bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic effect of peanut agglutinin following intravenous infusion into rats
Authors: Jordinson  , Fitzgerald  , Goodlad  , Brynes  , Grant  , Pignatelli  , Calam
Published: March 2003

Background:

Ingested peanut agglutinin stimulates colonic proliferation in humans. In rats, ingested peanut agglutinin stimulates hormone release and proliferation in the small and large intestines. Peanut agglutinin is absorbed into the circulation but little is known about the systemic effect of this lectin. Therefore, we studied the effect of intravenous peanut agglutinin on hormone release and intestinal growth.

Method:

Six rats per group received peanut agglutinin infusion at 0, 2, 20 or 200 μg/rat/day for 6 days via the right jugular vein. Organ weights were measured, pancreatic enzymes, DNA, RNA and protein levels were analysed. Plasma hormones were measured by radioimmunoassay. All tissues were examined histologically. Small intestinal and colonic proliferation rates were estimated by metaphase arrest.

Results:

High‐dose peanut agglutinin significantly reduced the wet weight of the stomach by 7% (P < 0.05) and large intestine by 10% (P < 0.05). Peanut agglutinin dose‐dependently released enteroglucagon; low‐, medium‐ and high‐dose by 64%, 126% (P < 0.01) and 180% (P < 0.01), respectively, and glucagon‐like peptide‐1 by 127% (P < 0.01), 169% (P < 0.01) and 315% (P < 0.001), respectively. Peanut agglutinin had no effect on cholesystokinin, gastrin or insulin levels. Peanut agglutinin, low‐, medium‐ and high‐dose stimulated proliferation in the mid colon by 42% (P < 0.01), 30% and 38%, respectively. Only high‐dose peanut agglutinin stimulated proliferation in the distal colon by 54% (P < 0.01). No histological changes were evident in any tissue.

Conclusion:

Intravenous peanut agglutinin released hormones and stimulated colonic proliferation. Proliferation of the small intestine seen after ingestion of peanut agglutinin in previous studies appears to require luminal contact between enterocytes and the lectin. Possible clinical applications include reversal of atrophy during total parenteral nutrition, anastomotic healing after surgery and restoration of mucosa integrity in colitis.
Managing heartburn at the ‘base’ of the GERD ‘iceberg’: effervescent ranitidine 150 mg b.d. provides faster and better heartburn relief than antacids
Authors: Earnest  , Robinson  , Rodriguez‐Stanley  , Ciociola  , Jaffe  , Silver  , Kleoudis  , Murdock
Published: March 2003

Background:

Many individuals with heartburn self‐medicate with antacids for relief of their symptoms.

Aim:

To compare efficacy of effervescent ranitidine to as‐needed calcium carbonate antacids in subjects who self‐treat heartburn.

Methods:

A total of 155 subjects with frequent antacid‐responsive heartburn were randomized to receive effervescent ranitidine 150 mg tablets b.d., or as‐needed calcium carbonate 750 mg for 12 weeks. Endoscopic oesophagitis severity and mucosal histology were assessed at baseline, and at weeks 6 and 12. Heartburn frequency, severity, and antacid consumption were recorded daily, and quality of life was assessed at baseline, and at weeks 6 and 12.

Results:

Heartburn frequency and severity were significantly decreased after 1 day of ranitidine (P < 0.02). By week 6, ranitidine had significantly decreased rescue antacid consumption (7.3 tablets, P < 0.001) vs. antacids (14.1 tablets). Endoscopic oesophagitis healing (≤ grade 1) was significantly better with ranitidine (55%, P=0.022) vs. antacids (29%). Quality of life was improved by both treatments; however, ranitidine was numerically superior for all quality of life parameters, statistically superior for several quality of life indices at week 6 and for the pain‐related index by week 12 (P < 0.05).

Conclusions:

For subjects self‐administering antacids for chronic heartburn, effervescent ranitidine 150 mg b.d. is more effective than antacids in reducing heartburn, healing erosive oesophagitis, alleviating pain, and improving quality of life.
Cisapride provides symptomatic relief in functional dyspepsia associated with gastric myoelectrical abnormality
Authors: Chen J. D. Z. , Ke M. Y. , Lin X. M. , Wang Z. , Zhang M.
Published: March 2003

Objective:

We evaluated the effects of cisapride (10 mg t.d.s. and 20 mg b.d.) on gastrointestinal symptoms and gastric myoelectrical activity in patients with functional dyspepsia. Myoelectrical activity was measured by electrogastrography.

Methods:

Patients with functional dyspepsia, defined as discomfort in the epigastrium, a negative endoscopy, and clinical symptoms of dyspepsia, were enrolled. A total of 38 patients participated in the study (23 female; 15 male; 24–72 years of age). Screening electrogastrography identified those with a normal electrogastrogram (14 subjects) and those with an abnormal electrogastrogram (24 patients). Patients were randomly assigned to 2 weeks of placebo or 2 weeks of cisapride (10 mg t.d.s.); both groups then received 2 weeks of cisapride (20 mg b.d.). Electrogastrograms were repeated at the end of each 2‐week treatment period.

Results:

Cisapride 10 mg t.d.s. significantly improved symptoms in all patients. An additional 2 weeks of treatment with cisapride 20 mg b.d. led to continued improvement in symptoms in all patients, with significant improvement in the group with abnormal baseline electrogastrograms. Cisapride significantly improved postprandial bloating and discomfort in patients with abnormal baseline electrogastrograms. Cisapride also significantly improved postprandial gastric myoelectrical activity as measured by electrogastrography in patients with abnormal baseline electrogastrograms.

Conclusion:

Cisapride provides symptomatic relief and improves gastric myoelectrical abnormalities in patients with functional dyspepsia.
Randomized comparison of unfractionated heparin with corticosteroids in severe active inflammatory bowel disease
Authors: Ang Y. S. , Mahmud N. , White B. , Byrne M. , Kelly A. , Lawler M. , Mcdonald G. S. A. , Smith O. P. , Keeling P. W. N.
Published: March 2003

Background:

Heparin therapy may be effective in steroid resistant inflammatory bowel disease.

Aim:

A randomized pilot study, to compare unfractionated heparin as a first‐line therapy with corticosteroids in colonic inflammatory bowel disease.

Methods:

Twenty patients with severe inflammatory bowel disease (ulcerative colitis, n=17; Crohn’s colitis, n=3) were randomized to either intravenous heparin for 5 days, followed by subcutaneous heparin for 5 weeks (n=8), or high‐dose intravenous hydrocortisone for 5 days followed by oral prednisolone 40 mg daily, reducing by 5 mg per day each week (n=12). After 5 days, non‐responders in each treatment group were commenced on combination therapy. Response to therapy was monitored by: clinical disease activity (ulcerative colitis: Truelove and Witt Index; Crohn’s colitis: Harvey and Bradshaw Index), stool frequency, serum C‐reactive protein and α1 acid glycoprotein, endoscopic and histopathological grading.

Results:

The response rates were similar in both treatment groups: clinical activity index (heparin vs. steroid; 75% vs. 67%; P=0.23), stool frequency (75% vs. 67%; P=0.61), endoscopic (75% vs. 67%; P=0.4) and histopathological grading (63% vs. 50%; P=0.67). Both treatments were well‐tolerated with no serious adverse events.

Conclusion:

Heparin as a first line therapy is as effective as corticosteroids in the treatment of colonic inflammatory bowel disease. Large multicentre randomized comparative studies are required to determine the role of heparin in the management of inflammatory bowel disease.
Review article: the clinical influence of Helicobacter pylori in effective acid suppression—implications for the treatment of gastro‐oesophageal reflux disease
Authors: Martínek J. , Kužela L. , Špičák J. , Vavrečka A.
Published: March 2003

The relationship between gastro‐oesophageal reflux disease (GERD) and Helicobacter pylori is unclear. Recent data indicate that H. pylori probably exerts a protective effect against GERD. In recent years, the interaction between H. pylori, proton pump inhibitors and GERD has been widely studied. Currently available proton pump inhibitors produce significantly higher intragastric pH in H. pylori‐positive patients than in those who are H. pylori negative, and this phenomenon may be clinically relevant.

The mechanisms responsible for this difference in efficacy are not fully understood, although there are two major theories. Ammonia, produced by H. pylori, is able to neutralize gastric acid, and thus apparently increase the effect of acid suppressive agents (the ‘ammonia theory’). The other theory is that decrease in acid output is due to the development of corpus gastritis during treatment with a proton pump inhibitor (the ‘gastritis theory’).

Treatment strategies to overcome this lowered sensitivity to acid suppression are to increase the frequency/dose of a proton pump inhibitor or to add an H2‐receptor antagonist in the evening—but both have pharmaco‐economic implications. An agent that could provide adequate pH control regardless of H. pylori status would be highly beneficial in the treatment of GERD, and may also lower treatment costs.
Pharmacodynamics and kinetics of omeprazole MUPS 20 mg and pantoprazole 40 mg during repeated oral administration in Helicobacter pylori‐negative subjects
Authors: Geus W. P. , Mathôt R. A. A. , Mulder P. G. H. , Lamers C. B. H. W.
Published: March 2003

Background:

Omeprazole has become available in a tablet formulation, a Multiple Unit Pellet System (MUPS) containing a large number of small individually enteric‐coated micropellets.

Aim:

To compare the acid‐inhibitory effect of omeprazole MUPS 20 mg with pantoprazole 40 mg and to describe the pharmacokinetics of both drugs following administration on day 1 and day 6.

Methods:

Randomized, two‐way crossover study. Sixteen Helicobacter pylori‐negative healthy subjects, whose gastric acidity fell below pH 4 for 70% of a 24‐h baseline period were included. Intragastric pH was measured continuously.

Results:

On day 1 both drugs significantly raised median 24‐h gastric pH compared to baseline. Median pH and percentages of time above pH 3 and 4 on day 1 and day 6 of administration were not significantly different, with the exception of median daytime pH on day 6, which was significantly higher with omeprazole (4.65 vs. 4.05). AUC and Cmax of omeprazole were significantly increased on day 6. AUC and Cmax of pantoprazole were not significantly increased.

Conclusions:

No significant difference in acid‐inhibitory effect on day 1. On day 6 median daytime pH was significantly higher with omeprazole MUPS, but the percentages of time spent above pH 3 and 4 were not significantly different. The significant increase in bioavailability of omeprazole may contribute to the increased effect on day 6.
Initial potency of lansoprazole and omeprazole tablets on pentagastrin‐stimulated gastric acid secretion—a placebo‐controlled study in healthy volunteers
Authors: Müller  , Göksu  , Fuchs  , Schlüter  , Simon
Published: March 2003

Background:

The new tablet formulation of omeprazole (Losec MUPS), is thought to have a stronger acid inhibition than the previously marketed capsules.

Methods:

The effects of the proton pump inhibitors lansoprazole and omeprazole tablets on pentagastrin‐stimulated acid secretion were compared in Helicobacter pylori‐negative healthy male volunteers (n=12). The study was placebo‐controlled, crossover matched and double‐blind for lansoprazole (Agopton) and placebo, and single‐blind for omeprazole tablets. Gastric acid response to sub‐maximal pentagastrin‐stimulation (0.6 μg · h/kg b.w.) was determined from 12.5 to 14.5 h after the first and second dose of the test drugs.

Results:

Lansoprazole 15 mg and 30 mg as well as omeprazole 20 mg tablets caused a marked decrease in gastric acid secretion, showing equipotency for 15 mg lansoprazole and 20 mg omeprazole tablets. Their efficacy, however, was lower than 30 mg lansoprazole. In addition, the inter‐individual variation after omeprazole tablets was higher than following lansoprazole. Neither 7.5 mg lansoprazole nor 10 mg omeprazole tablets were clearly different from placebo on the first 2 days.

The drugs were well‐tolerated. No clinically relevant influence was found on either laboratory screen or cardiovascular parameters.

Conclusion:

Lansoprazole 15–30 mg shows a stronger acid inhibition and a lower inter‐individual variability than the new omeprazole 20 mg tablets on days 1 and 2 of dosing.
Gastric acid secretion in cyclooxygenase‐1 deficient mice
Authors: Borrelli F. , Welsh N. J. , Sigthorsson G. , Simpson R. , Palizban A. , Bjarnason I. , Tavares I. A.
Published: March 2003

Background:

Constitutive cyclooxygenase‐1 enzyme synthesizes prostaglandins which are thought to play an important role in the functional integrity of the stomach gastric mucosa. Recently, it was shown that cyclooxygenase‐1 deficient mutant mice did not develop spontaneous gastric pathology and appear less sensitive to indomethacin‐induced gastric damage.

Aim:

To investigate gastric acid secretion in cyclooxygenase‐1 deficient mutant mice.

Methods:

The basal and histamine or isobutyl methylxanthine‐stimulated acid secretion in stomachs of cyclooxygenase‐1 deficient homozygous mice and the effect of indomethacin was compared with that of heterozygous and wild‐type mice using isolated lumen perfused mouse stomachs, in organ baths, monitored by pH‐electrodes.

Results:

There was no significant difference in the basal or histamine stimulated gastric acid secretion between wild‐type or heterozygous or homozygous mice. However, isobutyl methylxanthine was more potent in the cyclooxygenase‐1 deficient and heterozygous mice than in wild‐type mice. Indomethacin, at concentrations below 1 mM, had no effect on either basal or histamine stimulated acid secretion in any of the mice populations.

Conclusion:

Gastric acid secretion is maintained without prostaglandin involvement in cyclooxygenase‐1 deficient mice. The finding that basal and histamine‐stimulated gastric acid secretion was similar in the cyclooxygenase‐1 deficient, compared to wild‐type mice is consistent with the lack of spontaneous gastric pathology in the cyclooxygenase‐1 deficient mice.
Helicobacter pylori‐positive duodenal ulcer: three‐day antibiotic eradication regimen
Authors: Catalano F. , Branciforte G. , Catanzaro R. , Cipolla R. , Bentivegna C. , Brogna A.
Published: March 2003

Background:

The most widely used treatments for ulcer healing and Helicobacter pylori eradication consist of a 1–2 week regimen of a proton pump inhibitor plus two or three antimicrobials.

Aims:

To evaluate the efficacy, safety, cost, and tolerance of a three‐day regimen with three antibiotics vs. a 10‐day treatment with a proton pump inhibitor or vs. a ranitidine bismuth citrate triple therapy.

Methods:

Two hundred and twenty‐one patients with endoscopically‐proven H. pylori‐positive duodenal ulcers were recruited to the study. Recruited patients were assigned to one of the following four regimens: (I) omeprazole 40 mg o.m. plus amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. for 10 days (OAC: 55 patients); (ii) omeprazole 40 mg o.m. on days 1–5, plus amoxycillin 1 g b.d., clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. on days 3–5 (OACM: 56 patients); (iii) ranitidine bismuth citrate 400 mg b.d. plus amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. for 10 days (RAC: 54 patients); (iv) ranitidine bismuth citrate 400 mg b.d. on days 1–5, plus amoxycillin 1 g b.d., clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. on days 3–5 (RACM: 56 patients). Fisher’s exact test was used to compare data regarding healing and eradication in the four groups.

Results:

The intention‐to‐treat eradication and ulcer healing rates for the RACM regimen were 95% and 98%, respectively. Statistically significant differences were observed, relating to the eradication and healing of ulcers, between RACM and either the RAC or OAC regimens.

Conclusion:

The three‐day antibiotic therapy with amoxycillin, clarithromycin and metronidazole in addition to ranitidine bismuth citrate is a very effective anti‐H. pylori regimen.
Review article: effect of bile salt pool composition on hepatic and biliary functions
Authors: Carulli N. , Bertolotti M. , Carubbi F. , Concari M. , Martella P. , Carulli L. , Loria P.
Published: March 2003

The enterohepatic recirculation of bile salts exerts important regulatory effects on many hepatic, biliary and intestinal functions; such regulation is likely to depend, to a large extent, on the physical–chemical property of hydrophobicity of the recirculating pool. The present review summarizes the main experimental evidence carried out by our research group over the past two decades, in the attempt to investigate systematically the relationships between structural properties and biological effects of bile acids in humans. Hydrophobic bile acids (chenodeoxycholic acid, deoxycholic acid), but not hydrophilic acids (ursodeoxycholic acid), significantly suppressed hepatic activity of HMG‐CoA reductase, the limiting step of cholesterol synthesis, and in vivo cholesterol 7α‐hydroxylation, the limiting step of bile acid synthesis. The output of biliary cholesterol and phospholipid was also directly related to the hydrophobicity of the bile acid pool. Finally, treatment with chenodeoxycholic acid, but not with ursodeoxycholic acid, significantly decreased gall‐bladder emptying rates. When turning to the in vitro model of HepG2 cells, hydrophobic bile acids were found to induce greater cytotoxic and pro‐apoptotic effects. From this series of studies, we conclude that the regulatory effects of bile acids on the liver and biliary tract are largely dependent on the hydrophobic–hydrophilic balance of the recirculating bile acid pool.
Walking and chewing reduce postprandial acid reflux
Authors: Avidan B. , Sonnenberg A. , Schnell T. G. , Sontag S. J.
Published: March 2003

Background:

Gastro‐oesophageal reflux is worse after meals, and antacids are usually consumed after dietary indiscretion.

Aim:

To investigate whether walking or gum chewing affect meal‐induced gastro‐oesophageal reflux.

Methods:

The study population comprised 12 case subjects with gastro‐oesophageal reflux disease and 24 healthy controls. Each subject was studied using pH‐metry for 5 h on 3 separate days. After baseline recording of pH for 1 h, all subjects were fed a standard breakfast over a 20‐min period. On one of the days, oesophageal pH was recorded after the 20‐min eating period for an additional 4 h in the sitting position. On another day, postprandial oesophageal pH was recorded for the first hour whilst walking, and for 3 subsequent hours whilst sitting. During a third day, oesophageal pH was recorded for the first postprandial hour whilst gum‐chewing, followed by 3 h of sitting.

Results:

Food intake promoted gastro‐oesophageal reflux in case subjects with GERD as well as in healthy controls, although postprandial reflux was more pronounced amongst the refluxers than amongst the controls. Chewing gum for 1 h after the meal reduced the acid contact time in both groups, with a more profound effect in refluxers than in controls. Whilst the beneficial effect of 1‐h of gum‐chewing lasted for up to 3 h in both groups, the beneficial effect of 1‐h of walking was apparent only in refluxers, only to a mild degree, and only for a short duration.

Conclusions:

Chewing gum after a meal helps to reduce postprandial oesophageal acid exposure.
Eradication of Helicobacter pylori prevents ulcer development in patients with ulcer‐like functional dyspepsia
Authors: Hsu P.‐I. , Lai K.‐H. , Tseng H.‐H. , Lo G.‐H. , Lo C.‐C. , Lin C.‐K. , Cheng J.‐S. , Chan H.‐H. , Ku M.‐K. , Peng N.‐J. , Chien E.‐J. , Chen W. , Hsu P.‐N.
Published: March 2003

Background:

Although the eradication of Helicobacter pylori infection benefits patients with gastric or duodenal ulcers, the value of eradicating the infection in the patients with functional dyspepsia (FD) remains controversial.

Aims:

To determine whether eradicating H. pylori can prevent the subsequent development of ulcers or relieve the symptoms of functional dyspepsia patients.

Methods:

In a double‐blind, placebo‐controlled trial, 161 patients infected with H. pylori who had functional dyspepsia were randomly assigned to 7 days of treatment with a lansoprazole‐based triple therapy or placebo and then followed for 1 year. The main outcome measures were the development of peptic ulcers and the resolution of symptoms.

Results:

H. pylori was eradicated in 63 out of 81 patients (78%) in the treatment group and none of the 80 patients (0%) in the placebo group. During the follow‐up period, two patients in the treatment group and six patients in the placebo group developed peptic ulcers at repeat endoscopy (2.5% vs. 7.5%; 95% CI: –12 to 2). The reduction in ulcer rates was statistically significant in the ‘ulcer‐like’ sub‐group (0% vs. 16.7%; 95% CI: –32 to –2), but not in the ‘dysmotility‐like’ and ‘unclassifiable’ sub‐groups. Regarding symptom response, the resolution rates of symptoms were similar between the treatment and placebo groups (58.0% vs. 55.0%, 95% CI: –12 to 18). Additionally, no significant differences existed in the symptom responses between the treatment and control arms in each of the dyspepsia sub‐groups.

Conclusions:

Eradicating H. pylori can prevent the subsequent development of peptic ulcers in the patients with ‘ulcer‐like’ functional dyspepsia. However, this approach does not significantly reduce the symptoms of functional dyspepsia patients.
Pain versus discomfort—is differentiation clinically useful?
Authors: Stanghellini V.
Published: March 2003

Functional dyspepsia is highly variable in its clinical presentation and multifactorial in its underlying causes. Since many of the symptoms included in the definition of dyspepsia are intuitively suggestive of different pathogenic mechanisms, it has been proposed that patients with functional dyspepsia be divided into distinct dyspepsia sub‐groups according to symptom clusters. The goal was to classify patients more homogeneously for research purposes as well as to target treatment.

However, recent epidemiological, pathophysiological, and clinical studies indicate that a priori definitions based on the presence/absence of symptoms or clusters of symptoms have no clinical utility due to the considerable overlap between symptoms, as well as the poor correlation between pathogenic factors and responses to treatment.

Attention is now focused on identifying predominant symptoms. Recent studies suggest that the analysis of predominant symptoms, demographic features, and overlapping digestive syndromes can help to identify dyspepsia sub‐groups with different underlying pathophysiological features and aid in selecting appropriate treatment.

The utility of this approach has been demonstrated in gastro‐oesophageal reflux disease, which can be reliably diagnosed and managed on the basis of the presence and severity of the predominant symptom, heartburn. It is likely that precise symptom definitions and history‐taking will be of pivotal importance in management strategies for functional dyspepsia.
Oral versus combination mesalazine therapy in active ulcerative colitis: a double‐blind, double‐dummy, randomized multicentre study
Authors: Vecchi M. , Meucci G. , Gionchetti P. , Beltrami M. , Di Maurizio P. , Beretta L. , Ganio E. , Usai P. , Campieri M. , Fornaciari G. , De Franchis R.
Published: March 2003

Background:

Oral and topical mesalazine formulations are effective in active ulcerative colitis, but little is known on the efficacy of combined treatment.

Aim:

To compare the efficacy of oral mesalazine vs. combined oral and topical mesalazine in mildly to moderately active ulcerative colitis.

Methods:

Patients with mildly to moderately active ulcerative colitis (Clinical Activity Index, CAI 4–12) were identified at 15 participating centres. They were randomized to receive either mesalazine 4 g orally plus placebo enema, or mesalazine 2 g orally plus mesalazine 2 g rectally as a liquid enema for 6 weeks. The rate of clinical remission (CAI < 4) or clinical remission/improvement (reduction of CAI of 50% from baseline) at 6 weeks and time to clinical remission/improvement were primary end‐points; the rate of endoscopic remission was a secondary end‐point.

Results:

67 patients were assigned to oral treatment and 63 to combined treatment. One patient in the oral group and 2 in the combined group discontinued the treatment due to adverse events. Following an intention‐to‐treat analysis, the rate of clinical remission was 82% for oral treatment and 87% for combined treatment (P=0.56); the mean time to remission 22.2 and 20.2 days, respectively (P=0.29); the rate of clinical remission/improvement and the rate of endoscopic remission were 85% and 91% (P=0.503) and 58% and 71% (P=0.21), respectively.

Conclusions:

In patients with mild active ulcerative colitis, mesalazine 4 g orally and 2 g orally plus 2 g enema are equally effective in inducing disease remission.
Meta‐analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome
Authors: Poynard T. , Regimbeau C. , Benhamou Y.
Published: March 2003

Aim:

To update previous overviews of placebo‐controlled double‐blind trials assessing the efficacy and tolerance of smooth muscle relaxants in irritable bowel syndrome.

Methods and trials:

A total of 23 randomized clinical trials were selected for meta‐analyses of their efficacy and tolerance. Six drugs were analysed: cimetropium bromide (five trials), hyoscine butyl bromide (three trials), mebeverine (five trials), otilium bromide (four trials), pinaverium bromide (two trials) and trimebutine (four trials). The total number of patients included was 1888, of which 945 received an active drug and 943 a placebo.

Results:

The mean percentage of patients with global improvement was 38% in the placebo group (n=925) and 56% in the myorelaxant group (n=927), in favour of myorelaxants with a mean odds ratio of 2.13, P < 0.001 (95% CI: 1.77–2.58) and a mean risk difference of 22% P < 0.001 (95% CI: 13–32%). The percentage of patients with pain improvement was 41% in the placebo group (n=568) and 53% in the myorelaxant group (n=567): odds ratio 1.65, P < 0.001 (95% CI: 1.30–2.10) and risk difference 18%, P < 0.001 (95% CI: 7–28%). There was no significant difference for adverse events.

Conclusion:

Myorelaxants are superior to placebo in the management of irritable bowel syndrome.
Current endoscopic therapeutic options in the management of variceal bleeding
Authors: Helmy A. , Hayes P. C.
Published: March 2003

Variceal bleeding is a frequent and life‐threatening complication of portal hypertension. The first episode of variceal bleeding is not only associated with a high mortality, but also with a high recurrence rate in those who survive. Therefore, many studies and randomized clinical trials have focused on different therapeutic strategies aiming to prevent the first episode of variceal bleeding (primary prophylaxis), to control haemorrhage during the acute bleeding episode (emergency treatment), and to prevent re‐bleeding (secondary prophylaxis). These strategies involve pharmacological, endoscopic, surgical, and interventional radiological modalities.

This review concentrates on the clinical aspects of the endoscopic modalities used to treat oesophageal variceal haemorrhage, including variceal injection sclerotherapy, variceal band ligation, and the use of tissue adhesives (glue) and their substitutes. We also draw conclusions from the available literature regarding the use of endoscopic modalities in primary prophylaxis, emergency treatment, and secondary prophylaxis of variceal re‐bleeding. The management of gastric varices and variceal bleeding during pregnancy is also addressed.
Relationship between lactose digestion, gastrointestinal transit time and symptoms in lactose malabsorbers after dairy consumption
Authors: Labayen I. , Forga L. , González A. , Lenoir‐Wijnkoop I. , Nutr R. , Martínez J. A.
Published: March 2003

Background:

The relationship of symptoms with objective measurements, as well as some of the mechanisms involved in lactose tolerance after yoghurt consumption, remain unclear.

Methods:

The trial had a double‐blind design in which 22 lactose malabsorbers received 25 g daily lactose in fresh (living bacteria > 108 cfu/g) yoghurt or heated (< 102 cfu/g) yoghurt for 15 days, followed by a cross‐over (15 days) after a wash‐out period (14 days). The lactose digestion was determined by the breath H2 test, the gastric emptying (GE) with a 13C‐acetate breath test and the revealed transit time (OCTT) by 15N‐lactose‐ureide test. Subjects reported their gastrointestinal symptoms (GIS) in a validated questionnaire.

Results:

Breath H2 test indicated more effective lactose digestion after fresh yoghurt intake. The OCTT was shorter after heated yoghurt ingestion as compared with the fresh. There was lower severity of GIS (P < 0.05) after fresh yoghurt intake, and this showed an inverse correlation with OCTT (P < 0.05).

Conclusions:

Delayed orocoecal transit time was associated with fewer gastrointestinal symptoms. The improved lactose digestion and tolerance of fresh yoghurt should be mainly attributed to the presence of living bacteria.
Population‐based case control study of the safety of sulfasalazine use during pregnancy
Authors: Nørgård B. , Czeizel A. E. , Rockenbauer M. , Olsen J. , Sørensen H. T.
Published: March 2003

Background:

We studied the human teratogenic risk of sulfasalazine because this drug interferes with folate metabolism.

Methods:

Case control study within the Hungarian Case Control Surveillance of Congenital Abnormalities, 1980–1996; based on 22 865 new‐born infants or foetuses with congenital abnormalities, and 38 151 babies without any detected congenital abnormalities (control group).

Results:

Seventeen pregnant women (0.07%) were treated with sulfasalazine in the case group, and 26 (0.07%) in the control group. The overall adjusted adds ratio of congenital abnormalities after sulfasalazine treatment was odds ratio=1.2 (95% confidence interval: 0.6–2.1). None of the analyses indicated any significant increased prevalence of selected congenital abnormalities among the exposed compared with the not exposed.

Conclusions:

We found no significant increased prevalence of selected congenital abnormalities in the children of women treated with sulfasalazine during pregnancy. However, the amount of information is limited and additional data are needed to rule out a teratogenic effect.
Enhanced mucosal fibrinolytic activity in gastroduodenal ulcer haemorrhage and the beneficial effect of acid suppression
Authors: Vreeburg E. M. , Levi M. , Rauws E. A. J. , Deventer S. J. H. V. , Snel P. , Bartelsman J. W. F. M. , Ten Cate J. W. , Tytgat G. N. J.
Published: March 2003

Background:

The high mortality rate in patients with upper gastrointestinal bleeding appears to be particularly related to re‐bleeding. The haemostatic mechanisms that may influence the re‐bleeding of ulcers are largely unknown.

Aim:

We studied and analysed fibrinolytic activity in bleeding ulcer patients and the effect of acid suppression on this activity.

Methods:

Fibrinolytic activity was analysed in mucosal biopsies from 29 bleeding gastroduodenal ulcer patients and six controls. We analysed levels of D‐Dimer, fibrin plate lysis area, plasminogen activator activity, plasminogen activator inhibitor activity, and plasmin antiplasmin complexes.

Results:

Significantly more fibrinolytic activity was detected in biopsies from patients with bleeding ulcers compared to controls. Moreover, in patients with endoscopic stigmata of recent haemorrhage, mucosal fibrinolytic activity was higher compared to patients without stigmata of recent haemorrhage. In mucosal biopsies of patients that had used acid suppression before admission, a decreased fibrinolytic activity was found compared to patients without such therapy. This effect of acid suppression on fibrinolytic activity was confirmed in nine patients before and after a 24‐h ranitidine infusion.

Conclusions:

Fibrinolytic activity is enhanced in patients with bleeding gastroduodenal ulcers. Acid suppressive therapy decreases this increased activity, which may be one of the mechanisms explaining the potential beneficial effect of this therapy.
Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to CYP2C19 genotypes
Authors: Horai Y. , Kimura M. , Furuie H. , Matsuguma K. , Irie S. , Koga Y. , Nagahama T. , Murakami M. , Matsui T. , Yao T. , Urae A. , Ishizaki T.
Published: March 2003

Background:

S‐mephenytoin 4’‐hydroxylase (CYP2C19) catalyses the metabolism of rabeprazole to some extent. Based on the metabolic and pharmacokinetic differences among other proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole, rabeprazole appears to be the least affected proton pump inhibitor by the CYP2C19‐related genetic polymorphism.

Aim:

To determine whether the pharmacodynamic effects of rabeprazole on intragastric pH and serum gastrin levels, and its pharmacokinetics depend on the CYP2C19 genotype status.

Methods:

Eighteen healthy subjects, whose CYP2C19 genotype status was previously determined, participated in the study. They consisted of six each of homozygous extensive metabolisers (homo EMs), heterozygous extensive metabolisers (hetero EMs), and poor metabolisers (PMs). Helicobacter pylori status was determined by serology. After a single oral dose of 10 mg or 20 mg rabeprazole or water only (baseline data), intragastric pH values were monitored for 24 h. Plasma levels of rabeprazole and serum gastrin were also measured for 24 h post‐dose.

Results:

Five homo EM, six hetero EM and four PM subjects were H. pylori‐negative. After rabeprazole administration, significant differences in intragastric mean pH values, serum gastrin AUC0–24 and plasma levels of rabeprazole were observed among the three different genotype groups.

Conclusion:

The pharmacodynamic effects of rabeprazole and its pharmacokinetics depend on the CYP2C19 genotype status.
Modified seven‐day, quadruple therapy as a first line Helicobacter pylori treatment
Authors: Calvet X. , Garcia N. , Gené E. , Campo R. , Brullet E. , Sanfeliu I.
Published: March 2003

Background:

Cure rates of 7‐day triple therapy seem to be decreasing. Quadruple therapies may be an alternative, although their complex administration makes patient acceptance difficult.

Objective:

To test the usefulness of a thrice a day, quadruple therapy to cure Helicobacter pylori infection.

Patients and methods:

A total of 122 consecutive patients with peptic ulcer and Helicobacter pylori infection were treated with omeprazole 20 mg b.d., tetracycline chlorhydrate 500 mg t.d.s., metronidazole 500 mg t.d.s., and bismuth subcitrate 120 mg t.d.s. administered with meals for 7 days. Cure was tested by either endoscopy or breath test after 2 months, and by urea breath test 6 months after therapy.

Results:

Seven patients were lost to follow‐up. Of the remaining 115, 110 were cured at the first control, giving an intention‐to‐treat cure rate of 90.2% (95% CI: 83–95%) and a per protocol cure rate of 95.7% (95% CI: 90–98%). One hundred three patients returned for a 6‐month breath test; all but one were cured. Side‐effects were minimal or minor in 47 patients (40.8%) and moderate in four (3.4%). Compliance was good, 95% of patients taking more than 90% of the pills. Six (5%) patients stopped treatment after 1, 2, 4 (two patients) and 6 (two patients) days.

Conclusion:

Thrice a day quadruple therapy shows excellent cure rates, far above 90%, is well‐tolerated and compliance is easy. Head‐to‐head comparison with triple therapies as first line Helicobacter pylori treatment seems warranted.
Acid suppression in the management of gastro‐oesophageal reflux disease—an appraisal of treatment options in primary care
Authors: Jones R. , Bytzer P.
Published: March 2003

Gastro‐oesophageal reflux disease (GERD) is one of the most common conditions presenting to the primary care physician. Despite progress in understanding and treatment of the disease, strategies for capitalizing on these advances are less well developed. In many practices, H2‐receptor antagonists still remain the most widely prescribed treatment for GERD, despite the availability of the more effective acid‐suppressant proton pump inhibitors.

This review examines the relative efficacies of acid‐suppressant drugs in minimizing oesophageal acid exposure and outlines the evidence for the superiority of proton pump inhibitors over standard‐dose H2‐antagonists in symptom relief, erosion healing and prevention of relapse in GERD. Current prescribing patterns and considerations for the general practitioner are also examined. The availability and impact of over‐the‐counter H2‐antagonists on the treatment of GERD and their relative cost‐effectiveness vs. proton pump inhibitors are also addressed.

A hierarchy of drug efficacy (full‐dose proton pump inhibitor > half‐dose proton pump inhibitor > high‐dose H2‐antagonist > standard‐dose H2‐antagonist or prokinetic) applies in principle to all GERD patients, (with or without oesophagitis). The most effective initial therapy for GERD is also likely to be the most cost‐effective one, if treatment failure leads to higher utilization of medical resources.

The application of these recommendations to the management of non‐endoscoped GERD, endoscopy‐negative GERD and low‐grade oesophagitis as well as higher grade oesophagitis is also reviewed.
Anti‐inflammatory and tissue‐protectant drug effects: results from a randomized placebo‐controlled trial of gastritis patients at high risk for gastric cancer
Authors: Fischbach L. A. , Correa P. , Ramirez H. , Realpe J. L. , Collazos T. , Ruiz B. , Bravo L. E. , Bravo J. C. , Casabon A. L. , Schmidt B. A.
Published: March 2003

Background:

The inflammatory process involvingHelicobacter pylori‐associated gastritis is thought to lead to epithelial damage and contribute to the development of gastric cancer. Evidence exists from animal andin vitrostudies suggesting that tetracyclines have both anti‐inflammatory and tissue‐protectant effects unrelated to their antimicrobial activity. We attempted to modulate components ofH. pylori’sinflammatory process by: (i) eliminating the infection; (ii) using tetracycline to alter the host’s reaction to the infection without reducing the bacterial load; and (iii) using calcium to counteract the effect of excessive dietary salt.

Methods:

We conducted a 16‐week placebo‐controlled clinical trial with 374H. pylori‐associated gastritis patients randomly assigned to one of five groups: (1) triple therapy consisting of metronidazole, amoxicillin and bismuth subsalicylate for 2 weeks, followed by bismuth alone for 14 weeks; (2) calcium carbonate; (3) triple therapy and calcium carbonate; (4) tetracycline; or (5) placebo.

Results:

Subjects in the tetracycline and triple therapy groups, but not the calcium carbonate only group, showed a reduction in inflammation and epithelial damage vs. those in the placebo group, independent of a change inH. pyloridensity and other factors. Our results also indicate that epithelial damage may be affected by mechanisms independent ofH. pyloridensity or inflammation.

Conclusion:

The results are consistent with the hypothesis that tetracycline can decrease inflammation independent of a reduction in the bacterial load. More research is needed to investigate mechanisms leading to epithelial damage which are independent ofH. pyloridensity and inflammation.
Arrest of chronic acid suppressant drug use after successful Helicobacter pylori eradication in patients with peptic ulcer disease: a six‐month follow‐up study
Authors: Hurenkamp G. J. B. , Grundmeijer H. G. L. M. , Van Der Ende A. , Tytgat G. N. J. , Assendelft W. J. J. , Van Der Hulst R. W. M.
Published: March 2003

Background:

It remains controversial whether successful H. pylori eradication leads to relief of dyspepsia and the subsequent arrest or tapering of acid‐suppressant drug therapy, or to an aggravation of acid‐related dyspepsia requiring more acid‐suppressant drug intake.

Aim:

To evaluate prospectively the effect of H. pylori eradication on the requirement of acid‐suppressant drug or antacids and the evolution of dyspeptic symptoms in chronic acid‐suppressant drug users with peptic ulcer disease.

Materials and methods:

The use of acid‐suppressant drugs, rescue antacids and predominant symptoms were recorded prospectively during 24 weeks after H. pylori eradication therapy in 75 peptic ulcer disease patients.

Results:

In 71 patients with complete follow‐up, ulcers were healed at follow‐up endoscopy and H. pylori was successfully eradicated. After 6 months, 93% (66 out of 71) of chronic acid‐suppressant drug users had stopped acid‐suppressant drug intake. The mean daily acid‐suppressant drug dosage per patient decreased from 1.72 at entry to 0.03 units acid‐suppressant drug (98%; P < 0.0001) during follow‐up. The mean number of antacid tablets/day/patient was 0.26 during follow‐up for the relief of mild inter‐current dyspeptic symptoms. Medication use was not different in peptic ulcer disease patients with or without gastro‐oesophageal reflux disease at baseline. The prevalence of gastro‐oesophageal reflux disease decreased from 42% before to 35% after H. pylori eradication (N.S.).

Conclusion:

Successful H. pylori eradication in peptic ulcer disease patients almost completely eliminates the need for acid‐suppressant drug regardless of the presence or absence of gastro‐oesophageal reflux disease at entry.
Comparison of the effects of concanavalin‐A and epidermal growth factor on epithelial cell proliferation in the rat intestine
Authors: Fitzgerald A. J. , Jordinson M. , Rhodes J. M. , Singh R. , Calam J. , Goodlad R. A.
Published: March 2003

Background:

Concanavalin‐A, the lectin present in Jack beans, binds to mannose‐ and glucose‐containing residues and can interact with the epidermal growth factor receptor and moderate cell proliferation in vitro.

Aim:

To compare the actions of concanavalin‐A and epidermal growth factor on the gastrointestinal tract in vivo.

Methods:

Rats maintained on total parenteral nutrition were given intragastric concanavalin‐A, intravenous epidermal growth factor or concanavalin‐A and epidermal growth factor. Cell proliferation and crypt fission were assayed in ‘micro‐dissected’ crypts.

Results:

Concanavalin‐A and epidermal growth factor both significantly elevated proliferation in the small intestine and colon. No significant interaction between the effects of these two agents was seen, except in the mid small intestine where there was a synergistic interaction. Concanavalin‐A had no effect on crypt branching. Epidermal growth factor significantly reduced branching in the distal small intestine and mid colon.

Conclusion:

The effects of the two agents appeared to be separate, except in the mid small intestine where they were additive. This is in marked contrast with the actions reported in vitro, where concanavalin‐A is a powerful inhibitor of epidermal growth factor‐induced cell proliferation. Concanavalin‐A thus has potential for enhancing the functions of the small intestine.
Ranitidine bismuth citrate with clarithromycin alone or with metronidazole for the eradication of Helicobacter pylori
Authors: Bardhan K. D. , Morton D. , Perry M. J. , Sanders D. S. , Morris P. , Rowland A. , Thompson M. , Mitchell T. R. , Roberts P. M.
Published: March 2003

Background

: Both triple therapy with ranitidine bismuth citrate (RBC) plus two antibiotics for 7 days and dual therapy of RBC with clarithromycin for 14 days have been extensively studied; both regimens effectively eradicate Helicobacter pylori. However, few studies have assessed the efficacy of dual therapy given for 7 days.

Aim

: To compare the efficacy and safety of RBC 400 mg with clarithromycin 500 mg, alone or with metronidazole 400 mg, given twice daily for 7 days for the eradication of H. pylori.

Methods

: This single centre, randomized, double‐blind study involved 118 patients with dyspepsia or a history of peptic ulcer disease. H. pylori infection was detected initially by CLO test, and confirmed in 109 patients by urea breath test and/or microbiology culture. H. pylori eradication was assessed 4 and 12 weeks after the end of treatment by urea breath test. H. pylori antibiotic susceptibility was assessed pre‐study in all patients, and post‐treatment in patients with a positive post‐treatment urea breath test. Adverse events were recorded throughout the study.

Results

: H. pylori was eradicated in 93% of patients who received RBC with clarithromycin and metronidazole and in 84% of patients who received RBC with clarithromycin (intention‐to‐treat rates). Per protocol eradication rates were 98% and 90% for triple therapy and dual therapy, respectively. The eradication of metronidazole‐resistant H. pylori was achieved in 100% and 88% of patients following dual therapy and triple therapy, respectively, and acquired resistance to clarithromycin occurred in only one patient following treatment failure. Both treatments were well‐tolerated; only one patient (2%) was withdrawn from each treatment group due to adverse events.

Conclusions

: RBC with clarithromycin and metronidazole is a highly effective and well‐tolerated triple therapy regimen for the eradication of H. pylori. RBC with clarithromycin dual therapy has a similar efficacy, and offers an alternative to triple therapy when there are concerns about treatment with metronidazole or the use of multiple antibiotics. Both regimens are effective against antibiotic‐resistant strains of H. pylori.
Review article: over‐the‐counter drugs and the gastrointestinal tract
Authors: Sheen C. L. , Colin‐Jones D. G.
Published: March 2003

An increasing number of drugs are becoming available over‐the‐counter, empowering patients to treat them‐ selves. Although drugs presently available over‐the‐counter are generally safe, there are issues of safety and possible delays in diagnosis of serious conditions. Therefore it is vital that patients are made aware of the indications and limitations of over‐the‐counter drugs through improved communication and education. Pharmacists and drug companies will have an increasingly important role in giving information and advice to patients. This review looks at the present and future of over‐the‐counter medication, highlighting the safety aspects.
H2‐receptor antagonists in the treatment of functional (nonulcer) dyspepsia: a meta‐analysis of randomized controlled clinical trials
Authors: Redstone H. A. , Barrowman N. , Veldhuyzen Van Zanten S. J. O.
Published: March 2003

Aim:

To perform a meta‐analysis evaluating the efficacy of H2‐receptor antagonists in functional (nonulcer) dyspepsia.

Selection of studies:

A Medline search was used to identify placebo controlled randomized clinical trials, using the subject headings dyspepsia and H2‐receptor antagonist.

Outcome measures:

Global assessment by the patient of dyspepsia symptoms, improvement of epigastric pain and complete relief of epigastric pain.

Results:

Twenty‐two studies met the inclusion criteria, 15 of which reported the active drug to be superior to placebo. Many studies suffered from suboptimal study design. The odds ratio in favour of active drug was 1.48 (95% confidence interval: 0.9–2.3) for global assessment of dyspepsia symptoms, 2.3 (95% CI: 1.6–3.3) for improvement of epigastric pain, and 1.8 (95% CI: 1.2–2.8) for complete relief of epigastric pain.

Conclusion:

There is some evidence that H2‐receptor antagonists are superior to placebo in functional dyspepsia, but larger studies evaluating higher doses of H2‐receptor antagonists and of longer duration are necessary to determine the exact effect size.