Our aim was to investigate motor activity of the healthy, relatively unprepared colon in the ambulatory state. Twenty-five age- and gender-matched adults had a six-sensor solid-state probe inserted into the proximal transverse colon without sedation. Subjects ambulated freely and ate standard meals. In 528 h of recording, we found a lower (P < 0.05) area under the curve during the night. Waking induced a threefold increase in motility, whereas meals induced a twofold increase. Women showed less activity (P < 0.05) in the transverse/descending colon than men. The transverse/descending colon showed more (P < 0.05) activity than the rectosigmoid colon. Seven patterns were recognized; predominantly, they were simultaneous, propagated, or periodic bursts of 3-cycles/min (cpm) waves. A specialized propagating pressure wave with a high amplitude (>105 mmHg) and a prolonged duration (>14 s) occurred in all subjects (mean 10/day), mostly after waking, after meals, or with defecation. A 3-cpm motor activity was seen in the rectosigmoid region predominantly at night. The colon exhibits a wide spectrum of pressure activity around the clock, with gender and regional differences and circadian rhythm. This comprehensive study provides qualitative and quantitative normative data for colonic manometry.
Patients with slow-transit constipation exhibited either normal or decreased pressure activity with manometric features suggestive of colonic neuropathy or myopathy as evidenced by absent HAPC or attenuated colonic responses to meals and waking. In refractory patients, colonic manometry may be useful in characterizing the underlying pathophysiology and in guiding therapy.
This study represents the most comprehensive age- and gender-controlled assessment of anorectal function using solid state technology. Gender influences some parameters of anorectal function. Our results could serve as a valuable resource of normative data.
Whether physical exercise stimulates colonic motility is unclear. Our aim was to determine the immediate effects of graded exercise on colonic motility. Colonic motility was recorded at six sites in 11 untrained subjects, by colonoscopically placing a solid-state probe. Subjects were free to ambulate. The next day, subjects exercised on a bicycle at 25, 50, and 75% of peak oxygen uptake for 15 min, with each followed by a 15-min rest. Motor patterns, motility indexes, and regional variations before, during exercise, during rest, and during postexercise periods were compared. During exercise, there was an intensity-dependent decrease ( P < 0.001) in the number and area under the curve of pressure waves. The incidence of propagated or simultaneous pressure waves and cyclical events also decreased ( P < 0.05). After exercise, the pressure activity reverted to baseline, but the number and amplitude of propagated waves increased ( P < 0.01), whereas the simultaneous waves and cyclical events remained lower. Acute graded exercise decreases colonic phasic activity. This may offer less resistance to colonic flow, whereas the postexercise increase in propagated activity may enhance colonic propulsion.
Failure of local tumor control still poses a problem for radiotherapy and translates into reduced survival. Combining radiation with chemotherapy or other newer modalities has shown promising results. Immunological approaches to tumor therapy have found renewed interest due to improved insight into mechanisms involved in the immune response to tumors. In this paper, we studied tumor growth delay after various combination regimens of locally injected adenovirus constitutively expressing IL12 and B7.1 (AdIL12/B7.1) and fractionated radiotherapy in two nonimmunogenic murine tumor models, 4T1 and B16.F10. Effects of radiation and virus infection on surface antigen expression in these tumor lines were assessed. Mechanisms of action of AdIL12/B7.1 were studied by conducting additional experiments with and without depletion of NK-cells and/or T-cells, and by cytotoxic T-lymphocyte assays, and immunohistochemical evaluation of tumor blood vessels. Both B7.1 and IL12 were effectively expressed in both irradiated and unirradiated 4T1 and B16.F10 tumor cells but did not add significantly to radiation-induced cell killing in vitro. However, local tumor infection by AdIL12/B7.1 after irradiation significantly increases the effectiveness of radiotherapy when applied after completion of radiotherapy. The mechanism appears to be complicated, involving a host of factors that included the ability of IL12 to activate T-cells and NK-cells and to inhibit angiogenesis and the ability of radiation to induce apoptosis or necrosis among tumor cells. These data support the combination of radiotherapy with adenovirus-mediated immunotherapy and suggest that the concept of adding genetic immunotherapy after radiotherapy in a combined regimen merits further study.
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