Showing papers by "Simon Murch published in 1994"

Aetiology and pathogenesis of chronic inflammatory bowel disease

Abstract: Summary While Crohn's disease and ulcerative colitis are both conditions characterized by intestinal inflammation, with some overlap in their clinical and histological features, they are essentially different in pathogenesis. Crohn's disease appears to be primarily a condition of chronic T-lymphocyte activation, with tissue damage induced by secondary macrophage activation. What activates the T-cells is unknown. In this chapter we look at the evidence for and against cell-wall deficient mycobacteria species, viral infection of vascular endothelium and luminal contents as potential mechanisms of chronic activation. In ulcerative colitis, by contrast, there is no strong evidence for T-cell activation, and humoral mechanisms predominate. While the finding of atypical anti-neutrophil cytoplasmic antibodies (P-ANCAs) may be useful in screening, the only novel pathogenetic discovery is the co-localization of a 40 kD colonic autoantibody with immunoglobulins and complement on the apical enterocyte surface. Despite the fundamental differences in initiating mechanisms, the twoconditions have many ‘downstream’ inflammatory processes in common. We discuss the evidence for local production of cytokines, arachidonic acid metabolites and reactive oxygen and nitrogen radicals, highlighting the potential adverse consequences for intestinal vascular integrity.

Medical management of chronic inflammatory bowel disease

Abstract: Summary In the absence of a definitive cure for Crohn's disease and ulcerative colitis,the aim of therapy must be to induce and maintain clinical remission at acceptable cost to the patient in terms of adverse effects. Despite the differences in their pathogenesis, the first-line treatments for Crohn's disease and ulcerative colitis are still based upon combinations of aminosalicylic acid derivatives and corticosteroids, although the use of enteral nutrition regimes is becoming increasingly widespread in Crohn's disease. In this chapter we attempt to provide reasonably didactic guidance for the management of most cases of chronic inflammatory bowel disease. However, we have tried to go beyond this brief, motivated by the recent explosion in knowledge of inflammatory mechanisms, to suggest a rational approach to the choice of newer and less well tested therapeutic approaches in the affected child who is not responding effectively. The relative failure of cyclosporine therapy in Crohn's disease has been particularly disappointing in view of its ideal theoretical suitability. However, the encouraging early reports of treatment with anti-CD4 and anti-TNFα monoclonals suggest that the shift from broad spectrum immunomodulation to the targeting of critical components of the inflammatory cascade may yet field important dividends.