gastroesophageal reflux in children with otolaryngologic symptoms

OBJECTIVES Although many children with otolaryngologic (ENT) symptoms are being treated for gastroesophageal reflux (GER), how to diagnose GER in children with primarily or exclusively ENT symptoms has yet to be determined. This study compares the incidences of pathologic GER in the upper verses the lower esophagus in a cohort of children with ENT symptoms that were screened for GER. METHODS The results of extended dual channel intraesophageal pH probe monitoring obtained from 14 infants and 14 children with ENT symptoms were retrospectively analyzed. The percent of total monitoring time that the pH was less than 4, reflux index (RI) was determined. The upper limits of normal distal and proximal esophageal RI were based on published data. To evaluate our results, upper esophageal reflux (UER) was also determined in 27 infants and children without ENT or pulmonary symptoms, who had normal lower esophageal reflux (LER) values. RESULTS Mean upper esophageal RIs in the infants and children with normal LER were similar to previously published values for control infants and adults. Four (29%) of the ENT infants, 11 (79%) of the older ENT children, and 54% of the entire cohort had increased esophageal acid exposure. However, nine (60%) of the 15 pediatric ENT patients with GER had pH abnormalities limited to the upper esophagus. CONCLUSIONS Standard distal pH probe monitoring alone gives a false negative result in a substantial proportion of the infants and children with ENT symptoms being evaluated for GER. Beyond its value in clinical practice, UER testing should be employed in research studies that evaluate the impact of GER therapy on ENT symptoms.

ω-3 Fatty Acids Prevent Hepatic Steatosis, Independent of PPAR-α Activity, in a Murine Model of Parenteral Nutrition–Associated Liver Disease

OBJECTIVES ω-3 Fatty acids (FAs), natural ligands for the peroxisome proliferator-activated receptor-α (PPAR-α), attenuate parenteral nutrition-associated liver disease (PNALD). However, the mechanisms underlying the protective role of ω-3 FAs are still unknown. The aim of this study was to determine the effects of ω-3 FAs on hepatic triglyceride (TG) accumulation in a murine model of PNALD and to investigate the role of PPAR-α and microsomal triglyceride transfer protein (MTP) in this experimental setting. METHODS 129S1/SvImJ wild-type or 129S4/SvJaePparatm/Gonz/J PPAR-α knockout mice were fed chow and water (controls); oral, fat-free PN solution only (PN-O); PN-O plus intraperitoneal (IP) ω-6 FA-predominant supplements (PN-ω-6); or PN-O plus IP ω-3 FA (PN-ω-3). Control and PN-O groups received sham IP injections of 0.9% NaCl. Hepatic histology, TG and cholesterol, MTP activity, and PPAR-α messenger RNA were assessed after 19 days. RESULTS In all experimental groups, PN feeding increased hepatic TG and MTP activity compared with controls. Both PN-O and PN-ω-6 groups accumulated significantly greater amounts of TG when compared with PN-ω-3 mice. Studies in PPAR-α null animals showed that PN feeding increases hepatic TG as in wild-type mice. PPAR-α null mice in the PN-O and PN-ω-6 groups demonstrated variable degrees of hepatic steatosis, whereas no evidence of hepatic fat accumulation was found after 19 days of oral PN plus IP ω-3 FAs. CONCLUSIONS PN induces TG accumulation (steatosis) in wild-type and PPAR-α null mice. In PN-fed wild-type and PPAR-α null mice given IP ω-3 FAs, reduced hepatic TG accumulation and absent steatosis are found. Prevention of steatosis by ω-3 FAs results from PPAR-α-independent pathways.

Prevalence and characteristics of eosinophilic esophagitis in 2 ethnically distinct pediatric populations

To the Editor: Eosinophilic esophagitis (EoE) is an immune/antigenmediated disease characterized by symptoms related to esophageal dysfunction and by eosinophil-predominant mucosal inflammation. Age-dependent symptom variability is well recognized in children. A recent study in adult patients reported significant racial/ethnic EoE phenotypic differences; however, ethnic variations in the clinical/histopathologic properties of pediatric EoE have not been examined. Published data describe findings in predominantly white pediatric subjects. This report investigates EoE characteristics in a black, inner-city pediatric cohort, and compares findings with those in a rural white population. This study was approved by the respective institutional review boards at SUNY-Downstate Medical Center and at Marshall University. Children with EoE were identified from all pediatric diagnostic upper endoscopies performed at SUNY-Downstate Medical Center, Brooklyn, New York, and at Marshall University, Huntington, West Virginia, between January 1, 2003, and April 30, 2010. Subjects were excluded if symptoms resolved following acid suppressive treatment. Information obtained from patient records and reflecting standard practice for evaluating EoE at both sites included patient age, ethnicity, symptoms, personal and family history of atopy, peripheral eosinophilia, total IgE, radioallergosorbent test results (cow milk protein, soy protein, wheat, eggs, peanuts/tree nuts, seafood), and endoscopic and histopathologic findings. Endoscopic findings at diagnosis were identified by reviewing procedure photographs and written reports. Consistent with consensus recommendations and with routine protocols at both sites, at least 1 biopsy each was obtained from the distal and the midesophagus in all subjects. EoE (>_15 eosinophils in a single hpf) was confirmed on reexamination by a single pathologist (R.G.). Two-tailed, independent-samples mean tests (for continuous variables) and x analyses (for noncontinuous variables) were used (SPSS, version 17.0; IBM Corp, Armonk, NY). Ninety-six patients were eligible for this retrospective study: 44 from SUNY-Downstate and 52 from Marshall University. These numbers represent 3.1% and 3.3%, respectively, of all diagnostic (ie, initial) pediatric upper endoscopies performed at these centers during the study period. All 52 eligible subjects in theWVa cohort werewhite, and all were included. At SUNY-Downstate, 37 of the 44 eligible children were studied. Five black subjects had incomplete clinical data, and the only 2 white subjects with EoE were excluded to maintain group homogeneity. Males were more commonly affected than females in both groups (M:F [black vs white], 2.7:1 vs 3.0:1; P 5 not significant [ns]). Age ranges were similar (black 5 8 months to 17 years; white 5 6 months to 18 years); however, the mean age at diagnosis was significantly younger in black subjects (black vs white 5 4.5 vs 9.5 years, P < .001, 95% CI, 2.5-6.2). Fig 1 indicates presenting symptoms in both groups. Feeding difficulties, not including vomiting or regurgitation, were

The Liver in Pediatric Gastrointestinal Disease

Hepatic involvement is often encountered in gastrointestinal (GI) diseases, in part because of the close anatomic and physiologic relations between the liver and GI tract. Drainage of the mesenteric blood supply to the portal vein permits absorbed and/or translocated nutrients, toxins, bacterial elements, cytokines, and immunocytes to gain hepatic access. Liver problems in digestive disorders may range from nonspecific hepatocellular enzyme elevations to significant pathologic processes that may progress to end-stage liver disease. Hepatobiliary manifestations of primary GI diseases in childhood and adolescence are not uncommon and include several well-described associations, such as sclerosing cholangitis with inflammatory bowel disease. Liver damage may also result from the effects of drugs used to treat GI diseases, for example, the hepatotoxicity of immunomodulatory therapies. This review highlights the important features of the hepatic and biliary abnormalities associated with 3 common pediatric GI conditions: inflammatory bowel disease, celiac disease, and cystic fibrosis.

The role of folate receptor autoantibodies in preterm birth

OBJECTIVE Cellular uptake of folate is mediated by folate receptor (FR)α. Prior studies indicate that a FRα autoantibody (FRAb) is implicated in poor pregnancy outcomes. The aims of this study were to determine the prevalence of FRAbs in women with preterm and term pregnancies, and to investigate the role of maternal FRAbs in preterm birth. METHODS This prospective observational study included 23 mothers and 25 preterm infants (two twin births) born at gestational age (GA) ≤32 wk and/or birth weight ≤1500 g (group 1) and 25 mother-term infant pairs (infants born at GA ≥37 wk, group 2). Blocking and binding FRAbs in maternal and in cord blood were determined. The association between maternal FRAbs and pregnancy outcome was measured using multiple logistic regression, adjusted for maternal age and previous preterm birth. RESULTS The prevalence of FRAbs was 65.2% in women with preterm birth, which was twofold higher than in those with term pregnancy (28%; relative risk [RR], 2.3; 95% confidence interval [CI], 1.2-4.7). The prevalence of FRAbs in preterm infants (64%) was significantly higher than in term infants (24%; RR, 2.7; 95% CI, 1.3-5.7). Pregnant women with positive FRAbs had 4.9 times higher odds of having preterm birth (odds ratio, 4.9; 95% CI, 1.4-17.7), adjusted for maternal age and previous preterm birth. CONCLUSIONS These findings suggest that the presence of FRAbs might be a contributing factor to preterm birth, which could be prevented with appropriate testing and therapeutic interventions. Further studies are warranted to investigate the possible mechanisms of fetal sensitization resulting in FRAb production in utero and its possible clinical correlates.

Pediatric Helicobacter pylori gastropathy demonstrates a unique pattern of gastric foveolar hyperplasia

Helicobacter pylori (Hp) are the most common agents causing gastric mucosal injury worldwide. Foveolar hyperplasia is a key component of the stomachs reaction to injury. This study examines histopathologic characteristics associated with Helicobacter pylori and with non‐ Helicobacter pylori‐associated gastropathy in children and adolescents, and compares the prevalence of foveolar hyperplasia among these disease subgroups and normal control subjects.