bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of gastric ulcer healing: histological and ultrastructural assessment
Authors: TARNAWSKI A. , DOUGLASS T. G. , STACHURA J. , KRAUSE W. J.
Published: July 2010

It has long been assumed that the mucosa in areas of grossly ‘healed’gastric or duodenal ulcers returns to normal, either spontaneously or after treatment. This assumption is based almost entirely upon visual, superficial examination by endoscopy. Few, if any, histological and ultrastructural studies examined the deeper mucosa in the areas of grossly healed ulcers. In several experimental studies, we analysed the development, evolution, and healing of acetic acid‐induced gastric ulcers in rats and assessed the histological and ultrastructural features (structure and cellular composition) of the gastric mucosa in areas of grossly healed ulcers. The gastric mucosa of grossly ‘healed’ulcers showed re‐epithelialization of the mucosal surface at every study interval (2 weeks, 2, 3, and 4 months), but the subepithelial mucosa displayed prominent abnormalities. Two patterns of scarring were distinguished: (a) the mucosa in the area of healed ulcer was thinner (25–45 % thinner than normal mucosa) with increased connective tissue and poor differentiation and/or degenerative changes in the glandular cells; and (b) the mucosa displayed a marked dilation of gastric glands with poor differentiation of the glandular cells and a reduction in the supportive microvascular network. It is theorized that these abnormalities could interfere with oxygenation, nutrient supply, and mucosal resistance and defence; therefore, they could be a basis for ulcer recurrence. These observations indicate that the quality of mucosal structural restoration rather than the speed of ulcer healing is the most important factor in determining risk of ulcer recurrence. The clinical relevance of these findings is supported by a preliminary study in which marked histological abnormalities were found in the subepithelial mucosa in patients with ‘healed’duodenal ulcers.
Stress ulceration in the intensive care unit: use of H2‐receptor antagonists
Authors: MOORE J.G.
Published: July 2010

H2‐receptor antagonist drug therapy is the mainstay of peptic ulcer treatment in the USA. About 75 % of patients in intensive care units receive parenteral H2‐antagonists. The rationale for their use is that parenteral H2‐antagonists offer about a four‐fold protective effect compared with placebo against significant upper gastrointestinal haemorrhage. Parenteral administration of H2‐receptor antagonists appears to be preferred to oral antacid or sucralfate regimens because of ease of administration and, perhaps, lower treatment costs.

Recommended dosage schedules for intravenously administered H2‐receptor antagonists are at fixed intervals, 6‐ to 8‐h intervals for cimetidine and ranitidine and 12‐h intervals for famotidine. These dosage schedules assume a fixed dose‐response relationship (i.e. a given dose of H2‐antagonist results in equivalent acid suppression throughout the circadian, or 24‐h, period). However, human basal gastric acid secretion exhibits circadian variation, with peak rates occurring during the evening hours. Recent evidence from 24‐h continuous intragastric pH studies in fasting patients with healed duodenal ulcer suggests that larger doses of intravenous H2‐antagonists are required in the evening than in the morning to achieve equivalent acid suppression. These findings are consistent with a changing H2‐antagonist dose/acid‐inhibiting response over the circadian period. Continuous infusion has the advantage of providing consistent and sustained suppression of gastric acid secretion in patients at risk for stress ulceration. Results of a double‐blind, randomized, crossover study indicated that equally effective suppression of acidity and time‐to‐onset of pharmacological effect can be achieved with and without priming bolus doses of ranitidine, and presumably other H2‐receptor antagonists as well. Furthermore, continuous intravenous H2‐antagonist therapy, compared with intravenous bolus administration, appears to offer more effective control of 24‐h pH at a reduced cost. These cost savings may be augmented by administration of the H2‐antagonist with the patient's total parenteral nutrition.
Helicobacter pylori: review of research findings
Authors: DOOLEY C. P.
Published: July 2010

Helicobacter pylori attracted widespread interest from gastroenterologists because of its potential aetiologic role in disorders of the upper gastrointestinal tract. Based on extensive microbiological studies, Campylobacter pylori was renamed Helicobacter pylori, and the organism represents a new genus of bacteria. It is generally accepted that H. pylori causes chronic, non‐specific gastritis (type B gastritis). The inflammatory response occurs even though the bacterium does not penetrate the gastric epithelium; it is found on the surface of and adjacent to the epithelium. The clinical significance of histological gastritis is unknown. The bacterium is often found in asymptomatic subjects. In Caucasian adults, the prevalence of infection increases with increasing age. Higher rates of infection are found in blacks and Hispanics than would be expected for their age. Whether these different rates are the result of racial or socio‐economic factors is not known. It is theorized, but not proven, that high rates of infection with H. pylori at an early age may explain the high incidence of gastric carcinoma found in Hispanic populations. H. pylori is found in almost every patient with duodenal ulcer disease, although no direct evidence for a causal relationship exists. Indirect evidence is based on the findings that if H. pylori infection is eradicated, ulcer recurrence is less likely (up to one year of follow‐up). A small percentage of patients have a relapse despite eradication of the organism, suggesting a role for other factors in duodenal ulcer disease. The role of H. pylori in gastric ulcer disease is unknown. Seventy to eighty per cent of patients with gastric ulcer have evidence of H. pylori infection, and preliminary data seem to support the existence of two distinct aetiologic groups: those with gastric ulcers related to H. pylori infection and those with gastric ulcers related to use of non‐steroidal anti‐inflammatory drugs. The role of H. pylori in non‐ulcer dyspepsia is unknown. Some clinicians believe that H. pylori causes non‐ulcer dyspepsia and treat these patients for H. pylori infection. However, the data supporting this practice are poor. Treatment is only recommended for patients with resistant duodenal ulcers and patients who have frequent relapses of duodenal ulcers and who are willing to take triple‐drug therapy (bismuth compounds, metronidazole, tetracycline) for the infection. As 95% of patients with duodenal ulcer have evidence of H. pylori infection, there is probably little need to confirm the diagnosis of H. pylori infection.
Effects on the rat oxyntic mucosa of the histamine2‐antagonist loxtidine and the H+, K+‐ATPase inhibitor omepvazole
Authors: BRENNA E. , WALDUM H. L. , SANDVIK A. K. , SØGNEN B. SCHULZE , KRISTENSEN A.
Published: July 2010

The present study examined whether histamine could affect the growth of the enterochromaffin‐like (ECL) cell and the parietal cell. The effects of the unsurmountable histamine H2‐receptor antagonist loxtidine (80 mg/kg) and the H+, K+‐ATPase inhibitor omeprazole (100 μmol/kg) were compared in female Sprague‐Dawley rats. Both drugs were given by gavage once daily for 3 months. Omeprazole induced a more pronounced and sustained hypergastrinaemia than loxtidine. In spite of marked hypergastrinaemia during most of the day, even in the loxtidine‐treated rats, the weights of the stomach and oxyntic mucosa were elevated only in the omeprazole‐treated rats. The ECL cell density was slightly higher in the loxtidine‐ than in the omeprazole‐treated rats. Both treatments elevated the gastrin‐stimulated histamine release from the vascularly perfused stomach. The parietal cell density was unaffected by omeprazole treatment, whereas it tended to be reduced in the loxtidine‐treated rats. Simultaneous administration of loxtidine and omeprazole reduced the sustained hypergastrinaemia induced by omeprazole given alone. The present study may indicate that histamine inhibits the growth of the ECL cell, but further studies are needed to elucidate if histamine has any trophic effect on the parietal cells.
Night‐time or morning dosing with H2‐receptor antagonists: studies on acid inhibition in normal subjects
Authors: PATEL N. , WARD U. , ROGERS M. J. , PRIMROSE J. N.
Published: July 2010

H2‐receptor antagonists are conventionally given at night. However, it remains unproven whether this regimen affords superior acid inhibition or healing rates for patients with duodenal ulcers compared to morning dosing. We have therefore examined the acid inhibitory effect of 300 mg ranitidine at night compared to 300 mg ranitidine in the morning in 8 normal male subjects. Intragastric acidity was measured by the radiotelemetry method and acid inhibition calculated from the percentage decrease in the area under the curve for hydrogen ion activity against time. Night‐time ranitidine resulted in a significantly better (P < 0.02) decrease of intragastric acidity than the same dose given in the morning (66.8 (61.8–77.6)%vs. 34 (15.5–49.1)%). This difference was found to be due to the fact that morning ranitidine inhibited gastric acid secretion when the intragastric acidity was already buffered by food. These data support the superiority of nocturnal dosing with H2‐antagonists.
Compliance with anti‐ulcer medication during short‐term healing phase clinical trials
Authors: FARUP P. G.
Published: July 2010

Nine hundred and sixty‐six patients’compliance with drug therapy of peptic ulcerations and reflux oesophagitis in four clinical trials were studied. The mean compliance rates varied from 90.5% (95% C.I. 89.0–92.1%) to 99.2% (95% C.I. 98.2–100.1%). Compliance declined significantly with increasing complexity of the dosage schedule in all trials, and toward the end of the treatment period in two of them. Patients with adverse events had a significant drop in compliance during the Iast part of the treatment period in one of the trials. There was a significant inter‐centre variation in compliance. Overall, the variation was of little clinical significance. Patient compliance was independent of age, sex, use of alcohol and tobacco, effect of treatment, concomitant drug therapy and whether the pill was active drug or placebo. The study shows that a simplified dosage schedule, shortening of the treatment period, use of drugs with minimal side‐effects, and meticulous selection of centres could improve patient compliance with drug therapy in clinical trials.
Antioxidant therapy for recurrent pancreatitis: biochemical profiles in a placebo‐controlled trial
Authors: UDEN S. , SCHOFIELD D. , MILLER P. F. , DAY J. P. , BOTTIGLIERI T. , BRAGANZA J. M.
Published: July 2010

The usefulness of micronutrient antioxidant therapy for recurrent (non‐gallstone) pancreatitis has recently been endorsed by a 20‐week double‐blind double‐dummy cross‐over trial in 20 patients. Treatment was delivered as two types of tablets, providing daily doses of 600 μ g organic selenium, 9000 i.u. β ‐carotene, 0.54 g vitamin C, 270 i.u. vitamin E and 2 g methionine. We report antioxidant profiles in blood samples collected before entry, at the cross‐over stage and upon completion of trial. Baseline serum concentrations of selenium, β ‐carotene and vitamin E in the patients were significantly lower than in healthy controls, were unaltered by placebo and normalized by active treatment, but reverted to basal values in the subgroup that received placebo subsequently. The baseline serum concentration of a free radical marker—the 9‐cis, II‐trans isomer of linoleic acid—was significantly higher in the patients than in controls, fell inexplicably in the placebo phase and fell further upon active treatment. Discriminant analysis eliminated the overlap in free radical marker and selenium concentrations between control sera on the one hand and baseline or post‐placebo samples from the patients on the other: antioxidant treatment normalized the relationship between these biochemical parameters. Subnormal baseline serum levels of S‐adenosylmethionine drifted downwards upon active treatment whereas a sharp rise was noted when a relapse of pancreatitis occurred during the placebo phase. The results confirm that adequate exposure to antioxidants in the active treatment phase was associated with amelioration of oxidative stress, and that there was no residual effect 10 weeks after switching over to placebo treatment. Furthermore, the paradoxical behaviour of S‐adenosylmethionine may imply that the beneficial effect of micronutrient antioxidants in recurrent pancreatitis is linked with preservation of the methionine trans‐sulfuration pathway in pancreatic acinar cells.
Comparison of one‐day oral dosing with three bismuth compounds for the suppression of Helicobacter pylori assessed by the13C‐urea breath test
Authors: PREWETT E. J. , LUK Y. W. , FRASER A. G. , LAM W. M. , POUNDER R. E.
Published: July 2010

Assessment of intragastric urease activity by the 13C‐urea breath test was performed before and after one day of dosing with either De‐Noltabs (tripotassium dicitrato bismuthate, one tablet 1 q.d.s.), Pepto‐Bismol liquid (bismuth salicylate 30 ml q.d.s.), or Roter tablets (bismuth subnitrate, one tablet q.d.s.) in twelve Helicobacter pylori‐positive patient volunteers. There was a significant decrease in the excess of 13CO2 after one day of dosing with each of the three bismuth compounds, but analysis of variance could detect no difference between the effects of the three compounds.

Systemic absorption of bismuth following oral dosing with either Pepto‐Bismol or Roter is minimal, yet both compounds have a suppressive effect on H. pylori similar to that of De‐Noltab. This study suggests that the action of all three bismuth compounds is within the gastric lumen, and that systemic absorption of bismuth is not necessary for activity against H. pylori.
Improved maintenance of remission in ulcerative colitis by balsalazide 4 g/day compared with 2 g/day
Authors: GIAFFER M. H. , HOLDSWORTH C. D. , LENNARD‐JONES J. E. , RODRIGUES C. A. , MCINTYRE P. B. , MANJUNATHA S. , BARON J. H. , BARRISON I. G. , POLSON R. J. , HOARE A. M. , DAVIES G. S. R. , THORNTON P. C.
Published: July 2010

The efficacy of two doses of balsalazide for the maintenance of remission in patients with ulcerative colitis was compared in a double‐blind multicentre trial. Sixty‐five patients received a 2 g daily dose, and 68 a 4 g dose. The patient groups were similar at entry for sex, age, and disease distribution. Clinical assessment was carried out at 3‐monthly intervals, with sigmoidoscopy, rectal biopsy, and blood tests on entry and at 26 and 52 weeks. Clinical relapse over twelve months was significantly less common on the 4 g dose (36%), than on the 2 g dose (55%), P < 0.01. There were eight withdrawals on 2 g daily and 13 on 4 g daily, six and nine respectively being mainly due to gastrointestinal intolerance. It is concluded that balsalazide is a well‐tolerated drug, and is effective for the maintenance of remission in patients with ulcerative colitis, the optimal dose being greater than 2 g daily.
Review article: the treatment of alcoholic liver disease
Authors: BLENDIS L. M.
Published: July 2010

Over the past 20 years we have moved from a situation in which we had no therapy for alcoholic liver disease, through a period when any therapy we had was purely empirical, to an era where we have specific therapies for different aspects of this disease based upon sound pathogenic principles. In this short review, an attempt has been made to summarize these advances in the understanding of the pathogenesis of alcoholic liver disease. In particular, they explain why patients with severe acute alcoholic hepatitis continue to deteriorate in hospital despite withdrawal from alcohol, why they respond to corticosteroids, why only a small percentage of patients develop cirrhosis, and why propylthiouracil may offer Protection.
Comparison between a standard pancreatic supplement and a high enzyme preparation in cystic fibrosis
Authors: MORRISON G. , MORRISON J. M. , REDMOND A. O. B. , BYERS C. A. , McCRACKEN K. J. , DODGE J. A. , GUILFORDS S. A. , BOWDEN M. W.
Published: July 2010

This study compared the relative effectiveness of a standard pancreatic enzyme supplement (‘Creon’, Duphar) and a new preparation (‘Pancrease HL’, Cilag) containing about 3 times the lipase and more than 5 times the protease activity. Capsule dosage was adjusted to a ratio of approximately 3:1. Fat balances showed that absorption of fat did not change significantly on conversion to the new high‐lipase product, and the coefficient of absorption of total energy was similarly maintained. The coefficient of protein absorption was significantly enhanced with the high enzyme preparation (P < 0.01), which may explain the reported subjective improvement in stool odour. No adverse effects were recorded. Patient acceptability of the new compound was high; the great reduction in the number of capsules required at each meal was cited by all patients as the reason for their preference.
Omeprazole in the long‐term treatment of severe gastro‐oesophageal reflux disease in patients with systemic sclerosis
Authors: HENDEL L. , HAGE E. , HENDEL J. , STENTOFT P.
Published: July 2010

Twenty‐five patients with systemic sclerosis and severe gastro‐oesophageal reflux disease were treated with 20–80 mg omeprazole daily for up to 5 years. Efficacy of treatment was assessed by symptom score, by endoscopic and histopathological surveillance of the oesophageal and gastric mucosa, and by laboratory screening including serum gastrin concentration.

Statistically significant relief of symptoms and healing of oesophagitis confirmed the efficacy of this treatment. However, complete healing of oesophagitis was not achieved in half of the patients due to residual gastro‐oesophageal acid reflux. Repeated adjustments of the maintenance dose of omeprazole may be needed for this group of patients. From the safety point‐of‐view, nothing was observed to discourage the long‐term use of omeprazole in this group of patients.
The effects of 5‐aminosalicylic acid and acetyl‐5‐aminosalicylic acid on lipid peroxidation in erythrocytes and prostaglandin production by mononuclear cells
Authors: GREENFIELD S. M. , BOSWELL D. J. , PUNCHARD N. A. , THOMPSON R. P. H.
Published: July 2010

In parallel studies, the effects of 5‐aminosalicylic acid (5‐ASA) and acetyl‐5‐aminosalicylic acid (acetyl‐5‐ASA) on peroxidation of red‐cell membrane lipids and production of prostaglandins by peripheral blood mononuclear cells were assessed. 5‐ASA at concentrations of 10‐5, 10‐4 and 10‐3m significantly inhibited erythrocyte lipid peroxidation, measured as malondialdehyde production, by 20%, 56% and 63%, respectively, (P < 0.05, P < 0.002, P < 0.001, respectively) while acetyl‐ 5‐ASA had no effect. 10‐5 and 10‐4m 5‐ASA significantly increased production by stimulated peripheral blood mononuclear cells of PGE2 (by 31% and 30%, P < 0.01, P < 0.05, respectively) and PGF2α (by 30% and 25%, P < 0.05, P < 0.01, respectively). 10‐4 M 5‐ASA also significantly stimulated prostacyclin production measured as 6KF1α by 10% (P < 0.05). At 10‐3 M 5‐ASA there were significant falls in 6KF1α (by 37%) PGE2 (by 45%) and PGF2α (by 47%) (P < 0.01, P < 0.001, P < 0.001, respectively) although this was accompanied by a decrease in cell viability. Acetyl‐5‐ASA had little effect upon prostaglandin production. 5‐ASA scavenges free radicals and stimulates production of cyto‐protective prostaglandins.
Ranitidine, cimetidine, famotidine have no effect on post‐prandial absorption of ethanol 0.8 g/kg taken after an evening meal
Authors: FRASER A. C. , HUDSON M. , SAWYERR A. M. , SMITH M. , ROSALKI S. B. , POUNDER R. E.
Published: July 2010

Forty‐seven healthy male subjects were studied twice using a randomized, placebo‐controlled design. Each subject took an 8‐day course of two of the following four regimens; 300 mg ranitidine, 800 mg cimetidine, 40 mg famotidine or placebo (identical either to 300 mg ranitidine or 800 mg cimetidine). The systemic bioavailability of ethanol (integrated 6‐h plasma ethanol concentration, peak plasma ethanol concentration, and the time to peak plasma ethanol concentration) was measured after the oral ingestion of 0.8 g of ethanol per kg body weight, given one hour after an evening meal on Day 8 of each regimen.

There was no significant difference of integrated 6‐h plasma ethanol concentration, peak ethanol concentration, or time to reach peak ethanol concentration after dosing with either ranitidine, cimetidine or famotidine or placebo.
A comparison of upper gastrointestinal mucosal damage by standard and delayed‐release indomethacin
Authors: SWIFT G. L , ARNOLD J. , WILLIAMS G. T. , WILLIAMS B. D. , RHODES J. , KHAN F.
Published: July 2010

Forty‐five patients taking long‐term indomethacin and with endoscopic erosions or superficial ulcers in the oesophagus, stomach or duodenal bulb were randomized in a double‐blind study to continue with standard indomethacin or receive a ‘delayed‐release’ formulation. This consisted of microgranules of indomethacin coated with an acrylic resin, Eudragit L, which releases drug in the small intestine. Endoscopy was repeated after 8 weeks and biopsies taken on both occasions. Changes in endoscopic lesions and histological appearances were similar in both groups, although mucosal erythema was less in those given Eudragit L indomethacin. Systemic, rather than topical, effects of indomethacin may therefore be responsible for persistence of gastro‐duodenal mucosal lesions in these patients. There is reason to question the clinical practice of using expensive, delayed‐release preparations.
Dose‐dependent stimulation of gallbladder contraction by intravenous erythromycin in man
Authors: CATNACH S. M. , BALLINGER A. B. , LAW P. A. , NELLANS H. , FAIRCLOUGH P. D.
Published: July 2010

We have previously shown that a single oral dose of 500 nig erythromycin causes gallbladder contraction. The effect of intravenous erythromycin on antroduodenal motility is dose‐dependent; < 3 mg/kg body weight stimulates propagated contractions in a fashion similar to motilin while doses > 7 mg/kg cause giant non‐propagated antral contractions not seen with motilin. Using ultrasound, we have examined the effect of differing doses of intravenous erythromycin on gallbladder motility in man. Erythromycin (1 mg/kg) caused fasting gallbladder contraction to 52 % of basal gallbladder volume (P < 0.001), and increased gallbladder emptying following a liquid meal (maximal percentage emptied 75 ± 6.8% vs. 58 ± 9.0% following saline, P < 0.05). Erythromycin (7 mg/kg) however, had no effect on gallbladder fasting or post‐prandial motor activity. We conclude that the effect of erythromycin on gallbladder motility is dose‐dependent, with higher doses having no effect. It is possible that at higher doses erythromycin stimulates other receptors in addition to the motilin receptor, and that the combined effect is different to the stimulation of the motilin receptor alone.
Effect of putative carcinoid mediators on gastric and small bowel transit in rats and the role of 5‐HT receptors
Authors: VALDOVINOS M. A. , THOMFORDE G. M. , CAMILLERI M.
Published: July 2010

Whereas serotonin and substance P stimulate in‐vivo and in‐vitro myoelectric activity in the small intestine, their effects on transit are unclear. We used a validated in‐vivo transit model in the chloral hydrate‐anaesthetized rat to study the effects of serotonin, substance P and motilin, three putative mediators of carcinoid diarrhoea, on transit through the upper digestive tract. Intra‐arterial serotonin accelerated gastric emptying of a radiolabeled liquid, while motilin accelerated overall upper gastrointestinal transit. Substance P slowed overall upper gastrointestinal transit without altering gastric emptying. The antagonists to serotonin receptor subtypes, R‐zacopride (5‐HT3) and ketanserin (5‐HT2), also accelerated rat gastric emptying of liquids; in contrast, a 5‐HT4agonist, SC53116, resulted in a less pronounced effect on gastric emptying at the dose tested. We conclude that circulating substance P is unlikely to be an important accelerator of transit through the upper digestive tract; in contrast, hyperserotoninaemia significantly accelerates transit through the stomach, and 5‐HT2and 5‐HT3receptor subtypes may play a role in the motor effects of serotonin in the stomach.
Cimetidine improves GERD symptoms in patients selected by a validated GERD questionnaire
Authors: JOHNSSON F. , ROTH Y. , PEDERSEN N.‐E. DAMGAARD , JOELSSON B.
Published: July 2010

A questionnaire was constructed and validated to improve the accuracy of symptom assessment in diagnosing gastro‐oesophageal reflux disease (GERD). The GERD questionnaire consisted of four questions describing an upward moving, uncomfortable feeling in the chest frequently accompanied by retrosternal burning that is improved with antacids. It was found that if a patient answered yes to all four questions the likelihood was 85% that erosive oesophagitis would be detected on endoscopy or that pathological gastro‐oesophageal reflux on 24‐hour pH‐monitoring would be documented, or both.

The GERD questionnaire was used to identify 269 patients with probable GERD who after one week on placebo entered a 2‐week double‐blind placebo‐controlled study which was completed by 251 patients. Cimetidine (400 mg) b.d. was given to 124 patients and placebo to 127 patients. On diary cards the patients noted the number, the mean duration and the mean severity of GERD symptoms episodes. Cimetidine was significantly superior to placebo in increasing the percentage of symptom‐free days, and in reducing the median number of daily symptom episodes.

This trial demonstrates that 400 mg cimetidine b.d. is effective in improving GERD symptoms in patients identified by a descriptive, validated GERD questionnaire.
Efficacy of bile acid therapy for gallstone dissolution: a meta‐analysis of randomized trials
Authors: MAY G. R. , SUTHERLAND L. R. , SHAFFER E. A.
Published: July 2010

To define better the efficacy of bile acid therapy for dissolution of radiolucent gallstones, we performed a meta‐analysis of published trials from January 1966 to September 1992. Studies were identified using a MEDLINE computer search followed by an extensive manual search. The inclusion criteria used were: randomized trial, radiolucent gallstones in a visualizing gallbladder on oral cholecystography, and complete stone dissolution confirmed by oral cholecystography or ultrasound. Study results were pooled into 6 groups: placebo: high‐ and low‐dose chenodeoxycholic acid (CDCA) (≥10 mg.kg/day and < 10 mg.kg/day); high‐ and low‐dose ursodeoxycholic acid (UDCA) (< 7 mg. kg/day and < 7 mg. kg/day) and combined CDCA plus UDCA. Homogeneity calculations were performed and the percentage of complete stone dissolution calculated for each group with 95% confidence intervals. Of 66 trials identified, 23 comprising 1949 patients met the inclusion criteria. A total of 1062 patients were treated with CDCA, 819 with UDCA and 78 combination therapy. In studies > 6 months' duration, high‐dose UDCA completely dissolved stones in 37.3% of patients (95% C.I. 33–42%), low‐dose UDCA in 20.6%) and high‐dose CDCA 18.2% (95% C.I. 15–21%). Based on only two studies, combination therapy achieved dissolution in 62.8% (95% C.I. 51–74%) of patients. Stones less than 10 mm dissolved significantly more frequently than stones larger than 10 mm. This analysis shows that UDCA in doses greater than 7 mg. kg/day taken for greater than 6 months will dissolve radiolucent gallstones in 38% of patients. The combination of UDCA and CDCA may be more efficacious but this observation is based upon only 78 patients and requires confirmation in further randomized trials.
Two‐week eradication regimen for metronidazole‐resistant Helicobacter pylori
Authors: LOGAN R. P. H. , GUMMETT P. A. , MISIEWICZ J. J. , KARIM Q. N , WALKER M. M. , BARON J. H.
Published: July 2010

At present there is no generally accepted treatment regimen for eradicating metronidazole‐resistant Helicobacter pylori. This study determines the eradication rate after treatment with 40 mg omeprazole o.m. and 500 mg amoxycillin q.d.s. for 14 days, with 120 mg tripotassium dicitrato bismuthate q.d.s. for the first week (Days 1–7) and 750 mg ciprofloxacin b.d. for the second week (Days 8–14). Thirty patients (16 male, mean age 45 years, range 16–80 years) with duodenal ulcers (n= 18) or non‐ulcer dyspepsia (n= 2) and metronidazole‐resistant H. pylori detected by histology, culture, in vitro sensitivity tests and a positive 13C‐urea breath test entered the study. Follow‐up was by 13C‐urea breath test at the end of treatment and at 1, 3, 6, and 12 months. Eradication was denned as a negative 13C‐urea breath test at least 1 month after finishing treatment. H. pylori was successfully eradicated in 21/30 (71%) patients (median follow‐up 10.2 months, range 4–12 months). A pre‐treatment ciprofloxacin‐resistant strain was isolated in 1/9 patients in whom eradication failed. Of 30 patients 29 completed the 2‐week regimen; one patient experienced dizziness after 3 days of treatment. The most common side‐effect was increased stool frequency (n= 6). This 2‐week treatment regimen for metronidazole‐resistant H. pylori is well tolerated and achieves an eradication rate of 70%.
Reduction of rectal sensitivity and post‐prandial motility by granisetron, a 5 HT3‐receptor antagonist, in patients with irritable bowel syndrome
Authors: PRIOR A. , READ N. W.
Published: July 2010

The effect of granisetron, a specific 5‐hydroxytryptamine 3‐receptor antagonist, on the anorectal responses to rectal distension and a 1000‐calorie meal was assessed in 12 patients with irritable bowel syndrome. Each patient was studied on three occasions, receiving intravenously either 40 mcg/kg granisetron, 160 mcg/kg granisetron or normal saline. Granisetron caused a dose‐dependent reduction in rectal sensitivity, manifested by an increase in the threshold volumes at which the sensations of gas, desire to defecate, urgency and discomfort were perceived. This reached significance for all sensations at the higher dose level (P < 0.01). No significant changes in anal pressures, rectal compliance or distension‐induced motor activity occurred following drug administration. A dose‐dependent reduction in post‐prandial motility was observed following intravenous granisetron and this was highly significant at 160 mcg/kg (P= 0.005). These results suggest that the 5 hydroxytryptamine receptor antagonists may have a therapeutic role in patients with irritable bowel syndrome.
A placebo‐controlled investigation of duodenal ulcer recurrence after withdrawal of long‐term treatment with ranitidine
Authors: PENSTON J. G. , DIXON J. S. , BOYD E. J. S. , WORMSLEY K. G.
Published: July 2010

Ninety‐two patients with duodenal ulcer disease, who had received long‐term continuous treatment with ranitidine for an average of 7.5 years, participated in a double‐blind, placebo‐controlled study to determine whether stopping ranitidine resulted in ulcer recurrence. Patients were randomized to continue with ranitidine (n= 46) or to receive placebo (n= 46) and were followed up for six months. Treatment failure was defined as the first symptomatic recurrence of ulcer. The occurrence of epigastric pain during the follow‐up period was significantly less frequent in the ranitidine group (13%) than in the placebo group (43%) (P= 0.001). At six months, 9% of the ranitidine group had developed ulcer recurrence, compared with 48 % in the placebo group (P< 0.001, logrank test). Multivariate analysis using the Cox proportional hazards model showed that younger age (P= 0.041) and a long history of ulcer disease (P= 0.025) were risk factors for ulcer recurrence but gender, smoking and duration or dose of previous ranitidine treatment were not predictive of relapse during treatment with placebo. In conclusion, withdrawal of ranitidine after more than five years of continuous treatment results in almost half of the patients developing symptomatic ulcer recurrence within six months. Thus, long‐term continuous therapy does not alter the natural history of duodenal ulcer disease. Younger patients and those with a long history of ulcer disease appear to be at increased risk of developing ulcer recurrence if long‐term treatment is withdrawn.
Short report: high‐dose omeprazole and amoxycillin in the treatment of Helicobacter pylori‐associated duodenal ulcer
Authors: COLLINS R. , BEATTIE S. , XIA H. X. , O'MORAIN C.
Published: July 2010

Thirteen consecutive patients with active duodenal ulcer disease were assigned to a treatment schedule with high‐dose omeprazole and amoxycillin. Duodenal ulcer was diagnosed endoscopically in all patients, at which time antral biopsies were taken for culture and histology. All were positive for Helicobacter pylori and histological gastritis. Treatment was for 2 weeks: 80 mg omeprazole daily plus 500 mg amoxycillin syrup t.d.s. in the first week, followed by 40 mg omeprazole daily in the second week. Repeat gastroscopy was performed 4 weeks after completion of treatment in all patients. Duodenal ulcer healing occurred in 4/13 patients. H. pylori eradication was achieved in 2/4 patients with healed ulcers and in 3/9 patients with persistent ulceration. This study suggests that a short period of treatment with high‐dose omeprazole and amoxycillin achieves low rates of ulcer healing and H. pylori eradication.
Short report: octreotide in the treatment of external pancreatic fistulas
Authors: TULASSAY Z. , FLAUTNER L. , VADÁSZ A. , FEHÉRVÁRI I.
Published: July 2010

The efficacy of the long‐lasting somatostatin analogue, octreotide, in the treatment of high‐output pancreatic fistulas was investigated in this prospective, open study. Sixteen patients with post‐operative pancreatic fistulas were treated with subcutaneous injections of octreotide 0.1 mg b.d. The output of the fistulas before the somatostatin therapy ranged between 190 and 5 70 ml/day. The therapy was begun on average 17 days following the appearance of the fistula (range 4 to 35 days). The decrease in volume one day after initiation of therapy ranged from 26% to 69%. By the third day of treatment the fistula volume decreased to 0–45% of the initial output. The treatment resulted in the closure of 14 of the 16 fistulas; the time to closure ranging from 3 to 15 days. The results suggest that octreotide is a useful adjuvant agent in the treatment of an external pancreatic fistula.
Short report: Effect of two prokinetic drugs on the electrical and motor activity of the small bowel in dogs
Authors: DEFILIPPI C. , GOMEZ E.
Published: July 2010

The effects of trimebutine and domperidone, on the electrical and motor activity of the upper small bowel in dogs, were studied simultaneously by means of a suction electrode and a manometric catheter. Trimebutine, given during phases I and II of the migratory motor complex, was followed by a period of regular spike potentials and contractions; the increased motor activity was significantly greater when the drug was given during phase II. Domperidone, when injected in phase I, was followed by an irregular pattern of spike potentials and contractions of low amplitude. By contrast, activity was not augmented when the drug was given during phase II. We conclude that the effects of drugs, such as trimebutine and domperidone, on the canine small bowel are influenced by the phase of the migratory motor complex.
Short report: prednisolone withdrawal followed by lymphoblastoid interferon in the therapy of adult patients with presumed childhood‐acquired chronic hepatitis B virus infection
Authors: BROOK M. G. , MAIN J. , YAP I. , CHAN G. , KARAYIANNIS P. , CROSSEY M. , THOMAS H. C.
Published: July 2010

Eighteen patients with presumed childhood acquisition of chronic hepatitis B virus infection were initially entered into this randomized controlled trial. Twelve were treated with prednisolone for 4 weeks followed, after a 2‐week gap, by thrice weekly lymphoblastoid a‐interferon for 12 weeks. Two of these had previously acted as untreated controls. Three of the 12 patients (25%) [who were initially hepatitis B virus (HBV) surface antigen (HBsAg),‘e’ antigen (HBeAg) and HBV‐DNA positive] became HBeAg and HBV‐DNA negative during therapy and remained so after 12 months post‐therapy follow‐up. One of these also lost HBsAg. A further two patients lost HBeAg and HBV‐DNA during therapy but relapsed 6 and 9 months later. Two additional patients were HBV‐DNA negative but HBeAg positive at the end of follow‐up. None of the eight untreated control patients seroconverted during an identical follow‐up period. Two further patients were HBsAg and HBeAg positive but HBV‐DNA negative at the start of therapy. These were omitted from the final analysis: both subsequently lost HBeAg. The treatment response was associated with a rise in aspartate aminotransferase, peaking 2–6 weeks after prednisolone withdrawal, loss of HBV‐DNA 0–8 weeks later and subsequent normalization of liver function tests. Treatment was well tolerated.
Anti‐secretory effects and pharmacokinetics of low dose ranitidine
Authors: KOSS M. A. , HOGAN D. L. , LANE J. , STEINBACH J. H. , ISENBERG J. I.
Published: July 2010

The purpose of this study was to examine the anti‐secretory effect of low doses of orally administered ranitidine on meal‐stimulated gastric acid secretion and assess its pharmacokinetics. The effect of 20, 40, 60 and 80 mg of ranitidine p.o. and placebo were tested on 5 separate days (Latin square, double‐blind) in 15 healthy males (mean age 35 years). Gastric acid secretion was measured prior to and for 8 h following two sequential mixed liquid meals administered at 4‐h intervals. Venous blood samples were obtained at frequent intervals before and following each dose for determination of plasma ranitidine concentration by high pressure liquid chromatography. Each dose of ranitidine significantly (P < 0.01) decreased the peak and cumulative 4‐h acid secretory responses to the first meal (range 58–93 %), and the 60 and 80 mg doses significantly inhibited the response to the second meal by 31 and 43%, respectively. Total 8‐h meal‐stimulated acid outputs were decreased significantly in a dose‐related manner (range 38–73%). Peak plasma ranitidine occurred approximately 1 h after dosing. Ranitidine tmax, t½ and clearances were independent of dose; however, AUC and C. were dose‐related. Inhibition of acid secretion was related to plasma ranitidine concentration; the mean IC50 was 27 (± 6.4) ng/ml. We conclude that modest doses (equivalent to 7–27% of the daily therapeutic dose) of ranitidine effectively suppress meal‐stimulated gastric acid secretion in a dose‐related manner. If these doses are of clinical efficacy, it may be possible for substantial cost savings to occur.
The management of constipation in adults
Authors: GATTUSO J. M. , KAMM M. A.
Published: July 2010

The successful management of constipation depends on defining the patient's symptoms, excluding secondary causes, and characterizing the abnormality of defecation. Constipation without gut dilatation is found commonly in pregnancy, the elderly, and those with the irritable bowel syndrome. In addition, there is a group of patients that has intractable, severe idiopathic constipation. Some have ‘slow transit’ and open their bowels every 1–4 weeks. Others have a defecatory disorder with normal colonic transit. Constipation with gut dilatation is seen in Hirschsprung's disease, idiopathic megarectum and megacolon, chronic intestinal pseudo‐obstruction and Chagas' disease. Constipation can also result from disturbance to the autonomic outflow of the gastrointestinal tract, and colonic function may be also affected by psychological factors. This review article discusses the presentation, investigation and management of patients with constipation.
A prospective randomized study with mineral oil and oral lavage solution for treatment of faecal impaction in children
Authors: TOLIA V. , LIN C.‐H. , SUR Y. FLIT
Published: July 2010

Faecal impaction with or without encopresis is a very common problem. We performed a randomized, open‐label, prospective study to compare the efficacy and acceptability of the treatment of faecal impaction using either mineral oil or pineapple‐flavoured isotonic intestinal lavage solution containing polyethylene glycol‐3350 (Colyte). Thirty‐six patients over 2 years of age were randomized to receive either mineral oil or flavoured lavage solution. The dose of mineral oil was 2 to 8 tablespoons twice a day for two days (17 patients—Group I) and of lavage solution was 20 ml/kg/h for 4 hours on two consecutive days (19 patients—Group II). The patients were assessed for the presence of abdominal faecal masses, presence and consistency of rectal mass, perineal soiling before and two days after either of the randomly assigned treatment. The patients and parents were asked regarding the compliance with treatment, side‐effects, number of bowel movements after treatment and willingness to try similar treatment if faecal impaction recurred. Patients in the lavage group had more frequent bowel movements, and showed more effective clearance of abdominal and rectal lumps (P < 0.01) at the time of repeat examination at two days. However, they had some vomiting and were less compliant (P < 0.01) when compared to mineral oil patients. We conclude that balanced lavage solution effectively relieves faecal impaction, however, compliance with its use is poorer than that with mineral oil.
Gastric acid suppression is greater during intravenous ranitidine infusion versus bolus injections of famotidine
Authors: HOGAN D. L. , MCQUAID K. R. , KOSS M. A. , CROMBIE D. L. , HUNTER S. , METZ C. , EULER A. R. , ISENBERG J. I.
Published: July 2010

It has been proposed that famotidine may be effective in maintaining intragastric pH ≥ 4 for up to 12 h with a single i.v. 20 mg bolus injection and thereby prevent acute stress‐related mucosal haemorrhage, The present study was designed to compare a ranitidine continuous i.v. infusion (6.25 mg/h) vs. famotidine bolus injection (20 mg every 12 h) on 24‐h intragastric pH and gastric acid secretion. Twenty‐eight healthy volunteers (15 males, 13 females; 20–56 years) participated in two 24‐h treatment periods; each test was in random order separated by 7–10 days. After an overnight fast, subjects were intubated and gastric pH and acid secretion measured hourly. Whereas ranitidine maintained gastric pH above 4 for the entire 24‐h period, mean pH steadily decreased to a nadir of 2.9 and 3.7, respectively, 12 h after each famotidine injection (P < 0.01 vs. ranitidine). Furthermore, gastric acid secretion increased to 4.4 ± 1.2 mmol/h 12 h after famotidine injection compared to 1.1±0.3 mmol/h with ranitidine (P < 0.01). We conclude that ranitidine delivered as a continuous i.v. infusion (6.25 mg/h) is superior to bolus famotidine injections (20 mg) at 12‐h intervals in suppressing gastric acid secretion and maintaining an intragastric pH ≥. 4. More frequent famotidine dosing, or delivery by continuous i.v. infusion, may be required to provide prolonged acid suppression.
Use of omeprazole in Zollinger‐Ellison syndrome: a prospective nine‐year study of efficacy and safety
Authors: METZ D. C. , STRADER D. B. , ORBUCH M. , KOVIACK P. D. , FEIGENBAUM K. M. , JENSEN R. T.
Published: July 2010

H+, K+‐ATPase inhibitors such as omeprazole are the antisecretory agents of choice for the management of gastric acid hypersecretory states, including the Zollinger‐Ellison syndrome. However, long‐term follow‐up data on the overall efficacy and safety of these agents in large numbers of patients are lacking. In the current study we examined the long‐term efficacy and safety of omeprazole in 116 patients with Zollinger‐Ellison syndrome treated with oral omeprazole at a single centre for up to 114 months (mean ± S.E.M. = 38 ± 3 months). The initial omeprazole maintenance dose was established according to the acute upward dose titration method in 89/116 patients (77%). Gastric acid output was effectively controlled using 60 mg of omeprazole once daily in 41/89 patients (46%) and 22/89 patients (25 %) required twice daily omeprazole therapy. The mean ranitidine equivalent dose for patients who required 60 mg omeprazole once daily (2.5 ± 0.2 g/day) was significantly lower than the mean ranitidine equivalent dose for patients who required more than 60 mg omeprazole once daily (4.3 ± 0.3 g/day). Long‐term omeprazole maintenance therapy was discontinued in 36/116 patients (31%) but in no cases was discontinuation due either to drug‐induced side‐effects or uncontrolled gastric acid output. Fasting serum gastrin levels were significantly elevated above pre‐treatment levels at only one time point during follow‐up and were likely due to tumour growth rather than a drug effect. The final long‐term omeprazole maintenance doses were lower than the initial doses but correlated closely with the preomeprazole basal acid output (r= 0.41, P < 0.001) and ranitidine equivalent dose requirements (r= 0.49, P < 0.001). We conclude that omeprazole effectively and safely controls gastric acid hypersecretion in all patients with Zollinger‐Ellison syndrome for up to nine years without evidence by tachyphylaxis.
Peptic ulcer in the elderly—a double‐blind, short‐term study comparing nizatidine 300 mg with ranitidine 300 mg
Authors: BATTAGLIA G. , MARIO F. DI , VIGNERI S. , SANTO P. DAL , PILOTTO A. , MAZZACCA G. ,   GISU (INTERDISCIPLINARY ULCER STUDY GROUP),   OTHER ITALIAN CENTRES
Published: July 2010

This was a randomized, double‐blind, multicentre, short‐term study comparing ranitidine and nizatidine at the standard dosages of 300 mg at bedtime. In 49 centres in Italy, all peptic ulcer patients aged over 65 years and with endoscopically documented acute disease were considered eligible for the study. Clinical check‐ups were repeated every 3 weeks, while the endoscopic and biochemical assessments were scheduled at 6 and (in unhealed patients) 12 weeks. Statistics: chi‐squared test, Fisher's exact test, Student t‐test for unpaired data. The study included 170 duodenal ulcer and 75 gastric ulcer patients. Of these, 83/17 duodenal ulcer and 38/75 gastric ulcer patients were treated with nizatidine 300 mg and the remainder with ranitidine 300 mg. The groups were well‐matched for common clinical data. Eight patients dropped out. Healing rates at 6 and 12 weeks were 81.9% and 91.5% for nizatidine‐treated duodenal ulcer patients versus 78.1% and 94.2% for ranitidinetreated duodenal ulcer cases (P: N.S.); 6 and 12‐week healing rates were 76.3% and 89.5% for nizatidinetreated gastric ulcer patients versus 67.6% and 83.8% for ranitidine‐treated gastric ulcer patients (P: N.S.). No slow healing risk factors were found. Only minor adverse events were registered. In conclusion: ranitidine 300 mg and nizatidine 300 mg both proved effective and safe in the treatment of acute peptic ulceration in the elderly.