Association of Crohn's disease, thiopurines, and primary epstein-barr virus infection with hemophagocytic lymphohistiocytosis.

OBJECTIVE: To assess the incidence of hemophagocytic lymphohistiocytosis (HLH) in a well-defined population of children with inflammatory bowel disease (IBD) and evaluate the common clinical and laboratory characteristics of individuals with IBD who developed HLH. STUDY DESIGN: We conducted a retrospective study of all children who developed HLH over an 8-year period. The incidence of HLH in patients with IBD was calculated using US census data and a statewide project examining the epidemiology of pediatric IBD. RESULTS: Among children in Wisconsin, 20 cases of HLH occurred during the study period; 5 cases occurred in children with IBD. Common characteristics include: Crohn's disease (CD), thiopurine administration, fever lasting more than 5 days, lymphadenopathy, splenomegaly, anemia, lymphopenia, and elevated serum triglycerides and ferritin. Of the patients, 4 had primary Epstein-Barr virus infections. The incidence of HLH among all children in Wisconsin was 1.5 per 100 000 per year. The risk was more than 100-fold greater for children with CD (P < .00001). CONCLUSIONS: Pediatric patients with CD are at increased risk for developing HLH; primary Epstein-Barr virus infection and thiopurine administration may be risk factors.

Capsule endoscopy performed across the pediatric age range: indications, incomplete studies, and utility in management of inflammatory bowel disease.

BACKGROUND: Capsule endoscopy (CE) is used increasingly to evaluate the small bowel in children. An upper GI series is recommended before CE to evaluate the risk of obstruction. Despite normal findings on an upper GI series, CE may still be incomplete. Although large adult studies have demonstrated the safety and diagnostic yield of CE, similar pediatric studies have not been available. OBJECTIVE: To identify factors associated with incomplete studies and the diagnostic yield in pediatric patients. DESIGN: Retrospective review of consecutive CE studies from February 2005 through June 2008. SETTING: Large tertiary children's hospital. PATIENTS: A total of 123 CE studies in 117 patients; median age 12.9 years (range 0.8-22.4 years). MAIN OUTCOME MEASUREMENTS: Demographic information, indication, placement technique, pre-CE imaging results, and cecal completion status were recorded. Risk factors were analyzed with bivariate and multivariate regression analysis. RESULTS: There were 27 (22%) incomplete studies; of these, there were normal pre-CE radiologic study findings in 12 (44%), and findings requiring medical, endoscopic, or operative intervention in 6. Of the 117 patients, CE produced a new diagnosis in 21 (18%). Abnormal findings on previous imaging (odds ratio [OR] 3.0; 95% CI, 1.2-8.0), endoscopic placement (OR 3.1; 95% CI, 1.1-8.4), and female sex (OR 3.3; 95% CI, 1.2-9.4) were associated with incomplete studies. LIMITATIONS: Retrospective, incomplete follow-up. CONCLUSIONS: CE may be performed in children as small as 11.5 kg, with 18% yield in all studies, and 28% in pediatric known inflammatory bowel disease. Capsule retention requiring retrieval did not pose life-threatening risk in our series, and CE may be used to identify disease-associated small-bowel stenosis.

Can Nurturing the Young Be the Key to Tackling Chronic Diseases in the Old? A Narrative Review With a Global Perspective.

BACKGROUND: One of the greatest challenges in healthcare today is dealing with a growing burden of multimorbid chronic diseases in an aging population. Awareness is growing that a healthy start in life plays a critical role in reversing this trend, especially for young women, pregnant mothers, and children in their first 2 years of life. METHODS: We reviewed the international literature on early childhood nutrition and development, based on the landmark Lancet series on maternal and child nutrition and child development, and World Health Organization reports. RESULTS: Contemporary literature points to the importance of strategies that focus on early childhood for enhancing both health and socioeconomic outcomes. We discuss programs and initiatives that aim to improve the health of mothers and children at a global level, with a focus on high-income countries such as Australia and the United States. CONCLUSION: Tackling the epidemic of chronic diseases requires a comprehensive life course approach that must include pregnant women and their young children. Healthcare systems and professionals play an important role. The health and well-being of the next generation must be everyone's business.

GRS1, a yeast tRNA synthetase with a role in mRNA 3' end formation.

Transcription termination and 3' end formation are essential processes necessary for gene expression. However, the specific mechanisms responsible for these events remain elusive. A screen designed to identify trans-acting factors involved in these mechanisms in Saccharomyces cerevisiae identified a temperature-sensitive mutant that displayed phenotypes consistent with a role in transcription termination. The complementing gene was identified as GRS1, which encodes the S. cerevisiae glycyl-tRNA synthetase. This result, although unusual, is not unprecedented given that the involvement of tRNA synthetases in a variety of cellular processes other than translation has been well established. A direct role for the synthetase in transcription termination was determined through several in vitro assays using purified wild type and mutant enzyme. First, binding to two well characterized yeast mRNA 3' ends was demonstrated by cross-linking studies. In addition, it was found that all three substrates compete with each other for binding to GlyRS enzyme. Next, the affinity of the synthetase for the two mRNA 3' ends was found to be similar to that of its "natural" substrate, glycine tRNA in a nitrocellulose filter binding assay. The effect of the grs1-1 mutation was also examined and found to significantly reduce the affinity of the enzyme for the three RNA substrates. Taken together, these data indicate that not only does this synthetase interact with several different RNA substrates, but also that these substrates bind to the same site. These results establish a direct role for GRS1 in mRNA 3' end formation.