bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of acute and chronic acid suppression on plasma gastrin release in the rat
Authors: SCHUERER‐MALY C.‐C. , KROMER W. , FLOGERZP B. , VARGA L , POSTIUS S. , HALTER F.
Published: July 2010

The mechanisms by which administration of the H+, K+‐ATPase inhibitor B 831–78 or intragastric perfusion with NaHCO3 induces plasma gastrin release were studied in the rat. Experiments were performed after a washout of residual intragastric contents in fasted animals provided with chronic gastric fistulae. Acute and chronic administration of B 831–78 elevated plasma gastrin dose‐dependently up to 5–6 times above control levels, while the increase was only twofold with intragastric NaHCO3 infusion despite similar neutralization of gastric acidity.

The profound hypergastrinaemia induced by the H+, K+‐ATPase inhibitor, after both acute and chronic treatment, was completely prevented or reversed by intragastric perfusion with physiological amounts of acid (0.15 N HCl, 2.5 ml/h). The hypergastrinaemia was, however, largely resistant to high doses of atropine (4.3 μ mol/kg) and of the M1 selective muscarinic antagonist telenzepine (10 μ mol/kg). In contrast, the modest increase in plasma gastrin induced by gastric perfusion with NaHCO3 was completely suppressed by the high atropine dose and was attenuated by small doses of atropine or telenzepine (0.01 μ mol/kg and 1 μ mol/kg).

These results demonstrate that, in the rat, blockade of the H+, K+‐ATPase can potently induce gastrin release in the absence of a meal. Moreover, they suggest that interruption of the negative feedback between acid and gastrin release is the main mechanism through which this class of drugs releases gastrin in the rat. Since a similar degree of gastrin release cannot be achieved by alkalinization of gastric contents, additional hormonal or neural regulatory factors may contribute to the drug‐induced hypergastrinaemia.
Comparison of plasma bismuth levels after oral dosing with basic bismuth carbonate or tripotassium dicitrato bismuthate
Authors: MADAUS S. , SCHULTE‐FROHLINDE E. , SCHERER C. , KÄMMEREI? A. , SCHUSDZIARRA V. , CLASSEN M.
Published: July 2010

In 20 healthy subjects plasma bismuth concentration was measured after single oral doses of basic bismuth carbonate or tripotassium dicitrato bismuthate. The drugs were administered in the fasted state or immediately after ingestion of a standard breakfast. After basic bismuth carbonate, plasma bismuth rose to concentrations between 0.7 and 2.6, μg/L in the fasted state, while after the meal the maximal level was only 1.3, μg/L. In contrast to these very low levels after basic bismuth carbonate, the administration of tripotassium dicitrato bismuthate was paralleled by an increase of plasma bismuth to concentrations between 15 and 232 μg/L with a mean peak value of 64 ± 15.3 (S.E.M.), μg/L in the fasted state. Postprandial ingestion of tripotassium dicitrato bismuthate attenuated the peak concentrations to 10.9 ± 6.3, μg/L. One subject, however, had a value of 120 μg/L. This study demonstrates that basic bismuth carbonate leads to very low plasma bismuth concentrations, which are far below the critical range that might eventually be associated with bismuth neurotoxicity. Therefore this compound can be considered potentially useful for bismuth therapy of gastrointestinal disorders.
Sucralfate diminishes basal acid output without affecting gastrin, H. pylori or gastritis in duodenal ulcer patients
Authors: MOSS S. F. , THOMAS D. M. , AYESU K. , LEVI S. , CALAM J.
Published: July 2010

Twelve patients with active duodenal ulcer disease and Helicobacter pylori infection were treated with 1 g sucralfate q.d.s. for 1 month. Ulcers healed in 8 of the 12 patients without an alteration in the H. pylori‐associated antral gastritis. Sucralfate produced a significant fall in basal acid output in all the patients, from a median of 4.8 (range 2.1–12.1) to 1.6 (0.4–8) mmol/h, P < 0.01, whereas peak acid output was unchanged from 41 (21–59) before to 38 (24–55) mmol/h after treatment. Basal plasma gastrin concentrations and the meal‐stimulated integrated gastrin response were not altered significantly by sucralfate : 8 (2–17) pmol/L and 732 (188–1045) pmol. min/L pre‐treatment and 6 (2–17) pmol/L and 600 (140–1302) pmol. min/L post‐treatment, respectively. The fall in basal acid output observed may contribute to prolonged duodenal ulcer remission after treatment with sucralfate.
An Eudragit‐coated prednisolone preparation for ulcerative colitis: pharmacokinetics and preliminary therapeutic use
Authors: FORD G. A. , OLIVER P. S. , SHEPHERD N. A. , WILKINSON S. P.
Published: July 2010

Prednisolone metasulphabenzoate, a steroid with poor colonic absorption, was coated with the pH‐dependent acrylic resin Eudragit S, as a means of delivering an orally administered preparation to the proximal colon. The therapeutic potential of delivering this steroid with potentially less systemic side‐effects to the proximal colon was assessed in extensive ulcerative colitis. Plasma and urine prednisolone profiles in 6 healthy volunteers confirmed minimal absorption from Eudragit S‐coated prednisolone metasulphabenzoate compared to prednisolone acetate: peak plasma prednisolone concentrations 29 ± 21 ng/ml vs. 570 ± 185 ng/ml (P < 0.01), area under curve measurements 204 ± 214 vs. 2724 ± 1236 ng.h/ml (P < 0.01). Prednisolone metasulphabenzoate coated with Eudragit S (30–60 mg daily) was then administered for 12 weeks to 12 patients with colonoscopically proven extensive ulcerative colitis in relapse. Symptoms, sigmoidoscopic appearances and rectal histological abnormalities all improved during therapy. Complete clinical remission occurred in 7 patients, a partial response in 2 patients and no response in 3 patients. Cortisol responses to tetracosactrin demonstrated no significant adrenal suppression following treatment. Eudragit S‐coated prednisolone metasulphabenzoate may be a useful treatment for extensive ulcerative colitis, without risk of systemic steroid side‐effects.
The in‐vitro mucosal conjugation of ethinyloestradiol and the bioavailability of oral contraceptive steroids in patients with treated and untreated coeliac disease
Authors: GRIMMER S. F. M. , BACK D. J. , ORME M. L'E. , TJIA J. F. , GILMORE I. T. , ELLIS A.
Published: July 2010

The ethinyloestradiol (EO2) component of oral contraceptive steroids is extensively conjugated with sulphate by the gut wall. The ability of gastrointestinal mucosa to conjugate EO2 has been examined in vitro in samples of mucosa taken from normal women as well as from women with coeliac disease. The percentage conjugation per mg dry weight for normal tissue (n= 11) was 17.1 ± 6.4 (mean ± s.d.) while in untreated coeliac tissue (n= 6) the figure was 6.3 ± 3.6% (P < 0.01). In tissue from patients with treated coeliac disease (n= 5) the figure was 12.1 ± 3.2%.

Thus the ability of intestinal mucosa to conjugate ethinyloestradiol was significantly reduced in patients with coeliac disease, and restored towards normal following treatment. However, in patients with coeliac disease the pharmacokinetics of ethinyloestradiol were not significantly different from normal controls.
Oral or intravenous erythromycin has no effect on human distal colonic motility
Authors: JAMESON J. S. , ROGERS J. , MISIEWICZ J. J. , RAIMUNDO A. H. , HENRY M. M.
Published: July 2010

Erythromycin is a prokinetic agent for the lower oesophageal sphincter, the stomach, the gallbladder and the small bowel, acting directly on motilin receptors. Its effect on pressure activity of the human colon has not been investigated. Eight healthy volunteers were studied on 2 occasions and given intravenous or oral erythromycin, or placebo in a single‐blind, randomized crossover study. Sigmoid pressure activity was measured using a 4‐lumen water perfused system placed sigmoidoscopically at 50, 45, 30 and 15 cm from the anal verge. The pressures were analysed for activity index (mmHg.min) for the 35 cm colonic study segment using dedicated software. No significant difference was found in the activity index following oral erythromycin (500 mg) or placebo, or following intravenous erythromycin 1.8 mg/kg or placebo. A further 8 subjects were studied in a single‐blind crossover study to determine the effect of oral erythromycin (500 mg) b.d. on colonic transit, measured with radio‐opaque markers and a single abdominal X‐ray. Mean or segmental colonic transit times were not statistically significantly different (Student's paired t‐test) in the subjects on placebo or erythromycin. This lack of effect of erythromycin on the distal large intestine may indicate the absence of receptors for motilin in that part of the gut.
Ranitidine for erosive oesophagitis: a double‐blind, placebo‐controlled study
Authors: ROUFAIL W. , BELSITO A. , ROBINSON M. , BARISH C. , RUBIN A.
Published: July 2010

A multicentre, randomized, double‐blind, placebo‐controlled study was conducted to evaluate the efficacy and safety of ranitidine 150 mg and 300 mg in 342 patients with erosive oesophagitis. Treatment was given four times daily, and continued for 12 weeks or until healing (that is, normal or only erythematous mucosa). Erosive oesophagitis healing rates, as determined by endoscopy, were significantly greater in ranitidine‐treated patients by 4 weeks compared with those of placebo‐treated patients. By 12 weeks, erosive oesophagitis healing rates were 83 and 81% for ranitidine‐treated patients (150 and 300 mg, respectively) and 58% for placebo‐treated patients (P± 0.001, ranitidine vs. placebo). Symptomatic relief was achieved within 24 hours after starting either dosage of ranitidine. Heartburn frequency (P < 0.001) and severity (P < 0.001), as well as antacid consumed per week (P < 0.001), were reduced in both ranitidine groups in comparison with placebo. Healing rates and symptom relief were similar in the two ranitidine groups. Both dosages of ranitidine were well tolerated. Ranitidine (150 mg) given four times daily appears to be as effective as 300 mg ranitidine given four times daily in patients with moderate to severe oesophageal erosions.
Short report: comparison of two doses of balsalazide in maintaining ulcerative colitis in remission over 12 months
Authors: GREEN J. R. B. , SWAN C. H. J. , ROWLINSON A. , GIBSON J. A. , BROWN P. , KERR G. D. , SWARBRICK E. T. , THORNTON P.
Published: July 2010

In a four‐centre prospective double‐blind trial, 108 patients with ulcerative colitis in remission were randomized to receive balsalazide in doses of 3 g or 6 g/day for 12 months. The patients were assessed at 3‐monthly intervals clinically, sigmoidoscopically and with routine haematology and biochemistry. Remission rates of 77% (3 g/day) and 68% (6 g/day) at 12 months were not significantly different. Intolerance reactions leading to withdrawal from the study occurred in only 9 patients (8%), all occurring in the first 7 weeks of the study. Balsalazide is therefore both highly effective in maintaining remission in ulcerative colitis and well tolerated in both conventional and high dosage (the latter equivalent to 5.5 g/day of sulphasalazine). In this study no distinct advantage in maintenance of remission has been found for the higher dose of balsalazide.
The effects of flumazenil on alertness and hypoxia in elderly patients after ERCP
Authors: HAINES D. J. , BIBBEY D. , GREEN J. R. B.
Published: July 2010

It is not known whether hypoxia, associated with upper gastrointestinal endoscopic procedures when midazolam sedation is used without narcotics, persists into the post‐procedure recovery period. Thirty consecutive patients aged over 60 years, undergoing ERCP using midazolam sedation alone, were monitored clinically and by pulse oximetry before, during and for 2 hours after the procedure. They were randomized prospectively to receive either 0.5 mg flumazenil or normal saline on extubation. Results show that patients were most hypoxic in the first 30 minutes after the procedure and that mean oxygen saturation had not returned to pre‐sedation values by 2 hours. Treatment with flumazenil increased alertness 2 minutes after the procedure, and was associated with a significantly higher arterial oxygen saturation at 15 minutes.
Early evening nizatidine intake with a meal optimizes the antisecretory effect
Authors: DUROUX P. , EMDE C. , BAUERFEIND P. , BIOLLAZ J. , ARMSTRONG D. , BLUM A.‐L.
Published: July 2010

The importance of the temporal relationship between meal and nizatidine intake was studied in a six‐armed, double‐blind, placebo‐controlled trial. Eleven healthy volunteers received early (18.00 hours) or late (21.00 hours) supper, with either placebo, early (18.00 hours) nizatidine, or late (21.00 hours) 300 mg nizatidine. Ambulatory 21‐hour gastric pH‐metry was performed and plasma nizatidine concentrations were determined by high pressure liquid chromatography. Early‐nizatidine/early‐supper (median pH 2.50), but not late‐nizatidine/late supper (median pH 2.30), produced significantly higher median 21‐hour pH values than did early‐nizatidine/late‐supper (median pH 1.90). Concomitant food delayed the absorption of nizatidine but did not change the drug's bioavailability. Oral nizatidine should be taken with food, preferably early in the evening, to optimize its anti‐secretory effect.
The effect of trospium chloride on oesophageal motility
Authors: FRIELING T. , ENCK P. , DOHMANN R. , WIENBECK M. , LÜBKE H. J.
Published: July 2010

Trospium chloride is a muscarinergic antagonist acting on oesophageal smooth muscle and on ganglionic and/or myenteric neurons. The effect of this drug on oesophageal motility was tested in 16 healthy male subjects in a double‐blind randomized cross‐over examination of trospium chloride or placebo following phentolamine or placebo application. Each subject underwent two separate investigations at least one week apart. Trospium chloride was effective in the oesophagus to reduce contractile activity (amplitude and duration of peristalsis) in all parts of the oesophageal body, and this effect was not blocked by phentolamine. Its potent action and its minor side‐effects appear to be promising for clinical use in patients with motility disorders such as the hypercontractile oesophagus.
Oral tobramycin in ulcerative colitis: effect on maintenance of remission
Authors: LOBO A. J. , BURKE D. A. , SOBALA G. M. , AXON A. T. R.
Published: July 2010

Oral tobramycin for 7 days has been shown to be of benefit as an adjunct to conventional medication in acute ulcerative colitis. Eighty‐one patients (40 who had received tobramycin; 41 placebo) who had been enrolled in a double‐blind placebo‐controlled trial of this drug in acute disease were subsequently followed to determine whether this short‐term benefit persisted. Relapse was defined as a liquid stool frequency of three times daily with rectal bleeding. Results were analysed by the log‐rank test on Kaplan‐Meier survival curves. Treatment failure was defined as a lack of response by the end of the acute trial period, or subsequent relapse. In a second analysis, only those entering remission at the end of the acute trial were considered, and followed to relapse. Although at the start of the follow‐up period significantly fewer patients in the tobramycin group had failed (failed: tobramycin 9, placebo 24; not failed tobramycin 31; placebo 17;P= 0.001), the failure‐free survival curves subsequently converged and did not differ significantly. After 1 and 2 years, the failure‐free survival rates were 40% (S.E. = 7.8%) and 20% (S.E. = 6.3%) for the tobramycin group and 24% (S.E. = 6.7%) and 12% (S.E. = 5.1%) for the placebo group. When only those entering remission were considered, there was no significant difference in the relapse rates in the two groups. Benefit from tobramycin is therefore short‐lived and may reflect short‐term changes in the faecal flora.
A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis
Authors: GREENFIELD S. M. , GREEN A. T. , TEARE J. P. , JENKINS A. P. , PUNCHARD N. A. , AINLEY C. C. , H.THOMPSON R. P.
Published: July 2010

In a placebo‐controlled study, 43 patients with stable ulcerative colitis were randomized to receive either MaxEPA (n= 16), super evening primrose oil (n= 19), or olive oil as placebo (n= 8) for 6 months, in addition to their usual treatment. Treatment with MaxEPA increased red‐cell membrane concentrations of eicosapentaenoic acid (EPA) at 3 months by three‐fold and at 6 months by four‐fold (both P < 0.01), and doubled docosahexaenoic acid (DHA) levels at 6 months (P < 0.05). Treatment with super evening primrose oil increased red‐cell membrane concentrations of dihomogamma‐linolenic acid (DGLA) by 40% at 6 months (P < 0.05), whilst treatment with placebo reduced levels of DGLA and DHA at 6 months (both P < 0.05). Clinical outcome was assessed by patient diary cards, sigmoidoscopy and histology of rectal biopsy specimens. Super evening primrose oil significantly improved stool consistency compared to MaxEPA and placebo at 6 months, and this difference was maintained 3 months after treatment was discontinued (P < 0.05). There was however, no difference in stool frequency, rectal bleeding, disease relapse, sigmoidoscopic appearance or rectal histology in the three treatment groups. Despite manipulation of cell‐membrane fatty acids, fish oils do not exert a therapeutic effect in ulcerative colitis, while evening primrose oil may be of some benefit.
Cisapride in the treatment of gastro‐oesophageal reflux disease
Authors: ROBERTSON C. S. , EVANS D. F. , LEDINGHAM S. J. , ATKINSON M.
Published: July 2010

Prokinetic agents are being used increasingly in medical therapy for gastro‐oesophageal reflux disease (GERD). This study examined the effect of 10 mg q.d.s., oral cisapride, or placebo, taken for 12 weeks, on 48 patients with symptoms and endoscopic evidence of GERD. Objective evaluation of benefit was obtained by endoscopy and biopsy, oesophageal manometry, acid reflux provocation test and 24‐h oesophageal pH monitoring. Cisapride significantly increased lower oesophageal sphincter pressure (P= 0.003) against baseline and also against placebo, in patients (n= 9) with an hypotensive lower oesophageal sphincter pressure (P < 0.01). The frequency of dyspeptic symptoms was significantly improved in the cisapride group (P= 0.03). Antacid intake, global evaluation of symptoms and a VAS score for symptoms were all better than placebo but failed to reach significance (global evaluation by patients, P= 0.07). Overall, there was no significant improvement in oesophagitis at either 6 weeks (P < 0.05 > 0.3) or 12 weeks (P= 0.07). However, if patients with grades I and II oesophagitis at entry were excluded, cisapride had a significantly greater effect than placebo, 6 weeks (P= 0.05), 12 weeks (P= 0.04). In those with oesophageal ulceration, cisapride was significantly more effective than placebo in inducing healing. Gastro‐oesophageal reflux was very variable on both 24‐h pH monitoring and acid reflux provocation test. In spite of a 50% decrease in acid exposure on 24‐h pH monitoring (cisapride group, mean % pH < 4 day: entry 18.9%, 12 weeks 9.6%), there were no significant intra‐ or intergroup differences for percentage of time < pH 4, or frequency and duration of episodes, neither pre‐ or post‐prandially, day or night, except for the number of post‐prandial episodes during acid reflux provocation tests, which decreased significantly more with cisapride than with placebo (P < 0.05). Thus, oral cisapride when taken for 12 weeks promoted healing of oesophagitis and improved symptoms in patients with GERD; although an increase in lower oesophageal sphincter pressure was observed and a reduction in acid reflux was measured, no significant decrease of acid exposure was seen.
Effect of methylprednisolone on small bowel spleen and liver changes in a murine model of inflammatory bowel disease
Authors: BANIĆ M. , BRKIĆ T. , ANIĆ B. , ROTKVIĆ I. , GRABAREVIĆ Z. , DUVNJAK M. , TROSKOT B. , MIHATOV Š.
Published: July 2010

The aim of this study was to evaluate the influence of methylprednisolone (1 mg/kg, i.p.) on inflammatory lesions in the small bowel, liver (pericholangitis) and spleen (lymphofollicular proliferation), in a model of inflammatory bowel disease induced by 2,4‐dinitrofluorobenzene in previously sensitized BALB‐c mice. As a parameter of corticosteroid antiinflammatory and immunosuppressive action, we simultaneously investigated its effects on mononuclear cell accumulation within the ileal lamina propria and submucosa during the observed time period (1–30 days). We noted a significant decrease in accumulation of mononuclear cells within the lamina propria (P < 0.001). An effect on mononuclear cell infiltration within the ileal submucosa was also noted but was not statistically significant. In addition, pericholangitis in the liver and lymphofollicular proliferation in the spleen were not observed in the experimental group during treatment with methylprednisolone. The results of this study indicate that the previously described model of intestinal inflammation could be used in further research of present and new therapeutic modalities for inflammatory bowel disease.
The effect of beta‐adrenoreceptor agonists and antagonists on fructose absorption in man
Authors: McINTYRE A. S. , THOMPSON D. G. , BURNHAM W. R. , WALKER E.
Published: July 2010

To explore the effect of beta‐adrenoreceptor stimulation and blockade on the extraction of monosaccharide from the upper gut, we first established the malabsorption threshold in 26 normal volunteers using a series of test meals containing varying proportions of fructose and glucose. Incomplete small intestinal extraction and consequent arrival of carbohydrate into the caecum was identified by a rise in exhaled breath hydrogen concentration. The malabsorption threshold varied between individuals from 30 to 80 g fructose (median 40 g) but was reproducible within individuals, with 90% agreement of repeat studies. The malabsorption threshold for an individual was unrelated to body height (r= 0.007, P > 0.05) or weight (r= 0.003, P > 0.05) but correlated closely with time to onset of the breath hydrogen rise of a standard meal (r= 0.70, P < 0.001). Administration of the beta‐adrenoreceptor antagonist propranolol (160 mg) reduced the quantity of fructose required to exceed the malabsorption threshold from 45, 30–60 (median and range) to 40, 30–50 g (P= 0.03); administration of the beta‐adrenoreceptor agonist isoprenaline (0.015, μg. kg/min) increased the quantity of fructose required to exceed the malabsorption threshold by 10 g (55 (50–90) g; P < 0.02). The effect of both drugs correlated closely with their transit effect (r= 0.79, P < 0.01). A beta‐adrenoreceptor mediated pathway thus appears to be capable of influencing the extraction of monosaccharide from the small intestine in normal subjects both under resting and stimulated conditions, probably acting via an effect on upper gastrointestinal motility.
Endoscopy‐related infections
Authors: SCHEMBRE D. , BJORKMAN D. J.
Published: July 2010

Endoscopic procedures generate bacteraemia to different degrees. Under certain conditions, most notably valvular heart disease, clinically significant infections may occur. A large body of literature has grown around recommendations for antibiotic prophylaxis to prevent procedure‐related infections. Most of this literature is in the form of anecdotal reports. Few prospective randomized studies have been performed. In this paper, the literature on endoscopy‐related infections is reviewed. Recommendations for antibiotics from different sources are compared and a rational approach to prophylactic antibiotic therapy is presented.
Effects of indomethacin on intragastric pH and meal‐stimulated serum gastrin secretion in rheumatoid arthritis patients
Authors: JANSSEN M. , BAAK L. C. , JANSEN J. B. M. J. , DIJKMANS B. A. C. , VANDENBROUCKE J. P. , LAMERS C. B. H. W.
Published: July 2010

The effects of oral indomethacin on intragastric pH and serum gastrin were investigated in rheumatoid arthritis patients. Nine patients (1 male, 8 female) without a history of peptic ulcer disease and 6 patients with a history of peptic ulcer disease (5 male, 1 female) were studied. To obviate Helicobacter pylori infection as a confounding factor, only patients with positive H. pylori serology were included. After a 5‐day period of placebo treatment and after a 5‐day period of indomethacin (50 mg t.d.s.; total dose 750 mg), 24‐h intragastric pH and basal and meal‐stimulated serum gastrin levels were measured in a double‐blind placebo controlled cross‐over study.

There were no differences in the median 24‐h pH values between placebo and indomethacin irrespective of peptic ulcer disease history. Indomethacin resulted in a higher basal and stimulated gastrin response than placebo in patients with a history of peptic ulcer disease. The basal and incremental responses were lower in patients with a history of peptic ulcer disease than in patients without a history of peptic ulcer disease, both during indomethacin and placebo. The same basal and stimulated incremental serum gastrin responses were found during placebo and indomethacin treatment in patients without a history of peptic ulcer disease. No correlation was established between median 2‐h post‐prandial intragastric pH and post‐prandial incremental serum gastrin concentration. We conclude that indomethacin does not influence the intragastric pH of rheumatoid arthritis patients irrespective of history of peptic ulcer disease.
Exocrine pancreatic secretion in man following one week of M1‐muscarinic receptor blockade
Authors: MALFERTHEINER P. , NELSON D. K. , KEMMER T. P. , GLASBRENNER B. , SCHNEIDER A. , DITSCHUNEIT H.
Published: July 2010

A double‐blind, randomized, placebo‐controlled crossover study was performed to assess the influence of one week of selective M1‐muscarinic receptor blockade on pancreatic exocrine secretion in man. Ten healthy subjects received telenzepine (3 mg p.o.) and placebo each for 8 days, with a 6‐day drug‐free washout interval between treatment sequences. On Day 8 of each sequence, pancreatic secretion was stimulated for 2 h by infusion of submaximal secretin (0.2 U.kg/h) followed by maximal stimulation with secretin (1.0 U.kg/h) and ceruletide (120 ng.kg/h). Telenzepine had no significant effect on secretory parameters during submaximal stimulation with secretin. During maximal stimulation, total protein, secretory volume, and output of amylase, trypsin and bicarbonate were unexpectedly increased by telenzepine. These findings might be partially explained by removal of the inhibitory influence of pancreatic polypeptide, which was depressed by telenzepine. Acute studies have shown that M1‐receptor antagonists inhibit exocrine secretion. Our results suggest that adaptation of physiological mechanisms governing the exocrine pancreas may occur after one week of receptor blockade by a therapeutic dosage of telenzepine, to the extent that M1‐blockade no longer inhibits secretion.
Does 40 mg omeprazole daily offer additional benefit over 20 mg daily in patients requiring more than 4 weeks of treatment for symptomatic reflux oesophagitis?
Authors: BATE C. M. , BOOTH S. N. , CROWE J. P. , HEPWORTH‐JONES B. , TAYLOR M. D. , RICHARDSON P. D. I.
Published: July 2010

This study was designed to establish whether 40 mg omeprazole once daily exhibits sufficient additional efficacy over that of 20 mg omeprazole once daily in patients with symptomatic reflux oesophagitis requiring more than an initial 4‐week course of 20 mg omeprazole once daily (o.m.) to warrant routine use of the higher dose. Three hundred and thirteen patients were randomized to receive either 20 mg omeprazole (4 weeks) then 20 mg (second 4 weeks if not both healed and symptom‐free after 4 weeks), or 20 mg omeprazole (4 weeks) then 40 mg omeprazole o.m. (second 4 weeks). One hundred and twenty‐seven patients were healed and symptom‐free after 4 weeks and left the study at that point. Taking the second treatment period in isolation, the healing rate (64%vs. 45%, P < 0.02) and relief of heartburn (72%vs. 60%, P < 0.002) were greater among patients receiving 40 mg omeprazole o.m., demonstrating the existence of a dose–response relationship for omeprazole. However, on completion, there were no significant differences between the patients randomized to the 20/20 mg (healed 65%, asymptomatic 69%) or the 20/40 mg (healed 74%, asymptomatic 74%: both not significant differences compared with 20/20 mg) regimens. The magnitude of the difference in efficacy between 20 and 40 mg omeprazole in symptomatic reflux oesophagitis is insufficient to warrant the routine use of 40 mg in patients requiring more than 4 weeks' treatment with 20 mg omeprazole o.m.; continued treatment with 20 mg omeprazole for 4–8 weeks is the preferred option.
The extent and pattern of gastro‐oesophageal reflux in patients with scleroderma oesophagus: the effect of low‐dose omeprazole
Authors: SHOENUT J. P. , WIELER J. A. , MICFLIKIER A. B.
Published: July 2010

Ambulatory 24‐hour oesophageal pH studies were obtained from 11 patients with scleroderma who expressed either dysphagia (n= 6) or heartburn (n= 5) as their predominant oesophageal symptom. No significant differences were found in the extent of pattern of reflux between these two groups. The pH data of both scleroderma groups were combined and compared to an age‐ and sex‐matched group of control subjects (n= 11). The reflux demonstrated by scleroderma patients was significantly greater than the control group in every category (P < 0.01). The percentage of time the pH was < 4.0 was not significantly different (P > 0.05) upright (29.9 ± 19.8%) vs. supine (44.2 ± 28.5%) in patients with scleroderma. Eight scleroderma patients underwent repeat pH studies while taking low‐dose omeprazole (20 mg daily) and reflux was reduced significantly (P < 0.01) in all patients. The authors believe that 24‐hour ambulatory oesophageal pHmonitoring should be routinely conducted in scleroderma patients to provide quantitative reflux data, even when heartburn is not expressed as a symptom. Omeprazole, 20 mg daily, provides adequate protection from the H+ component of the refluxate.
Gastric retention of sucralfate gel and suspension in upper gastrointestinal diseases
Authors: VAIRA D. , CORBELLI C. , BRUNETTI G. , MENEGATTI M. , LEVORATO M. , MULE P. , COLOMBO P. , MIGLIOLI M. , BARBARA L.
Published: July 2010

This study was designed to compare by scintigraphy the gastric retention of a new dosage form of sucralfate as gel (Gastrogel) with that of sulcralfate suspension in 25 patients with upper gastrointestinal symptoms referred for routine endoscopy. After endoscopy 4 subgroups were defined: macroscopically normal mucosa (n= 7), antral gastritis and/or erosions (n= 6), gastric ulcer (n= 6) and duodenal ulcer (n= 6). Each patient received either sucralfate gel or sucralfate suspension in equivalent doses (5 ml containing 1 g sucralfate). Both formulations were labelled with 111 MBq 99m Tc‐DTPA before administration. The mean value of t½ in the total group was significantly longer when patients were taking sucralfate gel (61.6 min) compared to sucralfate suspension (33.8 min) (P < 0.001). The mean values of t½ were significantly longer for sucralfate gel compared to sucralfate suspension also among the subgroups (macroscopically normal P < 0.02, antral gastritis P < 0.05, gastric ulcer P < 0.02 and duodenal ulcer P < 0.05). After 2 and 3 hours, the percentage residual activity in the gastric area was significantly higher following administration of sucralfate gel compared to sucralfate suspension. This study has shown that, compared to sucralfate suspension, sucralfate gel persists longer in the stomach of patients with gastritis and peptic ulcer.
Does lansoprazole influence postprandial digestive function?
Authors: VIDON N. , DUTREUIL C. , SCOULE J. C. , DELCHIER J. C.
Published: July 2010

The effects of a potent proton pump inhibitor on postprandial digestive functions were compared with those of a placebo in a double‐blind randomized crossover study. Six healthy male volunteers received 30 mg/day of lansoprazole or placebo for 7 days, with a wash‐out period of 14 days. As compared to placebo, lansoprazole induced a marked decrease of mean ± S.E.M. 3‐h gastric acid secretion from 46.8 ± 10.8 mmol to 10.9 ± 2.5 mmol (P < 0.05), and a decrease of the volume of gastric contents emptying into the duodenum from 1043 ± 139 ml to 660 ± 87 ml (P < 0.05). However, gastric emptying remained unchanged with meal gastric emptying half times of 66 ± 5 min and 67 ± 13 min, respectively. During the 3‐h postprandial period, duodenal lipase and chymotrypsin outputs were 366 ± 123 KIU and 56 ± 11 KIU with lansoprazole and 436 ± 119 KIU and 49 ± 8 KIU with placebo (N.S.). Bile acid outputs were 5.3 ± 0.7 mmol and 6.0 ± 1.0 mmol, respectively (N.S.) There was no change in kinetic profiles of biliarypancreatic secretion. We conclude that potent inhibition of gastric secretion by chronic administration of a proton pump inhibitor at usual therapeutic dose alters neither meal gastric emptying nor postprandial biliary‐pancreatic secretion.
Cisapride and ranitidine in the treatment of gastro‐oesophageal reflux disease—a comparative randomized double‐blind trial
Authors: ARVANITAKIS C. , NIKOPOULOS A. , THEOHARIDIS A. , GIANNOULIS E. , VAGIOS I. , ANTHOPOULOU H. , MICHAILIDIS D. , TOURKANTONIS A.
Published: July 2010

Forty patients with gastro‐oesophageal reflux disease and oesophagitis, documented by endoscopy (grades I to III by the Savary‐Miller classification) were randomized to participate in a comparative doubleblind trial to receive cisapride (10 mg q.d.s.) or ranitidine (150 mg b.d.) for an 8‐week period. Upper gastrointestinal endoscopy was performed immediately before the entry to the trial and after the 8‐week period at the completion of the trial. The evaluable cohort included 37 patients who completed the trial, 18 in the cisapride group and 19 in the ranitidine group. Three patients were withdrawn from the trial; one on ranitidine developed severe anaphylactic reaction, one on cisapride severe dizziness and one on cisapride did not wish to continue on the trial. The results of the trial, regarding symptomatic and endoscopic improvement were comparable in the two groups. Both drugs were effective in controlling symptoms, such as acid regurgitation, retrosternal pain, retrosternal burning, epigastric fullness and discomfort (pain, burning, sense of pressure) and resulted in endoscopic healing of oesophagitis. With few exceptions, symptoms remained in remission 1 month after treatment in the majority of patients. Globally, both drugs were tolerated comparably, and adverse effects other than those which resulted in the withdrawal from the trial were minimal in both groups. The results of this trial indicate that cisapride and ranitidine, although of different pharmacological action, are comparable in their therapeutic effect in symptomatic improvement and endoscopic healing in patients with mild to moderate gastro‐oesophageal reflux disease.
Rolling review: gastrointestinal malignancy
Authors: LUK G. D.
Published: July 2010

The chemotherapy of gastrointestinal malignancies remain mostly investigational, although several adjuvant protocols in colorectal cancer and anal cancer are beginning to be accepted as standards against which newer regimens are to be compared. Chemotherapy regimens are best understood and appreciated with a basic understanding of cancer biology, tumour cell kinetics, and drug toxicities. An appreciation of chemotherapy‐induced toxicity and an awareness of their management will help the gastroenterologist be an active participant in the multidisciplinary team caring for the patient with gastrointestinal malignancies.
Proton pump inhibitors, enterochromaffin‐like cell growth and Helicobacter pylori gastritis
Authors: SOLCIA E. , VILLANI L. , LUINETT O. , FIOCCA R.
Published: July 2010

In both rodents and humans the development of gastrin‐promoted gastric argyrophil enterochromaffin‐like cell carcinoids requires the involvement of a genetic factor inherent to multiple endocrine neoplasia syndrome or of type A autoimmune chronic atrophic gastritis. Prolonged severe hypergastrinaemia acting on non‐gastritic mucosa, as in Zollinger‐Ellison syndrome patients, results in diffuse argyrophil enterochromaffin‐like cell hyperplasia but, as a rule, does not produce tumours. Combination of chronic atrophic gastritis (mostly related to Helicobacter pylori infection) with hypergastrinaemia frequently causes linear and micronodular hyperplasia of argyrophil cells, whereas carcinoids are exceptional. No tumours or preneoplastic lesions have been observed in patients treated long‐term with proton pump inhibitors, apart from rare cases in patients with combined Zollinger‐Ellison and multiple endocrine neoplasia syndromes. A moderate increase in the incidence of argyrophil cell clustering, with or without hyperplasia, probably results from the parallel evolution of ulcer‐associated Helicobacter gastritis into chronic atrophic gastritis. Eradication of H. pylori with a combination of proton pump inhibitors and antibiotics suppresses gastritis and prevents ulcer recurrence.
Prospective study of the long‐term efficacy and safety of lansoprazole in patients with the Zollinger‐Ellison syndrome
Authors: JENSEN R. T. , METZ D. C. , KOVIACK P. D. , FEIGENBAUM K. M.
Published: July 2010

The long‐term safety and efficacy of lansoprazole were studied in 21 patients with Zollinger‐Ellison syndrome. The initial maintenance dose was determined by acid inhibition studies. In all patients lansoprazole controlled gastric acid hypersecretion and peptic symptoms in both the short and long term. Patients were treated for a mean of 31 months (range 1–43 months) with all but 4 patients followed for > 18 months. The mean initial dose was 60 mg/day, with 2 patients requiring a twice daily dose and the others a single daily dose. During long‐term treatment 6 patients required an increased dosage, 5 within the first year. Long‐term maintenance doses were reduced in 5 of the 6 patients in whom this was attempted. No changes in serum gastrin concentration, haematological parameters, liver function studies or other biochemical parameters occurred due to lansoprazole. No patient developed a gastric carcinoid tumour while being treated with lansoprazole. These results demonstrate that long‐term treatment with lansoprazole is both safe and effective in patients with Zollinger‐Ellison syndrome, and suggest that this drug will be useful in such patients. Furthermore, maintenance doses of lansoprazole, determined by the currently recommended method of acute acid titration studies in patients with Zollinger‐Ellison syndrome, are too high.
An open trial of long‐term therapy with lansoprazole in patients with peptic ulceration resistant to extended high‐dose ranitidine treatment
Authors: BRUNNER G. , ARNOLD R. , HENNIG U. , FUCHS W.
Published: July 2010

Forty‐two patients with peptic ulceration of the duodenum, stomach or oesophagus, who had not responded to 3 or more months of high‐dose treatment with ranitidine (450 or 600 mg/day), were treated with oral lansoprazole at 30–60 mg daily. In 40 patients (95.2%) the ulcers healed within 2–12 weeks. In the remaining 2 patients healing took several months but eventually all ulcers healed. After healing, 40 patients underwent long‐term maintenance treatment with 30–60 mg lansoprazole daily for 1–3 years (continuing). During maintenance therapy with lansoprazole, no endoscopically verified relapses occurred when the drug was taken regularly. In 1 patient treatment had to be discontinued because of a drug‐related colitis that disappeared soon after treatment had been stopped. There were no significant changes in routine laboratory tests in any patient. Basal serum gastrin concentrations, which were already elevated by the previous high‐dose ranitidine treatment (125 ± 25 pg/ml), rose to four times the normal values after 4 weeks of treatment with lansoprazole (255 ± 65 pg/ml). Thereafter no further increases in basal serum gastrin concentrations were observed, even after 3 years of administration. The volume density of argyrophilic cells in the oxyntic mucosa increased slightly during lansoprazole treatment; until now no dysplasia of the enterochromaffin‐like cells has been observed. In conclusion, 30–60 mg lansoprazole daily healed ranitidine‐resistant peptic ulcers, and subsequent maintenance therapy with 30–60 mg lansoprazole daily was found to be highly effective and safe over the time observed.
Pharmaco‐economic considerations in the long‐term management of peptic ulcer disease
Authors: RUSZNIEWSKI P.
Published: July 2010

Pharmaco‐economic consequences of available therapeutic strategies in the management of duodenal ulcer disease are of increasing importance. Terminology and methodology in economic evaluation need to be clarified : direct and indirect costs of duodenal ulcer disease have to be calculated, and results expressed in terms of efficacy, utility or benefits. The economic analysis then compares costs or cost‐effectiveness ratios of various strategies. Macroeconomic evaluations conducted in France have shown that the overall cost of duodenal ulcer disease was FF 3.5 billion in 1987 in private practice. Several evaluations have shown that indirect costs accounted for more than 50% of the total expense. From a microeconomic point of view, several studies have been conducted with ranitidine and cimetidine. Our own study has shown that one year of treatment with ranitidine 150 mg/day resulted in a decrease in the use of medical resources (clinic visits, endoscopic investigations, duration of hospital stay) and work days lost, when compared with placebo. This resulted in a smaller cost of the ranitidine strategy (FF 2031 per patient for one year for the community, vs. FF 2823 for the placebo strategy). Similar cost‐effectiveness ratios for the ranitidine strategy have been shown in the USA. Costs savings have also been demonstrated during long‐term treatment with cimetidine for up to 3 years. Studies performed according to Markov's chain model have shown that the costs of continuous and intermittent treatments are identical, the expenses related to investigations and mortality being greater with the latter. More studies are warranted to evaluate the efficiency of the different strategies used in the treatment of duodenal ulcer disease. Available studies show that continuous treatment with an H2‐receptor antagonist is a cost‐effective management option.
Review article: controversies in NSAID‐induced gastroduodenal damage‐do they matter?
Authors: FENN G. C.
Published: July 2010

Background. This article reviews various issues surrounding NSAID‐induced gastroduodenal ulceration, about which there appear to be conflicting views and data in the literature. These issues include the size, clinical relevance and main site of the problem; when complications occur (early or late?); the relevance of non‐ulcer lesions and whether adaptation is a clinically relevant phenomenon. Method. A comprehensive literature search was carried out to identify relevant new data published since 1987.

Results. NSAIDs are causally associated with more gastric than duodenal ulcers but their use may be associated with duodenal ulcers or complications. Erosive lesions may progress to more severe damage. The theories of early or late onset of complications during a course of NSAID therapy may not be mutually exclusive.

Conclusions. Available data indicate that NSAID ulcers are at least as dangerous as classic peptic ulcers, and result in significant morbidity and mortality which in the patient population does not appear to be significantly reduced by processes such as adaptation.
Famotidine increases plasma alcohol concentration in healthy subjects
Authors: BURNHAM D. B. , MILLER D. , KARLSTADT R. , FRIEDMAN C. J. , PALMER R. H.
Published: July 2010

The effect of famotidine on plasma alcohol concentration was studied in 24 healthy male subjects who demonstrated high apparent ethanol first‐pass metabolism after oral (p.o.) and intravenous (i.v.) ethanol administration (i.e. AUCpo S 40% of AUCiv, where AUC is area under the plasma ethanol concentration‐time curve). Six of the original 30 subjects screened (20%) did not demonstrate high first‐pass metabolism and were excluded. In a randomized open crossover study, oral ethanol pharmacokinetics were assessed after breakfast in the morning following a 3‐day regimen of famotidine, 40 mg/day, and following a no‐drug control period. Famotidine increased the area under the plasma ethanol concentration‐time curve (AUC0‐t) by 29% (7.1 vs 5.5 mg.h/dL, P= 0.006) and maximal plasma concentration (Cmax) by 23% (9.2 vs 7.5 mg/dL, P= 0.013). The changes in ethanol AUC0‐t and Cmax may have been associated with changes in gastric emptying, as they were inversely correlated with changes in the time at which maximal plasma concentration was attained. There was considerable intra‐individual variation in ethanol AUC and Cmax. As a result, regression to the mean is a potentially confounding problem in ethanol pharmacokinetic studies when subjects are selected on the basis of having low AUCpo, and properly controlled randomized studies of substantial size are required to detect modest drug effects. Small effects on ethanol pharmacokinetics have now been demonstrated with all four of the major H2‐receptor antagonists, but these effects are seen only under specific experimental conditions and appear to be unimportant clinically.
Zollinger‐Ellison syndrome and antral G‐cell hyperfunction in patients with resistant duodenal ulcer disease
Authors: ANNIBALE B. , DE MAGISTRIS L. , CORLETO V. , D'AMBRA G. , MARIGNANI M. , IANNONI C. , DELLEFAVE G.
Published: July 2010

We measured basal and pentagastrin‐stimulated acid secretion, as well as basal and meal‐stimulated plasma gastrin concentration to determine, in 67 patients affected by resistant duodenal ulcer, whether their condition could be related to gastric acid secretion and/or gastrin‐related syndromes. We then compared them to 46 duodenal ulcer control patients. The outpatients were investigated consecutively. The resistant duodenal ulcer patients differed from the controls only in their higher complication rates (bleeding or perforation, P < 0.05). We identified five patients in the resistant duodenal ulcer group with Zollinger‐Ellison syndrome and 12 with antral G cell hyperfunction, whereas in the control group only one patient was affected by antral G cell hyperfunction. IgG anti‐Helicobacter pylori antibodies were positive for the presence of infection in 7 of the hypergastrinaemic patients. When Zollinger‐Ellison syndrome or antral G cell hyperfunction were excluded, no differences could be found in gastric acid secretion, or basal and meal‐stimulated plasma gastrin levels, between the resistant and control duodenal ulcer patients, except for basal acid hypersecretion (resistant duodenal ulcer 16%vs duodenal ulcer 2%P= 0.0144). In the presence of duodenal ulcer disease resistant to H2‐blockers, it is mandatory to measure basal plasma gastrin concentration since it was possible to diagnose the gastrin‐related syndromes, Zollinger‐Ellison syndrome and antral G cell hyperfunction, in 26% of this group of patients.