bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alendronate gastric ulcers
Authors: GRAHAM  , MALATY  
Published: March 2003

Background: It appears likely that drugs other than NSAIDs may cause ulcers and ulcer complications (e.g. potassium chloride). Alendronate (Fosamax) is used in the treatment and prevention of metabolic bone disease and has also been associated with severe oesophageal damage and stricture. We have previously shown that the dose of alendronate used for Paget's disease (40 mg) causes gastric damage similar to NSAIDs. The usual dose for the treatment of postmenopausal osteoporosis is 10 mg per day.Aim: To investigate whether the 10 mg dose of alendronate causes gastric ulcers.Methods: We performed an endoscopist‐blind, crossover, randomized, single‐centre comparison of 10 mg of alendronate/day and placebo in volunteers aged 40 years or more. Video‐endoscopy was used to evaluate the presence and degree of mucosal damage to the oesophagus, stomach, or duodenal bulb after 7 and 14 days of treatment.Results: Twenty‐four healthy volunteers participated, including 15 women and nine men, ranging in age from 41 to 52 years. Visible gastric mucosal damage was present in nine (38%) who received alendronate compared to three (13%) in the placebo group. There was a marked difference in the severity of mucosal damage; there were no ulcers or large erosions in those receiving placebo. In contrast, potentially clinically significant gastric mucosal injury was seen in six subjects receiving alendronate (two developed antral ulcers and four had large (4–8 mm) superficial antral erosions) compared to none in the placebo group (P = 0.0219). One subject developed oesophageal damage in the form of multiple linear superficial erosions in the mid and distal oesophagus. Duodenal injury was not seen.Conclusion: Alendronate causes gastric ulceration, suggesting that alendronate use may be associated with ulcer complications such as acute upper gastrointestinal bleeding. The results of this study suggest the need for post‐marketing surveillance to clarify the nature, frequency and magnitude of any potential gastrointestinal side‐effects associated with the use of this drug.
Effects of extracellular pH on restitution and proliferation of rabbit oesophageal epithelial cells
Authors: JIMENEZ  , LANAS  , PIAZUELO  , ESTEVA  
Published: March 2003

Background and Aims: Exposure to luminal acid induces mucosal damage in the oesophagus. The extent and degree of interaction of acid with wound repair mechanisms of the oesophagus have not been explored.Methods: Rabbit oesophageal cells were isolated, cultured and exposed to different extracellular pHs for several periods of time. Cell mortality was studied in both isolated and primary cultures of these cells by cell flow cytometry using fluorochrome propidium iodide and LDH release. Subconfluent cell cultures were used to study proliferative responses determined by [3H]‐thymidine incorporation into DNA. Restitution was studied in confluent monolayers wounded by mechanical denudation.Results: Isolated cells were resistant to acid when exposed to pH > 2 for 15 min. Cell proliferation increased with small pH decreases (7–6.5) if the period of exposure was less than 6 h, but was inhibited with lower pHs and/or longer periods of acid exposure. However, restitution was gradually inhibited with further pH decreases (6.5–3) and time of acid exposure (0.5–24 h).Conclusions: The wound repair activities of oesophageal epithelial cells are deeply affected by even small decreases in pH. These findings may help to explain the need for profound acid inhibition in acid‐related reflux oesophagitis.
Furazolidone‐containing short‐term triple therapies are effective in the treatment of Helicobacter pylori infection
Authors: LIU  , XIAO  , SHI  , WU  , ZHANG  , XU  , TYTGAT  
Published: March 2003

Background: A furazolidone‐containing therapeutic regimen for Helicobacter pylori infection has attracted special interest in the face of a rising world‐wide metronidazole resistant H. pylori, and the expense of currently used antimicrobial regimens.Aim: To evaluate the efficacy of furazolidone‐containing regimens in eradicating H. pylori.Methods: One‐hundred and forty H. pylori positive patients with endoscopically confirmed duodenal ulcer or functional dyspepsia received one of four different regimens to eradicate H. pylori. In the first trial, the patients were randomly assigned to receive a 1‐week course of furazolidone 100 mg b.d. and clarithromycin 250 mg b.d., with either tripotassium dicitrato bismuthate (TDB) 240 mg b.d. (FCB group) or lansoprazole 30 mg daily (FCL group). In the second trial, the patients were randomly assigned to receive a 1‐week course of clarithromycin 250 mg b.d. and omeprazole 20 mg daily, with either furazolidone 100 mg b.d. (FCO group) or metronidazole 400 mg b.d. (MCO group). Endoscopy was repeated 4 weeks following completion of therapy with re‐assessment of H. pylori status on gastric biopsies by histology and culture.Results: Four patients (1 in FCB, 1 in FCO and 2 in MCO groups) dropped out because they refused a follow‐up endoscopy. Eradication rates of H. pylori on an intention‐to‐treat basis in the FCB, FCL, FCO and MCO groups were 91% (32/35, 95% CI: 82–99%), 91% (32/35, CI: 82–99%), 86% (30/35, CI: 74–97%) and 74% (26/35, CI: 60–89%) (all P > 0.05), respectively. Mild side‐effects occurred in 15% of the 140 patients. In MCO group, the eradication rate in the patients infected with metronidazole‐sensitive isolates of H. pylori was 86%, but dropped to 67% in those with metronidazole‐resistance strains (P = 0.198).Conclusion: One‐week regimens containing furazolidone and clarithromycin in combination with TDB or a proton pump inhibitor fulfil the criteria for successful H. pylori therapy.
The optimal antibiotic combination in a 5‐day Helicobacter pylori eradication regimen
Authors: NEVILLE  , EVERETT  , LANGWORTHY  , TOMPKINS  , MAPSTONE  , AXON  , MOAYYEDI  
Published: March 2003

Background: Current guidelines for Helicobacter pylori eradication recommend 7 days of a proton‐pump inhibitor, clarithromycin (C), and either metronidazole (M) or amoxycillin (A). A shorter course would be cheaper and could be as effective.Aim: This study was designed to investigate the efficacy of three 5‐day regimens based on lansoprazole (L).Methods: 168 dyspepsia patients with H. pylori infection were randomized to receive a 5‐day course of either LCM, LAC or CALM, and a 13C‐urea breath test was performed after 4 weeks to assess eradication.Results: 160 patients completed the study. Intention‐to‐treat eradication rates were as follows: LCM 81%, LAC 59%, CALM 88%. LCM and CALM gave significantly better eradication rates than LAC. There was no significant difference in adverse events across the three groups. Logistical regression analysis showed that the specific regimen used and the age of the patient were the only factors influencing eradication outcome.Conclusions: Five days of CALM yields acceptable eradication rates, and is cheaper than conventional 7‐day proton pump inhibitor‐triple therapy. It appears to offer good results in metronidazole‐resistant strains of H. pylori. A randomized trial comparing 5‐day CALM with conventional 7‐day therapy is needed before this regimen can be recommended for routine use.
An evaluation of increasing doses of ranitidine for treatment of heartburn
Authors: PAPPA  , BUARON  , PAYNE  , SIRGO  , GIEFER  
Published: March 2003

Background: This was a randomized, double‐blind, placebo‐controlled, multicentre, parallel group, dose‐ranging trial of ranitidine tablets for relief of episodic heartburn. Adult out‐patients who reported heartburn relieved by antacids at least seven times per week were eligible.Methods: Patients who successfully completed a 1‐week single‐blind placebo run‐in phase and who did not achieve adequate relief in more than 50% of heartburn episodes were randomized to a 1‐week, double‐blind treatment phase during which they received ranitidine doses of 25, 75 or 125 mg, or placebo.Results: Of 577 patients randomized, 566 had at least one evaluable heartburn episode and were included in the intention‐to‐treat analysis. All three ranitidine doses were statistically significantly superior to placebo in providing overall episodic heartburn relief for the first episode (P < 0.002), last episode (P≤0.004), and all episodes combined (P <  0.001). The ranitidine 75 mg and 125 mg doses provided sustained relief (relief within 60 min of dosing that lasted throughout the 4‐h evaluation period) to a greater proportion of patients for each individual episode (43–56% for 75 mg and 42–57% for 125 mg) than the ranitidine 25 mg dose (35–50%) or placebo (21–29%). The incidence of adverse events was similar in all treatment groups.Conclusions: All three ranitidine doses (125, 75 and 25 mg) are safe and superior to placebo in providing adequate relief for heartburn. Ranitidine's onset of relief was progressive and clearly present by 30 min as shown by statistically significant differences for the 75 mg dose when compared to placebo. Similarly, patients treated with ranitidine 75 mg and 125 mg consumed statistically fewer rescue antacids than placebo‐treated patients for the first episode. All three doses were well tolerated, with adverse event profiles similar to those of placebo.
The effect of Helicobacter pylori eradication on intragastric pH during dosing with lansoprazole or ranitidine
Authors: Herwaarden M. A. van , Samsom M. , Nispen C. H. M. van , Mulder P. G. H. , Smout A. J. P. M. 
Published: March 2003

Background: The antisecretory effect of omeprazole on intragastric pH is decreased in the absence of Helicobacter pylori.Aim: To investigate the effect of H. pylori eradication on intragastric pH during lansoprazole or ranitidine dosing in 41 asymptomatic H. pylori‐positive subjects.Method: Two groups of healthy H. pylori‐positive volunteers were investigated. One group was dosed with lansoprazole 30 mg at 08.00 hours for at least 8 days, before and after 2 weeks of placebo‐controlled double‐blind eradication therapy using ranitidine bismuth citrate 400 mg b.d. and clarithromycin 500 mg b.d. The other group was dosed with ranitidine 300 mg at 23.00 hours for at least 8 days using the same trial design. An upper endoscopy was performed to establish H. pylori status by rapid urease test, culture and histology before both periods of dosing. Twenty‐four hour intragastric pH recording was performed on the final day of all periods of dosing.Results: H. pylori eradication significantly decreased the intragastric pH reached during lansoprazole treatment throughout all periods of the day. Intragastric pH during ranitidine treatment was not affected by H. pylori eradication, except for the late‐night period.Conclusion: H. pylori eradication has a more pronounced effect on the acid‐inhibiting properties of lansoprazole than on those of ranitidine.
Gastrointestinal safety and tolerance of ibuprofen at maximum over‐the‐counter dose
Authors: Doyle  , Furey  , Berlin  , Cooper  , Jayawardena  , Ashraf  , Baird  
Published: March 2003

Background:  Delineation of non‐steroidal anti‐inflammatory drug (NSAID) gastrointestinal toxicity has largely depended on retrospective epidemiologic studies which demonstrate that lower doses of NSAIDs pose a lower risk of gastrointestinal toxicity. Ibuprofen, a propionic acid NSAID, has, in most such studies, exhibited a favourable profile in terms of gastrointestinal bleeding. Since 1984, ibuprofen has been available as a non‐prescription analgesic/antipyretic with a limit of 1200 mg/day for 10 days of continuous use. Trials and spontaneously reported adverse experiences suggest that gastrointestinal symptoms and bleeding are rare.Methods: This study prospectively evaluated the gastrointestinal tolerability, as compared to placebo, of the maximum non‐prescription dose and duration of ibuprofen use in healthy subjects representative of a non‐prescription analgesic user population.Results: Gastrointestinal adverse experiences were similar in the placebo and ibuprofen groups (67 out of 413, 16% with placebo vs. 161 out of 833, 19% with ibuprofen). There was no difference between the two groups in the proportion discontinuing due to a gastrointestinal event. Gastrointestinal adverse experiences reported by ≥ 1% of subjects were: dyspepsia, abdominal pain, nausea, diarrhoea, flatulence, and constipation. Seventeen (1.4%) subjects had positive occult blood tests: their frequency was comparable between treatments.Conclusions: When used as directed to treat episodic pain, non‐prescription ibuprofen at the maximum dose of 1200 mg/day for 10 days, is well‐tolerated.
Omeprazole therapy decreases the need for dilatation of peptic oesophageal strictures
Authors: Barbezat  , Schlup  , Lubcke  
Published: March 2003

Background: Better control of gastric acid secretion with omeprazole appeared to decrease the need for dilatation of oesophageal strictures complicating gastro‐oesophageal reflux disease in our hospital‐based endoscopy service.Aim: To investigate whether the perceived decrease in the need for oesophageal dilatation could be documented from endoscopy records, and, if confirmed, whether this could be related to the treatment used.Patients and methods: Retrospective study of the records of 69 patients who had peptic oesophageal strictures dilated, followed by treatment with acid inhibition for at least 6 months. Mean duration of follow‐up was 3.9 years during treatment with H2‐receptor antagonists and 2.1 years while on omeprazole (258 and 78 patient‐years, respectively). Re‐dilatation rates were compared between those treated with H2‐receptor antagonists or omeprazole.Results: There has been a significant decrease in dilatations performed for gastro‐oesophageal reflux induced strictures (P < 0.001), while dilatation rates for other indications remained constant. Treatment with omeprazole not only decreased the need for further dilatations, but also prolonged the mean time between any further dilatations to 26.3 months compared to 9.3 months for those on an H2‐receptor antagonist (P < 0.0001).Conclusions: Following dilatation of peptic oesophageal strictures, treatment with omeprazole in place of an H2‐blocker significantly decreases the need for repeat dilatation.
Safety and efficacy of nabumetone in osteoarthritis: emphasis on gastrointestinal safety
Authors: Scott  , Palmer  
Published: March 2003

Aim:To compare the efficacy and gastrointestinal (GI) safety of nabumetone with two comparator non‐steroidal anti‐inflammatory drugs (NSAIDs), diclofenac SR and piroxicam.Methods:Two randomized, double‐blind, multicentre, parallel group trials were carried out in patients with moderate to severe osteoarthritis of the hip or knee. During the 6 month treatment phase, the safety and efficacy of nabumetone (1500–2000 mg/day) was compared to diclofenac SR (100 mg/day) or piroxicam (20–30 mg/day). GI safety was evaluated by reviewing all adverse events reported during the trials and presenting all cases of ulcers (complicated and uncomplicated), as well as other bleeding events that may have been associated with NSAID administration.Results:Most of the efficacy parameters showed no significant differences between the NSAIDs, although diclofenac SR was significantly better than nabumetone in one of 18 efficacy parameters. Nabumetone‐treated patients experienced significantly fewer ulcer and bleeding events compared to patients treated with the comparator NSAIDs [1.1% (4/348) vs. 4.3% (15/346), P= 0.01]. Bleeding events, including outright upper or lower GI bleeding or a significant decline in haemoglobin, occurred in significantly fewer patients treated with nabumetone than with the comparator NSAIDs [1.1% (4/348) vs. 3.5% (12/346), P < 0.05]. More importantly, complications associated with either ulcers (perforation) or bleeding (leading to hospitalization or withdrawal) occurred in significantly fewer patients receiving nabumetone [0% (0/348)] than with comparator NSAIDs [1.4% (5/346), (P < 0.05)].Conclusion:The results suggest that nabumetone was similar in efficacy by most criteria to diclofenac SR and piroxicam in relieving the symptoms of osteoarthritis; however, nabumetone’s GI safety profile was generally superior to that of both comparator NSAIDs. In the pooled analysis, nabumetone was associated with a significantly lower total incidence of ulcers and bleeding events, and a significantly lower incidence of complications associated with these events.
Equally high efficacy of 4, 7 and 10‐day triple therapies to eradicate Helicobacter pylori infection in patients with ulcer disease
Authors: Hurenkamp G. J. B. , Van Der Ende A. , Grundmeijer H. G. L. M. , Tytgat G. N. J. , Van Der Hulst R. W. M. 
Published: March 2003

Background:In patients with ulcer disease the optimal dose and duration of Helicobacter pylori treatment containing omeprazole (O), metronidazole (M) and clarithromycin (C) has yet to be established. The efficacy might be influenced by metronidazole‐ and clarithromycin‐resistance.Aim:To study the effect of duration of OMC treatment on its efficacy and influence of metronidazole‐resistance and clarithromycin‐resistance on the optimal duration.Materials and methods:Ulcer patients (n=76) were randomized to three double‐blind treatments of 10 days: OMC 4 consisted of 4 days b.d. 20 mg omeprazole, 400 mg metronidazole and 250 mg clarithromycin switched over to 6 days b.d. 20 mg omeprazole and placebo antibiotics (n=27); OMC 7 consisted of 7 days b.d. omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg and 3 days b.d. omeprazole 20 mg and placebo antibiotics (n=25); OMC 10 consisted of 10 days b.d. omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (n=24). H. pylori was assessed by biopsies for culture and histology pre‐ and 4–6 weeks after OMC therapy. Metronidazole‐resistance and clarithromycin‐resistance were assessed by the E‐test.Results:Intention‐to‐treat‐eradication rates were: OMC 4, 96%; OMC 7, 92%; and OMC 10, 96% (N.S.). All of the three per protocol eradication rates were 100% (95% CI: 85.2–100). Of 75 isolates, 16 were metronidazole‐resistant and one was clarithromycin‐resistant.Conclusion:In H. pylori‐positive ulcer patients, OMC 4 is highly efficacious and as effective as OMC 7 and OMC 10. No influence of metronidazole‐resistance or clarithromycin‐resistance was observed.
Local and systemic effects of peritoneal lavage with high concentrations of adenosine in rats
Authors: Jackson E. K. , Swamy R. S. , Herzer W. A. , Mi Z. 
Published: March 2003

Background:Adenosine exerts actions which may be beneficial in treating diseases of the gastrointestinal tract. However, administered systemically, adenosine causes a ‘stress reaction’ and may adversely affect blood pressure and cardiac and renal function.Aim:To determine whether peritoneal lavage with adenosine provides pharmacological levels of adenosine in the intestines without elevating adenosine levels in the systemic circulation.Methods:Rats received an intramesenteric artery infusion of angiotensin II (30 ng/min) plus methoxamine (3 μg/min) to reduce mesenteric blood flow by approximately 60%, and adenosine solutions were instilled into the abdominal cavity. In a second study, microdialysis probes were placed in the mesenteric vein and aortic arch of rats, and the peritoneal cavity was continuously lavaged with adenosine solutions.Results:High concentrations (10−3 M) of adenosine normalized the mesenteric blood flow without affecting blood pressure or heart rate. High concentrations of adenosine (10−3 M) induced micromolar levels of adenosine and inosine in the mesenteric vein, without affecting adenosine or inosine levels in the aorta.Conclusions:Peritoneal lavage with high concentrations of adenosine provides pharmacological levels of adenosine in the gastrointestinal tract without systemic side‐effects. Peritoneal lavage with high concentrations of adenosine may be useful for the treatment of a number of diseases of the gastrointestinal tract.
Potential therapeutic applications and mechanisms of action of heparin in inflammatory bowel disease
Authors: Papa A. , Danese S. , Gasbarrini A. , Gasbarrini G. 
Published: March 2003

Unfractioned heparin was recently reported to be beneficial in the treatment of inflammatory bowel disease. The available uncontrolled data show that it may be effective in steroid‐resistant ulcerative colitis with a percentage of complete clinical remission of over 70% after an average of 4–6 weeks of therapy. The administration of unfractioned heparin is not currently justified by the very limited available data.The worsening of rectal bleeding is infrequent in treated ulcerative colitis patients and only rarely does it require blood transfusion or a colectomy. Low molecular weight heparin was used in a single trial in patients with steroid‐refractory ulcerative colitis, with results similar to those observed with unfractioned heparin.Since a prothrombotic state has been described in inflammatory bowel disease, and microvascular intestinal occlusion seems to play a role in the pathogenesis of inflammatory bowel disease, it is reasonable that part of the beneficial effects of unfractioned heparin in inflammatory bowel disease may result from its anticoagulant properties. However, beyond its well‐known anticoagulant activity, unfractioned heparin also exhibits a broad spectrum of immunomodulating and anti‐inflammatory properties, by inhibiting the recruitment of neutrophils and reducing pro‐inflammatory cytokines. Moreover, it can restore the high‐affinity receptor binding of basic fibroblast growth factor and this would aid healing of the ulcerated mucosa.In conclusion, unfractioned heparin may represent a safe therapeutic option for severe, steroid‐resistant ulcerative colitis, although randomized, controlled trials are needed to confirm these data.
The effect of NSAIDs and a COX‐2 specific inhibitor on Helicobacter pylori‐induced PGE2 and HGF in human gastric fibroblasts
Authors: Takahashi M. , Katayama Y. , Takada H. , Kuwayama H. , Terano A. 
Published: March 2003

Summary Background: There is compelling evidence for the pivotal role of Helicobacter pylori in the pathogenesis of gastrointestinal ulcer disease. However, despite the bacterium's toxicity, the majority of H. pylori infections are not accompanied by gastric ulcers. This implies the existence of a host mechanism offsetting H. pylori toxicity. Aims: To evaluate gastric fibroblasts' expression of hepatocyte growth factor (HGF), which is known to facilitate gastric ulcer healing, in the presence of H. pylori; to compare the effect on H. pylori‐induced HGF expression of a COX‐2 selective inhibitor with that of nonselective nonsteroidal anti‐inflammatory drugs (NSAIDs). Methods: Human gastric fibroblasts were cultured from human gastric mucosa obtained at surgery. Prostaglandin E2 (PGE2) and HGF were measured by EIA. The expression of COX‐2 mRNA was assessed by the TaqMan quantitative RT‐PCR system. Results: H. pylori increased PGE2 release in gastric fibroblasts. H. pylori induced expression of COX‐2 mRNA, which indicates that PG induction by H. pylori is through COX‐2. Sulindac sulphide, etodolac and NS 398 all inhibited H. pylori‐induced PGE2 release to the same extent. These agents also inhibited H. pylori‐induced HGF release. Conclusion: Gastric fibroblasts produce PG and HGF in response to the presence of H. pylori, which may be considered part of the human body's defensive reaction to H. pylori toxicity. This defensive mechanism is inhibited not only by COX‐2 nonselective NSAIDs but also by a COX‐2 selective inhibitor. These findings indicate the importance of COX‐2 in chronic H. pylori infection.