A decade of experience with the primary pull-through for hirschsprung disease in the newborn period: a multicenter analysis of outcomes.

OBJECTIVE: To determine whether use of a primary pull-through would result in equivalent perioperative and long-term complications compared with the two-stage approach. SUMMARY BACKGROUND DATA: During the past decade, the authors have advanced the use of a primary pull-through for Hirschsprung disease in the newborn, and preliminary results have suggested excellent outcomes. METHODS: From May 1989 through September 1999, 78 infants underwent a primary endorectal pull-through (ERPT) procedure at four pediatric surgical sites. Data were collected from medical records and a parental telephone interview (if the child was older than 3 years) to assess stooling patterns. A similar group of patients treated in a two-stage fashion served as a historical control. RESULTS: Mean age at the time of ERPT was 17.8 days of life. Comparing primary ERPT with a two-stage approach showed a trend toward a higher incidence of enterocolitis in the primary ERPT group compared with those with a two-stage approach (42.0% vs. 22.0%). Other complications were either lower in the primary ERPT group or similar, including rate of soiling and development of a bowel obstruction. Median number of stools per day was two at a mean follow-up of 4.1 +/- 2.5 years, with 83% having three or fewer stools per day. CONCLUSIONS: Performance of a primary ERPT for Hirschsprung disease in the newborn is an excellent option. Results were comparable to those of the two-stage procedure. The greater incidence of enterocolitis appears to be due to a lower threshold in diagnosing enterocolitis in more recent years.

Müllerian inhibiting substance blocks epidermal growth factor receptor phosphorylation in fetal rat lung membranes.

Neonatal males develop respiratory distress syndrome more frequently than females for unknown reasons. The fetal testis secretes testosterone and müllerian inhibiting substance (MIS); MIS has been shown to inhibit fetal lung maturation in vitro and in vivo and to block phosphorylation of epidermal growth factor (EGF) receptors in A431 cells. We hypothesized that MIS would also inhibit membrane phosphorylation of EGF receptors in fetal lung, and that ultrastructural study of MIS-exposed lung might complement the biochemical data by assessing the effect of MIS on tissue morphology. Lung membranes were prepared from 19.5-day fetal rats and phosphorylation assays performed with 3 to 4 micrograms of membrane protein, with or without EGF (26 nmol/L), 0.025 mCi AT32P (0.136 mumol/L), and either recombinant human MIS (rhMIS, 30 pmol) from media of Chinese hamster ovary (CHO) cells, rhMIS dialysis buffer, or wild-type CHO media. The 170,000 molecular weight EGF receptor, visualized by autoradiography of polyacrylamide gels, was phosphorylated in both female and male membranes. rhMIS, when added to EGF-stimulated membranes, caused significant inhibition of EGF receptor phosphorylation (females: 32.42% +/- 11.5%; males: 32.3% +/- 19.1%, P less than 0.001; rhMIS-treated v EGF-stimulated state, P = NS, male v female, Cerenkov counting). Electron microscopy (EM) of rhMIS-exposed lung showed decreased lamellar bodies (LB) in both male alveolar spaces and female parenchyma, and, unexpectedly, increased numbers in female alveoli. Immunoabsorption experiments using coincubation of rhMIS with anti-rhMIS IgG polyclonal antibodies or equiprotein normal IgG demonstrated MIS antibody-specific reversal of rhMIS activity in membrane phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)