bluuebunny/crossref_metadata_2025 huggingface dataset:
Pantoprazole, azithromycin and tinidazole: short duration triple therapy for eradication of Helicobacter pylori infection
Authors: Calabrese C. , Di Febo G. , Areni A. , Scialpi C. , Biasco G. , Miglioli M.
Published: March 2003

Background:

Azithromycin is an acid‐stable macrolide that achieves remarkably high concentrations in gastric tissue, persisting above the MIC90 for Helicobacter pylori over a period of 5‐days, after a single 500 mg oral dose.

Aim:

To evaluate and compare the efficacy, safety, and tolerability of two eradicating regimens of pantoprazole, azithromycin and tinidazole.

Methods:

A total of 100 consecutive symptomatic H. pylori‐positive patients received pantoprazole 40 mg b.d. for 1 week, and were randomly assigned to either azithromycin 500 mg o.m. and tinidazole 500 mg b.d. during the first 3 days (early group, n=50) or during the last 3 days of therapy with pantoprazole (late group, n=50). H. pylori status was assessed by histology and rapid urease test at entry and by histology and 13C‐urea breath test 1 month after the end of the therapy.

Results:

Ninety‐nine patients completed the study. H. pylori was eradicated in 86% of patients in the early group (intention‐to‐treat 86%) and in 88% of patients in the late group (intention‐to‐treat 88%).

Conclusions:

This short triple therapy is effective for H. pylori eradication. The compliance was excellent and side‐effects negligible. Moreover, the pantoprazole pre‐treatment did not modify the efficacy of the therapy.
A double‐blind, randomized, dose response study testing the pharmacological efficacy of synthetic porcine secretin
Authors: Jowell P. S. , Robuck‐Mangum G. , Mergener K. , Branch M. S. , Purich E. D. , Fein S. H.
Published: March 2003

Background:

Biologically derived porcine secretin has been used as a diagnostic agent in clinical gastrointestinal practice for many years. Pure synthetic porcine secretin is now available for investigational clinical use.

Aim:

To compare the pharmacology of synthetic porcine secretin and biologically derived porcine secretin in healthy volunteers.

Methods:

Secretin stimulation tests were performed in 12 volunteer subjects in a double‐blind, randomized, Latin square crossover design study comparing three doses of synthetic porcine secretin (0.05, 0.2, and 0.4 μg/kg) with a standard dose of biologically derived porcine secretin (1 CU/kg). Duodenal aspirates were analysed for total volume and for bicarbonate concentration. Total bicarbonate output was calculated.

Results:

Twelve subjects completed four dosing regimens. A multiple comparison test was used to compare dosing regimens. The 0.2 and 0.4 μg/kg doses of synthetic porcine secretin were not different from the 1 CU/kg dose of biologically derived porcine secretin for volume, bicarbonate concentration and total output from 0 to 60 min. Only one patient had an adverse event, which was mild, transient flushing after the 0.2 and 0.4 μg/kg doses of synthetic porcine secretin and after the 1 CU/kg dose of biologically derived porcine secretin.

Conclusions:

Synthetic porcine secretin has identical pharmacologic effects to biologically derived porcine secretin in normal subjects. Both drugs were safe and well‐tolerated. This study validates synthetic porcine secretin as a substitute for biologically derived porcine secretin.
The roles of nitric oxide and prostaglandins in alterations of ulcerogenic and healing responses in adjuvant‐induced arthritic rat stomachs
Authors: Kato S. , Tanaka A. , Kunikata T. , Mizoguchi H. , Takeuchi K.
Published: March 2003

Aim: To examine alterations of gastric ulcerogenic and healing responses in adjuvant‐induced arthritic rats.

Methods: Arthritis was induced in male Dark Agouti rats by injection of Freund's complete adjuvant into the right hind paw.

Results: The gastric ulcerogenic response to indomethacin was markedly increased in AA rats, depending on the degree of arthritic change. By contrast, HCl/ethanol‐induced gastric lesions were significantly suppressed in arthritic rats when compared with normal rats. The increased ulcerogenic response to indomethacin was significantly prevented by L‐NAME and antineutrophil serum but not by FR167653, while the reduced ulcerogenic response to HCl/ethanol was significantly prevented by L‐NAME and partly by indomethacin or NS‐398. On the other hand, the healing of chronic gastric ulcers induced by thermal cauterization was also significantly delayed in arthritic rats when compared with normal rats. This delayed healing of gastric ulcers was affected by neither L‐NAME, indomethacin nor FR167653. The gastric mucosa of arthritic rats showed a significant increase in both inducible nitric oxide synthase (iNOS) activity and prostaglandin (PG) E2 contents.

Conclusions: Gastric ulcerogenic and healing responses were altered in arthritic rats. The ulcerogenic response to indomethacin was increased while that to HCl/ethanol was decreased. These changes in ulcerogenic responses may both be accounted for by increased production of NO/iNOS, with the latter also being partially related to elevated production of PGs/COX‐2. Moreover, the healing of gastric ulcers was also delayed in arthritic rats, but the mechanism was related to neither NO nor PGs.
Matrix metalloproteinase expression in cultured human gastric wall fibroblasts – interactions with Helicobacter pylori isolated from patients with ulcers
Authors: Yokoyama T. , Otani Y. , Kurihara N. , Sakurai Y. , Kameyama K. , Suzuki H. , Igarashi N. , Kimata M. , Wada N. , Kubota T. , Kumai K. , Kitajima M.
Published: March 2003

Background: Matrix metalloproteinases (MMPs), enzymes capable of degrading collagens and other extracellular matrix components, have been implicated in gastric ulcer formation. However, the effect on MMP expression of Helicobacter pylori, also implicated in these lesions, has not been studied to our knowledge.

Aim: To seek links between H. pylori and MMP expression likely to affect gastric ulcer formation. After fibroblasts from human gastric wall were cocultured with H. pylori, concentrations of MMP‐1 and ‐2 in the medium were determined by enzyme‐linked immuno‐sorbent assays.

Results: Whereas MMP‐1 was not detected in media from fibroblasts or H. pylori culture alone, MMP‐1 was detected in cocultures (P < 0.01). Similar amounts of MMP‐2 were detected in medium from fibroblasts cultured alone and with H. pylori. No MMP‐2 production by H. pylori cultured alone was detected.

Conclusions: MMP‐1 appears to be important in gastric ulcer pathogenesis, and MMP‐1 induction by H. pylori may impede gastric ulcer healing.
Is Helicobacter pylori relevant in the management of reflux disease?
Authors: Dent J.
Published: March 2003

Data on the interaction of reflux disease and Helicobacter pylori infection are limited in scope and rigour, controversial and difficult to interpret. Despite this, a framework of understanding is emerging, which is consistent with known effects on gastric acid secretion.

In patients with moderate to severe H. pylori‐induced corpus gastritis, eradication can increase substantially impaired gastric acid secretion sufficiently to precipitate reflux disease in people with pre‐existing sub‐clinical defective gastro‐oesophageal competence. By contrast, reflux disease in duodenal ulcer patients probably benefits from eradication of H. pylori. There appears to be no significant impact on reflux disease from eradication in healthy subjects or individuals whose primary problem is reflux disease.

Helicobacter pylori‐infected reflux disease patients respond slightly better to proton pump inhibitors. These agents cause a topographic alteration of gastritis from antrum to corpus, the clinical significance of which is controversial.

Many practitioners misjudge the risks and benefits of the effects of H. pylori eradication on reflux disease. Regardless of patient diagnosis, the balance is in favour of H. pylori eradication. For those in whom reflux oesophagitis development is a defined possibility, oesophagitis is mild, easily treated and most unlikely to be associated with any major risk for development of oesophageal adenocarcinoma.
Duration of effect of lansoprazole on gastric pH and acid secretion in normal male volunteers
Authors: Bell N. , Karol M. D. , Sachs G. , Greski‐Rose P. , Jennings D. E. , Hunt R. H.
Published: March 2003

Aim:

A double‐blind, placebo‐controlled study to assess the duration of effect of lansoprazole 30 mg o.m. on intragastric pH, acid secretion, gastrin levels, the potential for rebound acidity, and the relationship between gastric acid and drug pharmacokinetic parameters.

Methods:

Sixteen subjects were treated with lansoprazole 30 mg daily or placebo for 14 days, followed by a 7‐day post‐dosing period and a post‐study evaluation on day 28. Ambulatory 24‐h pH was recorded and pentagastrin‐stimulated acid secretion measured. Plasma kinetics of lansoprazole were determined.

Results:

Mean intragastric pH in the lansoprazole group increased significantly (P < 0.05) from baseline to day 14 compared to placebo. After cessation of treatment, secretory activity, as measured by intragastric pH, basal acid output and stimulated acid output, returned to baseline in 2 to 4 days without any overshoot, indicating the absence of acid rebound. Lansoprazole’s terminal disposition half‐life was 1.11 h. Mean pH and serum gastrin returned to baseline with half‐lives of 22 and 19 h, respectively.

Conclusions:

Lansoprazole 30 mg daily significantly increases mean intragastric pH without producing acid rebound. Regeneration of acid production depends primarily on de novo synthesis of the acid pump.
Lack of small intestinal ulcerogenecity of nitric oxide‐releasing indomethacin, NCX‐530, in rats
Authors: Mizoguchi H. , Hase S. , Tanaka A. , Takeuchi K.
Published: March 2003

Aim:

To evaluate the intestinal ulcerogenic property of nitric oxide‐releasing indomethacin (NCX‐530) in the rat, in comparison with indomethacin.

Methods:

Animals were given indomethacin or NCX‐530 subcutaneously and killed 24 h later for macroscopic examination of the small intestine.

Results:

A single administration of indomethacin (10 mg/kg) provoked damage, mainly in the jejunum and ileum, accompanied by an increase in myeloperoxidase and inducible nitric oxide synthase activities as well as bacterial translocation. NCX‐530 at an equimolar dose (14.2 mg/kg) caused no gross damage in the small intestine, nor any significant change in inducible nitric oxide synthase and myeloperoxidase activities or bacterial translocation. NOR‐3, the nitric oxide donor (6.0 mg/kg), when administered subcutaneously together with indomethacin, significantly prevented the occurrence of intestinal lesions and other mucosal changes. Indomethacin reduced mucus and fluid secretions in the small intestine, while both NCX‐530 and NOR‐3 enhanced these secretions. NCX‐530 reduced the mucosal prostaglandin E2 contents and exhibited an anti‐inflammatory action against carrageenan‐induced paw oedema, with equal effectiveness to indomethacin.

Conclusion:

NCX‐530 does not cause intestinal damage, despite inhibiting cyclooxygenase activity. The reduced intestinal toxicity of NCX‐530 may be attributable to inhibition of enterobacterial translocation, partly by increasing the mucus and fluid secretions mediated by nitric oxide released from this compound.
Minimal renal dysfunction in inflammatory bowel disease is related to disease activity but not to 5‐ASA use
Authors: Herrlinger K. R. , Noftz M. K. , Fellermann K. , Schmidt K. , Steinhoff J. , Stange E. F.
Published: March 2003

Background:

Conflicting data exist about proteinuria in inflammatory bowel diseases. It is still unclear whether the occurrence of proteinuria in inflammatory bowel disease patients is an extra‐intestinal manifestation of disease or the result of adverse effects to medication, especially to aminosalicylates (ASA).

Methods:

A total of 95 patients (51 with Crohn’s disease and 44 with ulcerative colitis) were enrolled in the study. Disease activity was assessed by Crohn’s Disease Activity Index (CDAI) or the Truelove index, respectively. Urine was collected over 24 h and protein excretion of specific marker proteins for tubular (α1‐microglobulin‐α1‐MG) and glomerular (albumin‐Alb, Immunoglobulin G‐IgG) dysfunction was measured using a highly sensitive immunoluminometric assay.

Results:

Out of 51 Crohn’s disease patients, 20 showed elevated urinary α1‐MG. The amount of α1‐MGuria was strongly correlated to the CDAI (r=0.6, P < 0.001). Only four Crohn’s disease patients showed slightly elevated values for glomerular proteins in urine. Similar results were obtained for ulcerative colitis: whereas only two ulcerative colitis patients showed albuminuria, tubular proteinuria was detected in 28 out of 44 ulcerative colitis patients. Proteinuria was strongly dependent on disease activity (P < 0.01) but was not related to ASA treatment.

Conclusions:

Proteinuria of tubular marker proteins occurs in the majority of inflammatory bowel disease patients and is related to disease activity rather than to ASA treatment. Tubular proteinuria seems to reflect a renal extra‐intestinal manifestation of inflammatory bowel disease and may serve as a new relevant marker of disease activity.
The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive oesophagitis: a 6‐month, randomized, double‐blind, placebo‐controlled study of efficacy and safety
Authors: Vakil N. B. , Shaker R. , Johnson D. A. , Kovacs T. , Baerg R. D. , Hwang C. , D'Amico D. , Hamelin B.
Published: March 2003

Background:

Esomeprazole, the S‐isomer of omeprazole, is the first proton pump inhibitor to be developed as an optical isomer. In patients with erosive oesophagitis, esomeprazole has produced significantly greater healing rates and improved symptom resolution vs. omeprazole.

Aim:

This study assesses the efficacy of esomeprazole for preventing relapse in patients with healed oesophagitis.

Methods:

In this 6‐month US multicentre randomized double‐blind placebo‐controlled trial, 375 Helicobacter pylori‐negative patients with endoscopically healed oesophagitis received esomeprazole 40 mg, 20 mg, 10 mg, or placebo once daily. The primary efficacy end‐point was maintenance of healing at 6 months. Secondary end‐points assessed changes in symptoms, and long‐term safety and tolerability.

Results:

Significantly (P < 0.001) more patients remained healed with esomeprazole 40 mg (87.9%), 20 mg (78.7%), or 10 mg (54.2%), than with placebo (29.1%). Relapse, when it occurred, was later with esomeprazole. Sustained resolution of heartburn was observed in the 40 mg and 20 mg groups; there was a high correlation between absence of heartburn and maintenance of healing. Adverse effects were mild, infrequent and not significantly different between groups.

Conclusions:

Esomeprazole is effective and well‐tolerated in the maintenance of healing of erosive oesophagitis. Esomeprazole 40 mg and 20 mg offer significant clinical benefit to patients.
Probiotic impact on microbial flora, inflammation and tumour development in IL‐10 knockout mice
Authors: O'Mahony L. , Feeney M. , O'Halloran S. , Murphy L. , Kiely B. , Fitzgibbon J. , Lee G. , O'Sullivan G. , Shanahan F. , Collins J. K.
Published: March 2003

Background:

The enteric bacterial flora has been implicated in the pathogenesis of enterocolitis and colon cancer in C57BL/6 IL‐10 knockout mice. Probiotic Lactobacilli modify the enteric flora and are thought to have a beneficial effect on enterocolitis. We conducted a controlled feeding trial in IL‐10 knockout mice using the probiotic Lactobacillus salivarius ssp. salivarius UCC118.

Aim:

To determine the effect of probiotic consumption on the gastrointestinal microflora, tumour development and colitis in IL‐10 knockout mice.

Methods:

Twenty IL‐10 knockout mice were studied (10 consumed probiotic organisms in milk and 10 consumed unmodified milk) for 16 weeks. Faecal microbial analysis was performed weekly to enumerate excretion of the probiotic UCC118, total lactobacilli, Clostridium perfringens, bacteroides, coliforms, bifidobacteria and enterococci. At sacrifice, the small and large bowel were microbiologically and histologically assessed.

Results:

L. salivarius UCC118 was detected in faeces from all mice in the probiotic fed group, but not the control group. Faecal coliform and enterococci levels were significantly reduced in probiotic fed animals compared to the controls (P < 0.05). At sacrifice, a significant reduction in C. perfringens numbers was observed in the test mice (P < 0.05). There were no fatalities in the test group compared to two deaths from fulminant colitis in the control group. Only one test mouse developed colonic adenocarcinoma compared to five in the control group. Test animal mucosal inflammation consistently scored lower than that of the control mice.

Conclusion:

In this placebo controlled trial, modification of enteric flora in IL‐10 knockout mice by probiotic lactobacilli was associated with reduced prevalence of colon cancer and mucosal inflammatory activity.
Comparison of 1‐week vs. 2‐ or 4‐week therapy regimens with ranitidine bismuth citrate plus two antibiotics for Helicobacter pylori eradication
Authors: Kamberoglou D. , Polymeros D. , Sanidas I. , Doulgeroglou V. , Savva S. , Patra E. , Tzias V.
Published: March 2003

Background:

Helicobacter pylori eradication therapies based on ranitidine bismuth citrate have recently been introduced in clinical practice.

Aim:

To compare the efficacy of three regimens containing ranitidine bismuth citrate given for 1, 2 and 4 weeks, combined with two antibiotics for the first week, in the eradication of H. pylori.

Methods:

Eighty‐six consecutive patients (50 duodenal ulcer disease, 36 non‐ulcer dyspepsia) with H. pylori infection were offered three eradication regimens: (a) 1‐week group (n=28), ranitidine bismuth citrate 400 mg b.d. for 7 days; (b) 2‐week group (n=29), ranitidine bismuth citrate 400 mg b.d. for 14 days; and (c) 4‐week group (n=29), ranitidine bismuth citrate 400 mg b.d. for 28 days. In all patients, clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. were given for the first week. Endoscopy was repeated 1 month after the end of treatment and eradication was considered to be successful if both rapid urease test and histology were negative.

Results:

Overall, H. pylori was eradicated in 84% (72/86) patients on intention‐to‐treat analysis, whereas the per protocol cure rate was 89% (72/81). Eradication rates were 23/27 (85%) (95% confidence interval (CI): 66–96%), 25/27 (92%) (95% CI: 76–99%) and 24/27 (89%) (95% CI: 71–98%) in the 1‐, 2‐ and 4‐week groups, respectively, on per protocol analysis, and 25/28 (82%) (95% CI: 63–94%), 25/29 (86%) (95% CI: 68–96%) and 24/29 (83%) (95% CI: 64–94%), respectively, on intention‐to‐treat analysis (P > 0.05, N.S.). No significant differences were observed between groups concerning duodenal ulcer healing, resolution of symptoms and adverse effects.

Conclusions:

The 1‐week regimen with ranitidine bismuth citrate, clarithromycin and metronidazole is effective in H. pylori eradication. Prolongation of treatment with ranitidine bismuth citrate for 2 or 4 weeks does not achieve a statistically significant more favourable outcome.
Gastrimmune‐induced antigastrin‐17 antibodies inhibit acid secretion in a rat fistula model
Authors: Smith A. M. , Morris T. , Justin T. , Michaeli D. , Watson S. A.
Published: March 2003

Background:

Gastrimmune is an immunogenic form of gastrin. It raises in situ antibodies against two proliferative forms of gastrin: amidated and glycine‐extended gastrin‐17. It has been shown to have a therapeutic action in several in vivo tumour models. Following immunization, due to the complex equilibrium that exists between the antibodies and gastrin, it is not technically feasible to assay for free gastrin.

Aim:

To determine the effect of Gastrimmune‐induced antigastrin antibodies on acid secretion.

Method:

A rat gastric fistula model was used. Animals (six per group) were immunized with a control immunogen or ascending doses of Gastrimmune. Acid output was measured following infusion of increasing doses of gastrin‐17 and pentagastrin.

Results:

Gastrimmune‐induced antibodies significantly reduced gastrin‐17‐stimulated acid output compared to control animals (Gastrimmune at 200 μg/rat vs. control; acid output following 30 ng gastrin‐17, 0.01 vs. 0.16, P < 0.001; following 120 ng gastrin‐17, 0.022 vs. 0.29, P < 0.001).

Conclusions:

Gastrimmune significantly inhibits gastrin‐17‐stimulated acid output. This biological assay suggests that the antigastrin antibodies effectively bind gastrin‐17. In addition to its use as an antineoplastic agent, Gastrimmune may have a role as an acid‐decreasing agent in oesophagogastric pathology.
Impairment of cytochrome P‐450‐dependent liver activity in cirrhotic patients with Helicobacter pylori infection
Authors: Giannini E. , Fasoli A. , Borro P. , Chiarbonello B. , Malfatti F. , Romagnoli P. , Botta F. , Testa E. , Fumagalli A. , Polegato S. , Savarino V. , Testa R.
Published: March 2003

Background:

Helicobacter pylori gastric infection has been associated with various digestive and extra‐digestive diseases. The systemic influence of gastric H. pylori infection seems to be mediated by the release of various cytokines. In liver disease, bacterial infections have been associated with the impairment of liver metabolic function.

Aims:

To evaluate the influence of H. pylori infection on liver function as assessed by means of the monoethylglycinexylidide test, which depends upon liver blood flow and cytochrome P‐450 activity, and the 13C‐galactose breath test, which depends on cytosolic enzymatic activity and is correlated with hepatic functional mass. Moreover, to evaluate whether H. pylori‐associated modifications of liver function may be related to tumour necrosis factor‐α serum levels.

Patients and methods:

Thirty‐five patients with liver cirrhosis of various aetiologies, who underwent monoethylglycinexylidide and 13C‐galactose breath tests, were retrospectively evaluated for H. pylori infection by means of anti‐H. pylori immunoglobulin G. The main clinical, biochemical and functional characteristics of the patients as well as their tumour necrosis factor‐α serum levels were then analysed on the basis of the presence of H. pylori infection.

Results:

Twenty‐one patients tested positive for H. pylori infection (60%), and 11 tested negative (31.4%). No clinical or biochemical differences were observed between H. pylori‐infected and non‐infected patients. H. pylori infection showed no difference in distribution according to Child–Pugh classes (A, 55%; B and C, 67%). The monoethylglycinexylidide test results were significantly lower at each sampling time in H. pylori‐positive patients compared to H. pylori‐negative patients (MEGX15, P=0.027; MEGX30, P=0.014; MEGX60, P=0.028), while 13C‐galactose breath test showed no significant differences considering both cumulative percentage dose and percentage dose/h. The median tumour necrosis factor‐α serum levels were no different between H. pylori‐positive (16.1 pg/mL, 95% confidence interval, 8.7–28.7) and H. pylori‐negative (12.3 pg/mL, 95% confidence interval, 8.7–23.4) patients.

Conclusions:

In cirrhotic patients, H. pylori infection seems to selectively affect cytochrome P‐450 liver activity, while hepatic functional mass does not seem to be impaired. Tumour necrosis factor‐α does not seem to be the mediator of this impairment. Further studies are needed to evaluate the impact of H. pylori eradication on parameters of liver function.
Gut mucosal uptake and retention characteristics contribute to the high intestinal selectivity of budesonide compared with prednisolone in the rat
Authors: Miller‐Larsson A. , Gustafsson B. , Persson C. G. A. , Brattsand R.
Published: March 2003

Background:

Budesonide and prednisolone are both effective for the treatment of inflammatory bowel disease, but budesonide produces fewer adverse systemic effects. High first‐pass hepatic inactivation of budesonide partially explains its favourable ratio between topical and systemic activity, but it is probable that its uptake and retention in intestinal target tissues are also contributory.

Aim:

To compare the uptake and retention of radio‐labelled budesonide and prednisolone in rat ileal mucosa in vivo.

Methods:

3H‐Budesonide and 3H‐prednisolone were applied for 10 min directly to a perfused segment of rat ileum in vivo, followed by saline lavage every 10 min. Steroid uptake into the mucosa and submucosa was assessed at 20 min and 4 h. The uptake of budesonide was also measured in allergen‐challenged animals vs. saline‐challenged controls to assess whether inflammation of the mucosa with ongoing plasma exudation would impair its uptake.

Results:

Budesonide was better absorbed into ileal tissue (15‐fold at 20 min) than prednisolone and better retained (50‐fold at 4 h) after topical administration. The uptake of budesonide was not impaired by exudation processes following allergen challenge.

Conclusions:

The higher uptake and retention characteristics of budesonide in gut mucosa should contribute to its greater intestinal selectivity compared with that of prednisolone.
Low‐dose lansoprazole and clarithromycin plus metronidazole vs. full‐dose lansoprazole and clarithromycin plus amoxicillin for eradication of Helicobacter pylori infection
Authors: Bazzoli F. , Zagari R. M. , Pozzato P. , Fossi S. , Ricciardiello L. , Nicolini G. , De Luca L. , Berretti D. , Alampi G. , Di Pietro C. , Morelli P. , Roda E.
Published: March 2003

Aim:

To compare, in a randomized controlled trial, the efficacy and tolerability of two 1‐week triple therapies for Helicobacter pylori eradication.

Methods:

One hundred and thirty‐four consecutive patients with non‐ulcer dyspepsia and H. pylori infection were randomized to receive lansoprazole 30 mg once daily, clarithromycin 250 mg twice daily, and metronidazole 500 mg twice daily (LCM group), or lansoprazole 30 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1000 mg twice daily (LCA group). H. pylori status was assessed by rapid urease test, histology and 13C‐urea breath test before and after therapy.

Results:

At 3 months, H. pylori eradication (intention‐ to‐treat/per protocol analysis) was 92.4%/93.8% in the LCM group and 83.1%/85.7% in the LCA group (P=N.S.). Side‐effects were more frequently reported in the LCA group (37.9%) than in the LCM group (19.7%) (P < 0.05).

Conclusions:

In this open, randomized controlled trial, eradication of H. pylori by low‐dose lansoprazole and clarithromycin plus metronidazole was higher with significantly less side‐effects than by full‐dose lansoprazole and clarithromycin plus amoxicillin. This finding may be related to the stronger synergism of clarithromycin plus metronidazole, even at lower doses, than of clarithromycin plus amoxicillin. Considering the lower cost as well, LCM should be preferred to LCA in the eradication of H. pylori.
Bifidobacterium animalis strain DN‐173 010 shortens the colonic transit time in healthy women: a double‐blind, randomized, controlled study
Authors: Marteau P. , Cuillerier E. , Meance S. , Gerhardt M. F. , Myara A. , Bouvier M. , Bouley C. , Tondu F. , Bommelaer G. , Grimaud J. C.
Published: March 2003

Background:

A previous study has suggested that Bifidobacterium animalis DN‐173 010 shortens the colonic transit time in women.

Aim:

To confirm this effect and to determine whether modifications of the faecal bacterial mass and/or faecal secondary bile salts may be the explanation.

Methods:

A double‐blind, cross‐over study was performed. Thirty‐six healthy women were studied in four consecutive 10‐day periods. During periods 2 and 4, they ingested three 125 g cups per day of a fermented milk which was either a product containing B. animalis DN‐173 010 or a control without bifidobacteria. Periods 1 and 3 were run‐in and washout periods, respectively. The total and segmental colonic transit times were assessed using a pellet method. In 12 subjects, all stools were collected and analysed for pH, faecal weight, bacterial mass and bile acids.

Results:

The total and sigmoid transit times were significantly shorter during dosing with B. animalis compared to the control period. The other transit times, faecal weight, pH, bacterial mass and bile acids were not significantly affected.

Conclusions:

B. animalis DN‐173 010 shortens the colonic transit time in healthy women. This effect is not explained by modifications of the faecal bacterial mass or secondary bile acids.
An approach toHelicobacter pyloriinfection in the elderly
Authors: Pilotto A. , Malfertheiner P.
Published: March 2003

The prevalence ofHelicobacter pyloriinfection increases with age world‐wide, reaching levels of 40–60% in asymptomatic elderly subjects and over 70% in elderly patients with gastroduodenal diseases. However, the percentage ofH. pylori‐positive elderly patients who are treated for their infection remains very low.

Data are now available that demonstrate the benefit of curingH. pyloriinfection in elderly patients withH. pylori‐associated peptic ulcer disease and severe chronic gastritis. Furthermore, the cure ofH. pylorimay prevent the progression of intestinal metaplasia and gastric atrophy. New studies are needed to clarify the role of eradication in elderly patients with non‐ulcer dyspepsia and gastro‐oesophageal reflux disease and in those who use non‐steroidal anti‐inflammatory drugs.

H. pyloriinfection may be easily diagnosed by histological evaluation, rapid urease test or culture performed on gastric biopsies taken during endoscopy. However, the biopsy site must be carefully selected in elderly patients. For non‐invasive monitoring ofH. pyloriinfection after treatment, the13C‐urea breath test has significantly higher accuracy than serology in the elderly; further studies are needed to clarify the role of theH. pyloristool antigen test in old age.

One‐week proton pump inhibitor‐based triple therapy regimens, including clarithromycin, amoxicillin and/or nitroimidazoles, are highly effective and well tolerated in elderly patients. Low doses of both proton pump inhibitors and clarithromycin (in combination with standard doses of amoxicillin or nitroimidazoles) are sufficient. Low compliance and antibiotic resistance are the main factors related to treatment failure in old age.
General principles to enhance practice patterns in gastrointestinal endoscopy
Authors: Sonnenberg A. , Gavin M. W.
Published: March 2003

Aim:

To develop general rules on how to pursue a therapeutic goal of interventional endoscopy without getting lost in abundant details.

Methods:

The influences of various medical interventions on the survival of a patient with gastrointestinal haemorrhage are modelled by an influence diagram. Survival is the focal point of multiple influences affecting its overall strength. Any downstream influence can represent the focal point of other preceding upstream influences. The mathematics underlying the influence diagram are similar to those of a decision tree with some notable exceptions. Its formalism allows one to consider inhibitory and additive influences and to include in the same analysis non‐commensurable qualities, such as correct diagnosis, haemostasis or survival.

Results:

The analysis reveals five general rules. First, the large number of factors involved in successful endoscopy render the influence of each individual factor less important. Second, a single factor that exerts its influence on many subsequent factors tends to be associated with an overall greater relevance. Third, remote influences are of lesser relevance than those directly linked to the final outcome. Fourth, factors multiplied by several consecutive probabilities lose their influence. Fifth, endoscopists need to assess the relevance of individual factors with respect to the immediate goals of endoscopy, as well as the general goals of patient well‐being.

Conclusions:

The influence model of endoscopic haemostasis reveals several general principles that can be utilized as tools in endoscopy training.
Hiatal hernia is the key factor determining the lansoprazole dosage required for effective intra‐oesophageal acid suppression
Authors: Frazzoni M. , De Micheli E. , Grisendi A. , Savarino V.
Published: March 2003

Background:

Effective intra‐oesophageal acid suppression can be achieved with lansoprazole. The daily dosage could be influenced by the presence of hiatal hernia.

Aim:

To assess the lansoprazole daily dosage required to normalize oesophageal acid exposure in patients with and without hiatal hernia.

Methods:

Fifty patients with complications or atypical manifestations of gastro‐oesophageal reflux disease were given lansoprazole, 30 mg once daily. Three to four weeks after the start of treatment, patients underwent oesophageal pH monitoring while on therapy. If the results were still abnormal, the lansoprazole dosage was doubled and 24‐h pH‐metry was repeated 20–30 days thereafter.

Results:

A 30‐mg daily dosage of lansoprazole normalized oesophageal acid exposure in 70% of cases, whilst a 60‐mg daily dosage was necessary in the remainder: the two groups differed only in the presence of hiatal hernia (28% vs. 100%, respectively; P=0.000). Effective intra‐oesophageal acid suppression was obtained in all 25 patients without hiatal hernia with the 30‐mg daily dosage of lansoprazole.

Conclusions:

Hiatal hernia is the key factor determining the lansoprazole dosage required for effective intra‐oesophageal acid suppression in complicated and atypical gastro‐oesophageal reflux disease. High efficacy of a 30‐mg daily dosage of lansoprazole can be predicted in the absence of hiatal hernia.
Helicobacter pylori infection, anti‐cagA antibodies and peptic ulcer: a case–control study in Italy
Authors: Palli D. , Menegatti M. , Masala G. , Ricci C. , Saieva C. , Holton J. , Gatta L. , Miglioli M. , Vaira D.
Published: March 2003

Aim:

To evaluate the association between infection with specific strains of Helicobacter pylori and peptic ulcer in patients referred for upper gastrointestinal endoscopy.

Methods:

One thousand, six hundred and twenty‐six consecutive dyspeptic patients, referred to one Endoscopy Unit in Bologna, Italy, were enrolled. For each participant, a blood sample was obtained for the measurement of distinct immunoglobulin G antibodies against H. pylori lysate and cytotoxin associated gene A (cagA). A case–control study included the whole series: patients diagnosed with duodenal (n=275) or gastric (n=71) ulcer were identified and independently compared with controls with non‐ulcer dyspepsia (n=1280).

Results:

H. pylori seroprevalence (at least one positive marker) was associated with increasing age, male sex and a diagnosis of peptic ulcer. This association was stronger with duodenal ulcer (multivariate odds ratio (OR), 5.2; 95% confidence interval (CI), 3.5–7.9) than with gastric ulcer (OR, 2.3; 95% CI, 1.2–4.4). Further analyses showed that H. pylori lysate+/cagA− subjects had a moderately increased risk of duodenal (OR, 3.2), but not gastric (OR, 1.1), ulcer. When cagA+ subjects were separately compared with seronegative patients, there was a six‐fold increased risk for duodenal ulcer and a three‐fold increased risk for gastric ulcer.

Conclusions:

A strong positive association between infection with a cagA+ H. pylori strain and the presence of peptic disease was found. The seroprevalence of anti‐cagA antibodies among patients with non‐ulcer dyspepsia is so high (41%) to preclude its use as a pre‐endoscopic screening test.
Low‐salt bowel cleansing preparation (LoSo Prep) as preparation for colonoscopy: a pilot study
Authors: Verghese V. J. , Ayub K. , Qureshi W. , Taupo T. , Graham D. Y.
Published: March 2003

Background : Currently available colon cleansing preparations are often poorly tolerated.

Aim : To evaluate the efficacy of a low‐volume, low‐salt preparation for colonoscopy.

Methods : This was a pilot study in patients scheduled for colonoscopy. The preparation consisted of 34 g of magnesium citrate and four bisacodyl tablets the day before the procedure, and one bisacodyl suppository on the morning of the procedure.

Results : Twenty patients (age range, 49–81 years; all males) were entered into the study. There were no significant side‐effects associated with the preparation. All rated the taste as ‘tolerable or better’. The examination was considered to be adequate, with no limitations, in 17 patients (85%), and was scored as good to excellent (no solid stool) in 11 (55%), acceptable (small amounts of solid stool) in six (30%) and poor in three (15%: two in‐patients and one out‐patient). Importantly, two of the failures then received a standard polyethylene glycol preparation and again failed to show adequate colon preparation.

Conclusions : This pilot study showed that the low‐salt colon cleansing preparation was an effective alternative preparation for colonoscopy.
Dose ranging pharmacokinetic trial of high‐dose alicaforsen (intercellular adhesion molecule‐1 antisense oligodeoxynucleotide) (ISIS 2302) in active Crohn's disease
Authors: Yacyshyn B. R. , Barish C. , Goff J. , Dalke D. , Gaspari M. , Yu R. , Tami J. , Dorr F. A. , Sewell K. L.
Published: March 2003

Background and aims : To evaluate the safety, pharmacokinetics and clinical efficacy of the intercellular adhesion molecule‐1 antisense phosphorothioate oligonucleotide alicaforsen (ISIS 2302) at 250–350 mg in Crohn's disease.

Methods : Patients (> 50 kg) with active Crohn's disease (Crohn's disease activity index ≥ 220) were assigned by gender, randomly, to two alicaforsen treatment groups: 300 or 350 mg, infused intravenously three times a week for 4 weeks. All patients weighing 36–50 kg received 250 mg of alicaforsen. Background aminosalicylates, antibiotics, immunosuppressives and corticosteroids were permitted, but tumour necrosis factor‐αinhibitors were prohibited. The primary end‐point wasclinical remission (Crohn's disease activity index ≤ 150).

Results : Twenty‐two patients were enrolled with a mean baseline Crohn's disease activity index of 304. Steroids were used by 27%, 5‐aminosalicylic acid by 68% and immunosuppressives by 27%; 23% had previously received infliximab. Five subjects withdrew after one to three infusions for infusion‐related symptoms. Nine patients (41%) experienced clinical remission. Fifty‐three per cent of the evaluable subjects receiving more than three infusions experienced remission (18% at week 8; 29% at week 12). The overall response, using a minimum decrease of 70 in the Crohn's disease activity index, was 41–47% for the evaluable group, at weeks 8 and 12. The median duration of remission was 14 weeks. Plasma pharmacokinetic results showed overlapping levels (Cmax, AUC) for the three doses. The infusion‐related reaction profile consisted of fever, chills, headache, nausea, emesis or arthralgias, typically occurring 2–4 h after completion of the first infusion. Reactions were less frequent in patients receiving background corticosteroids. The 2–4‐h transient post‐infusion partial thromboplastin time prolongation values, a class effect of phosphorothioate oligonucleotides, were 18, 21 and 23 s for 250, 300 and 350 mg, respectively.

Conclusions : Alicaforsen (ISIS 2302), at fixed doses of 300 and 350 mg, achieved the desired drug exposure and may be an effective therapy for Crohn's disease. Infusion‐related reactions were observed less frequently in patients on corticosteroids, and with decreasing frequency with continued treatment.
Cisapride inhibits meal‐stimulated gastric acid secretion and post‐prandial gastric acidity in subjects with gastro‐oesophageal reflux disease
Authors: Gardner J. D. , Rodriguez‐Stanley S. , Robinson M. , Miner P. B.
Published: March 2003

Background and aims : KCNQ1 potassium channels in human gastric parietal cells are thought to be involved in gastric acid secretion. As cisapride can inhibit similar channels in other tissues and is an effective treatment for nocturnal heartburn, we examined the effects of cisapride on gastric and oesophageal acidity, gastric emptying and heartburn severity in subjects with gastro‐oesophageal reflux disease.

Methods : Subjects (n=11) had suffered from heartburn four times or more per week for at least 6 months. Gastric pH and oesophageal pH were measured before, during and after a standard meal ingested over 15 min. Each subject received placebo or 10 mg cisapride orally, 30 min before the beginning of the meal. Meal‐stimulated gastric acid secretion was calculated from the amount of HCl required to titrate the homogenized standard meal to pH 2 in vitro and the time required for the pH of the ingested meal to decrease to pH 2 in vivo. Heartburn severity was assessed at 15‐min intervals beginning at the end of the meal. Gastric emptying of solids was measured using a [13C]‐octanoic acid breath test.

Results : Cisapride significantly decreased meal‐stimulated gastric acid secretion by 20%, decreased integrated gastric and oesophageal acidity by 50–60% and transiently increased the expiration of 13CO2. Cisapride did not significantly alter heartburn severity.

Conclusions : The cisapride‐induced decreases in meal‐stimulated gastric acid secretion, gastric acidity and oesophageal acidity in subjects with gastro‐oesophageal reflux disease can account for its beneficial clinical effects. These results also raise the possibility that gastric KCNQ1 potassium channels are important in meal‐stimulated gastric acid secretion and possibly in the pathophysiology of gastro‐oesophageal reflux disease.
Efficacy of triple therapy comprising rabeprazole, amoxicillin and metronidazole for second‐line Helicobacter pylori eradication in Japan, and the influence of metronidazole resistance
Authors: Murakami K. , Sato R. , Okimoto T. , Nasu M. , Fujioka T. , Kodama M. , Kagawa J.
Published: March 2003

Background : The widespread use of eradication therapy for Helicobacter pylori in Japan has led to an increase in antibiotic‐resistant strains and the problem of re‐treatment in cases of eradication failure.

Aim : To perform drug sensitivity testing for metronidazole in 92 H. pylori‐positive patients who had failed eradication treatment with first‐line triple therapy, consisting of a proton pump inhibitor, amoxicillin and clarithromycin, and were administered metronidazole‐containing second‐line therapy.

Methods : Second‐line eradication therapy, consisting of rabeprazole (20 mg b.d.), amoxicillin (750 mg b.d.) and metronidazole (250 mg b.d.), was administered for 1 week and the eradication rates and influence of metronidazole resistance were determined.

Results : The eradication rates for rabeprazole–amoxicillin–metronidazole were 88% (81/92) using intention‐to‐treat analysis and 91% (81/89) using per protocol analysis. The eradication rates were 97% (61/63) for metronidazole‐sensitive strains and 82% (18/22) for metronidazole‐resistant strains.

Conclusions : As second‐line H. pylori eradication treatment in Japan, rabeprazole–amoxicillin–metronidazole triple therapy is effective, even with metronidazole‐resistant strains.
Effect of peppermint oil and caraway oil on gastrointestinal motility in healthy volunteers: a pharmacodynamic study using simultaneous determination of gastric and gall‐bladder emptying and orocaecal transit time
Authors: Goerg K. J. , Spilker TH.
Published: March 2003

Background : Although peppermint oil and caraway oil are frequently used in herbal drugs for abdominal discomfort and pain, the pharmacological insights into their effects on the gastrointestinal tract are poor.

Methods : The pharmacodynamic effects of 90 mg peppermint oil (WS 1340) and 50 mg caraway oil (WS 1520) on the motility of the stomach and gall‐bladder, and on the orocaecal transit time, in comparison with placebo, 10 mg cisapride and 10 mg n‐butylscopolamine, were studied in 12 healthy volunteers. The study involved simultaneous ultrasonic determination of gastric and gall‐bladder emptying, together with assessment of the orocaecal transit time using the lactulose H2 breath test. The combination of these methods allows three gastrointestinal organs to be studied in one subject simultaneously.

Results : The antral filling time was comparable with placebo, peppermint oil, caraway oil and cisapride, whereas it was significantly shortened (P = 0.04, two‐sided paired t‐test) with n‐butylscopolamine. The gastric emptying time did not differ significantly between placebo, peppermint oil, caraway oil and cisapride, but was significantly prolonged by n‐butylscopolamine (P = 0.04, two‐sided paired t‐test). Complete inhibition of gall‐bladder emptying was caused by both oils and n‐butylscopolamine. Cisapride significantly shortened gall‐bladder emptying compared with placebo (P = 0.02, two‐sided signed rank test). The orocaecal transit time was significantly prolonged by peppermint oil (P = 0.004) and n‐butylscopolamine (P = 0.002), but not significantly prolonged by caraway oil (P = 0.06); it was significantly shortened by cisapride (P = 0.04, all two‐sided paired t‐test).

Conclusions : Peppermint oil and caraway oil show a relaxing effect on the gall‐bladder and the former slows small intestinal transit. Further studies should investigate the effects of both oils on a maximal contraction stimulus on the gall‐bladder, and in patients suffering from motility disorders.
Intensive care services; a crisis of increasing expressed demand
Authors: Parker A. , Wyatt R. , Ridley S.
Published: March 2003

Critical care services appear to face increasing demand. To attempt to identify factors which may predispose to such increases in demand, the patients and their treatment were reviewed. The patients' ages, referring specialty and their risk of hospital mortality were recorded on admission. The durations of respiratory and renal support (if required) were recorded. Pulmonary artery catheter insertion and the number of vasoactive drugs infused were also noted. During the study, the capacity of the intensive care unit was initially increased by one bed (from six to seven) and later by a six‐bedded high‐dependency unit. This capacity increase was not matched by a proportionate decrease in occupancy. The patients' mean ages increased by 1 year per year. The number of patients referred from general surgery consistently increased. The proportion of patients receiving vasoactive drugs and pulmonary artery catheters declined as did the duration of respiratory and renal support.
Complications of percutaneous dilatational tracheostomy in children
Authors: Scott C. J. , Darowski M. , Crabbe D. C. G.
Published: March 2003

Experience with percutaneous dilatational tracheostomy in children is limited. This report discusses two significant complications which occurred following the use of this technique