bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Game theory to analyse management options in gastro‐oesophageal reflux disease
Authors: Sonnenberg A.
Published: March 2003

This study aims to demonstrate the applicability of linear programming to threshold analysis, using, as an example, patients with new onset of gastro‐oesophageal reflux disease (GERD). The choice amongst competing management options is modelled as a decision tree, using threshold analysis, as well as an m × n matrix on an Excel spreadsheet. The different options of medical management correspond to the m rows, whilst the different disease states correspond to the n columns of the matrix. Each number at the intersection of a row and a column represents the outcome associated with that particular combination of management and disease state. The threshold values are calculated by the built‐in functions for linear programming of Excel using its Solver tool. Varying the cost estimates in the sensitivity analysis translates into solving a set of different matrices. Threshold analysis provides a formalism to phrase problems of medical decision analysis in a concise fashion.
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

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

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

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

Recent 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

There 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.
Comparative efficacy of new investigational agents against Helicobacter pylori
Authors: Osato M. S. , Reddy S. G. , Piergies A. A. , Bochenek W. J. , Testa R. T. , Graham D. Y.
Published: March 2003

Background:

Emergence of antibiotic resistant Helicobacter pylori has necessitated the identification of alternate therapies for the treatment of this infection.

Aim:

To assess the in vitro efficacy of two investigational agents: DMG‐MINO CL 344 (a N,N‐dimethylglycylamido derivative of minocycline), and davercin, a cyclic carbonate of erythromycin A as compared to older antibiotics (clarithromcyin, azithromycin, minocycline, tetracycline, ofloxacin, ciprofloxacin, cefixime) against clinical isolates of H. pylori.

Methods:

Testing was performed using the agar dilution method approved by the NCCLS subcommittee on antimicrobial susceptibility testing, Helicobacter pylori working group. Under these guidelines, Mueller–Hinton agar containing 5% aged sheep blood was used. All incubations were done under CampyPak Plus conditions for 72 h at 37 °C. The drug concentrations in the agar ranged from 0.016 to 16 μg/mL. Twenty‐one clarithromycin‐resistant and 16 clarithromycin‐susceptible clinical isolates of H. pylori obtained from patients with duodenal ulcer were used. H. pylori ATCC 43504 was used as the control in all determinations.

Results:

Against clarithromycin susceptible isolates, all antimicrobial agents except the fluoroquinolones were highly effective. Against clarithromycin‐resistant H. pylori, the MIC50/MIC90 values showed that the tetracyclines and cefixime were the most efficacious agents. The fluoroquinolones and macrolides were ineffective. Macrolide cross‐resistance was detected.

Conclusion:

Macrolide cross‐resistance prevents the use of this entire class of antimicrobials when clarithromycin resistance is present. Tetracyclines and cefixime are possible alternative agents for the treatment of H. pylori infection in these patients.
In‐vitro cyclosporin sensitivity of proliferating lymphocytes is predictive of in‐vivo therapeutic response in ulcerative colitis
Authors: McCormack G. , O'Donoghue D. , Baird A.
Published: March 2003

Background:

The efficacy of cyclosporin in the management of ulcerative colitis is recognized. Not all patients respond to this treatment. Existing clinical and laboratory parameters are of little use in identifying those most likely to respond.

Aims:

To determine whether in‐vitro sensitivity to cyclosporin as measured by a lymphocyte proliferation assay is predictive of in‐vivo response to therapy.

Methods:

The study comprised seven responders with ulcerative colitis, seven non‐responders, and 14 healthy matched controls. A lymphocyte proliferation assay was carried out in the presence of a range of concentrations of cyclosporin and a dose–response curve constructed for each subject. The IC50 value, the concentration of cyclosporin that resulted in 50% inhibition of proliferation, was calculated for each subject. IC50 values for responders, non‐responders and controls were compared using a Mann–Whitney test.

Results:

There was a wide range of values obtained for the study group as a whole. IC50 values for non‐responders were significantly higher than those of responders (P < 0.05).

Conclusions:

There is a population‐wide variation of in‐vitro sensitivity to cyclosporin. This is reflected in in‐vivo sensitivity as measured by clinical response to cyclosporin treatment. Future therapeutic strategies need to address this inherent variability of individual response to therapy.
Occurrence and relapse of bleeding from duodenal ulcer: respective roles of acid secretion and Helicobacter pylori infection
Authors: Capurso G. , Annibale B. , Osborn J. , D'Ambra G. , Martino G. , Lahner E. , Delle Fave G.
Published: March 2003

Background:

Helicobacter pylori infection, gastric acid hypersecretion and NSAID consumption may cause peptic ulcer.

Aim:

To investigate the respective roles of H. pylori and acid secretion in bleeding duodenal ulcer.

Patients and methods:

A total of 99 duodenal ulcer patients were referred for evaluation of acid secretion: seven with Zollinger–Ellison Syndrome; 14 with hypersecretory duodenal ulcer, defined by the coexistence of elevated basal acid output and pentagastrin acid output; and 78 duodenal ulcer patients with normal acid output. All non‐Zollinger–Ellison Syndrome patients were H. pylori‐positive and cured of infection. All patients were followed‐up for a 36‐month period, to assess the occurrence of bleeding episodes.

Results:

Twenty‐nine patients had at least one bleeding episode in the 4 years before the study. Bleeding was more frequent in males and in patients on NSAIDs. The mean basal acid output was not higher among bleeders. In the 21 patients (14 hypersecretory duodenal ulcer, seven Zollinger–Ellison Syndrome) with basal acid output > 10 meg/h and pentagastrin acid output > 44.5 meg/h, the risk of bleeding was higher (OR 6.5; 95% CI: 2–21). In the follow‐up period, three out of 83 (3.3%) non‐Zollinger–Ellison Syndrome patients had a H. pylori‐negative duodenal ulcer with bleeding. The risk of bleeding after H. pylori cure was not higher in hypersecretory duodenal ulcer patients (P > 0.3), nor among patients with previous bleeding episodes (P > 0.2).

Conclusions:

In H. pylori‐positive duodenal ulcer patients, the coexistence of elevated basal acid output and pentagastrin acid output leads to a sixfold increase in the risk of bleeding. After H. pylori cure, gastric acid hypersecretion is not a risk factor for bleeding. However, duodenal ulcer recurrence with bleeding may occasionally occur in patients cured of H. pylori, even if acid output is normal.
Healthcare resource utilization in the management of oesophageal adenocarcinoma
Authors: Soni A. , Sonnenberg A.
Published: March 2003

Objective:

To study the natural history of oesophageal adenocarcinoma in terms of utilization of the healthcare resources and associated medical costs.

Methods:

All 29 patients treated at the University of New Mexico Health Center between 1 January 1992 and 1 December 1998 for an oesophageal adenocarcinoma were included in the study. For each individual patient, all medical resources utilized, facility costs, and physician fees were retrieved from the computerized databases of the collection departments.

Results:

During the progress of the disease, the same type of diagnostic or therapeutic procedure became necessary a number of times, and patients underwent, on average, three (range one to eight) upper gastrointestinal endoscopies, five (range one to 11) computerized tomography scans, 35 (five to 143) X‐ray examinations, and 28 (three to 46) radiation therapies or 39 (10 to 74) chemotherapies. The large variation in the numbers of resources utilized was also reflected by a corresponding variation in total healthcare costs. The mean cost per patient was $48 127, ranging between $13 454 and $139 721. Facility costs comprised 88% of all costs compared to physician fees which comprised 12%. The largest cost items, in declining order, were physician encounters ($16 916), radiation plus chemotherapy ($9909 plus $4891, respectively), and pharmacy prescriptions ($7565).

Conclusions:

The prolonged disease process and the many diagnostic and therapeutic procedures result in complications, side‐effects, inconclusive tests, or failed therapies that all markedly increase the use of healthcare resources. Because such outcomes are the rule rather than the exception, the management of oesophageal adenocarcinoma is expensive.
Characteristics of patients with irritable bowel syndrome recruited from three sources: implications for clinical trials
Authors: Longstreth G. F. , Hawkey C. J. , Mayer E. A. , Jones R. H. , Naesdal J. , Wilson I. K. , Peacock R. A. , Wiklund I. K.
Published: March 2003

Background:

Variation in the characteristics of irritable bowel syndrome patients recruited for clinical trials from different sources could affect their response and the generalizability of trial results.

Aim:

To describe and compare the characteristics of three different groups of irritable bowel syndrome patients recruited into a ‘mock clinical trial.’

Methods:

We enrolled 245 irritable bowel syndrome patients from three sources: (i) 121 from British primary practitioners; (ii) 72 from California newspaper advertisements; and (iii) 52 from a California gastroenterologist’s practice. We obtained demographic, clinical, and Hospital Anxiety and Depression (HAD) Scale data.

Results:

Most patients were young to middle‐aged women; the majority reported symptoms for > 5 years in all three groups. Subject characteristics varied among the groups. Typically, primary care patients were anxious, smokers and daily alcohol drinkers who had sought care recently for irritable bowel syndrome and tried antispasmodic drugs. Their symptoms were intermediate in severity between those of the other two groups. Advertisement subjects were the oldest, most highly educated, most often depressed, and were least likely to have sought care recently for symptoms, which were almost uniformly only moderate in severity. Gastroenterologist patients tended to be anxious and had nearly all sought care recently for symptoms, which were the most severe and most likely to include all three pain‐related Rome I criteria.

Conclusion:

Recruitment methodology affects important characteristics of an irritable bowel syndrome study group.
Effect of Helicobacter pylori eradication on expression of cyclin D2 and p27 in gastric intestinal metaplasia
Authors: Yu J. , Leung W. K. , Ng E. K. W. , To K. F. , Ebert M. P. A. , Go M. Y. Y. , Chan W. Y. , Chan F. K. L. , Chung S. C. S. , Malfertheiner P. , Sung J. J. Y.
Published: March 2003

Background and aims:

Cyclins and cyclin‐dependent kinase inhibitors play a crucial role in the control of cell cycle transitions. Enhanced expression of cyclin D2 and reduced expression of p27kip1 (p27) have been implicated in the pathogenesis of cancer. Because intestinal metaplasia has been regarded as a pre‐malignant lesion, we investigated the expression of cyclin D2 and p27 in Helicobacter pylori‐associated chronic gastritis with and without intestinal metaplasia, and followed the changes after H. pylori eradication.

Methods:

Expression of cyclin D2 and p27 was studied by immunohistochemistry in 59 patients (including 35 patients with intestinal metaplasia) and in 10 gastric cancer patients. Among them, 29 H. pylori‐infected patients had serial gastric biopsies taken before and at 1‐year after eradication of H. pylori.

Results:

Expression of cyclin D2 was significantly higher in gastric cancers when compared to their adjacent non‐tumour tissues (median score 3 vs. 1, P=0.015). Over‐expression of cyclin D2 was detected in H. pylori‐associated chronic gastritis and intestinal metaplasia, which was reduced after eradication of the organism (median score 2 vs. 1, P=0.037 in chronic gastritis; median score 2 vs. 0, P=0.008 in intestinal metaplasia). While the normal gastric mucosa showed strong p27 expression, five of the 10 gastric cancer tissues exhibited reduced p27 expression (P=0.039). Diminished p27 expression was also seen in intestinal metaplasia, which was restored 1‐year after H. pylori eradication (eight out of 16 vs. one out of 16, P=0.018). Reduced expression of p27 was frequently associated with increased cyclin D2 expression in H. pylori‐associated intestinal metaplasia (P=0.02).

Conclusion:

Over‐expression of cyclin D2 and reduced expression of p27 are closely linked to H. pylori‐associated intestinal metaplasia. Eradication of H. pylori infection reverses the aberrant expression of cyclin D2 and p27 in intestinal metaplasia.
Review article: herbal treatment in gastrointestinal and liver disease—benefits and dangers
Authors: Langmead L. , Rampton D. S.
Published: March 2003

Herbal medicines are now used by up to 50% of the Western population, in a substantial minority of instances for the treatment or prevention of digestive disorders. Although most indications for the use of such remedies are anecdotally or traditionally derived, controlled trials suggest some benefits for ginger in nausea and vomiting, liquorice extracts in peptic ulceration, Chinese herbal medicine in irritable bowel syndrome, opium derivatives in diarrhoea and senna, ispaghula and sterculia in constipation. Herbal preparations contain many bioactive compounds with potentially deleterious as well as beneficial effects.

There is clearly a need for greater education of patients and doctors about herbal therapy, for legislation to control the quality of herbal preparations, and in particular for further randomized controlled trials to establish the value and safety of such preparations in digestive and other disorders.
Review article: current therapeutic options for radiation proctopathy
Authors: Hong J. J. , Park W. , Ehrenpreis E. D.
Published: March 2003

Radiation proctopathy is a common unfortunate complication following radiation therapy of pelvic malignancies. Symptoms of chronic radiation procto‐ pathy include haematochezia, urgency, constipation, tenesmus, diarrhoea and rectal pain.

Currently, a wide variety of pharmacological options, endoscopic cautery techniques and surgical procedures have been proposed for the treatment of chronic radiation proctopathy. Although these have been proposed primarily as treatment for rectal bleeding, the control of other symptoms has been noted with some of these agents. Pharmacological options include 5‐aminosalicylic acid preparations, coticosteroid enemas, sucralfate (oral, enemas), formalin, short chain fatty acid enemas, oestrogen/progesterone, hyperbaric oxygen, antioxidants, sodium pentosan polysulphate and miso‐prostol rectal suppositories. Of these, sucralfate and formalin therapy appear to be effective for bleeding control. Misoprostol rectal suppositories and oral sucralfate may be useful in the prevention of acute and chronic symptoms of radiation proctopathy.

Endoscopic cautery techniques have included the use of Nd:YAG laser and argon laser for coagulation of bleeding neovascular telangiectasias. Argon plasma coagulation offers a safe non‐contact method of delivering haemostasis which has proven to be particularly useful in targeting difficult to reach lesions tangentially.

Surgery is generally reserved for severe refractory cases involving ongoing haemorrhage, obstruction, stricture formation, fistulas and perforation.

Given that formal randomized placebo‐controlled studies are lacking for most treatments, the management of these patients is often challenging and unclear. Hence, there is a need for more research and education on radiation proctopathy.
Involvement of the corporal mucosa and related changes in gastric acid secretion characterize patients with iron deficiency anaemia associated with Helicobacter pylori infection
Authors: Capurso G. , Lahner E. , Marcheggiano A. , Caruana P. , Carnuccio A. , Bordi C. , Delle Fave G. , Annibale B.
Published: March 2003

Background:

Recent studies have reported an association between iron deficiency anaemia and Helicobacter pylori. Helicobacter pylori could cause iron deficiency anaemia by altering iron absorption. We observed that most patients with Helicobacter pylori infection and iron deficiency anaemia present a chronic superficial pangastritis.

Aim:

To investigate whether Helicobacter pylori‐positive patients with iron deficiency anaemia have peculiar histological and functional features when compared with non‐anaemic Helicobacter pylori‐positive subjects.

Patients:

Fifty‐one patients with iron deficiency anaemia, in whom chronic superficial Helicobacter pylori gastritis was the only gastrointestinal finding, and 103 non‐anaemic Helicobacter pylori‐positive controls were included in the study. Thirty‐seven patients were randomly matched with 37 controls of the same sex and age.

Methods:

Gastroscopy, with antral (n=3) and body (n=3) biopsies, was performed. Gastrin and pepsinogen I levels and antiparietal cell antibodies were evaluated. Intragastric pH was also measured.

Results:

Gastritis involved the corporal mucosa in 90% of patients compared to 42.7% of controls (P < 0.0001). The mean inflammatory score in the gastric body was significantly higher among patients than in controls (2.2 vs. 0.6; P=0.012). Gastrin was significantly higher in patients than in controls (mean 60.2 vs. 29 pg/mL; P=0.0069). Intragastric pH was higher in patients than in controls (median 5.7 vs. 2; P=0.0026).

Conclusions:

These data suggest that patients with iron deficiency anaemia and Helicobacter pylori infection have a peculiar pattern of gastritis with corporal involvement and related changes in intragastric pH.
Evaluation of the cost‐effectiveness of Helicobacter pylori eradication triple therapy vs. conventional therapy for ulcers in Japan
Authors: Ikeda S. , Tamamuro T. , Hamashima C. , Asaka M.
Published: March 2003

Background:

Helicobacter pylori eradication triple therapy with a combination of lansoprazole, amoxicillin and clarithromycin was approved in Japan in September 2000.

Aim:

To compare the cost‐effectiveness of this eradication therapy with conventional histamine‐2 receptor antagonist therapy in Japan.

Methods:

We established two Markov models for gastric and duodenal ulcers. The model design was based on the Japanese H. pylori eradication guideline and a specialist’s opinions, and the model inputs were obtained from a literature review. The models predict the direct medical costs, number of disease‐free days and cost per disease‐free day for 5 years.

Results:

In the gastric ulcer model, the expected total costs of eradication and conventional therapies per patient were ¥169 719 and ¥390 921, respectively; the expected numbers of disease‐free days were 1454 days and 1313 days, respectively. In the duodenal ulcer model, the expected total costs were ¥134 786 and ¥324 689, respectively; the expected numbers of disease‐free days were 1503 days and 1387 days, respectively. The sensitivity analyses showed that the results of the base case analysis were robust.

Conclusions:

This eradication therapy is less costly and more effective than conventional therapy for the treatment of gastric and duodenal ulcers in a Japanese medical setting.
One‐week regimens containing ranitidine bismuth citrate, furazolidone and either amoxicillin or tetracycline effectively eradicate Helicobacter pylori: a multicentre, randomized, double‐blind study
Authors: Lu H. , Zhang D.‐Z. , Hu P.‐J. , Li Z.‐S. , Lu X.‐H. , Fang X.‐C. , Xiao S.‐D.
Published: March 2003

Background:

The metronidazole resistance of Helicobacter pylori strains has increased rapidly.

Aim:

To evaluate the efficacy and safety of new 1‐week regimens containing ranitidine bismuth citrate, furazolidone and either amoxicillin or tetracycline.

Methods:

One hundred and twenty patients with H. pylori‐positive inactive duodenal ulcer or non‐ulcer dyspepsia diagnosed by endoscopy were recruited randomly to receive one of two regimens for 7 days: ranitidine bismuth citrate, 350 mg b.d., furazolidone, 100 mg b.d., and either amoxicillin, 1000 mg b.d. (n=60), or tetracycline, 500 mg b.d. (n=60). H. pylori infection was identified by rapid urease testing and histology. 13C‐Urea breath test was performed to evaluate the cure of H. pylori infection at least 4 weeks after completion of triple therapy.

Results:

The eradication rates of H. pylori by ranitidine bismuth citrate–furazolidone–amoxicillin and ranitidine bismuth citrate–furazolidone–tetracycline regimens were 82% and 85% (P > 0.05), respectively, by intention‐to‐treat analysis, and 85% and 91% (P > 0.05), respectively, by per protocol analysis. Adverse effects were mild in both ranitidine bismuth citrate–furazolidone–amoxicillin and ranitidine bismuth citrate–furazolidone–tetracycline groups.

Conclusions:

One‐week regimens containing ranitidine bismuth citrate, furazolidone and amoxicillin or tetracycline are well tolerated and effective for the eradication of H. pylori.
Intestinal anti‐inflammatory activity of morin on chronic experimental colitis in the rat
Authors: Gálvez J. , Coelho G. , Crespo M. E. , Cruz T. , Rodríguez‐Cabezas M. E. , Concha A. , Gonzalez M. , Zarzuelo A.
Published: March 2003

Background:

Morin, a bioflavonoid with antioxidant properties, shows intestinal anti‐inflammatory activity in the acute phase of the trinitrobenzenesulphonic acid model of rat colitis.

Aim:

To assess the anti‐inflammatory activity of morin in the chronic stages of trinitrobenzenesulphonic acid‐induced rat colitis.

Methods:

Rats were rendered colitic by a single colonic instillation of 30 mg of the hapten trinitrobenzenesulphonic acid dissolved in 0.25 mL of 50% ethanol. A group of colitic animals was given morin orally at doses of 25 mg/kg daily. Animals were sacrificed every week for 4 weeks. Colonic damage was evaluated macroscopically and microscopically. Different biochemical markers of colonic inflammation were also assayed, including myeloperoxidase activity, leukotriene B4 and interleukin‐1β synthesis, glutathione and malonyldialdehyde levels and nitric oxide synthase activity.

Results:

The administration of morin facilitated tissue recovery during the 4 weeks following colonic insult with trinitrobenzenesulphonic acid, as demonstrated macroscopically and microscopically, as well as biochemically by a reduction in myeloperoxidase activity. The intestinal anti‐inflammatory effect of morin was accompanied by a significant reduction in colonic leukotriene B4 and interleukin‐1β levels, improvement in colonic oxidative stress and inhibition of colonic nitric oxide synthase activity.

Conclusions:

Morin exerts a beneficial anti‐inflammatory effect in the chronic phase of trinitrobenzenesulphonic acid‐induced rat colitis through the down‐regulation of some of the mediators involved in the intestinal inflammatory response, including free radicals, cytokines, leukotriene B4 and nitric oxide.
Over‐the‐counter H2‐receptor antagonists do not compromise intragastric pH control with proton pump inhibitors
Authors: Tutuian R. , Katz P. O. , Ahmed F. , Korn S. , Castell D. O.
Published: March 2003

Background:

Proton pump inhibitors effectively suppress intragastric acid. Nocturnal acid breakthrough occurs on any dosing regimen of oral proton pump inhibitors. Histamine2‐receptor antagonists (H2RA) suppress intragastric acidity independently of meals and help to control nocturnal acid breakthrough. Because proton pump inhibitors require an acid intragastric milieu for activation, nocturnal dosing of H2RA might decrease the effect of proton pump inhibitors taken in the morning by decreasing their gastric‐acid‐driven activation.

Aim:

Assess intragastric acid control on omeprazole, 20 mg, taken every morning, after variable dosing of over‐the‐counter famotidine, 10 mg.

Methods:

Twelve Helicobacter pylori‐negative, healthy volunteers received omeprazole, 20 mg, every morning before breakfast for 15 days. Baseline studies on omeprazole, 20 mg, in the morning, were done on day 7. On nights between days 8–9, 11–12 and 14–15, famotidine, 10 mg at bedtime, and 10 mg at bedtime and/or at 05.30 h, was given in a three‐way, crossover, double‐blind randomized design. Intragastric pH monitoring was performed on days 9, 12 and 15, starting at 08.00 h.

Results:

Percentage times intragastric pH < 4 on omeprazole, 20 mg, in the morning of the day after receiving famotidine, 10 mg, at bedtime (58.6 ± 4.8); at 05.30 h (54.1 ± 5.1); or at bedtime and at 05.30 h (54.3 ± 5.0) did not differ significantly (P=0.65) from percentage times intragastric pH on day 7 of omeprazole, 20 mg, in the morning (49.5 ± 5.1).

Conclusion:

Concerns over inhibition of next‐day daytime proton‐pump inhibitor effect should not preclude use of nocturnal H2RAs in patients with gastro‐oesophageal reflux disease.
Minor effects of Helicobacter pylori on gastric secretion and dose of lansoprazole during long‐term treatment in ZE and non‐ZE acid hypersecretors
Authors: Hirschowitz B. I. , Simmons J. , Mohnen J.
Published: March 2003

Background:

Helicobacter pylori infection may increase or decrease acid secretion and may augment proton pump inhibitor efficacy. Pepsin effects have not been reported. In Zollinger–Ellison syndrome (ZE) specifically, H. pylori has been reported to decrease acid.

Aim:

To examine H. pylori effects on secretion and dose of medication in hypersecretors (basal acid output > 15 mmol/h) undergoing long‐term treatment with individually optimized lansoprazole doses.

Methods:

Sixty‐five patients (47 ZE and 18 non‐ZE), treated for > 3 months to 10 years, were tested every 6 months with endoscopy, gastric analysis and serum gastrin.

Results:

Forty‐three per cent were H. pylori‐positive. Acid, pepsin and gastrin were not different between H. pylori‐positive and H. pylori‐negative patients before or during long‐term lansoprazole treatment. Initially, H. pylori‐positive patients required less lansoprazole than H. pylori‐negative patients (68 ± 6 vs. 96 ± 8 mg/day), but after 3 years the doses converged (83 vs. 86 mg/day). The disappearance of H. pylori in 15 patients caused no significant changes in acid, pepsin, gastrin or lansoprazole dose in the following 4 years.

Conclusions:

H. pylori had no significant initial or long‐term physiological or potential clinical effects on acid or pepsin secretion or gastrin in these acid hypersecretors.