bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pharmacodynamics of lansoprazole administered via gastrostomy as intact, non‐encapsulated granules
Authors: Sharma  , Ugheoke  , Vasudeva  , Howden  
Published: March 2003

Background:Because of its acid‐labile nature, lansoprazole is usually administered as encapsulated enteric‐coated granules. The gelatin capsule and acid‐resistant coating of the granules have been considered essential for effective drug absorption and optimal bioavailability. Lansoprazole may attain effective plasma levels when given as non‐encapsulated intact granules, but effects on intragastric acidity are unknown.Aim:To test the effectiveness of non‐encapsulated, intact lansoprazole granules in suppressing intragastric acidity when administered through a gastrostomy.Methods:Eight men, each with an established gastrostomy, underwent baseline 24 h intragastric pH monitoring while off any acid‐suppressing medication. Via the gastrostomy, they then received 7 days of once‐daily dosing with 30 mg lansoprazole as intact granules in 3 fl. oz. of orange juice. Intragastric pH monitoring was repeated on day 7.Results:Mean intragastric pH pre‐dosing was 1.96 ± 0.5 (s.d.). This increased to 4.7 ± 0.6 on day 7 (P < 0.0001). Median intragastric pH rose from 1.5 to 5.2 (P < 0.0001). Before lansoprazole, the proportions of time when intragastric pH was above 3, 4 and 5 were 23.2, 13.5 and 7.5%, respectively. Corresponding values after 7 days of lansoprazole were 81.1, 70.2 and 52.3% (P < 0.0001 for each comparison).Conclusion:Lansoprazole can effectively suppress intragastric acidity when given through a gastrostomy as intact, non‐encapsulated granules in orange juice.
Effects of S‐0509, a novel CCKB/gastrin receptor antagonist, on acid secretion and experimental duodenal ulcers in rats
Authors: TAKEUCHI  , HIRATA  , YAMAMOTO  , KUNIKATA  , ISHIKAWA  , ISHIHARA  
Published: March 2003

Background:S‐0509, 2‐[(tert‐butoxycarbonylmethyl) [(m‐(carboxy‐phenyl)‐ureidomethyl‐carbonyl]] aminobenzo phenone, was developed as a potent and selective CCKB/gastrin receptor antagonist that does not affect the central nervous system.Methods:We evaluated the effects of S‐0509 on gastric acid secretion and duodenal ulcerogenic and healing responses in rats comparing it with L‐365,260, another CCKB/gastrin receptor antagonist.Results:S‐0509 (0.1~10 mg/kg, i.d.) was able to dose‐dependently decrease basal acid secretion and inhibit the acid secretory responses induced by both pentagastrin (60 μg/kg/h, i.v.) and peptone (10%, i.g.) but not histamine (4 mg/kg/hr, i.v.) or carbachol (60 μg/kg/h, i.v.). L‐365,260 (10 and 30 mg/kg, i.d.) caused only partial a suppression of the acid secretory response to pentagastrin but not to other stimuli, including peptone treatment. On the other hand, a duodenal ulcerogen, mepirizole (200 mg/kg, s.c.) caused an increase in acid secretion and resulted in penetrating ulcers in the proximal duodenum, and these ulcers gradually healed over 3 weeks. S‐0509 significantly inhibited both the acid secretory (> 1.0 mg/kg, i.d.) and ulcerogenic (> 3 mg/kg, p.o.) responses induced by mepirizole when it was given as a pre‐treatment. It also promoted significantly the healing of these ulcers (> 3 × 2 mg/kg, p.o.) when it was given twice daily for 14 days. In contrast, L‐365,260 (30 mg/kg) tended to reduce the severity of mepirizole‐induced duodenal ulcers, with a slight inhibition of acid secretion, but it caused no influence on the healing response of these ulcers.Conclusion:These results confirmed that S‐0509 is a selective CCKB/gastrin receptor antagonist with potent antisecretory action in vivo conditions, and further demonstrated that this agent not only prevents the development of duodenal ulcers but also shows healing promoting action on duodenal ulcers, probably through the blockade of CCKB/gastrin receptors.
Effects of pumaprazole (BY841), a novel reversible proton pump antagonist, and of omeprazole, on intragastric acidity before and after cure of Helicobacter pylori infection
Authors: MARTÍNEK  , BLUM  , STOLTE  , HARTMANN  , VERDÚ  , LÜHMANN  , DORTA  , WIESEL  
Published: March 2003

Background:Omeprazole produces a higher intragastric pH in the presence of Helicobacter pylori infection than after cure.Aim:To investigate whether this effect also occurs with pumaprazole (BY841), a reversible proton pump antagonist which, in contrast to omeprazole, does not require activation in the acid compartment of the parietal cell.Methods:In a randomized, crossover, double‐blind study, 24‐h intragastric pH was measured in 13 H. pylori‐positive subjects before and after a 1‐week course of omeprazole (20 mg o.d.) or of pumaprazole (100 mg b.d.). The studies were repeated after the infection was cured.Results:In the absence of drug administration, the median 24‐h pH values before cure (median 2.0, 90% CI: 1.2–3.2) did not differ from those after cure (median 1.5, 90% CI: 1.3–2.2; P = 0.115). The 24‐h pH values were higher before cure of the infection than after during both pumaprazole (6.0, 4.8–6.7 vs. 4.3, 2.6–5.7; P = 0.002) and omeprazole (5.8, 4.0–6.2 vs. 3.6, 2.8–5; P = 0.004). Both before and after cure, there were no significant differences between the two drugs with respect to acid inhibition over the 24‐h period. The median decrease in acid inhibition after cure of the infection (calculated as the difference in H+ activity in mmol/L) during pumaprazole (median 0.05, 90% CI: 6 × 10–4– 2.3) was no different from that during omeprazole (median 0.2, 90% CI: 3 × 10–3–1.5; P = 0.6).Conclusions:Both before and after cure of H. pylori infection, pumaprazole raised the intragastric pH over a 24‐h period to a similar degree as omeprazole. H. pylori infection similarly augments the pH‐increasing effect of both drugs. This effect is related to H. pylori infection and not to an increased activation of acid inhibitory agents in the parietal cell compartment.
Gastric emptying in hyperemesis gravidarum and non‐dyspeptic pregnancy
Authors: Maes  , Spitz  , Ghoos  , Hiele  , Evenepoel  , Rutgeerts  
Published: March 2003

Background:Emesis and hyperemesis are significant problems associated with early pregnancy. However, gastric emptying of solids has never been studied during early pregnancy in humans.Aim:To investigate gastric emptying of solids in patients recovering from hyperemesis gravidarum and in non‐dyspeptic pregnant women and to compare these results with a group of healthy non‐pregnant women.Methods:Fourteen patients with hyperemesis gravidarum, 10 non‐dyspeptic pregnant women and 36 non‐pregnant women in the first half of the menstrual cycle underwent a gastric emptying study. Seven non‐pregnant women repeated the test in the post‐ovulatory period.Results:Gastric emptying of solids was not significantly delayed in non‐dyspeptic pregnant women compared with non‐pregnant women. The emptying rate tended to be impaired in the post‐ovulatory period of the menstrual cycle. Solid emptying was significantly accelerated in patients recovering from hyperemesis gravidarum, correlating well with thyroid function in the latter group.Conclusion:Pregnancy in humans is not associated with decreased solid gastric emptying. In subjects recovering from hyperemesis gravidarum, solid emptying is increased, correlating well with thyroid function abnormalities. Nausea and vomiting in hyperemesis are therefore probably not due to upper gastrointestinal disorders.
Review article: the potential role of nitric oxide in chronic inflammatory bowel disorders
Authors: Perner  , Rask‐Madsen  
Published: March 2003

The aetiology of the chronic inflammatory bowel diseases—ulcerative colitis and Crohn’s disease—as well as ‘microscopic colitis’—both collagenous (COC) and lymphocytic colitis (LC)—remains unknown. Autoimmune mechanisms, cytokine polymorphism, commensal bacteria, infectious agents and vascular impairment have all been proposed as playing important roles in the pathogenesis of this spectrum of diseases.A variety of proinflammatory mediators, including tumour necrosis factor α, interleukin‐1β, interferon γ, leukotriene B4 and platelet activating factor, promote the adherence of phagocytes to the venular endothelium and extravasation of these cells into the colonic mucosa. In addition to large amounts of nitric oxide (NO), injurious peroxynitrite may be formed in the epithelium by the inducible nitric oxide synthase (iNOS), which is considered to elicit cytotoxicity by the generation of superoxide with reduced
L‐arginine availability. In active ulcerative colitis, and to a lesser extent in Crohn’s disease, a greatly increased production of NO has been demonstrated by indirect and direct measurements. Surprisingly, even higher rates of production have been observed in COC—a condition which is never associated with injurious inflammation. The latter observation favours the notion that NO promotes mucosal integrity. Further evidence for a protective role of NO in chronic inflammatory bowel disorders is provided by the observation of increased susceptibility to the induction of experi mental colitis in ‘knock‐out’ mice deficient in iNOS.Selective inhibitors of iNOS activity, as well as topical L‐arginine, may therefore prove beneficial in inflammatory bowel disease by reducing the production of superoxide by iNOS, while only the former option may be expected to reduce diarrhoea in chronic inflammatory bowel disorders. Clearly, further experimental work needs to be done before testing topical
L‐arginine in human inflammatory bowel disease.
Eradication of Helicobacter pylori infection after ranitidine bismuth citrate, metronidazole and tetracycline for 7 or 10 days
Authors: KNIGGE  , KELLY  , PETERSON  , FENNERTY  
Published: March 2003

Background: We assessed the efficacy, tolerance, and compliance of twice‐daily triple therapy for Helicobacter pylori with ranitidine bismuth citrate, metronidazole and tetracycline for 7 or 10 days.Methods: 105 subjects with H. pylori infection documented by the 13C‐urea breath test were randomly assigned to a 7 or 10‐day course of ranitidine bismuth citrate 400 mg b.d., metronidazole 500 mg b.d. and tetracycline 500 mg b.d. Subjects returned at the end of therapy for assessment of side‐effects and pill count. A repeat 13C‐urea breath test was obtained 4 or more weeks after completion of therapy and cure of infection was defined as a negative test result.Results: Poor compliance (< 80% of medications) was seen in 2% of subjects randomized to 7 days of therapy and in 10% randomized to 10 days of therapy (P = N.S.). Intention‐to‐treat eradication rates were 56% for 7‐day and 60% for 10‐day therapy (P = N.S.). Per protocol eradication rates were 58% for 7‐day and 61% for 10‐day therapy (P = N.S.). The 10‐day intention‐to‐treat eradication rate for males was 78% and 32% for females (P < 0.01) and per protocol eradication rates were 79% and 31%, respectively (P < 0.01).Conclusions: Despite excellent compliance and tolerance, neither 7 nor 10 days of therapy with twice‐daily ranitidine bismuth citrate, metronidazole and tetracycline are adequate as a treatment of H. pylori infection.
The influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate triple therapy regimens for Helicobacter pylori infection
Authors: WOUDEN E. J. VAN DER , THIJS  , ZWET A. A. VAN , KOOY  , KLEIBEUKER  
Published: March 2003

Aim: To assess the influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate‐based triple therapy regimens in two consecutive studies.Methods: In the first study, patients with a culture‐proven Helicobacter pylori infection were treated with ranitidine bismuth citrate 400 mg, metronidazole 500 mg, and clarithromycin 500 mg, all twice daily for 1 week (RMC). In the second study, amoxycillin 1000 mg was substituted for clarithromycin (RMA). Susceptibility testing for metronidazole was performed with the E‐test. Follow‐up endoscopy was performed after ≥ 4 weeks. Antral biopsy samples were taken for histology and urease test, and culture and corpus samples for histology and culture.Results: 112 patients, 53 males, age 55 ± 14 years (39 duodenal ulcer, 7 gastric ulcer and 66 gastritis) were treated with RMC, and 89 patients, 52 males, age 58 ± 15 years (23 duodenal ulcer, 7 gastric ulcer and 59 gastritis) were treated with RMA. For RMC, intention‐to‐treat eradication results were 98% (59/60, 95% CI: 91–100%) and 95% (20/21, 95% CI: 76–100%) for metronidazole susceptible and resistant strains, respectively (P = 0.45). For RMA these figures were 87% (53/61, 95% CI: 76–94%) for metronidazole susceptible strains and 22% (2/9, 95% CI: 3–60%) for resistant strains (P = 0.0001).Conclusion: Both regimens are effective in metronidazole susceptible strains. However, in contrast to the amoxycillin‐containing regimen, that containing clarithromycin is also effective in resistant strains.
Transjugular liver biopsy in the 1990s: a 2‐year audit
Authors: PAPATHEODORIDIS  , PATCH  , WATKINSON  , TIBBALLS  , BURROUGHS  
Published: March 2003

Background: In view of the changing nature of transjugular liver biopsy, we performed an audit of the safety, adequacy and clinical impact of such biopsies in our centre over a 2‐year period from 1995 to 1997.Methods: One hundred and fifty‐seven transjugular biopsies were carried out in 145 patients, with prothrombin time >5 s over control and/or platelet count <50 × 109/L and/or gross ascites.Results: Major complications were two (1.3%) capsular perforations, which were easily plugged with coils without sequelae. Biopsy sample was adequate for histological diagnosis in 90%, inadequate in 6% and technically unsuccessful in 4% of cases. Mean biopsy size was 14.8 ± 7.7 (1–51) mm. Adequacy did not differ between cases with and without cirrhosis. Transjugular biopsy had a clinical impact (specific diagnosis or influence on patient’s management) in 50% of acute liver disease, 62% of chronic liver disease and 87% of transplant patients (P < 0.001). In chronic liver disease, it had a significantly greater clinical impact in cases trying to establish the stage rather than diagnosis (84% vs. 35%, P < 0.001).Conclusions: Transjugular liver biopsy is a safe procedure for high‐risk patients providing an adequate liver sample even in cirrhosis. It has a clinical impact in more than 80% of transplant patients and for staging chronic liver disease, but in only 50% (acute) or 35% (chronic) of liver disease when a diagnosis is sought.
Protection against aspirin‐induced human gastric mucosal injury by bosentan, a new endothelin‐1 receptor antagonist
Authors: DUGGAN  , STACK  , HULL  , FILIPOWICZ  , KNIFTON  , CROME  , WEBER  , BISHOP  , POLAK  , HAWKEY  
Published: March 2003

Background: Gastric ulceration induced by aspirin and by non‐steroidal anti‐inflammatory drugs (NSAIDs) is a major clinical problem. The mechanism of injury is unclear. There is evidence that NSAID‐induced injury may cause endothelin activation. Endothelin‐induced vasoconstriction has been shown to be capable of causing gastric ulceration.Aim: To investigate whether acute gastroduodenal injury induced in humans by aspirin can be prevented by the endothelin‐1 antagonist, bosentan.Methods: Eighteen healthy volunteers each received 5 × 900 mg aspirin every 12 h on three separate occasions (with either placebo, bosentan 700 mg or misoprostol 400 mg). Treatment order was randomized by Latin square design. Subjects were endoscoped and erosions counted before and 90 min after the first and last dose of aspirin. Plasma concentrations of bosentan were measured up to 5 h post‐dose.Results: There was a significant reduction in the mean number of erosions in the aspirin plus bosentan and aspirin plus misoprostol groups after the first dose of aspirin, compared with controls (aspirin plus placebo) (P < 0.05). This was not sustained after the fifth dose of aspirin in the aspirin plus placebo and aspirin plus bosentan groups, but was still present in the aspirin plus misoprostol group. The mean plasma concentration of bosentan measured 3.5 h post‐dose fell from 4510 (95% CI: 2791–6230) ng/mL after the 1st dose to 2508 (95% CI: 1733–3283) ng/mL after the 5th dose (P = 0.02).Conclusion: Endothelin receptor antagonism by bosentan can protect the gastric mucosa against aspirin damage. After five doses, bosentan levels fell, possibly because of enzyme induction, and protection was no longer evident. Further investigation is needed to assess whether higher doses would be effective.
Management of uninvestigated and functional dyspepsia: a working party report for the World Congresses of Gastroenterology 1998
Authors: Talley  , Axon  , Bytzer  , Holtmann  , Lam  , Zanten S. Velohuyzen Van 
Published: March 2003

Background: The management of dyspepsia is controversial.Methods: An international Working Party was convened in 1998 to review management strategies for dyspepsia and functional dyspepsia, based on a review of the literature and best clinical practice.Results: Dyspepsia, defined as pain or discomfort centred in the upper abdomen, can be managed with reassurance and over‐the‐counter therapy if its duration is less than 4 weeks on initial presentation. For patients with chronic symptoms, clinical evaluation depends on alarm features including patient age. The age cut off selected should depend on the age specific incidence when gastric cancer begins to increase, but in Western nations 50 years is generally an acceptable age threshold. In younger patients without alarm features, Helicobacter pylori test and treatment is the approach recommended because of its value in eliminating the peptic ulcer disease diathesis. If, after eradication of H. pylori, symptoms either are not relieved or rapidly recur, then an empirical trial of therapy is recommended. Similarly, in H. pylori‐negative patients without alarm features, an empirical trial (with antisecretory or prokinetic therapy depending on the predominant symptom) for up to 8 weeks is recommended. If drugs fail, endoscopy should be considered because of its reassurance value although the yield will be low. In older patients or those with alarm features, prompt endoscopy is recommended. If endoscopy is non‐diagnostic, gastric biopsies are recommended to document H. pylori status unless already known. While treatment of H. pylori is unlikely to relieve the symptoms of functional dyspepsia, the long‐term benefits probably outweigh the risks and treatment can be considered on a case‐by‐case basis. In H. pylori‐negative patients with documented functional dyspepsia, antisecretory or prokinetic therapy, depending on the predominant symptom, is reasonable, assuming reassurance and explanation are insufficient, unless patients have already failed this approach. Other treatment options include antidepressants, antispasmodics, visceral analgesics such as serotonin type 3 receptor antagonists, and behavioural or psychotherapy although these are all of uncertain efficacy. Long‐term drug treatment in functional dyspepsia should be avoided; intermittent short courses of treatment as needed is preferred.Conclusion: The management of dyspepsia recommended is based on current best evidence but must be tailored to local factors such as practice setting, the background prevalence of H. pylori and structural disease, and costs.
Review article: malnutrition and maltreatment—a comment on orlistat for the treatment of obesity
Authors: Cahill  , Lean  
Published: March 2003

The prevalence of obesity has doubled in the last 10 years and is now reaching epidemic proportions. There is a significant comorbidity and financial cost associated with this disorder. Orlistat is an intestinal lipase inhibitor that is approved for the treatment of obesity.Recent randomized, double‐blind, placebo‐controlled trials have demonstrated the benefit of orlistat used in conjunction with a hypocaloric (low‐fat) diet in facilitating weight reduction and the long‐term maintenance of this weight loss. Patients treated with orlistat lost a greater amount of initial body weight compared to those who received placebo. After 24 months of treatment, weight loss of more than 5% was maintained in a greater number of those treated with orlistat. This was associated with significant reductions in cardiovascular risk factors (cholesterol, LDL cholesterol, LDL:HDL cholesterol ratio). The main adverse events are related to fat malabsorption, with potential losses of fat‐soluble vitamins and other compounds.Orlistat as a treatment for obesity, when prescribed within present guidelines, can aid modest weight loss in about one‐third of patients. More importantly, it can assist in the maintenance of weight loss with major medical benefits for these patients.
Helicobacter pylori infection is a protective factor for bleeding gastric ulcers but not for bleeding duodenal ulcers in NSAID users
Authors: Santolaria  , Lanas  , Benito  , Pérez‐Aisa  , Montoro  , Sainz  
Published: March 2003

Background: The effect of Helicobacter pylori infection on NSAID‐induced gastroduodenal damage is unclear.AimTo determine the role of H. pylori and NSAID use in complicated peptic ulcers.Methods: A total of 185 consecutive patients with bleeding peptic ulcers and 185 hospitalized matched controls were studied prospectively. Additionally, 75 consecutive uncomplicated peptic ulcers and 75 community controls were also studied. Active H. pylori infection was determined by urea breath test and/or both urease test and histology. Serum CagA and VacA status were determined at random in 135 infected patients and 82 controls. NSAID use was determined by structured data collection.Results: H. pylori (odds ratio [OR]=5.98; 2.9–12.3) and NSAID use (OR=5.74; 3.4–9.7) were independent risk factors for duodenal ulcer bleeding, whereas NSAID use was the main risk factor for bleeding gastric ulcers (OR=12.4; 5.5–27.9). Interaction of both factors was associated with reduced risk for bleeding gastric ulcers (OR=0.19; 0.04–0.88) but not for bleeding duodenal ulcers, which showed a similar risk to any one factor alone. This was observed for all types of NSAID use, including low‐dose aspirin, and infection by CagA positive strains. H. pylori was the only factor involved in common uncomplicated duodenal ulcers.Conclusion: Interaction of both H. pylori infection and NSAID use decreases the risk of bleeding due to gastric ulcers, but not that due to duodenal ulcers.
Randomised double‐blind comparison of simethicone with cisapride in functional dyspepsia
Authors: Holtmann  , Gschossmann  , Karaus  , Fischer  , Becker  , Mayr  , Gerken  
Published: March 2003

Aim: To compare the efficacy of simethicone with cisapride in patients with functional (non‐ulcer) dyspepsia.Methods: After standardized diagnostic work‐up and at least 6‐days wash‐out of medication, 177 patients with functional dyspepsia were enrolled; 173 of them (age 19–71 years) were randomized and treated using a double‐dummy technique with simethicone (84 mg t.d.s.) or cisapride (10 mg t.d.s.). At baseline and after 2 and 4 weeks, the intensity of the symptoms was scored from 0 (absent) to 3 (severe) using a standardized symptom questionnaire. Efficacy of the treatment was judged by the patients as ‘very good’, ‘good’, ‘moderate’ or ‘no effect’.Results: A total of 166 patients completed the trial. After 2 and 4 weeks, 34% and 46% (respectively), of the patients treated with simethicone judged the improvement in symptoms to be excellent compared to 13% and 22% (respectively) of patients treated with cisapride (P < 0.01). After 2 weeks the difference in the improvement in the global symptom score was significantly better (Δ30.7%, P < 0.001) for simethicone than for cisapride, while this difference failed statistical significance after 4 weeks (Δ10.2%, P=0.11).Conclusions: In patients with functional dyspepsia, simethicone relieves symptoms during the first 2 weeks of treatment significantly better than cisapride.