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Introduction: Our knowledge of normal human colonic motility remains incomplete. Historically, this has been due to the relative inaccessibility of this organ for study, and the lack of standardisation of methods used to investigate it. Recent device development has provided us with advanced tools by which to assess colonic motility, namely pancolonic manometry, and the wireless motility capsule (WMC). Using traditional diagnostic tests, a subgroup of patients presenting with severe intractable symptoms, but without organic disease, are found to have slow transit constipation (STC). This is believed to be primarily due to colonic dysmotility, although colonic motor functions remain poorly understood in this group also. Aims: The principal aims of this thesis were to: (1) explore the effect of pancolonic manometric recording technique on colonic motility; (2) describe pancolonic motility in STC, compared to healthy control subjects; (3) using the wireless motility capsule (WMC), validate the precise location of the pH fall around the ileo-caecal junction as a landmark for measuring colonic motility; (4) obtain normative data for colonic motility (transit and contractility) and intraluminal pH in a large cohort of healthy volunteers using the WMC, and compare this to patients with STC. Methods: The following methods were used: (1) prolonged pancolonic manometry in healthy volunteers and patients with STC; (2) a dual scintigraphic technique, involving radioactive-labelling of the WMC in healthy volunteers; (3) wireless motility capsule studies of colonic motility in healthy volunteers and in patients with STC. Results: Colonic manometric recording technique (bowel preparation or not, and different catheter types) significantly influences some characteristics of propagating sequence (PS) activity, including frequency, amplitude, polarity, relationship between consecutive PSs, and circadian rhythm. Patients with STC display dysregulated colonic motor function represented by disorganised spatiotemporal patterning and loss of 'regional linkage' among PSs. The fall in pH measured by the WMC was confirmed to be either in the caecum, ascending colon, or as the capsule moved from the caecum to the ascending colon. Using the WMC, the upper limit of normal colonic transit time (CTT) was found to be 51 h; however, CTT is not a continuous variable and exhibits peaks every 24 h. CTT is significantly prolonged in females and affected by the study protocol employed. In patients with STC, colonic contractility (motility index) is increased in comparison with healthy controls, and intraluminal pH is more acidic in the proximal colon, and more alkaline in the distal colon. Conclusions: The method of pancolonic manometry requires standardisation. However, novel metrics derived from prolonged pancolonic recordings have improved our understanding of the physiology of colonic motor function in health, and also pathophysiology in constipation. The WMC provides an alternative, less invasive method to investigate colonic motility; this technique also requires standardisation, but early results in patients with STC complement those from manometry, and also reveal alterations in intraluminal pH that may be of pathophysiological significance.

Thesis (Ph. D.)--University of Missouri--Columbia, 2001. / "December 2001." Typescript. Vita. Includes bibliographical references (leaves 95-113). Also available on the Internet.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Thesis (Ph.D.)--Virginia Commonwealth University, 2008. / Title from title-page of electronic thesis. Prepared for: Dept. of Microbiology & Immunology. Bibliography: leaves 289-332.

Thesis (Ph.D.)--Virginia Commonwealth University, 2008. / Prepared for: Dept. of Microbiology and Immunology. Bibliography: leaves 289-332. Also available online via the Internet.

The major cell types in the canine colon musculature are interstitial cells of Cajal (ICC), circular muscle (CM) cells and longitudinal muscle (LM) cells. In isolated muscle strip studies, spontaneous membrane potential oscillations (slow waves) are generated in the submucosal border of the circular muscle where a gap junctionally well-coupled network of ICC and CM is found. CM devoid of LM and submucosal pacemaker region (CM preparations) are spontaneously quiescent. The research undertaken was to understand the mechanism of slow wave propagation into the circular muscle and to investigate the consequences to the electrical activity in CM after coupling with different electrical activities from different cells types. Our results show that CM cells, although spontaneously quiescent because of high K+ conductance, are excitable and can actively participate in slow wave generation. The electrical oscillations induced in the CM preparations could easily be potentiated by an L-type Ca2+ channel activator, Bay K 8644, and abolished by a L-type Ca2+ antagonist, D600, suggesting involvement of the conductance in the induced activity. The induced oscillations are similar to the SLAPs in the longitudinal muscle which shows that it is not necessary to have a specialized pacemaker cells for generating SLAPs. Using a cross sectioned preparation with all intact muscle layers, we also showed that the heterogeneity in the electrical activity of CM, such as: the resting membrane potential gradient, depolarization of plateau potential in the myenteric border and "apparent" decay in slow wave amplitude, is due to electrical interactions between different intrinsic activities from different cell types. Morphological evidence was obtained for the possible communication pathways in the submucosal and the myenteric borders of the circular muscle. Different coupling mechanisms in different areas were hypothesized. In addition, the 3-dimensional aspects of the submucosal ICC network in the ca.nine colon were clarified. / Thesis / Master of Engineering (ME)

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.