bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endogenous nitric oxide in the regulation of gastric secretory and motor activity in humans
Authors: Konturek  , Fischer  , Gromotka  , Konturek  , Domschke  
Published: March 2003

Background:Studies in animals have shown that nitric oxide (NO) affects gastric secretory and motor functions. However, little information is available about the involvement of this substance in the control of gastric secretory and motor activity in man.Methods:This study, performed on 18 healthy, Helicobacter pylori‐negative volunteers, was designed to evaluate the role of NO in the control of gastric acid secretion and of gastrin and somatostatin release in response to ordinary feeding (group A) and on gastric motor and electrical activity (group B). Gastric acid secretion was determined by means of intragastric pH‐metry before and after feeding with a semi‐liquid meal. Plasma levels of gastrin and somatostatin were measured using specific radioimmunoassays. Gastric emptying rate was measured using the 13C‐acetate breath test, antral motor activity using a manometric catheter and myoelectric activity using cutaneous electrogastrography. Studies were repeated following pre‐treatment with NG‐monomethyl‐
L‐Arginine (
L‐NMMA),
L‐Arginine (
L‐Arg) or their combination.Results: L‐NMMA delayed the recovery of intragastric pH to the pre‐meal value, and suppressed postprandial gastrin release while increasing the plasma somatostatin level.
L‐Arg did not affect postprandial pH and plasma hormones, but reversed
L‐NMMA‐induced alterations in intragastric pH and in plasma gastrin and somatostatin levels. Both postprandial antral motor activity (motility index) and gastric emptying significantly increased in tests with
L‐NMMA, but this was not observed when
L‐NMMA was given in combination with
L‐Arg or when
L‐Arg alone was used. The gastric electrical pattern, as measured by cutaneous electrogastrography, was not affected by
L‐NMMA,
L‐Arg or their combination.Conclusions:(1) Endogenous NO appears to be involved in the regulation of postprandial gastric acid secretion. This effect may be mediated by the changes in release of gastrin and somatostatin. (2) Endogenous NO delays gastric emptying and antral motor activity without affecting gastric myoelectrical activity.
Low molecular weight heparin as adjuvant therapy in active ulcerative colitis
Authors: Törkvist  , Thorlacius  , Sjöqvist  , Bohman  , Lapidus  , Flood  , Ågren  , Raud  , Löfberg  
Published: March 2003

Background: Heparin given intravenously has shown beneficial effects in the treatment of refractory ulcerative colitis in open trials. Low molecular weight heparin (LMWH) offers advantages in the method of administration but have not been evaluated in inflammatory bowel disease conditions.Aim: To assess the tolerability and safety of subcutaneous self‐administered LMWH in outpatients with refractory ulcerative colitis and to evaluate any potential adjuvant therapeutic effect.Patients and Methods: Twelve patients with mild to moderately active ulcerative colitis were included in the trial. The patients had either responded poorly to treatment with conventional therapy, including oral and/or rectal glucocorticosteroids, or had experienced a rapid relapse during or shortly after GCS therapy. Dalteparin sodium 5000 units s.c. injection was administered twice daily for 12 weeks. Patients were monitored for possible adverse events and changes in clinical symptoms, and endoscopic and histological scores were analysed. Leucocyte scanning was performed at inclusion and at the end of the study.Results: Tolerability and compliance were excellent and no serious adverse events occurred. Eleven patients improved symptomatically and six (50%) attained complete remission after 12 weeks of treatment. Endoscopic, scintigraphic and histological scores were found to be significantly improved.Conclusion: Self‐administered LMWH given s.c. may be a safe adjuvant therapy for patients with active, glucocorticosteroids‐refractory ulcerative colitis. A controlled trial should be undertaken to confirm the positive effects found in this study.
Effect of prucalopride, a new enterokinetic agent, on gastrointestinal transit and anorectal function in healthy volunteers
Authors: Poen  , Felt‐Bersma  , Van Dongen  , Meuwissen  
Published: March 2003

Background: Prucalopride (PR) is a novel 5‐HT4 agonist enterokinetic compound.Aim: To evaluate its effect on bowel function, gut transit and anorectal function in healthy volunteers using a double‐blind, placebo‐controlled crossover study.Methods: Twenty‐four healthy volunteers (12 men, 12 women, mean age 25 years, range 20–53 years) were randomly assigned to 1 mg/placebo or 2 mg/placebo (PL). The trial consisted of five consecutive 1 week periods: no drug treatment, PR treatment or PL, washout, PL or PR, no treatment. Subjects maintained a diary of bowel function during the entire study period. Total intestinal transit time (TITT), mean colonic transit time (MCTT) and anorectal function (anal manometry, rectal sensitivity and rectal compliance) were assessed at the end of both treatment periods. Electrocardiography and blood sampling were performed for safety analysis; blood sampling was also used to check compliance.Results: No subjects withdrew from the study. Treatment with PR 2 mg showed a statistically significant increase in mean number of weekly stools (11.5 vs. 7.1 compared to PL, P = 0.04) and in the percentage of loose/watery stools (48 vs. 12% compared to PL, P = 0.005). Within 1 week, stool frequency and consistency returned to baseline values when treatment was stopped. MCTT was shortened significantly with both doses, i.e. from 35 h on PL to 25 h on PR 1 mg (P = 0.01) and from 43 h on PL to 22 h on PR 2 mg (P = 0.02). Anorectal function was unaffected by PR. Transient and moderate headache occurred in nine subjects during PR treatment and in six subjects during PL treatment.Conclusion: Prucalopride is well tolerated by healthy subjects and has a marked and consistent effect on stool frequency and consistency, and on colonic transit. In the present study prucalopride did not affect visceral sensitivity or sphincter function. It holds promise for patients with slow transit constipation.
The prevalence of dyspepsia and use of antisecretory medication in North Glasgow: role of Helicobacter pylori vs. lifestyle factors
Authors: Woodward  , Morrison  , Mccoll  
Published: March 2003

Aims: To determine the prevalence of dyspepsia and associated antisecretory medication usage, and their associations with H. pylori infection in the general population. In addition, to compare the importance of H. pylori infection relative to other potential causes of dyspepsia: alcohol, smoking and obesity.Methods: The study examined a random population sample of 784 men and 827 women from Glasgow. They completed a validated dyspepsia questionnaire and had their H. pylori status determined by serology.Results: The overall prevalence of dyspepsia was 12%; prescribed antisecretory medication had been used over the last 6 months by 7%. The odds ratio (95% CI) for dyspepsia, comparing H. pylori‐positives to negatives was 1.79 (1.03, 3.09) for men and 1.11 (0.70, 1.78) for women. Ever‐smoking (both sexes) and obesity (women) had higher odds ratios for dyspepsia than did H. pylori. Adjustment for age, social class, ever‐smoking, ever‐drinking and obesity reduced the H. pylori odds ratios for dyspepsia to 1.38 (0.73, 2.60) for men and 0.99 (0.57, 1.73) for women. The association between H. pylori and antisecretory medication usage was similar to that for dyspepsia.Conclusion: Obesity and smoking are more important risk factors, for dyspepsia and antisecretory medication usage, than is H. pylori. Reducing the burden and cost of dyspepsia will require lifestyle modification and not merely H. pylori eradication.
Mucosal healing and a fall in mucosal pro‐inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn’s disease
Authors: Fell  , Paintin  , Arnaud‐Battandier  , Beattie  , Hollis  , Kitching  , Donnet‐Hughes  , Macdonald  , Walker‐Smith  
Published: March 2003

Background:Although enteral nutrition is a recognized form of treatment for intestinal Crohn’s disease, there are persisting problems with feed palatability and only limited data as to its mode of action.Aim:To assess the effects of a specific oral polymeric diet (CT3211; Nestle, Vevey, Switzerland), which is rich in transforming growth factor β2, on the mucosal inflammatory process.Methods:Twenty‐nine consecutive children with active intestinal Crohn’s disease were treated with CT3211 as the sole source of nutrition for 8 weeks. Patients were assessed clinically, and endoscopically, whilst cytokine mRNA was measured in mucosal biopsies before and after treatment by quantitative reverse transcriptase polymerase chain reaction.Results:After 8 weeks 79% of children were in complete clinical remission. Macroscopic and histological healing in the terminal ileum and colon was associated with a decline in ileal and colonic interleukin‐1β mRNA (pre‐treatment to post‐treatment ratio 0.008 and 0.06: P < 0.001, P = 0.006). In the ileum there was also a fall in interferon γ mRNA (ratio 0.15, P < 0.001) with a rise in transforming growth factor β1 mRNA (ratio 10, P = 0.04), whilst in the colon interleukin‐8 mRNA fell with treatment (ratio 0.06, P < 0.05).Conclusions:The clinical response to oral polymeric diet CT3211 is associated with mucosal healing and a down regulation of mucosal pro‐inflammatory cytokine mRNA in both the terminal ileum and colon. In the ileum there was also an increase in transforming growth factor β1 mRNA.
Can Helicobacter pylori serology still be applied as a surrogate marker to identify peptic ulcer disease in dyspepsia?
Authors: Xia  , Kalantar  , Mitchell  , Talley  
Published: March 2003

Background: Helicobacter pylori infection and associated peptic ulcer disease (PUD) has become less common in some countries.Aim:To determine if H. pylori serology alone or combined with a history of ingestion of non‐steroidal anti‐inflammatory drugs (NSAIDs) and an age threshold can be used as an indirect ulcer test.Methods:Two hundred and fifty‐two consecutive Australian patients (121 males, mean age 52 years) referred for endoscopy were enrolled. Blood was tested by a validated ELISA. At endoscopy, eight biopsies were taken for CLO‐testing, culture and histology. NSAID use over the prior 3 months was recorded.Results:One hundred and six (42%) patients were seropositive for H. pylori, 48 (19%) patients had PUD and 30 (12%) used NSAIDs. Serology alone had a sensitivity of 52% and a specificity of 60% for identifying PUD; the sensitivity and specificity were 60% and 55%, respectively, when combined with a history of NSAID use. Serology, regardless of NSAID use, would have saved 23% in endoscopy workload but would have missed 17% of PUD cases if an age threshold of < 45 years was chosen for omitting endoscopy.Conclusions:Serology was a poor ulcer test despite an excellent performance for detecting H. pylori. A strategy combining serology and an age threshold with a history of NSAID use to reduce endoscopy workloads may not always be appropriate.
Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID‐enteropathy in the rat
Authors: Somasundaram  , Sigthorsson  , Simpson  , Watts  , Jacob  , Tavares  , Rafi  , Roseth  , Foster  , Price  , Wrigglesworth  , Bjarnason  
Published: March 2003

Background:The pathogenesis of NSAID‐induced gastrointestinal damage is believed to involve a nonprostaglandin dependent effect as well as prostaglandin dependent effects. One suggestion is that the nonprostaglandin mechanism involves uncoupling of mitochondrial oxidative phosphorylation.Aims:To assess the role of uncoupling of mitochondrial oxidative phosphorylation in the pathogenesis of small intestinal damage in the rat.Methods:We compared key pathophysiologic events in the small bowel following (i) dinitrophenol, an uncoupling agent (ii) parenteral aspirin, to inhibit cyclooxygenase without causing a ‘topical’ effect and (iii) the two together, using (iv) indomethacin as a positive control.Results:Dinitrophenol altered intestinal mitochondrial morphology, increased intestinal permeability and caused inflammation without affecting gastric permeability or intestinal prostanoid levels. Parenteral aspirin decreased mucosal prostanoids without affecting intestinal mitochondria in vivo, gastric or intestinal permeability. Aspirin caused no inflammation or ulcers. When dinitrophenol and aspirin were given together the changes in intestinal mitochondrial morphology, permeability, inflammation and prostanoid levels and the macro‐ and microscopic appearances of intestinal ulcers were similar to indomethacin.Conclusions:These studies allow dissociation of the contribution and consequences of uncoupling of mitochondrial oxidative phosphorylation and cyclooxygenase inhibition in the pathophysiology of NSAID enteropathy. While uncoupling of enterocyte mitochondrial oxidative phosphorylation leads to increased intestinal permeability and low grade inflammation, concurrent decreases in mucosal prostanoids appear to be important in the development of ulcers.
Selective action of a CCK‐B/gastrin receptor antagonist, S‐0509, on pentagastrin‐, peptone meal‐ and beer‐stimulated gastric acid secretion in dogs
Authors: Sasaki  , Matsuno  , Okabe  
Published: March 2003

Background:The pharmacological effects of a novel CCK‐B/gastrin receptor antagonist, S‐0509, on gastric acid secretion in dogs remain unknown.Aim:To evaluate the antisecretory effects of S‐0509 on gastric acid secretion and to compare such effects with famotidine or atropine in dogs stimulated with various gastric stimulants.Methods:Ten beagle dogs with a denervated Heidenhain pouch and three beagle dogs with an innervated gastric fistula were used. Gastric acid secretion was stimulated by either continuous intravenous administration of pentagastrin, carbachol or histamine, or oral administration of a peptone meal or beer.Results:In the Heidenhain pouch model, both intravenously administered and orally administered S‐0509 significantly inhibited the gastric acid secretion stimulated by pentagastrin, peptone meal and beer. Nonetheless, the drug had little or no effect on carbachol‐stimulated or histamine‐stimulated acid secretion. Famotidine extensively inhibited all gastric acid secretion stimulated by the above stimulants in a non‐selective manner. Atropine also significantly inhibited the acid secretion stimulated by pentagastrin, peptone meal, beer or carbachol, but was not able to inhibit stimulation due to histamine. Oral administration of peptone meal or beer significantly increased the plasma gastrin level. Similarly to the Heidenhain pouch model, even in the gastric fistula (GF) model, S‐0509 significantly inhibited pentagastrin‐stimulated gastric acid secretion, yet the drug had no effect on carbachol‐stimulated secretion.Conclusions:S‐0509 is a selective CCK‐B/gastrin receptor antagonist in dogs that inhibits gastric acid secretion stimulated by pentagastrin and gastrin‐releasing substances, but does not inhibit histamine‐stimulated and carbachol‐stimulated acid secretion.
Effects of midazolam on small bowel motility in humans
Authors: Castedal  , Björnsson  , Abrahamsson  
Published: March 2003

Background:Benzodiazepines are used as sedatives for some intestinal procedures and as hypnotics, and this is the reason for studying their effects on duodenojejunal motility.Methods:Antroduodenojejunal manometry was performed in 13 healthy volunteers on two different occasions, when placebo or midazolam were given intravenously (randomized, double‐blind). A bolus dose of midazolam 0.03 mg/kg was followed by 0.015 mg/kg after 1.5, 3 and 4.5 h. After 5 h observation of interdigestive motility, the volunteers were given a test meal and recording continued for another hour. Twenty‐eight motility variables were compared.Results:With midazolam the median motility index of phase III in the proximal duodenum was increased by 37% (P < 0.05), which was a consequence of both a longer duration (P < 0.01) and higher pressure amplitudes (P < 0.05), compared with placebo. A longer duration (9%) of phase III was also seen in the distal duodenum (P < 0.05). With midazolam the duration of the migrating motor complex was shortened by 27% (P < 0.05). No statistically significant difference was found for the number of episodes of phase III registered (P=0.09), or for the other 22 motility variables compared including the duodenal retroperistalsis in late phase III.Conclusion:Midazolam does affect some aspects of duodenal motility, especially in the proximal part, but phase III‐related retroperistalsis is not affected.
Systemic effect of peanut agglutinin following intravenous infusion into rats
Authors: Jordinson  , Fitzgerald  , Goodlad  , Brynes  , Grant  , Pignatelli  , Calam  
Published: March 2003

Background:Ingested peanut agglutinin stimulates colonic proliferation in humans. In rats, ingested peanut agglutinin stimulates hormone release and proliferation in the small and large intestines. Peanut agglutinin is absorbed into the circulation but little is known about the systemic effect of this lectin. Therefore, we studied the effect of intravenous peanut agglutinin on hormone release and intestinal growth.Method:Six rats per group received peanut agglutinin infusion at 0, 2, 20 or 200 μg/rat/day for 6 days via the right jugular vein. Organ weights were measured, pancreatic enzymes, DNA, RNA and protein levels were analysed. Plasma hormones were measured by radioimmunoassay. All tissues were examined histologically. Small intestinal and colonic proliferation rates were estimated by metaphase arrest.Results:High‐dose peanut agglutinin significantly reduced the wet weight of the stomach by 7% (P < 0.05) and large intestine by 10% (P < 0.05). Peanut agglutinin dose‐dependently released enteroglucagon; low‐, medium‐ and high‐dose by 64%, 126% (P < 0.01) and 180% (P < 0.01), respectively, and glucagon‐like peptide‐1 by 127% (P < 0.01), 169% (P < 0.01) and 315% (P < 0.001), respectively. Peanut agglutinin had no effect on cholesystokinin, gastrin or insulin levels. Peanut agglutinin, low‐, medium‐ and high‐dose stimulated proliferation in the mid colon by 42% (P < 0.01), 30% and 38%, respectively. Only high‐dose peanut agglutinin stimulated proliferation in the distal colon by 54% (P < 0.01). No histological changes were evident in any tissue.Conclusion:Intravenous peanut agglutinin released hormones and stimulated colonic proliferation. Proliferation of the small intestine seen after ingestion of peanut agglutinin in previous studies appears to require luminal contact between enterocytes and the lectin. Possible clinical applications include reversal of atrophy during total parenteral nutrition, anastomotic healing after surgery and restoration of mucosa integrity in colitis.
Managing heartburn at the ‘base’ of the GERD ‘iceberg’: effervescent ranitidine 150 mg b.d. provides faster and better heartburn relief than antacids
Authors: Earnest  , Robinson  , Rodriguez‐Stanley  , Ciociola  , Jaffe  , Silver  , Kleoudis  , Murdock  
Published: March 2003

Background:Many individuals with heartburn self‐medicate with antacids for relief of their symptoms.Aim:To compare efficacy of effervescent ranitidine to as‐needed calcium carbonate antacids in subjects who self‐treat heartburn.Methods:A total of 155 subjects with frequent antacid‐responsive heartburn were randomized to receive effervescent ranitidine 150 mg tablets b.d., or as‐needed calcium carbonate 750 mg for 12 weeks. Endoscopic oesophagitis severity and mucosal histology were assessed at baseline, and at weeks 6 and 12. Heartburn frequency, severity, and antacid consumption were recorded daily, and quality of life was assessed at baseline, and at weeks 6 and 12.Results:Heartburn frequency and severity were significantly decreased after 1 day of ranitidine (P < 0.02). By week 6, ranitidine had significantly decreased rescue antacid consumption (7.3 tablets, P < 0.001) vs. antacids (14.1 tablets). Endoscopic oesophagitis healing (≤ grade 1) was significantly better with ranitidine (55%, P=0.022) vs. antacids (29%). Quality of life was improved by both treatments; however, ranitidine was numerically superior for all quality of life parameters, statistically superior for several quality of life indices at week 6 and for the pain‐related index by week 12 (P < 0.05).Conclusions:For subjects self‐administering antacids for chronic heartburn, effervescent ranitidine 150 mg b.d. is more effective than antacids in reducing heartburn, healing erosive oesophagitis, alleviating pain, and improving quality of life.
Cisapride provides symptomatic relief in functional dyspepsia associated with gastric myoelectrical abnormality
Authors: Chen J. D. Z. , Ke M. Y. , Lin X. M. , Wang Z. , Zhang M. 
Published: March 2003

Objective:We evaluated the effects of cisapride (10 mg t.d.s. and 20 mg b.d.) on gastrointestinal symptoms and gastric myoelectrical activity in patients with functional dyspepsia. Myoelectrical activity was measured by electrogastrography.Methods:Patients with functional dyspepsia, defined as discomfort in the epigastrium, a negative endoscopy, and clinical symptoms of dyspepsia, were enrolled. A total of 38 patients participated in the study (23 female; 15 male; 24–72 years of age). Screening electrogastrography identified those with a normal electrogastrogram (14 subjects) and those with an abnormal electrogastrogram (24 patients). Patients were randomly assigned to 2 weeks of placebo or 2 weeks of cisapride (10 mg t.d.s.); both groups then received 2 weeks of cisapride (20 mg b.d.). Electrogastrograms were repeated at the end of each 2‐week treatment period.Results:Cisapride 10 mg t.d.s. significantly improved symptoms in all patients. An additional 2 weeks of treatment with cisapride 20 mg b.d. led to continued improvement in symptoms in all patients, with significant improvement in the group with abnormal baseline electrogastrograms. Cisapride significantly improved postprandial bloating and discomfort in patients with abnormal baseline electrogastrograms. Cisapride also significantly improved postprandial gastric myoelectrical activity as measured by electrogastrography in patients with abnormal baseline electrogastrograms.Conclusion:Cisapride provides symptomatic relief and improves gastric myoelectrical abnormalities in patients with functional dyspepsia.