bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients
Authors: Jones  , Holtmann  , Rodrigo  , Ehsanullah  , Crompton  , Jacques  , Mills  
Published: March 2003

Background: Irritable bowel syndrome is one of the most common gastrointestinal disorders, yet no therapy convincingly controls the multiple symptoms of this syndrome.Aim: To compare the efficacy and tolerability of the new 5‐HT3‐receptor antagonist alosetron and the smooth muscle relaxant mebeverine in a double‐blind, multicentre, randomized trial.Methods: Six hundred and twenty‐three nonconstipated females with irritable bowel syndrome were randomized to receive alosetron 1 mg twice daily (n=319) or mebeverine 135 mg three times daily (n=304) for 12 weeks, followed by a 4‐week post‐treatment period. The primary efficacy end‐point was monthly responders for adequate relief of irritable bowel syndrome related abdominal pain and discomfort (defined as patients reporting adequate relief on at least 2 out of 4 weeks). Secondary end‐points included assessments of bowel function, including urgency, stool frequency and stool consistency.Results: There were significantly more responders in the alosetron group compared with mebeverine at months 2 and 3 (P < 0.01). Compared with mebeverine, the alosetron group experienced significant decreases in proportion of days with urgency and mean stool frequency, and had firmer stools within 1 week of starting treatment. A similar proportion of patients reported adverse events in the two treatment groups.Conclusions: In nonconstipated female irritable bowel syndrome patients, alosetron is significantly more effective than mebeverine in improving symptoms.
Nasogastric lansoprazole is effective in suppressing gastric acid secretion in critically ill patients
Authors: Tsai  , Poon  , Yu  , Chang  , Yeh  , Ko  , Chen  
Published: March 2003

Aim:To evaluate the effect of nasogastric lansoprazole on acid suppression in critically ill patients.Methods:Patients were eligible for the study if they had a nasogastric tube in place and had not received acid‐suppressive agents for 3 days prior to enrolment into the study. Patients with active gastrointestinal bleeding or a baseline gastric pH > 4.0 were excluded. Patients served as their own controls during a 24 h lead‐in period. Lansoprazole 30 mg was administered once daily with water through a nasogastric tube for 2 days. Intragastric pH was measured by continuous 24 h pH‐metry for 3 days.Results:Fifteen patients were enrolled into the study. The baseline median 24 h intragastric pH was 2.25 ± 1.01, and increased to 6.70 ± 0.82 (P= 0.001) after 2 days of lansoprazole. Mean percentage of time intragastric pH was ≥ 4.0 was 25 ± 13% at baseline, and increased to 84 ± 14% (P=0.001) after 2 days of lansoprazole.Conclusions:Nasogastric lansoprazole 30 mg daily is effective in suppressing gastric acid secretion in critically ill patients.
The effects of capsaicin on reflux, gastric emptying and dyspepsia
Authors: Rodriguez‐Stanley  , Collings  , Robinson  , Owen  , Miner  
Published: March 2003

Aims:To evaluate capsaicin’s effects on heartburn, dyspepsia, gastric acidity and emptying, and gastro‐oesophageal reflux, and to test the hypothesis that capsaicin induces heartburn and exacerbates symptoms by sensitizing the oesophagus.Methods:Eleven heartburn sufferers underwent two separate pH monitoring sessions and assessments of gastric emptying (13C‐octanoic acid breath test), heartburn and dyspepsia (100 mm VAS) after a non‐irritant meal. The meal consisted of a sausage biscuit with egg, cheese and 30 g raw onion, 8 oz chocolate milk and a peppermint patty. Thirty minutes prior to meal consumption, subjects were administered a placebo capsule. On visit 1, subjects consumed the meal containing 100 μl 13C‐octanoic acid cooked in the egg, over 15 min. On visit 2, subjects consumed the meal plus 5 mg capsaicin in gelatin capsules.Results:Oesophageal and gastric pH profiles and gastric emptying were not different between meals. Capsaicin did not alter mean heartburn and dyspepsia scores (P > 0.05), but significantly decreased time to peak heartburn (120 min vs. 247 min; P < 0.003). Time to peak dyspepsia was not altered by capsaicin (P > 0.05).Conclusion:Capsaicin enhances noxious postprandial heartburn, presumably by direct effects on sensory neurons.
Endothelial changes precede mucosal ulceration induced by indomethacin: an experimental study in the rat
Authors: Kelly  , Anthony  , Piasecki  , Lewin  , Pounder  , Wakefield  
Published: March 2003

Background: Indomethacin has been shown to damage the villous microvasculature concomitant with alterations in villous blood flow in the rat.Aim: To test the hypothesis that alterations in blood flow result from ultrastructural damage to microvasculature endothelium.Methods: In anaesthetized rats, jejunal villi were exteriorized in a chamber and blood flow in surface capillaries visualized by fluorescence microscopy. Villi were exposed both luminally and systemically to indomethacin (100 μg/mL) for 10 min or until blood slowing or stasis had occurred in superficial capillaries (n=3 per group). Control animals received both a luminal and intravenous vehicle for 45 min (n=3). The small intestines were vascular perfusion‐fixed with 1.5% glutaraldehyde and studied by transmission electron microscopy.Results: All controls appeared to be ultrastructurally normal. A 10 min exposure to indomethacin had no effect upon the epithelium but resulted in mild endothelial vacuolization and the development of small finger‐like projections into the lumen of villus surface microvasculature. At the point of blood slowing, villus tip epithelium was again normal but the endothelial vacuolization and finger‐like projections became more obvious. The endothelial projections and vacuolization became severe at the point of blood stasis; this also coincided with epithelial degeneration.Conclusion: This study shows that villus surface microvasculature is the earliest site of morphological damage after indomethacin exposure.
The effect of motilin agonist ABT‐229 on gastro‐oesophageal reflux, oesophageal motility and lower oesophageal sphincter characteristics in GERD patients
Authors: Van Herwaarden  , Samsom  , Van Nispen  , Verlinden  , Smout  
Published: March 2003

Background:ABT‐229, a motilin agonist without antibacterial activity, has been shown to enhance both lower oesophageal sphincter pressure in cats and gastric emptying in humans.Aim:To investigate the effect of oral treatment with ABT‐229 10 mg b.d., ABT‐229 5 mg b.d. and cisapride 10 mg q.d.s. on gastro‐oesophageal reflux, lower oesophageal sphincter pressure, transient lower oesophageal sphincter relaxations and symptoms in GERD patients.Methods:Twenty‐four GERD patients completed the study. A randomized, double‐blind, placebo‐controlled, three‐period incomplete crossover design was used with three dosing periods of 7 days. All patients received ABT‐229 10 mg b.d. and placebo during two of the three periods. In the remaining period 12 patients were given ABT‐229 5 mg b.d. and 12 received cisapride 10 mg q.d.s. Ambulatory 24 h recordings of oesophageal pH and pharyngeal, oesophageal, lower oesophageal sphincter and gastric pressures were performed on day 7 using an assembly incorporating a Dent sleeve connected to a portable water‐perfused manometric system.Results:Oesophageal acid exposure was not affected by ABT‐229 or cisapride, but the incidence of reflux episodes was reduced by cisapride. None of the drugs affected oesophageal motility, lower oesophageal sphincter pressure or the incidence of transient lower oesophageal sphincter relaxations. Both ABT‐229 10 mg b.d. and cisapride reduced the severity of daytime heartburn.Conclusion:The value of ABT‐229 in the treatment of GERD appears to be limited.
Beta(β)3‐adrenergic receptors in human pancreatic islet and duodenal somatostatin neuroendocrine cells
Authors: Anthony  , Sim  , Guillaume  , Strosberg  , Dhillon  , Pounder  , Wakefield  
Published: March 2003

Background:We previously localized β3‐adrenergic receptors immunohistochemically in human gastrointestinal smooth muscle and incidently found a population of human pancreatic islet cells and duodenal epithelial neuroendocrine cells that also expressed β3‐adrenergic receptors.Aim:To identify the nature of the islet and duodenal cells that stained positive for β3‐adrenergic receptors.Methods:Paraffin sections of human pancreas and duodenum and Chinese hamster ovary cells transfected with the human β3‐adrenergic receptor were immuno‐stained for β3‐adrenergic receptors using an affinity‐purified rabbit polyclonal antibody (anti‐P12) raised against a 15 amino acid sequence (P12) of the human receptor. Immunohistochemical staining for the receptor was carried out in the presence and absence of P12 peptide and both somatostatin 14 and 18 peptides. β3‐adrenergic receptor‐stained sections were also double‐immunostained with anti‐insulin, ‐glucagon, ‐somatostatin and ‐pancreatic polypeptide antibodies.Results:A subpopulation of human pancreatic islet cells and duodenal epithelial cells expressed positive cytoplasmic β3‐adrenergic receptor immunostaining. Using distribution and double‐staining techniques, these cells were found to be somatostatin‐positive D cells but not A or B cells. The positive staining of D cells with anti‐P12 antibody was inhibited by prior incubation of the antibody with P12 peptide but not somatostatin‐14 or ‐28 peptides. Pancreatic vascular smooth muscle and duodenal vascular and non‐vascular smooth muscle also stained with anti‐P12 antibody. Transfected Chinese hamster ovary cells showed positive membrane staining.Conclusion:We have identified a population of neuroendocrine cells in the human pancreas and duodenum that express β3‐adrenergic receptors. These cells appear to be somatostatin D cells.
Gastrin and Colorectal Cancer
Authors: Smith A. M. , Watson S. A. 
Published: March 2003

The polypeptide hormone gastrin was identified nearly a hundred years ago and its role in the regulation of acid secretion is well established. Gastrin also acts as a growth factor and is trophic for the normal gastric oxyntic mucosa. This growth promoting action has led to the extensive investigation of its role in carcinogenesis, in particular colorectal neoplasia. The relationship between gastrin and colorectal adenocarcinoma has been subject to controversy, however the findings from several recent studies have resulted in a clearer understanding of the mechanism of action of gastrin in this is common cancer.The majority of colorectal cancers produce their own gastrin, which may act in an autocrine manner. The tumour cells also express gastrin/CCKB receptors (and/or a combination of isoforms) which mediate the proliferative action. This locally produced gastrin gives rise to a small increase in systemic gastrin levels. Autocrine gastrin may also have a role in tumour development, as expression occurs early in the adenoma–carcinoma sequence. In addition, several studies using animal models have shown that systemic hypergastrinaemia promotes the proliferation of both normal and neoplastic colonic epithelium. Hyperproliferative colonic epithelium in the presence of hypergastrinaemia has been recorded in humans and a well‐designed epidemiological study has demonstrated an increased incidence of colorectal cancer.Gastrin is a potential therapeutic target in the treatment of colorectal cancer and several approaches have been assessed. Receptor antagonists and antisecretory agents have been demonstrated to be ineffectual. Novel methods of inhibition, including the use of anti‐gastrin antibodies, are currently being evaluated.
Gastric acid secretion in dogs in response to combinations of beer, ethanol and peptone meal – the role of endogenous gastrin
Authors: Matsuno K. , Sasaki N. , Okabe S. 
Published: March 2003

Summary Aim: To examine the effects of beer, ethanol, peptone meal and combinations of either peptone meal and beer or peptone meal and ethanol on gastric acid secretion in vagally denervated pouch dogs. Methods and Results: The oral administration of either 200 mL of beer, 5% ethanol or 10% peptone meal significantly stimulated gastric acid secretion for 60–90 min in these dogs. With 5% ethanol the plasma gastrin concentration was not affected for 90 min. Combinations of 10% peptone and beer (peptone–beer) or 10% peptone and 5% ethanol (peptone–ethanol) potentiated the acid secretion and increased the plasma gastrin level. While a selective cholecystokinin‐B/gastrin receptor antagonist, S‐0509, had no effect on ethanol‐stimulated acid secretion, the compound markedly inhibited both peptone–beer‐stimulated and peptone–ethanol‐stimulated gastric acid secretion. Famotidine and atropine significantly inhibited gastric acid secretion stimulated by 5% ethanol, peptone–beer and peptone–ethanol. Conclusions: The mechanisms by which peptone–beer and peptone–ethanol stimulate gastric acid secretion may be mediated not only by increased plasma gastrin, but also by the action of histamine and acetylcholine coupled with the increased plasma gastrin. Ethanol‐stimulated secretion appears to be unrelated to circulating gastrin, yet may be related to the acid regulatory mechanism involving histamine and acetylcholine.
Protective role of intracellular glutathione against nitric oxide‐induced necrosis in rat gastric mucosal cells
Authors: Naito Y. , Yoshikawa T. , Boku Y. , Fujii T. , Masui Y. , Tanaka Y. , Fujita N. , Yoshida N. , Kondo M. 
Published: March 2003

Summary Background: Nitric oxide synthase activity is increased in the stomach in association with Helicobacter pylori infection and portal hypertension, but the mechanism by which nitric oxide contributes to mucosal damage remains unclear. Aim: To examine whether nitric oxide injures gastric mucosal cells and whether cellular glutathione affects nitric oxide‐induced cytotoxicity. Methods: A confluent monolayer of RGM‐1 gastric mucosal cells was exposed to nitric oxide donors (NOC5 or NOC12). Cell viability was determined by trypan blue dye exclusion, lactate dehydrogenase release and supravital staining with Hoechst 33342 and propidium iodide. The kinetics of the reduced/oxidized forms of glutathione were also measured, as well as the effect of glutathione‐depletion or glutathione‐precursor treatment on nitric oxide‐induced cytotoxicity. Results: Excess exogenous nitric oxide produced by NOC5 or NOC12 induced necrosis in RGM‐1 cells in a time‐ and concentration‐dependent manner. The level of reduced glutathione drastically decreased prior to the loss of cell viability and remained low, but oxidized glutathione was not affected. Glutathione depletion increased necrosis of both NOCs in an NOC‐concentration‐related fashion, while pre‐treatment with γ‐glutamylcysteine ethyl ester reduced their necrotic susceptibility. Conclusion: Exogenous nitric oxide induced necrosis in gastric mucosal cells, and intracellular reduced glutathione protects gastric mucosal cells from damage by nitric oxide.
Effects of growth factors on aspirin‐induced inhibition of wound repair in a rabbit gastric epithelial cell model
Authors: Yoshizawa T. , Watanabe S. , Hirose M. , Yamamoto J. , Osada T. , Sato K. , Oide H. , Kitamura T. , Takei Y. , Ogihara T. , Miwa H. , Miyazaki A. , Sato N. 
Published: March 2003

Summary Background: Aspirin is known to cause adverse effects, including gastric mucosal injury, and to retard gastric wound healing. Growth factors including hepatocyte growth factor (HGF), epidermal growth factor (EGF) and insulin‐like growth factor‐I (IGF‐I) have been shown to play an important role in the repair of gastric mucosal injury. Aim: To employ the cultured gastric epithelial cell model to elucidate the effects of aspirin, as well as several growth factors (HGF, EGF and IGF‐I), on gastric wound repair. Methods: Isolated rabbit gastric epithelial cells (92% mucous cells) were cultured in F‐12 medium and formed a complete monolayer cell sheet in 48 h. A wound with a cell‐free area of constant size (2 mm
2) was then created and the wound repair process was monitored by measuring wound size every 12 h. Proliferating cells were detected by BrdU staining. Effects of aspirin (8 m
m), HGF (10 ng/mL), EGF (10 ng/mL) and IGF‐I (30 ng/mL) were assessed. Results: Aspirin significantly retarded wound healing, but simultaneous addition of growth factors significantly accelerated wound repair compared with aspirin alone. Growth factors reversed the aspirin‐induced inhibition of cell proliferation. Conclusion: Growth factors, including HGF, EGF and IGF‐I, reversed the aspirin‐induced inhibition of wound repair through their cytoprotective effects on gastric epithelial cells.
Comparison between in vivo and in vitro chemokine production in Helicobacter pylori infection
Authors: Ohsuga M. , Kusugami K. , Ina K. , Ando T. , Yamaguchi H. , Imada A. , Nishio Y. , Shimada M. , Tsuzuki T. , Noshiro M. , Konagaya T. , Kaneko H. 
Published: March 2003

Summary Background: Enhanced gastric mucosal chemokine activity has been demonstrated in patients with Helicobacter pylori infection. However, little is known about the mechanisms involved in this phenomenon. Aim: To examine whether in vivo chemokine activity is similar to in vitro response of gastric epithelial cells infected by H. pylori. Patients and Methods: Antral biopsy specimens were obtained from patients with H. pylori infection for organ culture, isolation of H. pylori and histological examination. Results: In organ cultures of mucosal tissues, the levels of interleukin‐8 and growth‐related gene product α were elevated in patients with peptic ulcer disease compared with those with erosive gastritis or endoscopically normal mucosa. However, there were no significant differences in in vitro cultures of MKN45 or KATO III cells that were infected with H. pylori isolated from these same patients. These in vivo and in vitroα‐chemokine levels showed no significant association with the presence of cagA gene and CagA protein, ureB genotype, or binding capacity to MKN45 or KATO III cells in individual H. pylori isolates. In contrast, in vivo mucosal α‐chemokine activity correlated with H. pylori colonization density. Conclusion: Mucosal chemokine profiles and inflammatory responses in H. pylori infection may be associated more closely with host factors, including those determining bacterial adhesiveness, than with differences in H. pylori strains.
Review article: in vitro studies of gall‐bladder smooth muscle function. Relevance in cholesterol gallstone disease
Authors: Portincasa P. , Minerva F. , Moschetta A. , Venneman N. , Vanberge‐Henegouwen G. P. , Palasciano G. 
Published: March 2003

SummaryThe interplay between contraction and relaxation in the gall‐bladder muscularis leads to appropriate gall‐bladder emptying and refilling during fasting and in the postprandial state in vivo. Several studies in both human and animal models have focused on cellular and molecular events in the gall‐bladder wall in health and disease in vitro. Principal methods to study gall‐bladder smooth muscle function include receptor binding studies (at the level of plasmamembranes or histological sections), phase contrast microscopy (at the level of isolated smooth muscle cells), and tensiometry (at the level of smooth muscle strips or the whole gall‐bladder). At a very early stage, cholesterol gallstone disease is characterized by exposure of the gall‐bladder wall to excess of biliary cholesterol and the cytotoxic effect of the bile salt deoxycholate. On a long‐term basis, a form of gall‐bladder leiomyopathy develops with defects involving the mechanisms of signal transduction at the level of plasmamembranes. The end‐stage result is pathological contraction and/or relaxation of smooth musculature, impaired gall‐bladder motility and gall‐bladder stasis, all key factors in the pathogenesis of biliary cholesterol crystallization and gallstones.
Review article: measurement of gall‐bladder motor function in health and disease
Authors: Jazrawi R. P. 
Published: March 2003

SummaryNormal gall‐bladder (GB) motor function plays an important role in the enterohepatic circulation of bile acids in health, and abnormal GB motor function has serious clinical implications. The old concept that the GB empties gradually during meals and fills between meals is still believed by many. This paper describes the techniques used in the measurement of GB motor function and discusses the information provided by these techniques in health and disease.
The prescribing of acid suppressants prior to the endoscopic diagnosis of Barrett’s oesophagus and oesophagitis
Authors: Todd J. A. , Weston T. , Macdonald T. M. , Johnston D. A. , Dillon J. F. 
Published: March 2003

Background:There has been a dramatic rise in incidences of Barrett’s oesophagus and oesophageal adenocarcinoma. It has been suggested that the introduction and use of acid suppression therapy may be a factor in the rising incidences of Barrett’s oesophagus and oesophageal adenocarcinoma.Methods:This was a record linkage study, using a prescribing database and an endoscopy database. Patients who had undergone their first endoscopy during the period 1992–1995 and received the diagnosis of Barrett’s oesophagus or oesophagitis were identified. The prescribing of acid suppressants was compared for the 3 years prior to endoscopy, between those with Barrett’s oesophagus and those with oesophagitis.Results:There was no significant difference between the Barrett’s patients and the oesophagitis patients in the proportion that had been exposed to acid suppression therapy (53.4% vs. 51.7%, P=0.704). The mean number of days of prescribing among those who had been exposed to acid suppression therapy was higher in the Barrett’s group (340.5 vs. 237.0 days, P=0.001).Conclusions:Patients with Barrett’s oesophagus have received more acid suppressant therapy prior to diagnosis. The reasons for this are not clear. However, 46.6% of Barrett’s patients have not been exposed to acid suppressant therapy.
There are some benefits for eradicating Helicobacter pylori in patients with non‐ulcer dyspepsia
Authors: Des Varannes S. Bruley , Fléjou J. F. , Colin R. , Zaïm M. , Meunier A. , Bidaut‐Mazel C. 
Published: March 2003

Background: The relationship between Helicobacter pylori infection and non‐ulcer dyspepsia is not established.Aim: To determine whether eradication of H. pylori might be of benefit in non‐ulcer dyspepsia patients.Methods: We randomly assigned 129 H. pylori infected patients with severe epigastric pain, without gastro‐oesophageal reflux symptoms, to receive twice daily treatment with 300 mg of ranitidine, 1000 mg of amoxicillin, and 500 mg of clarithromycin for 7 days and 124 such patients to receive identical‐appearing placebos.Results: Treatment was successful (decrease of symptoms at 12 months) in 62% of patients in the active‐treatment group and in 60% of the placebo group (N.S.). At 12 months, the rate of eradication of H. pylori was 69% in the active‐treatment group and 18% in the placebo group (P < 0.001). Complete relief of symptoms occurred significantly more frequently in patients on the active treatment (43%) than in placebo‐treated patients (31%, P=0.048). Within the active‐treatment group, therapeutic success was significantly more frequent in the non‐infected patients (84% vs. 64%, P=0.04).Conclusions: Although eradicating H. pylori is not likely to relieve symptoms in the majority of patients with non‐ulcer dyspepsia, a small proportion of H. pylori‐infected patients may benefit from eradication treatment.