TURNOVER OF RADIOACTIVE MUCIN PRECURSORS IN THE COLON OF PATIENTS WITH HIRSCHSPRUNGS-DISEASE CORRELATES WITH THE DEVELOPMENT OF ENTEROCOLITIS

Background/Purpose: Mucin glycoproteins (mucins) in the colonic mucus gel layer interact with pathogens performing protective functions by a variety of mechanisms. It is recognised that patients with Hirschspru ng's disease (HD) are prone to episodes of enterocolitis even after co rrective surgery, the aetiology of which is poorly understood. The aut hors correlated the turnover of radioactive mucin precursors in organ culture of the proximal ganglionated colon at the time of pull-through with the development of postoperative enterocolitis. Methods: The col onic mucins in the retained proximal ganglionated colon of nine HD pat ients at the time of pull-through were studied. Organ culture of intac t mucosa was performed with radioactive mucin precursors 35S-sulphate and 3H-glucosamine. Mucins in the secretions and epithelial cells were then purified by gel filtration. Turnover of the isotopes was determi ned by relating radioactivity to tissue DNA content. These patients we re followed up prospectively for a mean duration of 30.8 months. The p atients were assigned to one of two groups according to the criteria o f requiring hospital admission for enterocolitis during this period. T here were five patients in the group that remained well after correcti ve surgery and four in the group that developed entercolitis. The turn over values of both radioisotopes were analysed for differences in the two groups of patients. Results: Patients in the enterocolitis group had a median value for turnover of 331 dpm/mu g DNA, and the group tha t was well had a median value of 2044 dpm/mu g DNA. These differences were statistically significant (Mann-Whitney, p = .037). Conclusions: A reduced turnover of mucins as shown by incorporation of radioactive precursors will give rise to a defective colonic mucus-defensive barri er. It can be inferred that the lower the turnover, the more prone a p atient is to postoperative enterocolitis. It is therefore possible tha t organ culture with radioactive mucin precursors of the proximal gang lionated mucosa performed at the time of pull-through has a predictive value in the development of postoperative enterocolitis. Copyright (C ) 1998 by W.B. Saunders Company.