bluuebunny/crossref_metadata_2025 huggingface dataset:
Review article: new developments in the use of 5‐aminosalicylic acid in patients with inflammatory bowel disease
Authors: THOMSON A. B. R.
Published: July 2010

Sulphasalazine is composed of sulphapyridine and mesalazine (5‐aminosalicylic acid, 5‐ASA or mesalazine) joined by an azo bond. Sulphasalazine has been used clinically for 40 years but less than 10 years ago it was recognized that the active moiety is 5‐ASA. Sulphapyridine appears to act only as a carrier molecule to deliver mesalazine to the bowel, yet it is the sulphapyridine which appears to be responsible for many of the adverse effects observed with sulphasalazine. Normally, mesalazine is rapidly absorbed from the upper gastrointestinal tract. Since the action of mesalazine is thought to be locally at the site of disease in the intestine, the 5‐ASA must be ‘protected’ to ensure its release in the terminal ileum and colon, the site of bowel inflammation in patients with Crohn's disease or ulcerative colitis. Recent clinical studies have confirmed the efficacy of topical (suppositories and enemas) therapy for ulcerative proctitis and left‐sided colitis; oral mesalazine has been proven to be useful for the treatment of acute ulcerative colitis and for the maintenance of remission. There is preliminary evidence for the clinical usefulness of mesalazine in acute Crohn's disease as well as for the maintenance of remission.
Is topical therapy necessary in acute distal colitis? Double‐blind comparison of high‐dose oral mesalazine versus steroid enemas in the treatment of active distal ulcerative colitis
Authors: COBDEN I. , AL‐MARDINI H. , ZAITOUN A. , RECORD C. O.
Published: July 2010

Thirty‐seven patients suffering an attack of acute distal ulcerative colitis of mild or moderate severity were randomized in a double‐blind, doubledummy fashion to receive either 800 mg oral mesalazine four times daily (18 patients) or steroid enemas twice daily (19 patients) for 4 weeks. Both treatments were well tolerated with no adverse effects. Three patients in each group were withdrawn because of clinical deterioration but both treatments produced significant clinical improvement with decreases in stool frequency and scores for urgency, bleeding and tenesmus. There were no significant differences between the treatments although there was a slight trend in favour of the enemas for reduction in rectal bleeding. Activity of the colitis as graded at sigmoidoscopy also decreased significantly with both treatments and there were corresponding improvements in histological parameters of inflammatory activity assessed with the aid of a computerized morphometric system. Little correlation was seen between clinical, sigmoidoscopic and histological changes.
Famotidine (20 mg) b.d. relieves gastrooesophageal reflux symptoms in patients without erosive oesophagitis
Authors: ROBINSON M. , DECKTOR D. L. , STONE R. C. , PEVELERY M. , BARDEN P. , MOYER R. , HOLT S. , ROOT J. , HUFNAGEL K. , HUMPHRIES T. J. , BERLIN R. D.
Published: July 2010

Previous clinical trials have evaluated a large number of symptomatic individuals with heartburn. Most studies have documented the need for multiple daily dosing with H2‐antagonists to achieve clinical and statistical efficacy for symptom relief. The purpose of this study was to compare the safety profile and efficacy of famotidine oral dosing regimens, 40 mg nocte and 20 mg b.d. with placebo in the relief of symptoms in patients suffering from frequent heartburn found to have endoscopically normal oesophageal mucosa or mild non‐erosive oesophagitis. Famotidine (20 mg) b.d. reduced and eventually completely relieved gastro‐oesophageal reflux disease symptoms in most patients during the 6‐week trial. Global assessment of improvement at 2 and 6 weeks indicated significantly greater improvement with a b.d. treatment regimen than with either a 40 mg nocte or placebo treatment. No statistically significant differences between famotidine and placebo in the number of patients who experienced clinical adverse experiences were noted and no serious adverse events attributable to famotidine occurred. Based upon these findings, patients with gastro‐oesophageal reflux symptoms experience good relief of their complaints with twice daily famotidine in standard doses.
Role of acid suppressants in patients with Zollinger–Ellison Syndrome
Authors: MATON P. N.
Published: July 2010

Virtually all symptoms in patients with Zollinger‐Ellison syndrome are due to acid hypersecretion, thus the control of acid secretion is the first and most important step in the management of patients with this syndrome. Antisecretory medication is prescribed as soon as the diagnosis of Zollinger‐Ellison syndrome is made, as patients may bleed or perforate with little warning. Acid output is reduced to < 10 mmol/h to heal mucosal lesions, but in patients with a Billroth I or II gastrectomy and those with severe oesophagitis and stricture formation, acid output is reduced to < 5 or < 1 mmol/h. Acid output and not symptomatic response is a reliable guide of the adequacy of therapy. In sufficient doses, all H2‐receptor antagonists are useful; however, side effects associated with cimetidine therapy limit its use. The ratio of potencies of cimetidine: ranitidine: famotidine is 1:4:32.

Ranitidine given as a 50‐mg intravenous bolus, followed by a continuous infusion of 0.5 mg. kg/h, controls acid hypersecretion acutely in patients with Zollinger‐Ellison syndrome. Acid output is checked after 4 h, and the dose increased until acid output is < 10 mmol/h. In 70% of patients with Zollinger‐Ellison syndrome, 1 mg. kg/h reduces acid output to < 10 mmol/h; however, doses up to 4 mg. kg/h have been used. When patients are switched to oral ranitidine, a useful dosage conversion is to administer 1.5 times the total daily intravenous dose in four equal doses every 6 h. Four doses of oral drug are given before the infusion is stopped. Six hours after the first/last oral dose, acid output is checked. In our patients, the mean dose of ranitidine was 2100 mg/day (range, 450–9200 mg/day). No serious toxicity was observed.

Omeprazole, which has a long duration of action and is a potent inhibitor of gastric acid secretion, has simplified management. Once‐daily dosing is sufficient in most patients, and a reasonable starting dose is 60 mg daily. The dose may be increased to 120 mg once daily; if this dosage fails to control acid secretion, 60 mg is administered every 12 h. In our studies, the median dose was 90 mg/day (range, 20–120 mg/day). Omeprazole was more effective than H2‐receptor antagonists in providing symptom relief and mucosal healing and did not cause significant toxicity. In particular, no gastric carcinoid tumours developed during four years of use. Omeprazole is, therefore, the treatment of choice for control of acid secretion in patients with Zollinger‐Ellison syndrome.

Surgery plays a minor role in the control of acid hypersecretion. Parathyroidectomy in patients with Zollinger‐Ellison syndrome as part of multiple endocrine neoplasia type I, or highly selective vagotomy decrease gastric acid output and lower drug requirements but do not cure the patient. Except when resection of gastrinoma is curative, lifelong medical therapy for control of acid secretion in patients with Zollinger‐Ellison syndrome is required.
Rationale for high‐dose H2‐receptor blockade in the treatment of gastro‐oesophageal reflux disease
Authors: CASTELL D. O.
Published: July 2010

Chronic gastro‐oesophageal reflux disease is a common clinical problem. The underlying pathophysiology is considered to be acid injury to the oesophageal mucosa secondary to reflux of gastric contents across an incompetent lower oesophageal sphincter. Evidence suggests that gastrooesophageal reflux disease is primarily a motility disorder, possibly the combined effect of decreased lower oesophageal sphincter pressure, abnormal oesophageal peristalsis, and, perhaps, delayed gastric emptying. The rationale for the use of acid‐suppressing drugs in chronic gastrooesophageal reflux disease is based on control of the known destructive role of acid and pepsin. Recent evidence indicates, however, that standard doses of H2‐receptor blockers are often inadequate to control gastric acid‐induced injury in many patients with chronic reflux. Long‐term maintenance therapy with standard doses of these drugs has proved unsuccessful in approximately 50% of patients. More recent studies show that greater symptom relief and improved healing can be achieved with the use of larger doses of H2‐receptor antagonists. This has been shown particularly with ranitidine at a dosage of 300 mg four times daily.
The long‐term management of duodenal ulceration using an H2‐antagonist: symptomatic self‐care compared with maintenance treatment
Authors: POUNDER R. E. , FESTEN H. , KORMAN M.
Published: July 2010

In a 48‐week study of 319 duodenal ulcer patients, symptomatic self‐care with an histamine H2‐receptor antagonist (flexible self‐chosen dosing with cimetidine 0, 400 or 800 mg/day) was compared with maintenance treatment (cimetidine 400 mg nocte). The rate of withdrawal from the study was similar in both groups. The mean consumption of cimetidine 400 mg tablets was significantly higher in the maintenance group (7.2vs. 5.4 tablets/week; P < 0.0001), but the mean cumulative number of days with ulcer symptoms was higher in the symptomatic self‐care group (47.2vs.29.1 days in 48 weeks). The estimated number of days of work‐loss due to ulcer symptoms was similar in both groups (approximately 4 days in the 48 weeks of observation).

It is concluded that symptomatic self‐care using an H2‐antagonist can provide not only an economic but also an effective strategy for the long‐term management of uncomplicated duodenal ulceration.
The effects of lansoprazole, a new H+,K+‐ATPase inhibitor, on gastric pH and serum gastrin
Authors: SANDERS S. W. , TOLMAN K. G. , GRESKI P. A. , JENNINGS D. E. , HOYOS P. A. , PAGE J. G.
Published: July 2010

This study examined the effects of dose and time of administration of lansoprazole on gastric pH and serum gastrin in healthy male volunteers. Three groups of six subjects received 10, 20 or 60 mg doses of lansoprazole or placebo. Doses were administered at 22.00 hours daily for 7 days. An additional 18 subjects received once daily 30 mg oral doses of lansoprazole or placebo; these subjects were dosed at either 08.00 hours or 22.00 hours in a randomized, crossover fashion with a 2‐week washout period. Gastric pH was monitored for 24 h following the first and final dose, and 1 week following the completion of dosing.

Lansoprazole, at all doses except 20 mg/day, significantly increased the median 24‐hour gastric pH following 7 days of dosing (P < 0.05). In addition, morning dosing in the 30‐mg crossover group led to a higher 24‐h median pH than evening dosing (P= 0.003). There was no difference in night‐time median pH between morning and evening dosing. Morning dosing also led to a significant increase in gastric pH on study Day 1 (P < 0.05). Plasma concentrations of lansoprazole were highly variable between subjects, but there was a significant correlation between AUC and the median 24‐h gastric pH. Plasma concentrations and AUCs were higher on Day 7 than on Day 1 for subjects receiving 10 or 20 mg, but not for those receiving 30 or 60 mg doses. Lansoprazole bioavailability demonstrated a circadian effect manifested by higher plasma concentrations following morning dosing. Serum gastrin concentrations were elevated in all active medication groups.
Short report: twenty‐four‐hour hyperpepsinogenaemia in Helicobacter pylori‐positive subjects is abolished by eradication of the infection
Authors: FRASER A. G. , PREWETT E. J. , POUNDER R. E. , SAMLOFF I. M.
Published: July 2010

Twenty‐four‐hour plasma pepsinogen I and II concentrations were determined in 8 healthy subjects with antibody to Helicobacter pylori, before and after treatment with tripotassium dicitrato bismuthate, amoxycillin and metronidazole, Therapy was successful in the 5 subjects with active H. pylori infection. In these subjects, median integrated 24‐h plasma pepsinogen I and II concentrations significantly decreased from 2288 and 357 μg.h/L before treatment, respectively, to 1811 and 171 μg.h/L at 4–6 weeks after treatment, and 1643 and 150 μg.h/L at 20–24 weeks. By contrast, in the 3 subjects without evidence of active H. pylori infection, pre‐treatment plasma pepsinogen I and II concentrations were similar to values found in the H. pylori‐infected subjects after successful therapy, and they did not change significantly in response to therapy. H. pylori infection is associated with reversible hyperpepsinogenaemia.
Effecf of treatment with cisapride alone or in combination with domperidone on gastric emptying and gastrointestinal symptoms in dyspeptic patients
Authors: TATSUTA M. , IISHI H. , NAKAIZUMI A. , OKUDA S.
Published: July 2010

The effects on gastric emptying and gastrointestinal symptoms of treatment with cisapride alone and in combination with domperidone were investigated in 25 patients with chronic idiopathic dyspepsia. In a double‐blind study, 9 patients were randomly assigned to receive cisapride 2.5 mg three times daily, and 8 patients to receive placebo. After 7 days of treatment, gastric emptying was significantly accelerated and the score of gastrointestinal symptoms was significantly reduced in patients treated with cisapride. Placebo treatment had no significant effect. A randomized, double‐blind crossover study of 8 patients compared the effects of combined treatment with cisapride 2.5 mg plus domperidone 10 mg three times daily for 7 days against the effects of cisapride plus placebo. Administration of cisapride plus domperidone gave significantly higher gastric emptying and lower gastrointestinal symptoms than cisapride plus placebo.
Inhibition of human exocrine pancreatic secretion by the long‐acting somatostatin analogue octreotide (SMS 201‐995)
Authors: KEMMER T. P. , MALFERTHEINER P. , BÜCHLER M. , FRIESS H. , MESCHENMOSER L. , DITSCHUNEIT H.
Published: July 2010

The new long‐acting somatostatin analogue octreotide (SMS 201–995) was investigated for its influence on segretatagogue‐stimulated human exocrine pancreatic secretion. Eighteen healthy volunteers participated in the study. During duodenal intubation with a background stimulation of either secretin 1 U.kg/h or secretin 1 U. kg/h + ceruletide, 120 ng.kg/h, octreotide was infused at doses of 5, 20 and 80 μg/h in a placebo‐controlled randomized double‐blind crossover trial. Duodenal juice samples were collected in 10‐min intervals, and amylase, trypsin, chymotrypsin, and bicarbonate were measured in the individual fractions.

During secretin stimulation, amylase was inhibited between 41 and 59%, trypsin between 28 and 72%, chymotrypsin between 55 and 70%, and bicarbonate between 0 and 31% with 5, 20 and 80 μg/h octreotide. During secretin and ceruletide stimulation, amylase was significantly inhibited by 84%, 78%, 81%, trypsin by 76%, 55%, 52%, chymotrypsin by 77%, 55%, 60%, and bicarbonate by 25%, 11%, 19% with 5, 20, and 80 μg/h octreotide, respectively (all decreases P < 0.05).

The long‐acting somatostatin analogue octreotide was confirmed to be a potent inhibitor of stimulated human exocrine pancreatic secretion. The near maximal inhibitory potency of octreotide was achieved at a dose of only 5 μg/h. This finding may be of value in the planning of therapeutic studies with octreotide.
A comparison of indomethacin with ibuprofen on gastrointestinal mucosal integrity in conventional and germ‐free rats
Authors: MELARANGE R. , MOORE G. , BLOWER P. R. , COATES M. E. , WARD F. W. , RONAASEN V.
Published: July 2010

The effects of indomethacin and ibuprofen on gastrointestinal mucosal integrity were studied in conventional and germ‐free rats. Only ibuprofen induced significant gastric erosion formation in both conventional and germ‐free animals, demonstrating that the presence of micro‐organisms is not required in this form of damage. Both indomethacin and ibuprofen caused significant intestinal damage and blood loss in germ‐free animals. However, in the conventional counterparts, damage due to indomethacin was enhanced whereas that induced by ibuprofen was not. The results from the present work would suggest that non‐steroidal anti‐inflammatory drugs such as indomethacin, which are secreted largely in the bile, unlike ibuprofen, may act in concert with bacteria and the constituents of bile to induce, in part, intestinal damage and blood loss.
Influence of the timing of administration of 300 mg ranitidine on 24‐hour gastvic pH in patients with acute duodenal ulcer
Authors: CORTOT A. , GUILLEMOT F. , MOREAU J. , SOULE J. C. , VEYRAC M. , ALBEROLA B. , PAPPO M.
Published: July 2010

The 24‐hour intragastric pH of 12 patients with an acute duodenal ulcer was recorded with the aim of comparing the effects of two different times of administration of 300 mg ranitidine: post evening meal, or bedtime. This double‐blind crossover trial involved 3 centres. Twenty‐four‐hour gastric pH was measured under standard conditions (meals, time schedule) at the middle of each 14‐day treatment period. The analysis was performed on the percentage of times spent at pH levels below 1.5, 2, 3 and 4 for different periods and for the total 24 hours. During the whole day and night combined, as well as during the afternoon (12.00 hours‐19.00 hours), there was no difference between the 2 regimens regardless of the pH profile studied. During the morning (07.30 hours‐12.00 hours), the time spent below pH 1.5 and 2 was less when the drug was taken at bedtime (P < 0.05). In contrast, during the whole night (19.00 hours‐07.30 hours) the percentage of time spent below pH 1.5, 2 and 3 was significantly less when the drug was taken at post evening meal (P < 0.05). These results show that in patients with acute duodenal ulcer, 300 mg ranitidine administered at the end of the evening meal provides better control of nocturnal acidity than administration at bedtime and hence is suggested for optimization of therapeutic efficacy.
Short report: cefprozil for the eradication of Helicobacter pylori infection
Authors: MALATY H. , KLEIN P. D. , GRAHAM D. Y.
Published: July 2010

Helicobacter pylori infection has proven to be extraordinarily difficult to eradicate. Antimicrobial monotherapies have been particularly disappointing, with most eradication rates in the range of 0 to 15%. We evaluated cefprozil (250 mg q.d.s. for 14 days) in 12 H. pylori‐infected subjects. The 13C‐urea breath test was used to evaluate effectiveness of therapy. Eradication was defined as a negative urea breath test 4 to 6 weeks after the end of treatment. Suppression of H. pylori was demonstrated in 4 of 12 (33%) by a negative urea breath test two days after start of treatment. H. pylori infection was not eradicated in any subject (0%). Adverse events were intermittent and mild. Cefprozil does not appear to offer promise as monotherapy for the eradication of H. pylori.
The effect of H2‐blockade on plasma gastrin concentration in patients with an achlorhydric stomach
Authors: FULLARTON G. M. , ARDILL J. E. S. , McCOLL K. E. L.
Published: July 2010

The mechanisms of hypergastrinaemia during H2‐receptor antagonist therapy remain unclear. In addition, the effect of food stimulation in conditions of hypergastrinaemia is poorly understood. These effects may be important when considering long‐term therapy with potent acid inhibitory agents. To investigate this we studied the effect of H2‐receptor antagonist therapy on basal and meal‐stimulated plasma gastrin concentrations in 9 patients with pentagastrin fast gastric achlorhydria associated with pernicious anaemia. The subjects received in double‐blind randomized fashion 28‐day courses of 300 mg ranitidine q.d.s. and placebo, with one‐month wash‐out between. The fasting and peptone meal‐stimulated gastrin concentrations were studied on the final day of each course of treatment. The median fasting gastrin concentrations (ng/L) were similar following placebo (1100, range 25–2100), and 300 mg ranitidine q.d.s. (1075, range 15–2600) and both markedly elevated when compared with our laboratory's normal range of 0—100. Despite the elevated basal levels the pernicious anaemia patients still showed a further increase in response to the peptone meal. Their median peak percentage rise over basal in response to the meal was similar following placebo (96%, range 0–375) and 300 mg ranitidine q.d.s. (100%, range 25–425) (both P < 0.02 c.f. basal).

This study shows that: (a) in hypergastrinaemia in pernicious anaemia subjects, meal stimulation leads to a marked and prolonged increase in plasma gastrin concentrations; (b) H2‐receptor antagonists have no effect on plasma gastrin in the neutral stomach and this is consistent with their gastrin effect being entirely secondary to acid inhibition.
Nine years of maintenance treatment with ranitidine for patients with duodenal ulcer disease
Authors: PENSTON J. G. , WORMSLEY K. G.
Published: July 2010

Four hundred and sixty‐four patients with duodenal ulcer disease received continuous maintenance treatment with ranitidine for up to 9 years. Treatment failure was defined as either the first symptomatic recurrence of ulcer or the first ulcer recurrence accompanied by haemorrhage. Life tables were constructed using the Kaplan‐Meier product‐limit method; comparisons of survival curves were performed using the log‐rank test; and multivariate analysis was carried out using the Cox proportional hazards model.

Results. The proportion of patients remaining free from symptomatic recurrence of ulcer during maintenance treatment with either 150 mg/day or 300 mg/day ranitidine was: 95% at 1 year; 88% at 3 years; 86% at 5 years; and 81% at 7 and 9 years (95% C.I. 76–86%). Young age and the absence of exposure to non‐steroidal anti‐inflammatory drugs (NSAIDs) at the time of diagnosis of ulcer were shown to increase the likelihood of developing ulcer recurrence. The rate of ulcer recurrence after 9 years of maintenance treatment (17%) was significantly less than that after 5 years without active anti‐ulcer therapy (80%),P= 0.0001.

The proportion of patients who remained free from ulcer haemorrhage during maintenance treatment was: 99.1% at 1 year and 98.1 % at 5 and 9 years (95 % C.I. 96.7–99.6%). The risk of haemorrhage was significantly greater in patients who were not receiving active treatment (12.4% at 5 years) than in patients receiving maintenance treatment (< 2% at 9 years),P= 0.0001 (log‐rank test). Patients who had originally presented with haemorrhage had an increased risk of further ulcer bleeding compared with patients who presented with pain (P= 0.0013). A significantly greater proportion of patients with NSAID‐associated duodenal ulcers remained free from ulcer recurrence during maintenance treatment compared with patients suffering from‘idiopathic’ ulcers (P= 0.0238), although there was no difference between the two groups in respect of haemorrhage during maintenance treatment.

Concltisions

(a) Continuous maintenance treatment with ranitidine for up to nine years successfully prevents ulcer recurrence in more than 80% of patients with duodenal ulcer disease.

(b) Young age increases the risk of ulcer recurrence during maintenance treatment with ranitidine. Ulcers associated with NSAID‐intake at the time of diagnosis have a lesser risk of recurrence during maintenance treatment.

(c) The risk of haemorrhage in patients with ulcer disease receiving maintenance treatment with ranitidine for nine years was < 2% compared with > 12% in untreated patients observed for 5 years.

(d) Patients whose ulcer disease presents with haemorrhage have a greater risk of further bleeding than patients who present with pain.
Review article: promotility drugs in the treatment of gastro‐oesophageal reflux disease
Authors: RAMIREZ B. , RICHTER J. E.
Published: July 2010

Prokinetic agents are drugs that increase contractile force and accelerate intraluminal transit. They are often used in treating disorders of gastrointestinal motility including gastro‐oesophageal reflux disease (GERD). The most widely studied agents include bethanechol, metoclopramide, domperidone and cisapride. These drugs act either by enhancing the effect of acetylcholine or by blocking the effect of an inhibitory neurotransmitter such as dopamine. With the exception of cisapride, the clinical efficacy of the various prokinetic agents in treating GERD has not been confirmed consistently. These agents have variable effects on oesophageal and gastric motor function and are fraught with side‐effects. They are effective in relieving mild reflux symptoms but do not predictably heal oesophagitis. On the other hand, cisapride is thus far the most effective prokinetic agent studied for the treatment of GERD. It relieves reflux symptoms and promotes healing of grade I–II oesophagitis, with few side‐effects or tachyphylaxis. Its most important role may be in the maintenance treatment of GERD either as a single agent or in combination therapy with an H2‐antagonist after oesophagitis healing.
Ileo‐caecal ulceration associated with the use of diclofenac slow release
Authors: HUDSON N. , WILKINSON M.J. , SWANNELL A. J. , STEELE R. J. , HAWKEY C. J.
Published: July 2010

A 38‐year‐old man with seropositive arthropathy on long‐standing treatment with diclofenac slow release presented with abdominal pain, diarrhoea and anaemia. Upper gastrointestinal endoscopy and barium series were unremarkable. Five months later he presented with a right iliac fossa mass. Investigations revealed discrete ulceration in the terminal ileum and caecum confirmed at laparotomy. Other possible causes of intestinal ulceration were excluded suggesting a diagnosis of non‐steroidal anti‐inflammatory drug associated intestinal ulceration.
The eflects of 300 mg ranitidine at night, twice daily and four times daily on intragastric acidity in normal subjects
Authors: PRIMROSE J. N. , ROGERS M. J. , HOLMFIELD J. H. M.
Published: July 2010

The aim of this study was to compare to placebo the effects of 300 mg ranitidine nocte, b.d. and q.d. on intragastric acidity. The study was performed on healthy male subjects and intragastric acidity measured by radiotelemetry. All active treatments significantly decreased 24‐hr acidity, with a median suppression of 61.0% with 300 mg ranitidine nocte, 77.7% with 300 mg b.d. and 78.0% with 300 mg q.d.s. There was no significant difference between the effects of two higher dose regimens: although the 300 mg q.d.s. suppressed daytime acidity more than 300 mg b.d. (88.9%vs. 77.8%), it suppressed nocturnal acidity less effectively (65.5%) than either 300 mg nocte (92.9%) or 300 mg b.d. (90.0%). These data suggest that only modest additional therapeutic acid inhibition can be achieved by increasing the dose of ranitidine above 600 mg daily.
Thrornboxanes in inflammatory bowel disease—pathogenic and therapeutic implications
Authors: RAMPTON D. S. , COLLINS C. E.
Published: July 2010

Recent work suggests that thromboxanes may play a major pathogenic role in inflammatory bowel disease. Thromboxanes are produced in excess not only in inflamed mucosa but also in Crohn's disease, by uninflamed bowel and by isolated intestinal and peripheral blood mononuclear cells. Their cellular source is likely to include platelets, neutrophils, endothelial and epithelial cells as well as mononuclear cells, possible stimuli to their overproduction being chemotactic peptides, lipopolysaccharide, leucotrienes, platelet activating factor, interleukin‐1, bradykinin and angiotensinII. The pro‐inflammatory effects of thromboxanes are both direct (diapedesis and activation of neutrophils, mucosal ulceration, reduction of suppressor T‐cell activity) and indirect (vasoconstriction, platelet activation). Although corticosteroids and aminosalicylates inhibit thromboxane synthesis, this action does not necessarily explain their therapeutic effect in inflammatory bowel disease. Selective thromboxane synthesis inhibitors and receptor antagonists, however, ameliorate experimental colitis in animals. Picotamide and ridogrel are dual thromboxane pathway blockers already used in man. Drugs of this type could prove useful not only for the prevention of systemic thrombo‐embolism but also for suppressing intestinal mucosal inflammation in patients with inflammatory bowel disease.
Pharmacokinetics of budesonide enema in patients with distal ulcerative colitis or proctitis
Authors: DANIELSSON Å. , EDSBÄCKER S. , LÖFBERG R. , NILSSON Å. , NYMAN‐PANTELIDIS M. , OLSSON O. , SUHR O. , WILLÉN R.
Published: July 2010

Pharmacokinetic data obtained after one dose of a 2‐mg budesonide enema were compared with data obtained after the last dose of four weeks of daily treatment in 24 patients with active distal ulcerative colitis or proctitis. This open multicentre study involved 28 eligible patients. Sigmoidoscopy and biopsy scores improved significantly (P < 0.002) during the four‐week treatment period. Maximal plasma concentration (Cmax) of budesonide was 2.1 nmol/L 1.3 h after the first dose and 2.5 nmol/L 1.2 h after the last dose; the difference was not significant. The area under the curve (AUC) of plasma concentration vs. time was after the first dose 9.7 nmol h/L and after the last dose 11.6 nmol h/L (P < 0.03). The small increase in AUC may be attributed to improved absorption. During the last dose interval, minimal plasma concentration was below the limit of quantitation in most subjects. The Cmax and AUC of budesonide increased slightly after four weeks of treatment, but budesonide did not accumulate. Mean morning plasma cortisol values did not change significantly during treatment (P= 0.083), although a small change in cortisol levels between the first visit (pre‐treatment) and last visit was positively correlated to the C. of budesonide measured at the last visit (P= 0.012).
Omeprazole versus famotidine in the healing and relapse of duodenal ulcer
Authors: MISRA S. C. , DASARATHY S. , SHARMA M. P.
Published: July 2010

Sixty patients with symptomatic duodenal ulcer were randomized to receive either omeprazole (20 mg each morning) or famotidine (40 mg at night time) for 2–4 weeks in a double‐blind parallel group clinical trial. Healing rates were higher with omeprazole in comparison with famotidine after 2 weeks (77%vs. 40%, P < 0.001) and 4 weeks (93%vs. 80%, P= 0.2) of treatment. Assessment of daily diary cards completed by all patients revealed that omeprazole rapidly relieved ulcer‐related day pain and nocturnal pain in comparison to famotidine. Treatment with omeprazole for 2 weeks was also associated with lower cumulative antacid intake (P < 0.05) and reduced absenteeism from work. Helicobacter pylori infection was present in all patients and remained unaffected by treatment with either of the drugs. None of the drugs produced any significant adverse effects. During 6 months follow‐up of all the patients after ulcer healing (without maintenance therapy), ulcer relapse was seen in 40% of omeprazole‐ and 37% of famotidine‐treated patients (P > 0.1). The duration of ulcer‐free period following initial healing of ulcer was also similar in both the groups (median time: 22 weeks for omeprazole, 21 weeks for famotidine). We conclude that omeprazole is superior to famotidine in rapidly healing duodenal ulcers and achieving more rapid pain relief, but does not influence subsequent ulcer relapse.
The management of Zollinger—Ellison syndrome
Authors: MATON P. N.
Published: July 2010

Awareness of the sometimes subtle features of Zollinger–Ellison syndrome is important in order not to miss the diagnosis. Immediately after initial diagnostic tests, the patient should be given antisecretory medication, while tests for the type of Zollinger–Ellison syndrome and tumour extent can be delayed. Acid output should be decreased to < 10 mmol/h to control symptoms and prevent complications. Histamine H2‐ antagonists remain the best available intravenous therapy but omeprazole is the most effective long‐term oral therapy and has proved to be safe in nearly 10 years of continuous use. The management of the gastrinoma has changed in recent years since the discovery that the majority of gastrinomas arise outside the pancreas. Exploratory surgery with tumour resection is the treatment of choice in sporadic Zolliiger‐Ellison syndrome but there are few indications for surgery in patients with Zollinger–Ellison syndrome and multiple endocrine neoplasia type‐1. None of the available therapies for metastatic gastrinoma is very effective.
Review article: the use of gastric acid‐inhibitory drugs—physiological and pathophysiological considerations
Authors: WALDUM H. L. , BRENNA E. , KLEVELAND P. M. , SANDVIK A. K. , SYVERSEN U.
Published: July 2010

All vertebrates secrete gastric acid. Acid denatures the proteins in the food and thus makes them more accessible to proteolytic enzymes, and it kills swallowed micro‐organisms. Gastric acid plays an important pathogenetic role in peptic ulcer disease and reflux oesophagitis. In these diseases, drugs that inhibit secretion of gastric acid will heal the lesions and suppress the symptoms. However, both reflux oesophagitis and peptic ulcer tend to recur when the acid‐inhibitory treatment is stopped. Therefore, these patients often require long‐term treatment with acid‐inhibitors. In this overview the potential risks of long‐term profound inhibition of acid secretion, raising the pH above 4 for a considerable time, resulting in reduced killing of micro‐organisms and secondary hypergastrinaemia, are discussed. Gastrin regulates both the function (production and release of histamine) and growth of the enterochromaffin‐like (ECL) cell. Hitherto, the role that this cell plays in gastric carcinogenesis appears to have been underestimated.
Lansoprazole in the treatment of reflux oesophagitis: a survey of clinical studies
Authors: BERSTAD A. , HATLEBAKK J. G.
Published: July 2010

The newly developed proton pump inhibitor lansoprazole has been compared to placebo, ranitidine and with omeprazole in a number of clinical studies in patients with reflux oesophagitis. In three comparative studies against ranitidine, lansoprazole was found to be superior in terms of healing rates and symptom relief. In two studies against omeprazole, no significant difference was found in healing rates, while a Scandinavian study demonstrated more prompt relief from heartburn. Further studies are presently being conducted to evaluate the potential of lansoprazole in long‐term treatment of reflux oesophagitis. It is concluded that lansoprazole is a safe, effective therapy for reflux oesophagitis, superior to ranitidine and comparable with omeprazole.
Acute treatment of duodenal ulcer: experience with lansoprazole
Authors: MIGNON M. , VALLOT T.
Published: July 2010

Clinical experience with lansoprazole in the acute treatment of duodenal ulcer patients has been compared with treatment using placebo, H2‐antagonists or omeprazole. Among the various lansoprazole dosage regimens that have been tested, 30 mg daily for 4 weeks appears to be the optimal regimen to relieve pain rapidly and to heal ulceration in up to 90–95% of patients. Lansoprazole tolerability in the short term appears excellent, most adverse effects are trivial and not dose related. Duodenal ulcer relapse after ulcer healing with lansoprazole appears to occur at a rate similar to that observed after treatment with omeprazole or histamine H2‐antagonists.
A decade of experience with long‐term continuous treatment of peptic ulcers with H2‐receptor antagonists
Authors: PENSTON J. G.
Published: July 2010

Patients with peptic ulcer disease are troubled by recurrent episodes of ulcer pain, and remain at risk of developing the serious and occasionally lethal complications of haemorrhage and perforation. As the disease is chronic and persists over many years, a long‐term strategy for the management of patients with peptic ulcer is required. Continuous, long‐term treatment with H2‐receptor antagonists successfully achieves the dual objectives of preventing painful ulcer recurrence and reducing the risk of complications. During nine years of continuous therapy with ranitidine, more than 80% of patients with duodenal ulcers remain free from symptomatic ulcer recurrence, less than 2% suffer from ulcer haemorrhage, and the risk of perforation is 0%. Similar beneficial effects of long‐term treatment have been observed in patients with gastric ulcer. Long‐term continuous treatment with H2‐receptor antagonists may not alter the natural history of ulcer disease. Even after seven years of continuous therapy with ranitidine, ulcers recur in 50% of patients within six months of stopping treatment. Hence, long‐term therapy with H2‐receptor antagonists may need to be continued beyond 10 years. Patients with peptic ulcer who are elderly, those taking NSAIDs, aspirin or anti‐coagulants, those with a previous history of an ulcer complication and those with serious co‐existent disease are at increased risk from haemorrhage and perforation. These patients should receive long‐term prophylactic therapy with an H2‐receptor antagonist.
Oral mesalazine (5‐aminosalicylic acid; Asacol) for the prevention of post‐operative recurrence of Crohn's disease
Authors: CAPRILLI R. , ANDREOLI A. , CAPURSO L. , CORRAO G. , ALBASIO G. D. , GIOIENI A. , ASSUERO LANFRANCHI G. , PALADINI I. , PALLONE F. , PONTI V. , RIGO G. P. , ROSSINI F. P. , STURNIOLO G. C. , TONELLI F. , VALPIANI D. ,   THE GRUPPO ITALIANO PER LO STUDIO DEL COLON E DEL RETTO (GISC)
Published: July 2010

Methods:A multicentre randomized controlled trial was conducted to evaluate the efficacy of oral mesalazine (5‐aminosalicylic acid) for the prevention of post‐operative recurrence in 110 patients operated on for Crohn's disease by first intestinal resection. Patients were randomly allocated to receive 2.4 g/day of mesalazine, or no treatment at all. The protocol included colonoscopy with ileoscopy at 6 months and yearly thereafter. Recurrence was denned on the basis of endoscopic criteria and classified as mild or severe.

Results: The demographic and pre‐trial characteristics were very similar in the two groups of patients. The cumulative proportion of recurrence at 6, 12 and 24 months was significantly lower in the mesalazine group than in untreated group (P= 0.002). At 24 months the cumulative proportions of endoscopic recurrence were 0.52 + 0.12 (± S.E.M.) and 0.85 (±0.07), respectively. At the same time the cumulative proportions of symptomatic recurrence were 0.18 + 0.09 and 0.41 + 0.09 (P= 0.006). The cumulative proportions of the severe recurrence was also significantly lower in the mesalazine group (0.17±0.09vs.0.38±0.09;P= 0.021).Conclusions: The preliminary results of this study show that administration of oral mesalazine soon after surgery is effective in preventing post‐operative endoscopic recurrence in Crohn's disease over a 2‐year period. It is estimated that this treatment prevents 39% of all recurrences and 55% of the severe recurrences.
Randomized, placebo‐controlled comparison of famotidine 20 mg b.d. or 40 mg b.d. in patients with erosive oesophagitis
Authors: SIMON T. J. , BERENSON M. M. , BERLIN R. G. , SNAPINN S. , CAGLIOLA A.
Published: July 2010

Methods: this US multicentre, randomized, double‐blind, placebo‐controlled, parallel group study determined the effects of two twice daily oral famotidine regimens on symptom relief and healing of erosive oesophagitis in patients with gastro‐oesophageal reflux disease. Three hundred and eighteen patients were enrolled: 66 received placebo, 125 received famotidine 20 mg b.d., and 127 received famotidine 40 mg b.d. Patients maintained diaries of their symptoms. Endoscopy was performed at weeks 0 and 6, and again at week 12 if healing had not occurred.

Results: healing at 6 and 12 weeks was (respectively) 48% (P < 0.01 vs. placebo) and 69% (P≫ 0.01 vs.placebo) for famotidine 40 mg b.d.; 32% and 54% (P≫ 0.01 vs. placebo) for famotidine 20 mg b.d., and 18% and 29% for placebo. At both 6 and 12 weeks the healing rates of famotidine 40 mg b.d. were significantly greater than placebo and famotidine 20 mg b.d. Compared to placebo, famotidine produced more frequent global symptom improvement and more rapid heartburn relief. There were no significant differences among treatment groups in the incidence of clinical or laboratory adverse events.

Conclusions: famotidine 40 mg b.d. was a better regimen than famotidine 20 mg b.d. or placebo. The clinical efficacy paralleled the previously documented effect of the famotidine regimens on decrease of oesophageal acid exposure.
Addition of cisapride shortens colonoscopy preparation with lavage in elderly patients
Authors: UEDA S. , HSHI H. , TATSUTA M. , ODA K. , OSAKA S.
Published: July 2010

Methods: The effect of pre‐treatment with cisapride on colonoscopy preparation with lavage solution was compared in 120 out‐patients less than 60 years and 73 out‐patients 60 years or older, who were scheduled for total colonoscopy. By random allocation, patients were assigned to receive cisapride 10 mg or placebo 30 minutes before ingesting the magnesium citrate lavage solution.

Results: The cleansing results and patients’acceptance did not differ significantly in the two treatment groups in either age group. The time from the start of ingesting magnesium citrate until the rectal effluent became clear was significantly shorter in cisapride‐treated patients of 60 years or more. Moreover, the residual fluid volume removed by suction during colonoscopy was significantly less in the patients above aged 60 years who received cisapride.

Conclusion: These findings indicate that the combination of cisapride and magnesium citrate is more effective than magnesium citrate alone in cleansing the colon for colonoscopy in elderly patients.
Efsect ofursodeoxycholic acid on in vivo and in vitro toxic liver injury in rats
Authors: SIMKO V. , MICHAEL S.
Published: July 2010

Background: Benefits of ursodeoxycholic acid (UDCA) cholestatic disorders have been well documented. However, the therapeutic potential of UDCA in parenchymal liver disease is unclear.

Methods: We tested UDCA in rat models of hepatotoxicity: (a) in subacute liver injury induced by repetitive CCl4 and dietary ethyl alcohol (ETH) over seven weeks while receiving oral UDCA; and, (b) in liver slides incubated with CCI4, ETH or p‐acetaminophen (APAP) when UDCA was added to the incubating solution.

Results: Experiment 1: CCI4 combined with ETH reduced the body weights and resulted in 43% mortality. There was a significant rise in serum ALT, alkaline phosphatase, lipoperoxides (LPO) and in hepatic weight, triglycerides, LPO and histological scores of liver injury. Experiment 2: When liver slides were incubated with hepatotoxins there was an increased transfer of AST and LPO from the tissue into the incubate and a reduction in the valine and thymidine incorporation into the liver proteins or DNA. In none of these situations, whether the liver damage was severe or mild, in vivo or in vitro, UDCA did abolish these hepatotoxic effects.

Conclusion: In contrast to clinical cholestatic disorders where the reported benefits of UDCA depend on replacement of the accumulated hydrophobic bile acids, these bile acids have a less prominent role in toxic liver injury and UDCA is ineffective.
Comparative effects of intraduodenal psyllium and senna on canine small bowel motility
Authors: ASHRAF W. , LOF J. , JIN G. , QUIGLEY E. M. M.
Published: July 2010

Background/aim: To define the possible contribution of altered small intestinal motor activity to side‐effects of bulking fibres, we sought to compare the relative effects of intraduodenal and intracolonic administration of the bulking fibre psyllium and the anthraquinone laxative senna on canine small intestinal motor activity.

Methods: Motor activity was recorded by serosal strain gauges implanted along the small intestine in 6 dogs. In random order, the motor responses to the instillation of psyllium (in doses of 5 or 10 g), senna (10 mg/kg) or appropriate vehicle (200 ml water infusion or saline 5 ml bolus) into either the proximal duodenum or proximal colon were assessed.

Results: The intra‐duodenal administration of psyllium in either dose consistently induced a prolonged burst of‘clustered’contractions; in contrast, clusters were infrequent and of short duration following instillation of either vehicle or senna (P< 0.05). Intraduodenal instillation of psyllium inhibited migrating motor complex (MMC) migration and consistently delayed the onset of the next MMC cycle; a similar inhibition occurred with vehicle, however. Neither senna nor its vehicle inhibited MMC migration. None of these agents had any effect on small intestinal motor activity when instilled directly into the colon.

Conclusions: Psyllium administered directly into the duodenum inhibits MMC activity and consistently induces‘clustered’contractions. Whilst the MMC‐inhibitory effect appears to be a non‐specific volumerelated phenomenon, the induction of clusters is independent of volume or laxation. These motor effects of psyllium may contribute to the gastrointestinal symptomatology related to such agents and could be avoided by the preferential release of psyllium in the colon.
Review article: gastroduodenal bicarbonate secretion
Authors: HOGAN D. L. , AINSWORTH M. A. , ISENBERG J. I.
Published: July 2010

The gastroduodenal epithelium is covered by an adherent mucus layer into which bicarbonate is secreted by surface epithelial cells. This mucus‐bicarbonate barrier is an important first line of defence against damage by gastric acid and pepsin, and has been demonstrated in all species including human. Similar to gastric acid secretion, regulation of gastric and duodenal bicarbonate secretion can be divided into three phases: cephalic, gastric and duodenal. In humans, sham‐feeding increases bicarbonate secretion in both the stomach and duodenum which is mediated by cholinergic vagal fibres in the stomach, but seems to be noncholinergic in the duodenum. Gastric distention and luminal acidification increases gastric bicarbonate production. Whereas there are no data relating to the gastric phase of human duodenal bicarbonate secretion, in animals, food and acid in the stomach independently stimulate duodenal bicarbonate output. To date, the duodenal phase of human gastric bicarbonate secretion has not been studied, but data from animals reveal that duodenal acidification augments bicarbonate secretion in the stomach. In all species tested, direct acidification of the duodenum is a potent stimulant of local bicarbonate production. In humans, the pH threshold for bicarbonate secretion is pH 3.0. Mediation of gastroduodenal bicarbonate secretion is provided by a variety of agonists and antagonists, tested mainly in animals, but some have been evaluated in humans. Prostaglandins of the E class and VIP are major factors that control bicarbonate secretion. Bicarbonate secretion, and the mucus‐bicarbonate layer in general, is adversely effected by ulcerogenic factors such as aspirin, NSAIDs, bile salts, and cigarette smoking. Furthermore, duodenal ulcer patients have an impairment in bicarbonate production within the duodenal bulb, at rest and in response to stimulation. These findings indicate that the mucus‐bicarbonate barrier is an important first line of defence in the pathogenesis of peptic ulcer disease.