Abel, Robin Michael; (1998) The ontogeny of the peptide innervation of the human pylorus with special reference to understanding the etiology and pathogenesis of infantile hypertrophic pyloric stenosis. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Despite many studies the aetiology of infantile hypertrophic pyloric stenosis is unknown. The ontogeny of the peptide innervation and structure of the normal pylorus have not been described. None of the published studies have been quantified to account for the dilutional reduction in neural tissue present. In none of the documented animal models have the sequence of changes been described. A. To examine the Ontogeny of the Peptide Innervation of the pylorus. B. To quantify the Histochemical and Morphological changes in infantile hypertrophic pyloric stenosis. C. To quantify the Histochemical changes in Natural and Experimental animal models of infantile hypertrophic pyloric stenosis. Conventional histology, immunohistochemitry, and carbocyanine neural tracers were used to examine the sequence of changes in the pattern of development of the normal human pylorus. The pattern of innervation was closely related to the expression was closely related to the gestational age and morphology of the pylorus. The expression of a wide range of neurtoransmitters was immunohistochemically examined and the morphological changes in infantile hypertrophic pyloric stenosis were qantified. The longitudinal muscle layer was hypertrophied, nerves in different tissue layers had abnormal morphology, the ganglia were smaller, and there were selective changes in the expression of neurotranmitters in different tissues. The expression of Nitric Oxide Synthase was most greatly diminished. The morphological and histochemical changes within the pylorus of a natural, canine, model and experimental, hph-1 mouse, animal model of pyloric stenosis were examined. The chronological sequence of morphological and histochemical changes were documented in the hph-1 mice. The histological changes in this model were very similar to those in infants and dogs suffering pyloric stenosis. The ontogeny of the peptide innervation of the human pylorus is developmentally regulated. Selective changes in the expression of neurotransmitters occur in infantile hypertrophic pyloric stenosis. The fundamental abnormality appears to be aberrant Nitric Oxide Synthase activity.

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