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Morphological assessment of enteric neuromuscular disease causing intestinal pseudo-obstruction

Smith, Virpi Vanamo; (1993) Morphological assessment of enteric neuromuscular disease causing intestinal pseudo-obstruction. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Disorders of intestinal motility which cause functional obstruction (chronic idiopathic intestinal pseudo-obstruction; CUP) can be divided into two broad categories (neuropathic or myopathic) distinguishable by electrophysiological studies. Hirschsprung’s disease (HD), the commonest variety of CUP, is associated with a distal aganglionic segment of intestine of variable length, but the morphological changes in other rarer forms of CUP are less well defined. This thesis investigates currently available morphological methods and examines some immunohistochemical techniques in evaluating abnormalities in the smooth muscle and nerve cell cytoskeleton and the interface between these two elements as possible pathogenic factors in these puzzling conditions. Morphometric studies of myenteric neuronal densities have established a baseline against which some neurogenic forms of CUP, such as intestinal neuronal dysplasia (hyperganglionosis) and hypoganglionosis can be validated. A study of rectal suction biopsies, seeking changes reportedly indicative of intestinal neuronal dysplasia has suggested that some apparent abnormalities may merely be age-related variations. Similarly, previously reported abnormalities observed by silver staining of the myenteric plexus appear to be normal for the developing intestine. The majority of patients with neurogenic CIIP, identified clinically by electrophysiology, have no morphological abnormality of enteric innervation recognisable by conventional histological techniques and immunohistochemical studies of neurofilaments (NF), neural cell adhesion molecule (N-CAM) or muscarinic receptors were similarly unrewarding. In contrast, in myopathic CIIP some important new ultrastructural observations have been made regarding fibrosis, atrophy and central vacuolation of intestinal muscle. Peripheral vacuolation and folding of the smooth muscle plasma membrane are considered to be artifacts. Immunohistochemical studies using NF antibodies, originally applied to detect neuropathic abnormalities, demonstrated a striking increase in nerves in the circular muscle in myopathic CIIP. Probably of greatest significance was the identification of contractile protein isoform abnormalities in intestinal myopathies. This new approach has demonstrated notable changes, unrecognised by conventional methods, that may affect enteric muscular function. It also opens the way to further studies at the molecular and genetic levels.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Morphological assessment of enteric neuromuscular disease causing intestinal pseudo-obstruction
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10102256
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