bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of signal transduction pathways in rat gastric epithelial cells stimulated with interleukin‐1β
Authors: Tominaga K. , Higuchi K. , Tsuno M. , Watanabe T. , Fujiwara Y. , Kim S. , Arakawa T. , Iwao H. , Kuroki T.
Published: March 2003

Background: Interleukin‐1β (IL‐1β) participates in cell growth, differentiation and apoptosis via activation of several kinases in a variety of cells. Mitogen‐activated protein (MAP) kinases are important intermediates of the signal transduction pathway from the cell surface to the nucleus, leading to activation of transcription factors. There are no reports on the effect of IL‐1β on these pathways in gastric epithelial cells.

Aim: To investigate whether IL‐1β activates MAP kinases [extracellular signal‐regulated kinases (ERKs), c‐Jun NH2‐terminal kinases (JNKs) and p38 MAP kinase (p38 MAPK)] and nuclear factor (NF)‐κB, a transcription factor, in gastric epithelial cells (RGM1).

Methods: The activities of ERKs and JNKs were estimated by in‐gel kinase assay, and p38 MAPK activity was measured by in vitro kinase assay at various time points (0–40 min) after addition of IL‐1β (100 pg/mL) for 20 min. The activity of NF‐κB was analysed using gel mobility shift assay at times from 0 to 4 h after addition of IL‐1β.

Results: Activity of ERKs was detectable at 10 min, peaked at 20 min, and continued at increased levels until 40 min. Activity of both JNKs and p38 MAPK were detectable during 5–20 min, and then decreased within 40 min. Activation of NF‐κB occurred at 30 min, and increased activity continued for 6 h. Interleukin‐1β activated MAP kinases and NF‐κB in RGM1 cells.

Conclusion: The activation induced by this cytokine may play an important role in the initiation of the inflammatory process in gastric mucosa.
Mechanism of prevention by capsaicin of ethanol‐induced gastric mucosal injury – a study in the rat using intravital microscopy
Authors: Saeki T. , Ohno T. , Boku K. , Saigenji K. , Katori M. , Majima M.
Published: March 2003

Background: Capsaicin acts specifically on primary afferent neurones to release neuropeptides, including calcitonin gene‐related peptide (CGRP), and prevents ethanol‐induced mucosal injury.

Aim: To investigate the microvascular changes in the gastric mucosa in response to ethanol using intravital microscopy to elucidate the mechanism of capsaicin‐induced gastroprotection.

Methods: The posterior gastric wall in the rat was secured in an observation chamber and perfused with Tyrode's solution. The microcirculation was observed through a window made by removing a limited area of smooth muscle.

Results: Ethanol (50%) applied to the mucosa constricted the collecting venules and venules but dilated arterioles. The constriction of the collecting venules resulted in mucosal congestion, which caused mucosal injury. Application of capsaicin to the mucosa dilated the arterioles but not the collecting venules or venules. Arteriolar dilation was inhibited by a CGRP antagonist, CGRP‐(8–37). Prior application of capsaicin prevented ethanol‐induced constriction of the collecting venules, and the action of capsaicin was inhibited by prior application of CGRP‐(8–37).

Conclusions: The results suggest that the inhibition of ethanol‐induced gastric injury by capsaicin is attributable to the suppression of collecting venule constriction, via CGRP release.
Review: low caloric intake and gall‐bladder motor function
Authors: Festi D. , Colecchia A. , Larocca A. , Villanova N. , Mazzella G. , Petroni M. L. , Romano F. , Roda E.
Published: March 2003

Cholelithiasis is the primary expression of obesity in the hepatobiliary system. In obese subjects the risk of developing gallstones is increased due to a higher cholesterol saturation of gall‐bladder bile. During weight reduction with very low calorie diets (VLCD) the incidence of gallstones increases, but the mechanism for gallstone formation is not completely understood and several pathogenetic mechanisms have been suggested: increased saturation of bile, increased gall‐bladder secretion of mucin and calcium, increased presence of prostaglandins and arachidonic acid. Alterations in gall‐bladder motility may contribute to gallstone formation, but few studies have addressed the issue of gall‐bladder motility during rapid weight loss and its possible role in gallstone formation. VLCD have been associated with a gall‐bladder stasis, as a consequence of reduced gall‐bladder stimulation by low fat content of the diets. A threshold quantity of fat (10 g) has been documented to obtain efficient gall‐bladder emptying. Ursodeoxycholic acid administered during VLCD seems to have a protective role in developing a biliary cholesterol crystals. Gall‐bladder emptying was lower in response to low fat meals with respect to relative higher fat meals, before as well as during the VLCD. This may account the possibility of an adaptative response of the gall‐bladder motility to a given diet regimen. Adequate fat content of the VLCD may prevent gallstone formation, maintaining adequate gall‐bladder motility and may be more economic and physiologically acceptable than administration of a pharmacological agent.
Helicobacter pylori: where are we and where are we going?
Authors: Tytgat G. N. J.
Published: March 2003

This paper contains a personal view on what has been achieved in Helicobacter pylori research and what the expectations might be for further developments. Knowledge about the organism is already extensive. Particularly intriguing are the differences in genetic make‐up in the various geographical regions. Sadly, detailed knowledge on how the organism spreads is still lacking. The clinical spectrum of the disease in man is largely known, but as H. pylori is disappearing worldwide, the relative frequency of H. pylori‐negative ulcer disease is increasing. To what extent H. pylori disappearance and eradication is responsible for the decreasing incidence of gastric cancer remains uncertain. Antimicrobial therapy is dominated by proton pump inhibitor triple therapy as first line with quadruple therapy as second‐line therapy. The long‐term consequences of the rising resistance to the ‘key’ antimicrobials are so far unknown and speculative.
Helicobacter pylori effects on gastritis, gastrin and enterochromaffin‐like cells in Zollinger–Ellison syndrome and non‐Zollinger–Ellison syndrome acid hypersecretors treated long‐term with lansoprazole
Authors: Hirschowitz B. I. , Haber M. M.
Published: March 2003

Background:

Helicobacter pylori is said to cause atrophy of the gastric corpus and enterochromaffin‐like cell proliferation in gastro‐oesophageal reflux disease (GERD) patients treated long‐term with a proton pump inhibitor.

Aims:

To determine the effect of H. pylori infection on gastritis, enterochromaffin‐like cell density and hyperplasia, mucosal atrophy and serum gastrin in patients with gastric hypersecretion (basal acid output gt; 15 mmol/h) with either hypergastrinemia (Zollinger–Ellison syndrome) or normal gastrin (non‐Zollinger–Ellison syndrome) before and during long‐term treatment with lansoprazole.

Methods:

Lansoprazole was individually titrated to reduce basal acid output to < 5 mmol/h (< 1 mmol/h in post‐surgical Zollinger–Ellison syndrome). Gastric corpus biopsies were obtained every 6 months before treatment and up to 8 years later.

Results:

H. pylori was present in corpus biopsies in ≈ 50%, causing active gastritis which resolved rapidly in 15 subjects after elimination of H. pylori. Patchy mild/moderate corpus atrophy was present at entry in two and at the end in four out of 60 patients, one being H. pylori‐positive. Intestinal metaplasia (< 10%) was seen in six isolated biopsies (1% of total). H. pylori did not affect serum gastrin, enterochromaffin‐like cell density or hyperplasia. Enterochromaffin‐like cell density was twice as high in Zollinger–Ellison syndrome as in non‐Zollinger–Ellison syndrome patients (241 vs. 126 cells/mm2, P < 0.001). Enterochromaffin‐like cells remained normal in the non‐Zollinger–Ellison syndrome hypersecretors regardless of H. pylori status.

Conclusion:

Corpus enterochromaffin‐like cell increases were related to serum gastrin elevation, but neither H. pylori nor long‐term treatment with lansoprazole alone or together had any effect on enterochromaffin‐like cell density or hyperplasia. Corpus acute gastritis resulted from H. pylori infection, but did not result in mucosal atrophy despite long‐term proton pump inhibitor treatment and promptly resolved with loss of H. pylori.
Non‐Helicobacter pylori bacterial flora during acid‐suppressive therapy: differential findings in gastric juice and gastric mucosa
Authors: Sanduleanu S. , Jonkers D. , De Bruine A. , Hameeteman W. , Stockbrügger R. W.
Published: March 2003

Background:

Intragastric growth of non‐Helicobacter pylori bacteria commonly occurs during acid‐suppressive therapy. The long‐term clinical consequences are still unclear.

Aim:

To investigate the luminal and mucosal bacterial growth during gastric acid inhibition, in relation to the type and duration of acid‐inhibitory treatment, as well as to concomitant H. pylori infection.

Methods:

A total of 145 patients on continuous acid inhibition with either proton pump inhibitors (n=109) or histamine2‐receptor antagonists (H2RAs, n=36) for gastro‐oesophageal reflux disease, and 75 dyspeptic patients without acid inhibition (control group) were included. At endoscopy, fasting gastric juice was obtained for pH measurement and bacteriological culture. Gastric biopsy specimens were examined for detection of H. pylori (immunohistochemistry) and of non‐H. pylori bacteria (modified Giemsa stain‐positive and immunohistochemistry‐negative at the same location).

Results:

Non‐H. pylori flora was detected in the gastric juice of 92 (41.8%) patients and in the gastric mucosa of 109 (49.6%) patients. In gastric juice, prevalence rate for non‐H. pylori bacteria was higher in patients taking proton pump inhibitors than controls and those taking H2RAs (58.7% vs. 22.6% and vs. 30.6%, P < 0.0001 and P < 0.003, respectively), but did not differ statistically between H2RAs and controls. In gastric mucosa, prevalence rates for non‐H. pylori bacteria were higher in patients taking proton pump inhibitors and H2RAs than in the controls (antrum: 46.9% and 48.6% vs. 25%, P < 0.05 for both; corpus: 52.2% and 56.8% vs. 23.7%, P < 0.001 for both), but did not differ between proton pump inhibitors and H2RAs. Both luminal and mucosal growth of non‐H. pylori bacteria were significantly greater in H. pylori‐positive than ‐negative patients taking proton pump inhibitors (P < 0.05 for both). Luminal growth of non‐H. pylori flora increased with the intragastric pH level, whilst mucosal bacterial growth increased with the duration of acid inhibition.

Conclusions:

Non‐H. pylori flora not only contaminates the gastric juice but also colonizes the gastric mucosa of a large proportion of patients treated long‐term with acid inhibition. The relationship between H. pylori and non‐H. pylori bacteria in the pathogenesis of atrophic gastritis and gastric cancer needs further elucidation.
Combination therapy with ribavirin and alpha interferon for the treatment of chronic hepatitis C refractory to interferon
Authors: Cozzolongo R. , Cuppone R. , Giannuzzi V. , Amati L. , Caradonna L. , Tamborrino V. , Jirillo E. , Manghisi O. G.
Published: March 2003

Background:

Up to 80% of hepatitis C patients are refractory to treatment with interferon‐α. These patients are not likely to benefit from higher dosages or longer duration of interferon alone. The addition of ribavirin has been shown to improve the response rate in patients resistant to a previous course of interferon‐α alone.

Aim:

To evaluate whether a sustained hepatitis C virus (HCV) RNA response could be obtained with combination therapy of interferon‐α and ribavirin in patients who did not respond to or relapsed after a standard interferon‐α treatment.

Methods:

A total of 73 patients, 59 non‐responders and 14 relapsers after interferon‐α alone, were treated with a combination of ribavirin (1000–1200 mg/day) and interferon‐α (3 MU three times a week) for 24 weeks. Alanine aminotransferase levels and HCV RNA were checked for 24 weeks after completion of therapy.

Results:

At the end of the combination therapy, 36 patients (49%) showed alanine aminotransferase normalization and in 20 patients (27%), HCV RNA was undetectable in serum. At the end of the 24 weeks follow‐up period, only 12 patients (16%) had a sustained response with serum negativity of HCV RNA. This response was significantly higher in relapsers than in non‐responders: five (36%) vs. seven (12%) patients (P=0.03), respectively. Adverse effects were restricted to flu‐like symptoms and moderate haemolytic anaemia.

Conclusions:

Combination of interferon‐α and ribavirin is quite limited, both in scope and efficacy, in HCV patients who had a non‐response to monotherapy with interferon. Better results may be expected in relapsers, but larger studies are necessary.
A multicentre study on eradication of Helicobacter pylori using four 1‐week triple therapies in China
Authors:   CHINESE NATIONAL COOPERATIVE STUDY GROUP FOR HELICOBACTER PYLORI, Xiao S.‐D. , Liu W.‐Z. , Hu P.‐J. , Ouyang Q. , Wang J.‐L. , Zhou L.‐Y. , Cheng N.‐N.
Published: March 2003

Background:

Short‐term proton pump inhibitor‐based triple therapies for the eradication of Helicobacter pylori are used widely. The eradication rates vary greatly from country to country and from region to region.

Aim:

To assess the efficacy at eradicating H. pylori of 1‐week regimens containing three medications: omeprazole (O) or colloidal bismuth subcitrate (B), furazolidone (F) or metronidazole (M), and amoxicillin (A) or clarithromycin (C).

Methods:

A multicentre study involving 20 hospitals in different regions of China. A total of 892 patients with H. pylori‐positive non‐ulcer dyspepsia or healed duodenal ulcer confirmed by endoscopy were recruited to receive, randomly, one of four regimens: OMC, OFC, OFA, and BFC, b.d. for 7 days. 13C‐urea breath test was performed 4–8 weeks after completion of treatment.

Results:

The eradication rates with per protocol/intention‐to‐treat analyses were: OMC (n=217/219) 66%/65%; OFC (n=227/229) 69%/69%; OFA (n=223/225) 87%/86%; and BFC (n=214/219) 80%/78%. The eradication rate (per protocol analysis) in duodenal ulcer (79%) was higher than that in non‐ulcer dyspepsia (73%, P=0.033). Patient compliance was good. The adverse events of the four regimens were mild, and mainly gastrointestinal.

Conclusions:

The omeprazole, furazolidine and amoxicillin regimen achieves a high H. pylori eradication rate in different geographical regions of China.
Iron and inflammatory bowel disease
Authors: Oldenburg B. , Koningsberger J. C. , Van Berge Henegouwen G. P. , Van Asbeck B. S. , Marx J. J. M.
Published: March 2003

Both anaemia of iron deficiency and anaemia of chronic disease are frequently encountered in inflammatory bowel disease. Anaemia of iron deficiency is mostly due to inadequate intake or loss of iron. Anaemia of chronic disease probably results from decreased erythropoiesis, secondary to increased levels of proinflammatory cytokines, reactive oxygen metabolites and nitric oxide.

Assessment of the iron status in a condition associated with inflammation, such as inflammatory bowel disease, is difficult. The combination of serum transferrin receptor with ferritin concentrations, however, allows a reliable assessment of the iron deficit.

The best treatment for anaemia of chronic disease is the cure of the underlying disease. Erythropoietin reportedly may increase haemoglobin levels in some of these patients. The anaemia of iron deficiency is usually treated with oral iron supplements. Iron supplementation may lead to an increased inflammatory activity through the generation of reactive oxygen species. To date, data from studies in animal models of inflammatory bowel disease support the theoretical disadvantage of iron supplementation in this respect. The results, however, cannot easily be extrapolated to the human situation, because the amount of supplemented iron in these experiments was much higher than the dose used in patients with iron deficiency.
Octreotide 24‐h prophylaxis in patients at high risk for post‐ERCP pancreatitis: results of a multicenter, randomized, controlled trial
Authors: Testoni P. A. , Bagnolo F. , Andriulli A. , Bernasconi G. , Crotta S. , Lella F. , Lomazzi A. , Minoli G. , Natale C. , Prada A. , Toti G. L. , Zambelli A.
Published: March 2003

Background:

Pharmacological prophylaxis of post‐ERCP pancreatitis is costly and not useful in most non‐selected patients, in whom the incidence of pancreatitis is 5% or less. However, it could be useful and probably cost‐effective, in patients at high risk for this complication, where the post‐procedure pancreatitis rate is 10% and more.

Aim:

To assess the efficacy of octreotide in reducing the incidence and severity of post‐ERCP pancreatitis and procedure‐related hospital stay, in subjects with known patient‐related risk factors.

Methods:

A total of 120 patients were randomly allocated to receive octreotide or not, in a multicentre, randomized, controlled trial. The drug was given subcutaneously, 200 μg t.d.s., starting 24 h before the ERCP procedure, in patients with either sphincter of Oddi dysfunction, or a history of relapsing pancreatitis or post‐ERCP pancreatitis, or who were aged under 35 years, or who had a small common bile duct diameter (< 8 mm).

Results:

A total of 114 patients (58 in the octreotide group and 56 in the control group) completed the trial. Post‐procedure pancreatitis occurred in seven octreotide‐treated patients (12.0%) and eight controls (14.3%). The two groups showed no significant differences in the incidence or severity of pancreatitis. Twenty‐four hours after the procedure, severe hyperamylasemia (more than five times the upper normal limit) without pancreatic‐like pain was recorded in three octreotide‐treated patients (5.2%) and six controls (10.7%), the difference being not significant.

Conclusion:

Twenty‐four‐hour prophylaxis with octreotide proved ineffective in preventing post‐ERCP pancreatitis and in avoiding 24‐h severe hyperamylasemia in high‐risk patients.
Safety and efficacy of azathioprine in the maintenance of ciclosporin‐induced remission of ulcerative colitis
Authors: Actis G. C. , Bresso F. , Astegiano M. , Demarchi B. , Sapone N. , Boscaglia C. , Rizzetto M.
Published: March 2003

Background:

It has been shown that azathioprine prolongs the response to ciclosporin of steroid‐refractory ulcerative colitis, but no specific data are available concerning its toxicity in this indication.

Aim and methods:

The charts of 21 patients with steroid‐refractory ulcerative colitis who received azathioprine overlapping with a successful ciclosporin course were reviewed for the onset of toxicity. The controls consisted of 48 initial responders to steroids who received azathioprine for steroid‐dependence or resistance/toxicity.

Results:

Two of the 21 patients were withdrawn because of hypersensitivity to azathioprine. The remaining 19 were treated for a median of 18 months together with a median daily steroid dose of 35 mg (10–75 mg) to be tapered off. Toxicity (31%) included leukopenia alone (two cases), cholestasis alone (one case), cholestasis and increased amylase (one case), increased amylase alone (one case), and cutaneous infection (one case). The frequency of withdrawal was 21%. The mean daily steroid doses were reduced from 38 mg to 3.8 mg in the study cohort, and from 25 mg to 8 mg in the controls, among whom toxicity (27%) included four cases each of leukopenia and increased amylase, two cases each of alteration of liver enzymes and infection, and one case of gastric intolerance. Ten of the 48 controls (20%) were withdrawn from the study.

Conclusion:

Azathioprine is as effective and safe in the maintenance of the response of patients with steroid‐refractory ulcerative colitis to ciclosporin as it is in the treatment of those who respond to steroids.
A triple therapy regimen after failed Helicobacter pylori treatments
Authors: Zullo A. , Hassan C. , Campo S. M. A. , Lorenzetti R. , Febbraro I. , De Matthaeis M. , Porto D. , Morini S.
Published: March 2003

Background

: Following standard triple therapy, up to 20% of patients require further Helicobacter pylori eradication treatment. Data regarding the efficacy of re‐treatment in these patients are scarce.

Aim

: To evaluate the efficacy of a triple therapy after one or more consecutive treatment failures.

Methods

: A total of 51 patients with persistent H. pylori infection after at least one unsuccessful standard 1‐week regimen were enrolled in the study. H. pylori infection at entry was assessed by rapid urease test and histology on biopsies from the antrum and the corpus. Patients were given a 2‐week triple therapy, comprising ranitidine bismuth citrate 400 mg b.d., tetracycline 500 mg t.d.s., and tinidazole 500 mg b.d. Ranitidine bismuth citrate was given during meals, whilst tetracycline and tinidazole was given after meals. Bacterial eradication was assessed by endoscopy (36 patients) or 13C‐urea breath test (15 patients) 4–6 weeks after therapy had ended.

Results

: All 51 patients completed the study and H. pylori eradication was achieved in 46, with an eradication rate of 90% (95% CI: 82–98). In detail, bacterial eradication was obtained in 96% of patients who had previously failed one course of clarithromycin–amoxicillin based triple therapy, in 88% patients who had failed a clarithromycin–tinidazole based triple therapy, in 83% patients who had failed both treatment schedules, and in the only patient who had failed three consecutive therapeutic attempts. Two patients took the therapy for 9 and 10 days instead of the full 14 day‐course. No major side‐effects were reported, whilst six (12%) patients complained of mild side‐effects.

Conclusion

: This study demonstrates that this triple therapy regimen is effective for re‐treatment of H. pylori infection.
Glucocorticoids and IL‐10, but not 6‐MP, 5‐ASA or sulfasalazine block endothelial expression of MAdCAM‐1: implications for inflammatory bowel disease therapy
Authors: Oshima T. , Pavlick K. , Grisham M. B. , Jordan P. , Manas K. , Joh T. , Itoh M. , Alexander J. S.
Published: March 2003

Background

: Enhanced MAdCAM‐1 (mucosal addressin cell adhesion molecule‐1) expression is associated with the aetiology of inflammatory bowel disease, but little is known about MAdCAM‐1: regulation, or how inflammatory bowel disease therapies modulate MAdCAM‐1.

Aim

: To examine how agents currently used to treat inflammatory bowel disease affect MAdCAM‐1: induced by tnf‐α in an in vitro model of inflammatory bowel disease.

Methods

: Endothelial monolayers were pretreated with dexamethasone (DEX): 5‐aminosalicylic acid (5‐ASA), 6‐mercaptopurine (6‐MP), sulfasalazine or interleukin‐10: (IL‐10: prior to TNF‐α (20 ng/mL), and MAdCAM‐1: measured by Western blotting, RT‐PCR, EMSA and lymphocyte adhesion assays.

Results

: MAdCAM‐1: was induced dose‐ and time‐dependently by TNF‐α on endothelial cells. Either dexamethasone or IL‐10: reduced TNF‐α‐induced MAdCAM‐1: protein, mRNA and lymphocyte adhesion. However, neither 5‐ASA, sulfasalazine nor 6‐MP blocked MAdCAM‐1 induction.

Conclusions

: Our data indicate that dexamethasone or IL‐10 can exert therapeutic activity in inflammatory bowel disease through MAdCAM‐1 inhibition. 5‐ASA, sulfasalazine and 6‐MP, while beneficial in inflammatory bowel disease, do not directly control MAdCAM‐1, and are beneficial through inhibition of other inflammatory processes.
Bedtime H2 blockers improve nocturnal gastric acid control in GERD patients on proton pump inhibitors
Authors: Xue S. , Katz P. O. , Banerjee P. , Tutuian R. , Castell D. O.
Published: March 2003

Aim:

Proton pump inhibitors taken twice daily before meals (proton pump inhibitor b.d. AC) effectively controls daytime gastric pH; however, nocturnal gastric acid breakthrough (NAB) occurs in more than 75% of patients. Adding an H2‐blocker at bedtime decreases NAB in normal subjects. The efficacy of this regimen has not been evaluated in GERD patients. The aim of this study was to assess the effects of proton pump inhibitor b.d., both with and without bedtime H2‐blocker on intragastric pH and the occurrence of NAB in GERD patients.

Methods:

Prolonged ambulatory pH studies in GERD patients were reviewed. Group A: 60 patients (mean age 53 years, male 30) taking either omeprazole 20 mg or lansoprazole 30 mg b.d. Group B: 45 patients (mean age 49 years, male 23) on proton pump inhibitor b.d. (omeprazole 20 mg or lansoprazole 30 mg) plus an H2‐blocker at bedtime (ranitidine 300 mg, famotidine 40 mg or nizatidine 300 mg). Eleven patients were evaluated during treatment with both regimens (group C). The percentage time of nocturnal and daytime intragastric pH > 4 and per cent of patients with gastric NAB were analysed. In the patients with NAB, its duration and associated oesophageal acid exposure also were analysed.

Results:

Median percentage time intragastric pH > 4 overnight was 51% in group A, compared to 96% in group B (P < 0.0001). Median percentage daytime pH > 4 was 73% in group A and 79.8% in group B (P=0.14). Median percentage time intragastric pH >p 4 overnight increased from 54.6% without H2RA to 96.5% after adding bedtime H2RA (P=0.0013) in group C patients. NAB occurred in 82% patients in group A and 40% in group B (P < 0.0001). The mean duration of oesophageal acid exposure during NAB was significantly shorter in group B (18 ± 6 min) than in group A (42 ± 9 min, P=0.04).

Adding a bedtime H2‐blocker to the treatment enhanced nocturnal gastric pH control and decreased NAB compared to the proton pump inhibitor b.d. regimen. A bedtime H2‐blocker also decreased oesophageal acid exposure during NAB.

Conclusion:

Adding a bedtime H2‐blocker to a proton pump inhibitor b.d. regimen should be considered in patients who require continued nocturnal gastric acid control whilst taking proton pump inhibitor b.d.
Extracorporeal photochemotherapy in patients with steroid‐dependent Crohn’s disease: a prospective pilot study
Authors: Reinisch W. , Nahavandi H. , Santella R. , Zhang Y. , Gasché C. , Moser G. , Waldhör T. , Gangl A. , Vogelsang H. , Knobler R.
Published: March 2003

Background:

Extracorporeal photochemotherapy has been proven effective in selected T‐cell mediated diseases.

Aim:

To evaluate the safety and efficacy of extracorporeal photochemotherapy in patients with steroid‐dependent Crohn’s disease by an open, monocentric trial in three phases of 24 weeks each.

Methods:

In phase 1 standardized steroid tapering was initiated in patients with a history of steroid‐dependent Crohn’s disease. Those with a prospectively evaluated maintenance dose of at least 10 mg/day prednisolone continued steroid‐withdrawal under the application of extracorporeal photochemotherapy in phase 2. The duration of remission or response was followed during phase 3. Colonic tissue bioptically obtained before and after extracorporeal photochemotherapy was studied by immunofluorescence microscopy for the presence of photoadduct positive cells.

Results:

Out of 24 patients included in phase 1, 10 entered phase 2 for extracorporeal photochemotherapy. Four subjects achieved remission and four others response. Significant reductions in serum C‐reactive protein levels and intestinal permeability were measured, as well as increases in quality of life and plasma adrenocorticotropic hormone levels. No major side‐effects were observed. Remission remained stable in three out of four patients during phase 3. In three patients, positive nuclear stainings of photoadducts were detected in colonic mononuclear cells after extracorporeal photochemotherapy.

Conclusions:

Extracorporeal photochemotherapy represents a safe steroid‐sparing approach in patients with Crohn’s disease and is associated with intestinal homing of photopheresed cells.
Helicobacter pylori antimicrobial resistance in the United Kingdom: the effect of age, sex and socio‐economic status
Authors: Parsons H. K. , Carter M. J. , Sanders D. S. , Winstanley T. , Lobo A. J.
Published: March 2003

Background:

Helicobacter pylori antimicrobial resistance is the most common reason for eradication failure. Small studies have shown metronidazole resistance to be more prevalent in certain population groups.

Aim:

To determine the resistance rates in a large cohort of patients from a single centre in the UK, and to evaluate resistance patterns over time, according to age, sex and socio‐economic status.

Methods:

Consecutive patients with H. pylori‐positive antral gastric biopsy samples were studied from 1994 to 1999. Susceptibility testing was performed to metronidazole, tetracycline, macrolide and amoxicillin by the modified disk diffusion method. The Jarman under‐privileged area score was used as a measure of socio‐economic status.

Results:

A total of 1064 patients were studied. Overall metronidazole resistance was 40.3%, decreasing with age (P < 0.0001, odds ratio for patients over 60 years 0.63, 95% CI: 0.48–0.80). Women were more likely to have metronidazole resistant strains (P=0.003, odds ratio 1.5, 95% CI: 1.15–1.91), but there was no association with Jarman score. Macrolide resistance was associated with metronidazole resistance (P=0.03, odds ratio 2.14, 95% CI: 1.07–4.28).

Conclusions:

Metronidazole resistance in H. pylori is highly prevalent and more common in women and the young, but does not appear to be related to socio‐economic status.
A comparison of simplified lansoprazole suspension administered nasogastrically and pantoprazole administered intravenously: effects on 24‐h intragastric pH
Authors: Täubel J. J. , Sharma V. K. , Chiu Y. L. , Lukasik N. L. , Pilmer B. L. , Pan W. J.
Published: March 2003

Aim:

To compare the 24‐h intragastric pH effects of simplified lansoprazole suspension, 30 mg, administered nasogastrically, with pantoprazole, 40 mg, administered intravenously.

Methods:

Thirty‐six healthy adults were enrolled and given simplified lansoprazole suspension, 30 mg (nasogastrically), or pantoprazole, 40 mg (intravenously), once daily for five consecutive days in a cross‐over fashion. Intragastric pH was monitored at baseline and on Days 1 and 5 of each treatment period. The pharmacokinetic parameters of lansoprazole and pantoprazole were also determined on Days 1 and 5.

Results:

No statistically significant changes in pharmacokinetic parameters occurred between Days 1 and 5 with either regimen, except for pantoprazole Cmax. On Days 1 and 5, significantly higher mean 24‐h intragastric pH values were observed with 30 mg simplified lansoprazole suspension compared with 40 mg intravenous pantoprazole (Day 1, 3.13 vs. 2.67; Day 5, 3.95 vs. 3.61, respectively; P < 0.05). Additionally, 30 mg simplified lansoprazole suspension produced significantly (P < 0.05) higher percentages of time intragastric pH was above 3, 4, 5 or 6 as compared with 40 mg intravenous pantoprazole throughout Days 1 and 5.

Conclusions:

A 30 mg dose of simplified lansoprazole suspension administered nasogastrically was consistently more effective at controlling intragastric pH than pantoprazole, 40 mg, administered intravenously.
Nizatidine and cisapride enhance salivary secretion in humans
Authors: Adachi K. , Ono M. , Kawamura A. , Yuki M. , Fujishiro H. , Kinoshita Y.
Published: March 2003

Background:

Salivation plays an important role in the defence of the oesophageal mucosa against gastric acidic reflux and can be evoked by cholinergic stimulation. Both nizatidine and cisapride have been reported to increase acetylcholine concentrations in the cholinergic system.

Aim:

To investigate the effect of nizatidine and cisapride on salivary secretion, salivary epidermal growth factor and bicarbonate output.

Methods:

The salivary volume and concentration of salivary epidermal growth factor and bicarbonate were measured after the administration of nizatidine (150 mg), famotidine (20 mg) and cisapride (5 mg) in 30 male healthy volunteers.

Results:

Basal and stimulated salivary secretions were found to be increased after the administration of nizatidine and cisapride. In contrast, salivary secretion was not increased by famotidine. Although epidermal growth factor content was not augmented, nizatidine and cisapride administration also increased the bicarbonate output in mastication‐stimulated saliva.

Conclusions:

Increased salivary secretion and bicarbonate output induced by nizatidine may be useful for the treatment of patients with gastro‐oesophageal reflux disease.
Antibiotic prophylaxis prior to endoscopic retrograde cholangiopancreatography in patients with obstructive jaundice: is it worth the cost?
Authors: Thompson B. F. , Arguedas M. R. , Wilcox C. M.
Published: March 2003

Background:

There are few published data concerning the economic impact of antibiotic prophylaxis prior to endoscopic retrograde cholangiopancreatography in the setting of biliary obstruction.

Aim:

To perform decision analysis to determine the costs of prophylaxis in patients undergoing endoscopic retrograde cholangiopancreatography for obstructive jaundice.

Methods:

A decision analysis model was constructed. The probability of biliary sepsis, death and endoscopic retrograde cholangiopancreatography complications was obtained from the medical literature and from a retrospective analysis of our own experience. Costs were obtained from Medicare reimbursement at our institution. The strategies evaluated were endoscopic retrograde cholangiopancreatography with and without single‐dose antibiotic prophylaxis. We compared the total costs, number of episodes of cholangitis and deaths associated with each strategy.

Results:

Based on published data and the results of our retrospective analysis, the strategy of administering single‐dose prophylactic antibiotics prior to endoscopic retrograde cholangiopancreatography in patients with obstructive jaundice resulted in lower total costs, fewer episodes of cholangitis and fewer deaths compared to a strategy of not administering antibiotics. The results were sensitive to the rates of cholangitis, cost of antibiotics and the cost of treating an episode of cholangitis.

Conclusions:

Antibiotic prophylaxis prior to endoscopic retrograde cholangiopancreatography results in fewer cases of cholangitis and is cost saving when compared to a strategy of no prophylaxis in patients with obstructive jaundice.
Specific identification of three low molecular weight membrane‐associated antigens of Helicobacter pylori
Authors: Voland P. , Weeks D. L. , Vaira D. , Prinz C. , Sachs G.
Published: March 2003

Background:

A large number of Helicobacter pylori proteins are antigenic, but antibodies to these proteins persist in spite of the eradication of the infection.

Methods and results:

The analysis of sera from H. pylori‐infected and non‐infected patients, before and 3 and 5 months after eradication, showed that the antibody response against unknown H. pylori antigens at 32, 30, 22 and 14 kDa in sodium dodecylsulphate polyacrylamide gel electrophoresis decreased by ≥ 60% at 3 months and ≥ 70% at 5 months after treatment. Two‐dimensional gel electrophoresis and mass spectrometry allowed the identification of eight proteins at these positions: neuraminyl‐lactose‐binding haemagglutinin precursor, 3‐oxoadipate CoA‐transferase subunit A, elongation factor P, peptidoglycan‐associated lipoprotein precursor, hypothetical protein HP0596, adhesin‐thiol peroxidase, 50S ribosomal protein L7/L12 and subunit b′ of the F0 ATP synthase. Three of these eight, expressed as recombinant proteins (32 kDa neuraminyl‐lactose‐binding haemagglutinin precursor, 30 kDa peptidoglycan‐associated lipoprotein precursor and 22 kDa hypothetical protein HP0596), reacted specifically with sera from infected patients, while the 14 kDa 50S ribosomal protein L7/L12 cross‐reacted with one out of five sera from H. pylori‐negative patients. The other recombinant proteins did not show significant immunoreactivity.

Conclusions:

Four low molecular weight antigens were identified by these methods, three of which were specific. Immunoreaction with these three proteins (neuraminyl‐lactose‐binding haemagglutinin precursor, peptidoglycan‐associated lipoprotein precursor and hypothetical protein HP0596) could provide a serological assessment not only of H. pylori infection, but also of eradication.
Domperidone is more effective than cisapride in children with diabetic gastroparesis
Authors: Franzese A. , Borrelli O. , Corrado G. , Rea P. , Di Nardo G. , Grandinetti A. L. , Dito L. , Cucchiara S.
Published: March 2003

Background:

Disorders of gastrointestinal motility are commonly detected in patients with insulin‐dependent diabetes mellitus and are associated with significant morbidity. They contribute to poor metabolic control of diabetes.

Aim:

To assess the effect of an 8‐week course of domperidone or cisapride on gastric electrical activity, gastric emptying time and dyspeptic symptoms in children with insulin‐dependent diabetes mellitus and gastroparesis.

Methods:

Dyspeptic symptoms were assessed by a score system, gastric emptying time was measured by ultrasonography and gastric electrical activity was obtained by electrogastrography. Fourteen children received domperidone and 14 received cisapride. The median (range) ages were 11.6 years (5–15 years) and 12 years (6–16.9 years), respectively. Symptom assessment, ultrasonography and electrogastrography were repeated at the end of the trial. Fasting and fed (180 min after feeding) glycaemia and haemoglobin A, C (HbA1c) levels were also measured.

Results:

At the end of the trial both groups showed a significant decrease in symptomatic score; however, the score was markedly lower in the domperidone group than in the cisapride group (P < 0.01). Domperidone was significantly more effective than cisapride in reducing the gastric emptying time (P < 0.05), normalizing gastric electrical activity (P < 0.05) and decreasing the prevalence of episodes of gastric dysrhythmia (P < 0.01). Domperidone was also more effective than cisapride in improving diabetic metabolic control. No potentially drug‐related adverse effects occurred.

Conclusions:

In children with insulin‐dependent diabetes mellitus complicated by dyspeptic symptoms and gastroparesis, domperidone is superior to cisapride in reversing gastric emptying delay and gastric electrical abnormalities, as well as in improving dyspeptic symptoms and diabetic metabolic control.
Effectiveness of Helicobacter pylori eradication treatments in a primary care setting in Italy
Authors: Monica P. Della , Lavagna A. , Masoero G. , Lombardo L. , Crocellá L. , Pera A.
Published: March 2003

Aim:

To evaluate the choice and relative effectiveness of Helicobacter pylori eradication regimens in a primary care setting.

Patients and methods:

Patients referred to our department, who had been treated for H. pylori infection during the preceding 6 months, were enrolled between September 1998 and July 1999. H. pylori status was assessed by urea breath test. Information on the drugs administered, compliance and side‐effects was recorded.

Results:

The mean eradication rate was 72% in patients receiving their first course of treatment (1863 cases; 45% male; mean age, 53 ± 14 years); a double therapy regimen was prescribed to 14% of patients, triple therapy to 85% and quadruple therapy to 1%. Maastricht Consensus proton pump inhibitor‐based regimens were prescribed in 80% of cases, with a mean eradication rate of 73%. No statistically significant correlation was found between eradication failure and sex, age, endoscopic findings or administered treatment.

Conclusions:

In Italy, in a primary care setting, first‐line H. pylori eradication therapies reflect international guidelines. The efficacy of such regimens is lower than that reported by controlled trials. These results are relevant when making pharmacoeconomic evaluations of H. pylori management.
Safety and efficacy of two reduced dosing regimens of sodium phosphate tablets for preparation prior to colonoscopy
Authors: Rex D. K. , Chasen R. , Pochapin M. B.
Published: March 2003

Objectives:

To evaluate the safety and efficacy of two reduced dosing regimens of sodium phosphate tablets (Visicol, InKine Pharmaceutical Co. Inc., Blue Bell, PA, USA) for colon cleansing prior to colonoscopy.

Methods:

In a randomized, multicentre, endoscopist‐blinded clinical study, adults undergoing colonoscopy received either 28 tablets (42 g) or 32 tablets (48 g) of sodium phosphate for colon cleansing. The endoscopist used a validated four‐point scale to rate the overall quality of colon cleansing, as well as cleansing in the ascending colon. Adverse events were collected and evaluated.

Results:

The quality of overall colon cleansing was `excellent' or `good' in 84% or more of both groups, with no significant difference between the two doses. No patient had a preparation rated as `inadequate' or required a repeat procedure. All patients were able to complete the assigned dose of tablets, and there were no deaths, serious adverse events or dropouts from the study.

Conclusions:

A reduced tablet regimen for sodium phosphate tablets, using either 28 or 32 tablets, is well tolerated and effective for colon cleansing prior to colonoscopy.
Effects of anti‐tumour necrosis factor‐α therapy on the quality of life in Crohn's disease
Authors: Van Balkom B. P. J. , Schoon E. J. , Stockbrügger R. W. , Wolters F. L. , Van Hogezand R. A. , Van Deventer S. J. H. , Oldenburg B. , Van Dullemen H. M. , Russel M. G. V. M.
Published: March 2003

Background : Infusion of anti‐tumour necrosis factor‐α appears to be highly effective in patients with Crohn's disease.

Aim : To assess the effect of infliximab on the quality of life in patients with active or fistulizing disease, as measured by the inflammatory bowel disease questionnaire, and to examine the impact on its four dimensions.

Methods : An observational study was conducted in 65 patients. An infusion of 5 mg/kg infliximab was given at week 0 in patients with active disease and at week 0, 2 and 6 in fistulizing disease. Changes from baseline in the total and dimensional inflammatory bowel disease questionnaire scores were calculated and compared between the patient groups. Potential predictors of change in the quality of life were identified.

Results : In the active disease group, at week 4, the mean total and dimensional inflammatory bowel disease questionnaire scores improved compared to baseline (P < 0.001). In the fistulizing group, at week 6, all scores changed from baseline (P < 0.05). Improvement in the total inflammatory bowel disease questionnaire score correlated well with the improvement of the Crohn's disease activity index. Systemic and social scores improved more than bowel and emotional scores. Inflammatory Crohn's disease and a young age at diagnosis were predictors for a better response to infliximab therapy.

Conclusions : Infliximab therapy improves all dimensions of the quality of life in patients with Crohn's disease.
Prucalopride, a systemic enterokinetic, for the treatment of constipation
Authors: Emmanuel A. V. , Roy A. J. , Nicholls T. J. , Kamm M. A.
Published: March 2003

Background : Laxatives are frequently ineffective in treating constipation. An alternative therapeutic approach is to target serotonin‐4 receptors, which are involved in initiating peristalsis.

Aim : In a double‐blind, placebo‐controlled trial, to assess the efficacy and safety of a systemically active serotonin‐4 agonist, prucalopride.

Methods : Seventy‐four women with constipation were stratified into slow or normal transit groups, and each group was randomized to receive either placebo or 1 mg prucalopride daily for 4 weeks. A bowel function diary was maintained. Whole‐gut and orocaecal transit, visceral sensitivity, quality of life and psychological state were assessed before and after treatment.

Results : Prucalopride, not placebo, increased spontaneous stool frequency (P=0.008) and reduced time to first stool (P < 0.001). Prucalopride reduced the number of retained markers in all patients compared to placebo (P=0.004). Prucalopride reduced the mean number of retained markers in slow transit (P=0.069), but did not alter the marker count in normal transit (P=0.86). Orocaecal transit was accelerated by prucalopride, not placebo (P=0.004). Prucalopride, notplacebo, increased rectal sensitivity to distension (urge volume, P=0.01) and electrical stimulation (P=0.001). Prucalopride significantly improved several domains of the Short Form Health Status Survey and the disease‐specific quality of life. Adverse effects were similar for prucalopride and placebo.

Conclusions : Prucalopride improves symptoms, upper gut transit and gut sensitivity in constipated patients with both slow and normal transit. It improves transit in patients with slow transit. These changes are associated with improved well‐being.
One‐week triple vs. quadruple therapy for Helicobacter pylori infection — a randomized trial
Authors: Calvet X. , Ducons J. , Guardiola J. , Tito L. , Andreu V. , Bory F. , Guirao R. ,   The Group for Eradication Studies from Catalonia and Aragón (Gresca)
Published: March 2003

Background : Seven‐day triple therapy including omeprazole, clarithromycin and amoxicillin has become the treatment of choice for Helicobacter pylori infection. However, 7 days of classical quadruple therapy combining omeprazole, tetracycline, metronidazole and bismuth may be an alternative to triple therapy.

Aim : To compare triple vs. quadruple therapy for H.pylori eradication.

Methods : Three hundred and thirty‐nine patients with peptic ulcer and H. pylori infection were included in the study. Patients were randomized to receive omeprazole,20 mg, amoxicillin, 1 g, and clarithromycin, 500 mg, all b.d., or omeprazole, 20 mg b.d., tetracycline chloride, 500 mg, metronidazole, 500 mg, and bismuth subcitrate, 120 mg, all t.d.s. Cure was defined as a negative urea breath test at least 2 months after treatment.

Results : Per protocol and intention‐to‐treat cure rates were 86%[95% confidence interval (CI), 80–91%] and 77% (95% CI, 70–83%) for triple therapy, and 89% (95% CI, 82–93%) and 83% (95% CI, 76–88%) for quadruple therapy. No significant differences between the groups were found in the cure rates, compliance or side‐effects.

Conclusion : One‐week triple and quadruple therapy show similar results when used as first‐line eradication treatment.
The use of ciclosporin in paediatric inflammatory bowel disease: an Italian experience
Authors: Barabino A. , Torrente F. , Castellano E. , Gandullia P. , Calvi A. , Cucchiara S. , De 'Angelis G. L. , Fontana M. , Lionetti P. , De Giacomo C. , Gissi A.
Published: March 2003

Aim : To asses the efficacy and safety of ciclosporin in a paediatric population with inflammatory bowel disease.

Patients and methods : Twenty‐three Italian children treated with ciclosporin were studied retrospectively. The indications for treatment were severe unresponsive colitis, chronic active colitis or severe fistulizing Crohn's disease. The treatment duration, follow‐up and causes of drug discontinuation were assessed.

Results : Sixteen patients were treated intravenously for a mean time of 10 ± 7 days (1–24 days) and 19 orally for a mean time of 133 days (17–660 days). The mean follow‐up of all patients was 13.2 months. Ciclosporin was totally ineffective, being discontinued for surgery, in nine of 23 patients (39%); it was discontinued for partial response in three patients (13%). During treatment, clinical remission was achieved in eight children (35%) and maintained after drug withdrawal in four (17%). In severe unresponsive colitis, urgent colectomy was avoided in 12 (85%) of 14 patients who tolerated the drug. Side‐effects appeared in six of 23 patients (26%), and three (13%) required ciclosporin to be discontinued due to neurotoxicity.

Conclusions : Ciclosporin shows disappointing long‐term results in the treatment of refractory inflammatory bowel disease, but can play an important role in preventing urgent surgery in unresponsive severe colitis. Severe side‐effects can occur.