bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of four narcotics on cholecystokinin octapeptide stimulated gallbladder contraction
Authors: HAHN M. , BAKER R. , SULLIVAN S.
Published: July 2010

In an attempt to find the ideal analgesic to treat biliary tract pain we compared the effects of saline and equianalgesic doses of morphine, pentazocine, pethidine, and butorphanol on CCK—OP stimulated gallbladder emptying in healthy volunteers. Morphine produced a profound delay in gallbladder emptying while the other narcotics produced a significant delay in comparison to saline, but less than morphine. None of the drugs affected common bile duct diameter, bilirubin, liver enzymes or amylase. We recommend avoiding the use of morphine in the treatment of biliary and pancreatic pain, but although pethidine, pentazocine and butorphanol may be potentially detrimental we could find no definite superiority of one versus the others.
The effect of nicotine on the delay of gastric emptying
Authors: GRITZ E. R. , IPPOLITI A. , JARVIK M. E. , ROSE J. E. , SHIFFMAN S. , HARRISON A. , VUNAKIS H. VAN
Published: July 2010

The effect of cigarette smoking and its active component, nicotine, on the gastric emptying of solid food was assessed in a randomized double‐blind crossover design. Ten regular smokers were studied after a 6 h fast and least 18 h after their last cigarette. Subjects smoked a total of three high (1.91 mg) or low (0.17 mg) nicotine cigarettes, before and after a technetium‐labelled solid meal and were scanned by gamma camera periodically over a 2‐h period. All calculations of gastric emptying revealed a significant delay after smoking highversuslow nicotine cigarettes in: mean per cent isotope remaining in the stomach at each measurement point from 90–120 min; amount of meal remaining in the stomach at 2 h; and mean time at which 50% of the meal had emptied (T1/2). Delay in gastric emptying was significantly correlated with increase in serum nicotine concentration on the high nicotine day.
Inhibition of intestinal macrophage chemotaxis to leukotriene B4 by sulphasalazine, olsalazine, and 5‐aminosalicylic acid
Authors: NIELSEN O. H. , VERSPAGET H. W. , ELMGREEN J.
Published: July 2010

Purified intestinal macrophages obtained at resections for colonic neoplasms were investigated for chemotaxis to leukotriene B4 (LTB4) by the Millipore filter assay and leading front technique. Possible inhibition by drugs effective in the treatment of chronic inflammatory bowel disease (sulphasalazine, olsalazine, its active moiety 5‐aminosalicylic acid (5‐ASA), and the 5‐ASA metabolite N‐acetylated‐5‐ASA (ac‐5‐ASA)) was tested at therapeutic colonic concentrations of 0.01–10 mm. Leukotriene B4 at a dose of 10 nm was equipotent with casein (5 g litre—1) as regards chemoattraction of macrophages. Sulphasalazine, olsalazine and 5‐ASA were potent inhibitors of macrophages chemotaxis to LTB4 with IC50 values of 0.43, 0.39 and 0.24 mm, respectively. These concentrations are below the lowest concentration of 5—ASA (2 mm) in the colonic lumen during conventional sulphasalazine treatment of patients with chronic inflammatory bowel disease. The inhibition of macrophage chemotaxis by these drugs may be important for this limitation of the local inflammatory process in chronic inflammatory bowel disease, and may in part explain the beneficial effect of systemic and local treatment with sulphasalazine. Leukotriene B4 appears to be an important inflammatory mediator for the activation of macrophages in colonic inflammation.
Dose—response effect of famotidine on patterns of gastro‐oesophageal reflux
Authors: ORR W. C. , ROBINSON M. G. , HUMPHRIES T. J. , ANTONELLO J. , CAGLIOLA A.
Published: July 2010

The present study attempts to assess the alteration in patterns of gastro‐oesophageal reflux as assessed by 24‐h oesophageal pH monitoring by varying degrees of H2‐receptor blockade with famotidine. Subjects were 12 patients with complaints of daily heartburn who demonstrated at least 6% of acid mucosal contact time by 24‐h ambulatory oesophageal pH monitoring. All subjects had a positive Bernstein test, and nine of the 12 subjects had erosive oesophagitis. The study was conducted as a double‐blind crossover design utilizing 40 mg nocte, 20 mg b.d., and 40 mg b.d. and placebo treatments. Results indicated that all treatments significantly reduced the 24‐h percentage acid contact time (P < 0.05) compared to placebo. The two b.d. treatment regimens also significantly (P < 0.05) reduced the number of episodes lasting longer than 5 min. Only the b.d. regimens successfully lowered the percentage of upright acid exposure. All treatments significantly (P < 0.01) reduced the percentage of supine acid contact time, as well as the number of episodes lasting more than 5 min. It is concluded that gastro‐oesophageal reflux disease may well require a b.d. dosing regimen with farnotidine in order to achieve optimal mucosal healing and day time symptom control.
Successful treatment of a VIPoma by continuous subcutaneous infusion of somatostatin analogue (SMS 201‐995)
Authors: NIITSU Y. , GOTO Y. , MAEDA M. , TSUSHIMA N. , WATANABE N. , KOHGO Y. , URUSHIZAKI I.
Published: July 2010

A case with WDHA syndrome due to VIPoma is reported. Injection of somatostatin analogue SMS 201‐995 was followed by prompt suppression of vasoactive intestinal polypeptide levels (VIP), decreased stool volume, and restoration of the serum potassium concentration to normal. Long‐term treatment with SMS 201‐995 for up to 20 weeks produced excellent clinical control and a decrease in tumour size. No adverse effects were noted except for localized pain at the site of injection. This was overcome by using a continuous subcutaneous infusion pump which also enabled the effective daily dosage to be reduced and thereby adverse reactions to be avoided.
No correlation between indomethacin‐induced gastroduodenal damage and inhibition of gastric prostanoid synthesis
Authors: GOLDIN E. , STALNIKOWICZ R. , WENGROWER D. , ELIAKIM R. , FICH A. , LIGUMSKY M. , KARMELI F. , RACHMILEWITZ D.
Published: July 2010

The effect of 1 week of treatment with indomethacin 150 mg/day on human gastric prostanoid synthesis was correlated with its effect on gastric and duodenal mucosa. Before and following 1 week of treatment, endoscopic appearance of the mucosa was evaluated and scored. Following 1 week of treatment with indomethacin, antral PGE2 and 6‐keto‐PGF1α were significantly lower than in normal subjects, but similar in patients with significant or with no mucosal damage. Co‐treatment with ranitidine 150 mg b.d. or with cimetidine 400 mg b.d. reduced the mean mucosal damage score but did not affect gastric prostanoid synthesis, which was similar irrespective of the presence or absence of mucosal damage. It is therefore suggested that there is no correlation between indomethacin‐induced inhibition of gastric prostanoid synthesis and its induction of mucosal damage.
Comparative irritancy of oxaprozin on the gastrointestinal tract of rats and mice: relationship to drug uptake and effects in vivo on eicosanoid metabolism
Authors: RAINSFORD K. D.
Published: July 2010

Studies were performed in rats and mice to investigate the mechanisms of the comparatively low irritancy in the gastrointestinal (GI) tract of oxaprozin, relative to that of other non‐steroidal anti‐inflammatory drugs. A single dose of oxaprozin (100 mg/kg), given orally to rats, reduced the concentration of prostaglandin E2, but did not produce any gastric lesions or mucosal irritation, either visibly or when the mucosa was examined by scanning or transmission electronmicroscopy. The low gastric irritancy was reflected by lower concentrations of the drug in the gastric mucosa, compared with those in the upper intestinal tract, following oral administration of 100 mg/kg of [14C]oxaprozin. This distribution of the drug in the gastrointestinal tract reflected the absence of gastric irritancy when the drug was given repeatedly for 5 days by the oral route to rats. It was only after intraperitoneal administration of high doses of the drug that intestinal ulcers and peritonitis became evident, and then no gastric irritancy was observed. As with other non‐steroidal anti‐inflammatory drugs, there was some, but appreciably less, enhancement of gastric irritancy observed when the drug was given to mice treated with the cholinomimetic, bethanechol chloride (to enhance secretion of acid and pepsin). It is suggested that the inhibition of mucosal prostaglandin production by oxaprozin may be considered a ‘priming’ reaction, and that subsequent enhancement of irritancy occurs by stimulation of acid and pepsin. Structure—activity relationships of oxaprozin analogues were studied. The addition of electron‐withdrawing substituents, which markedly enhance the gastric ulcerogenic effects of other non‐steroidal anti‐inflammatory drugs, only slightly enhanced the irritancy of oxaprozin, thus providing further evidence for the inherent low ulcerogenicity of this molecule.
Treatment of steatorrhoea in cystic fibrosis: a comparison of enteric‐coated microspheres of pancreatin versus non‐enteric‐coated pancreatin and adjuvant cimetidine
Authors: STEAD R. J. , SKYPALA I. , HUDSON M. E.
Published: July 2010

Enteric‐coated microspheres of pancreatin were compared with non‐enteric‐coated pancreatin combined with cimetidine taken 40 min before meals in the treatment of patients with cystic fibrosis. Fourteen adults with steatorrhoea due to cystic fibrosis were investigated in an open, randomized crossover study, over two consecutive 28‐day treatment periods. Lipase intake was adjusted to each patient's previous requirements and was the same during both months; they were instructed to continue with their normal diet. Patients collected faeces for 72 h at the end of each month and completed diary cards daily throughout. Bowel actions were less frequent on enteric‐coated microspheres of pancreatin than on non‐enteric‐coated pancreatin/cimetidine (1.7 vs. 2.4/day; P < 0.001) and stool character was improved (P < 0.001). Mean daily faecal weight was similar on enteric‐coated microspheres of pancreatin to that on the combination (254 g vs. 291 g; N.S.), whereas daily faecal fat excretion tended to be less on enteric‐coated microspheres of pancreatin (21 g vs. 27 g; N.S.), and percentage fat absorption tended to be greater (81%vs. 73%; N.S.). Mean body weight increased by 0.3 kg on enteric‐coated microspheres of pancreatin and fell by 0.1 kg on the combination (N.S.). These data indicate that enteric‐coated microspheres of pancreatin are at least as effective as non‐enteric‐coated pancreatin with cimetidine in the treatment of steatorrhoea in cystic fibrosis.
Loss of predictive value of gastric ulcer symptoms in a randomized treatment trial
Authors: FEURLE G. E. , BRÖKER H.‐J. , BLUM A. L.
Published: July 2010

Analysis of clinical data obtained in a double‐blind randomized study, which compared liquid antacid (neutralizing capacity 120 mmol per day) with 1 g cimetidine in the treatment of 125 patients with gastric ulcer, revealed that, before starting treatment 71 % of the patients complained of epigastric pain, approximately 50% of bloating, and approximately 30 % of nausea, heartburn, constipation or vomiting.

Epigastric pain before treatment was significantly more frequent in patients with large ulcers (P < 0.05) and in patients with ulcers unhealed after 4 weeks of therapy (P < 0.05). This finding was the result of a highly significant correlation between diurnal epigastric pain and ulcer size and delayed healing (P < 0.005). Nocturnal pain did not correlate with prognosis.

In contrast to this correlation between pain before therapy and healing, the disappearance of epigastric pain with therapy did not signify ulcer healing. Only 14 (38%) of the 37 patients with healed ulcer were free from pain after the 4 weeks of therapy, whereas 25 (49%) of the 52 patients with persistent ulcers had no pain at this time. Placebo pain tablets relieved ulcer pain effectively in more than 85% of the patients, irrespective of whether the ulcer was healing or not. The other symptoms (bloating, nausea, heartburn, constipation or vomiting) were also alleviated by 4 weeks of therapy but no correlation was found with ulcer size or prognosis.

The loss of the prognostic significance of ulcer pain is probably due to a complex interaction of the trial schedule on the patient's level of consciousness. The highly effective placebo pain tablets and improvement of symptoms, which are unlikely to be due to gastric ulcer symptoms that are also unlikely to be affected by a decrease in gastric acidity such as bloating and constipation), suggest that ulcer treatment in a controlled trial changes pain perception. We conclude that treatment trials have effects that go beyond the rates of healing.
Meta‐analysis of randomized controlled trials as a method of estimating rare complications of non‐steroidal anti‐inflammatory drug therapy
Authors: CHALMERS T.C. , BERRIER J. , HEWITT P. , BERLIN J. , REITMAN D. , NAGALINGAM R. , SACKS H.
Published: July 2010

The design of randomized controlled trials to assess the efficacy of pharmacological measures for the prevention of the gastrointestinal side‐effects of anti‐inflammatory drugs requires an accurate estimate of excess risk under controlled conditions. Photocopies of 952 randomized controlled trial publications were obtained after scanning titles and abstracts of a MEDLINE computer search, 427 were excluded for obvious reasons, and 525 were again photocopied after obliterating source and results. Selection criteria were: the presence of a non‐anti‐inflammatory drug control group; at least 4 days of therapy; at least 3 days without anti‐inflammatory drugs before randomization; no complicating background drugs; mention of side‐effects; and a clear differentiation of gastrointestinal complications. Observer error, with two independent readings, for inclusion suitability in the study was 19% for Methods and 9% for Results. For the 44 aspirin trials, the mean therapy duration was 357 days; the unweighted rate difference between therapy and control groups (± 1 S.E.M.) for ulcer was 0.006 ± 0.003, for gross haemorrhage 0.006 ± 0.002 and for unspecified gastric symptoms 0.03 ± 0.01. In 123 non‐aspirin non‐steroidal anti‐inflammatory drug (NA—NSAID) trials, the mean duration was 67 days; the unweighted rate difference for ulcer was 0.0005 ± 0.0003, for gross haemorrhage 0.007 ± 0.004 and for unspecified gastric symptoms 0.02 ± 0.005. Risk differences were also pooled using the DerSimonian and Laird method, which weights studies inversely according to variance. Using this method, only the unspecified gastric symptoms for non‐aspirin non‐steroidal anti‐inflammatory drugs (NA—NSAIDs) and the haemorrhage for aspirin were found to be statistically significant. Longer studies have higher risk differences. Randomized control trials to determine prophylactic efficacy against haemorrhage (that is, to demonstrate a reduction of ulcer rate in the therapy group to the rate of controls) would require 190 patients in each group for NA—NSAIDs in studies of 2–6 months; 950 subjects would be needed to detect a 50% reduction. Randomized control trials to determine a reduction in ulcer rate to that of controls in patients on aspirin for more than 6 months would require 700 subjects in each group; 3346 subjects would be needed to detect a 50% reduction. Such studies are feasible.
Ulcer and ulcer complications from non‐steroidal anti‐inflammatory drugs: what is the risk?
Authors: LANGMAN M. J. S.
Published: July 2010

Gastroenterologists believe that non‐steroidal anti‐inflammatory drugs (NSAIDs) cause dyspepsia, may cause ulcers to developde novoand cause ulcer bleeding and perforation. Regulatory authorities are aware that NSAID‐associated adverse events are reported more often than for any other drug class, and that gastrointestinal events are most common and often serious. A case‐control study in the UK indicates that those who use NSAIDs may be between two and four times as liable to gastrointestinal bleeding and probably perforation as non‐users, particularly if elderly. It has further been suggested that the chances of dying of ulcer complications are very high in NSAID users. By contrast, studies in the USA conducted prospectively and post‐marketing surveillance in the UK have appeared to show little risk. Differences may be partially, if not completely, explained by the variable methodologies employed. Dispute also exists about the rank order and significance of toxic effects among the various agents.
Treatment of endoscopy‐negative NSAID‐induced upper gastrointestinal symptoms with cimetidine: an international multicentre collaborative study
Authors: BIJLSMA J.W.J.
Published: July 2010

In this double‐blind multicentre trial, 127 patients on non‐steroidal anti‐inflammatory drugs (NSAIDs) who experienced gastrointestinal symptoms significant enough to warrant endoscopic evaluation, but without endoscopic evidence of mucosal damage, were randomized to receive cimetidine 400 mg b.d. or placebo for 4 weeks. Non‐steroidal anti‐inflammatory drug therapy was maintained at pre‐trial doses for the duration of the study. After 4 weeks, 72 % of cimetidine‐treated patients experienced complete symptom resolution, as defined by a global symptom score of zero, compared with 49% on placebo. Complete disappearance of upper abdominal pain was achieved in 72 % of the cimetidine‐treated patients as opposed to 47% on placebo. Relief of heartburn was experienced by 87 % of patients on cimetidine compared with 60 % on placebo. Throughout treatment, the proportion of cimetidine‐treated patients with nausea was consistently lower than in patients on placebo, while the two groups were similar with respect to disappearance of vomiting. At the completion of acute treatment, 27% of placebo‐treated patients but only 12% of those on cimetidine were ineligible to continue maintenance due to persisting gastrointestinal symptoms. Patients who were symptom‐free and required continuation of NSAID therapy were followed for 6 months during which they were re‐randomized to receive cimetidine 400 mg nocte or placebo. Of the 105 patients included in this maintenance treatment phase of the study, 11% of the cimetidine‐treated patients and 10% of those on placebo experienced relapse of symptoms. However, the mean time to relapse was 120 days with cimetidine compared with 35 days with placebo. The results of this study indicate that cimetidine is effective in the treatment of endoscopy‐negative NSAID‐induced GI symptoms, specifically pain and heartburn, in patients continuing NSAID therapy.
Surgery in the management of the gastric side‐effects of NSAIDs
Authors: VENABLES C. W.
Published: July 2010

It is now accepted that the administration of non‐steroidal anti‐inflammatory drugs (NSAIDs) can result in peptic ulceration. Not infrequently, the first presentation of the ulcer is as a life‐threatening complication such as a perforation or gastrointestinal bleed. Surgeons often become involved in management when one of these complications occurs. This paper discusses the ways in which NSAID‐induced peptic ulceration may present to the surgeon and the special features that distinguish patients with NSAID‐induced ulcers from the remainder of patients with peptic ulcer disease. It is pointed out how little has been written on the surgical management of this group of patients. The importance of the overall assessment of these patients, with the correction of nutritional deficiencies and the use of appropriate prophylactic therapeutic measures in their surgical management, is stressed. The criteria for determining what surgical procedure is used and results are described.
Cost of treating arthritis and NSAID‐related gastrointestinal side‐effects
Authors: BLOOM B. S.
Published: July 2010

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are efficacious in the treatment of arthritis. However, side‐effects particularly gastrointestinal toxicity, have been well documented with their use. Thus, in assessing total direct medical costs in the treatment of arthritis, the expenses involved in treating these side‐effects must be taken into account. A retrospective analysis was undertaken of all direct medical costs related to care of a group of Medicaid recipients treated for arthritis during a 2‐year period. Data were obtained from the Medicaid Management Information System of Washington, D.C., USA. The actual expenditure of treating arthritis as well as the medical costs of associated NSAID‐induced gastrointestinal side‐effects were determined. Arthritis treatment costs per quarter were found to be $145 per patient. Approximately 25 % of the population experienced NSAID‐related gastrointestinal side‐effects requiring further medical care. Treatment of these adverse effects cost an additional $66 per quarter per patient, thus adding 45.5% to the cost of arthritis treatment. Pharmaceutical claims comprised 42.4% of total adverse drug reaction treatment costs, while the few hospital claims accounted for 37.9% and physician charges 19.7%. It has been estimated that in 1983 direct medical costs of arthritis treatment in the USA was $8.6 billion. By extrapolating the costs in this study, it can be estimated that a further $3.9 billion was spent on treating gastrointestinal side‐effects of NSAIDs, making a total of $12.5 billion.
Effect of the bile‐acid sequestrant colestipol on postprandial serum bile‐acid concentration: evaluation by bioluminescent enzymic analysis
Authors: ROSSI S. S. , WAYNE M. L. , SMITH R. B. , WRIGHT C. E. , ANDREADIS N. A. , HOFMANN A. F.
Published: July 2010

Chronic ingestion of bile‐acid sequestrants has been shown to decrease the serum cholesterol concentration and coronary events in hypercholesterolaemic patients. To develop improved sequestrants, a rapid, convenient method for testing the bile‐acid binding efficacy of sequestrants is needed. Serum bile‐acid concentrations could be used to detect bile‐acid binding by an administered sequestrant, since the serum bile‐acid concentration is determined largely by the rate of intestinal absorption in healthy individuals. To test this, serum bile‐acid concentrations were measured at frequent intervals over 24 h in five otherwise healthy hypercholesterolaemic subjects during the ingestion of three standard meals, with or without the addition of 5 g colestipol granules administered 30 min before each meal.

Total serum bile‐acid concentration was measured with a previously reported bioluminescent enzymic assay, that uses a 3α‐hydroxysteroid dehydrogenase, an oxido‐reductase, and a bacterial luciferase co‐immobilized on to Sepharose beads. Bile acids in 1 ml of serum were isolated by solid‐phase extraction chromatography with reversed‐phase C18 cartridges.
Symptom relief and duodenal ulcer healing with omeprazole or cimetidine
Authors: CROWE J. P. , WILKINSON S. P. , BATE C. M. , WILLOUGHBY C. P. , PEERS E. M. , RICHARDSON P. D. I. ,   OPUS (OMEPRAZOLE PEPTIC ULCER STUDY) RESEARCI GROUP
Published: July 2010

In a double‐blind parallel‐group study, 98 patients with symptomatic duodenal ulcer received omeprazole 20 mg o.m. and 91 cimetidine 800 mg nocte for 2 or, if then not healed, 4 weeks. After 2 weeks the healing rates on an intention‐to‐treat basis were: for omeprazole 62% and for cimetidine 33% (P < 0.001), and at 4 weeks 85% and 61%, respectively (P < 0.001). The proportions symptom‐free at 2 weeks were 83% of the omeprazole and 63% of the cimetidine‐group (P < 0.01) and at 4 weeks 84% and 72% (P= 0.01). Patients receiving omeprazole took fewer antacid tablets than those receiving cimetidine. Patient tolerance of both drugs was similar and good. In the treatment of duodenal ulcer, omeprazole 20 mg o.m. gives faster symptom relief than cimetidine 800 mg nocte, as well as healing a greater proportion of ulcers within 2 and 4 weeks.
A multicentre, randomized, double‐blind study comparing nocte famotidine or ranitidine for the treatment of active duodenal ulceration
Authors: SANTAELLA R. ALCALÁ , GUARDIA J. , PAJARES J. , PIQUÉ J. , PITA L. , ALVÁREZ E. , CASTELLANOS P. , GUARNER L. , ORTIZ J. , PESQUERA R. , VARGAS V. , RUIZ‐CAPELLÁN R.
Published: July 2010

The efficacy and safety of famotidine and ranitidine in the treatment of active duodenal ulcer were compared in a multicentre, randomized, double‐blind study. The study was carried out in five centres which included a total of 143 patients with endoscopically documented active duodenal ulcer. The patients received either famotidine (one tablet of 40 mg at night) or ranitidine (two tablets of 150 mg at night). Endoscopic examinations were performed at 4 and 6 weeks of active treatment. Daytime and nocturnal pain were also monitored, and the laboratory and clinical profiles evaluated. One hundred and thirty‐three patients fulfilled the evaluation criteria (66 patients in the famotidine group and 67 in the ranitidine group). Healing rates at 4 or 6 weeks of treatment showed no significant differences between the famotidine and ranitidine groups. The healing rates were 80% at week 4 and 97% at week 6 in the famotidine group, and 77% at week 4 and 96% at week 6 in the ranitidine group. Similar results were observed in both treatment groups with regard to pain resolution, decrease in antacid intake and safety profile.
Acute treatment of reflux oesophagitis: a multicentre study to compare 150 mg ranitidine twice daily with 300 mg ranitidine at bedtime
Authors: HALVORSEN L. , LEE F. I. , WESDORP I. C. E. , JOHNSON N. J. , MILLS J. G. , WOOD J. R.
Published: July 2010

A randomized, double‐blind, clinical trial was undertaken to compare 150 mg ranitidine b.d. with 300 mg ranitidine nocte in the treatment of reflux oesophagitis. Endoscopy data were evaluable for 336 patients after 8 weeks of treatment. At this time 75% of patients who received 150 mg ranitidine b.d., and 73% of those who received 300 mg nocte, had healed or showed endoscopic improvement to grade I oesophagitis. At 12 weeks these rates had increased to 89 and 88%, respectively. Oesophageal biopsies from 258 patients at 8 weeks showed histological improvement in 44 and 47% of those treated with 150 mg ranitidine b.d. and 300 mg ranitidine nocte, respectively. After 12 weeks histological improvement was apparent in 57 and 54% of biopsies from each group, respectively. Symptom severity and frequency was reduced to a similar extent by both treatments. Adverse events were reported by 15 patients. A 300–mg bedtime dose of ranitidine was found to be a well‐tolerated, effective alternative to twice daily treatment in reflux oesophagitis.
Human gastric acid secretion following repeated doses of AG‐1749
Authors: MÜLLER P. , DAMMANN H. G. , LEUCHT U. , SIMON B.
Published: July 2010

The effect of increasing doses (15 mg, 30 mg and 60 mg) of the substituted benzimidazole, AG‐1749, on gastric acid secretion and fasting serum gastrin concentration has been studied after repeated administration to healthy volunteers.

AG‐1749 produced a dose‐dependent and profound decrease in basal and stimulated gastric acid secretion in all volunteers, with almost total suppression at the highest dose. The extent of inhibition increased between Day 2 and Day 8 with the 15 and 30 mg doses of AG‐1749. The inhibitory effect of AG‐1749 appears to be fully reversible as control levels of acid output were reached 7 days after drug withdrawal.

Seven days’dosing with 60 mg AG‐1749 induced a more than threefold increment of fasting serum gastrin concentration, but this increase was still within the normal range. Seven days after cessation of dosing, fasting serum gastrin concentration returned to a pre‐dose level.
A single night‐time dose of famotidine is equivalent to ranitidine in decreasing 24‐hour gastric acidity in asymptomatic duodenal ulcer subjects
Authors: THOMSON A. B. R. , PINCHBECK B. R. , KIRDEIKIS J. , ZUK L. , MARRIAGE B. , PRAT A.
Published: July 2010

Six asymptomatic, non‐smoking men with endoscopically proven duodenal ulcer disease received single nocturnal doses of placebo, 40 mg famotidine and 300 mg ranitidine each for 1 week prior to serial measurement of pH, peptic activity and serum gastrin concentrations over 24 h and of acid output. The intragastric pH fluctuated between 1.53 and 5.07 when subjects were given placebo but within 2 h of taking famotidine or ranitidine it rose to 5.57 or higher; the effect lasted for 12 h from midnight. Peptic activity fell during famotidine and ranitidine treatment and the decline was somewhat greater 8–15 h after using famotidine. Serum gastrin levels did not change materially with any treatment. The study shows the equivalent effect of standard bed‐time doses of famotidine and ranitidine on intragastric pH, acid output and serum gastrin concentrations in asymptomatic men with duodenal ulcer disease.
Evaluation of three oral rehydration solutions designed for use in developed communities
Authors: ELLIOTT E. J. , FERREIRA R. M. DA CUNHA , CAMERON D. , FARTHING M. J. G. , WALKER‐SMITH J. A.
Published: July 2010

One hundred and sixteen children (less than 2 years old) admitted to a London hospital with acute gastroenteritis were randomized to receive either an oral rehydration solution (ORS) with low sodium and high glucose concentration (Na+ 35, glucose 200 mmol/L), an ORS with a high sodium but low glucose concentration (Na+ 60, glucose 111 mmol/L), or an ORS containing glycine and a glucose polymer (Na+ 50, glucose 50, glycine 50 mmol/L). Clinical, biochemical and haematological features of the three groups were similar on admission. Rotavirus was common (31%); the majority of children had minimal dehydration or acid–base disturbance.

The clinical outcome, including ORS intake, prevention of dehydration, rehydration, and duration of hospital stay was similar in the three treatment groups. All initial electrolyte abnormalities were corrected; no child developed hypernatraemia or hyponatraemia. At 24 h, the mean serum urea was higher in those who received the ORS containing glycine than in other groups, and it had not fallen significantly since admission. Eighteen per cent of children had carbohydrate intolerance : four children with ≥2% reducing substances in their stool had all received ORS with a high glucose content and had numerous watery green stools containing rotavirus.

All ORS solutions were safe and effective for rehydration and correction of biochemical abnormalities, however carbohydrate intolerance was more prevalent in children who received the ORS with a high glucose content.
Comparison between single morning and bedtime doses of 40 mg famotidine for the treatment of duodenal ulcer
Authors: DE PRETIS G. , DOBRILLA G. , FERRARI A. , FONTANA G. , MAIOLO P. , MARENCO G. , MENARDO G. , PALLINI P. , ROSSINI F. P. , SAGGIORO A.
Published: July 2010

The aim of this study was to compare the duodenal ulcer healing effects of morning (08.00 hours) vs. single bedtime (22.00 hours) doses of 40 mg famotidine, bearing in mind that the known efficacy of bedtime doses of H2–antagonists is regarded as evidence of the predominance of nocturnal gastric acidity in the pathogenesis of duodenal ulcer.

This randomized double‐blind multicentre trial was conducted in a total of 127 patients with endoscopically proven active duodenal ulcer. Nine patients dropped out and thus 118 were included in the final analysis. The duration of treatment was 4 weeks, and this was extended to 8 weeks in patients whose ulcers failed to heal by week 4. The patients in the two treatment groups were well matched for age and sex.

The therapeutic efficacy parameters were endoscopic healing of the ulcer lesion and disappearance of pain. Results were compared using the χ‐square method.

The 4–and 8–week (cumulative) ulcer healing rates in the patients treated with the morning dose of famotidine were 77.2% and 86%, respectively, compared with 78.6% and 91.8% in those who received the bedtime dose. The differences failed to prove statistically significant either at week 4 (P= 0.85) or at week 8 (P= 0.31). The percentages of patients with ulcer pain, evaluated weekly, were similar in the two treatment groups.

The equivalent efficacy of the morning and bedtime famotidine regimens raises doubts concerning the predominance of nocturnal gastric acidity in the pathogenesis of duodenal ulcer.
Quadruple antimycobacterial chemotherapy in Crohn's disease: results at 9 months of a pilot study in 20 patients
Authors: HAMPSON S. J. , PARKER M. C. , SAVERYMUTTU S. H. , JOSEPH A. E. , MCFADDEN J.‐J. P. , HERMON‐TAYLOR J.
Published: July 2010

Twenty patients with active Crohn's disease, the majority refractory to conventional therapy, were treated with rifampicin, ethambutol, isoniazid, and pyrazinamide or clofazamine for 9 months. After this period, 10 were in remission (Crohn's disease activity index < 150). Of the 10 not in remission, three had been at 6 months, but had relapsed on treatment. Nine of 10 patients on steroids at the beginning were off steroids at 9 months. Six patients came to surgery during the period, five for stricture formation without evidence of florid Crohn's disease outside the strictured segment. Three young patients with severe Crohn's disease facing total colectomy were spared surgery. No serious drug‐related side‐effects were encountered. The results of this pilot study suggest that controlled trials of antimycobacterial chemotherapy, using four or more of the best agents available, are worthy of assessment in Crohn's disease.
Repeated high oral doses of omeprazole do not affect intrinsic factor secretion: proof of a selective mode of action*
Authors: FESTEN H. P. M. , TUYNMAN H. A. R. E. , DEN HOLLANDER W. , MEUWISSEN S. G. M.
Published: July 2010

The effect of 60 mg oral omeprazole daily for 9 days on intrinsic factor and gastric acid secretion was studied in eight healthy volunteers. Gastric secretion studies were performed during saline and 0.1 M HCl perfusion before and after omeprazole administration. During dosing with omeprazole, basal gastric acid output diminished by 94%, and pentagastrin‐stimulated acid output by 97%. Basal, peak and steady‐state stimulated intrinsic factor output were unaffected by omeprazole. It is concluded that high oral doses of omeprazole suppress gastric acid secretion to very low levels but they do not affect intrinsic factor secretion. Intrinsic factor secretion was also unaffected by profound hypochlorhydria.
Omeprazole (20 mg o.m.) versus ranitidine (150 mg b.d.) in duodenal ulcer healing and pain relief
Authors: MULDER C J. J. , TIJTGAT G. N. J. , CLUYSENAER O. J. J. , NICOLAI J. J. , MEYER W. W. , HAZENBERG B. P. , VOGTEN A. J. M. , GERRITS C. , STUIFBERGEN W. H. N. N.
Published: July 2010

The object of this double‐blind, multicentre study was to compare duodenal ulcer healing rates after 2 and 4 weeks of treatment with either 20 mg omeprazole o.m. or 150 mg ranitidine b.d. One hundred and eighty‐one patients were randomized: 91 received omeprazole and 90 received ranitidine.

In a per protocol analysis at 2 weeks, 63% of the patients were healed on omeprazole and 65% of the patients were healed on ranitidine (N.S.); at 4 weeks 91% were healed in the omeprazole group and 96% were healed in the ranitidine group. There were no differences in ulcer symptom relief between the two groups. There were no significant changes in laboratory values in either of the groups. Adverse events were few and mainly mild and transient.

We conclude that both omeprazole (20 mg o.m.) and ranitidine (150 mg b.d.) result in rapid, ulcer healing rates.
Effects of the glucosidase inhibitor acarbose in patients with liver cirrhosis
Authors: ZILLIKENS M. C. , SWART G. R. , VAN DEN BERG J. W. O. , WILSON J. H. P.
Published: July 2010

In this preliminary study, we examined the effects of acarbose and placebo together with a standardized breakfast on blood glucose levels, on breath hydrogen excretion and on plasma insulin and glucagon levels, in addition, the effects on fasting blood levels of metabolites were studied following an evening meal with acarbose or placebo. Acarbose significantly reduced blood glucose levels in 10 patients with alcoholic cirrhosis following a meal containing 100 g of carbohydrate. There were no significant changes in plasma insulin after breakfast but glucagon levels were increased at 1 h after the meal. Breath hydrogen excretion did not change significantly. Acarbose given with a late evening snack reduced fasting β‐hydroxybutyrate levels the next morning in these cirrhotic patients.
The effect of cisapride on defaecation in normal human subjects—lack of effect on faecal excretion of water, fat, and bile acids
Authors: BERGER V. , ARMBRECHT U. , HEUSINGER A. , WIENBECK M. , STOCKBRÜGGER R.
Published: July 2010

In order to elucidate whether or not the increased stool frequency that occurs during cisapride treatment is a result of malabsorption of water, fat, and bile acids, 12 healthy volunteers were dosed with either tablets of placebo q.d.s. or tablets of 10 mg cisapride q.d.s. during two periods of 5 days in a double‐blind, crossover study.

Stool frequency, stool consistency, and side‐effects were recorded each day. Total faecal mass, faecal water content, and faecal excretion of fat and bile acids were determined during the last 72 h of each study period.

Mean daily stool frequency was 18.8% higher during cisapride [1.68 ± 0.12 (S.E.M.)] administration than during placebo (1.42 ± 0.12); P= 0.038. The stool consistency score increased by 11.8% towards softer stools during cisapride dosing (N.S.). There were no significant differences in total faecal mass (placebo 399.4 g/72 h; cisapride; 414.5 g/72 h), faecal water content (placebo; 75.6%: cisapride 76.2%), or faecal excretion of fat (placebo; 12.7 g/72 h: cisapride; 11.6 g/72 h) and total bile acids (placebo; 2212 μmol/72 h: cisapride; 2261 μmol/72 h). The side‐effects reported during placebo were constipation (n = 3), and during cisapride meteorism (n = 4) and increased appetite (n = 2).

The increased stool frequency during cisapride treatment is not caused by malabsorption of water, fat, or bile acids, but seems to be the consequence of a direct motor effect.
Safety and efficacy of acetarsol suppositories in unresponsive proctitis
Authors: FORBES A. , BRITTON T. C. , HOUSE I. M. , GAZZARD B. G.
Published: July 2010

In a prospective open study, 10 patients with intractable proctitis were treated with acetarsol suppositories (250 mg b.d. for 4 weeks) and were monitored clinically, biochemically and toxicologically.

Proctitis resolved symptomatically and sigmoidoscopically within 2 weeks in nine patients; one patient was unaffected. The only side‐effect was of transient thrombocytosis in a single patient. Maximal blood and urinary arsenic concentrations occurred after 1 week's treatment with a total inorganic arsenic in the hazardous range in six patients; subsequent concentrations fell despite continuing therapy and at 4 weeks potentially hazardous values persisted in only two patients. Continued renal excretion and diminished absorption across an improved rectal mucosa is thought to be responsible for this paradox. Arsenic levels fell rapidly when acetarsol was withdrawn and were indistinguishable from pretreatment values within 4 weeks.

Short‐term acetarsol therapy offers a useful additional measure when local steroids have failed to control ulcerative proctitis; it appears to be safe and formal controlled comparisons with other therapeutic options are therefore legitimate.
The effect of SK&F 94482 (BMY‐25368) on 24‐hour intragastric acidity and plasma gastrin concentration in healthy subjects
Authors: GAVEY C. J. , SMITH J. T. L. , NWOKOLO C. U. , POUNDER R. E.
Published: July 2010

In a double‐blind, placebo‐controlled study of SK&F 94482 (BMY‐25368) (400‐mg, post‐evening meal, for 7 days in 11 healthy subjects), there was a significant 75% decrease in median integrated 24‐h intragastric acidity during dosing with the drug (218 mmol h/L) compared with placebo (883 mmol h/L; P= 0.003). The single daily dose of 400 mg SK&F 94482 decreased median hourly intragastric acidity until the time of the next dose 24 h later. There was also a sustained and significant 80% rise in median 24‐h integrated plasma‐gastrin concentration during dosing with SK&F 94482 (364 pmol h/L) when compared with placebo (202 pmol h/L; P= 0.003). The study demonstrates a significant inverse correlation between 24‐h integrated intragastric acidity and 24‐h plasma gastrin concentration (rs=−0.484; P < 0.001).

The study shows that a single oral daily dose of an H2‐antagonist can provide control of intragastric acidity throughout the day and night, decreased acidity being associated with statistically significantly, but modestly elevated plasma‐gastrin levels.
Efficacy of a standard United Kingdom oral rehydration solution (ORS) and a hypotonic ORS assessed by human intestinal perfusion
Authors: HUNT I. B. , ELLIOTT E. J. , FARTHING M. J. G.
Published: July 2010

Human triple‐lumen intestinal perfusion was used to compare water and solute absorption from the oral rehydration solution (ORS) most widely used in the United Kingdom and a new experimental hypotonic ORS (HYPO‐ORS). HYPO‐ORS (osmolality 210 mOsm/kg) promoted significantly greater water absorption than UK‐ORS (7.03 ± 1.1 vs 2.73 ± 1.0 ml cm−1 h−1; P < 0.01). HYPO‐ORS produced net sodium and chloride absorption whereas the low sodium UK‐ORS produced a net secretion of these ions. Bicarbonate absorption was also greater from HYPO‐ORS although potassium and glucose absorption were similar from both solutions. This study suggests that UK‐ORS may not promote optimal water and solute absorption and that clinical studies with HYPO‐ORS are indicated.
Review article: bile acid therapy
Authors: LANZINI A. , NORTHFIELD T. C.
Published: July 2010

Over the past 3 years there has been a renewed interest in bile acid therapy not only because of the promising results obtained by combining this therapy with extracorporeal shock‐wave lithotripsy for rapid gallstone dissolution, but also because of its novel use as a treatment for primary biliary cirrhosis. This article reviews the use of bile acids for both these indications.
Dosage of colloidal bismuth subcitrate in duodenal ulcer healing and clearance of Campylobacter pylori
Authors: COGHLAN J. , HUTCHINSON L. , GILLIGAN D. , McKENNA D. , KEANE C. , SWEENEY E. , O'MORAIN C.
Published: July 2010

Sixty consecutive patients with endoscopically proven duodenal ulcers were given colloidal bismuth subcitrate tablets either as 120 mg q.d.s. or 240 mg b.d., in a randomized single‐blind study. The efficacy of each regimen was determined by endoscopic examination and antral biopsy at 4 weeks; if the ulcer remained unhealed, treatment was continued and endoscopy repeated at 8 weeks. The ulcer‐healing efficacy of the two regimens was identical; however, in the four times daily group only 27% remained Campylobacter pylori positive after 8 weeks of treatment compared with 58% of the twice‐daily group. Similarly, only 21% of twice daily patients were free of histological gastritis compared with 42% of the four times daily patients.
Omepmazole or high‐dose ranitidine in the treatment of patients with reflux oesophagitis not responding to ‘standard doses’of H2‐receptor antagonists
Authors: LUNDELL L. , BACKMAN L. , EKSTRÖM P. , ENANDER L.‐H. , FAUSA O. , LIND T. , LÖNROTH H. , SANDMARK S. , SANDZÉN B. , UNGE P. , WESTIN I. H.
Published: July 2010

Ninety‐eight patients (26 females), who presented with erosive and/or ulcerative oesophagitis, despite at least a 3‐month period of treatment with standard doses of cimetidine (≥ 1200 mg daily) or ranitidine (≥ 300 mg daily), were included in a double‐blind, randomized trial to compare omeprazole (40 mg o.m.) with a high dose of ranitidine (300 mg b.d.). The treatment was given for 4–12 weeks; endoscopy assessment and laboratory screening were performed on entry to the trial and thereafter every fourth week. Endoscopic healing was defined as complete epithelialization of all macroscopic erosions or ulcers in the squamous epithelium. An ‘intention‐to‐treat’analysis of the clinical datarevealed omeprazole to be superior to ranitidine : 63 % of those patients who were given omeprazole were heaIed endoscopically after a 4‐week period of treatment, compared with only 17 % of those given ranitidine. This difference in healing rate persisted during the 12‐week study period (90% DS 47% after 12 weeks; P < 0.0001). Reflux symptoms were more rapidly and completely relieved with omeprazole : heartburn resolved completely in 86% of patients treated with omeprazole for 4 weeks compared with 32% in the ranitidine group (P < 0.0001). The mean basal gastrin concentrations increased only in those given omeprazole from 18.9 pmol/L at pre‐entry to a mean value of 31.7 pmol/L on the last day of omeprazole administration. In ranitidine‐treated patients no significant increase in basal gastrin concentration was observed. Both drugs were well tolerated with few adverse events, which were mainly mild and transient. These results demonstrate the superiority of omeprazole over a high dose of ranitidine in the treatment of resistant reflux oesophagitis.
The safety and efficacy of tripotassium dicitrato bismuthate (De‐Nol) maintenance therapy in patients with duodenal ulceration
Authors: DUNK A. A. , PRABHU U. , TOBIN A. , O'MORAIN C. , MOWAT N. A. G.
Published: July 2010

Seventy‐one patients whose duodenal ulcers had healed after a 4‐week treatment period with tripotassium dicitrato bismuthate (TDB) were randomly allocated to receive maintenance treatment with either one TDB swallow tablet nocte (equivalent to 120 mg Bi2 O3) or an identical placebo. During 12 months of follow‐up, no side‐effects were reported by TDB‐treated patients, blood bismuth levels did not rise above discontinuation threshold concentrations (> 50 μg/L in the first 6 months, or > 100 μg/L in the second 6 months), and there were no adverse effects on haematological or biochemical indices. Ulcer relapse was significantly less in TDB‐treated patients (P < 0.025). Cumulative relapse rates at 6 and 12 months were 51% and 66%, respectively, for placebotreated patients and 26% and 31%, respectively, for those who received TDB. It is likely that TDB is a safe and effective maintenance treatment for patients with duodenal ulcer disease.
Effect of ranitidine and indomethacin on nocturnal gastric acidity in normal subjects
Authors: WALT R. P. , DANESHMEND T. K. , PRICHARD P. , LANGMAN M. J. S.
Published: July 2010

To assess the effect of indomethacin on gastric acidity and to identify a potential pharmacodynamic interaction between indomethacin and ranitidine, we measured nocturnal acidity on half‐hourly aliquots of gastric contents from 10 volunteers on the seveneth day of four dosing regimens given in a randomized double‐blind manner. These were indomethacin (50 mg t.d.s.) and ranitidine (300 mg in the evening) together or alone with matching placebos. Median nocturnal acidity on placebo was 41.7 mmol/L (range 67.6–25.1 mmol/L) and was 39.8 mmol/L (63.1–24.0 mmol/L) on indomethacin (N.S.). During ranitidine dosing it was 0.4 mmol/L (21.3–0.0 mmol/L) without and 0.8 mmol/L (43.7–0.0 mmol/L) with concurrent indomethacin, representing 99 and 98% decreases in gastric acidity (P< 0.01) compared with placebo. Indomethacin did not increase overnight gastric acidity and did not influence the suppression of acidity produced by ranitidine. It is unlikely that the ulcerogenic potential of indomethacin is explicable by an effect on gastric acidity.