SummaryAltered glycosylation and/or expression of dystroglycan have been reported in forms of congenital muscular dystrophy as well as in cancers of the breast, colon, and oral epithelium. To date, however, there has been no study of the expression of dystroglycan in pediatric solid tumors. Using a combination of immunostaining on tissue microarrays and immunoblotting of snap-frozen unfixed tissues, we demonstrate a significant reduction in native α dystroglycan expression in pediatric alveolar rhabdomyosarcoma (RMS), embryonal RMS, neuroblastoma (NBL), and medulloblastoma, whereas expression of β dystroglycan, which is cotranslated with α dystroglycan, is largely unchanged. Loss of native α dystroglycan expression was significantly more pronounced in stage 4 NBL than in pooled samples of stage 1 and stage 2 NBL, suggesting that loss of native α dystroglycan expression increases with advancing tumor stage. Neuroblastoma and RMS samples with reduced expression of native α dystroglycan also showed reduced laminin binding in laminin overlay experiments. Expression of natively glycosylated α dystroglycan was not altered in several other pediatric tumor types when compared with appropriate normal tissue controls. These data provide the first evidence that α dystroglycan glycosylation and laminin binding to α dystroglycan are altered in certain pediatric solid tumors and suggest that aberrant dystroglycan glycosylation may contribute to tumor cell biology in patients with RMS, medulloblastoma, and NBL.

Despite improved technology and knowledge, chronic lung disease (CLD) continues to be a significant problem for infants in Neonatal Intensive Care Unit (NICU) settings. Many new management strategies have been developed in hopes of reducing the incidence and consequences of CLD. In our Level III NICU, we instituted such a strategy called "The Golden Hour" Guideline. Important components of the Golden Hour Guideline are: use of the Neopuff TM device in the delivery room (DR) and during transport to the NICU, surfactant administration in the DR before 15 minutes of life, and attempted DR extubation if the infant Ն 28 weeks gestational age and/or 1 kg in weight. Specific aims of this project were to examine the impact of this guideline on: incidence of CLD, number of ventilator hours, rates of infant steroid use, and number of continuous positive airway pressure (CPAP) hours, oxygen use at time of discharge, and rates of extubation failure. The sample was comprised of infants who were Յ 31 weeks gestation on admission to the NICU between January, 2001 and January, 2004. This group was subdivided into two subgroups: infants admitted before the institution of the Golden Hour Guideline (July, 2002) and those admitted after. Data collected included: infant demographics (e.g., gender, ethnicity, gestational age, birth weight, etc.), maternal demographics (e.g., maternal age, ethnicity, medical conditions, medications, etc.), total number of ventilator hours, postnatal steroid use, total number of CPAP hours, number of surfactant doses, oxygen use at time of discharge, number and reasons for reintubations (extubation failures), and presence of CLD. The Vermont Oxford Network (VON), along with chart review, was used for data collection. Extubation failure was defined as reintubation within 72 hours of extubation. Chronic lung disease was defined as continued oxygen dependency at 36 weeks post-conceptual age. Data collection is almost complete. Data analysis will evaluate between-group differences (pre and post-guideline) using chi-square, t-test, and Mann-Whitney U test as appropriate. The results of this study will provide important information on the efficacy of the Golden Hour Guideline in decreasing CLD and will provide direction for further refinements in neonatal care.