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  • 1
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Tegaserod is a 5-hydroxytryptamine-4 receptor partial agonist. Oral administration causes gastrointestinal effects resulting in increased gastrointestinal motility and attenuation of visceral sensation.Aim : To determine the long-term safety and tolerability of tegaserod in patients suffering from irritable bowel syndrome with constipation as the predominant symptom of altered bowel habits.Method : A multicentre, open-label study with flexible dose titration of tegaserod in out-patients suffering from constipation-predominant irritable bowel syndrome.Results : A total of 579 patients with constipation-predominant irritable bowel syndrome were treated with tegaserod. Of these, 304 (53%) completed the trial. The most common adverse events, classified as related to tegaserod for any dose, were mild and transient diarrhoea (10.1%), headache (8.3%), abdominal pain (7.4%) and flatulence (5.5%). Forty serious adverse events were reported in 25 patients (4.4% of patients) leading to discontinuation in six patients. There was one serious adverse event, acute abdominal pain, classified as possibly related to tegaserod. There were no consistent differences in adverse events between patients previously exposed to tegaserod and those treated de novo. No pattern-forming tegaserod-related abnormalities in haematological and biochemical laboratory tests, urinalysis, blood pressure, pulse rate or electrocardiograms were found.Conclusions : Tegaserod appears to be well tolerated in the treatment of patients with constipation-predominant irritable bowel syndrome. The adverse event profile, clinical laboratory evaluations, vital signs and electrocardiogram recordings revealed no evidence of any unexpected adverse events, and suggest that treatment is safe over a 12-month period.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 1 (1956), S. 507-511 
    ISSN: 1573-2568
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 36 (1991), S. 168-173 
    ISSN: 1573-2568
    Keywords: enteric nerves ; electrical field stimulation ; ketanserine ; methysergide ; ICS 205-930
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of 5-hydroxytryptamine (5HT) was studied in circular and longitudinal muscle from the proximal and distal colon of New Zealand white rabbits. 5HT stimulated a dose-dependent isometric contraction of distal and proximal circular muscle that was greater than in distal longitudinal muscle (P〈0.01). 5HT did not stimulate taenia coli longitudinal muscle. The EC50 for 5HT stimulation of distal circular muscle (−7.0±0.1), distal longitudinal muscle, and proximal circular muscle was similar. Methysergide dose-dependently inhibited the 5HT stimulation of both proximal and distal circular muscle. The IC50 for methysergide inhibition of 5HT (5×10−7 M) stimulation was −5.5±0.2. Ketanserine and ICS 205-930 did not inhibit 5HT stimulation of colonic muscle. Tetrodotoxin (TTX) decreased the potency, but not the efficacy of 5HT stimulation of proximal and distal circular muscle. Atropine decreased the potency (EC50=−6.6±0.1) (P〈0.05) and the efficacy by 40%. Electrical field stimulation (EFS) caused an on-contraction and off-contraction of distal circular muscle and an on-contraction of proximal circular muscle. 5HT decreased the off-contraction of the distal circular muscle but did not affect the on-contraction of the other muscle strips. 5HT receptor antagonists did not affect EFS of the tissue. The studies suggest: (1) 5HT stimulates circular colonic muscle with greater efficacy than longitudinal muscle, (2) 5HT stimulates circular muscle through a 5HT1 receptor, (3) there is atropine-sensitive and atropine-insensitive 5HT stimulation of circular colonic muscle, (4) 5HT inhibits neurons responsible for the off-contraction in distal circular muscle without affecting the on-contraction. Thus, 5HT affects colonic contraction by a direct effect on muscle and indirectly through the enteric nerves.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-2568
    Keywords: duodenal ulcer ; acute therapy ; substituted benzimidazole ; omeprazole ; H2-antagonist ; ranitidine ; gastrin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To assess the comparative efficacy of omeprazole 20 mg, a proton pump inhibitor, versus ranitidine 150 mg twice a day, an H2-receptor antagonist, in healing duodenal ulcers we performed a randomized, double-blind, multicenter trial in 309 patients with endoscopically diagnosed ulcers. Patients were treated for up to four weeks and were seen at week 2 and at week 4, if unhealed at week 2, for determination of ulcer status by endoscopy, review of daily self-assessment symptom diaries, and clinical laboratory including fasting serum gastrin. Gastrin levels were repeated two weeks after cessation of study medication. Evaluation of baseline demographic and laboratory parameters demonstrated no significant differences between the two groups at entry. At week 2, 42% of the omeprazole and 34% of the ranitidine-treated patients were healed (P=NS). At week 4, there was a 19% advantage in ulcer healing for the omeprazole-treated patients in comparison to those treated with ranitidine (82% vs 63%, respectively,P〈0.05). Healing of ulcers ≥1.0 cm occurred in 83% of those treated with omeprazole versus 37% treated with ranitidine (P〈0.01). There were no significant differences in rate of pain relief or incidence of clinical laboratory abnormalities. Mean fasting serum gastrin value during treatment increased over the baseline in both groups, (P〈0.05). The percent change was significantly greater with omeprazole but few patients had elevations above the upper limit of normal for the assay. Both drugs were well tolerated. Omeprazole 20 mg demonstrated superiority in healing duodenal ulcers at four weeks in comparison to ranitidine 150 mg twice daily and was more effective in healing ulcers 〉-1.0 cm.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 30 (1985), S. 40-44 
    ISSN: 1573-2568
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Colonic smooth muscle spike potentials and contractility were recorded during the periods of stress by a bipolar electrode-perfused catheter apparatus placed in the rectosigmoid colon. Healthy subjects and patients with the irritable colon syndrome (ICS) were exposed to three standardized stressful conditions: (1) ice-water immersion, (2) Stroop stimulus differentiation test, and (3) ball sorting. In healthy controls, colonic motility. An increase in colonic motility occurred in patients with the irritable colon 〈0.5), or ball sorting. Respiratory frequency also increased after exposure to the stressful stimuli. However, repeat exposures to the stress tests did not stimulate colonic motility. An increase in colonic motility occurred in patients with the irritable colon syndrome pretreated with a placebo after exposure to ice water (P〈0.05), Stroop Test, or ball sorting (P〈0.05). However, after exposure to the stressful situations patients pretreated with chlordiazepoxide had a diminished increase in colonic motility or in respiratory frequency. These studies suggest: (1) in healthy controls habituation reduces the stress-related increase in colonic motility, and (2) in patients with the irritable colon syndrome, chlordiazepoxide decreases the stress-related increase in colonic motility.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 32 (1987), S. 833-840 
    ISSN: 1573-2568
    Keywords: M2-muscarinic receptor antagonist ; computer analysis of motility ; slow wave ; gastrocolonic response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of secoverine on colonic smooth muscle was measured in pationts with diverticular disease and in healthy subjects. The frequency of slow wave activity was determined using the fast Fourier transform (FFT) and peak identification analysis (SWSA). The mean slow wave frequency was similar (6 cycles/minute) in healthy subjects using both analytic methods. The slow wave frequency in patients with diverticular disease was similar to that in healthy subjects. The peak frequency measured with SWSA was uniformly higher than that measured with FFT. Secoverine, a muscarinic antagonist, did not affect the slow wave frequency. Eating a 1000-kcal meal initiates an increase in colonic spike activity (22±2 spike potential/30 min) (P〈0.001) in healthy subjects during the immediate postprandial period. The gastrocolonic response in patients with diverticular disease was prolonged for 60 min. Secoverine inhibited the gastrocolonic response in patients with diverticular disease. These studies suggest (1) patients with diverticular disease have a similar slow wave frequency as healthy subjects, (2) the gastrocolonic response is prolonged in patients with diverticular disease, and (3) secoverine inhibits the colonic response.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 33 (1988), S. 65S 
    ISSN: 1573-2568
    Keywords: experimental colitis ; electrical field stimulation ; bethanechol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Patients with ulcerative colitis have a decrease in colonic motility which may increase their diarrheal symptoms. Studies in patients with ulcerative colitis showed that the postprandial spike response was slightly decreased and the intraluminal pressure response was absent. In vitro studies showed that the circular smooth muscle, obtained from patients with ulcerative colitis or from a rabbit model of experimental colitis, generated decreased force compared to muscle not associated with mucosal inflammation. The decrease in muscle contraction was observed with bethanechol stimulation or electrical field stimulation. Since the response to an increased extracellular concentration of potassium ([K+]0) was also diminished, the decreased response appears to be caused by an abnormality in the intrinsic contractile mechanism of colonic smooth muscle. Further studies are necessary to determine if metabolic abnormalities are present in the colonic muscle in patients with colitis.
    Type of Medium: Electronic Resource
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