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Br J Pharmacol. 2000 Jun;130(3):706-12.
Increased defecation during stress or after 5-hydroxytryptophan: selective inhibition by the 5-HT(4) receptor antagonist, SB-207266.

Sanger GJ, Yoshida M, Yahyah M, Kitazumi K.

Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, Third Avenue, Harlow, Essex, CM19 5AW.

5-HT(4) receptor antagonism prevents the ability of exogenous 5-HT or 5-HTP to sensitize the intestinal peristaltic reflex and increase the rate of defecation, generally without affecting non-stimulated intestinal function. In this study we confirmed the ability of the selective 5-HT(4) receptor antagonist SB-207266 1 - 1000 microg kg(-1) p.o., to prevent the increase in defecation evoked over a 60 min period by 5-HTP 10 mg kg(-1) s.c. in conscious mice, in the absence of an apparent constipating action. The role of endogenous 5-HT in the mechanisms of increased defecation and/or diarrhoea was then investigated in conscious, fed rats. This was evoked by 180 min exposure to restraint stress, which increased both the number and mean weight of formed, faecal pellets excreted over the entire time period. SB-207266 1 - 1000 microg kg(-1) p.o. (dosed 30 min before restraint) did not affect the increase in defecation evoked during the first 60 min of restraint stress, but significantly and dose-dependently reduced or prevented the increased defecation during the remaining 120 min of the experiment; this action occurred in the absence of an apparent constipating action of SB-207266. In fasted rats exposed to restraint stress, watery diarrhoea developed and although there was a tendency for SB-207266 1 - 1000 microg kg(-1) p.o. (dosed 30 min before restraint) to reduce the incidence of diarrhoea, this inhibition was not complete. We conclude that selective 5-HT(4) receptor antagonism prevents disruptions in defecation behaviours caused by exogenous or endogenous enteric 5-HT and that this activity is not accompanied by a concomitant suppression of activity (constipation-like)

Prim. Care Update Ob Gyns. 1998 Jul 1;5(4):197.
Are the long-term adverse effects of laparoscopic presacral neurectomy for the management of central pain associated with endometriosis acceptable?

Nezhat CH, Seidman DS, Nezhat F, Nezhat C.

Department of Gyn/Ob, Stanford University School of Medicine, California, Stanford, USA

Objective: To assess the long-term genitourinary and gastrointestinal complaints following presacral neurectomy.Design: A prospective postoperative follow-up of patients who underwent laparoscopic presacral neurectomy and treatment of endometriosis.Materials and Methods: The mean follow-up of the 67 women (mean age 27.5 years, range 16-58 years) was an average of 36.8 months with a range of 6-69 years. Main outcome variables include diarrhea, constipation, bladder and urinary complaints, vaginal dryness, dyspareunia, and orgasm. The degree of pain and dysmenorrhea after surgery was also elevated.Results: Diarrhea was reported to have improved after surgery in 39.1% of the patients and none reported any worsening. Constipation improved in 28.6% and worsened in 12.5%. Only one patient suffered from debilitating constipation. Bladder and urinary problems were improved on 25.0% and worsened in 19.2%. A similar proportion of women (19.6%) reported improvement and worsening vaginal dryness. Pain during intercourse improved in 58.9% and worsened in 8.9%. The ability to achieve orgasm improved in 21.6% and worsened in 2.7%. Postoperatively, pain was improved by 80-100% in 46.6% of the women, by 50-80% in 36.5%, by less than 50% in 6.4%, and did not improve in 9.5%. Dysmenorrhea was improved by 80-100% in 35.2% of the women, by 50-80% in 38.8%, by less than 50% in 14.9%, and did not improve in 11.1%. Twelve of 16 patients trying to become pregnant were successful following surgery, two with the aid of in vitro fertilization.Conclusion: After laparoscopic presacral neurectomy, constipation and bladder and urinary problems were reported to have worsened in only a minority of patients. How

Gastrointest Endosc. 2000 Jun;51(6):647-51.
Colonic neoplasia in patients with nonspecific GI symptoms.

Lieberman DA, de Garmo PL, Fleischer DE, Eisen GM, Chan BK, Helfand M.

Departments of Medicine, Oregon Health Sciences University, Portland 97207, USA.

BACKGROUND: The purpose of this study was to determine the prevalence rate of colonic polyps or masses 1 cm or greater in diameter in patients with nonspecific abdominal symptoms, from diverse practice settings, using a national endoscopic database. METHODS: Consecutive patients undergoing colonoscopy were included based on procedure indication. Endoscopic data were generated with a computer database at each practice site, transmitted to a central data bank and merged with data from multiple sites for analysis. Group 1 patients had nonspecific abdominal symptoms, which were defined as pain, constipation and diarrhea. Group 2 patients had a positive fecal occult blood test. Group 3 patients were asymptomatic, undergoing screening colonoscopy. Serious colon pathology was defined as a polyp or mass greater than 9 mm in size. RESULTS: Data were collected from 31 practice sites in 21 states during a period of 18 months. Of the 20,745 colonoscopy examinations, 9.2% were performed to evaluate patients with nonspecific abdominal symptoms, excluding other indications. Among patients with nonspecific symptoms 7.27% had polyp(s) 1 cm or greater in diameter compared with 17.05% of patients with positive fecal occult blood test (odds ratio 2.12: CI [1.73, 2.60]; p < 0.001). Patients with nonspecific symptoms had similar rates of large polyps as asymptomatic patients (7.27% vs. 6.45%, p = 0.32). Multivariate analysis identified several independent variables including increasing age, male gender and practice site at a Veterans Affairs Medical Center. CONCLUSIONS: In diverse, practice-based settings, patients with nonspecific abdominal symptoms who are referred for colonoscopy do not have a higher risk of serious colonic pathology than asymptomatic patient

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