The past five years' work supported by this grant have led us to conclude that the ileocolonic sphincter (ICS), at least in the dog and man, is only one of several elements that control motility and transit at the ileocolonic junction (ICJ). Mechanical factors, specifically the angulation of the terminal ileum upon the proximal colon, also contributes; but the major controlling mechanisms reside in the integrated and sometimes unique, motor patterns among distal ileum, ICS and proximal colon. Of the special motor events that are important in controlling transit at the ICJ, several have been identified and characterized by the current program. These include a) frequent ileal phasic bursts that migrate from terminal ileum into the ICS; indeed, these migrating phasic contractions constitute most the resistance at the ICS, b) ileal peristaltic waves (""""""""PPC's""""""""), these are powerful propagated contractions that begin in the ileum, pass through the ICS and then involve variable lengths of colon, c) receptive relaxation of the proximal colon, ahead of the peristaltic wave, d) unique ileocolonic motility in the late postprandial period, when food residue reaches the area. The past five years work has also yielded several powerful new methodologies, now validated to the point of broad application. These include, a) dual phase (liquid/solid) or dual site (gastric-small bowel and segmental large bowel) transit studies by which the unprepared colon can be studied noninvasively, b) application of the electromechanical barostat to the human and dog colons. Accordingly, this proposal will address the following Specific Aims: 1. To define the role of tonic changes in the wall of the colon in the control of transit at the ICJ; to explore mechanisms whereby tone is modified. 2. To define the patterns of specialized motility at the ICJ when food residue reaches the region; to determine the effects of these motor patterns on transit; to explore the control of these motilities. 3. To further establish the role of disordered ileocolonic motility and transit in human disease. Located between two segments of gut that are physiologically and ecologically distinct, the ileocolonic junction contributes importantly to homeostasis by optimizing retention of meal residues in the small bowel till digestion is largely complete. Conversely, to guard against the deleterious effects of bacterial overgrowth, coloileal reflux is minimized. The ICJ is the last important region of the gut to be studied in detail; it has proven to be the source of pathophysiologies of direct clinical relevance. These need to be further investigated.
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