Turnover of radioactive mucin precursors in the colon of patients with Hirschsprung's disease correlates with the development of enterocolitis

Abstract

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 Hirschsprung's disease (HD) are prone to episodes of enterocolitis even after corrective surgery, the aetiology of which is poorly understood. The authors 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 colonic mucins in the retained proximal ganglionated colon of nine HD patients at the time of pull-through were studied. Organ culture of intact 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 determined by relating radioactivity to tissue DNA content. These patients were followed up prospectively for a mean duration of 30.8 months. The patients were assigned to one of two groups according to the criteria of requiring hospital admission for enterocolitis during this period. There were five patients in the group that remained well after corrective surgery and four in the group that developed entercolitis. The turnover 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/μg DNA, and the group that was well had a median value of 2044 dpm/μg 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 barrier. It can be inferred that the lower the turnover, the more prone a patient is to postoperative enterocolitis. It is therefore possible that organ culture with radioactive mucin precursors of the proximal ganglionated mucosa performed at the time of pull-through has a predictive value in the development of postoperative enterocolitis.