bluuebunny/crossref_metadata_2025 huggingface dataset:
Review article: should we kill or should we save Helicobacter pylori?
Authors: Hunt R.H. , Sumanac K. , Huang J.‐Q.
Published: March 2003

Results from epidemiological studies and therapeutic clinical trials have shown that Helicobacter pylori infection causes acute and chronic active gastritis and is the initiating factor for the majority of peptic ulcer disease. Eradication of the infection with antibiotics resolves gastritis and restores normal gastric physiology, accelerates healing of peptic ulcer disease, and virtually eliminates recurrence of duodenal ulcer disease.

The infection also plays an important role in the initiation and/or progression of gastric atrophy and intestinal metaplasia, which may eventually lead to the development of distal gastric cancer. Furthermore, almost all patients with gastric MALT lymphoma are infected with H. pylori and cure of the infection leads to histological regression of the tumor and maintains the regression in over 80% of patients during long‐term follow‐up.

Preliminary uncontrolled data from Japan show that eradication of the infection significantly reduced metachronous intestinal‐type gastric cancer following initial endoscopic resection of early gastric cancer and might also prevent the progression of gastric adenoma to gastric dysplasia or gastric cancer.

Although this overwhelming evidence has demonstrated that H. pylori infection is bad for humans, some have questioned the wisdom of eradicating the infection in all those infected. Their arguments are largely based on hypothesis and circumstantial evidence: 1) Less than 20% of all H. pylori infected persons will develop significant clinical consequences in their lifetime. 2) H. pylori strains are highly diverse at a genetic level and are of different virulence. 3) The antiquity of H. pylori infection in humans and their co‐evolution suggests that H. pylori may be a commensal to humans. Eradication of H. pylori may remove some beneficial bacterial strains and may provoke esophageal disease or gastric cancer at the cardia.

However, careful review of the literature confirms that H. pylori infection is a serious pathogen albeit in a minority of those infected. It remains for carefully designed prospective studies, rather than hypothesis to make changes in the current consensus position.
Post‐treatment diagnostic accuracy of a new enzyme immunoassay to detect Helicobacter pylori in stools
Authors: Costa F. , Mumolo M. G. , Bellini M. , Romano M. R. , Manghetti M. , Paci A. , Maltinti G. , Marchi S.
Published: March 2003

Background:

Helicobacter pylori has attracted increasing attention among gastroenterologists because of its pathogenic potential, stimulating the search for non‐invasive diagnostic tests.

Aims:

In this study the efficacy of a new enzyme immunoassay designed to detect H. pylori antigens in stools (HpSA) was evaluated before and after eradication therapy.

Methods:

HpSA was performed on stool samples collected from 268 patients whose H. pylori status was defined on the basis of concordant results for the 13C‐urea breath test, rapid urease test and histology. The H. pylori‐positive patients were treated with a 1‐week triple therapy to eradicate the infection. One (T30) and 3 months (T90) after the end of therapy, 13C‐urea breath test and HpSA were repeated in the treated patients.

Results:

The overall diagnostic accuracy of HpSA at T30 (83%, 95% confidence interval (CI) 77–89%) was significantly lower in comparison to the values obtained at baseline (94%, 95% CI: 91–97%) and at T90 (97%, 95% CI: 94–99%). No significant difference was found between the diagnostic accuracy of HpSA at baseline and at T90 (P=0.253).

Conclusions:

The present data suggest that HpSA provides a low diagnostic accuracy when used shortly after treatment. It needs a longer period of follow‐up (8–12 weeks) to reach a reliability comparable to the 13C‐urea breath test.
The prevention of colorectal cancer
Authors: Dove‐Edwin I. , Thomas H. J. W.
Published: March 2003

Colorectal cancer is a leading cause of cancer mortality in the industrialized world. Survival remains poor because most cases are diagnosed at an advanced stage. It is a preventable disease as colorectal cancers usually develop slowly from an identifiable precursor lesion, the adenoma.

The existing strategies for colorectal cancer prevention include dietary prevention, chemoprevention and endoscopic intervention. The exact relationship between diet, particularly fibre, and colorectal cancer remains unclear, with the most recent studies suggesting that dietary fibre may not decrease colorectal cancer risk as previously thought.

Non‐steroidal anti‐inflammatory drugs have been shown to have a protective effect against colorectal cancer, but the adverse effect profile of the non COX‐2 selective drugs, particularly the risk of gastrointestinal haemorrhage, precludes their widespread use.

There is increasing evidence that colorectal cancer incidence and mortality can be decreased from endoscopic polypectomy and early detection of cancer. Faecal occult blood testing in the general population (‘average‐risk’) has been shown in randomized trials to decrease mortality from colorectal cancer by 15–33%. Long‐term results of randomized trials of the effectiveness of flexible sigmoidoscopy and colonoscopy screening in the general population are awaited.

Targeting high risk individuals may also be an effective and efficient way to decrease the colorectal cancer burden. As many as 15–30% of colorectal cases may be due to hereditary factors. Individuals with one or two direct relatives affected are at moderate risk for colorectal cancer (empirical lifetime mortality from colorectal cancer approximately 10%) and approximately 2–3% of cases arise in individuals harbouring highly penetrant autosomal dominant mutations, which puts them at high‐risk for colorectal cancer. Surveillance colonoscopy is offered to individuals at moderate and high risk for colorectal cancer.
Effect of an enteric‐release formulation of naloxone on intestinal transit in volunteers taking codeine
Authors: Hawkes N. D. , Richardson C. , Evans B. K. , Rhodes J. , Lewis S. J. , Thomas G. A. O.
Published: March 2003

Introduction:

Constipation is a common side‐effect of opioid therapy; in addition to their analgesic effect, opioids reduce intestinal secretion and motility with an increase in whole‐gut transit time. Naloxone, a specific opioid antagonist, reverses these effects but may also cause symptoms of opioid withdrawal in patients on long‐term therapy.

Aim:

To use an enteric‐release formulation, designed to produce a topical effect in the gut, with minimum systemic effects.

Methods:

Naloxone 10 mg b.d. and codeine 30 mg b.d. were used with identical placebo capsules in four sets of studies; 12 male volunteers were given the drugs alone and in combination, with a control study involving double placebo, during each of four study periods. Whole‐gut transit time was calculated and compared for each treatment period.

Results:

Naloxone, both alone and with codeine, significantly shortened the mean whole‐gut transit time compared with the control period, respectively, from 53.1 to 42.1 h (P=0.005) and to 40.7 h (P=0.024). Urgency to defecate was reported by two volunteers on naloxone alone and by three on combination therapy.

Conclusions:

The results show that the naloxone formulation counteracts the effect of codeine on intestinal transit, suggesting that it may have useful clinical applications.
Fish oil (Eicosapen) is less effective than metronidazole, in combination with pantoprazole and clarithromycin, for Helicobacter pylori eradication
Authors: Meier R. , Wettstein A. , Drewe J. , Geiser H. R. ,   THE SWISS HELICOBACTER‐STUDY GROUP
Published: March 2003

Background:

In vitroω‐3‐fatty acids (Eicosapen) are bacteriostatic to Helicobacter pylori and have a variety of immuno‐modulating effects.

Aim:

To investigate the efficacy and tolerability of eicosapen (E) as an antibiotic‐sparing component of a triple H. pylori eradication regimen in non‐ulcer dyspepsia patients in a randomized, double‐blind trial.

Methods:

Non‐ulcer dyspepsia patients (n=199), with a normal upper endoscopy and a positive 13C‐urea breath test (UBT) were randomly assigned to either pantoprazole, clarithromycin and metronidazole (PCM) or pantoprazole, clarithromycin and eicosapen (PCE) for 7 days. Four weeks after treatment, H. pylori eradication was determined by UBT. Symptoms were followed up to 16 months.

Results:

In the intention‐to‐treat population, PCM eradicated infection in 78% but PCE was successful in only 34% (P < 0.001). Symptomatic improvement occurred in both groups, and was not related to H. pylori eradication.

Conclusion:

Eicosapen is unlikely to be useful in H. pylori eradication regimens.
The pharmacology of the internal anal sphincter and new treatments of ano‐rectal disorders
Authors: Cook T. A. , Brading A. F. , Mortensen N. J. McC.
Published: March 2003

Surgical options for faecal incontinence in the presence of intact sphincters are limited. Furthermore, in patients with fissures, lateral sphincterotomy reduces anal sphincter hypertonia but there has been concern about complications. A greater understanding of the basic pharmacology of the internal anal sphincter has led to the development of novel treatments for both these disorders. A Medline review was undertaken for internal anal sphincter pharmacology, anal fissures and faecal incontinence. This review is based on these articles and those found by further cross‐referencing.  Nitric oxide released from non‐adrenergic non‐cholinergic nerves is the main inhibitory agent in the internal anal sphincter. Relaxations are also mediated through β‐adrenoceptors and muscarinic receptors. Stimulation of α‐receptors results in contraction. Calcium and its entry through L‐type calcium channels is important for the maintenance of tone. Nitric oxide donors produce reductions in resting anal tone and heal fissures but are associated with side‐effects. Muscarinic agents and calcium channel antagonists show promise as low side‐effect alternatives. Botulinum toxin appears more efficacious than other agents in healing fissures. To date, α‐receptor agonists have been disappointing at improving incontinence.

Further understanding of the pharmacology of the internal anal sphincter may permit the development of new agents to selectively target the tissue with greater efficacy and fewer side‐effects.
Abnormal bone turnover in long‐standing Crohn’s disease in remission
Authors: Schoon E. J. , Geerling B. G. , Van Dooren I. M. A. , Schurgers L. J. , Vermeer C. , Brummer R.‐J. M. , Stockbrügger R. W.
Published: March 2003

Background:

A high prevalence of osteoporosis is found in patients with Crohn’s disease. The pathogenesis of this condition seems to be multifactorial and its pathophysiology is still not completely understood.

Aim:

To elucidate the pathophysiology of osteopenia in quiescent Crohn’s disease.

Methods:

Bone turnover was studied in 26 patients (13 males and 13 females) with long‐standing quiescent Crohn’s disease and small bowel involvement. Bone mineral density was assessed by dual energy X‐ray absorptiometry. Biochemical markers for bone formation (osteocalcin and bone‐specific alkaline phosphatase) and for bone resorption (deoxypyridinoline and collagen type I C‐terminal crosslinks) were measured. Urinary calcium excretion was determined.

Results:

Markers for bone formation were significantly lower in patients than in controls (osteocalcin: P= 0.027, bone‐specific alkaline phosphatase: P < 0.001), but both bone resorption markers were not significantly different. Urine calcium excretion was significantly decreased in patients (P=0.002) compared to controls. Bone mineral density of the lumbar spine was significantly and inversely correlated with bone‐specific alkaline phosphatase and collagen type I C‐terminal crosslinks.

Conclusions:

Bone turnover in long‐standing Crohn’s disease in clinical remission is characterized by suppressed bone formation and normal bone resorption. Urine calcium excretion is decreased. Hence, interventions and therapy should be directed towards the improvement of bone formation.
Ranitidine bismuth citrate‐based triple therapies after failure of the standard ‘Maastricht triple therapy’: a promising alternative to the quadruple therapy?
Authors: Perri F. , Villani M. R. , Quitadamo M. , Annese V. , Niro G. A. , Andriulli A.
Published: March 2003

Background:

Triple therapy with proton pump inhibitor, clarythromycin, and amoxicillin has been proposed in Maastricht as the first‐line treatment of H. pylori infection.

Aim:

To determine whether ranitidine bismuth citrate (RBC) based regimens may be used as second‐line treatments after ‘Maastricht therapy’ failure.

Methods:

A total of 285 patients with H. pylori infection were given a 7‐day treatment with pantoprazole 40 mg b.d., clarythromycin 500 mg b.d., and amoxicillin 1 g b.d. Patients who were still infected were randomly given one of the following 14‐day treatments: RBC 400 mg b.d. plus amoxicillin 1 g b.d. and tinidazole 500 mg b.d. (RAT group), RBC 400 mg b.d. plus amoxicillin 1 g b.d. and clarythromycin 500 mg b.d. (RAC group), and RBC 400 mg b.d. plus clarythromycin 500 mg b.d. and tinidazole 500 mg b.d. (RCT group).

Results:

The ‘Maastricht therapy’ achieved an eradication rate of 59% (95% CI: 54–65) on intention‐to‐treat analysis. The RAT, RAC, and RCT regimens achieved eradication rates of 81% (95% CI: 67–94), 43% (95% CI: 26–60), and 62% (95% CI: 44–80), respectively, on intention‐to‐treat analysis. Patient compliance was optimal in RAT and RAC groups.

Conclusion:

RBC plus tinidazole and either amoxicillin or clarythromycin can be used as second‐line therapies after failure of the Maastricht triple therapy.
When William of Ockham meets Thomas Bayes: finding a few diagnoses among a great many symptoms
Authors: Sonnenberg A.
Published: March 2003

Bayes’ formula is a means to estimate disease probability based on the presence of symptoms and the outcome of clinical tests. The probability helps to decide among competing diagnostic options. If, however, several diseases present with similar symptoms, they may appear equally probable, and Bayes’ formula will fail as an aid to reach a diagnostic decision. The aim of this study is to show how a merger of Bayes’ principle with that of Ockham can help to decide in favour of one diagnosis among multiple, seemingly equally probable diagnostic hypotheses. The hypotheses are compared to each other with respect to those tests and symptoms which they fail to explain. The unexplained tests and symptoms are used to estimate the probabilities for a set of secondary diagnoses that match each one of the primary diagnoses. The more likely a secondary diagnosis appears, the less likely its corresponding primary diagnosis will remain as the sole diagnosis to explain all the clinical findings. Even without a detailed calculation, the proposed concept of using unexplained tests and symptoms to rate competing differential diagnoses could help the clinician to select the most probable diagnosis.
Lamivudine treatment for fulminant hepatic failure due to acute exacerbation of chronic hepatitis B infection
Authors: Tsang S. W. C. , Chan H. L. Y. , Leung N. W. Y. , Chau T. N. , Lai S. T. , Chan F. K. L. , Sung J. J. Y.
Published: March 2003

Background:

Exacerbation of chronic hepatitis B infection can lead to fulminant hepatic failure with a mortality of up to 90%.

Aim:

To evaluate the efficacy of lamivudine in the treatment of this subgroup of patients.

Methods:

Twenty‐four patients with exacerbation of chronic hepatitis B infection and fulminant hepatic failure were treated with lamivudine, 100 mg daily. Hepatitis A, C, D and human immunodeficiency virus co‐infections and hepatocellular carcinoma were excluded.

Results:

The median age was 53 years (range, 24–77 years) with a male predominance of 20:4. Seventeen patients were hepatitis B e antigen positive. Mean hepatitis B virus DNA was 2079 Meq/mL. Eight patients (33%) survived (group A). Thirteen patients died and three patients received liver transplantation (67%) (group B). Baseline laboratory results were comparable between the two groups, including serum albumin, bilirubin, alanine aminotransferase, prothrombin time and creatinine. Group B patients had significantly more comorbid illnesses at baseline and more complications, including sepsis and renal failure, compared with group A patients. Six out of eight survivors (75%) had full hepatitis B e antigen seroconversion, but this was not sustained in four patients.

Conclusions:

Lamivudine may be useful in treating patients with fulminant hepatic failure due to exacerbation of chronic hepatitis B. Hepatitis B e antigen seroconversion was less durable in this subgroup of patients and long‐term therapy may be required.
Effects of anti‐tumour necrosis factor, interleukin‐10 and antibiotic therapy in the indometacin‐induced bowel inflammation rat model
Authors: Colpaert S. , Liu Z. , De Greef B. , Rutgeerts P. , Ceuppens J. L. , Geboes K.
Published: March 2003

Background:

The administration of indometacin to rats increases intestinal permeability and induces inflammatory pathology of the small bowel. This represents a potential model for Crohn’s disease.

Aims:

To analyse the pathogenic role of T cells, tumour necrosis factor and bacterial flora in indometacin‐induced changes in small bowel permeability and inflammation.

Methods:

Rats were given indometacin, 13 mg/kg, on day 1 and day 2. The effects of antibiotic (metronidazole, aztreonam and amoxicillin/clavulanic acid), anti‐ tumour necrosis factor and interleukin‐10 therapy were evaluated. The parameters used were weight change, serum haemoglobin, chromium‐51 ethylenediaminetetra‐acetate permeability and macro‐and microscopic score on day 5. Results in conventionally harboured rats were compared with those in T‐cell‐free rats. Additional in vitro experiments were carried out to test the effect of metronidazole on tumour necrosis factor production.

Results:

Indometacin administration resulted in small bowel ulcers and inflammation, independently of T cells. Metronidazole was more potent than amoxicillin/clavulanic acid and anti‐tumour necrosis factor in improving the indometacin‐induced small bowel inflammation. Only part of the efficacy was through improvement of increased intestinal permeability. Aztreonam and interleukin‐10 had no effect. Metronidazole also suppressed in vitro lipopolysaccharide‐induced tumour necrosis factor production, suggesting a therapeutic effect of this drug through the inhibition of tumour necrosis factor.

Conclusions:

These data implicate anaerobic bacteria and tumour necrosis factor production, but not T cells, as essential elements of the pathogenesis of indometacin‐induced small bowel inflammation. Tumour necrosis factor is also involved in the change in intestinal permeability. Metronidazole was the most efficacious drug in this model, probably because it suppressed anaerobic bacteria and directly inhibited tumour necrosis factor production.
Non‐surgical treatment of hepatocellular carcinoma
Authors: Alsowmely A. M. , Hodgson H. J. F.
Published: March 2003

Primary hepatocellular cancer is a disease with a poor prognosis for which there is little consensus on treatment and a paucity of comparative trials. The coexistence of cancer with cirrhosis complicates treatment, and also confers a high risk for the development of further tumours. Surgery, either by hepatic resection or orthotopic liver transplantation, is only a feasible option in a minority of patients.

This article surveys the non‐surgical approaches to the treatment of hepatocellular cancers—local ablation techniques, arterial embolization with and without chemotherapy, conventional chemotherapy and hormonal modulation, and targeted and external irradiation.
Optimal serological tests for the detection of Helicobacter pylori infection in the Chinese population
Authors: Xia H. H. ‐X. , Wong B. C. Y. , Wong W. M. , Tang V. S. Y. , Cheung H. K. L. , Sham F. N. F. , Fung F. M. Y. , Lai K. C. , Hu W. H. C. , Chan C. K. , Lam S. K.
Published: March 2003

Background:

Numerous serological tests for the detection of Helicobacter pylori infection have been developed. However, many perform poorly when evaluated in the Chinese population.

Aim:

To search for optimal serological tests for the detection of H. pylori infection in Chinese patients.

Methods:

Consecutive dyspeptic patients referred for upper endoscopy were recruited. During endoscopy, gastric biopsies were taken for the CLOtest™ and histological examination. Patients were then given a 13C‐urea breath test. Sera were used to test for H. pylori infection, employing three commercial enzyme‐linked immunosorbent assay kits (pylori DTect, HP IgG and GAP IgG). Results were compared with the gold standard defined by the CLOtest™, histology and 13C‐urea breath test.

Results:

Among the 142 patients (47 male, 95 female; mean age, 49 years) recruited, 81 (57%) were H. pylori‐positive, 57 (40%) were H. pylori‐negative and four (3%) were defined to be indeterminate. Using a self‐defined cut‐off value after calculation, the best accuracies for the pylori DTect, HP IgG and GAP IgG tests were 97%, 91% and 80%, respectively.

Conclusions:

The pylori DTect test is an optimal serological test for the detection of H. pylori infection in Hong Kong Chinese patients. The HP IgG test may be used as an alternative.
Chemotherapy for colon cancer in a well‐defined French population: is it under‐ or over‐prescribed?
Authors: Faivre‐Finn C. , Bouvier A.‐M. , Mitry E. , Rassiat E. , Clinard F. , Faivre J.
Published: March 2003

Background:

It has been demonstrated that adjuvant chemotherapy in TNM stage III and palliative chemotherapy are effective treatments for colon cancer.

Aim:

To determine changes over a 10‐year period in the practice of adjuvant and palliative chemotherapy for colon cancer in a well‐defined French population.

Methods:

Some 4093 patients with colon adenocarcinoma diagnosed between 1989 and 1998 were studied. To estimate the independent effect of the studied variables, a non‐conditional logistical regression was performed.

Results:

The proportion of patients with stage II disease treated with adjuvant chemotherapy increased from 2.3% (1989–90) to 20.5% (1997–98). The corresponding figures for stage III patients were 7.1% and 54.9%. This increase was particularly marked in younger patients, with 47.3% of stage II and 86.1% of stage III patients under the age of 65 years being treated in the 1997–98 period, compared with 4.9% and 24.4% of those over 75 years for the same period (P < 0.0001). The use of palliative chemotherapy increased over time from 13.6% (1989–90) to 38.9% (1997–98). Again, this increase was more dramatic in the younger age group.

Conclusions:

The use of adjuvant chemotherapy has increased for stage II disease despite the absence of proven effectiveness. Both adjuvant and palliative chemotherapy are still under‐prescribed in patients over the age of 75 years.
The effects of the specific 5HT4 receptor agonist, prucalopride, on colonic motility in healthy volunteers
Authors: De Schryver A. M. P. , Andriesse G. I. , Samsom M. , Smout A. J. P. M. , Gooszen H. G. , Akkermans L. M. A.
Published: March 2003

Background:

Prucalopride is a selective and specific 5‐hydroxytryptamine4 receptor agonist that is known to increase stool frequency and to accelerate colonic transit.

Aim:

To investigate the effect of prucalopride on high‐amplitude propagated contractions and segmental pressure waves in healthy volunteers.

Methods:

After 1 week of dosing (prucalopride or placebo in a double‐blind, randomized, crossover fashion), colonic pressures were recorded in 10 healthy subjects using a solid‐state pressure catheter with six sensors spaced 10 cm apart. Subjects kept diary records of their bowel habits (frequency, consistency and straining). High‐amplitude propagated contractions were analysed visually, comparing their total numbers and using 10‐min time windows. Segmental pressure waves were analysed using computer algorithms, quantifying the incidence, amplitude, duration and area under the curve of all detected peaks.

Results:

When taking prucalopride, stool frequency increased, consistency decreased and subjects strained less. Prucalopride just failed to increase the total number of high‐amplitude propagated contractions (P=0.055). The number of 10‐min time windows containing high‐amplitude propagated contractions was increased by prucalopride (P=0.019). Prucalopride increased the area under the curve per 24 h (P=0.026).

Conclusions:

The 5‐hydroxytryptamine4 receptor agonist prucalopride stimulates high‐amplitude propagated contractions and increases segmental contractions, which is likely to be the underlying mechanism of its effect on bowel habits in healthy volunteers.
Effects of prucalopride on colonic transit, anorectal function and bowel habits in patients with chronic constipation
Authors: Sloots C. E. J. , Poen A. C. , Kerstens R. , Stevens M. , De Pauw M. , Van Oene J. C. , Meuwissen S. G. M. , Felt‐Bersma R. J. F.
Published: March 2003

Background:

There is a need for better tolerated drugs to normalize bowel function in chronic constipation. Prucalopride is a highly selective, specific, serotonin4 receptor agonist with enterokinetic properties.

Aim:

To evaluate the effects of prucalopride on bowel function, colonic transit and anorectal function in patients with chronic constipation.

Methods:

Twenty‐eight patients were enrolled in this double‐blind, placebo‐controlled, crossover study (prucalopride: 1 mg, n=12; 2 mg, n=16). Patients kept a bowel function diary. Colonic transit times and anorectal function (anal manometry, rectal sensitivity and rectal compliance) were assessed.

Results:

Prucalopride (1 mg) compared to placebo significantly increased the mean number of spontaneous complete, spontaneous and all bowel movements per week. Prucalopride (1 mg) significantly decreased the percentage of bowel movements with hard/lumpy stools and straining and increased the urge to defecate. Prucalopride (1 and 2 mg) decreased the mean total colonic transit time by 12.0 h (prucalopride 42.8 h vs. placebo 54.8 h; P=0.074). No statistically significant effects were found in any of the anorectal function parameters. Prucalopride was well tolerated. There were no clinically relevant changes in standard safety parameters.

Conclusions:

Prucalopride significantly improves stool frequency and consistency, and the urge to defecate, and may decrease colonic transit times in patients with chronic constipation.
Corpus gastritis in patients with endoscopic diagnosis of reflux oesophagitis and Barrett's oesophagus
Authors: Laheij R. J. F. , Van Rossum L. G. M. , De Boer W. A. , Jansen J. B. M. J.
Published: March 2003

Background:

A high level of gastric acid secretion is considered to be a risk factor for reflux oesophagitis or Barrett's oesophagus. Corpus gastritis may have a protective effect on the oesophagus, because of decreased gastric acid output.

Aim:

To determine if corpus gastritis is associated with reflux oesophagitis or Barrett's oesophagus.

Methods:

Three antral and two corpus biopsies were taken from consecutive patients in whom Helicobacter pylori testing was requested during endoscopy at a single centre between January 1995 and May 1997. Antral and corpus gastritis was studied by histology; H. pylori was studied by histology, culture and CLO test. A regression model was used to test for correlation between reflux oesophagitis, Barrett's oesophagus and risk factors.

Results:

During the study period, 676 patients had biopsies taken during upper gastrointestinal endoscopy. Endoscopic signs of reflux oesophagitis and Barrett's oesophagus were observed in 125 and 23 patients, respectively. Corpus gastritis was found in 59% of patients without reflux oesophagitis or Barrett's oesophagus, 45% of patients with reflux oesophagitis and 30% of patients with Barrett's oesophagus. Two hundred and fifty‐seven patients underwent follow‐up endoscopy after H. pylori therapy. During a mean follow‐up of 3 months, the incidence of reflux oesophagitis was not statistically different for patients with healing of corpus gastritis (10/98; 10%) and patients with persistent gastritis (8/97; 8%).

Conclusions:

Corpus gastritis was less common in patients with an endoscopic diagnosis of reflux oesophagitis or Barrett's oesophagus.
Duodenal ulcer healing with 1‐week eradication triple therapy followed, or not, by anti‐secretory treatment: a multicentre double‐blind placebo‐controlled trial
Authors: Colin R. ,   For The Hepylog Investigator Study Group
Published: March 2003

Background:

In the management of Helicobacter pylori induced duodenal ulcer, it is still controversial whether anti‐secretory treatment needs to be continued following a 1‐week course of eradication therapy.

Methods:

150 patients with H. pylori active duodenal ulcer (diameter ≥ 5 mm) were included. After a 1‐week eradication treatment combining omeprazole 20 mg b.d., amoxicillin 1000 mg b.d. and clarithromycin 500 mg b.d. (OAC), patients were randomized to omeprazole 20 mg or placebo for 3 additional weeks. The primary variable was ulcer healing assessed at 4 weeks. Eradication was verified 4 weeks after cessation of study drugs by 13C‐urea breath test. Intention‐to‐treat analysis (ITT) included 131 patients with positive histopathology at inclusion.

Results:

Healing rates were not statistically different, at 89% and 87%, respectively, in the OAC–omeprazole and OAC–placebo groups (95% CI: –8.7; 13.7). Numerically, healing rates in patients with successful eradication was higher [94/104 (90%)] than in patients with failed eradication [21/27 (78%)]. However, the difference was not statistically significant (P < 0.1).

Conclusions:

One‐week OAC eradication triple therapy achieves excellent healing rates in patients with uncomplicated duodenal ulcer disease. Although the confidence interval of the difference in healing suggests little or no benefit of continued omeprazole treatment after 1 week, larger studies are needed to address this issue definitively.
Amoxicillin and ampicillin are not transferred to gastric juice irrespective of Helicobacter pylori status or acid blockade by omeprazole
Authors: Ortiz R. A. M. , Calafatti S. A. , Corazzi A. , Souza J. M. , Deguer M. , De Souza C. A. F. , Marchioretto M. A. M. , Bernasconi G. , Ferraz J. G. P. , Pedrazzoli J.
Published: March 2003

Background:

The effects of proton pump inhibitors and Helicobacter pylori infection on the distribution of drugs used for the eradication of the bacteria are poorly understood.

Aim:

The aim of this study was to investigate the effects of a 7‐day administration of 20 mg of omeprazole on the pharmacokinetics of amoxicillin and ampicillin in the plasma, saliva and gastric juice of individuals with and without H. pylori infection.

Methods:

Fifty‐four healthy volunteers without endoscopic lesions were enrolled. Twenty‐six volunteers were included in the amoxicillin study and 28 individuals in the ampicillin study. Each study had an open randomized two‐period crossover design and a 21‐day washout period between phases. Plasma, saliva and gastric juice concentrations of amoxicillin and ampicillin in subjects with and without omeprazole pre‐treatment were measured by reversed‐phase HPLC using UV detection.

Results:

Neither pre‐treatment with omeprazole nor H. pylori infection interfered with the plasma bioavailability of amoxicillin or ampicillin, as assessed by the AUC0–2 h. Neither ampicillin nor amoxicillin were detected in saliva or gastric juice in any study phase.

Conclusion:

Short‐term treatment with omeprazole does not interfere with the pharmacokinetics of amoxicillin or ampicillin. Our results also exclude the presence of a transfer mechanism for amoxicillin or ampicillin from the plasma to the gastric lumen.
The treatment of functional dyspepsia with red pepper
Authors: Bortolotti M. , Coccia G. , Grossi G. , Miglioli M.
Published: March 2003

Aim : To decrease the intensity of dyspeptic symptoms by impairing the visceral nociceptive C‐type fibres with capsaicin, contained in red pepper powder.

Methods : The study was performed on 30 patients with functional dyspepsia and without gastro‐oesophageal reflux disease and irritable bowel syndrome. After a 2‐week washout period, 15 patients received, before meals randomly and in a double‐blind manner, 2.5 g/day of red pepper powder for 5 weeks, and 15 patients received placebo. A diary sheet was given to each patient to record, each day, the scores of individual and overall symptom intensity, which subsequently were averaged weekly and over the entire treatment duration.

Results : The overall symptom score and the epigastric pain, fullness and nausea scores of the red pepper group were significantly lower than those of the placebo group, starting from the third week of treatment. The decrease reached about 60% at the end of treatment in the red pepper group, whilst placebo scores decreased by less than 30%.

Conclusions : Red pepper was more effective than placebo in decreasing the intensity of dyspeptic symptoms, probably through a desensitization of gastric nociceptive C‐fibres induced by its content of capsaicin. It could represent a potential therapy for functional dyspepsia.
Impact of Helicobacter pylori eradication on heartburn in patients with gastric or duodenal ulcer disease — results from a randomized trial programme
Authors: Malfertheiner P. , Dent J. , Zeijlon L. , Sipponen P. , Veldhuyzen Van Zanten S. J. O. , Burman C.‐F. , Lind T , Wrangstadh M , BayerdÖrffer E , Lonovics J
Published: March 2003

Background : Helicobacter pylori infection has been proposed as a protective factor against the development of gastro‐oesophageal reflux disease.

Aim : To study heartburn and endoscopic findings before and after H. pylori eradication therapy in patients with peptic ulcer disease.

Methods : In a multicentre trial programme, patients (n = 1497) were randomized to the omeprazole triple therapy group or to the control group, and were followed for 1–6 months after treatment. Patients in whom the infection was eradicated were compared with those in whom infection persisted. The severity of heartburn was measured at baseline and at each return visit. Endoscopy was performed 6 months after therapy in two of the five studies.

Results : In patients with duodenal ulcer, there was a significantly lower prevalence of heartburn after successful eradication of H. pylori relative to that after failed eradication (estimated odds ratio, 0.48). The reduction in the prevalence of heartburn in patients with gastric ulcer was independent of the post‐treatment H. pylori status. In studies in which ulcer relapse was included in the model, this factor emerged as a significant factor for heartburn. The observed incidence of oesophagitis at the last visit was not influenced by H. pylori status.

Conclusions : Eradication of H. pylori in patients with peptic ulcer disease was associated with a reduced prevalence of heartburn. Prevention of ulcer relapse could be the true cause of this reduction.
Effects of rabeprazole, 20 mg, or esomeprazole, 20 mg, on 24‐h intragastric pH and serum gastrin in healthy subjects
Authors: Warrington S. , Baisley K. , Boyce M. , Tejura B. , Morocutti A. , Miller N.
Published: March 2003

Aim : To compare the antisecretory effects of rabeprazole and esomeprazole in an open, randomized, two‐way crossover, clinical pharmacology study.

Methods : Twenty‐four healthy subjects (14 men, 10 women; mean age 26.8 years) received rabeprazole 20 mg or esomeprazole 20 mg daily on days 1–5, witha 14‐day ‘wash‐out’. Intragastric pHwasrecordedcontinuously, and serum gastrin measured, on days 0, 1 and 5.

Results : On day 0, mean intragastric pH AUC was significantly higher before the esomeprazole than before the rabeprazole treatment in four of the five time intervals analysed. On days 1 and 5, mean intragastric pH AUC was higher after rabeprazole than esomeprazole during 5–11, 14–24 and 0–24 h after dosing. Mean pH AUC in the first 5 h after dosing on day 5 was higher after esomeprazole than rabeprazole (P=0.012). On day 1, mean per cent times pH > 3 and > 4 were significantly greater after rabeprazole than esomeprazole during 0–14, 14–24 and 0–24 h. On day 5, mean serum gastrin AUC0‐4 was higher (P = 0.017) after rabeprazole than esomeprazole (335 vs. 316 pg/mL.h).

Conclusion : In this clinical pharmacology study, rabeprazole 20 mg daily was more effective than esomeprazole 20 mg daily in increasing intragastric pH and maintaining pH > 3 and > 4. On day 5, mean pH AUC was higher after esomeprazole than rabeprazole.
Gastroenterology and the pharmaceutical industry
Authors: Rakatansky H.
Published: March 2003

Physicians’ relationships with industry derive from the moral imperative to advocate and work for the best interests of patients. Private industry generally operates to satisfy the best interests of the stockholders or owners. Conflicts arise between these interests and are magnified by the inequality of the financial positions of physicians and industry. Because the ultimate consumer of the products (drugs, medical devices, etc.) of the biomedical industry must enlist a physician as an intermediary, the physician has become the target of industry in a sophisticated marketing effort that includes the offering of financial and other incentives. These conflicts and incentives are pervasive throughout clinical and research endeavors. Standards for resolution, if not elimination, of these conflicts have been proposed by various respected organizations. Individual physicians and medical organizations should evaluate these standards and, if pertinent and appropriate, endorse and follow them.
Comparison of the efficacy of pantoprazole vs. nizatidine in the treatment of erosive oesophagitis: a randomized, active‐controlled, double‐blind study
Authors: Kovacs T. O. G. , Wilcox C. M. , Devault K. , Miska D. , Bochenek W. ,   THE PANTOPRAZOLE US GERD STUDY GROUP B
Published: March 2003

Background : Pantoprazole is a proton pump inhibitor approved for the treatment of erosive oesophagitis and gastro‐oesophageal reflux disease.

Aim : To compare the efficacy and safety of pantoprazole vs. nizatidine for the treatment of symptomatic gastro‐oesophageal reflux disease and endoscopically documented erosive oesophagitis (grade ≥ 2).

Methods : A multicentre, double‐blind, randomized, active‐controlled study (221 patients) was performed to compare 20 and 40 mg pantoprazole daily with nizatidine 150 mg b.d. (maximum, 8 weeks). The primary end‐point was endoscopic healing of erosive oesophagitis (grade 1 or 0). The secondary end‐point was symptomatic improvement.

Results : Healing averaged 61%, 64% and 22% for pantoprazole 20 mg, pantoprazole 40 mg and nizatidine 150 mg, respectively, at 4 weeks, and 79%, 83% and 41% at 8 weeks (P < 0.05, differences between groups at both points). Starting on day 1 of symptom assessment, significantly fewer pantoprazole‐treated patients reported night‐time heartburn and regurgitation compared with nizatidine‐treated patients. Symptoms of gastro‐oesophageal reflux disease were completely eliminated in 68% and 65% of patients in the pantoprazole 20‐mg and 40‐mg groups and in 28% of patients in the nizatidine group at study completion. The difference between each pantoprazole group and the nizatidine group was significant (P < 0.05).

Conclusions : Pantoprazole, at single daily doses of 20 mg and 40 mg for up to 8 weeks, provides more rapid relief of symptoms and superior healing of erosive oesophagitis than nizatidine 150 mg b.d., and is well tolerated.
Long‐term aminosalicylate therapy is under‐used in patients with ulcerative colitis: a cross‐sectional survey
Authors: Rubin G. , Hungin A. P. S. , Chinn D. , Dwarakanath A. D. , Green L. , Bates J.
Published: March 2003

Background : There is evidence from case–control studies that aminosalicylate drugs can reduce colorectal cancer risk by 75–81% in patients with ulcerative colitis. Patients may fail to comply with long‐term therapies, however, or may have been advised to discontinue treatment once in remission.

Aim : To describe the usage of long‐term aminosalicylate therapy in patients with ulcerative colitis.

Methods : A cross‐sectional study was performed using data extracted from general practitioner clinical records on demographic features, extent and duration of disease, use of aminosalicylate therapy and specialist care.

Results : Three hundred and sixty‐three people had ulcerative colitis and no history of colorectal surgery. Ninety‐five of 175 (54%) patients with proctitis, 78 of 123 (63%) patients with left‐sided colitis and 28 of 45 (62%) patients with extensive colitis were currently taking an aminosalicylate drug. Those doing so were more likely to be under specialist care than to be definitely or possibly discharged (odds ratio, 4.9; 95% confidence interval, 2.9–8.4). The likelihood of current aminosalicylate therapy was not related to gender or the extent of disease, but was negatively related to the duration of disease.

Conclusions : A substantial minority of patients with ulcerative colitis does not take long‐term aminosalicylate therapy. Those who do are more likely to be under specialist care, to be older or to have disease of shorter duration.
A randomized, double‐blind, placebo‐controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation
Authors: Novick J. , Miner P. , Krause R. , Glebas K. , Bliesath H. , Ligozio G. , Rüegg P. , Lefkowitz M.
Published: March 2003

Background : Irritable bowel syndrome is a common functional gastrointestinal disorder which affects up to 20% of the population, with a predominance in females.

Aim : To evaluate the efficacy and safety of tegaserod in female patients with irritable bowel syndrome characterized by symptoms of abdominal pain/discomfort and constipation.

Methods : In a randomized, double‐blind, multicentre study, 1519 women received either tegaserod, 6 mg b.d. (n = 767), or placebo (n = 752) for 12 weeks, preceded by a 4‐week baseline period without treatment and followed by a 4‐week open withdrawal period. The primary efficacy evaluation was the patient's symptomatic response as measured by the Subject's Global Assessment of Relief. Other efficacy variables included abdominal pain/discomfort, bowel habits and bloating.

Results : Tegaserod produced significant (P < 0.05) improvements in the Subject's Global Assessment of Relief and other efficacy variables. These improvements were seen within the first week, and were maintained throughout the treatment period. After withdrawal of treatment, the symptoms rapidly returned. Overall, tegaserod was well tolerated. Diarrhoea was the most frequent adverse event; however, this led to discontinuation in only 1.6% of tegaserod‐treated patients.

Conclusions : Tegaserod, 6 mg b.d., produced rapid and sustained improvement of symptoms in female irritable bowel syndrome patients and was well tolerated.
Oxidative stress as a pathogenic factor in inflammatory bowel disease — radicals or ridiculous?
Authors: Kruidenier L. , Verspaget H. W.
Published: March 2003

Virtually all inflammatory mediators investigated to date seem to be dysregulated in the inflamed intestinal mucosa of patients with inflammatory bowel disease. However, which of these are actually involved in the initiation and perpetuation of intestinal tissue damage is still not fully understood. Amongst these mediators are the reactive oxygen metabolites, produced in large amounts by the massively infiltrating leucocytes. These reactive oxygen metabolites are believed to constitute a major tissue‐destructive force and may contribute significantly to the pathogenesis of inflammatory bowel disease.

This paper provides a concise overview of reactive oxygen metabolite biochemistry, the types of cell and tissue damage potentially inflicted by them, and the endogenous antioxidants which should prevent these harmful effects. An up‐to‐date summary of the available human experimental data suggests that reactive oxygen metabolite‐mediated injury is important in both the primary and downstream secondary pathophysiological mechanisms underlying intestinal inflammation. Nonetheless, how the individual components of the mucosal antioxidant enzymatic cascade respond to inflammatory conditions is a neglected area of research. This particular aspect of intestinal mucosal oxidative stress therefore merits further study, in order to provide a sound, scientific basis for the design of antioxidant‐directed treatment strategies for inflammatory bowel disease patients.
High‐dose interferon α‐2a with ribavirin and amantadine in naïve chronic hepatitis C patients — results of a randomized, prospective, pilot study
Authors: Ullerich H. , Avenhaus W. , Poremba C. , Domschke W. , Menzel J.
Published: March 2003

Background : Hepatitis C viral kinetic studies have demonstrated the increased anti‐viral effect of higher than standard dosages of interferon and of daily treatment schedules.

Aim : To compare, in a prospective, randomized, controlled trial, the efficacy and safety of high‐dose interferon‐α therapy vs. standard‐dosage interferon‐α therapy, in a triple therapy combination with ribavirin and amantadine.

Methods : Previously untreated patients with chronic hepatitis C were randomized to the standard interferon‐α group (n = 15), receiving thrice weekly 6 MU interferon‐α for 12 weeks, followed by 3 MU interferon‐α for 36 weeks, or the high‐dose interferon‐α group (n = 15), receiving daily 9 MU interferon‐α for 4 weeks, followed by 6 MU (weeks 5–8), 3 MU (weeks 9–12) and 1.5 MU (weeks 13–48) interferon‐α. All patients were given ribavirin (1000–1200 mg) and amantadine (200 mg) daily for 48 weeks.

Results : At the end of treatment and after the 24‐week follow‐up period, serum hepatitis C virus RNA was undetectable in eight (53%) and six (40%) patients treated with standard‐dosage interferon‐α, respectively, compared with 11 (73%) and 10 (67%) treated with high‐dose interferon‐α, respectively (not significant). The safety profile of both treatment regimens was similar. Severe adverse events leading to withdrawal from the study occurred in one patient (7%) in each group, and in both groups one patient (7%) was lost during therapy for unknown reasons.

Conclusions : The findings suggest that, although the difference between the response rates of standard and high‐dose interferon‐α regimens (within a triple anti‐viral therapy combination) did not reach statistical significance, there was a clear trend towards a higher response with high‐dose interferon‐α therapy and an equal safety profile.