bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of omepmzole and cimetidine on duodenal ulcer healing and ihe relief of symptoms
Authors: DAHLGREN S. , DOMELLÖF L , HRADSKY M. , NORRYD C. , BRUNKWALL J. , SVENSSON G. , SVENSSON J.‐O. , KARLSSON J. , KNUTSON U. , GASSLANDER T. , LINDHAGEN J. , ARBMAN G. , JANSSON R. , SANDSTRÖM R. , HULDT B. , PETTERSSON B.‐G. , JANUNGER K.‐G. , SJÖLUND B. , HERNQVIST H.
Published: July 2010

In a Swedish double‐blind multicentre study, omeprazole (30 mg o.m.) was compared with the H2‐receptor antagonist cimetidine (400 mg b.d.) in 152 patients. Clinical assessments and laboratory investigations were carried out at 2 and 4 weeks, and again at 6 weeks in unhealed patients. Endoscopy was performed at 2 weeks, and again at 4 and 6 weeks in unhealed patients. The patients in the two groups were well‐matched prior to treatment.

Omeprazole was superior to cimetidine in ulcer‐healing rate after 2, 4 and 6 weeks. After 2 weeks of treatment, 66% of the omeprazole‐ and 45 % of the cimetidine‐treated patients were healed (P= 0.02), after 4 weeks 97 and 84% (P= 0.01), and after 6 weeks 100 and 92% (P= 0.02), respectively.

There was a more pronounced improvement in the patients' symptoms in the omeprazole group after 2 weeks (P= 0.05).

Both drugs were well‐tolerated, but there was a high prevalence of patients with adverse events in the cimetidine group (51%, compared to 30% of the omeprazole group; P= 0.02).

A total of 125 patients were followed for 6 months after healing. The patients were investigated by endoscopy after 6 months, or whenever symptoms occurred. There was no significant difference in the rate of relapse within 6 months between the two treatment groups: 54% relapsed in the omeprazole group and 52 % in the cimetidine group.

In conclusion, 30 mg of omeprazole, given once daily, is superior to 400 mg of cimetidine twice daily in duodenal ulcer healing; but ulcer relapse in the two groups appears to be equivalent.
The benefit of pancreatic enzyme substitution after total gastrectomy
Authors: ARMBRECHT U. , LUNDELL L. , STOCKBRÜGGER R. W.
Published: July 2010

The aim of the present study was to evaluate the effect of the pancreatic enzyme preparation Kreon on abdominal symptoms, bowel habits, faecal fat excretion and oro‐caecal transit time in patients after total gastrectomy for carcinoma of the stomach with Roux‐en‐Y anastomosis. A hydrogen breath test was carried out in each patient to detect bacterial overgrowth.

In a double‐blind crossover trial, 15 patients were treated with either Kreon or placebo (3.6 g/day) in two test‐periods each of seven days.

During treatment with the active substance, the stool consistency became more solid (P < 0.05). The number of bowel movements and the abdominal symptoms, however, remained statistically unchanged.

Treatment with Kreon did not influence the oro‐caecal transit time. Faecal fat excretion did not significantly decrease in the whole group of patients. However, in those patients with massive steatorrhoea (free and esterified fatty acids > 350 mmol/72 h; upper reference limit 60 mmol/72 h) a significant (P < 0.05) reduction from a median excretion of 643 mmol/72 h to 501 mmol/72 h was seen. Such a decrease in faecal fat excretion did not occur in patients with steatorrhoea below this limit. Bacterial overgrowth or rapid upper intestinal transit were not over‐represented in patients with a high‐degree of steatorrhoea.

We conclude that after total gastrectomy pancreatic enzyme substitution reduces massive steatorrhoea and improves stool consistency.
Should we use non‐steroidal anti‐inflammatory drugs?
Authors: HASLOCK I.
Published: July 2010

Both the relative efficacy and inefficacy of non‐steroidal anti‐inflammatory drugs (NSAIDs) contribute to their use in chronic rheumatic diseases. There are also sociological trends in patients, and in the population as a whole, increasing demand for treatment. In view of the risks of such treatment, the most rational approach to prescribing would be the use of a scientific risk‐benefit analysis. Unfortunately, the data, especially those related to symptom relief, are inadequate for such an analysis. Until more meaningful figures are produced, good clinical practise concentrates on the responsibilities of physicians who both start and stop drugs, and makes it essential that strategies to minimize risk are produced.
The role of H2‐receptor antagonists in the prevention of NSAID‐induced gastrointestinal damage
Authors: RACHMILEWITZ D.
Published: July 2010

Non‐steroidal anti‐inflammatory drugs (NSAIDs) induce gastric and duodenal damage in animals and humans. The possible protection afforded by cimetidine against acute and short‐term NSAID‐induced mucosal damage was evaluated in five studies. Cimetidine 200 mg once daily and 400 mg once daily was found to protect the gastric mucosa against damage induced by a single dose of aspirin 1300 mg; this protection was found to be independent of gastric acid secretion. Cimetidine 200 mg q.d.s. was found to protect the stomach and duodenum against damage induced by 14 days’treatment with aspirin 650 mg q.d.s. Duodenal and gastric damage induced during a 7‐day treatment period with naproxen 500 mg b.d. was prevented by cimetidine 400 mg b.d.; this dose of cimetidine also provided significant duodenal protection against damage induced by I week of therapy with indomethacin 50 mg t.d.s. There is no correlation between upper gastrointestinal symptoms, or between mucosal prostanoids, and the presence or absence of mucosal damage. Cimetidine is therefore effective in the prevention of mucosal damage induced by short‐term treatment with NSAIDs.
Treatment of NSAID‐induced gastrointestinal lesions with cimetidine: an international multicentre collaborative study
Authors: BIJLSMA J.W.J.
Published: July 2010

The efficacy of cimetidine 800 mg nocte in the treatment of erosions or ulcers induced by non‐steroidal anti‐inflammatory drugs (NSAIDs) was evaluated in an uncontrolled multicentre study of 187 patients requiring continuation of their NSAID therapy. After 4 weeks of treatment, endoscopic healing was achieved in 62 % of patients. After 8 weeks of therapy, 88% of patients were lesion‐free. Patients with ulcer had a healing rate of 49% at week 4, which increased to 81 % at the completion of 8 weeks. The majority of patients (82 %) with erosions healed in 4 weeks. By week 8, erosions were healed in 97 % of patients. Following endoscopically verified lesion healing, 113 patients entered a maintenance phase of the study, which assessed the efficacy of cimetidine 400 mg nocte in preventing recurrence of erosions or ulcers while continuing NSAID therapy. During a 6‐month observation period, the cumulative probability of endoscopically observed recurrence of lesions was 12 % (with a mean time to recurrence of 116 days), which is similar to the incidence of relapse achieved with cimetidine 400 mg nocte in patients with uncomplicated peptic ulcer. The results of this study suggest that cimetidine 800 mg nocte is effective in healing NSAlD‐induced lesions despite continued NSAID use, and that maintenance treatment with cimetidine 400 mg nocte can prevent lesions and reduce lesion recurrence during chronic NSAID administration.
Bismuth accumulates in the body during treatment with tripotassium dicitrato bismuthate
Authors: GAVEY C. J. , SZETO M.‐L. , NWOKOLO C. U. , SERCOMBE J. , POUNDER R. E.
Published: July 2010

Bismuth concentration was measured in plasma, dried leucocytes and urie in nine patients before, during and after treatment with tripotassium dicitrato bismuthate (De‐Noltab 2 b.d.) for 6 weeks. During treatment there was an 8.5‐fold rise in median plasma bismuth concentration (P < 0.01), a non‐significant doubling of leucocyte bismuth content, and a 349‐fold rise in 24‐h urinary bismuth excretion (P < 0.01). The significantly increased urinary bismuth excretion continued for at least 3 months after cessation of treatment with tripotassium dicitrato bismuthate, indicating accumulation of bismuth during treatment with this drug.
Effect of omeprazole on intragastric and duodenal bulb acidity in duodenal ulcer patients
Authors: BENDTSEN F. , OVESEN L. , ROSENKILDE‐GRAM B. , RUNE S. J.
Published: July 2010

Intraluminal pH was measured simultaneously in the stomach and duodenal bulb with six small, glass electrodes tied together at 1.5‐cm intervals. Ten patients with duodenal ulcer disease were studied under fasting conditions and for 3 h after a standard liquid meal on three occasions: day 1, before treatment; day 8, when the proton pump blocker omeprazole had been taken in a daily dose of 30 mg for 7 days consecutively, including the day of the pH study; day 9, 24 h after the last dose of omeprazole. Mean hydrogen ion activity and the percentage of time with pH below 3 was calculated from the digital pH data sampled at a frequency of 1 per second from each electrode.

On day 8, five of the patients were permanently anacidic (pH > 4) in the stomach and duodenum, while the food‐stimulation broke off anacidity for shorter periods in the other five patients. The pH pattern in the duodenal bulb was markedly altered in all patients with disappearance of the typical pH fluctuations, and a decrease in the time that the pH was below 3 from a median value of 30% before treatment to 0% in seven patients and close to 0% in three patients. On day 9, a large patient‐to‐patient variation was observed in gastric pH: three patients were still anacidic, four were markedly suppressed, but three patients reached near pre‐treatment acidity. Duodenal bulb acidity was still decreased significantly on day 9 in all patients, with post‐prandial pH below 3 for less than 5% of the time, compared with 30% before treatment.
Review article: dissolution of gallstones in the biliary tree
Authors: SUMMERFIELD J. A.
Published: July 2010

There are a variety of methods for dissolving gallstones in the biliary tree, which include oral therapy and direct contact dissolution. Cholesterol gallstones are most amenable to dissolution. Developments in non‐operative physical methods to remove gallstones (particularly endoscopic papillotomy and extracorporeal shock‐wave lithotripsy have diminished the use of chemical dissolution. However, in selected patients, there remains a place for chemical dissolution, but often in conjunction with the physical techniques.
Review article: mechanisms of drug release from tablets and capsules. I: Disintegration
Authors: MELIA C. D. , DAVIS S. S.
Published: July 2010

Variable drug release from solid oral dosage forms has been an important cause of bioavailability problems in the past, and is a factor now carefully controlled in pharmaceutical products. In two reviews, we describe briefly the composition and manufacture of tablets and capsules, and the two main processes by which they release drugs; disintegration and dissolution. We will explain what is presently understood of the actual mechanisms of drug release and the physico‐chemical factors that affect the release process. The strategies adopted by pharmaceutical scientists in designing modern oral solid dose forms to release drugs at reproducible and therapeutically optimal rates will be discussed. Finally, the role of gamma scintigraphy in assessing dosage form performance in vivo will be described.
Effect of BMY‐25368, a potent and long‐acting histamine H2‐receptor antagonist, on gastric secretion and aspirin‐induced gastric lesions in the dog
Authors: CAVANAGH R. L. , BUYNISKI J. P.
Published: July 2010

BMY‐25368, 1‐amino‐2‐[3‐(3‐piperidinomethylphenoxy) propylamino]‐1‐cyclobutene‐3,4‐dione, a new histamine H2‐receptor antagonist, has been compared to ranitidine as an inhibitor of gastric acid secretion in the Heidenhain pouch dog. Intravenous infusion of BMY‐25368 antagonized histamine‐stimulated gastric secretion in a competitive manner. BMY‐25368 also antagonized gastric secretion stimulated by pentagastrin, bethanechol and food. When compared to ranitidine in histamine‐stimulated dogs, BMY‐25368 was nine times more potent after bolus intravenous administration. Oral potency relative to ranitidine and ranged from 2.8 to 4.4, depending on the secretagogue used. BMY‐25368 also exhibited a significantly longer duration of action than ranitidine. Thus, its potency relative to ranitidine after oral administration, in histamine‐stimulated dogs, increased from 3.2 to 28 when determined 1–3 and 10–12 h post dose, respectively. BMY‐25368 administered orally also antagonized aspirin‐induced gastric lesions in the dog and was nine times more potent than ranitidine in this respect.
Octreotide (a somatostatin analogue) improves the quality of life in some patients with a short intestine
Authors: NIGHTINGALE J. M. D. , WALKER E. R. , BURNHAM W. R. , FARTHING M. J. G. , LENNARD‐JONES J. E.
Published: July 2010

Six patients with short intestine (jejunal length 25–70 cm) on long‐term parenteral nutrition, needing 4–5 L of intravenous fluid daily, were given octreotide (a somatostatin analogue, SMS 201–995) to investigate whether it would reduce beneficially their secretory diarrhoea (3.6–6.9 kg/day). They consumed the same diet for 2 control days, followed by 2 test days. Octreotide was given intravenously, initially in a dose of 50 μg b.d. through the central feeding line. There was a significant reduction of daily stomal output (0.5–5.0 kg) and daily sodium and potassium output; however there was no significant change in energy absorption. The response to octreotide was greatest in those patients who absorbed least nutrients. A dose increase to 100 μg t.d.s. gave no further measurable benefit though the patients found it smoothed‐out the post‐prandial rise in stomal output. Two patients were continued on long‐term octreotide therapy, which allowed for a daily reduction in intravenous fluid of 1 and 1.5 L. Octreotide's anti‐secretory effect was found to have been maintained when it was retested in one patient after a year of continuous therapy.
The effect of tripotassium dicitrato bismuthate on pepsin activity
Authors: DE BEAUX A. C. , DEFIZE J. , HUNT R. H.
Published: July 2010

We have studied the effect of tripotassium dicitrato bismuthate on the peptic activity of gastric juice, both basal and pentagastrin‐stimulated, from five healthy volunteers using porcine pepsin solution as a control. Tripotassium dicitrato bismuthate showed no inhibition of the proteolytic activity of either the pure porcine or the human pepsin in the gastric juice. The ulcer healing efficacy of tripotassium dicitrato bismuthate is unlikely to be related to a gastric anti‐protease effect.
A comparison of metoclopramide and trimebutine on small bowel motility in humans
Authors: GRANDJOUAN S. , CHAUSSADE S. , COUTURIER D. , THIERMAN‐DUFFAUD D. , HENRY J. F.
Published: July 2010

Trimebutine maleate and metoclopramide increase small bowel motility. The present manometric study of the human normal interdigestive duodeno‐jejunal motility demonstrated two different pharmacological effects in 15 healthy volunteers. Trimebutine constantly induced a premature phase 3 activity (0.81 ± 0.4 min after a 100‐mg intravenous injection) with patterns similar to spontaneous phase 3. Metoclopramide increased the motility index (contractile activity) during phase 2 without inducing a premature phase 3. No significant variations in plasma motilin concentration were noticed after either trimebutine or metoclopramide. The pancreatic polypeptide concentration rose significantly after metoclopramide injection.
A pilot study of thymus extract in chronic non‐A, non‐B hepatitis
Authors: CIVEIRA M. P. , CASTILLA A. , MORTE S. , SERRANO M. , PRIETO J.
Published: July 2010

In previous studies it has been suggested that activation of cellular immunity may have a role in controlling the activity of chronic non‐A, non‐B liver disease. We conducted a pilot study of therapy with a bovine thymus extract for 6 weeks in 15 consecutive patients with chronic non‐A, non‐B hepatitis, most of them sporadic cases. Treatment induced immunomodulation, and in five patients a significant but transient diminution in aminotransferase levels was observed associated with increments in several parameters of cellular immunity. This suggests that a longer administration of this or other related compounds, or treatment with a more potent immunomodulating agent, might be effective in these patients.
The effects of fasting on 24‐h gastric secretion of patients with duodenal ulcers resistant to ranitidine
Authors: JOHNSTON D. A. , WORMSLEY K. G.
Published: July 2010

We compared the effects of fasting and feeding on the antisecretory actions of ranitidine in 19 patients whose duodenal ulcers remained unhealed or relapsed despite treatment with the drug. Nine of the patients received, and continued with, 150 mg ranitidine b.d. and 10 took 300 mg ranitidine b.d. In all patients, gastric secretion was inhibited during the night, with near‐neutral pH and acid output less than an average of 2 mmol in 8 h. Gastric secretion was not inhibited during the day by either of the therapeutic regimens. However, on the day when the patients fasted, gastric acidity was, on average, 20–50 mmol/L less than on the day when food was consumed. Food‐induced interference with the therapeutic inhibition of gastric secretion produced by H2‐receptor antagonists may be responsible for the unsatisfactory clinical response of some patients with duodenal ulcers. Prolonged fasting can improve the control of gastric secretion and may allow resistant ulcers to heal.
Nature and time‐course of piroxicam‐induced injury to human gastric mucosa
Authors: FELLOWS I. W. , BHASKAR N. K. , HAWKEY C. J.
Published: July 2010

The nature and time‐course of acute piroxicam‐induced gastric mucosal injury was determined in ten healthy volunteers treated with 10 mg piroxicam twice daily by mouth for 21 days. Mucosal injury was measured endoscopically by visual analogue scales and by the method of Lanza, and luminal blood loss by haemoglobin measurements in gastric washings, 10 h after the first drug dose and then after 5, 10 and 21 days.

Acute mucosal injury, consisting mainly of haemorrhagic lesions in the gastric body, developed to a maximum extent within 10 h of the first dose of piroxicam, and did not increase thereafter. By contrast intraluminal bleeding increased little for 10 days and then rose significantly at 21 days, when plasma piroxicam levels reached values likely to affect platelet function.

We conclude that gastric mucosal injury and bleeding may be dissociated and may constitute different targets for prophylaxis. Gastric mucosal injury is probably exerted topically as it is maximal at low plasma drug concentrations, whereas bleeding may arise because of interference with platelet‐dependent mechanisms.
A comparison of low‐dose maintenance treatment with enprostil against ranitidine in the prevention of duodenal ulcer recurrence
Authors: BARDHAN K. D. , MORRIS P. , HINCHLIFFE R. F. C. , SAUNDERS J. H. B. , MACDOUGALL B. R. D. , BOLD J. M. , FREEMAN P. R.
Published: July 2010

Enprostil, a prostaglandin E2 analogue, is effective in healing acute duodenal ulcer but its value in preventing recurrence, when given daily for maintenance therapy, is uncertain. In this three‐centre study we compared enprostil and ranitidine maintenance therapy; the latter is known to reduce duodenal ulcer relapse rates. Patients whose duodenal ulcers had been healed by treatment with an H2‐receptor antagonist were randomized to receive single‐blind treatment with either 35 μg enprostil (n = 64) or 150 mg ranitidine (n = 64) at bedtime for periods of up to 1 year. Endoscopy was routinely performed at 3 months at one centre, and at 6 and 12 months at all three centres, or whenever ulcer symptoms recurred. Clinical assessment and laboratory investigations were performed every 3 months. Relapse, defined as recurrent ulcer with or without pain, or erosions with pain, was significantly greater in patients on enprostil, the comparative rates at 3, 6 and 12 months were: enprostil 23, 31 and 36% ranitidine 6, 12 and 17% (P= 0.013; P= 0.03 and P= 0.03, respectively).
Review article: mechanisms of drug release from tablets and capsules. 2. Dissolution
Authors: MELIA C. D. , DAVIS S. S.
Published: July 2010

Optimal drug dissolution is crucial to the success of oral drug therapy. Slow dissolution has frequently been correlated with poor or erratic performance of oral dosage forms in vivo, and drugs of low aqueous solubility provide a major challenge to the designer of modern oral dosage forms. In this second of two reviews, we briefly describe the physical process of dissolution, the principal factors controlling drug dissolution from tablets and capsules, and the strategies that are utilized by pharmaceutical scientists to enhance drug dissolution of orally administered drugs.

Dissolution, Tablets, Drug release, Bioavailability.
Prolonged inhibition of meal‐stimulated acid secretion and gastrin release following single subcutaneous administration of octreotide (SMS 201–995) in man
Authors: KARNES W. E. , MAXWELL V. , SYTNIK B. , CHEW P. , WALSH J. H.
Published: July 2010

Single subcutaneous doses of the somatostatin analogue, SMS 201–995, were evaluated for the degree and duration of effects on acid secretion, serum gastrin levels, and gastric emptying in eight human male subjects (mean age 44 years) over an 8‐h period. All the subjects received subcutaneous 50‐μg and 100‐μg doses of SMS 201–995 and placebo on three separate days in a double‐blind random order. Drug or placebo was administered at time 0 followed by peptone meals at time 0, 2, 4, and 6‐h. Peptone meals were evacuated at time 1, 3, 5 and 7‐h to create ‘basal’conditions between alternate hours. Gastric acid secretion was determined hourly beginning at time −1. Both the 50‐μg and 100‐μg doses of SMS 201–995 significantly inhibited ‘basal’and peptone meal‐stimulated gastric acid secretion throughout the 8‐h measurement period. The minimum effective plasma concentration of SMS 201–995 for inhibition of peptone meal‐stimulated gastric acid secretion was approximately 1000 pg/ml. Peptone meal‐stimulated plasma gastrin
A double‐blind placebo‐controlled trial of omeprazole on characteristics of the migrating motor complex in healthy volunteers
Authors: VINTER‐JENSEN L. , KRAGLUND K. , PEDERSEN S. A.
Published: July 2010

The aim of the study was to investigate a possible effect of omeprazole on the characteristics of the migrating motor complex. The study was performed as a double‐blind crossover study and the pressure recordings were performed after 3 days of treatment with placebo or omeprazole 40 mg o.m. The calculations were based on 5 h of recording in each subject and in both investigations. There were two characteristics in the omeprazole group which were significantly different from placebo. Firstly, duodenal phase III was more often accompanied by an antral phase III and secondly, the duration of duodenal phase III was increased. The results suggest that the rapid cleaning mechanism, represented by phase III activity, is more pronounced after omeprazole treatment, possibly arising from its antisecretory effect.
The relationship between suppression of acidity and gastric ulcer healing rates
Authors: HOWDEN C. W. , HUNT R. H.
Published: July 2010

We have investigated the relationship between the suppression of acidity by antisecretory drugs for the treatment of benign gastric ulcer and their corresponding ulcer‐healing rates. For a variety of antisecretory drug regimens, there was a significant correlation between suppression of 24‐h intragastric acidity and ulcer healing rates after 2, 4 and 8 weeks of treatment. There was a lesser degree of correlation between healing and suppression of nocturnal acidity and the association between suppression of acidity and gastric‐ulcer healing rates was less marked than that previously described for duodenal ulcer.
The value of flumazenil in the reversal of midazolam‐induced sedation for upper gastrointestinal endoscopy
Authors: DUNK A. A. , NORTON A. C. , HUDSON M. , DUNDAS C. R. , MOWAT N. ASHLEY G.
Published: July 2010

Fifty patients who underwent diagnostic upper gastrointestinal endoscopy after midazolam sedation were randomized to receive (after completion of the examination) either the benzodiazepine receptor antagonist flumazenil or an identical‐looking placebo. The speed of recovery from sedation was assessed by reaction time testing, measurement of critical flicker fusion frequency, and the semi‐quantitative SOCA scoring system. Measurements were made up to 6 h post examination in all subjects, and at 12 and 24 h in all in‐patients (n= 20). Flumazenil‐treated patients were significantly more alert than those who received placebo at 10 min, 30 min, 1 h and 2 h (P < 0.001 in all instances). Thereafter the two groups were similar. There was no evidence of recurrence of sedation in flumazenil‐treated patients, nor did this drug adversely affect the period of anterograde amnesia between the administration of midazolam and flumazenil.
Rapid intravenous low‐dose diazepam as sedation for upper gastrointestinal endoscopy
Authors: SWAIN D. G. , ELLIS D. J. , BRADBY H.
Published: July 2010

One hundred patients for endoscopy, aged, between 18 and 74 years were randomly allocated to two equal groups. Group A received 10 mg diazepam intravenously rapidly over 2–4 s; Group B received diazepam intravenously over 1–2 min, titrated to provide a satisfactory level of sedation (mean dose 15.9 mg).

Patient co‐operation during endoscopy was similar in both groups, but one patient in Group A developed respiratory depression. Tests of psychomotor function after endoscopy showed greater impairment 30 min following injection for Group B, compared with Group A (P < 0.02).

Total or partial amnesia for endoscopy was present in 62% of Group A, and 90% in Group B (P < 0.005). However, postal follow‐up showed that endoscopy was acceptable to 96% of Group A and 98% of Group B. Delayed sedation later in the day was reported by 26% of Group A compared with 48% of Group B.
Intravenous omeprazole: effect of a loading dose on 24‐h intragastric pH
Authors: ANDERSEN J , STRÖM M. , NÆSDAL J. , LEIRE K. , WALAN A.
Published: July 2010

To determine the effect of three times daily dosing with intravenous omeprazole on intragastric acidity, 24 h intragastric pH was measured continuously with a monocrystalline antimony electrode system in 11 patients with inactive duodenal ulceration during fasting conditions. After a baseline investigation, two different dosage regimens of intravenous omeprazole were compared in a double‐blind crossover study, with regard to their ability to keep the pH ≥ 4 for as long as possible. Success in the individual patient was defined as pH ≥ 4 for at least 90% over the 24‐h period. Two doses of omeprazole [40 mg t.d.s. (120 mg) and 80 mg + 40 mg + 40 mg (160 mg)] were compared.

Omeprazole (120 mg) increased the median of individual median intragastric 24‐h pH from 1.49 to 6.67. The pH was ± 4 for ≥ 90% of the 24 h in three of the 11 patients. With omeprazole, 160 mg (a loading dose of 80 mg), the median of individual median intragastric 24‐h pH increased to 7.33. The pH was ≥ 4 for ≥ 90% of the 24 h in seven of the 11 patients. Median time to reach pH 4 was 39 min after 40 mg and 20 min after 80 mg omeprazole.

An initial loading dose of 80 mg omeprazole seems preferable to 40 mg to achieve a fast and sustained increase in intragastric pH to above 4 in the fasting patient.
Review article: premedication and intravenous sedation for upper gastrointestinal endoscopy
Authors: BELL G. D.
Published: July 2010

Upper gastrointestinal endoscopy can be performed without intravenous sedation but the evidence suggests that, in the United Kingdom and United States, most patients and endoscopists prefer that some form of premedication is given. Intravenous diazepam or midazolam are used by the majority of endoscopists. In the UK, the ratio of diazepam to midazolam users is approximately 2:1, while in the USA more endoscopists are now using midazolam. Midazolam is approximately twice as potent as diazepam but, when allowance is made for this, there is probably little or no difference in the propensity of the two drugs to produce respiratory depression. The antegrade amnesic effect of midazolam is significantly superior to that of diazepam. A benzodiazepine/narcotic combination can achieve a smoother and more rapid induction with less gagging and choking, but the incidence of adverse outcomes—particularly respiratory depression—is increased significantly. Over 50% of the deaths that are associated with upper gastrointestinal endoscopy are due to cardiopulmonary problems. Hypoxia is very common if measured using non‐invasive monitoring equipment, such as a pulse oximeter. Methods of preventing oxygen desaturation and thus, by inference, most cardiac arrhythmias associated with endoscopy are discussed, as is the role of flumazenil, the new benzodiazepine antagonist.
Amino acid tolerance in cirrhotic patients following oral protein and amino acid loads
Authors: MORGAN M. Y. , HAWLEY K. E. , STAMBUK D.
Published: July 2010

Plasma amino acid and venous blood ammonia concentrations were measured in six patients with well‐compensated cirrhosis and in six healthy volunteers, both in the fasting state and serially for 5 h following ingestion of 30 g mixed protein and 30 g amino acid mixture, administered on separate occasions.

Mean fasting plasma concentrations of threonine, serine, proline, glycine, and of the three branched‐chain amino acids, valine, isoleucine and leucine, were significantly reduced in the cirrhotic patients compared with the control subjects, while mean (μ 1 s.d.) fasting venous blood ammonia concentrations were comparable 71.2 ± 31.4 cf. 56.0 ± 25.4 μmol/L

Following the oral protein and amino acid loads, increases were observed in plasma amino acid concentrations in the majority of subjects with a return to baseline values by the end of the study. Changes in the circulating concentrations of most amino acids were independent of their concentration in the oral protein and amino acid loads, and their relative distribution in the circulation varied over time. The increases in the concentrations of the three branched‐chain amino acids did, however, reflect their concentrations in the two nitrogen loads and did remain constant, relative to one another, over time.
Some effects of tripotassium dicitrato bismuthate on gastric secretion and the mucus barrier
Authors: SIDEBOTHAM R. L. , BATTEN J. J. , LI K. , SPENCER J. , BARON J. H.
Published: July 2010

The effect of tripotassium dicitrato bismuthate (De‐Nol) on the breakdown of the gastric mucus barrier was investigated by measuring the output of mucus glycoprotein in pentagastrin‐stimulated secretion from 13 patients before and after treatment for peptic ulcer, and by examining the accumulation of dialysable peptides and amino acids (DPAA) in stimulated secretion from ten of these patients. The accumulation of DPAA was significantly reduced after De‐Nol (by 54%) and to a greater extent than was the output of mucus glycoprotein (by 27%). These observations are consistent with a decrease in the rate of breakdown of the mucus barrier as a result of De‐Nol treatment. De‐Nol significantly reduced pepsin output (by 32%) in the same group of patients. Comparison of the change in pepsin output with the change in accumulation of DPAA in stimulated juice indicated that De‐Nol increases the resistance of the mucus barrier to acid‐pepsin proteolysis and/or inhibits the secretion of amino acids and peptides from gastric mucosa.
The timing of the evening meal affects the pattern of 24‐hour intragastric acidity
Authors: LANZON‐MILLER S. , POUNDER R. E. , MCISAAC R. L. , WOOD J. R.
Published: July 2010

The object of the study was to examine the effect of varying the time of the evening meal on the pattern of 24‐h intragastric acidity. Ten healthy subjects were studied; they ate regular meals throughout the day, but between 17.00 and 21.35 hours were separated into three groups. On three different days each group was fed the same dinner at either 17.15, 19.15, or 21.15 hours (early, standard or late). Variation in the evening meal's time caused significant changes in the pattern of acidity in the afternoon and evening, but did not affect 24‐h intragastric acidity or nocturnal acidity. Integrated afternoon acidity (14.00 hours to dinner) was 69, 169 and 324 mmol. h/L when the subjects ate early, standard and late meals, respectively; evening acidity (dinner to midnight) was 235, 43 and 1 mmol. h/L with the three meals, respectively. The results suggest that, to control intragastric acidity, when the evening meal is eaten early (17.15 hours) dosing with an H2‐antagonist should be after that meal, when eaten at the standard time (19.15 hours) dosing should be at bedtime, but when dinner is late (21.15 hours) the optimal regimen may involve dosing after lunch and also at bedtime.
In‐vivo anti‐reflux and raft properties of alginates
Authors: LAMBERT J. R. , KORMAN M. G. , NICHOLSON LESLEY , CHAN J. G.
Published: July 2010

The comparative efficacy of two alginate‐containing anti‐reflux preparations (Gaviscon, Algicon) was assessed in a single blind crossover study of 20 patients with gastro‐oesophageal reflux disease. The clinical efficacy study was preceded by two studies in healthy volunteers to assess the intragastric effects of Algicon and Gaviscon by pH measurement, endoscopic visualization and gamma scintigraphy.

Algicon and Gaviscon were shown to form a raft in the fasting and fed human stomach, with Algicon alone having a potent antacid effect below and within the raft. Both Algicon and Gaviscon liquids significantly reduced the frequency and severity of reflux symptoms from baseline when given at their recommended doses (10 ml and 20 ml four times daily, respectively). There were no significant differences between Algicon and Gaviscon, although 12 patients preferred Algicon (vs 5 for Gaviscon) for control of reflux symptoms. It was concluded that both Algicon and Gaviscon were effective for the symptomatic control of gastro‐oesophageal reflux disease.
Inhibition of gastrin‐ and histamine‐stimulated gastric acid secretion by gastrin and cholecystokinin antagonists in the rat
Authors: HIRST B. H. , ELLIOTT K. J. , RYDER H. , SZELKE M.
Published: July 2010

The gastric acid inhibitory activities of a peptide‐like gastrin receptor antagonist, Boc‐βAla‐Trp‐Leu‐Asp‐O(CH2)2‐Ph‐4‐F (CH‐486), a non‐peptide gastrin/CCK‐B antagonist (L‐365,260), and a CCK‐A antagonist (L‐364,718), were investigated in the gastric lumen‐perfused anaesthetized rat. A single i.v. injection of CH‐486, 100 μmol/kg, reduced acid secretion stimulated by pentagastrin, 15 μg kg/h, to unstimulated levels, with no recovery within 50 min. Histamine‐, 0.1 μmol kg/min, and carbamylcholine‐, 0.1 mg kg/h, stimulated acid secretion were also reduced to unstimulated levels by CH‐486, 100 μmol/kg, although with these latter two stimulants the inhibition was transient. L‐365,260 and L‐364,718, 10 μmol/kg, significantly inhibited both pentagastrin‐ and histamine‐stimulated acid secretion, the latter again transiently. We conclude that the non‐selective nature of the gastric acid inhibitory activity of gastrin antagonists might allow novel approaches to control gastric acid secretion in peptic ulcer disease.
Comparison of rat and human intestinal perfusion models for assessing efficacy of oral rehydration solutions
Authors: HUNT J. B. , ELLIOTT E. J. , FARTHING M. J. G.
Published: July 2010

The optimal composition for oral rehydration solutions remains controversial. Animal models have been used to assess the efficacy of new formulations but the relevance of these studies to the handling of oral rehydration solutions in human intestine during diarrhoeal disease states remains uncertain. Using steady state perfusion techniques we have compared water and solute transport from a variety of oral rehydration solutions in both the entire rat small intestine and in the human jejunum. Overall the pattern of water, sodium and glucose absorption was similar from the three oral rehydration solutions tested, indicating close parallelism between the two models despite the species and methodological differences. Although the relationship between the findings of these studies to the handling of oral rehydration solution in diarrhoeal disease states remains uncertain, we believe they do support the view that animal models may have a part to play in the preliminary screening of oral rehydration solutions before clinical trial.
Review article: improved preservation of the liver for transplantation
Authors: JAMIESON N. V.
Published: July 2010

This paper reviews the development of the techniques used for liver preservation and describes their clinical use. Recent advances with the introduction of lactobionate based solutions for simple cold storage are described and illustrated by their effect on the Cambridge/King's College Hospital transplant programmes. Better preservation of the liver has simplified the logistics of the transplant procedure, improving organ usage and allowing increased sharing of livers for urgent or paediatric cases.
Nocturnal therapy with famotidine for 1 year is effective in preventing relapse of gastric ulcer
Authors: BERLIN R. G. , ROOT J. K. , COOK T. J.
Published: July 2010

A multicentre, double‐blind, randomized, placebo‐controlled trial was undertaken to investigate the therapeutic efficacy of a nocturnal dose of famotidine 20 mg to reduce the 1 year relapse rate of recently healed gastric ulcers. Twenty investigators in eight countries randomized 202 patients with endoscopically confirmed healed gastric ulcers. Repeat endoscopies were performed at 6 and 12 months or for symptoms compatible with ulcer relapse. A per protocol analysis of cumulative life table relapse at 12 months showed that famotidine 20 mg was superior to placebo in reducing gastric ulcer relapse, 24 versus 50%, respectively (P < 0.01). Both placebo and famotidine were well tolerated. Since nocturnal dosing with famotidine 20 mg is effective in preventing gastric ulcer relapse over a 1‐year period and is well tolerated, it offers a therapeutic option for the long‐term treatment of patients with gastric ulcer.
The effect of ranitidine, cimetidine or famotidine on low‐dose post‐prandial alcohol absorption
Authors: FRASER A. G. , PREWETT E. J. , HUDSON M. , SAWYERR A. M. , ROSALKI S. B. , POUNDER R. E.
Published: July 2010

Plasma alcohol concentration following oral ingestion of 0.3 g/kg of alcohol (ethyl alcohol), one hour after an evening meal, was measured in four groups of 12 healthy subjects. Each group had a control study and a repeat study after 7 days dosing with either placebo or an H2‐receptor antagonist (300 mg ranitidine nocte, 800 mg cimetidine nocte, or 40 mg famotidine nocte). There was no significant difference between the control and post‐dosing studies in the integrated 4‐h plasma alcohol concentration, peak plasma alcohol concentration, or time to reach peak alcohol concentration. This study shows that post‐prandial alcohol absorption after 0.3 g/kg of alcohol is not affected by ranitidine, cimetidine or famotidine.
Hydroxyproline in the oesophageal mucosa of patients with progressive systemic sclerosis during omeprazole‐induced healing of reflux oesophagitis
Authors: HENDEL L.
Published: July 2010

Hydroxyproline concentration in oesophageal mucosal biopsies was used as an index of collagen in an attempt to evaluate the potential for stricture formation in patients with progressive systemic sclerosis. Eight patients suffering from progressive systemic sclerosis with complicating gastro‐oesophageal reflux, 8 patients with idiopathic gastro‐oesophageal reflux, and 7 normal controls were compared. Acid gastro‐oesophageal reflux was assessed with 24‐h pH‐metry; degree of oesophagitis was evaluated both endoscopically and histopathologically. The patients with progressive systemic sclerosis were investigated at the start of the study and later when healing of oesophagitis was accomplished with omeprazole therapy. The hydroxyproline concentration was significantly increased (P < 0.01) in the oesophageal mucosa from patients with progressive systemic sclerosis (median 21.8 nmol/mg) as compared to patients with idiopathic gastro‐oesophageal reflux (median 6.4 nmol/mg) and normal controls (median 8.1 nmol/mg).

Hydroxyproline concentration in oesophageal mucosa from patients with progressive systemic sclerosis decreased significantly and to a normal level (median 6.5 nmol/pg; P= 0.014) when healing of oesophagitis was achieved.
Cisapride in the treatment of post‐operative ileus
Authors: HALLERBÄCK B. , BERGMAN B. , BONG H. , EKSTRÖM P. , GLISE H. , LUNDGREN K. , RISBERG O.
Published: July 2010

The effect of cisapride on duration of post‐operative ileus after surgery was investigated in a randomized, double‐blind, placebo‐controlled study. Patients undergoing elective upper gastrointestinal (n= 47) or colonic (n= 22) surgery were pre‐operatively randomly allocated to treatment with either cisapride 30 mg t.d.s., by rectal administration, or placebo. Treatment started exactly 48 h after surgery if the patient at this time had not passed stool. Time to passage of first stool after surgery was estimated.

Mean time to passage of stool was 85 (32) h (s.d.) for cisapridetreated and 91 (43) h for placebo‐treated patients. No difference between the treatment groups was noted.

Treatment with cisapride did not shorten the duration of postoperative ileus after either upper gastrointestinal or colonic surgery.
The pro‐drug sulindac may reduce the risk of intestinal damage associated with the use of conventional non‐steroidal anti‐inflammatory drugs
Authors: DAVIES G. R. , RAMPTON D. S.
Published: July 2010

To test the hypothesis that administration of a non‐steroidal anti‐inflammatory drug formulated as a pro‐drug, inactive as a cyclooxygenase inhibitor until after absorption, might cause less intestinal damage than conventional non‐steroidal anti‐inflammatory drugs, intestinal permeation to 51Cr‐EDTA and mannitol was assessed in healthy volunteers before and after oral treatment for 1 week with either the pro‐drug sulindac or the conventional non‐steroidal anti‐inflammatory drug indomethacin. Indomethacin, but not sulindac, significantly increased intestinal permeation to 51Cr‐EDTA and reduced haemoglobin and haematocrit; neither affected mannitol permeation.
Effects of ranitidine, given t.d.s., on intragastric and oesophageal pH in patients with gastrooesophageal reflux
Authors: RUSSELL J. , ORR W. C. , WILSON T. , FINN A. L.
Published: July 2010

The purpose of this study was to determine the effects of 150 mg ranitidine, 300 mg ranitidine or placebo, administered every 8 h, on gastro‐oesophageal pH and heartburn parameters in reflux patients. Twelve symptomatic reflux patients received each of the three treatments in a randomized, double‐blind, crossover fashion. Intragastric and oesophageal pH were monitored continuously for a 24 h period. Meals were standardized, consumed at set times and patients were allowed to recline and sleep from 23.00 hours until 06.00 hours only. The gastric record was analysed for the percentage of time that the pH was ≧ 4. The oesophageal record was analysed for acid contact time (percentage time (%) pH ≦ 4.0) and reflux episode frequency. Finally, patients recorded each new episode of heartburn and graded daytime heartburn severity at the end of each hour. Ranitidine increased the median (%) time that the intragastric pH remained at or above 4, from 4.5 (placebo) to 33.9% (150 mg dose) and 33.3% (300 mg dose). Ranitidine dose‐dependently reduced the median 24‐hour oesophageal acid contact time from 13.3% (placebo) to 6.8% (150 mg dose) and 2.5% (300 mg dose). The 300 mg dose significantly reduced daytime heartburn episode frequency and severity while the 150 mg dose reduced heartburn severity only. We conclude that 150 and 300 mg doses of ranitidine administered every 8 h have major, sometimes dose‐dependent effects on the objective parameters and symptoms of gastro‐oesophageal reflux.
Challenges in acid/peptic disorders: a symposium overview
Authors: CLEARFIELD H. R.
Published: July 2010

Before 1977, the treatment of peptic ulcer disease consisted primarily of dietary, antacid, and anticholinergic programmes. There were heated controversies regarding rigid vs. liberal ulcer diets, a variety of antacids and dosing patterns to choose from, and conflicting claims over the benefit of various anticholinergic therapies. It was hoped that the dramatic introduction of the H2‐receptor antagonists would simplify our approach to the treatment of peptic ulcer and reflux oesophagitis. Standard doses of H2‐receptor antagonists are effective for acid/peptic disorders, yet it has become clear that some subsets of patients present special management problems, including recurrent ulcers, non‐steroidal anti‐inflammatory drug (NSAID)‐induced disease, stress ulcers, and refractory oesophagitis. New regimens, such as maintenance therapy and once‐daily nocturnal dosing, have been indicated for peptic ulcer disease. New drugs have been introduced, such as sucralfate, misoprostol, and omeprazole, each with a different mechanism of action. Therefore, while we have learned considerably more about the pathogenesis of peptic disease, treatment decisions have become more complicated.

The Transatlantic Conference on Acid/Peptic Disorders was held on 19 21 January 1990, in Wesley Chapel, Florida. A faculty from the United Kingdom, the United States, and Canada reviewed pathophysiology and the role of pharmacologic agents in the treatment of acid/peptic disorders and outlined clinically useful treatment strategies. The conference was organized into five segments: acid suppression and ulcer healing; acid suppression and control of reflux disease; NSAID‐induced ulceration; stress ulceration, rationale for control of rebleeding, and drug interactions; and controversies. The proceedings of the symposium are presented in this supplement.
Maintenance therapy for peptic ulcer disease
Authors: WORMSLEY K. G.
Published: July 2010

Peptic ulcers tend to recur; recurrence may be associated with an increased risk of potentially lethal complications, such as haemorrhage or perforation. Therapy aims to keep ulcers in remission. Currently, the optimal maintenance therapy is long‐term, continuous administration of antisecretory drugs. More than 80% of patients remain in remission during maintenance therapy. Maintenance therapy may be required for the life of the patient, but it is acceptable to patients and is safe.
Experience with omeprazole in erosive oesophagitis
Authors: ROBINSON M. G. , DECKTOR D. L.
Published: July 2010

Omeprazole is a potent, highly specific, and clinically efficacious antisecretory agent. Current clinical data suggest that omeprazole could be a useful drug in the short‐term treatment of patients with severe erosive oesophagitis resistant to standard H2‐receptor antagonist therapy. The magnitude of omeprazole's eventual role in the treatment of acid secretory‐related disorders will depend on the results of its expanded postmarketing clinical experience and upon resolution of concerns regarding potential adverse effects associated with long‐term administration.