bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of cisapride on the topography of oesophageal peristalsis
Authors: STAIANO A. , CLOUSE R. E.
Published: October 2003

Background: Topographic analysis of oesophageal motility in humans demonstrates sequential pressure regions in the peristaltic wave. This study was designed to see if cisapride preferentially affects any of the topographic regions.

Methods: Fifteen asymptomatic volunteers received placebo, 10 mg or 20 mg of cisapride orally in a double‐blind, single‐dose trial. Topographic plots of oesophageal peristalsis through the oesophageal body and lower sphincter were analysed before and after drug administration for each subject.

Results: Four sequential contraction segments through the oesophageal body and lower sphincter, separated by amplitude troughs, were again identified on contour plots in normal subjects. Dose‐related increases from cisapride were found in the contraction volume of the first smooth‐muscle segment (P<0.0001), in total contraction volume (P=0.005) and in the amplitude of the trough separating smooth‐muscle segments of the oesophageal body (P=0.005). Within the distal smooth‐muscle segment, significant drug effects were seen only in the cephalad half (P=0.03). Significant effects on conventional manometric parameters could not be demonstrated.

Conclusions: Cisapride enhances contraction in the proximal smooth‐muscle segment of the oesophageal body and partially obliterates the pressure trough separating the adjacent smooth‐muscle segment. Considering the known effects of this agent on neural function, our findings support a gradient in cholinergic influence on peristalsis through the human smooth‐muscle oesophagus. Topographic analysis is a novel and sensitive way of examining the effects of pharmacological manipulations on oesophageal peristalsis.
Helicobacter pylori eradication in clinical practice: one‐week low‐dose triple therapy is preferable to classical bismuth based triple therapy
Authors: GODDARD A. F. , SPILLER R. C.
Published: October 2003

Background: Both classical 2‐week bismuth based triple therapy and the newer 1‐week low‐dose omeprazole based triple therapies achieve high Helicobacter pylori eradication rates in controlled clinical trials and are in widespread use in routine clinical practice. However, their efficacy and acceptability in this setting is unproved.

Methods: Over a 1‐year period, the notes for patients attending a dedicated H. pylori treatment clinic were audited. Assessments were made of patient demographics, diagnosis, smoking habits, use of H2‐antagonists, regimen used, efficacy of treatment, compliance and side‐effects experienced.

Results: 223 sets of notes were audited. 89 patients received bismuth, tetracycline and metronidazole for two weeks and 111 patients received omeprazole, clarithromycin and either metronidazole (63 patients) or tinidazole (48 patients) for 1 week. Successful eradication was achieved in 75/89 (84.3%), 56/63 (89%) and 42/48 (88%), respectively, (P = N.S.). Severe side‐effects occurred in 11 (12%) of patients receiving bismuth based treatment compared to 1 (0.9%) patient receiving omeprazole based regimens (P<0.02). Treatment failure in patients receiving omeprazole based treatment was associated with smoking (P<0.05).

Conclusions: Outside the context of clinical trials, both regimens achieved acceptable eradication rates. However, 1‐week low‐dose therapy is preferable due to the lower incidence of severe side‐effects.
One week triple therapy with omeprazole, clarithromycin and tinidazole for Helicobacter pylori: differing efficacy in previously treated and untreated patients
Authors: MOSHKOWITZ M. , KONIKOFF F. M. , PELED Y. , BRILL S. , HALLAK A. , TIOMNY E. , SANTO M. , BUJANOVER Y. , GILAT T.
Published: October 2003

Background: Triple therapy with omeprazole, clarithromycin, and tinidazole (OCT) has been found to be highly effective against Helicobacter pylori infection. However, its efficacy as a second line regimen for patients who failed metronidazole‐based triple therapy has not been evaluated.

Aim: The aim of this study was to evaluate the efficacy of low‐dose, short‐term OCT therapy in an Israeli population, and to compare results obtained in previously treated and untreated patients.

Methods: Patients with duodenal or gastric ulcers and chronic antral gastritis with H. pylori infection as assessed by rapid urease test and/or 14C urea breath test (14C‐UBT), were studied. All patients received omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. for 7 days. Eradication was assessed by 14C‐UBT 4 weeks after treatment.

Results: One hundred and fourty‐four patients (M/F=81/63) were enrolled (mean age 48.1 years, range 12–78). Eradication of H. pylori was significantly different between patients who were initially treated with this regimen (90/94, 96%) and patients who had previously failed to eradicate H. pylori with standard triple therapy (27/50, 54%). Moreover, the eradication rate was significantly decreased in patients with more than one previous failure (9/22, 41%) compared to that in patients with only one failure (18/29, 62%). No other differences such as age, gastric pathology, ethnic origin, smoking habits, or pre‐treatment urease activity were found to influence the eradication rate.

Conclusions: One‐week low‐dose triple therapy with OCT is highly effective as an initial therapy in eradicating H. pylori infection. The efficacy is significantly lower when given as a second line treatment in patients who have previously failed to eradicate H. pylori with bismuth‐based standard triple therapy.
Treatment of left‐sided ulcerative colitis with butyrate enemas: a controlled trial
Authors: STEINHART A. H. , HIRUKI T. , BRZEZINSKI A. , BAKER J. P.
Published: October 2003

Background: The colonic mucosa is highly dependent upon the presence of luminal nutrients. This dependence is most marked in the distal colon. The major luminal nutrients are short chain fatty acids that are produced as a by‐product of colonic fermentation of carbohydrates. Butyrate appears to be the short chain fatty acid most avidly metabolized by the colonic mucosa. It has been suggested that ulcerative colitis is, at least in part, related to an energy deficiency state of the colonic mucosa which may be secondary to impaired short chain fatty acid production, uptake or utilization. The objective of this study was to determine if butyrate given as enema therapy is effective in the treatment of active distal ulcerative colitis.

Methods: Thirty‐eight patients with distal ulcerative colitis were randomly assigned to receive nightly butyrate (n=19) or saline/placebo (n=19) enemas. Butyrate enemas consisted of 60 mL of 80 mm sodium butyrate titrated to a pH of 7.0. Patients were assessed clinically and endoscopically at baseline and at 3 and 6 weeks follow‐up. Pre‐ and post‐treatment mucosal biopsies were assessed histologically. Response to therapy was determined by changes in a 12‐point clinical disease activity index score based on patient symptoms, endoscopic mucosal appearance and physicians' global assessment.

Results: Clinical improvement was noted in seven of 19 (37%) butyrate‐treated patients and nine of 19 (47%) placebo‐treated patients (P=0.51). Clinical remission was achieved in three patients in each group (16%). No toxicity was observed in either treatment arm.

Conclusions: The results suggests that once nightly 60 mL butyrate enemas (80 mmol/L) are not efficacious in the treatment of distal ulcerative colitis.
Nocturnal intragastric acidity after over‐the‐counter doses of famotidine, ranitidine or placebo
Authors: GRIMLEY C. E. , COTTRELL J. , MANN S. G. , STAUFFER L. , NWOKOLO C. U.
Published: October 2003

Aim:

To compare the inhibitory effects of over‐the‐counter doses of famotidine or ranitidine on nocturnal intragastric acidity in a placebo‐controlled study.

Methods:

Twelve‐hour intragastric acidity was measured simultaneously in 24 healthy subjects who ate a standard meal at 18.30 h and were dosed (at 19.30 h) with either famotidine 10 mg, ranitidine 75 mg or placebo in a balanced three‐period crossover design. Five‐millilitre aliquots of gastric juice were aspirated half‐hourly 0–3 h post‐dose, and then hourly until the end of the study. pH was measured with a glass electrode. Integrated pH (area under the curve (AUC) of the pH–time curve) was calculated for the intervals 0–12 h and 9–12 h post‐dose. Statistical analysis was by ANOVA.

Results:

In the 0–12 h post‐dose period, when the 24 subjects were dosed with placebo, mean AUC was 2.12, dosed increasing by 75% to 3.70 with famotidine (P < 0.001) and by 81% to 3.83 with ranitidine (P < 0.001). In the 9–12 h post‐dose period, when the subjects were dosed with placebo, mean AUC was 2.13 increasing by 91% to 4.07 with famotidine (P < 0.001) and by 79% to 3.82 with ranitidine (P < 0.001). There was no significant difference between the pH‐raising effects of famotidine and ranitidine in both periods.

Conclusions:

Famotidine and ranitidine in over‐the‐counter doses have a similar, sustained, effect on post‐prandial nocturnal intragastric acidity in healthy subjects lasting up to 12 h after oral dosing.
Topical benzocaine anaesthesia lacks analgesic effects in painful non‐acid oesophagitis
Authors: BECKER K. , BECKER C. , FRIELING T. , HÄUSSINGER D.
Published: October 2003

Background

No established treatment exists for pain relief in symptomatic non‐acid oesophagitis. One of the most common topical anaesthetics is benzocaine which has been demonstrated to produce excellent analgesia on oral mucous membranes.

Methods

In a prospective, placebo‐controlled, balanced, single‐blinded study, 26 patients with retrosternal discomfort or odynophagia due to painful non‐acid oesophagitis were treated either with oral benzocaine 0.75% solution (n = 14) or with benzocaine‐free solvent (placebo, n = 12) at a daily dose of 20–40 mL, for up to 6 consecutive days (median 5.5 days). During the study period patients recorded subjective pain scores for both complaints on visual analogue scales.

Results

Benzocaine did not affect pain scores for any of the two symptoms, nor did it alter global subjective or objective assessment of therapy outcome in treated compared to untreated subjects (P > 0.05). There was a non‐significant tendency for placebo patients to stop prematurely their study medication more often, because of lack of analgesic efficacy (P = 0.098).

Conclusions

Topical benzocaine cannot be recommended for routine symptomatic pain relief in non‐acid oesophagitis. By indirect evidence, it is assumed that pain perception of non‐acid oesophagitis is not preferentially mediated by superficially located mucosal nociceptors.
Effect of omeprazole on the bioavailability of unmodified and phospholipid‐complexed aspirin in rats
Authors: GIRAUD M.‐N. , SANDUJA S. K. , FELDER T. B. , ILLICH P. A. , DIAL E. J. , LICHTENBERGER L. M.
Published: October 2003

Background:

Treatment and prevention of non‐steroidal anti‐inflammatory drug‐induced gastropathy involve the concurrent use of antisecretory drugs. Recently, we have shown that the ability of these drugs to increase the intragastric pH to values pKa of NSAIDs compromises their therapeutic activity. In the present study, we evaluated the potential of omeprazole to interfere with the bioavailability of aspirin administered to rats either alone or complexed with the zwitterionic phospholipid, dipalmitoylphosphatidylcholine (DPPC).

Methods:

Aspirin or aspirin/DPPC was administered intragastrically to rats pre‐dosed with either saline or omeprazole. Concentrations of aspirin and salicylic acid in the blood and the gastric mucosa were assessed by HPLC and the 6‐keto‐PGF1α gastric mucosal concentration by radioimmunoassay.

Results:

Gastric absorption of aspirin and its relative bioavailability were reduced by an antisecretory dose of omeprazole; its inhibitory effect on gastric prostaglandin synthesis was consequently attenuated. However, these effects could be partly overcome if aspirin was administered as a complex with DPPC.

Conclusions:

These observations suggest that: (i) DPPC increases the lipid solubility and gastric permeability of NSAIDs; and (ii) neutralization of the gastric pH results in a shift of aspirin absorption toward the intestine where it could be degraded to salicylic acid.
Nicotine enemas for active ulcerative colitis—a pilot study
Authors: GREEN J. T. , THOMAS G. A. O. , RHODES J. , WILLIAMS G. T. , EVANS B. K. , RUSSELL M. A. H. , FEYERABEND C. , RHODES P. , SANDBORN W. J.
Published: October 2003

Background

Since transdermal nicotine is of value in the treatment of active ulcerative colitis but is often associated with side‐effects, an alternative in the form of topical therapy with nicotine enemas has been developed.

Methods

In an open study, 22 patients with active colitis, all non‐smokers, were asked to take a 100 mL enema containing 6 mg of nicotine every night for 4 weeks. Pre‐trial treatment using mesalazine (n=16), oral prednisolone (8), cyclosporin (1) and azathioprine (1) was kept constant for the month prior to assessment and during the study period. Symptoms, with stool frequency, were recorded on a diary card and an endoscopy was performed with rectal biopsy at the beginning of the study and after 4 weeks.

Results

Seventeen of the 22 patients completed 1 month of treatment. Mean duration of relapse was 29 weeks, range 3–94. Sixteen of 17 improved their St Mark's score. Urgency and stool frequency improved in 12 patients, sigmoidoscopic and histological scores in 10. Three patients had a full remission of symptoms with normal sigmoidoscopy. Six of 10 with a partial response continued with the enemas for a second month and five showed further improvement with full remission in two. The enema appeared effective when added to conventional treatment and produced few side‐effects.

Conclusion

Topical nicotine therapy for ulcerative colitis may have a place in future management, but controlled studies are needed.
Short‐course therapy with amoxycillin–clarithromycin triple therapy for 10 days (ACT‐10) eradicates Helicobacter pylori and heals duodenal ulcer
Authors: WURZER H. , RODRIGO L. , STAMLER D. , ARCHAMBAULT A. , ROKKAS T. , SKANDALIS N. , FEDORAK R. , BAZZOLI F. , HENTSCHEL E. , MORA P. , ARCHIMANDRITIS A. , MEGRAUD F.
Published: October 2003

Background:

Whilst the role of Helicobacter pylori eradication in managing duodenal ulcers has been established, consensus regarding the ideal regimen has not been achieved.

Methods:

Patients with H. pylori‐positive active duodenal ulcer were randomly assigned to receive triple therapy with amoxycillin 1000 mg b.d. + clarithromycin 500 mg b.d. + omeprazole 20 mg daily for 10 days (ACT‐10) or dual therapy with clarithromycin 500 mg t.d.s. + omeprazole 40 mg daily for 14 days (Dual). No additional acid suppression was provided following eradication therapy. Endoscopy, with biopsy for culture and histology, as well as 13C‐urea breath testing (13C‐UBT) were performed pre‐treatment to assess H. pylori infection. H. pylori eradication was established at 4–6 weeks follow‐up with culture (2 antral, 1 corpus biopsies), histology (2 antral biopsies), and 13C‐UBT. Ulcer healing by endoscopy and change in clinical symptoms were also assessed at 4–6 weeks.

Results:

Two hundred and sixty‐seven (267) patients were randomized to ACT‐10 (n=137) or Dual therapy (n=130). By per‐protocol and intention‐to‐treat analyses, H. pylori eradication at 4–6 weeks follow‐up was 91% (115/127) and 88% (120/136), respectively, for ACT‐10 patients and 59% (68/115) and 55% (72/130), respectively, for Dual therapy patients (P<0.001 for both analyses). Ulcer healing was high in both treatment groups: ACT‐10, 93% (118/127) and 90% (122/136), respectively; and Dual therapy, 91% (104/114) and 85% (111/130), respectively. Pre‐treatment resistance to clarithromycin was low (4%, 8/214) as compared to metronidazole resistance which was over 40%. Emergence of resistance to clarithromycin was observed in 2% of patients receiving ACT‐10 and in 25% of those receiving Dual therapy. ACT‐10 and Dual therapy patients experienced similar rates of drug‐related adverse events (33% vs. 32%, respectively) and discontinuation from therapy due to an adverse event (1.5% vs. 5%, respectively). More than 90% of patients were compliant with each prescribed medication.

Conclusion:

In patients with active duodenal ulcer, a 10‐day course of amoxycillin–clarithromycin‐based triple therapy without additional acid suppression is highly effective in eradicating H. pylori and healing duodenal ulcer.
Inhibition of intragastric acidity in healthy subjects dosed with ranitidine 75 mg: a comparative study with cimetidine and placebo
Authors: GRIMLEY C. E. , CONSTANTINIDES S. , SNELL C. C. , MILLS J. G. , NWOKOLO C. U.
Published: October 2003

Background

Despite the widespread use of over‐the‐counter H2‐receptor antagonists little is known about their duration of action on human gastric acid secretion. There are studies reporting inhibitory effects for up to 9 h post‐dose but few data beyond this period.

Methods

Profiles of 20‐h intragastric acidity were measured simultaneously in 24 healthy subjects who were dosed (at 12.30 h) with either ranitidine 75 mg, cimetidine 200 mg or placebo in a three‐way crossover study, according to a standard protocol. Five‐millilitre aliquots of gastric juice were aspirated half‐hourly during the day (0–10 h post‐dose) and hourly overnight (10–20 h post‐dose). pH was measured to three decimal places with a glass electrode. Weighted intragastric acidity (AUC/time) was calculated for both day‐ and night‐times using 2.5‐h intervals during the day and 5‐h intervals at night. Statistical analysis was by ANOVA.

Results

The results are expressed as mean weighted intragastric acidity (mmol/L). (i) Daytime (0–10 h post‐dose): when dosed with placebo the weighted intragastric acidity was 31.03, decreasing to 10.37 (P < 0.001 vs. placebo) and 16.23 (P < 0.001 vs. placebo) when treated with ranitidine and cimetidine, respectively. Ranitidine inhibited weighted intragastric acidity to a greater degree than cimetidine (P < 0.001) during this period. (ii) Night‐time (10–20 h post‐dose): when dosed with placebo the weighted intragastric acidity was 21.36 decreasing to 16.65 (P < 0.001 vs. placebo) when dosed with ranitidine and remaining unchanged at 20.03 (P = 0.886 vs. placebo) when dosed with cimetidine. Ranitidine inhibited weighted intragastric acidity to a greater degree than cimetidine (P = 0.010) during this period. A sub‐analysis of the two 5‐h intervals showed that compared to placebo, ranitidine inhibited weighted intragastric acidity significantly in the 10–15 h period. However, its effect in the 15–20 h period did not differ from placebo.

Conclusions

In healthy subjects, the inhibitory effect of ranitidine 75 mg on intragastric acidity can be detected 10–15 h after an oral dose. By contrast, the inhibitory effect of cimetidine 200 mg seems to be restricted to the first 10 h.
A United States multicentre trial of dual and proton pump inhibitor‐based triple therapies for Helicobacter pylori
Authors: LAINE L. , FRANTZ J. E. , BAKER A. , NEIL G. A.
Published: October 2003

Background:

One‐week proton pump inhibitor‐based triple therapies are very popular in the US despite limited US data documenting efficacy. We assessed 1‐week proton pump inhibitor triple therapies for Helicobacter pylori, and compared them to dual antibiotic therapies (to assess benefit of omeprazole) and to omeprazole–amoxycillin (to assess benefit of clarithro‐ mycin) in a large, randomized, US multicentre study.

Methods:

Healthy subjects who were H. pylori‐positive by rapid serological test and 13C‐urea breath test were randomly assigned to (i) omeprazole (O) 20 mg b.d. + amoxycillin (A) 1 g t.d.s. for 14 days (OA); (ii) A 1 g b.d. + clarithromycin (C) 500 mg b.d. for 7 days (AC); (iii) C 250 mg b.d. + metronidazole (M) 500 mg b.d. for 7 days (CM); (iv) O 20 mg b.d. + C 250 mg b.d. + M 500 mg b.d. for 7 days (MOC); or (v) O 20 mg b.d. + C 500 mg b.d. + A 1 g b.d. for 7 days (OAC). Repeat breath tests were done at 6 weeks to assess H. pylori status.

Results:

Three hundred and two H. pylori‐positive subjects at 25 centres received medication. Intention‐to‐treat cure rate was significantly higher for OAC (82%) than for MOC (67%), CM (59%), AC (18%) or OA (58%). Per‐protocol cure rates were 85% for OAC and 75% for MOC. Discontinuation of therapy due to a side‐effect occurred in 0–3% of each study group.

Conclusions:

One‐week twice‐daily triple therapy with omeprazole, amoxycillin and clarithromycin provides the best rate of eradication of the five regimens studied. However, treatment in the US for 7 days may be unable to achieve eradication rates of ≥ 90% with proton pump inhibitor‐based triple therapy.
Clarithromycin, amoxycillin and H2‐receptor antagonist therapy for Helicobacter pylori peptic ulcer disease in Korea
Authors: BREUER T. , KIM J. G. , EL‐ZIMAITY H. M. T. , NIKAJIMA S. , OTA H. , OSATO M. , GRAHAM D. Y.
Published: October 2003

Background:

Effective anti‐Helicobacter pylori therapies with few side‐effects are needed. We previously showed that the regimen of amoxycillin, clarithromycin and an H2‐receptor antagonist was effective in the United States. The current study tested whether this therapy would also be successful in Korea.

Methods:

Patients with gastric or duodenal ulcers received amoxycillin (750 mg t.d.s.) plus clarithromycin (500 mg t.d.s.) for 2 weeks and nizatidine 300 mg at bedtime for 6 weeks. Endoscopic examinations were performed before treatment and 4 or more weeks after ending antimicrobial therapy. H. pylori status was confirmed by rapid urease testing and histological examination of gastric antrum and corpus biopsies using the Genta stain. Antibiotic resistance was tested using the E‐test method. Cure was defined as no evidence of H. pylori infection 4 or more weeks after ending therapy.

Results:

Seventy‐two patients (59 males and 13 females; mean age 46 years), including 35 with duodenal ulcers, 30 with gastric ulcers and seven with both, were studied. H. pylori infection was cured in 95.8% (69/72 patients; 95% CI = 88.3–99.1%). Two of the treatment failures had culture data and one had pre‐treatment resistance to clarithromycin. Smoking did not have an adverse effect on therapy. Ten patients (15%) developed side‐effects during treatment, but all were mild and did not require treatment interruption. No case of reinfection was noted during follow‐up.

Conclusion:

The combination of amoxycillin, clarithromycin and an H2‐receptor antagonist is effective in Korean patients with H. pylori infection.
Misoprostol in the treatment of chronic refractory constipation: results of a long‐term open label trial
Authors: ROARTY T. P. , WEBER F. , SOYKAN I. , McCALLUM R. W.
Published: October 2003

Background:

Misoprostol is known to be effective in stimulating intestinal transit both in healthy individuals and in patients with chronic constipation when evaluated in short‐term trials. The aim of this study was to determine the utility of misoprostol in the long‐term management of patients with chronic refractory constipation.

Methods:

Eighteen patients were offered misoprostol (600–2400 μg/day) as adjunctive therapy in an open‐ended, non‐blinded trial. All patients were encouraged to continue the drug for a minimum of 4 weeks, after which time the effect on bowel movement patterns was evaluated and continued use of misoprostol was offered to those patients who demonstrated a clinical benefit.

Results:

Six patients withdrew prior to 4 weeks because of side‐effects. In the 12 patients who continued the treatment and were evaluated at 4 weeks, the mean interval between bowel movement frequency had decreased from a baseline of 11.25 to 4.8 days (P=0.0004). Eight patients continued the long‐term treatment, with sustained response seen in six. In a subset of patients (n=4) the effect of single‐dose misoprostol (400 μg) was evaluated compared to healthy controls (n=5) on post‐prandial segmental colonic motility. Misoprostol augmented the colonic motility response to a meal throughout the colon, and this was significantly greater in the left versus right colonic segments (P < 0.05).

Conclusions:

Misoprostol can be effective as part of the long‐term medical treatment of patients with chronic refractory constipation, but side‐effects are observed at higher doses and can be a limiting factor. Part of misoprostol's action may be mediated through the augmentation of colonic motility, particularly of the left colon.
Haemodynamic responses to a combination of terlipressin and octreotide in portal hypertensive rats
Authors: MOREAU R. , CAILMAIL S. , VALLA D. , LEBREC D.
Published: October 2003

Background:

An enhancement of the haemodynamic effects of terlipressin by octreotide (and vice versa) may be useful in the treatment of portal hypertension. The aim of this study was to investigate the short‐term effects of terlipressin, octreotide or a combination of these substances on splanchnic and systemic haemodynamics in rats with portal vein stenosis.

Methods:

Eight rats received an intravenous (i.v.) infusion of isotonic saline (10 μL/min for 15 min). Eight rats received terlipressin first (0.05 mg/kg) and then an i.v. infusion of octreotide (8 μg.h/kg for 15 min) 15 min later. Eight other rats first received an i.v. infusion of octreotide and then terlipressin 15 min later. Splanchnic and systemic haemodynamics (radioactive microsphere method) were measured after saline, after terlipressin or octreotide alone, and after the combined treatments.

Results:

Terlipressin and octreotide alone significantly decreased portal pressure, portal tributary blood flow

and cardiac index. Terlipressin, but not octreotide, significantly increased heptocollateral vascular resistance and arterial pressure. Octreotide administration in rats pre‐treated with terlipressin did not change portal pressure, caused portal tributary blood flow to increase and decreased hepatocollateral vascular resistance; it also decreased arterial pressure but not cardiac index. Terlipressin administration in rats pre‐treated with octreotide further decreased portal pressure, portal tributary blood flow and increased hepatocollateral vascular resistance; terlipressin increased arterial pressure and further decreased cardiac index.

Conclusions:

In rats with portal vein stenosis, octreotide decreased short‐term splanchnic and systemic vasoconstriction due to terlipressin. In contrast, terlipressin enhanced the splanchnic and systemic vasoconstriction due to octreotide. Thus, the haemodynamic responses to the combination of octreotide and terlipressin depend on the order of administration of these substances.
Effects of a new motilide, ABT‐229, on gastric emptying and postprandial antroduodenal motility in healthy volunteers
Authors: VERHAGEN M. A. M. T. , SAMSOM M. , MAES B. , GEYPENS B. J. , GHOOS Y. F. , SMOUT A. J. P. M.
Published: October 2003

Methods:

ABT‐229 is a recently developed derivative of erythromycin, devoid of antibiotic activity. We studied the effect of ABT‐229 on gastric emptying and postprandial antroduodenal motility in healthy volunteers.

Methods:

Placebo, 4 and 16 mg ABT‐229 were given as a single oral dose to nine healthy volunteers, in a randomized, 3‐period crossover design. A solid meal (250 kcal) was given twice, 45 min after drug ingestion and 4 h later. Gastric emptying of each meal was studied using the 13C‐octanoic breath test. Antroduodenal motility was recorded during the total 9‐h period.

Results:

After the first meal, both the 4 and 16 mg doses increased the gastric emptying rate to a similar extent. ABT‐229 stimulated the contractile motility of the antrum dose‐dependently. The half‐emptying time and the lag‐phase of gastric emptying correlated with the number of pressure waves that were propagated over the antrum and the mean amplitude of antral pressure waves. After the second meal no significant effects of ABT‐229 were found.

Conclusions:

A single dose of the new motilin agonist ABT‐229 strongly increases the gastric emptying rate in healthy volunteers by increasing the strength and length of propagation of antral pressure waves. ABT‐229 has the potential to become a new prokinetic drug.
Review article: treatment of Clostridium difficile infection
Authors: ZIMMERMAN M. J. , BAK A. , SUTHERLAND L. R.
Published: October 2003

Aim:

A systematic review of controlled trials of therapy of Clostridium difficile intestinal infection using methodology described by the Cochrane Collaboration.

Methods:

Trials were identified by searching computer databases over the years 1978–1996. Trials were included if they were (a) prospective randomized, controlled trials and (b) included patients with symptomatic disease. The primary end‐point was clinical resolution of diarrhoea. Secondary end‐points were clinical relapse and stool clearance of C. difficile and C. difficile toxin.

Results:

Nine trials (469 patients) satisfying the inclusion criteria were identified. Two trials were placebo controlled. Six trials compared vancomycin to other antibiotics (fusidic acid, bacitracin, teicoplanin and metronidazole). For clinical resolution response rates ranged from 21 (placebo) to 100% (vancomycin). On pooling the trials, no antibiotic showed clear therapeutic superiority. Rates of clinical relapse ranged from 5 to 42%. Only one trial showed significant advantage of one antibiotic over another for prevention of relapse (teicoplanin vs. fusidic acid).

Conclusion:

The published data are limited, and further studies are required.
A comparison between gastric and oesophageal variceal haemorrhage treated with transjugular intrahepatic portosystemic stent shunt (TIPSS)
Authors: STANLEY A. J. , JALAN R. , IRELAND H. M. , REDHEAD D. N. , BOUCHIER I. A. D. , HAYES P. C.
Published: October 2003

Background: Transjugular intrahepatic portosystemic stent‐shunts (TIPSS) are becoming widely used in the management of oesophageal variceal haemorrhage (OVH). Their place in the treatment of gastric variceal haemorrhage (GVH), a condition with a traditionally poor prognosis, remains unclear. The aims of our study were to compare portal haemodynamics and patient outcome in patients undergoing TIPSS for either GVH or OVH.

Patients and Methods: 106 consecutive patients undergoing TIPSS at our institution for either GVH (32 patients) or OVH (74 patients) were studied. The groups were similar with regard to patient age, aetiology and severity of liver disease and number of procedures carried out as an emergency (34.4% vs. 36.5%). Episodes of shunt insufficiency, rebleeding, encephalopathy and other clinical sequela were recorded. Mean follow‐up was similar in both patient groups (14.2 vs. 12.1 months).

Results: Baseline portocaval pressure gradient was lower in patients with GVH compared with those with OVH (13.0±0.9 mmHg vs. 19.0±0.6 mmHg) (P< 0.001). Rates of variceal rebleeding, encephalopathy and shunt insufficiency during follow‐up were similar in both groups and there was no difference in survival.

Conclusion: Patients with GVH had markedly lower portocaval pressure gradients than those with OVH, but shunt and clinical complications and survival were similar during follow‐up. TIPSS appears to be an effective treatment for GVH and should be compared with endoscopic or surgical techniques in controlled trials.
NO‐naproxen vs. naproxen: ulcerogenic, analgesic and anti‐inflammatory effects
Authors: DAVIES N. M. , RØSETH A. G. , APPLEYARD C. B. , MCKNIGHT W. , DEL SOLDATO P. , CALIGNANO A. , CIRINO G. , WALLACE J. L.
Published: October 2003

Background: A novel class of nitric oxide‐releasing nonsteroidal anti‐inflammatory drug (NO‐NSAID) derivatives has recently been described which exert anti‐inflammatory activities but produce significantly less gastrointestinal injury than the parent NSAID from which they are derived. The present studies were performed to determine if a nitroxybutylester derivative of naproxen was less ulcerogenic to the gastrointestinal tract than its parent NSAID, and if it exerted comparable analgesic and anti‐inflammatory properties to the parent NSAID.

Methods: The two drugs were compared in an acute gastric injury model, an antral ulcer model and after twice‐daily administration for 18 days (small intestinal damage model). Anti‐inflammatory activity was examined in the carrageenan‐induced paw oedema model, while analgesia was examined in the acetic acid‐induced writhing model. The pharmacokinetic profiles of naproxen vs. NO‐naproxen were compared by HPLC analysis.

Results: NO‐naproxen was found to produce significantly less gastric damage despite inducing similar increases in plasma TNFα to naproxen. With chronic administration, small intestinal damage was markedly less with NO‐naproxen than with the parent NSAID. However, NO‐naproxen exerted superior analgesic and comparable anti‐inflammatory effects to naproxen. NO‐naproxen was not completely converted to naproxen, but the reduced plasma levels of the latter was not the underlying reason for reduced gastrointestinal toxicity of NO‐naproxen.

Conclusion: NO‐naproxen represents a novel, gastrointestinal‐sparing NSAID derivative with superior analgesic and comparable anti‐inflammatory properties to naproxen.
One‐day intensified lansoprazole‐quadruple therapy for cure of Helicobacter pylori infection
Authors: DE BOER W. A. , VAN ETTEN R. J. X. M. , SCHADE R. W. B. , OUWEHAND M. E. , SCHNEEBERGER P. M. , VAN UNNIK A. J. M. , TYTGAT G. N. J.
Published: October 2003

Background: Peptic ulcer patients need to be treated with antimicrobials to cure Helicobacter pylori infection. Seven‐day quadruple therapy is the regimen with the highest cure rates. An ultra‐short quadruple therapy was evaluated prospectively.

Methods: Forty‐six consecutive H. pylori positive patients (33 had proven ulcer disease) were prescribed lansoprazole 30 mg b.d. on days 1–4, and on day 4 they received in addition tripotassium dicitrato bismuthate 120 mg, tetracycline 250 mg and metronidazole 250 mg at 09.00, 11.00, 13.00, 15.00, 17.00, 19.00, 21.00, 23.00 hours. Repeat endoscopy with biopsies for CLOtest, Giemsa stain and culture was carried out 6 weeks later.

Results: Follow‐up was complete. Overall cure rate (all three biopsy‐based tests negative) was 26/46 (57%; 95% CI: 41–71%). Antibiotic sensitivity was available in 42. Thirty‐nine carried a metronidazole sensitive strain and 23/39 (59%) were cured, three carried a resistant strain and therapy failed in all. Three out of four in whom susceptibility was unknown were cured. Metronidazole resistance was induced in 8 out of 16 with a sensitive strain. Only one patient (3%) reported severe side effects.

Conclusions: This convenient quadruple regimen showed that a short contact time is sufficient to kill H. pylori in vivo. Since 57% of patients are cured with a 14‐h treatment, a slightly longer treatment duration may increase the cure rate to above 90%.
Review article: the role of pharmaco‐therapy for acute variceal haemorrhage in the era of endoscopic haemostasis
Authors: CHAN L. Y. , SUNG J. J. Y.
Published: October 2003

In the last decade, endoscopic haemostasis, including injection sclerotherapy and variceal ligation has become the standard method for the treatment of variceal haemorrhage. While the use of vasopressin has been hampered by severe side effects, the development of new vasoactive agents such as terlipressin, somatostatin and octreotide has opened new indications for these pharmacological therapies. These agents are effective, safe and easy to use. They could be recommended as stop‐gap treatment before endoscopy can be arranged. They can also be used as adjunct therapy for endoscopic haemostasis in acute variceal haemorrhage.
Efficacy and tolerance of mesalazine suppositories vs. hydrocortisone foam in proctitis
Authors: LUCIDARME D. , MARTEAU P. , FOUCAULT M. , VAUTRIN B. , FILOCHE B.
Published: October 2003

Background: Topical treatments with steroids or mesalazine are the most effective treatments for idiopathic proctitis.

Aim: to compare the efficacy and tolerance of mesalazine suppositories vs. hydrocortisone acetate foam in the treatment of acute proctitis.

Patients and methods: 242 patients with active idiopathic proctitis were randomized to receive once daily either one Pentasa suppository (mesalazine 1 g) or 100 mg hydrocortisone (Colofoam) for 14–21 days (until remission). Disease activity and tolerance of the treatments were assessed using a daily questionnaire, by physician assessment, and endoscopy score.

Results: Both treatments induced a significant reduction in disease activity. Mesalazine suppositories were significantly more effective than hydrocortisone on rectal blood loss (P=0.002) and mucus (P=0.02) parameters, and on the degree of the decrease in endoscopy score (P=0.02). No significant difference was observed between treatments concerning histology or tolerance.

Conclusion: Mesalazine suppositories were as well‐tolerated as hydrocortisone foam, but were more effective for some parameters of disease activity.
Anti‐thyroid drugs decrease mucosal damage in a rat model of experimental colitis
Authors: OREN R. , MAARAVI Y. , KARMELI F. , KENET G. , ZEIDEL L. , HUBERT A. , ELIAKIM R.
Published: October 2003

Background: Methimazole, an anti‐thyroid drug, was recently found to be useful in the treatment of systemic lupus erythematosus and other autoimmune diseases. Moreover, decreased thyroid hormone production is associated with a variety of immunological manifestations, such as reduced activation of CD4+ cells, increased CD8+ cell activity and reduced soluble IL‐2 receptors. In the present study we examined the effects of methimazole and propylthiouracil on a rat model of experimental colitis.

Methods: Colitis was induced by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB). Two weeks prior to induction of colitis, rats were treated by either methimaziole (0.04%) or propylthiouracil (0.01%) in drinking water after a week of free access to water. Rats were sacrificed 48 h or 7 days after induction of colitis. The colon was isolated, rinsed with ice‐cold water and weighed. Damage was assessed both macroscopically and microscopically and myeloperoxidase (MPO) activity determined.

Results: All treated rats were hypothyroid as manifested by a significant elevation of thyroid stimulating hormone (TSH), by comparison with the control groups (mean ‐1.82±0.40 versus 0.11±0.02 mmol/L, respectively). The inflammatory response elicited by TNB resulted in severe mucosal damage 48 h after damage induction, which persisted for 7 days. Pre‐treatment with either methimazole 0.04% or propylthiouracil 0.01% significantly decreased mucosal damage macroscopically (lesion area, lesion score and segmental weight) microscopically and also significantly decreased MPO level at both time points (P<0.01).

Conclusions: Methimazole and propylthiouracil significantly reduce mucosal damage and colonic weight in a rat model of colitis. The mode by which they do so remains to be studied.
Efficacy and tolerability of a one‐week triple therapy consisting of pantoprazole, clarithromycin and amoxycillin for cure of Helicobacter pylori infection in patients with duodenal ulcer
Authors: LABENZ J. , TILLENBURG B. , WEISMÜLLER J. , LÜTKE A. , STOLTE M.
Published: October 2003

Background: Previous studies have shown that one‐week triple therapy consisting of omeprazole, clarithromycin and amoxycillin may cure Helicobacter pylori infection in the vast majority of patients. The present study was designed to test the hypothesis that a triple therapy with pantoprazole, clarithromycin and amoxycillin cures the infection in 80% of duodenal ulcer patients infected with H. pylori.

Methods: In an open two‐centre study, 60 duodenal ulcer patients were treated with pantoprazole 40 mg b.d., clarithromycin 500 mg b.d. and amoxycillin 1 g b.d. for 1 week. During the second week patients received pantoprazole 40 mg once in the morning. We assessed H. pylori infection before treatment and 4 weeks after cessation of the study medication by a rapid urease test, histology after Warthin–Starry stain and a 13C‐urea breath test.

Results: Sixty patients (42 males, mean age 47.4 years) entered the trial. All patients were infected with H. pylori. One patient was withdrawn from the study because of allergy to penicillin and six patients were protocol violators. H. pylori infection was cured in 47 out of 53 patients who completed the trial according to the protocol (89%; 95% CI: 80–97%) and in 49 of 60 patients included in the trial (82%; 95% CI: 72–92%). Four weeks after the last administration of study drugs, 55 out of 60 ulcers had healed (92%). Twenty‐nine patients reported 51 adverse events that were mostly mild to moderate.

Conclusions: One‐week triple therapy consisting of pantoprazole, clarithromycin and amoxycillin is a simple and effective approach to the cure of H. pylori infection in patients with duodenal ulcer. In those patients who took the drugs as prescribed the H. pylori cure rate was 89%, with the lower 95% confidence limit being 80%.
Helicobacter pylori serology and the management of young dyspeptics: a UK survey of gastroenterologists and general practitioners with an interest in gastroenterology
Authors: LIM A. G. , MARTIN R. M. , MONTILEONE M. , WALKER A. C. , GOULD S. R.
Published: October 2003

Aim: To survey the current use of Helicobacter pylori serology for pre‐endoscopy screening and management of young dyspeptics amongst gastroenterologists and general practitioners with an interest in gastroenterology in the United Kingdom.

Methods: A postal questionnaire was sent to 536 members of the British Society of Gastroenterology and 164 members of the Primary Care Society in Gastroenterology.

Results: Of those who responded (66%), 25% of general practitioners and 17% of gastroenterologists were using H. pylori serology as a screening test for young dyspeptics. General practitioners and gastroenterologists differed in their use of serology to guide management strategies (P<0.0003): general practitioners eradicate infection from sero‐positive patients prior to endoscopy (92%), whilst the majority of gastroenterologists endoscope sero‐positive patients before treatment (55%). More gastroenterologists (89%) would re‐test all or selected patients to assess eradication compared to general practitioners (45%). 106 different drug regimes were being used as first line treatment.

Conclusions: H. pylori serology as a pre‐endoscopy screening test for young dyspeptic patients was used by only a fifth of respondents. There were wide variations in attitudes and practice in the way H. pylori serology was used in the management of young dyspeptics. Trials comparing clinical outcome and cost‐effectiveness of different serology‐based strategies are needed.
An increasing dose of omeprazole combined with amoxycillin cures Helicobacter pylori infection more effectively
Authors: MIEHLKE S. , MANNES G. A. , LEHN N. , HELE C. , STOLTE M. , BAYERDÖRFFER E.
Published: October 2003

Background: The combination of omeprazole and amoxycillin has demonstrated effectiveness with very few side‐effects in the treatment of H. pylori infection, however cure rates have varied widely. The present study addresses the question as to the extent to which the cure rate of H. pylori infection depends on the size of the daily omeprazole dose, and investigates other patient‐related factors that influence treatment success.

Methods: In a randomized, controlled and investigator‐blinded trial, 163 hospitalized patients with H. pylori‐associated gastritis were treated with 20 mg omeprazole once daily in the morning, 20 mg omeprazole b.d., 40 mg omeprazole b.d. or 60 mg omeprazole b.d. for 14 days. In addition, all patients received 1000 mg amoxycillin b.d. on days 5–14. Endoscopic and histological examinations were performed prior to treatment, at the end of treatment and 4 weeks after completion of treatment.

Results: H. pylori infection was cured in 18 of 40 (45%, 95% CI: 29–62%), in 22 of 39 (56.4%, 95% CI: 40–72%), in 25 of 38 (65.8%, 95% CI: 49–80%), and in 33 of 40 (82.5%, 95% CI: 67–93%) patients, respectively, (P<0.001). Side‐effects leading to discontinuation of treatment occurred in only 1.2%.

Conclusion: The daily dose of omeprazole is an important factor for the success of dual therapy comprising omeprazole and amoxycillin in curing H. pylori infection. Cure of H. pylori infection correlates positively and significantly with the size of the daily omeprazole dose. The combination of high‐dose omeprazole and amoxycillin is an effective and well‐tolerated regimen for the treatment of H. pylori‐associated diseases.
The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress
Authors: FRANCIS C. Y. , MORRIS J. , WHORWELL P. J.
Published: October 2003

Background: The clinical assessment and investigation of irritable bowel syndrome would be greatly facilitated by the introduction of a simple, easy to use severity scoring system. Such a system, developed in our department over a number of years, has been submitted to validation in a total of 141 patients and 40 healthy controls.

Methods: The system, incorporating pain, distension, bowel dysfunction and quality of life/global well‐being, was assessed for its ability to reliably score patients previously classified as mild, moderate or severe. The reproducibility and sensitivity to change of the system was also assessed.

Results: The maximum achievable score was 500. Mild, moderate and severe cases were indicated by scores of 75 to 175, 175 to 300 and >300 respectively. Controls scored below 75 and patients scoring in this range can be considered to be in remission. There was a highly significant difference between controls and patients as a whole (P=0.0001) as well as significant differences (P<0.01) between all severity categories. Scores repeated within 24 h were very reproducible and sensitivity to change was also extremely good (P<0.001) with a change of 50 reliably indicating improvement.

Conclusion: These results suggest that this scoring system should prove to be a valuable instrument in helping to meet the many challenges offered by irritable bowel syndrome.
Effect of oral pancreatic enzyme administration on digestive function in healthy subjects: comparison between two enzyme preparations
Authors: DOMÍNGUEZ‐MUÑOZ J. E. , BIRCKELBACH U. , GLASBRENNER B. , SAUERBRUCH T. , MALFERTHEINER P.
Published: October 2003

Background: Intraduodenal proteases exert a negative feedback on pancreatic secretion.

Aim: To investigate the effect of two pancreatic enzyme preparations (enteric‐coated tablets, and capsules with enteric‐coated microtablets) on postprandial pancreatic and bile acid secretion, gastroduodenal motility and release of gastrin and pancreatic polypeptide in healthy humans.

Methods: Twenty healthy males were studied on two different days one week apart. After an overnight fast a nine‐lumen motility tube was positioned with the distal tip at the Treitz angle. On each study day, 30 min after an interdigestive migrating motor complex‐phase III, a semi‐liquid test meal was given either alone (n=20) or with enzymes (3 tablets (n=10) or 2 capsules with microtablets (n=10); 40000 U lipase and 2000 proteases) in a randomized order, and the study continued over 2 h. Motility was continuously recorded with four ports in the antrum and three in the duodenum, using a low‐compliance pneumohydraulic perfusion system. Secretion of human‐specific pancreatic elastase and bile acids was measured by a standard duodenal intubation perfusion technique. Plasma concentrations of gastrin and pancreatic polypeptide were measured by specific radioimmunoassays.

Results: Postprandial pancreatic secretion was significantly reduced by administration of microtablets (median 82 mg/2 h vs. 70 mg/2 h, P<0.02) but not by tablets (median 59 mg/2 h vs. 58 mg/2 h, N.S.). No changes were observed in bile acid secretion, antroduodenal motility or release of gastrin and pancreatic polypeptide.

Conclusions: Oral administration of pancreatic enzymes at normal therapeutic doses significantly inhibits postprandial pancreatic secretion in healthy humans, when capsules with enteric‐coated microtablets are given. Exogenous pancreatic enzymes have no significant effect on bile acid secretion, gastroduodenal motility and hormone release.