bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in prescribing H2‐receptor antagonists and proton pump inhibitors in primary care
Authors: Martin  , Lim  , Kerry  , Hilton  
Published: March 2003

Background:H2‐receptor antagonists and proton pump inhibitors account for approximately 15% of primary care prescribing costs in the UK.Aim:To examine the use of antisecretory drugs in primary care between October 1991 and September 1996.Method:Analysis of prescribing data from an ongoing postal survey performed every 3 months on a rolling quota of 250 UK general practitioners (GPs), identified from a representative sampling frame of 1000 GPs.Results:There were 8811 new courses of proton pump inhibitors and 11 948 new courses of H2‐receptor antagonists during this study. The number of new prescriptions for proton pump inhibitors increased by 174.5%, but decreased for H2‐receptor antagonists by 12.5%. Proton pump inhibitors were mostly prescribed for reflux disease (52.7%) and H2‐receptor antagonists for non‐specific dyspepsia (43.6%). Proton pump inhibitors (14.1%) were less likely to be stopped than H2‐receptor antagonists (35.3%) overall, and they were less likely to be stopped because of perceived ineffectiveness (5.3%) than H2‐receptor antagonists (23.8%). The rate of stopping treatment because of side‐effects was about 3% for both classes of drug.Conclusions:Prescribing of proton pump inhibitors has increased sharply each year since 1991. One reason may be that GPs perceive proton pump inhibitors to be more effective than H2‐receptor antagonists.
Evidence for impaired assimilation and increased colonic fermentation of protein, related to gastric acid suppression therapy
Authors: Evenepoel  , Claus  , Geypens  , Maes  , Hiele  , Rutgeerts  , Ghoos  
Published: March 2003

Background:Although the role of gastric digestion (by acid‐dependent pepsins) in overall protein assimilation has never thoroughly been studied, it is generally considered to be limited. Protein that escapes assimilation in the small intestine is intensely fermented by the colonic flora. Phenol and p‐cresol are specific bacterial metabolites of tyrosine.Aim:To elucidate the role of gastric digestion of protein by evaluating the influence of acid suppression therapy on overall protein assimilation and fermentation.Methods:Protein assimilation was studied in 16 healthy subjects under basal conditions and after omeprazole treatment using the combined 14C‐octanoic acid/13C‐egg white breath test. The degree of protein fermentation was estimated by measuring the urinary output of phenol and p‐cresol in 41 healthy volunteers and in 17 patients treated for more than 1 month with omeprazole because of peptic disease.Results:Protein assimilation was significantly impaired after omeprazole treatment. Gastric emptying, conversely, was not affected. The urinary output of phenol and p‐cresol was increased in patients treated with omeprazole as compared to untreated controls.Conclusion:Gastric acid suppression therapy hampers protein assimilation and may promote protein malabsorption. Gastric digestion is likely to play a substantial role in overall protein assimilation.
Effects of somatostatin on proximal gastric motor function and visceral perception
Authors: Mearadji  , Straathof  , Biemond  , Lamers  , Masclee  
Published: March 2003

Background:Somatostatin affects gastrointestinal motility and secretion and visceral sensation, but little is known about its effects on the proximal stomach.Aim:To evaluate the effects of somatostatin on proximal gastric motor function and perception of symptoms.Methods:Six healthy subjects participated in two experiments performed in random order during continuous intravenous infusion of saline or somatostatin (250 μg/h). Proximal gastric motor function was evaluated using a barostat. We performed pressure and volume distensions and a barostat procedure (minimal distending pressure + 2 mmHg). Symptoms were evaluated at regular intervals using visual analogue scales (VAS).Results:Neither minimal distending pressure nor gastric fundal tone were significantly different between somatostatin and saline. Pressure–volume curves during distensions were not influenced by somatostatin. However, phasic volume waves were significantly (P < 0.001) reduced by somatostatin, and somatostatin significantly (P < 0.05) reduced symptom perception of fullness and abdominal pressure during stepwise distensions.Conclusions:Continuous infusion of somatostatin does not influence gastric compliance but it inhibits phasic volume waves and significantly reduces visceral perception.
Soluble adhesion molecules correlate with liver inflammation and fibrosis in chronic hepatitis C treated with interferon‐α
Authors: Iacono  , García‐Monzón  , Almasio  , García‐Buey  , Craxí  , Moreno‐Otero  
Published: March 2003

Background:In chronic hepatitis C the relation of circulating adhesion molecules to disease features before, during and after therapy has not been completely established.Aim:To analyse the basal levels of circulating adhesins and the changes induced by interferon in these patients.Methods:We studied, using ELISA assays, the serum levels of soluble intercellular adhesion molecule‐1 (sICAM‐1) and vascular cell adhesion molecule‐1 (sVCAM‐1) in 52 patients with chronic hepatitis C on entry, prior to finalizing a 6‐month course of interferon‐α therapy and at the end of the follow‐up. Correlations with clinical, virological and histological features, including inflammation and fibrosis, were calculated by Pearson’s r‐test.Results:Liver necroinflammation was more closely related to sICAM‐1 (r = 0.54, P = 0.0000) than to sVCAM‐1 (r = 0.32, P = 0.02). Fibrosis, both as serum pIIIP and histological scoring, was, however, clearly related to sVCAM‐1 (1071 ± 291 in patients who scored 0–2 vs. 1870 ± 458 in patients who scored 3–4; P = 0.0000). Severe fibrosis was never found below a sVCAM‐1 cut‐off threshold of 1300 ng/mL. Levels of both adhesins did not correlate with viraemia and were comparable among 1b and non‐1b genotypes. Sustained response to interferon was significantly related to low viraemia (P = 0.03), non‐1b type (P = 0.04) and low sICAM‐1 (P = 0.04), but not to sVCAM‐1. On finalizing therapy, patients with normal transaminases had reduced sICAM‐1 (P = 0.0005), but not sVCAM‐1 levels.Conclusions:In chronic hepatitis C, sICAM‐1 was a marker of liver necroinflammation while sVCAM‐1 reflected fibrosis. Both low sVCAM‐1 and pIIIP serum concentrations were strictly linked, suggesting that measuring sVCAM‐1 could give information on the degree of liver fibroplasia.
Review article: rabeprazole’s profile in patients with gastrointestinal diseases
Authors: Humphries  , Barth  
Published: March 2003

The selection of agents to treat patients with acid‐related gastrointestinal diseases requires knowledge of their efficacy, tolerability, and ease of dosing among individuals with differing disease severities and other baseline characteristics. The efficacy and favourable benefit–risk profile of rabeprazole, a new proton pump inhibitor, has been demonstrated in controlled clinical trials of patients with gastro‐oesophageal reflux disease (GERD), duodenal ulcers, and gastric ulcers.In comparative trials, rabeprazole is at least as effective as omeprazole for the treatment of GERD, duodenal ulcers, and gastric ulcers, and it is superior to histamine2‐receptor antagonists for the treatment of GERD and duodenal ulcers. Its once‐daily dosing regimen and low potential for interaction with drugs metabolized by the cytochrome P450 system make it a particularly attractive option for the treatment of acid‐related diseases among older individuals.Rabeprazole is likely to be a valuable new addition to its class in treating patients with acid‐related gastrointestinal diseases given its efficacy in acid suppression, high healing rates, rapid symptom relief, and convenient dosing.
Low‐dose lansoprazole provides greater relief of heartburn and epigastric pain than low‐dose omeprazole in patients with acid‐related dyspepsia
Authors: JONES  , CROUCH  
Published: March 2003

Aim: To compare the relative efficacies of lansoprazole 15 mg o.m. and omeprazole 10 mg o.m. in relieving heartburn and epigastric pain in patients with acid‐related dyspepsia. In addition, the study compared the safety profiles of the two treatments.Methods: This double‐blind, parallel group, randomised, multicentre study was conducted in 52 general practices in the UK. A total of 609 patients was recruited, 562 of whom were eligible for inclusion in the intention‐to‐treat analysis. All of the patients had experienced at least mild heartburn or mild epigastric pain persistently on at least 4 of the previous 7 days; patients with severe symptoms were excluded. 283 patients received lansoprazole 15 mg and 279 received omeprazole 10 mg, both for 4 weeks. The main efficacy measure was relief of symptoms, based on physician assessments.Results: In the intention‐to‐treat population, a complete relief of overall primary symptoms of dyspepsia was achieved after 2 weeks in 53% of patients receiving lansoprazole and in 41% of patients receiving omeprazole (P = 0.007). After 4 weeks, 59% of the lansoprazole group and 51% of the omeprazole group had achieved complete symptom relief (P = 0.078). Antacids were taken for additional relief of symptoms in fewer patients given lansoprazole compared to the omeprazole group in the third and fourth weeks (P = 0.035) and also significantly fewer antacids were taken by patients in the lansoprazole group compared with patients in the omeprazole group (P = 0.033). The proportion of patients reporting adverse events was similar in both groups.Conclusion: Low‐dose lansoprazole is more effective than low‐dose omeprazole in the treatment of patients with mild heartburn or epigastric pain in general practice.
Prescription of acid‐suppressing drugs in relation to endoscopic diagnosis: a record‐linkage study
Authors: PRACH  , MCGILCHRIST  , MURRAY  , JOHNSTON  , MACDONALD  
Published: March 2003

Background: Although widely used, few data are available on the appropriateness of prescribing of acid‐suppressing drugs (ASDs), despite guidelines on the investigation and treatment of dyspeptic patients.Methods: We created a database of 62 000 endoscopy examinations and record‐linked these to a prescribing database. Endoscopic diagnoses were classified into peptic, nonpeptic and others. The H2‐antagonists, omeprazole and misoprostol, were studied.Results: 35 000 patients had one or more endoscopies during 1978–93; two‐thirds were over 45 years of age at first endoscopy. A quarter of all patients who had been endoscoped had consistently normal examinations. Peptic oesophageal pathology was the commonest positive finding. A quarter of those prescribed ASDs between 1989 and 1993 had been endoscoped between 1978 and 1993. In those with a peptic diagnosis prescribed any ASD, the pathologies found were: oesophageal (42.9%), duodenal (36.3%) and gastro‐pyloric (21.3%). Patients prescribed omeprazole were more likely to have undergone endoscopy than those prescribed other ASDs, and they were also more likely to have peptic oesophageal pathology. Long‐term prescribing (>56 days per year) occurred in two‐thirds of patients prescribed ASDs and 40% had at least one endoscopy. In those prescribed short‐term ASDs, 20% had undergone at least one endoscopy. Peptic and nonpeptic endoscopic pathology was associated with increased ASD prescribing, but a normal endoscopy did not reduce prescribing.Conclusion: ASD prescribing appeared to be mainly symptom‐driven. Positive endoscopic findings increased the prescribing of ASDs, but normal findings did not reduce it.
The effect of curcumin and placebo on human gall‐bladder function: an ultrasound study
Authors: Rasyid  , Lelo  
Published: March 2003

Background:The extract of medicinal plants containing curcumin is traditionally believed to have a positive contraction effect on the human gall‐bladder.Aims:To compare the effect of 20 mg curcumin or placebo on the gall‐bladder volume of healthy volunteers.Methods:A randomized, double blind and crossover design study was carried out in 12 healthy volunteers (seven males and five females). Ultrasonography examination was carried out serially to measure the gall‐bladder volume. The data obtained was analysed by paired Student’s t‐test.ResultsThe fasting gall‐bladder volumes of 15.74 ± 4.29 mL on curcumin and 15.98 ± 4.08 mL on placebo were similar (P > 0.20). The gall‐bladder volume was reduced within the period after curcumin administration. The percentage of gall‐bladder volume reduction at 0.5, 1.0, 1.5 and 2.0 h after 20 mg curcumin administration were 11.8 ± 6.9, 16.8 ± 7.4, 22.0 ± 8.5 and 29.3 ± 8.3%, respectively, which was statistically significant compared to placebo.Conclusion:On the basis of the present findings, it appears that curcumin induces contraction of the human gall‐bladder.
Serum gastrin and chromogranin A during medium‐ and long‐term acid suppressive therapy: a case‐control study
Authors: Sanduleanu  , Stridsberg  , Jonkers  , Hameeteman  , Biemond  , Lundqvist  , Lamers  , Stockbrügger  
Published: March 2003

Background:Serum chromogranin A (CgA) is regarded as a reliable marker of neuroendocrine proliferation. We previously described increased serum CgA levels during short‐term profound gastric acid inhibition.Aim:To investigate serum gastrin and CgA levels in dyspeptic patients during continuous medium‐ (6 weeks to 1 year), or long‐term (1–8 years) gastric acid suppressive therapy.Patients and methods:114 consecutive dyspeptic patients referred for upper gastrointestinal endoscopy were enrolled in a cross‐sectional, case‐control study [62 patients on continuous antisecretory therapy, either with proton pump inhibitors (n = 47) or H2‐receptor antagonists (H2RA) (n = 15) for gastro‐oesophageal reflux disease with or without Barrett’s oesophagus or functional dyspepsia, and 52 age‐ and sex‐matched patients without medical acid inhibition and with normal endoscopic findings (control group)]. Omeprazole doses ranged from 20 mg to 80 mg daily and ranitidine from 150 mg to 450 mg daily. Fasting serum CgA and serum gastrin levels were measured by radioimmunoassay (reference values: serum CgA < 4.0 nmol/L; serum gastrin < 85 ng/L).Results:Fasting serum CgA levels positively correlated with serum gastrin in the entire study population (r = 0.55, P = 0.0001). Median serum CgA values were higher in patients treated with a proton pump inhibitor than H2RA [2.8 (2.0–5.9) nmol/L vs. 2 (1.9–2.3) nmol/L, P < 0.002] and controls [2.8 (2.0–5.9) nmol/L vs. 1.8 (1.5–2.2) nmol/L, P < 0.0001) and did not differ between patients treated with H2RA or controls. Serum gastrin and CgA levels in patients on proton pump inhibitor therapy positively correlated with the degree and duration of acid inhibition. Patients on long‐term proton pump inhibitor therapy had significantly higher fasting serum gastrin and CgA than those on medium‐term proton pump inhibitor therapy [127 (73–217) ng/L vs. 49 (29–78) ng/L, P < 0.0001 and 4.8 (2.8–8) ng/L vs. 2.1 (1.9–2.6) ng/L, P < 0.001]. No such relation was found in patients on medium‐ vs. long‐term H2RA. Overall, patients with positive Helicobacter pylori serology had higher serum gastrin and CgA levels than those with negative H. pylori serology [51 (27–119) ng/L vs. 27 (14–79) ng/L, P = 0.01, 2.4 (1.9–3.4) nmol/L vs. 2.0 (1.7–2.5) nmol/L, P = 0.05].Conclusions:During long‐term continuous proton pump inhibitor treatment, serum gastrin and CgA levels are significantly elevated compared to H2RA treatment and nontreated dyspeptic controls. H. pylori infection seems to affect gastric ECL cell secretory function. Increased serum CgA values during long‐term profound gastric acid inhibition could reflect either gastric enterochromaffin‐like cell hyperfunction or proliferative changes.
Effects of octreotide treatment on early TNF‐α production and localization in experimental chronic colitis
Authors: LAMRANI  , TULLIEZ  , CHAUVELOT‐MOACHON L , CHAUSSADE  , MAUPRIVEZ  , HAGNÉRÉ  , VIDON  
Published: March 2003

Background: Colitis induced by trinitrobenzene sulphonic acid (TNB) is a model of Th1 disease, mainly explored from the third day of induction. It has recently been shown that octreotide and other somatostatin analogues can modify inflammatory/immune processes by acting on cytokines.Aim: To examine TNFα production and the effect of preventive treatment with octreotide, during the early phase of TNB‐colitis.Methods: Thirty milligrams TNB with 50% ethanol was instilled into the colon of male Wistar rats. Treated groups received octreotide (2 × 10 μg.day/rat) or dexamethasone (1 × 2 mg.day/kg), subcutaneously, with the first injection before TNB. Eight and 80 h later, the colon was excised and processed for histology, TNFα immunohistochemistry, quantification of cytokine release ex vivo and tissue‐inducible NO synthase (iNOS) activity.Results: Maximal TNFα production was observed at the 8th hour, associated with intense immunostaining of the external muscle layer. Octreotide treatment decreased TNFα expression (staining and activity) and iNOS activity. At the 80th hour, submucosal macrophages were positive for TNFα and colonic production of IL1β and interferon γ was increased; all these effects were reduced by octreotide treatment.Conclusions: TNFα was expressed early by resident muscle cells, before staining of infiltrated immune cells and increased production of interferon γ. TNFα regulation by octreotide suggests that this drug might exert anti‐inflammatory properties via smooth muscle cells.
The effect of cisapride on duodenal acid exposure in the proximal duodenum in healthy subjects
Authors: VERHAGEN  , ROELOFS  , EDELBROEK  , SMOUT  , AKKERMANS  
Published: March 2003

Aim: To investigate the effect of the prokinetic drug, cisapride, on fasting and postprandial acid exposure in the proximal duodenum.Methods: Using a double‐blind, placebo‐controlled crossover study design, 12 healthy male volunteers were studied. After 1 week of dosing (cisapride 20 mg b.d. orally or placebo), fasting and postprandial antroduodenal pH‐and pressure‐recordings were made. Using a small‐caliber (4 mm) catheter, containing one antral and two duodenal pH electrodes, and two antral and three duodenal pressure recording sites. Transmucosal potential difference was measured to ensure proper catheter position. Infusions of 0.1 N HCl were given in the duodenal bulb.Results: Endogenous acidification of the duodenal bulb occurred more frequently during phase II and post‐ prandially, compared to phase I (P < 0.001). During phase I, alkalinization of the antrum was observed. Cisapride significantly increased the postprandial number of duodenal acidic periods (P < 0.02), but shortened their duration (P < 0.04). The duodenal motor response elicited by exogenous acid was lower during phase I (P < 0.05).Conclusions: Antral and proximal duodenal acidity vary with the phases of the interdigestive motor complex. Cisapride shortens the individual periods of duodenal acidification.
Specific inhibition of cyclooxygenase‐2 with MK‐0966 is associated with less gastroduodenal damage than either aspirin or ibuprofen
Authors: Lanza F. L. , Rack M. F. , Simon T. J. , Quan H. , Bolognese J. A. , Hoover M. E. , Wilson F. R. , Harper S. E. 
Published: March 2003

Background: Compared with currently available NSAIDs (which inhibit COX‐1 and COX‐2 isoforms of cyclooxy‐ genase), MK‐0966 (a specific COX‐2 inhibitor) is expected to cause less gastrointestinal toxicity.Aim: To compare the effect on the upper gastrointestinal mucosae of a high dose of MK‐0966 with that of conventional doses of ibuprofen and aspirin.MethodsHealthy subjects (n = 170; age range 18–54 years) with endoscopically normal gastric and duodenal mucosa were randomized to either MK‐0966 250 mg q.d. (n = 51), ibuprofen 800 mg t.d.s. (n = 51), aspirin 650 mg q.d.s. (n = 17), or placebo (n = 51) in this 7‐day, double‐blind, parallel‐group study. The mucosae were evaluated by endoscopy using a predefined scale; scores could range from 0 to 4. The primary end‐point was the percentage of subjects who developed a mucosal score ≥ 2 (i.e. the development of one or more erosions). To evaluate COX‐1 activity, serum thromboxane B2 levels were determined in a subset of the population.ResultsThe percentage of subjects who developed a mucosal score ≥ 2 in the MK‐0966 group (12%) was significantly lower (P < 0.001) than that in the ibuprofen (71%) and aspirin (94%) groups, and was similar to that in the placebo group (8%). Only ibuprofen and aspirin significantly (P < 0.0001) reduced baseline thromboxane B2 levels. All treatments were generally well tolerated.ConclusionsIn this acute short‐term endoscopic study, MK‐0966 250 mg q.d. (a dose at least 10 times higher than that demonstrated to reduce the signs and symptoms of osteoarthritis) produced significantly less gastrointestinal mucosal damage than either ibuprofen 800 mg t.d.s. or aspirin 650 mg q.d.s. and was comparable to placebo in this regard.
A new quadruple therapy for Helicobacter pylori: influence of resistant strains on treatment outcome
Authors: Okada M. , Nishimura H. , Kawashima M. , Okabe N. , Maeda K. , Seo M. , Ohkuma K. , Takata T. 
Published: March 2003

Background: There have been no reports concerning the efficacy and safety of a 1‐week quadruple therapy regimen of omeprazole, amoxycillin, roxithromycin and metronidazole for Helicobacter pylori infections and the impact of primary resistance on the eradication rate.Methods: One hundred and sixty‐nine consecutive patients with peptic ulcer disease as well as gastritis with biopsy‐proven H. pylori infection were entered into an open study of omeprazole 20 mg o.m., amoxycillin 500 mg t.d.s., roxithromycin 150 mg b.d., and metronidazole 250 mg t.d.s. Helicobacter pylori status was determined by urease test, histology and culture. Susceptibility to amoxycillin, metronidazole and roxithromycin was determined by the E‐test.Results: H. pylori was eradicated in 155 out of 169 (92%; 95% CI 88–96%) by intention‐to‐treat analysis, and in 155 out of 163 (95%; 95% CI 92–98%) by per protocol analysis. The prevalence of primary resistance against amoxycillin, roxithromycin and metronidazole was 2 out of 166 (1%), 16 out of 166 (10%) and 27 out of 166 (16%), respectively. H. pylori was eradicated in 25 out of 27 (93%) patients with metronidazole‐resistant strains compared with 130 out of 136 (96%) in patients with metronidazole‐sensitive strains of H. pylori. It was eradicated in 15 out of 16 (94%) patients with roxithromycin‐resistant strains while in 140 out of 147 (95%) patients with roxithromycin‐sensitive strains of H. pylori, and in two out of two (100%) patients with amoxycillin‐resistant stains compared with 153 out of 161 (95%) in patients with amoxycillin‐sensitive strains. H. pylori was eradicated in three out of four (75%) patients with double resistance against metronidazole and roxithromycin compared with 152 out of 159 (96%) patients with sensitive strains to metronidazole and or roxithromycin. None of these differences were statistically significant. Severe side‐effects were found in only one out of 169 patients—anaphylaxis due to penicillin.Conclusions: The 1‐week quadruple therapy with omeprazole, amoxycillin, metronidazole and roxithromycin was found to eradicate H. pylori in over 90% of all patients. This regimen was also found to be beneficial for patients with pre‐treatment resistant strains to metronidazole, roxithromycin or amoxycillin, and was observed to be safe and well‐tolerated.