bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: potential gastrointestinal effects of long‐term acid suppression with proton pump inhibitors
Authors: Laine  , Ahnen  , Mcclain  , Solcia  , Walsh  
Published: March 2003

This review examines the evidence for the development of adverse effects due to prolonged gastric acid suppression with proton pump inhibitors. Potential areas of concern regarding long‐term proton pump inhibitor use have included: carcinoid formation; development of gastric adenocarcinoma (especially in patients with Helicobacter pylori infection); bacterial overgrowth; enteric infections; and malabsorption of fat, minerals, and vitamins.Prolonged proton pump inhibitor use may lead to enterochromaffin‐like cell hyperplasia, but has not been demonstrated to increase the risk of carcinoid formation. Long‐term proton pump inhibitor treatment has not been documented to hasten the development or the progression of atrophic gastritis to intestinal metaplasia and gastric cancer, although long‐term studies are required to allow definitive conclusions. At present, we do not recommend that patients be tested routinely for H. pylori infection when using proton pump inhibitors for prolonged periods. Gastric bacterial overgrowth does increase with acid suppression, but important clinical sequelae, such a higher rate of gastric adenocarcinoma, have not been seen. The risk of enteric infection may increase with acid suppression, although this does not seem to be a common clinical problem with prolonged proton pump inhibitor use. The absorption of fats and minerals does not appear to be significantly impaired with chronic acid suppression. However, vitamin B12 concentration may be decreased when gastric acid is markedly suppressed for prolonged periods (e.g. Zolllinger–Ellison syndrome), and vitamin B12 levels should probably be assessed in patients taking high‐dose proton pump inhibitors for many years.Thus, current evidence suggests that prolonged gastric acid suppression with proton pump inhibitors rarely, if ever, produces adverse events. Nevertheless, continued follow‐up of patients taking proton pump inhibitors for extended periods will provide greater experience regarding the potential gastrointestinal adverse effects of long‐term acid suppression.
Rabeprazole produces rapid, potent, and long‐acting inhibition of gastric acid secretion in subjects with Helicobacter pylori infection
Authors: Ohning  , Barbuti  , Kovacs  , Sytnik  , Humphries  , Walsh  
Published: March 2003

Aim:To compare acid inhibiting activity and duration of action of different doses of rabeprazole, a substituted benzimidazole characterized as a highly potent and irreversible H+, K+‐ATPase inhibitor, administered for 7 days to subjects infected with Helicobacter pylori.Methods:A total of 38 subjects (mean age 39.3 years) were enrolled in a single‐centre, double‐blind, randomized, crossover study. All subjects were confirmed positive for H. pylori by 14C urea breath test and ELISA serologies. Subjects were divided into two groups of 19 to receive two doses of rabeprazole, either 5 and 20 mg or 10 and 40 mg, and placebo, given in random order daily in the morning for 7 days. Peptone‐stimulated acid, pH, and gastrin measurements were made for 24 h after the 1st dose and for 48 h after the 7th dose.Results:Peptone‐stimulated acid secretion rates were decreased from 12.5 to 6.7, 4.0, 1.5, and 0.26 h after initial 5, 10, 20, and 40 mg doses, respectively; to 7.3, 4.3, 2.1, and 1.2 mmol/h 23 h after the initial dose; and to 2.4, 2.6, 0.6, and 0.8 mmol/h 23 h after the 7th dose. After 48 h, stimulated acid secretion had recovered less than 40% for all treatment groups compared to placebo. Median intragastric pH also increased from 2.0 with placebo to 4.9, 6.2, 6.6 and 6.9 during the 24‐h period after the 7th dose of 5, 10, 20, and 40 mg. The 20 mg dose of rabeprazole produced equivalent acid inhibition to the 40 mg dose with less increase in plasma gastrin.Conclusion:Rabeprazole in doses from 5 to 40 mg was a highly effective inhibitor of gastric acid secretion in subjects infected with H. pylori. The inhibition was rapid, dose‐related, and long‐acting, with less than 50% recovery of acid by 48 h after the 7th dose. The optimal acid inhibitory dose in these subjects appeared to be 20 mg daily, however 5 mg and 10 mg doses produced potent inhibition of gastric acid secretion.
Topical and intravenous administration of trefoil factors protect the gastric mucosa from ethanol‐induced injury in the rat
Authors: Mckenzie C. , Thim L. , Parsons M. E. 
Published: March 2003

Background:hTFF2 and pTFF2 (formerly PSP and hSP, respectively) are members of the trefoil factor family (TFF) and are distributed throughout the gastrointestinal tract in both normal and diseased tissue. Trefoil factors have been shown to exert a mucosal protectant and/or healing role in a number of animal models but controversy exists surrounding this property in relation to their dose and route of administration.Aim:To investigate the effects of topically applied and intravenously infused trefoil factors (hTFF2 and pTFF2) and prostaglandin E2 on ethanol‐induced gastric mucosal damage in rats.Method:A gastric chamber preparation in the anaesthetized rat was used. Injury was caused by exposing the gastric mucosa to absolute ethanol for 1 min. Trefoil factors or prostaglandin E2 were administered either intravenously or topically before and after the introduction of absolute ethanol onto the gastric mucosa. Damage was assessed by measurement of gastric mucosal Na+ leakage and area of macroscopic injury.Results:Like prostaglandin E2, intravenous administration of hTFF2 and pTFF2 reduced both the gastric mucosal Na+ leakage and the mean area of damage caused by ethanol. Similarly, treatment of the gastric mucosa with topical application of hTFF2 at doses of 120 μg/kg and above reduced the Na+ leakage and the area of damage. pTFF2 at 120 μg/kg and 1.2 mg/kg applied topically produced a marked reduction in total area of damage.Conclusion:Intravenously infused hTFF2 and pTFF2 protect the gastric mucosa from ethanol‐induced damage in the anaesthetized rat. In addition, topical application of trefoil factors also was effective at protecting the gastric mucosa from injury at doses lower than previously reported.
Role of antibiotic therapy on long‐term germ excretion in faeces and digestive symptoms after Salmonella infection
Authors: Barbara  , Stanghellini  , Berti‐Ceroni  , De Giorgio  , Salvioli  , Corradi  , Cremon  , Corinaldesi  
Published: March 2003

Background:The role of antibiotic therapy on Salmonella faecal excretion is controversial. Acute Salmonella gastroenteritis induces long‐lasting digestive symptoms in up to one‐third of subjects. The role of antimicrobial therapy on persistent post‐infectious symptoms is unknown.Aim:To investigate the role of antibiotic therapy on long‐term germ faecal excretion and digestive symptoms after Salmonella infection.Subjects and methods:1543 subjects [518 aged between 3 and 5 years (35.3%); 950 between 6 and 10 years (64.7%) and 75 adults (4.9%)] involved in a single outbreak of Salmonella enteritis fulfilled the study criteria by repeating stool cultures and answering a symptom questionnaire 3 months post‐infection.Results:327 subjects (21.2%) were treated with antibiotics during the acute infection [121 children aged 3–5 years (23.4%), 175 children aged 6–10 years (18.4%) and 31 adults (41.3%)]. Antibiotic treatment did not affect Salmonella excretion at any of the time points studied up to three months post‐infection in any age group as compared to age‐matched untreated controls. Persistent digestive symptoms were more common among the patients treated with antibiotics (9.5% vs. 2.9%; P=0.003).Conclusions:Antibiotic therapy does not affect Salmonella enteritis excretion. Digestive symptoms after clearance of the infectious agent are significantly higher in patients treated with antibiotics during acute gastroenteritis.
Unfavourable effects of colchicine in combination with interferon‐α in the treatment of chronic hepatitis C
Authors: Angelico M. , Cepparulo M. , Barlattani A. , Liuti A. , Gentile S. , Hurtova M. , Ombres D. , Guarascio P. , Rocchi G. , Angelico F. 
Published: March 2003

Background:The prognosis of chronic hepatitis depends on the progression of hepatic fibrosis.Aim:To investigate whether the antifibrotic drug colchicine, in combination with interferon‐α has a role in the treatment of chronic hepatitis C.Methods:Sixty‐five HCV–RNA positive patients with chronic hepatitis were randomized to receive interferon‐α, 6 MU t.i.w. for 6 months followed by 3 MU t.i.w. for further 6 months, with or without the adjunct of colchicine, 1 mg o.d., 6 days a week, for 3 years. We report an interim analysis after the first 18 months.Results:Thirty‐four patients received interferon‐α and 31 received interferon‐α and colchicine. The two groups were comparable for baseline data, including HCV–RNA levels, genotypes and histological grading/staging. Drop‐outs and side‐effects were similar. The proportion of patients who achieved alanine transaminase normalization or undetectable HCV–RNA at month 6 was higher in the interferon‐α (68% and 47%, respectively) than in the interferon‐α plus colchicine group (32% and 23%, P=0.004 and P=0.04, respectively). End‐of‐treatment biochemical and virological response occurred in 41% and 29% of the interferon‐α and 19% and 10% of the combination group, respectively (P=0.05 and P=0.05). Sustained biochemical response occurred in 26% of the interferon‐α and 6% of the interferon‐α plus colchicine group (P=0.03), corresponding percentages of sustained HCV–RNA loss being 21% and 3% (P=0.04).Conclusions:The combination of colchicine and interferon‐α worsens the effectiveness of interferon‐α alone in HCV chronic hepatitis. These alarming findings prompted us to interrupt the trial at this stage.
Phytomenadione or menadiol in the management of an elevated international normalized ratio (prothrombin time)
Authors: Green B. , Cairns S. , Harvey R. , Pettit M. 
Published: March 2003

Aim:To evaluate the efficacy of oral menadiol compared to intravenous phytomenadione when correcting coagulopathies associated with cholestasis.Methods:A total of 26 patients with cholestasis and an international normalized ratio (prothrombin time) greater than 1.2, were randomized to receive either 20 mg o.d. for 3 days of oral menadiol (n=12), or 10 mg o.d. of intravenous phytomenadione (n=14) prior to endoscopic retrograde cholangeopancreatography. Liver function tests and international normalized ratio were measured daily for 3 days.Results:Liver function tests and international normalized ratio were comparable between groups at entry into the study (P > 0.05), but serum albumin was significantly lower in the intravenous phytomenadione group following treatment (P < 0.05). A decrease in international normalized ratio occurred in both groups following administration of vitamin K (P < 0.05). Two patients in the intravenous group required fresh frozen plasma, as failure to normalize international normalized ratio was observed. No adverse drug reactions were observed in either group, and no patient required re‐admission for bleeding during a 4‐week follow‐up period after cholangeopancreatography.Conclusion:Oral menadiol appears to be an effective alternative to intravenous phytomenadione in the correction of coagulopathies associated with obstructive liver disease. This simplifies the care of patients with deranged clotting times requiring cholangeopancreatography, particularly those to be managed as out‐patients.
Placebo‐controlled, randomized, evaluator‐blinded endoscopy study of risedronate vs. aspirin in healthy postmenopausal women
Authors: Lanza F. L. , Rack M. F. , Li Z. , Krajewski S. A. , Blank M. A. 
Published: March 2003

Background:Bisphosphonates are effective treatments for osteoporosis. Since some primary amino bisphosphonates are associated with oesophageal injury, we conducted a study of the upper gastrointestinal effects of risedronate, a pyridinyl bisphosphonate.Methods:Healthy, postmenopausal women received risedronate 5 mg (n=26), aspirin 2600 mg (n=27), or placebo (n=27) daily for 14 days and underwent endoscopy at baseline, Day 8 and Day 15.Results:Oesophageal erosions were noted in one subject in the aspirin group, two in the placebo group, and none in the risedronate group, and an ulcer in one aspirin‐treated subject. Gastric erosions and ulcers were observed most frequently in the aspirin group. Gastric ulcers were noted in eight subjects in the aspirin group, one in the placebo group, and none in the risedronate group (P=0.010, placebo vs. aspirin; P=0.002, risedronate vs. aspirin). Duodenal erosions and ulcers were observed in the aspirin group only. Gastroduodenal erosion scores of three or more occurred more frequently in the aspirin than in the risedronate and placebo groups (P < 0.001).Conclusions:Risedronate 5 mg was not associated with oesophageal or gastroduodenal ulcers in healthy, postmenopausal women, a population representative of patients who will receive risedronate in the clinical setting.
The effects of aspirin on antioxidant defences of cultured rat gastric mucosal cells
Authors: Mitobe Y. , Hiraishi H. , Sasai T. , Shimada T. , Terano A. 
Published: March 2003

Summary Background: Helicobacter pylori‐associated inflammation leads to exposure of the gastric epithelium to reactive oxygen species (ROS) generated in the gastric mucosa. In some pathological conditions, such as those induced by nonsteroidal anti‐inflammatory drugs, the gastric mucosa may become more susceptible to ROS. Aim: To examine the effects of aspirin on antioxidant defenses as well as on oxidant injury in cultured rat gastric mucosal cells. Methods: Primary monolayer cultures of rat gastric fundic mucosa were exposed to an ROS‐generating system, hypoxanthine/xanthine oxidase (XOD). Cytotoxicity was quantified by measuring 51Cr release from prelabelled cells. The effects of aspirin on antioxidants and on cellular injury brought about by the ROS‐generating system were determined. Results: XOD, in the presence of hypoxanthine, caused a dose‐dependent increase in specific 51Cr release, which corresponded to the ability of XOD to produce ROS (as assessed by the production of uric acid from hypoxanthine). Incubation of cells with aspirin (1–100 μm) produced a dose‐dependent increase in XOD‐induced 51Cr release. Aspirin did not affect cellular glutathione content or activity of glutathione peroxidase, glutathione reductase or endogenous catalase. By contrast, aspirin caused a dose‐dependent reduction in mucus synthesis, as assessed by incorporation of [3H]‐glucosamine hydrochloride into the cells. Conclusions: Aspirin at therapeutically relevant concentrations rendered cultured gastric cells more susceptible to subsequent exposure to ROS. Aspirin affected neither the glutathione redox cycle nor catalase activity. Thus, the enhancement of ROS‐induced injury by aspirin may be accomplished through diminished gastric mucus synthesis, since mucus is a potent scavenger of ROS. These findings provide insight into how gastric inflammation and injury (such as that induced by H. pylori infection) in human gastric mucosa is modulated by the administration of nonsteroidal anti‐inflammatory drugs.
Is autonomic dysfunction a necessary condition for chronic peptic ulcer formation?
Authors: Nomura M. , Yukinaka M. , Miyajima H. , Nada T. , Kondo Y. , Okahisa T. , Shibata H. , Okamura S. , Honda H. , Shimizu I. , Saito K. , Oki T. , Nakaya Y. , Ito S. 
Published: March 2003

Summary Background: The relationship between 1/f fluctuation of the heart rate variability and Helicobacter pylori infection was evaluated, in order to clarify whether autonomic nervous dysfunction is a necessary condition for chronic peptic ulcer formation. Methods: The subjects were 11 patients with recurrent chronic peptic ulcer and 20 age‐matched normal subjects. Holter ECGs were recorded over 24 h, and the 1/f –x fluctuation of the heart rate was computed. The 1/f –x fluctuation of the heart rate is a novel index of autonomic function that has been shown to reflect a patient's pleasant mood. For 1/f –x fluctuation, the slope of the regression line (–x) was determined and cosine fitting of the absolute slope of the regression line over a 24‐h period was performed. Results: For the normal group, the absolute slope of the regression line during daytime and night‐time were 0.53 ± 0.16 and 1.05 ± 0.18, respectively. For the peptic ulcer group, the corresponding values during daytime and night‐time were 0.94 ± 0.15 and 1.84 ± 0.18, respectively. The mean value of the cosine curve was 0.76 ± 0.23 in the normal group and 1.12 ± 0.25 in the peptic ulcer group. Thus, these values were significantly higher for the latter group than for the former group (P < 0.05). No statistically significant difference in H. pylori infection between the two groups was observed. Conclusions: Autonomic nervous dysfunction as well as H. pylori infection appears to be a necessary condition for chronic peptic ulcer formation.
The effect of sofalcone on indomethacin‐induced gastric ulcers in a Helicobacter pylori‐infected gnotobiotic murine model
Authors: Kabir A. M. A. , Shimizu K. , Aiba Y. , Igarashi M. , Takagi A. , Koga Y. 
Published: March 2003

Summary Background: Sofalcone has been reported to exert anti‐ulcer and gastroprotective actions, but its exact mechanism of action remains unknown. In our laboratory, we found that indomethacin‐induced gastric ulcers become worse when associated with Helicobacter pylori infection. Methods: We employed the H. pylori‐infected gnotobiotic murine model to examine the effect of sofalcone on indomethacin‐induced gastric ulcers in the presence of H. pylori infection. In vitro experiments were also done to evaluate the effects of sofalcone on H. pylori growth, adherence of H. pylori to the MKN45 cells (a human gastric epithelial cell line), and these cells' IL‐8 production in the presence of H. pylori. Results: We found that sofalcone produced a significant improvement in ulcer size as well as a substantial reduction in the number of H. pylori colonies in H. pylori‐infected gnotobiotic mice. In vitro sofalcone has a significant bacteriocidal effect against H. pylori and can also significantly prevent adherence of this bacterium to MKN45 cells, thus remarkably reducing IL‐8 production of these cells in response to stimulation by H. pylori. Conclusion: Our results suggest that sofalcone can improve ulcer healing by the mechanisms mentioned above.
Review article: epidemiology of gall‐bladder disease – role of intestinal transit
Authors: Heaton K. W. 
Published: March 2003

SummaryRecent epidemiological studies have suggested that hyperinsulinaemia may be a central factor in the pathogenesis of cholesterol gallstones, explaining a probable link with physical inactivity as well as abdominal adiposity. There is also increasing evidence for the hypothesis that enrichment of bile with DCA, ‘the colonic bile acid', leads to enrichment of bile with cholesterol. Biliary DCA can be raised and lowered by slowing down and speeding up colonic transit, respectively. Slow transit is characteristic of non‐obese British women with gallstones and of non‐obese peasants in a gallstone‐prone mountain community. High biliary DCA predicts recurrence of gallstones and so does laxative usage, a pointer to constipation and therefore to slow transit. In some studies, at least, a high fibre intake is protective against gallstones. Much else besides fibre influences colonic function. Future studies of gallstone aetiology should include measurements of colonic function. Measures that speed up colonic transit should be tested for their ability to prevent gallstone formation in high‐risk individuals.
Review article: gall‐bladder motility after intestinal surgery
Authors: Qvist N. 
Published: March 2003

SummaryThere is a close relationship in humans between gall‐bladder motility and gastrointestinal motility during the fasting state, as well as in the post‐prandial period. Only a minority of publications take this relationship into account in the description of biliary dysmotility after various surgical procedures. Most publications deal with post‐prandial gall‐bladder motility or with stimulation of gall‐bladder contraction from various prokinetic drugs or gastrointestinal hormones. Impaired gall‐bladder motility has been demonstrated after Billroth II gastric resection, pyloroplasty and colectomy, but the epidemiological data on the risk of gallstone formation in these patients are too scarce and equivocal to recommend prophylactic cholecystectomy. Future studies on gall‐bladder motility after surgical procedures should include measurements of gall‐bladder motility during the fasting state, as well as in the post‐prandial period. The measurements should be related to the migrating motor complexes, and this necessitates a simultaneous recording of gastrointestinal motility.
Severe impairment of postprandial cholecystokinin release and gall‐bladder emptying and high risk of gallstone formation in acromegalic patients during Sandostatin LAR
Authors: Moschetta A. , Stolk M. F. J. , Rehfeld J. F. , Portincasa P. , Slee P. H. TH. J. , Koppeschaar H. P. F. , Van Erpecum K. J. , Vanberge‐Henegouwen G. P. 
Published: March 2003

Background:Acromegalic patients treated three times daily with subcutaneous injections of the somatostatin analogue octreotide frequently develop gallstones, due to suppressed cholecystokinin release and impaired gall‐bladder emptying.Aim:To elucidate the effects of a new long‐acting octreotide formulation (Sandostatin LAR) on gall‐bladder emptying, cholecystokinin release and gallstone formation.Methods:Postprandial gall‐bladder and gastric emptying were determined by ultrasonography and cholecystokinin release was measured in seven patients on days 0, 14, 28, and 75 (Sandostatin LAR, 20 mg intramuscularly on days 1, 30, and 60).Results:During treatment, fasting gall‐bladder volumes increased from 26.5 ± 3.2 mL to 61.4 ± 7.5 mL, but postprandial cholecystokinin release and gall‐bladder emptying (from 63.9 ± 3.8% to 12.3 ± 3.5%) were severely suppressed. Gallstones formed in six out of seven patients within 8 months of treatment. Gastric emptying did not change during the therapy.Conclusions:The risk of gallstone formation is greatly increased during Sandostatin LAR. This is probably related to profound suppression of cholecystokinin release and gall‐bladder emptying.
High prevalence of mixed infections by Helicobacter pylori in Hong Kong: metronidazole sensitivity and overall genotype
Authors: Wong B. C. Y. , Wang W. H. , Berg D. E. , Fung F. M. Y. , Wong K. W. , Wong W. M. , Lai K. C. , Cho C. H. , Hui W. M. , Lam S. K. 
Published: March 2003

Background:Diversity in metronidazole susceptibility and genotypes of Helicobacter pylori have been reported with varying results in different areas.Aims:To investigate the prevalence of multiple strain infection in a symptomatic Chinese population and to determine the metronidazole susceptibility pattern and genotypic characteristics of these infecting strains.Methods:Gastric biopsies from antrum, body and cardia were taken during upper endoscopy in symptomatic patients referred to our department. Pooled cultures and single colony isolates were obtained and tested for metronidazole susceptibility and random amplified polymorphic DNA (RAPD) fingerprint patterns.Results:A total of 461 isolates were successfully cultured from 46 patients. Fifty‐seven per cent of subjects had metronidazole‐resistant strains. Among them, 77% carried a mixture of sensitive and resistant strains, non‐uniformly distributed in the gastric mucosa. Mixed genotypes were found by RAPD typing in 24% of subjects. These did not correlate with the metronidazole susceptibility/resistance pattern.Conclusion: H. pylori infections with mixed metronidazole sensitive/resistant strains and mixed genotypes are common in Hong Kong. This makes it prudent to use bacterial strains from several biopsy sites when testing for traits such as drug resistance or virulence in relation to disease.