bluuebunny/crossref_metadata_2025 huggingface dataset:
pH‐Profile and regional transit times of the normal gut measured by a radiotelemetry device
Authors: FALLINGBORG J. , CHRISTENSEN L. A. , INGEMAN‐NIELSEN M. , JACOBSEN B. A. , ABILDGAARD K. , RASMUSSEN H. H.
Published: July 2010

The pH of the gut lumen was measured in 39 healthy persons using a pH‐sensitive, radiotransmitting capsule. Thirteen persons were studied twice. The location of the capsule was determined by X‐ray. The pH rose from 6.4 in the duodenum to 7.3 in the distal part of the small intestine. In 17 persons the pH dropped by 0.1–0.8 pH units during the last hours of the small intestinal transit. The pH was 5.7 in the caecum, but rose to 6.6 in the rectum. Gastric residence time was 1.1 h, small intestinal transit was 8 h, and colonic transit time was 17.5 h (median values). The results provide a firmer basis for prediction of the level, and the rate of release of active substance from pH‐dependent sustained‐release oral preparations.
The effect of enprostil on duodeno‐jejunal motility in man
Authors: DUCROTTE P. , PARENT B. , MASLIAH C. , JOUBERT M. , COLIN R. , DENIS P.
Published: July 2010

Motor changes could be involved in the pathogenesis of diarrhoea that complicates the treatment of ulcer disease by prostaglandins. Our aim was to assess the effect of enprostil, a synthetic analogue of PGE2, on duodeno‐jejunal motility. During this randomized double‐blind crossover study, two manometric recordings, each lasting 20 h (12.00‐08.00 hours), were carried out during dosing with 35 μg enprostil b.d. or placebo (eight volunteers: part 1), or during dosing with 35 or 70 μg enprostil b.d. (nine volunteers: part 2). Subjects were only allowed a standard dinner at 18.00 hours.

During fasting, in part 1, the number of phase 3 activity patterns (PIIIs) was higher with enprostil than with placebo (P < 0.01), without any difference in their characteristics; the overall duration of phase 1 activity was longer with enprostil than with placebo (P < 0.01). In part 2, during fasting the number and characteristics of the PIIIs were not different, but there was a dose‐related increase in PI, and decrease in PII activity. Fed motor patterns did not differ between the two doses of enprostil.
Pharmacokinetics of famotidine in normal subjects and in patients with chronic liver disease
Authors: MORGAN M. Y. , STAMBUK D. , COTTRELL J. , MANN S. G.
Published: July 2010

The pharmacokinetics of famotidine were studied in seven healthy control subjects and in 14 patients with cirrhosis, following single oral and intravenous 20‐mg dose administration, and after seven daily doses of 40 mg.

Following intravenous (i.v.) administration, the mean (range) total plasma clearance values were not significantly different in the patients with compensated cirrhosis (n= 7), 337 (241–576) ml/min or in the patients with decompensated cirrhosis (n= 7), 270 (120–408) ml/min compared with the control group, 370 (154–612) ml/min. The mean halflife in the compensated cirrhotics, 2.86 (1.87–4.98) h, was similar to that in the control group 2.91 (1.86–6.03) h, but it was insignificantly prolonged in the decompensated cirrhotics 3.35 (2.00–5.77) h.

The mean, maximum, plasma famotidine concentrations after single oral doses were comparable between the groups but there was considerable inter‐subject variability, with individual values ranging from 17 to 139 ng/ml. Peak plasma concentrations were reached within 2–3 h, although more variability was observed among patients with decompensated cirrhosis. The mean systemic availability of the drug, estimated from urinary recovery, was 0.39 (0.15‐0.64) in the healthy controls, 0.35 (0.14‐0.51) in the patients with compensated cirrhosis and 0.38 (0.13‐0.77) in the patients with decompensated cirrhosis.

No significant increases were observed in plasma trough famotidine concentrations following multiple oral dosing in any of the subjects, and the kinetic variables after the seventh dose were not significantly different from those following the single oral dose. in control subjects or in patients between the pre‐study day and day seven of the multiple oral dose phase.

No significant changes were observed in psychometric performance
Duodenal ulcer healing on 2 g of sucralfate daily at bedtime compared to 1 g four times daily
Authors: BENDTSEN F. , EBBEHØJ N. , FALLINGBORG J. , ABILDGAARD K. , MORTENSEN P. BRØBECH , MATZEN P. , KRAG E. , KROMANN‐ANDERSEN H.
Published: July 2010

Seventy‐seven patients with endoscopically verified duodenal ulcers were randomized to treatment with either 2 g sucralfate daily at bedtime or 1 g sucralfate q.d.s. in a controlled double‐blind comparative study. After a 4‐week treatment period, the healing rate was 68% for the former and 69% for the latter treatment.
The absorption of bismuth and salicylate from oral doses of Pepto‐Bismol (bismuth salicylate)
Authors: NWOKOLO C U. , MISTRY P. , POUNDER R. E.
Published: July 2010

Plasma bismuth and plasma salicylate concentrations were measured before and after three 30‐ml oral doses of bismuth salicylate (Pepto‐Bismol liquid) in 10 fasting healthy subjects. From 0 to 120 min following the first dose of bismuth salicylate, the plasma bismuth concentration was less than 1 ng/ml. The peak median plasma bismuth concentration was at + 240 min (1.7 ng/ml; range 0.8–5.3 ng/ml). Salicylate appeared in the plasma of all subjects at + 30 min, and it reached a peak at + 120 min (median 61 mg/L; range 46–104 mg/L).

The study demonstrates that, despite rapid and substantial absorption of salicylate, there is negligible absorption of bismuth into the bloodstream from standard oral doses of bismuth salicylate.
Review article: metronidazole and the anaerobic gut flora
Authors: ELLIOTT T. S. J. , STONE J. W.
Published: July 2010

Metronidazole is a nitro‐imidazole drug which was discovered nearly 30 years ago. Metronidazole has remained the mainstay of anti‐anaerobic therapy following a chance observation that its activity included anaerobic organisms. The predominant human reservoir of these anaerobic organisms is the gastrointestinal tract. In this review, the anaerobic flora and their pathogenic potential are described. The main characteristics of metronidazole and the role of selective decontamination of the gastrointestinal tract are also discussed.
Gastrointestinal pH and transit times in healthy subjects with ileostomy
Authors: FALLINGBORG J. , CHRISTENSEN L. A. , INGEMAN‐NIELSEN M. , JACOBSEN B. A. , ABILDGAARD K. , RASMUSSEN H. H. , RASMUSSEN S. NØRBY
Published: July 2010

Gastrointestinal pH in 11 healthy subjects with ileostomy was determined with a pH‐sensitive, radiotransmitting capsule. Median pH was 7.0 in duodenum, dropped to pH 6.3 in the proximal part, but rose to 7.3 in the distal part of the small intestine. In five subjects the pH of the ileostomy effluents was determined with the pH capsule as well as with a pH meter. Median pH was 7.2 measured with the capsule and 7.4 with the pH meter. The difference between the results obtained with the two methods ranged from 0.1 to 0.3 pH units. The median gastrointestinal transit time of the capsule was 10.5 h (range 6.2–12.8 h). Gastric residence time was 0.6 h (range 0.2–3.8 h), and small intestinal transit time was 10.3 h (range 5.6–11.9 h). Thus the small intestinal transit time in ileostomates is slightly increased compared with values reported from studies on subjects with intact gut. However, no statistically significant correlation was found between the small intestinal transit time and the time elapsed after the creation of the ileostomy. We conclude that colectomy does not alter small intestinal pH but seems to increase the small intestinal transit time of single units.
Immune complex induced experimental colitis: beneficial effect of sulphasalazine in rabbits
Authors: AXELSSON L.‐G. , AHLSTEDT S.
Published: July 2010

Experimental colitis was induced in rabbits by exposing the colon mucosa to 1% formalin followed by i.v. injections of soluble immune complexes made with antigen in excess. The animals were preimmunized with Esherichia coli 014:K7:H — inducing antibodies cross‐reactive to intestinal epithelium.

Animals with this colitis were divided in two groups. One group was treated with sulphasalazine and the other was given vehicle only. Sulphasalazine was administered daily at 125.5 μmol (50 mg) per kg body weight. The administration was started at the same day as the colitis was initiated. At Day 6, 13 and 30 following induction of colitis, biopsies were sampled and histologically evaluated. Inflammation was assessed by scores for inflammatory cells, crypt distortion, decreased crypt number and presence of crypt abscesses, thus corresponding to the picture seen in humans. A statistically significant lower score of inflammation was seen on Day 6 and 13 (P < 0.01) and on Day 30 (P < 0.05) following induction of colitis in animals treated with sulphasalazine.
Twenty‐four‐hour intragastric acidity and nocturnal gastric secretion in gastric ulcer patients—the effects of cimetidine
Authors: DERODRA J. K. , HOWDEN C. W. , BURGET D. W. , HUNT R. H.
Published: July 2010

In a double‐blind randomized study, the profile of 24‐h intragastric acidity and nocturnal gastric secretion was measured in a group of patients with healed gastric ulcer on placebo and 400 mg cimetidine b.d. and 800 mg nocte. Neither cimetidine regimen significantly decreased daytime intragastric acidity, but the 800 mg nocte dose caused a significant decrease in both nocturnal acidity (18.1 to 5.5 mmol/L; P < 0.05) and acid output (11.0 to 1.7 mmol 7 h; P < 0.05). The decrease in nocturnal gastric secretion by 400 mg cimetidine b.d. was not significant.

As in duodenal ulcer, 800 mg cimetidine nocte will effectively suppress night‐time acid secretion in patients with gastric ulcer while leaving acid secretion during the day unaffected.
NSAID‐associated gastroduodenal damage: does famotidine protection extend into the mid‐and distal duodenum?
Authors: AABAKKEN L. , BJØRNBETH B. A. , WEBERG R. , VIKSMOEN L. , LARSEN S. , OSNES M.
Published: July 2010

Eighteen healthy volunteers were included in a cross‐over, double‐blind study where 500 mg naproxen b.d. was given for 1 week with 20 mg famotidine b.d., 40 mg nocte or placebo. Endoscopic evaluation of the gastroduodenal mucosa was performed before and after each treatment period, with separate evaluation of the mid‐ and distal duodenum. 51Cr‐EDTA‐permeability tests were done to study effects on the mid‐ and distal gut, and, in addition, symptom registration was performed. The mucosal damage was significant in all treatment periods, and a statistically significant reduction was seen with 20 mg famotidine b.d. for erosive lesions in the stomach/duodenal bulb region as well as for the sum of damage score in the mid‐ and distal duodenum. The reduction was considerable in a few subjects with extensive duodenal damage. The reduction was considerable in a few subjects with extensive duodenal damage. Intestinal permeation increased significantly in all periods, and was not reduced by famotidine. Symptoms were modest and equal in all periods.
Review article: treatment of the gastrointestinal manifestations of AIDS
Authors: GAZZARD B. G.
Published: July 2010

The Acquired Immune Deficiency Syndrome (AIDS) is frequently associated with infections, infestations, or diseases of the gastrointestinal tract. This review describes the practical aspects of treating oral and oesophageal disease, the management of weight loss and diarrhoea, the role for zidovudine, and the management of Kaposi's sarcoma.
Rectal bismuth subsalicylate as therapy for ulcerative colitis
Authors: RYDER S. D. , WALKER R. J. , JONES H. , RHODES J. M.
Published: July 2010

In a prospective open study, 15 patients with ulcerative colitis which was unresponsive to conventional therapy were treated with enemas containing bismuth subsalicylate (700 or 800 mg b.d.).

Nine out of the 15 patients showed a significant clinical response, and 6 had gone into complete clinical remission after 8 weeks. treatment. Sigmoidoscopic appearances of the rectal mucosa showed improvement in 9 out of 15 patients at 2 weeks, and 11 out of 15 at 8 weeks. The mucosa appeared sigmoidoscopically normal in 6 out of 15 at 8 weeks. It proved possible to reduce the oral prednisolone dosage from a median of 15 mg/day (range 10 to 35 mg/day) to 6 mg/day (range 0 to 18 mg/day) after 8 weeks of treatment; 5 patients were no longer taking oral steroids at this time.

Rectal bismuth subsalicylate appears likely to be an effective therapy in ulcerative colitis and controlled trials are now required.
Gastric histology and plasma gastrin response to a meal in patients with duodenal ulcer disease after five years treatment with ranitidine
Authors: PENSTON J. G. , DIXON J. S. , SELWAY S. A. M. , WORMSLEY K. G.
Published: July 2010

Fifty asymptomatic patients with duodenal ulcer disease, aged 31–82 years, who had received ranitidine maintenance therapy continuously for five or more years without a symptomatic recurrence, were studied. Fasting plasma gastrin concentrations were normal (mean 24 pmol/L, S.D. ± 22) while the post‐prandial gastrin response was variable with maximum plasma concentrations ranging from 16 to 309 pmol/L. Endoscopy revealed six asymptomatic peptic ulcers. Histological examination of gastric biopsies showed mild, superficial inflammatory cell infiltration of the fundic mucosa, but more extensive inflammatory cell infiltration with some atrophy of the mucosal glands in the antral mucosa. Patchy intestinal metaplasia was evident in the antral mucosa of 18 patients. No fundic ECL cell hyperplasia was seen. Helicobacter pylori were detected in the corpus and antrum of most patients. These results suggest that maintenance treatment with ranitidine for 5 years is not associated with either significant hypergastrinaemia or with changes in the fundic mucosa which could be interpreted as pre‐malignant.
Bolus or slow titrated injection of midazolam prior to upper gastrointestinal endoscopy? Relative effect on oxygen saturation and prophylactic value of supplemental oxygen
Authors: BELL G. D. , ANTROBUS J. H. L. , LEE J. , COADY T. , MORDEN A.
Published: July 2010

A total of 131 patients undergoing upper gastrointestinal endoscopy were sedated with midazolam given as a bolus injection over 5 seconds. The oxygen saturation was continuously measured using a pulse oximeter. Supplemental oxygen was given via nasal cannulae at a rate of 3 litres per minute to 54 patients, while the remaining 77 patients only received oxygen if their oxygen saturation dropped below 85%. Both groups in the present series were compared with 3 previously published series of patients, in whom we had used intravenous midazolam as a slow titrated injection.

Despite using on average only two‐thirds of the dose of midazolam, following bolus injection the degree of oxygen desaturation during the endoscopic procedure was greater, and the ability of supplemental oxygen delivered via nasal cannulae to prevent hypoxia was less (P < 0.01), than with a slow titrated injection.
Review article: towards safer parenteral nutrition
Authors: PENNINGTON C. R.
Published: July 2010

Central parenteral nutrition can cause serious complications, particularly in association with the feeding catheter, previously in relation to nutrient provision, and occasionally in other organ systems, notably disease of the liver and abnormalities of bone composition.

Developments in catheter design, the introduction of catheter care protocols based on an understanding of the common routes of catheter infection, and the identification of factors associated with central vein thrombosis have all reduced dramatically the incidence of complications. Furthermore, problems such as catheter occlusion, catheter infection and central vein thrombosis can now be treated effectively in many patients without the loss of the feeding catheter.

This review summarizes the common and important complications of parenteral feeding with emphasis on their practical prevention and management.
Effects of PGE2, carbenoxolone, cholecystokinin, and the thromboxane‐mimetic u46619 on protein and glycoprotein production by isolated pig gastric mucosal cells
Authors: HEIM H.‐K. , OESTMANN A. , SEWING K.‐Fr.
Published: July 2010

We studied the effects of prostaglandin (PG) E2, carbenoxolone, cholecystokinin‐octapeptide (CCK‐OP), and the thromboxane‐mimetic U46619, all known to stimulate gastric mucus secretion in vivo, on protein and glycoprotein synthesis in and release from isolated and enriched pig gastric mucous cells, as measured by the incorporation of [3H]L‐leucine and N‐acetyl‐[14C]D‐glucosamine respectively into cellular and released acid insoluble material. PGE2 stimulated glycoprotein and protein synthesis (EC50 7 and 30 nmol/L, respectively) and release (EC50 50 and 140 nmol/L, respectively) in a concentration‐dependent manner, whereas carbenoxolone, CCK‐OP and U46619 failed to enhance the incorporation of the tracers. We conclude that stimulation of mucus secretion by PGE2 is related to direct effects on protein and glycoprotein production of gastric non‐parietal cells, whereas indirect effects may be involved in the stimulation by carbenoxolone, CCK‐OP, and U46619.
The role of platelet activating actor in acute gastric injury and its protection by sucralfate
Authors: LIGUMSKY M. , SESTIERI M. , KARMELI F. , OKON E. , RACHMILEWITZ D.
Published: July 2010

Platelet activating factor, a potent inflammatory mediator, has been reported to induce gastrointestinal damage, whereas its inhibition or antagonism is associated with mucosal protection. The aim of the present study was to elucidate the association between acute experimental gastric damage and mucosal platelet activating factor generation in the rat, and to evaluate the protective effect of sucralfate in relation to mucosal platelet activating factor formation. Gastric damage in the rat was induced by either subcutaneous injection of indomethacin 30 mg/kg or intragastric administration of aspirin 100 mg/kg, hydrochloric acid 0.6 N, taurocholate 30 mM, ethanol 96%, or sodium chloride 25%. All agents induced a significant increase in mucosal platelet activating factor levels concomittently with induction of mucosal damage. Pretreatment with sucralfate 150 mg/rat provided a significant macroscopic and microscopic mucosal protection in all experimental models. This protection was associated with a significant decrease in mucosal platelet activating factor level in the hydrochloric acid, taurocholate, ethanol and hyperosmolar sodium chloride treated rats, whereas it remained unchanged in the aspirin and indomethacin treated rats. The data imply that platelet activating factor may have a limited role in the pathogenesis of indomethacin or aspirin induced damage, where other mechanisms such as cyclooxygenase inhibition dominate. In the damage induced by topical strong irritants, platelet activating factor may have a major pathogenetic role.
Helicobacter pylori associated chronic gastritis and peptic ulceration in patients taking non‐steroidal anti‐inflammatory drugs
Authors: SHALLCROSS T. M. , RATHBONE B. J. , WYATT J. I. , HEATLEY R. V.
Published: July 2010

Helicobacter pylori is now recognized as a frequent cause of histological chronic gastritis, and this has radically changed our understanding of this common condition. In the light of these developments, the traditional view that non‐steroidal anti‐inflammatory drugs are one of the common ‘environmental’causes of chronic gastritis has been re‐examined.

Gastric mucosal biopsies have been studied from 430 patients undergoing routine upper gastrointestinal endoscopy, 99 of whom had recently been taking non‐steroidal anti‐inflammatory drugs. No significant association was found between the use of these drugs and either the presence of chronic gastritis or the frequency of colonization with H. pylori, although there was a strong association (P < 0.0001) between H. pylori and gastritis. Non‐steroidal anti‐inflammatory drugs appear, however, to modify the inflammatory process in the gastric body, leading to a lower frequency of atrophic gastritis (P < 0.05). The majority of peptic ulcers were associated with H. pylori irrespective of non‐steroidal anti‐inflammatory drug use, but there was a higher frequency of H. pylori negative ulceration in the patients who had used these agents (P < 0.04). Peptic ulceration was uncommon in the absence of either H. pylori or recent non‐steroidal anti‐inflammatory drug use.
Asymptomatic duodenal ulcers occurring during maintenance treatment with ranitidine
Authors: PENSTON J. G. , WORMSLEY K. G.
Published: July 2010

Fifty‐seven patients who developed asymptomatic recurrence of duodenal ulceration during maintenance treatment with ranitidine were followed up to assess the risk of developing symptoms or complications of ulcer disease. The risk of development of symptomatic ulcer recurrence was 4% in the first year of follow‐up during continuous maintenance treatment, irrespective of whether or not the asymptomatic ulcer had been actively treated (by doubling the dose of ranitidine used for maintenance therapy). The asymptomatic duodenal ulceration during maintenance treatment did not predispose to complications such as haemorrhage or perforation. It seems, therefore, that patients receiving maintenance treatment for duodenal ulceration do not require endoscopic re‐examination unless symptoms have recurred, because the asymptomatic recurrences of duodenal ulceration occurring during maintenance treatment are clinically benign, usually heal spontaneously if maintenance treatment is continued, and do not require active medical intervention.
Luminal concentrations of orally ingested 4‐aminosalicylic acid as determined by in‐vivo equilibrium dialysis
Authors: BEEKEN W. , NASR B. , BIGELOW J. , ROFF N.
Published: July 2010

We measured 4‐aminosalicylic acid (4‐ASA) levels in faecal water by in‐vivo equilibrium dialysis during oral ingestion of drug by two different dose protocols (A and B). In Protocol A, 5 normal subjects ingested 3 g of 4‐ASA as the free acid and 20 mg of metaclopromide per day. On Day 5, small dialysis sacs filled with dextran 40 were ingested and the oral drug was continued until the sacs were retrieved from the stool. Protocol B followed the same format except that 3 g of 4‐ASA was ingested twice daily and metaclopromide was omitted. In both protocols concentrations of 4‐ASA and N‐acetylated 4‐ASA in sac contents were measured by HPLC. In‐vitro dialysis studies showed bi‐directional equilibrium was reached within 120 min. During Protocol A, intraluminal concentrations of total 4‐ASA ranged from 14.0 to 32.2 mmol/L with a mean of 20.6 mmol/L. With Protocol B, total 4‐ASA levels ranged from 20.1 to 41.3 mmol/L with a mean of 33.9 mmol/L. From 90 to 99% of the drug in the dialysates was N‐acetylated. These concentrations of total 4‐ASA are similar to those of 5‐ASA after ingestion of therapeutic doses of sulphasalazine or absorption‐resistant formulations of 5‐ASA. Thus, oral 4‐ASA could have a role in the treatment of inflammatory bowel disease.
Effect of enprostil on the gastroduodenal mucosa of healthy volunteers
Authors: LANZA F. L. , ROBINSON M. G. , ISENBERG J. I. , BASUK P. M. , KARLIN D. A.
Published: July 2010

Enprostil is a synthetic dehydro‐prostaglandin E2 with gastroduodenal ulcer‐healing and mucosal‐protective properties. One hundred and three healthy volunteers were randomized to receive capsules of enprostil 35 μg b.d. (the clinically recommended dose), enprostil 70 μg b.d., or placebo b.d. All underwent endoscopic assessment of the gastroduodenal mucosa, scored using a 0–4 scale, at baseline and on Days 3, 7, 14, 21 and 28 of dosing. Mean and median maximum scores demonstrated a dose response, and the mean maximum scores were statistically significantly higher for both enprostil groups on each endoscopy day when compared with placebo. The majority of enprostil‐treated subjects had petechial haemorrhages. The proportion of volunteers with small white‐based mucosal breaks (erosions) was significantly higher for the fundus in the enprostil 70‐μg group on Days 21 and 28 when compared with placebo, but there were no significant differences between treatment groups for any area on the other study days. The 70‐μg dose was
The effect of colestipol dose on postprandial serum bile acid concentration: assessment by an enzymic bioluminescence procedure
Authors: FLEISHAKER J. C. , ROSSI S. S. , SMITH R. B. , WELSHMAN I. R. , DAEI F. , ANGELLOTTI M. A. , HOFMANN A. F.
Published: July 2010

A dose‐response study was performed with three doses of colestipol, using postprandial serum bile acid levels to assess bile acid sequestering activity in 40 volunteers with asymptomatic hyperlipidaemia. Subjects who entered the study had total serum cholesterol concentrations greater than 220 mg/dl and triglyceride concentrations less than 200 mg/dl. They were randomly assigned to one of four parallel treatment groups: (a) placebo b.d., colestipol (as Colestid hydrochloride granules) 2.5 g b.d., (c) colestipol 5 g b.d., and (d) colestipol 7.5 g b.d. Subjects were maintained on a constant repeating solid diet throughout the 6‐day study period, and colestipol was ingested 30 min before breakfast and dinner. No drug was administered on Days 1–3; baseline (pre‐treatment) serum bile acid concentration profiles were determined on Day 3. The above treatments were given on Days 4–6, and total serum bile acid
A comparison between enprostil and ranitidine in the management of gastric ulceration
Authors: MORGAN A. G. , PACSOO C. , TAYLOR P. , McADAM W. A. F.
Published: July 2010

In a randomly allocated, double‐blind, endoscopically controlled study, 98 patients with gastric ulcers were treated with either (a synthetic prostaglandin of E2‐like structure) enprostil 70 μg b.d. or 150 mg ranitidine b.d. The healing rates at 4, 8 and 12 weeks were enprostil 57, 91 and 94% and for ranitidine 55, 88 and 98%, respectively. Following ulcer healing, half the patients were followed for 1 year without treatment and the others were given 70 μg enprostil nocte. Endoscopy was repeated in both groups after 6 and 12 months or if dyspeptic symptoms returned. The recurrence rate without maintenance at 6 and 12 months, following ranitidine therapy, was 67 and 75%, and after enprostil therapy 50 and 61%, respectively. On maintenance enprostil, the recurrence rates were 28 and 40%. Forty‐seven per cent of patients who completed maintenance treatment had a proven ulcer recurrence within 6 months of stopping therapy. Diarrhoea was a common sideeffect of enprostil therapy. Seven patients were withdrawn because of diarrhoea or abdominal pain.
The effect of portal hypertension on indomethacin‐induced small intestinal ulceration in the rat
Authors: JONAS G. M. , ERICKSON R. A. , CHUNG K.
Published: July 2010

The purpose of this study was to determine whether portal hypertension potentiates intestinal ulceration induced by indomethacin. Portal hypertension was produced in male Sprague‐Dawley rats by two‐staged ligation of the portal vein. Sham‐operated rats were used as controls. The rats were given 20 mg/kg of indomethacin intragastrically, 7 and 14 days, respectively, after complete portal vein ligation. Forty‐eight and 72 h after indomethacin, portal pressures were measured and the whole small intestine removed for quantitative measurement of the percent of the mucosa ulcerated by computerized image analysis. There were no differences in the area of ulceration between the portal hypertensive and sham‐operated rats at either 7 or 14 days, despite the presence of significant portal hypertension. Portal hypertension does not appear to potentiate small intestinal ulceration induced by indomethacin in rats.
Colloidal bismuth subcitrate causes sustained release of gastric mucosal prostaglandin E2
Authors: MERTZ‐NIELSEN A. , STEENBERG P. , NEUMARK T. , BUKHAVE K. , RASK‐MADSEN J.
Published: July 2010

Gastric application of high doses of colloidal bismuth subcitrate (CBS) stimulates mucosal prostaglandin E2 (PGE2) production, which is considered part of the mechanism by which the drug accelerates peptic ulcer healing. Whether therapeutic, orally administered, doses of CBS cause a sustained stimulation of prostaglandin production is not known. We have, therefore, determined gastric luminal release of PGE2 during ‘steady‐state’perfusion of the stomach with CBS (10 mg/ml; isotonic mannitol 5 ml/min) and 4 h after the last oral dose of the drug (240 mg b.d.) for 2 weeks (isotonic mannitol 5 ml/min) in 8 healthy volunteers. A significant increase in PGE2 concentrations (712 (409–1076) vs. control 334 (252–655) pg/ml; medians with Q50 ranges; P < 0.02) and PGE2 output (12.5 (7.3–14.3) vs. control 4.8 (4.1–7.3) ng/15 min; P < 0.02) occurred during gastric perfusion with CBS. A similar increase in PGE2 concentrations (630 (297–1429) pg/ml; P < 0.02) and PGE2 output (12.6 (6.4–22.2) ng/15 min; P < 0.02) was observed following treatment with CBS for 2 weeks. These results suggest that therapeutic doses of CBS cause a sustained stimulation of gastric mucosal PGE2 formation.
Efficacy of misoprostol and ranitidine in the prevention of duodenal ulcer relapse and its correlation with endogenous gastric prostanoid synthesis
Authors: GOLDIN E. , KARMELI F. , RACHMILEWITZ D.
Published: July 2010

We determined endogenous gastric prostaglandin synthesis and its correlation with the prevention of duodenal ulcer relapse by misoprostol and ranitidine. Sixty‐one patients with recent endoscopically healed duodenal ulcer were randomly allocated in a double‐blind fashion for one year of treatment with misoprostol 400 μmUg nocte, ranitidine 150 mg nocte or placebo. Patients were followed every two months. Endoscopy was repeated at six and 12 months or beforehand, if relapse was suspected. Antral and fundic biopsies, 3–4 from each region, were obtained at each endoscopy for determination of prostaglandin synthesis. During the one year of treatment, 11 out of the 12 placebo treated patients flared up, as opposed to 10 out of 25 and four out of 24 misoprostol and ranitidine treated patients, respectively. The difference between all treatment groups was significant (P < 0.0001). In all subjects who flared up, pretrial endogenous antral and fundic prostaglandin E2 synthesis were not different from their respective synthesis in those who did not relapse. These results indicate that one year of treatment with both ranitidine and misoprostol prevents ulcer relapse better than placebo. However, ranitidine is significantly better than misoprostol. Both at six and 12 months there was no significant difference between the two treatment groups in the trend towards enhanced synthesis of gastric prostanoids.

These results indicate that one year of treatment with both ranitidine and misoprostol prevents ulcer relapse better than placebo. However, ranitidine is significantly better than misoprostol. Both at six and 12 months there was no significant difference between the two treatment groups in the trend towards enhanced synthesis of gastric prostanoids.
Steady‐state pharmacokinetics of enteric coated 5‐amino‐salicylic acid tablets in healthy volunteers and in patients with Crohn's disease or ulcerative colitis
Authors: NORLANDER B. , GOTTHARD R. , STRÖM M.
Published: July 2010

An Eudragit‐L coated oral 5‐aminosalicylic acid (5‐ASA; mesalazine) product (Mesasal), has been formulated to deliver 5‐ASA to the distal small bowel and colon for the treatment of inflammatory bowel disease. The purpose of this study was to compare the pharmacokinetic profile of this product at steady‐state between healthy volunteers and two different patient groups with inflammation of either the small or the large bowel.

Two carefully selected groups of patients, nine with Crohn's disease restricted to the small intestine and ten with total ulcerative colitis and one group of ten healthy volunteers received two 250 mg Mesasal tablets three times daily for 10 days to reach steady‐state. Plasma 5‐ASA and acetyl‐5‐ASA concentrations were followed for 48 h and urinary excretion for 72 h.

There was a great variation in most pharmacokinetic parameters within each group and no significant differences were noticed between the groups. The location of the inflammatory process probably does not influence the pharmacokinetics of 5‐ASA in any significant way in patients with either Crohn's disease in the small bowel or total ulcerative colitis.
Omeprazole and Helicobacter Pylori: temporary suppression rather than true eradication
Authors: WEIL J. , BELL G. D. , POWELL K. , MORDEN A. , HARRISON G. , GANT P. W. , JONES P. H. , TROWELL J. E.
Published: July 2010

Twenty‐four Helicobacter pylori (H. pylori)‐positive patients were treated for 28 days with either 20 mg omeprazole o.m. (n= 12) or 40 mg omeprazole o.m. (n= 12). Clearance (absence of H. pylori at the end of or shortly after treatment) and eradication (absence of H. pylori 1 month after cessation of treatment) were assessed using the 14C‐urea breath test. Observed clearance and eradication were: 20 mg omeprazole 3/12 and 0/12; 40 mg omeprazole 6/12 and 1/12 respectively. The effect on H. pylori is probably due to the change in gastric pH from acid to neutral, however it is insufficient to recommend the inclusion of omeprazole in regimens aimed at eradicating H. pylori.
Colchicine in primary biliary cirrhosis
Authors: WARNES T. W.
Published: July 2010

Colchicine, which has been used for hundreds of years in the treatment of gout, has found a new use in the treatment of cirrhosis. In the experimental animal, and in vitro, colchicine decreases inflammation, inhibits collagen synthesis and also increases collagen degradation by activating collagenase. Many of the putative beneficial actions of the drug in cirrhosis, as well as its toxic side effects, are due to the fact that it binds to tubulin and thereby disrupts microtubules; however, it is unclear which of these actions, mostly demonstrated in the experimental animal, are present in the doses currently used in man.

There have been 4 controlled trials of colchicine in various forms of cirrhosis, three of which have concerned primary biliary cirrhosis. Data are currently available on 146 colchicine‐treated patients, of which 92 had primary biliary cirrhosis. Colchicine improves the conventional liver function tests in primary biliary cirrhosis and also reverses the basic defect in hepatic excretory capacity characteristic of this disease. The drug appears to have no significant effect on symptoms, clinical features or liver histology, but in 2 of the 3 primary biliary cirrhosis trials, as in the Mexican study of alcoholic and post‐hepatitic cirrhosis, colchicine treatment was associated with improved survival.
Somatostatin and octreotide in gastroenterology
Authors: BURROUGHS A. K. , McCORMICK P. A.
Published: July 2010

Somatostatin and octreotide have a definitive role in the management of symptomatic gut neuroendocrine tumours, particularly VIPomas and carcinoid. They probably also have a role in variceal bleeding, but this needs further confirmatory randomized trials. At present there is a potential role in the management of short bowel syndrome, dumping syndrome and gastrointestinal fistulae, but randomized clinical studies are needed. Possibly there is a role in AIDS‐related diarrhoea and ‘idiopathic’ secretory diarrhoea, but more evidence is required. They have no role in acute pancreatitis and peptic ulcer bleeding. Irritable bowel syndrome remains unexplored but unlikely to benefit.
Fate of orally ingested enzymes in pancreatic insufficiency: comparison of two pancreatic enzyme preparations
Authors: DELCHIER J.‐C. , VIDON N. , GIRARDIN M.‐F. SAINT‐MARC , SOULE J.‐C. , MOULIN C. , HUCHET B. , ZYLBERBERG P.
Published: July 2010

The effect on steatorrhoea of a pH‐sensitive enteric‐coated pancreatic preparation (Eurobiol 25 000) was compared with a conventional pancreatic enzyme preparation (Eurobiol) in six adult patients with exocrine pancreatic insufficiency. In addition, the fate of orally ingested pancreatic enzymes in the upper digestive tract was evaluated by measuring gastric and duodenal pH, amount of enzymes in the stomach, duodenal enzyme output, and fat absorption at the angle of Treitz for the 4 hours following a standard meal. When compared with placebo, Eurobiol and Eurobiol 25 000 reduced daily faecal fat excretion by 24% (not significant) and 43% (P < 0.05), respectively. With the conventional preparation, enzyme output and fat absorption at the duodeno‐jejunal flexure were significantly improved (P < 0.05). Marked inter‐individual differences in duodenal enzyme recovery (lipase 3% to 80%; chymotrypsin 26% to 100%) and, consequently, in the reduction of steatorrhoea (0% to 67%) were observed, with the gastric emptying rate emerging as a key determinant factor. With the enteric‐coated preparation, enzyme output and fat absorption at the duodenojejunal flexure were not significantly improved. Discrepancy between the marked reduction of faecal fat excretion and the low duodenal enzyme recovery could indicate that enzyme delivery from microtablets occurs further down in the small bowel. Efficacy of enteric‐coated preparations could be enhanced by adding unprotected enzymes, especially in patients with rapid gastric emptying.
Pattern of breathing during upper gastrointestinal endoscopy: implications for administration of supplemental oxygen
Authors: BELL G. D. , ANTROBUS J. H. L. , LEE J. , COADY T. J. , MORDEN A.
Published: July 2010

Cardiopulmonary complications account for half the deaths associated with upper gastrointestinal endoscopy. The incidence of hypoxia at the time of upper gastrointestinal endoscopy can be greatly reduced by the administration of supplemental oxygen via nasal cannulae. Using dual thermistors in the mouth and nostrils of patients undergoing upper gastrointestinal endoscopy, the present study demonstrates that most patients breathe predominantly via the oral, rather than the nasal, route following intubation of the oesophagus. The implication from the study is that, if supplemental oxygen is to be used in ‘at risk’patients, it would be logical to employ an oral, rather than nasal, route of administration.
Review article: assessment of drug therapy in inflammatory bowel disease
Authors: HODGSON H. J. F. , MAZLAM M. Z.
Published: July 2010

This review article surveys the clinical and laboratory parameters used to assess and quantitate inflammation in ulcerative colitis and Crohn's disease, with particular reference to their usage in controlled trials of drugs in inflammatory bowel disease.
Influence of cisapride on antroduodenal motor function in healthy subjects and diabetics with autonomic neuropathy
Authors: WEHRMANN T. , LEMBCKE B. , CASPARY W. F.
Published: July 2010

Antroduodenal manometry was used to assess motility in 10 healthy volunteers and 15 diabetics with cardiac autonomic neuropathy whilst they received 20 mg cisapride orally or an apparently identical placebo. Interdigestive motility was recorded after an overnight fast and for 2 hours following a 500 kcal liquid meal. Active treatment did not influence the number or duration of interdigestive motility cycles in either group although antroduodenal co‐ordination in both the fasting and the fed state was enhanced by cisapride (P < 0.05). In diabetics the postprandial antral motility index was increased by cisapride, whereas in healthy subjects antral and duodenal motility indices were increased both fasting and in the fed state (P < 0.05).

These results suggest that impaired antroduodenal co‐ordination is of importance in delaying gastric emptying by diabetic subjects.
Effect of different doses of omeprazole on 24‐hour oesophageal acid exposure in patients with gastro‐oesophageal reflux
Authors: ROBINSON M. , MATON P. N. , ALLEN M. L. , HUMPHRIES T. J. , McINTOSH D. , CAGLIOLA A. J. , BRADSTREET T. E.
Published: July 2010

To define the optimum doses of omeprazole appropriate for acute and long‐term therapy of patients with gastro‐oesophageal reflux disease, 24‐h oesophageal pH was measured in 12 patients with symptomatic reflux and an abnormal 24‐h oesophageal acid exposure time (> 6%) in a randomized, double‐blind, four‐way crossover study comparing the effects of omeprazole 10, 20, or 40 mg/day and placebo. Total reflux time over 24 hours, number of reflux episodes per hour, and the number of reflux episodes lasting > 5 minutes were measured by ambulatory 24‐h oesophageal pH monitoring. All doses of omeprazole were superior to placebo in decreasing gastro‐oesophageal reflux as measured by each index.

With placebo, oesophageal acid exposure was 16.3 % of the 24 hours, 10 mg omeprazole/day reduced that to 6.3 %, 20 mg/day lowered acid exposure to 0.9%, and 40 mg/day to 0.6%. Thus only the 20 and 40 mg doses reduced acid exposure to within the normal range. Similar results were obtained with the other indices of reflux. These data suggest that a rational dose regimen for reflux oesophagitis is 20 mg/day, a regimen that has proved effective in clinical trials. The present study indicates that 24‐hour oesophageal pH monitoring is a practical approach to the determination of drug dosage in patients with gastro‐oesophageal reflux.
Non‐steroidal anti‐inflammatory drug‐induced gastroduodenal injury: therapeutic recommendations
Authors: CURTIS W. D. , GRIFFIN J. W.
Published: July 2010

Non‐steroidal anti‐inflammatory drug (NSAID) use is associated with gastro‐duodenal erosions and ulcers. Bleeding and perforation are reported complications in NSAID users. Therapeutic recommendations for NSAID‐induced gastroduodenal injury are necessary because of our rapidly growing geriatric population, a steady increase in prescriptions for NSAIDs, and the widespread use of over‐the‐counter NSAIDs. Studies seem to indicate that there is no relationship between acute NSAID‐induced mucosal injury and potential damage from chronic NSAID ingestion. Ranitidine (150 mg) b.d. effectively reduces the incidence of duodenal ulcer in NSAID users, but the same dose does not reduce the incidence of gastric ulcer. Misoprostol is effective in reducing the incidence of gastric ulcer in NSAID users, although confirmatory data on its effectiveness in preventing NSAID‐induced duodenal ulcer are lacking. In addition to anti‐ulcer therapy, treatment of NSAID‐induced ulcers includes discontinuing the drug, reducing the dose, or switching to a less potent NSAID. Longer courses of anti‐ulcer treatment may be required to achieve expected healing rates when NSAIDs are not discontinued. Results of treatment of NSAID‐related ulcers with currently available anti‐ulcer medications vary. Several studies have shown that 150 mg ranitidine b.d. heals both gastric and duodenal NSAID‐induced ulcers. Sucralfate has also been shown to heal NSAID‐induced duodenal ulcers. Misoprostol treatment of NSAID‐induced ulcers is not well documented, although there are placebo‐controlled data that substantiate its benefit in gastric ulcer patients not taking NSAIDs.
Review article: the treatment of Helicobacter pylori infection
Authors: HEATLEY R. V.
Published: July 2010

The discovery of Helicobacter pylori has stimulated great interest in its role in gastritis, non‐ulcer dyspepsia and peptic ulceration. Treatment regimens to eradicate this organism from gastric mucosa have also received considerable attention. Current recommendations limit the use of triple drug combinations only to specific patient groups.
Does a previous course of tripotassium dicitrato bismuthate afect the subsequent chances of successful Helicobacter pylori eradication?
Authors: BELL G. D. , POWELL K. , BURRIDGE S. M. , HARRISON G. , WEIL J. , GANT P. W. , JONES P. H. , TROWELL J. E.
Published: July 2010

We have performed a retrospective study of 103 patients with either peptic ulcer or non‐ulcer dyspepsia, infected with metronidazole‐sensitive strains of Helicobacter pylori (H. pylori), who were treated with a combination of tripotassium dicitrato bismuthate and metronidazole for a period of at least two weeks.

Dual therapy with tripotassium dicitrato bismuthate plus metronidazole showed similarly high eradication rates (≥ 80%) of H. pylori from patients irrespective of age, gender or clinical diagnosis. Most importantly, dual therapy achieved a similar eradication rate of H. pylori infection in 41 patients who had previously been treated with tripotassium dicitrato bismuthate alone or in combination with an antibiotic other than metronidazole. It therefore appears that H. pylori does not become resistant to treatment with tripotassium dicitrato bismuthate.
Verapanzil inhibits in‐vitro leucotriene B4 release by rectal mucosa in active ulcerative colitis
Authors: GERTNER D. J. , RAMPTON D. S. , STEVENS T. R. J. , LENNARD‐JONES J. E.
Published: July 2010

Increased mucosal eicosanoid synthesis occurs in active ulcerative colitis; suppression of the synthesis of pro‐inflammatory leucotrienes could be therapeutically useful. Neutrophil 5‐lipoxygenase is calcium‐dependent. In this study, the effect of the calcium channel antagonist, verapamil, on the release of eicosanoids by colitic rectal mucosal biopsies has been examined. Verapamil in therapeutic concentration (5 μ g/ml, 10‐5 M) reduced leucotriene B4 release from actively inflamed rectal mucosa by 30% (from 60 (5.0 S.E.M.) ng/g wet weight/20 min without, to 42 (5.7 S.E.M.) with verapamil, P < 0.05), but had no effect on leucotriene B4 release by rectal biopsies taken from patients with quiescent ulcerative colitis (39 (2.8 S.E.M.) ng/g wet weight/20 min without, and 43 (5.0 S.E.M.) with verapamil). Verapamil did not affect mucosal prostaglandin E2 release. The results suggest that, in active ulcerative colitis, verapamil inhibits mucosal 5‐lipoxygenase activity and warrants therapeutic evaluation.
Cholestasis in transplant patients—what is the role of cyclosporin?
Authors: BLUHM R. E. , RODGERS W. H. , BLACK D. L. , WILKINSON G. R. , BRANCH R.
Published: July 2010

The use of the drug cyclosporin is limited by toxicity. It would be advantageous to develop therapeutic monitoring of cyclosporin which would predict the development of clinical toxicity. In the present study, alternative methods of measuring cyclosporin levels were evaluated in a heterogenous population of transplant patients, comparing a fluorescent polarization immunoassay using a non‐specific polyclonal antibody, which measures both cyclosporin and its main metabolites, and a specific high‐performance liquid chromatography assay for unchanged cyclosporin in blood.

Neither measured variable alone correlated with laboratory evidence of renal toxicity (serum creatinine) or liver toxicity (serum glutamate transaminase, lactic dehydrogenase, alkaline phosphatase, or serum bilirubin). The relationship between metabolites and parent cyclosporin was quantitated using the ratio of cyclosporin levels determined by fluorescent polarization immunoassay over levels determined by high‐performance liquid chromatography. A cohort of patients with markedly elevated ratios of cyclosporin were identified. When patients’data were reviewed collectively and individually there was a correlation between an elevated ratio and the serum bilirubin (r= 0.41, P < 0.001). This association could be either due to cyclosporin as a cause of cholestasis or to cholestasis from any cause resulting in netaboite accumulation. Further studies are needed to clarify the role of cyclosportin in hepatic dysfunction and develop erly, specific markers for this cyclosporin‐associated toxicity.