bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of trimebutine on sphincter of Oddi motility in patients with post‐cholecystectomy pain
Authors: Barthet  , Bouvier  , Pecout  , Berdah  , Viviand  , Mambrini  , Abou  , Salducci  , Grimaud
Published: March 2003

Background:

Trimebutine is an opiate modulator of the gastrointestinal motility that interacts with enkephalinergic receptors.

Aim:

To evaluate the effects of trimebutine (50 mg intravenous injection) on the motility of the sphincter of Oddi (SO) as assessed by endoscopic manometry.

Methods:

Endoscopic manometry was performed on 15 cholecystectomized patients who presented with symptoms suggestive of SO dysfunction. Prior to the endoscopic manometry, endoscopic ultrasonography was performed in order to rule out the possible presence of a bile duct stone.

Results:

Injecting trimebutine resulted in a significant increase in the SO antegrade phasic contraction rate (P = 0.02). Trimebutine decreased the basal pressure of the SO (32.5 vs. 27.5 mmHg), but the difference is not statistically significant (P = 0.11). The effects of trimebutine differed depending on the basal SO motility anomalies involved, but the period of latency was similar (mean 89 s; range 30–240 s). The basal anomalies were an increased basal SO pressure of > 40 mmHg in three patients, a tachyoddia (frequency of phasic contractions (PC) > 10/min) in six patients, prolonged PC (> 10 s) in two patients and an absence of phasic contraction in one patient. The basal pressure of the SO decreased in the three patients presenting with SO hyperpressure, but returned to a normal value in one case. The frequency of the PC decreased to normal in three out of the six patients with tachyoddia. The duration of the PC returned to normal in the two patients with prolonged PC whereas their frequencies increased. Prolonged PC developed in the patient without any detectable phasic contraction.

Conclusions:

Trimebutine modulates SO motility in various ways depending on the basal SO motility anomaly observed after cholecystectomy. This regulatory effect suggests the existence of encephalinergic control of SO motility.
Activation of genes for spasmolytic peptide, transforming growth factor alpha and for cyclooxygenase (COX)‐1 and COX‐2 during gastric adaptation to aspirin damage in rats
Authors: Konturek  , Brzozowski  , Pierzchalski  , Kwiecien  , Pajdo  , Hahn  , Konturek
Published: March 2003

Background:

NSAIDs, such as aspirin (ASA), cause widespread mucosal damage, but repeated ASA insults appear to induce mucosal tolerance (adaptation) to this␣injury. The mechanism of the gastric adaptation to the damage induced by ASA has not been fully explained.

Aim:

To determine the role of the mucosal gene expression for spasmolitic peptide (SP) (a member of trefoil peptides) and transforming growth factor alpha (TGFα) as well as for cyclooxygenase (COX)‐1 and COX‐2 during gastric adaptation to ASA in rats.

Methods:

Gastric lesions were produced by ASA (100 mg/kg in 1.5 mL of 0.2 M HCl) applied intragastrically (i.g.) as a single dose, every day for 5 days. Control rats were given 1.5 mL of vehicle (0.2 M HCl i.g.) as a single dose, during 5 consecutive days. Gastric blood flow (GBF) was measured by H2‐gas clearance technique and gastric mucosal specimens were taken for the assessment of cell␣proliferation rate in gastric mucosa by bromodeoxyuridine (BrdU) uptake, mucosal generation of prostaglandin E2 measured by radioimmunoassay, and for expression of SP, TGFα COX‐1 and COX‐2 mRNA as determined by RT‐PCR. To quantify the relative amounts of mRNA for SP and TGFα, southern blotting analysis of the PCR products was performed and the intensity of PCR products was compared with that of β‐actin used as a standard.

Results:

ASA applied once produced numerous gastric erosions, but with repeated ASA doses the adaptation to this NSAID developed, the area of gastric lesions being reduced by 86% after six consecutive ASA insults. This adaptation to ASA was accompanied by approximately a 90% reduction in prostaglandin E2 biosynthesis, by a significant rise in BrdU uptake by glandular cells predominantly in the neck region of gastric glands and by expression of SP (SP/β‐actin ratio; 0.96 ± 0.08 in ASA‐adapted mucosa vs. 0.38 ± 0.05 in the control mucosa) and TGFα (TGFα/β‐actin ratio: 0.97 ± 0.07 in ASA‐adapted mucosa vs. 0.77 ± 0.06 in the control mucosa). COX‐1 expression was detected in vehicle‐control gastric mucosa and after single exposure to ASA or after six consecutive ASA insults, while COX‐2 mRNA was not detected in vehicle‐control gastric mucosa, but appeared after single ASA insult and was sustained after subsequent ASA doses.

Conclusions:

(i) Gastric adaptation to aspirin injury involves enhanced cell proliferation which appears to be mediated by increased expression of SP and TGFα, and (ii) rapid upregulation of COX‐2 expression following single and repeated ASA insults may represent a compensatory response to suppression of prostaglandin generation by this NSAID.
Review article: current treatment and optimal patient management in pancreatic cancer
Authors: Haycox  , Lombard  , Neoptolemos  , Walley
Published: March 2003

This review analyses the current state of knowledge and understanding concerning the optimum treatment and therapeutic management of patients who suffer from pancreatic cancer. It outlines recent advances in scientific understanding and assesses their potential future value to clinicians in confronting this disease. Despite a significant expansion in scientific knowledge relating to factors underlying the early development of pancreatic carcinoma, the clinician continues to be restricted to a severely limited therapeutic armoury for this disease. Local therapies (surgery and radiation) are inevitably of limited value in the face of a disease that is normally encountered at a stage where metastasis is already highly developed. Despite such limitations, however, surgery performed in specialist units may be of value for 10–20% of patients, with a 5‐year survival rate in such units of between 10 and 24%. This may be improved even further by appropriate use of adjuvant treatment. The advanced stage of the disease when normally encountered emphasizes the potential value of systemic treatment in this therapeutic area. Unfortunately systemic treatment (chemotherapy) has been found to be ineffective to date in significantly extending survival, with a low rate and duration of remission being identified in most trials. The challenge for both the health service and the pharmaceutical industry is to harness recent and future developments in scientific knowledge to the practical benefit of clinicians. Where cure is possible it should be vigorously pursued; where it is not, in this field above all others, clinicians have a duty of care. To achieve this it is necessary to abandon the therapeutic nihilism that has characterized the attitudes of clinicians towards this disease in the past. It is time that such nihilism was replaced by a recognition of the challenges and the opportunities available to clinicians in enhancing the quantity and quality of life available to patients. The dictum of ‘curing whenever possible but caring always’ should be the future therapeutic philosophy used to guide clinicians in this important and rapidly changing therapeutic area.
The Leeds Dyspepsia Questionnaire: a valid tool for measuring the presence and severity of dyspepsia
Authors: Moayyedi  , Duffett  , Braunholtz  , Mason  , Richards  , Dowell  , Axon
Published: March 2003

Background

There is currently no validated questionnaire that assesses both the presence and severity of dyspepsia.

Aim

To develop the Leeds Dyspepsia Questionnaire (LDQ) as a measure of the presence and severity of dyspepsia, and to assess the validity, reliability and responsiveness of this instrument.

Methods

Unselected patients attending either a hospital dyspepsia clinic or a general practice surgery were interviewed by a trained gastroenterologist or a general practitioner on the presence and severity of dyspepsia. This opinion was compared with the results of the nurse‐administered LDQ. Test–retest reliability was assessed by the same research nurse re‐administering the LDQ 4–7 days after the initial visit in a subgroup of hospital patients. In a further subgroup of patients one researcher interviewed the patients and a second researcher re‐administered the LDQ within 30 min to evaluate inter‐rater reliability. The responsiveness of the LDQ was measured by repeating it in patients with endoscopically proven peptic ulcer or oesophagitis 1 month after receiving appropriate therapy.

Results

The LDQ was administered to 99 general practice and 215 hospital patients. In the GP population 41/98 (42%) had dyspepsia according to the GP and the LDQ had a sensitivity of 80% (95% CI: 65–91%) and a specificity of 79% (95% CI: 66–89%). The weighted kappa statistic for the agreement between the LDQ and the clinician for the severity of dyspepsia was 0.58 in the GP population and 0.49 in hospital patients. The kappa statistic for test–retest reliability was 0.83 in 107 patients. The LDQ had excellent inter‐rater reliability with a kappa statistic of 0.90 in 42 patients. The median LDQ score fell from 22.5 (range 9–36) to 4.5 (range 0–27) in 12 patients 1 month after receiving appropriate therapy (Wilcoxon signed rank test, P < 0.0001).

Conclusion

The LDQ is a valid, reliable and responsive instrument for measuring the presence and severity of dyspepsia.
Review article: evaluation of drugs in experimental gut distension models
Authors: Pappas T.N. , Mangel A.W. , Lawson C.
Published: March 2003

Distension of the gastrointestinal tract elicits abdominal pain, as well as sensations such as discomfort or fullness. Many patients with irritable bowel syndrome have been reported to show a reduced threshold to the pain or discomfort due to experimental rectal distension. This hypersensitivity of the gut may be characteristic of the irritable bowel, as well as other functional gastrointestinal disorders. Intestinal distension in animals induces a range of responses which have been used as indexes of visceral nociception. This paper reviews a recently introduced canine model used to assess the antinociceptive properties of a novel 5‐HT3 receptor antagonist, alosetron.
Review article: current perspectives on hypergastrinaemia and enterochromaffin‐like‐cell hyperplasia
Authors: Robinson
Published: March 2003

Rabeprazole, a new benzimidazole proton pump inhibitor (PPI), is among a class of agents known to be very potent inhibitors of gastric acid secretion. PPIs inhibit hydrogen‐potassium adenosine triphosphatase activity on the luminal surface of the parietal cell, effectively blocking the final common pathway for gastric acid secretion. Raising gastric pH stimulates the production of gastrin by G cells in the antrum of the stomach, which can lead to enterochromaffin‐like (ECL)‐cell hyperplasia. In the past, these changes have been viewed with concern, particularly in the light of studies in rats indicating that hypergastrinaemia and ECL‐cell hyperplasia induce gastric carcinoid tumour formation. All available clinical data indicate that long‐term PPI use does not lead to carcinoid tumour formation in humans. In fact, both serum gastrin elevation and ECL‐cell hyperplasia are now generally viewed as normal physiological responses to gastric acid suppression. Serum gastrin concentrations, in particular, correlate well with gastric acid suppression, which has led to the use of gastrin response by some investigators as a surrogate marker of antisecretory effectiveness. Long‐term tolerability data indicate that PPIs have a favourable side‐effect profile. Data obtained from patients receiving acute or long‐term maintenance rabeprazole therapy support this conclusion. Furthermore, neither animal nor human data obtained with rabeprazole suggest a significant risk for neoplastic changes secondary to hypergastrinaemia.
Protective effects of zinc in indomethacin‐induced gastric mucosal injury: evidence for a dual mechanism involving lipid peroxidation and nitric oxide
Authors: Joseph  , Varela  , Kanji  , Subramony  , Mihas
Published: March 2003

Background:

Indomethacin causes gastric mucosal injury, although the pathogenesis is not fully understood. Zinc, is known to have gastroprotective effects in both humans and experimental animals. Aim: To determine (i) the protective effects of zinc in indomethacin‐induced gastric mucosal injury in rats, and (ii) whether these cytoprotective effects are mediated by changes in gastric lipid peroxidation and/or nitric oxide synthase activity.

Methods:

Gastric lesions were induced in rats by the intragastric administration of indomethacin. Morphological changes, lipid peroxidation (malondialdehyde levels) and nitric oxide synthase activity were determined in animals pre‐treated with zinc sulphate and in controls.

Results:

Indomethacin significantly increased malondialdehyde levels and decreased NOS activity. These effects were attenuated by pre‐treatment with zinc (P < 0.005 and 0.0001, respectively). The protective effects of zinc were readily abolished in animals pre‐treated with N‐nitro‐L‐arginine methyl ester (L‐NAME). Morphologically, indomethacin induced large areas of mucosal ulcerations, which were completely prevented by zinc pre‐treatment.

Conclusions:

Zinc provides protection against indomethacin‐induced gastric mucosal injury. These protective effects result from the inhibition of lipid peroxidation and the preservation of mucosal nitric oxide synthase.
Eradication of Helicobacter pylori increases gastric acidity in patients with atrophic gastritis of the corpus—evaluation of 24‐h pH monitoring
Authors: Haruma  , Mihara  , Okamoto  , Kusunoki  , Hananoki  , Tanaka  , Yoshihara  , Sumii  , Kajiyama
Published: March 2003

Background:

Recent studies have shown that the eradication of Helicobacter pylori results in a gastric acid secretion which decreases to normal levels in patients with duodenal ulcer disease. The aim of this study was to evaluate the effect of eradication of H. pylori in a 24‐h study of gastric acidity in patients with atrophic gastritis of the corpus.

Methods:

Intragastric acidity was measured by continuous 24‐h pH monitoring, and the histology of the gastric antrum and corpus were evaluated in 14 H. pylori‐positive patients with histologically proven atrophic gastritis of the corpus (10 men, 4 women; mean age, 57 years) before and 1 year after anti‐H. pylori therapy.

Results:

H. pylori was absent in 13 of 14 patients 1 year after treatment. Both gastritis and atrophy scores were significantly lower after eradication therapy (P < 0.01). The 24‐h median pH and the percentage of 24‐h pH readings above 4.0 units were significantly decreased after eradication therapy (from 5.12 ± 0.36 to 2.69 ± 0.21, and from 65.5 ± 6.6% to 28.2 ± 6.1%, P < 0.01, respectively.)

Conclusion:

Eradication of H. pylori increases 24‐h gastric acidity in patients with atrophic gastritis of the corpus. Improvement of the histology of the gastric antrum and corpus may lead to the normalization of gastric acidity.
Glucose metabolism and insulin sensitivity in inactive inflammatory bowel disease
Authors: Capristo  , Mingrone  , Addolorato  , Greco  , Gasbarrini
Published: March 2003

Background:

Inflammatory mediator concentration was found to be increased in active inflammatory bowel disease, and this could be related to an insulin‐resistant state. Moreover, glucocorticoids, which are widely used in the treatment of inflammatory bowel disease, are notoriously related to insulin resistance.

Aim:

To measure body composition, whole body glucose uptake and oxidation in Crohn’s disease and ulcerative colitis patients with inactive disease.

Methods:

All patients had clinical, ultrasound and biochemical assessment. Body composition was determined by isotopic dilution technique; basal metabolic rate and substrate oxidation were measured by indirect calorimetry. Insulin sensitivity was assessed by the euglycaemic hyperinsulinaemic clamp. Ten patients with inactive Crohn’s disease (five males, aged 31.1 ± 7.0 years) and 10 patients with inactive ulcerative colitis (five males, aged 33.4 ± 8.8 years) participated in the study. Forty healthy subjects, matched for age and height were used as a control group.

Results:

Crohn’s disease patients showed lower BMI (P < 0.001), fat mass (P < 0.05) and respiratory quotient (P < 0.001) values compared to both ulcerative colitis and control subjects. No difference in peripheral glucose uptake (μmol/kg/min) was found between groups (respectively 42.5 ± 6.78 in Crohn’s disease, 40.2 ± 8.00 in ulcerative colitis and 41.4 ± 10.8 in control subjects). Glucose storage and oxidation did not differ between groups.

Conclusion:

Our data showed that inflammatory bowel disease patients in a remission phase of the disease activity had a whole body glucose uptake and oxidation similar to those of control subjects, probably due to fat‐free mass preservation and low blood and tissue cytokine concentration.
Triple therapy for Helicobacter pylori eradication is more effective than long‐term maintenance antisecretory treatment in the prevention of recurrence of duodenal ulcer: a prospective long‐term follow‐up study
Authors: WONG  , LAM  , LAI  , HU  , CHING  , HO  , YUEN  , CHAN  , LAU  , LAI
Published: March 2003

Background

: The effectiveness of Helicobacter pylori eradication treatment and long term acid suppression maintenance in the natural course of duodenal ulcer has not been directly compared.

Aim

: To compare in a prospective randomized study the effectiveness of H. pylori eradication on the prevention of recurrence of duodenal ulcer with long‐term maintenance acid suppression therapy.

Methods

: One hundred and fourteen duodenal ulcer patients were randomized to the treatment over a 12‐month period. Fifty‐seven of them received triple therapy consisting of 1 g sucralfate q.d.s. for 28 days, 300 mg metronidazole q.d.s. for 14 days and 250 mg clarithromycin q.d.s. for 14 days. Another 57 received 20 mg omeprazole q.d.s. for 12 months. An upper endoscopy was performed before treatment, at 6 weeks, and 2, 6 and 12 months after the first endoscopy. Side‐effects were self‐recorded and clinical follow‐ups were arranged for up to 4.25 years.

Results

: The ulcer healing rate was 90.2% (95% confidence interval (95% CI): 79–97%) in the omeprazole group at 6 weeks as compared to 83.3% (95% CI: 70–93%) in the triple therapy group (P = 0.38). There was a higher success rate of pain control in the omeprazole group. Side‐effects were more frequently reported and compliance was poorer in the triple therapy group during the first 4 weeks. During follow‐up, more relapses were seen in the omeprazole group (9.8%, 95% CI: 3–21%) than the triple therapy group (4.2%, 95% CI: 1–13%) at 1 year (P = 0.44). All relapses were due to the persistence of H. pylori infection. At the 1 year follow‐up, none of the patients who were H. pylori negative had an endoscopic relapse compared to 7 out of 56 patients who remained H. pylori positive (12.5%, 95% CI: 5–24%, P = 0.018). After a mean follow‐up of 4.07 years, none of those who remained H. pylori negative had an ulcer relapse while the 11 out of 41 who remained H. pylori positive had an ulcer relapse (26.8%, 95% CI 14–43, P = 0.0005).

Conclusions

: Both regimens were highly effective in healing ulcers. The eradication of H. pylori infection was associated with more side‐effects and poor compliance but was more effective than the maintenance therapy in reducing the recurrence of duodenal ulcers. For the prevention of ulcer recurrence, testing of H. pylori status after triple therapy is more important than maintenance therapy.
Lack of effect of spearmint on lower oesophageal sphincter function and acid reflux in healthy volunteers
Authors: Bulat R. , Fachnie E. , Chauhan U. , Chen Ying , Tougas G.
Published: March 2003

Background

: Spearmint is commonly used as an antispasmodic and as a flavouring in several medications including antacids. It can produce heartburn, presumably by lowering lower oesophageal sphincter (LES) tone, but the mechanism has not previously been objectively examined.

Aim

: To study the effect of spearmint on LES function, acid reflux and symptoms.

Methods

: In healthy volunteers, a Dent Sleeve and a pH electrode were placed in the distal oesophagus. They were then given spearmint either in a flavouring (0.5 mg), or a high (500 mg) dose, or a placebo, using a double‐blind randomized crossover design. LES pressure, oesophageal pH and symptoms were recorded for 30 min before and after administration.

Results

: LES pressure was not affected by spearmint, either high dose (19.6 vs. 16.0 mmHg), flavouring dose (20.2 vs. 19.8 mmHg) or placebo (20.5 vs. 19.2 mmHg, all N.S.). There were no differences in reflux occurrence following high dose (mean = 0.65 vs. 0.85 episodes), low dose (0.4 vs. 0.5 episodes) or placebo (0.7 vs. 1.10 episodes, all N.S.). There was a significant increase in mean symptom scores following high‐dose spearmint (0 vs. 0.35, P = 0.03), but not low dose (0 vs. 0.2) or placebo (0 vs. 0.5, both N.S.). One subject reported symptoms with placebo, one with low dose, and six with high dose; all without increased reflux episodes or decreased sphincter pressure.

Conclusion

: Spearmint has no effect on LES pressure or acid reflux. Flavouring doses of spearmint do not produce more symptoms than placebo while high doses can be associated with symptoms, presumably from direct mucosal irritation but not reflux.
Antibiotic combination therapy in patients with chronic, treatment‐resistant pouchitis
Authors: Gionchetti P. , Rizzello F. , Venturi A. , Ugolini F. , Rossi M. , Brigidi P. , Johansson R. , Ferrieri A. , Poggioli G. , Campieri M.
Published: March 2003

Background

: Pouchitis is the major long‐term complication after ileal pouch‐anal anastomosis for ulcerative colitis. About 15% of patients have a chronic, treatment‐resistant disease.

Aims

: To evaluate the efficacy of an antibiotic combination for chronic active, treatment‐resistant pouchitis.

Patients and Methods

: Eighteen patients were treated orally with rifaximin 1 g b.d. + ciprofloxacin 500 mg b.d. for 15 days. Symptoms assessment, endoscopic and histological evaluations were performed at screening and after 15 days using the Pouchitis Disease Activity Index (PDAI). Improvement was defined as a decrease of at least 3 points in PDAI score, and remission as a PDAI score of 0. Systemic absorption of rifaximin was determined by high performance liquid chromatography. Faecal samples were collected before and after antibiotic treatment for stool culture.

Results

: Sixteen out of 18 patients (88.8%) either improved (n=10) or went into remission (n=6); the median PDAI scores before and after therapy were 11 (range 9–17) and 4 (range 0–16), respectively (P < 0.002). No side‐effects were reported. Rifaximin plasma levels and urinary excretion were negligible, confirming its mainly topical activity. A significant decrease in total anaerobes and aerobes, enterococci, lactobacilli, bifidobacteria and bacteroides in faecal samples was observed, while the reduction in number of coliforms and Clostridium perfringens did not reach a statistical significance.

Conclusions

: A combination of rifaximin and ciprofloxacin was effective in patients with active chronic, treatment‐resistant pouchitis, suggesting the need, in these patients, for treatment using antibiotic agents with wide antibacterial spectrum of activity.
A systematic review of Helicobacter pylori eradication therapy—the impact of antimicrobial resistance on eradication rates
Authors: Houben  , Beek D. Van De , Hensen  , Craen A. J. M. De , Rauws  , Tytgat
Published: March 2003

Background

: We systematically reviewed all available data in the literature to determine the overall eradication rates of currently advised Helicobacter pylori eradication regimens and to resolve conflicting evidence on the impact of antimicrobial resistance on the eradication rates.

Methods

: A comprehensive search of all published trials on H. pylori eradication therapy was carried out via an electronic database search, hand‐searching and checking reference lists of pharmaceutical companies and other reviews. Full papers and abstracts in the English language which study currently advised eradication regimes were included.

Results

: 770 study‐arms were analysed. Mean eradication rates for bismuth based triple, proton pump inhibitor triple, quadruple and ranitidine bismuth citrate combination therapies vary from 65 to 92%. In case of nitroimidazole resistance, a drop in efficacy of up to 50% was found for bismuth‐based triple and proton pump inhibitor‐based triple therapies. For quadruple therapy, a significant difference in efficacy was found in the equal‐effects analysis; however, this could not be confirmed in the random‐effects analysis. In case of clarithromycin resistance, a mean drop in efficacy of 56% was found for one‐ and two‐week clarithromycin containing proton pump inhibitor‐triple therapies and of 58% for two‐week ranitidine bismuth citrate combined with clarithromycin therapies. For ranitidine bismuth citrate combined with clarithromycin and nitroimidazole, no difference in efficacy was found in case of nitroimidazole or clarithromycin resistance, but data are still scarce.

Conclusions

: The cure rate with most regimens dropped significantly, in case of nitroimidazole‐resistant strains, compared to nitroimidazole‐susceptible strains. In case of clarithromycin resistance, the efficacy of most regimens is also decreased; however, data are still scarce. These data should allow physicians to make a better choice of an appropriate therapy for their patients.
Sustained response to interferon‐α or to interferon‐α plus ribavirin in hepatitis C virus‐associated symptomatic mixed cryoglobulinaemia
Authors: Calleja  , Albillos  , Moreno‐Otero  , Rossi  , Cacho  , Domper  , Yebra  , Escartín
Published: March 2003

Background

: Hepatitis C virus (HCV) infection has been associated with mixed cryoglobulinaemia.

Aim

: To investigate the efficacy of anti‐viral therapy on the eradication of HCV and its clinical manifestations in patients with HCV‐associated symptomatic mixed cryoglobulinaemia.

Patients and methods

: 18 out of 32 patients with symptomatic mixed cryoglobulinaemia (MC group) received a 12‐month course of interferon (3 MU three times a week, subcutaneously). Nonresponders or relapsers to this therapy were treated with interferon plus ribavirin (1200 mg/day, orally) for 12‐months. 226 patients with HCV infection and without cryoglobulins were studied in comparison (Hepatitis C group). Serial quantification of serum HCV‐RNA and cryoglobulins were performed.

Results

: In the MC group, 10 out of 18 patients (55%) receiving interferon showed an end of treatment response, but at the end of follow‐up, only five (28%) patients had a sustained response. In the hepatitis C group, 91 patients (47%) showed an end of treatment response but only 42 (20%) a sustained response. In the MC group alanine transaminase, cryocrit and rheumatoid factor decreased significantly in responders, with an improvement or dissapearance of the MC‐associated clinical manifestations. Alanine transaminase, cryocrit and rheumatoid factor increased in the relapsers and the clinical manifestations reappeared. Nonresponders and relapsers to interferon in the MC group were retreated with interferon plus ribavirin. Five out of eight nonresponders showed a end of treatment response but it was sustained in three of them. In the relapsers, treatment with combined therapy achieved a sustained response in four out of the five patients (80%).

Conclusions

: Interferon as monotherapy or combined with ribavirin is a safe and effective treatment in patients with HCV‐associated MC. The presence of cryoglobulins does not affect the response to anti‐viral treatment in patients with HCV infection. The eradication of HCV is associated with an improvement or dissapearance of MC‐associated clinical manifestations.
Lansoprazole pharmacokinetics differ in patients with oesophagitis compared to healthy volunteers
Authors: Barclay  , Begg  , Robson  , Peters  , Ketelbey
Published: March 2003

Aim

: To compare the pharmacokinetics of lansoprazole in patients with reflux oesophagitis and in healthy volunteers, after a single dose and at steady‐state.

Patients and methods

: A 30 mg dose of lansoprazole was administered orally daily for 7 days in eight healthy male volunteers aged 21–24 years, and in 16 patients aged 29–65 years with grade 2 or 3 reflux oesophagitis. The pharmacokinetics were assessed over the 24 h dose interval following the first dose and again after the 7th dose.

Results

: Within both the patient and volunteers groups, there were no significant differences between day 1 and day 7 in any of the pharmacokinetic parameters including maximum concentration (Cmax), area under the concentration–time curve (AUC), and terminal half‐life of elimination (t½). However, on both days 1 and 7, values were significantly higher in the patients than in the healthy volunteers. On day 7, Cmax was 1343 ng/mL in patients compared with 765 ng/mL in healthy volunteers, AUC was 3458 ng.h/mL vs. 1350 ng.h/mL and t½ was 1.62 h vs. 0.90 h.

Conclusion

: The differences in results for the pharmacokinetics reflect reduced lansoprazole clearance in the patient group. Other research has not found a difference in pharmacokinetics when comparing healthy volunteers with patients with acid‐related disorders. The difference in lansoprazole clearance in this study may be related to a variety of factors that are different in patients compared with young normal volunteers, such as age, gender, other drugs, and reduced general well‐being.
Endogenous nitric oxide in the regulation of gastric secretory and motor activity in humans
Authors: Konturek  , Fischer  , Gromotka  , Konturek  , Domschke
Published: March 2003

Background:

Studies in animals have shown that nitric oxide (NO) affects gastric secretory and motor functions. However, little information is available about the involvement of this substance in the control of gastric secretory and motor activity in man.

Methods:

This study, performed on 18 healthy, Helicobacter pylori‐negative volunteers, was designed to evaluate the role of NO in the control of gastric acid secretion and of gastrin and somatostatin release in response to ordinary feeding (group A) and on gastric motor and electrical activity (group B). Gastric acid secretion was determined by means of intragastric pH‐metry before and after feeding with a semi‐liquid meal. Plasma levels of gastrin and somatostatin were measured using specific radioimmunoassays. Gastric emptying rate was measured using the 13C‐acetate breath test, antral motor activity using a manometric catheter and myoelectric activity using cutaneous electrogastrography. Studies were repeated following pre‐treatment with NG‐monomethyl‐
L‐Arginine (
L‐NMMA),
L‐Arginine (
L‐Arg) or their combination.

Results:

L‐NMMA delayed the recovery of intragastric pH to the pre‐meal value, and suppressed postprandial gastrin release while increasing the plasma somatostatin level.
L‐Arg did not affect postprandial pH and plasma hormones, but reversed
L‐NMMA‐induced alterations in intragastric pH and in plasma gastrin and somatostatin levels. Both postprandial antral motor activity (motility index) and gastric emptying significantly increased in tests with
L‐NMMA, but this was not observed when
L‐NMMA was given in combination with
L‐Arg or when
L‐Arg alone was used. The gastric electrical pattern, as measured by cutaneous electrogastrography, was not affected by
L‐NMMA,
L‐Arg or their combination.

Conclusions:

(1) Endogenous NO appears to be involved in the regulation of postprandial gastric acid secretion. This effect may be mediated by the changes in release of gastrin and somatostatin. (2) Endogenous NO delays gastric emptying and antral motor activity without affecting gastric myoelectrical activity.
Low molecular weight heparin as adjuvant therapy in active ulcerative colitis
Authors: Törkvist  , Thorlacius  , Sjöqvist  , Bohman  , Lapidus  , Flood  , Ågren  , Raud  , Löfberg
Published: March 2003

Background

: Heparin given intravenously has shown beneficial effects in the treatment of refractory ulcerative colitis in open trials. Low molecular weight heparin (LMWH) offers advantages in the method of administration but have not been evaluated in inflammatory bowel disease conditions.

Aim

: To assess the tolerability and safety of subcutaneous self‐administered LMWH in outpatients with refractory ulcerative colitis and to evaluate any potential adjuvant therapeutic effect.

Patients and Methods

: Twelve patients with mild to moderately active ulcerative colitis were included in the trial. The patients had either responded poorly to treatment with conventional therapy, including oral and/or rectal glucocorticosteroids, or had experienced a rapid relapse during or shortly after GCS therapy. Dalteparin sodium 5000 units s.c. injection was administered twice daily for 12 weeks. Patients were monitored for possible adverse events and changes in clinical symptoms, and endoscopic and histological scores were analysed. Leucocyte scanning was performed at inclusion and at the end of the study.

Results

: Tolerability and compliance were excellent and no serious adverse events occurred. Eleven patients improved symptomatically and six (50%) attained complete remission after 12 weeks of treatment. Endoscopic, scintigraphic and histological scores were found to be significantly improved.

Conclusion

: Self‐administered LMWH given s.c. may be a safe adjuvant therapy for patients with active, glucocorticosteroids‐refractory ulcerative colitis. A controlled trial should be undertaken to confirm the positive effects found in this study.
Effect of prucalopride, a new enterokinetic agent, on gastrointestinal transit and anorectal function in healthy volunteers
Authors: Poen  , Felt‐Bersma  , Van Dongen  , Meuwissen
Published: March 2003

Background

: Prucalopride (PR) is a novel 5‐HT4 agonist enterokinetic compound.

Aim

: To evaluate its effect on bowel function, gut transit and anorectal function in healthy volunteers using a double‐blind, placebo‐controlled crossover study.

Methods

: Twenty‐four healthy volunteers (12 men, 12 women, mean age 25 years, range 20–53 years) were randomly assigned to 1 mg/placebo or 2 mg/placebo (PL). The trial consisted of five consecutive 1 week periods: no drug treatment, PR treatment or PL, washout, PL or PR, no treatment. Subjects maintained a diary of bowel function during the entire study period. Total intestinal transit time (TITT), mean colonic transit time (MCTT) and anorectal function (anal manometry, rectal sensitivity and rectal compliance) were assessed at the end of both treatment periods. Electrocardiography and blood sampling were performed for safety analysis; blood sampling was also used to check compliance.

Results

: No subjects withdrew from the study. Treatment with PR 2 mg showed a statistically significant increase in mean number of weekly stools (11.5 vs. 7.1 compared to PL, P = 0.04) and in the percentage of loose/watery stools (48 vs. 12% compared to PL, P = 0.005). Within 1 week, stool frequency and consistency returned to baseline values when treatment was stopped. MCTT was shortened significantly with both doses, i.e. from 35 h on PL to 25 h on PR 1 mg (P = 0.01) and from 43 h on PL to 22 h on PR 2 mg (P = 0.02). Anorectal function was unaffected by PR. Transient and moderate headache occurred in nine subjects during PR treatment and in six subjects during PL treatment.

Conclusion

: Prucalopride is well tolerated by healthy subjects and has a marked and consistent effect on stool frequency and consistency, and on colonic transit. In the present study prucalopride did not affect visceral sensitivity or sphincter function. It holds promise for patients with slow transit constipation.
The prevalence of dyspepsia and use of antisecretory medication in North Glasgow: role of Helicobacter pylori vs. lifestyle factors
Authors: Woodward  , Morrison  , Mccoll
Published: March 2003

Aims

: To determine the prevalence of dyspepsia and associated antisecretory medication usage, and their associations with H. pylori infection in the general population. In addition, to compare the importance of H. pylori infection relative to other potential causes of dyspepsia: alcohol, smoking and obesity.

Methods

: The study examined a random population sample of 784 men and 827 women from Glasgow. They completed a validated dyspepsia questionnaire and had their H. pylori status determined by serology.

Results

: The overall prevalence of dyspepsia was 12%; prescribed antisecretory medication had been used over the last 6 months by 7%. The odds ratio (95% CI) for dyspepsia, comparing H. pylori‐positives to negatives was 1.79 (1.03, 3.09) for men and 1.11 (0.70, 1.78) for women. Ever‐smoking (both sexes) and obesity (women) had higher odds ratios for dyspepsia than did H. pylori. Adjustment for age, social class, ever‐smoking, ever‐drinking and obesity reduced the H. pylori odds ratios for dyspepsia to 1.38 (0.73, 2.60) for men and 0.99 (0.57, 1.73) for women. The association between H. pylori and antisecretory medication usage was similar to that for dyspepsia.

Conclusion

: Obesity and smoking are more important risk factors, for dyspepsia and antisecretory medication usage, than is H. pylori. Reducing the burden and cost of dyspepsia will require lifestyle modification and not merely H. pylori eradication.
Mucosal healing and a fall in mucosal pro‐inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn’s disease
Authors: Fell  , Paintin  , Arnaud‐Battandier  , Beattie  , Hollis  , Kitching  , Donnet‐Hughes  , Macdonald  , Walker‐Smith
Published: March 2003

Background:

Although enteral nutrition is a recognized form of treatment for intestinal Crohn’s disease, there are persisting problems with feed palatability and only limited data as to its mode of action.

Aim:

To assess the effects of a specific oral polymeric diet (CT3211; Nestle, Vevey, Switzerland), which is rich in transforming growth factor β2, on the mucosal inflammatory process.

Methods:

Twenty‐nine consecutive children with active intestinal Crohn’s disease were treated with CT3211 as the sole source of nutrition for 8 weeks. Patients were assessed clinically, and endoscopically, whilst cytokine mRNA was measured in mucosal biopsies before and after treatment by quantitative reverse transcriptase polymerase chain reaction.

Results:

After 8 weeks 79% of children were in complete clinical remission. Macroscopic and histological healing in the terminal ileum and colon was associated with a decline in ileal and colonic interleukin‐1β mRNA (pre‐treatment to post‐treatment ratio 0.008 and 0.06: P < 0.001, P = 0.006). In the ileum there was also a fall in interferon γ mRNA (ratio 0.15, P < 0.001) with a rise in transforming growth factor β1 mRNA (ratio 10, P = 0.04), whilst in the colon interleukin‐8 mRNA fell with treatment (ratio 0.06, P < 0.05).

Conclusions:

The clinical response to oral polymeric diet CT3211 is associated with mucosal healing and a down regulation of mucosal pro‐inflammatory cytokine mRNA in both the terminal ileum and colon. In the ileum there was also an increase in transforming growth factor β1 mRNA.
Can Helicobacter pylori serology still be applied as a surrogate marker to identify peptic ulcer disease in dyspepsia?
Authors: Xia  , Kalantar  , Mitchell  , Talley
Published: March 2003

Background:

Helicobacter pylori infection and associated peptic ulcer disease (PUD) has become less common in some countries.

Aim:

To determine if H. pylori serology alone or combined with a history of ingestion of non‐steroidal anti‐inflammatory drugs (NSAIDs) and an age threshold can be used as an indirect ulcer test.

Methods:

Two hundred and fifty‐two consecutive Australian patients (121 males, mean age 52 years) referred for endoscopy were enrolled. Blood was tested by a validated ELISA. At endoscopy, eight biopsies were taken for CLO‐testing, culture and histology. NSAID use over the prior 3 months was recorded.

Results:

One hundred and six (42%) patients were seropositive for H. pylori, 48 (19%) patients had PUD and 30 (12%) used NSAIDs. Serology alone had a sensitivity of 52% and a specificity of 60% for identifying PUD; the sensitivity and specificity were 60% and 55%, respectively, when combined with a history of NSAID use. Serology, regardless of NSAID use, would have saved 23% in endoscopy workload but would have missed 17% of PUD cases if an age threshold of < 45 years was chosen for omitting endoscopy.

Conclusions:

Serology was a poor ulcer test despite an excellent performance for detecting H. pylori. A strategy combining serology and an age threshold with a history of NSAID use to reduce endoscopy workloads may not always be appropriate.
Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID‐enteropathy in the rat
Authors: Somasundaram  , Sigthorsson  , Simpson  , Watts  , Jacob  , Tavares  , Rafi  , Roseth  , Foster  , Price  , Wrigglesworth  , Bjarnason
Published: March 2003

Background:

The pathogenesis of NSAID‐induced gastrointestinal damage is believed to involve a nonprostaglandin dependent effect as well as prostaglandin dependent effects. One suggestion is that the nonprostaglandin mechanism involves uncoupling of mitochondrial oxidative phosphorylation.

Aims:

To assess the role of uncoupling of mitochondrial oxidative phosphorylation in the pathogenesis of small intestinal damage in the rat.

Methods:

We compared key pathophysiologic events in the small bowel following (i) dinitrophenol, an uncoupling agent (ii) parenteral aspirin, to inhibit cyclooxygenase without causing a ‘topical’ effect and (iii) the two together, using (iv) indomethacin as a positive control.

Results:

Dinitrophenol altered intestinal mitochondrial morphology, increased intestinal permeability and caused inflammation without affecting gastric permeability or intestinal prostanoid levels. Parenteral aspirin decreased mucosal prostanoids without affecting intestinal mitochondria in vivo, gastric or intestinal permeability. Aspirin caused no inflammation or ulcers. When dinitrophenol and aspirin were given together the changes in intestinal mitochondrial morphology, permeability, inflammation and prostanoid levels and the macro‐ and microscopic appearances of intestinal ulcers were similar to indomethacin.

Conclusions:

These studies allow dissociation of the contribution and consequences of uncoupling of mitochondrial oxidative phosphorylation and cyclooxygenase inhibition in the pathophysiology of NSAID enteropathy. While uncoupling of enterocyte mitochondrial oxidative phosphorylation leads to increased intestinal permeability and low grade inflammation, concurrent decreases in mucosal prostanoids appear to be important in the development of ulcers.
Selective action of a CCK‐B/gastrin receptor antagonist, S‐0509, on pentagastrin‐, peptone meal‐ and beer‐stimulated gastric acid secretion in dogs
Authors: Sasaki  , Matsuno  , Okabe
Published: March 2003

Background:

The pharmacological effects of a novel CCK‐B/gastrin receptor antagonist, S‐0509, on gastric acid secretion in dogs remain unknown.

Aim:

To evaluate the antisecretory effects of S‐0509 on gastric acid secretion and to compare such effects with famotidine or atropine in dogs stimulated with various gastric stimulants.

Methods:

Ten beagle dogs with a denervated Heidenhain pouch and three beagle dogs with an innervated gastric fistula were used. Gastric acid secretion was stimulated by either continuous intravenous administration of pentagastrin, carbachol or histamine, or oral administration of a peptone meal or beer.

Results:

In the Heidenhain pouch model, both intravenously administered and orally administered S‐0509 significantly inhibited the gastric acid secretion stimulated by pentagastrin, peptone meal and beer. Nonetheless, the drug had little or no effect on carbachol‐stimulated or histamine‐stimulated acid secretion. Famotidine extensively inhibited all gastric acid secretion stimulated by the above stimulants in a non‐selective manner. Atropine also significantly inhibited the acid secretion stimulated by pentagastrin, peptone meal, beer or carbachol, but was not able to inhibit stimulation due to histamine. Oral administration of peptone meal or beer significantly increased the plasma gastrin level. Similarly to the Heidenhain pouch model, even in the gastric fistula (GF) model, S‐0509 significantly inhibited pentagastrin‐stimulated gastric acid secretion, yet the drug had no effect on carbachol‐stimulated secretion.

Conclusions:

S‐0509 is a selective CCK‐B/gastrin receptor antagonist in dogs that inhibits gastric acid secretion stimulated by pentagastrin and gastrin‐releasing substances, but does not inhibit histamine‐stimulated and carbachol‐stimulated acid secretion.
Effects of midazolam on small bowel motility in humans
Authors: Castedal  , Björnsson  , Abrahamsson
Published: March 2003

Background:

Benzodiazepines are used as sedatives for some intestinal procedures and as hypnotics, and this is the reason for studying their effects on duodenojejunal motility.

Methods:

Antroduodenojejunal manometry was performed in 13 healthy volunteers on two different occasions, when placebo or midazolam were given intravenously (randomized, double‐blind). A bolus dose of midazolam 0.03 mg/kg was followed by 0.015 mg/kg after 1.5, 3 and 4.5 h. After 5 h observation of interdigestive motility, the volunteers were given a test meal and recording continued for another hour. Twenty‐eight motility variables were compared.

Results:

With midazolam the median motility index of phase III in the proximal duodenum was increased by 37% (P < 0.05), which was a consequence of both a longer duration (P < 0.01) and higher pressure amplitudes (P < 0.05), compared with placebo. A longer duration (9%) of phase III was also seen in the distal duodenum (P < 0.05). With midazolam the duration of the migrating motor complex was shortened by 27% (P < 0.05). No statistically significant difference was found for the number of episodes of phase III registered (P=0.09), or for the other 22 motility variables compared including the duodenal retroperistalsis in late phase III.

Conclusion:

Midazolam does affect some aspects of duodenal motility, especially in the proximal part, but phase III‐related retroperistalsis is not affected.
Review article: new insights into the pathogenesis of radiation‐induced intestinal dysfunction
Authors: Macnaughton
Published: March 2003

Exposure of the abdomino‐pelvic region to ionizing radiation, such as that received during radiotherapy, is associated with the development of a number of untoward symptoms which may limit the course of therapy or which may involve serious chronic intestinal disease. While the mucosal dysfunction surrounding acute radiation enteritis is generally ascribed to the effects of ionizing radiation on the cell cycle of epithelial stem cells of the intestinal crypts and subsequent epithelial loss, recent evidence suggests that other, earlier events also play a role. The severity of these early events may determine the incidence and severity of chronic enteritis. The mechanism for this is unclear, but may relate to radiation‐induced compromise of host defence responses to luminal pathogens or antigens. This review will address the current state of knowledge of the pathogenesis of radiation‐induced intestinal dysfunction, focusing on events which occur in the mucosa, and will discuss what the future may hold with respect to the treatment of radiation‐associated diseases of the intestinal tract.