Recent comprehensive guidelines developed by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition define the common entities of gastroesophageal reflux (GER) as the physiologic passage of gastric contents into the esophagus and gastroesophageal reflux disease (GERD) as reflux associated with troublesome symptoms or complications. The ability to distinguish between GER and GERD is increasingly important to implement best practices in the management of acid reflux in patients across all pediatric age groups, as children with GERD may benefit from further evaluation and treatment, whereas conservative recommendations are the only indicated therapy in those with uncomplicated physiologic reflux. This clinical report endorses the rigorously developed, well-referenced North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines and likewise emphasizes important concepts for the general pediatrician. A key issue is distinguishing between clinical manifestations of GER and GERD in term infants, children, and adolescents to identify patients who can be managed with conservative treatment by the pediatrician and to refer patients who require consultation with the gastroenterologist. Accordingly, the evidence basis presented by the guidelines for diagnostic approaches as well as treatments is discussed. Lifestyle changes are emphasized as first-line therapy in both GER and GERD, whereas medications are explicitly indicated only for patients with GERD. Surgical therapies are reserved for children with intractable symptoms or who are at risk for life-threatening complications of GERD. Recent black box warnings from the US Food and Drug Administration are discussed, and caution is underlined when using promoters of gastric emptying and motility. Finally, attention is paid to increasing evidence of inappropriate prescriptions for proton pump inhibitors in the pediatric population.

This is the fi rst clinical practice guideline from the American Academy of Pediatrics that specifi cally applies to patients who have experienced an apparent life-threatening event (ALTE). This clinical practice guideline has 3 objectives. First, it recommends the replacement of the term ALTE with a new term, brief resolved unexplained event (BRUE). Second, it provides an approach to patient evaluation that is based on the risk that the infant will have a repeat event or has a serious underlying disorder. Finally, it provides management recommendations, or key action statements, for lower-risk infants. The term BRUE is defi ned as an event occurring in an infant younger than 1 year when the observer reports a sudden, brief, and now resolved episode of ≥1 of the following: (1) cyanosis or pallor; (2) absent, decreased, or irregular breathing; (3) marked change in tone (hyper-or hypotonia); and (4) altered level of responsiveness. A BRUE is diagnosed only when there is no explanation for a qualifying event after conducting an appropriate history and physical examination. By using this defi nition and framework, infants younger than 1 year who present with a BRUE are categorized either as (1) a lower-risk patient on the basis of history and physical examination for whom evidence-based recommendations for evaluation and management are offered or (2) a higher-risk patient whose history and physical examination suggest the need for further investigation and treatment but for whom recommendations are not offered. This clinical practice guideline is intended to foster a patient-and family-centered approach to care, reduce unnecessary and costly medical interventions, improve patient outcomes, support implementation, and provide direction for future research. Each key action statement indicates a level of evidence, the benefi t-harm relationship, and the strength of recommendation.

The gene encoding the mitochondrial citrate transport protein (CTP) in the yeast Saccharomyces cerevisiae has been identified, and its protein product has been overexpressed in Escherichia coli. The expressed CTP accumulates in inclusion bodies and can be solubilized with sarkosyl. Approximately 25 mg of solubilized CTP at a purity of 75% is obtained per liter of E. coli culture. The function of the solubilized CTP has been reconstituted in a liposomal system where both its kinetic parameters (i.e. Km = 0.36 mM and Vmax = 2.5 mumol/min/mg protein) and its substrate specificity have been determined. Notably, the yeast CTP displays a stricter specificity for tricarboxylates than do CTPs from higher eukaryotic organisms. Dot matrix analysis of the yeast CTP sequence indicates the presence of three homologous sequence domains (each approximately 100 residues in length), which are also related to domains in other CTPs. Thus, the yeast CTP displays the tripartite structure characteristic of other mitochondrial transporters. Alignment of the yeast CTP sequence with CTPs from other sources defines a consensus sequence that displays 89 positions of amino acid identity, as well as the more generalized mitochondrial transporter-associated sequence motif. Based on hydropathy analysis, the yeast CTP contains six putative membrane-spanning alpha-helices. Finally, Southern blot analysis indicates that the yeast genome contains a single gene encoding the mitochondrial CTP. Our data indicate that, based on both its structural and functional properties, the expressed yeast CTP can be assigned membership in the mitochondrial carrier family. The identification of the yeast CTP gene, and the expression and purification of large quantities of its protein product, pave the way for investigations into the roles of specific amino acids in the CTP translocation mechanism, as well as for the initiation of crystallization trials.

Polyethylene glycol (PEG) 3350 and lactulose were compared in an unblinded, randomized, crossover design for treatment of constipation in 37 children aged 2 to 16 years. Subjects received lactulose (1.3 g/kg/d divided twice daily up to 20 g) or PEG 3350 (10 g/m2/day) for 2 weeks. PEG 3350 significantly decreased the total colonic transit time compared to lactulose (47.6+/-2.7 vs 55.3+/-2.4 hours, mean +/- SE, PEG 3350 vs lactulose, respectively, p = 0.038). The stool frequency, form, and the ease of passage were similar for each laxative. Polyethylene glycol 3350 is an effective laxative for the treatment of chronic constipation in children.

Two gastroesophageal reflux disease (GERD) symptom questionnaires were developed and tested prospectively in a pilot study conducted in infants (1 through 11 months) and young children (1 through 4 years) with and without a clinical diagnosis of GERD. A pediatric gastroenterologist made the clinical diagnosis of GERD. Parents or guardians at 4 study sites completed the questionnaires, providing information on the frequency and severity of symptoms appropriate to the 2 age cohorts. In infants, symptoms assessed were back arching, choking or gagging, hiccups, irritability, refusal to feed and vomiting or regurgitation. In young children, symptoms assessed were abdominal pain, burping or belching, choking when eating, difficulty swallowing, refusal to eat and vomiting or regurgitation. Respondents were asked to describe additional symptoms. Symptom frequency was the number of occurrences of each symptom in the 7 days before completion of the questionnaire. Symptom severity was rated from 1 (not at all severe) to 7 (most severe). An individual symptom score was calculated as the product of symptom frequency and severity scores. The composite symptom score was the sum of the individual symptom scores. The mean composite symptom and individual symptom scores were higher in infants (P<0.001 and P<0.05, respectively) and young children (P<0.001 and P<0.05, respectively) with GERD than controls. Vomiting/regurgitation was particularly prevalent in infants with GERD (90%). Both groups with GERD were more likely to experience greater severity of symptoms. We found the GERD Symptom Questionnaire useful in distinguishing infants and young children with symptomatic GERD from healthy children.