Chagas disease frequently causes megacolon. We investigated the enteric nervous systems in patients with chagasic megacolon compared to idiopathic megacolon and controls. Surgical specimens were obtained from 12 patients with chagasic megacolon (1 woman, 11 men, age range 41 to 72 y) and 9 patients with idiopathic megacolon (3 women, 6 men, age range 39 to 68 y), undergoing surgery for intractable constipation. A control group of 10 patients (9 women, 1 man, age range 43 to 75 y) undergoing left hemicolectomy for nonobstructing colorectal cancer was also studied. Colonic sections were investigated by conventional and immunohistochemical methods, also taking into consideration the presence of lymphocytes. Compared to controls, the 2 megacolon groups showed a decrease of enteric neurons (not due to increased apoptosis) and of enteric glial cells (all more important in chagasic patients). The interstitial cells of Cajal subtypes were decreased but not absent in megacolons, although an increase of the intramuscular subtype was found, suggesting a possible compensative mechanism. An increased amount of fibrosis was found in the smooth muscle and the myenteric plexus of chagasic patients compared to the idiopathic megacolon and the control group. A mild lymphocytic infiltration of the enteric plexuses (more evident in Chagas disease) was also found in megacolons but not in controls. Patients with chagasic megacolon display important abnormalities of several components of the enteric nervous system. Similar alterations, although of lesser severity, may be found in patients with idiopathic megacolon.
Background and aims-Gastrointestinal disorders is one of the clinical manifestations of chronic Chagas' disease. The pathogenesis seems to be associated with autonomic dysfunction. Here, we consider the muscarinic cholinoceptor mediated alteration in distal colon function in chagasic megacolon. Patients-Patients were divided into four groups: group I, chronic chagasic patients with megacolon; group II, chronic chagasic patients without megacolon; group III, nonchagasic patients with megacolon; and group IV, normal healthy volunteers (control). Methods-Binding assay and immunoblot of cholinoceptors from human and rat colon and enzyme immunoassay (ELISA) using a synthetic 24mer peptide corresponding to the second extracellular loop of human M 2 muscarinic acetylcholine receptors (mAChR) were used to detect the presence of serum antibodies. The eVect of antibodies on basal tone and 3',5'-cyclic monophosphate (cAMP) production of human and rat distal colon strips were also tested. Results-Group I but not the other groups had circulating antibodies capable of interacting with human colon activating M 2 mAChR, as they competed with binding of specific radioligand to mAChR and interacted with the second extracellular loop of human M 2 mAChR. Moreover, aYnity purified anti-M 2 peptide IgG from group I, in common with monoclonal antihuman M 2 mAChR, recognised bands with a molecular weight corresponding to colon mAChR. This antibody also displayed an agonist-like activity, increasing basal tone and decreasing cAMP accumulation. Both eVects were blunted by AF-DX 116 and neutralised by the synthetic peptide. Conclusions-In chagasic patients with megacolon there are antibodies that can recognise and activate M 2 mAChR. The implications of these autoantibodies in the pathogenesis of chagasic megacolon is discussed. (Gut 2001;49:699-705)
The human colon is still a relatively unknown viscus, especially concerning its motor activity. However, in recent years, techniques have been perfected that allow a better understanding of colonic motility, especially through prolonged recording periods. In this way, it has been demonstrated that the viscus contracts according to a circadian trend, is responsive to physiological stimuli (meals, sleep), and features high amplitude, propulsive contractions that are part of the complex dynamic of the defecatory process. These physiological properties and their alterations in patients with chronic idiopathic constipation are reviewed in this article.
Fecal incontinence is a disabling disease, often observed in young subjects, that may have devastating psycho-social consequences. In the last years, numerous evidences have been reported on the efficacy of bio-feedback techniques for the treatment of this disorder. Overall, the literature data claim a success rate in more than 70% of cases in the short term. However, recent controlled trials have not confirmed this optimistic view, thus emphasizing the role of standard care. Nonetheless, many authors believe that this should be the first therapeutic approach for fecal incontinence due to the efficacy, lack of side-effects, and scarce invasiveness. Well-designed randomized, controlled trial are eagerly awaited to solve this therapeutic dilemma.
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