bluuebunny/crossref_metadata_2025 huggingface dataset:
Relevance of thiopurine methyltransferase activity in inflammatory bowel disease patients maintained on low‐dose azathioprine
Authors: Campbell S. , Kingstone K. , Ghosh S.
Published: March 2003

Background:

It is well‐recognized that patients with low thiopurine methyltransferase activity are more susceptible to the development of bone marrow suppression side‐effects.

Aim:

To study the impact of thiopurine methyltransferase activity on the clinical course of inflammatory bowel disease patients treated with low‐dose azathioprine (< 2 mg/kg).

Methods:

We measured the thiopurine methyltransferase activity of blood samples from 113 inflammatory bowel disease patients who were taking azathiopurine, had discontinued azathioprine because of side‐effects, or had never taken azathioprine. The thiopurine methyltransferase activity was compared with that of 17 healthy controls. Relapse rates and time to first relapse were compared in inflammatory bowel disease patients and stratified according to their thiopurine methyltransferase activity.

Results:

Patients who became neutropenic had a significantly lower mean thiopurine methyltransferase activity than that of patients who developed other side‐effects (analysis of variance, P < 0.05). Survival curves were constructed (time to first relapse) for patients treated with low‐dose azathioprine for thiopurine methyltransferase activities of < 20 and > 20 nmol/mL red blood cells/h. There was a significantly lower number of relapses in inflammatory bowel disease patients with lower thiopurine methyltransferase levels (P < 0.05).

Conclusions:

The mean thiopurine methyltransferase activity was significantly lower in patients on a low dose of azathioprine in remission compared with those who relapsed. The thiopurine methyltransferase activity was significantly lower in patients who discontinued azathioprine due to neutropenia than in those who discontinued due to other side‐effects.
Helicobacter pylori and dyspepsia: physicians' attitudes, clinical practice, and prescribing habits
Authors: O'Connor H. J.
Published: March 2003

Background:

Consensus guidelines have been published on the management of Helicobacter pylori infection and it is assumed that these guidelines are adhered to in clinical practice.

Aim:

To assess the changing attitudes of medical practitioners to H. pylori, and the impact of H. pylori infection on everyday clinical practice and prescribing patterns.

Methods:

Data for this review were gathered up to December 2000 from detailed review of medical journals, the biomedical database MEDLINE, and relevant abstracts.

Results:

Physician surveys show widespread acceptance of H. pylori as a causal agent in peptic ulcer disease. Gastroenterologists adopted H. pylori therapy for peptic ulcer earlier and more comprehensively than primary care physicians. Despite a low level of belief in H. pylori as a causal agent in nonulcer dyspepsia and gastro‐oesophageal reflux disease (GERD), H. pylori therapy is widely prescribed for these conditions. Proton pump inhibitor‐based triple therapy is the eradication regimen of choice by all physician groups. In routine clinical practice, there appears to be significant under‐treatment of peptic ulcer disease with H. pylori therapy, but extensive use for nonulcer indications. Prescription of H. pylori treatment regimens of doubtful efficacy appears commonplace, and are more likely in primary care. Despite the advent of H. pylori therapy, the prescription of antisecretory therapy, particularly of proton pump inhibitors, continues to rise.

Conclusions:

Publication of consensus guidelines per se is not enough to ensure optimal management of H. pylori infection. Innovative and ongoing educational measures are needed to encourage best practice in relation to H. pylori infection. These measures might be best directed at primary care, where the majority of dyspepsia is managed.
Different effects of short‐term omeprazole, lansoprazole or pantoprazole on the accuracy of the 13C‐urea breath test
Authors: Parente F. , Sainaghi M. , Sangaletti O. , Imbesi V. , Maconi G. , Anderloni A. , Bianchi Porro G.
Published: March 2003

Background:

Proton pump inhibitors may interfere with the accuracy of the 13C‐urea breath test, but little information is available on the effect of standard doses of various proton pump inhibitors on this test.

Aim:

To evaluate the effect of short‐term standard doses of omeprazole, lansoprazole and pantoprazole on the accuracy of the standardized 13C‐urea breath test.

Methods:

A total of 124 patients with Helicobacter pylori infection, diagnosed on the basis of gastric histology, rapid urease test and 13C‐urea breath test, were studied. These patients received omeprazole, 20 mg/day, lansoprazole, 30 mg/day, or pantoprazole, 40 mg/day, for 2 weeks according to a randomized protocol. 13C‐Urea breath test was repeated on days 4, 7 and 14 while on therapy and 7 days after proton pump inhibitor withdrawal.

Results:

Of the patients receiving omeprazole and lansoprazole, 30% (12/40) and 20% (8/41), respectively, became 13C‐urea breath test negative during therapy, compared with none of the 42 patients treated with pantoprazole (P < 0.05). All the false negative 13C‐urea breath test results returned to positive within 1 week of drug withdrawal, with a mean recovery to 84.7 ± 15.6% of baseline δ13CO2.

Conclusions:

Short‐term omeprazole and lansoprazole interfere with the 13C‐urea breath test, although a return to positive test results invariably occurs within 1 week of proton pump inhibitor withdrawal. In contrast, the accuracy of the 13C‐urea breath test does not appear to be significantly impaired by short‐term pantoprazole, which therefore may not necessarily be withdrawn before this test.
A randomized trial of high‐dose interferon alpha‐2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon
Authors: Malik A. H. , Kumar K. S. , Malet P. F. , Ostapowicz G. , Adams G. , Wood M. , Yarbrough K. , Jones A. , Lee W. M.
Published: March 2003

Background:

Conventional interferon monotherapy fails to achieve virological clearance in most hepatitis C‐infected patients. The use of high‐dose induction regimens may improve the initial clearance of virus, while the addition of ribavirin appears to improve the rates of sustained response once clearance is achieved.

Aim:

To compare the efficacy and safety of re‐treatment with an induction regimen of high‐dose interferon alpha‐2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon monotherapy.

Methods:

Previous virological non‐responders to standard dose interferon (3–5 MU three times weekly for ≥ 12 weeks) were randomized to receive, unblind, either 10 MU interferon alpha‐2b daily for 10 days, then 5 MU daily for 74 days, then 5 MU three times weekly for 24 weeks (total 36 weeks) (group A), or the above regimen with the addition of ribavirin, 1000–1200 mg/day, at day 11 (group B). All patients were followed up for 24 weeks after completion of therapy.

Results:

End of treatment virological response was noted in one of 10 (10%) patients in group A and in eight of 15 (54%) patients in group B (P=0.04). The sole end treatment responder in group A and three in group B relapsed on follow‐up. The apparent improvement in response in group B compared to group A nearly reached statistical significance (group B 5/15 vs. group A 0/10; P=0.06).

Conclusions:

In this small pilot study, a 36‐week high‐dose induction interferon monotherapy protocol did not yield sustained responses in previous non‐responders to standard dose interferon. However, the same regimen with ribavirin yielded a 33% sustained response rate, nearly reaching statistical significance. The therapy was well tolerated, despite the higher doses of interferon used and the addition of ribavirin. High‐dose interferon with ribavirin appears to be a therapeutic option for non‐responders to conventional interferon monotherapy.
Effect of octreotide on fluid absorption and secretion by the normal human jejunum and ileum in vivo
Authors: Högenauer C. , Aichbichler B. , Santa Ana C. , Porter J. , Fordtran J.
Published: March 2003

Background:

We hypothesized that part of the non‐specific antidiarrhoeal effect of octreotide is mediated by a proabsorptive or antisecretory effect on small intestinal active electrolyte transport.

Methods:

To measure the effect of octreotide on net absorption, the jejunum and ileum of normal human subjects were perfused with a balanced electrolyte solution; to measure the effect of octreotide on normal active chloride secretion, the jejunum was perfused with a bicarbonate‐free solution.

Results:

During perfusion of a balanced electrolyte solution, octreotide increased basal net fluid absorption in the jejunum and ileum by about 40 mL/h per 30 cm. In the jejunum, octreotide markedly inhibited basal and sham feeding‐stimulated active chloride secretion and inhibited water secretion by 28 and 51 mL/h per 30 cm, respectively.

Conclusions:

Octreotide causes an increase in the net epithelial cell absorption rate of a balanced electrolyte solution in the normal jejunum and ileum. In the jejunum, this proabsorptive effect is mediated mainly by the reduction of normal active electrolyte secretion, rather than by stimulation of normal active electrolyte absorption. These results support the hypothesis that part of the antidiarrhoeal action of octreotide is due to its effects on active electrolyte transport mechanisms by normal epithelial cells of the small intestine.
Comparison of lansoprazole and famotidine for gastric acid inhibition during the daytime and night‐time in different CYP2C19 genotype groups
Authors: Shirai N. , Furuta T. , Xiao F. , Kajimura M. , Hanai H. , Ohashi K. , Ishizaki T.
Published: March 2003

Background:

The acid inhibitory effect of lansoprazole depends on the S‐mephenytoin 4′‐hydroxylase (CYP2C19) genotype status. The effect of famotidine is independent of this genotype.

Aim:

To investigate the acid inhibitory effects of lansoprazole vs. famotidine during the daytime and night‐time with reference to different CYP2C19 genotypes.

Methods:

Fifteen healthy volunteers were given 20 mg famotidine twice a day or 30 mg lansoprazole once a day for 8 days. On post‐dose day 8, 24‐h intragastric pH monitoring was performed.

Results:

During the daytime, the intragastric pH with lansoprazole was significantly higher than that with famotidine in the heterozygous extensive metabolizer group, whereas no significant difference was observed in the homozygous extensive metabolizer group. During the night‐time, the intragastric pH with famotidine was quite similar to that with lansoprazole in the heterozygous extensive metabolizer and poor metabolizer groups. However, during the night‐time, the intragastric pH with famotidine was significantly higher than that with lansoprazole in the homozygous extensive metabolizer group.

Conclusions:

An insufficient acid inhibition by lansoprazole during the night‐time in the homozygous extensive metabolizer group could be compensated for by famotidine. CYP2C19 genotype testing appears to be useful for predicting the optimal acid inhibitory drug treatment collated with circadian intragastric pH change.
Dose finding study of mosapride in functional dyspepsia: a placebo‐controlled, randomized study
Authors: Hallerbäck B. I. , Bommelaer G. , Bredberg E. , Campbell M. , Hellblom M. , Lauritsen K. , Wienbeck M. , Holmgren L. ‐L.
Published: March 2003

Background:

Prokinetic agents have shown variable efficacy in the treatment of functional dyspepsia. Mosapride is a new prokinetic 5‐hydroxytryptamine‐4 agonistic agent.

Aim:

To evaluate the efficacy of three dosage regimens of mosapride compared with placebo in the treatment of functional dyspepsia.

Methods:

Patients were randomly allocated to treatment with placebo or mosapride (5 mg b.d., 10 mg b.d. or 7.5 mg t.d.s.) in a double‐blind, prospective, multicentre, multinational study. The change in symptom severity score from an untreated baseline week to the sixth week of treatment was used to compare treatment efficacy.

Results:

There were 141, 140, 143 and 142 patients valid for evaluation in the intention‐to‐treat population in the placebo, mosapride 5 mg b.d., mosapride 10 mg b.d. and mosapride 7.5 mg t.d.s. groups, respectively. The mean changes in the overall dyspeptic symptom score were – 0.90, – 0.94, – 0.88 and – 0.89, respectively, and the proportions of patients feeling better at the end of the treatment period were 60%, 59%, 59% and 61%, respectively. No statistically significant difference was seen.

Conclusions:

Treatment of functional dyspepsia with mosapride was not superior to placebo. The result raises the question of whether treatment with prokinetic agents is appropriate for functional dyspepsia.
Baclofen‐mediated gastro‐oesophageal acid reflux control in patients with established reflux disease
Authors: Cange L. , Johnsson E. , Rydholm H. , Lehmann A. , Finizia C. , Lundell L. , Ruth M.
Published: March 2003

Aim:

To explore the effect of baclofen on oesophageal acid exposure in patients with gastro‐oesophageal reflux disease.

Methods and materials:

Twenty patients with established reflux disease were included in this double‐blind, randomized, crossover study. Baclofen, 40 mg, or placebo was given as a single dose with a washout period of 4 weeks. Symptoms were assessed by a visual analogue scale. Oesophageal pH was registered for 12 h and analysed for the whole period and for the 0–4‐h, 4–8‐h, 8–12‐h and 2‐h post‐prandial periods.

Results:

Baclofen significantly reduced the number of reflux episodes during the 0–4‐h (7.9 vs. 16.5, P < 0.0001; post‐prandially: 6.0 vs. 11.2, P < 0.0001) and 0–12‐h (46.5 vs. 73, P=0.0001; post‐prandially: 18.8 vs. 29.3, P < 0.0001) periods. The fraction of time with pH < 4 was significantly lowered during the 0–4‐h period (9.3 vs. 15.6, P=0.0019; post‐prandially: 16.1 vs. 23.5, P=0.0083). Similar results were also obtained in patients with a hiatus hernia (n=13). Belching was significantly reduced (32 vs. 69 episodes, P < 0.01).

Conclusions:

A single oral dose of 40 mg baclofen significantly reduced both the number of reflux episodes and the fraction of time with pH < 4, an effect primarily found during the first 4 h after dosing.
Induction and maintenance of clinical remission by interferon‐β in patients with steroid‐refractory active ulcerative colitis—an open long‐term pilot trial
Authors: Musch E. , Andus T. , Malek M.
Published: March 2003

Background:

The imbalance of pro‐ and anti‐inflammatory cytokines plays an important role in the pathogenesis of inflammatory bowel disease. Shifting this disturbed ratio by means of TNF‐antibodies or interferon has been shown to be helpful in treating Crohn's disease and multiple sclerosis, respectively.

Aim:

This pilot study investigated whether interferon‐β can induce clinical remission in corticoid‐refractory ulcerative colitis.

Methods:

Twenty‐five patients with steroid‐refractory active ulcerative colitis (Clinical activity index according to Rachmilewitz: 13.5 ± 5.2) were treated in an open pilot trial with 0.5 MIU human natural interferon‐β (hn‐IFN‐β) i.v. (n=18) or 1 MIU recombinant interferon‐β‐1a (r‐IFN‐β‐1‐a) s.c. (n=7) daily with the goal of induction of remission. Subsequent maintenance treatment was carried out for 52.0 ± 78.8 weeks (range 4–336 weeks) with the same dose, three times per week.

Results:

Twenty‐two of 25 patients (88%) went into remission during induction treatment (hn‐IFN‐β 16/18, r‐IFN‐β‐1a 6/7). Mean time to response was 3.0 ± 1.3 weeks. Mean length of remission was 13.0 ± 19.7 months. Only eight of 22 patients in remission relapsed during maintenance treatment. Five of these went into remission again after increasing the dose. Adverse events consisted of slight to moderate flu‐like symptoms and slight to moderate hair loss in five of 15 female patients.

Conclusion:

Although this open pilot study included only a small number of patients, the high response rate suggests that interferon‐β may be a safe and effective treatment for steroid‐refractory active ulcerative colitis.
Meta‐analysis: the efficacy of intravenous H2‐receptor antagonists in bleeding peptic ulcer
Authors: Levine J. E. , Leontiadis G. I. , Sharma V. K. , Howden C. W.
Published: March 2003

Background : Although a previous meta‐analysis found that intravenous H2‐receptor antagonists were only weakly beneficial in bleeding gastric ulcer and of no benefit in bleeding duodenal ulcer, patients with ulcer bleeding continue to receive such treatment.

Aim : To re‐evaluate the efficacy of intravenous H2‐receptor antagonists in ulcer re‐bleeding, surgery and mortality by updating the previous meta‐analysis.

Methods : After two independent literature searches, randomized, placebo‐controlled trials of intravenous H2‐receptor antagonists in bleeding ulcer published between 1984 and 2000 were added to those from the initial meta‐analysis. Pooled rates of re‐bleeding, surgery and death were re‐calculated, together with the relative risk reduction, absolute risk reduction, number needed to treat and Mantel–Haenszel odds ratio.

Results : Intravenous H2‐receptor antagonists did not significantly reduce re‐bleeding, surgery or death in bleeding duodenal ulcer. There were small but significant reductions in re‐bleeding, surgery and death in bleeding gastric ulcer; the absolute risk reductions were 7.2%, 6.7% and 3.2%, respectively.

Conclusions : Intravenous H2‐receptor antagonists are of no value in bleeding duodenal ulcer, although they may be mildly beneficial in bleeding gastric ulcer. Because proton pump inhibitors have a greater inhibitory effect on gastric acid secretion than H2‐receptor antagonists, they may be more effective in ulcer bleeding and should be further evaluated for that indication.
The importance of endoscopic ultrasonography in the management of low‐grade gastric mucosa‐associated lymphoid tissue lymphoma
Authors: Caletti G. , Zinzani P. L. , Fusaroli P. , Buscarini E. , Parente F. , Federici T. , Peyre S. , De Angelis C. , Bonanno G. , Togliani T. , Pileri S. , Tura S. ,   THE ITALIAN GASTRIC LYMPHOMA STUDY GROUP
Published: March 2003

Background : Anti‐Helicobacter pylori therapy has been reported to cause regression of low‐grade gastric mucosa‐associated lymphoid tissue lymphoma in a high percentage of patients. However, in some patients, these lesions persist despite antibiotic treatment.

Aim : To determine the various endosonographic findings that may predict the regression of low‐grade gastric mucosa‐associated lymphoid tissue lymphoma post‐antibiotics.

Methods : Seventy‐six patients with Helicobacter pylori‐positive gastric mucosa‐associated lymphoid tissue lymphoma were studied. Follow‐up data were available on 51 patients. All patients were treated with antibiotics. Participants underwent pre‐ and post‐anti‐Helicobacter pylori therapy endoscopy with gastric biopsies, followed by endoscopic ultrasonography examination of the stomach.

Results : Helicobacter pylori was eradicated in 45 of 51 (88%) patients. At the 2‐year follow‐up, complete regression of mucosa‐associated lymphoid tissue lymphoma was seen in 28 of 51 (55%) patients: 12 of 16 (75%) patients in stage T1m N0, 11 of 19 (58%) patients in stage T1sm N0, four of eight (50%) patients in stages T1m N1 and T1sm N1, and one of four (25%) patients in stage T2 N0. None of the stage T2 N1 patients achieved clinical regression.

Conclusions : Endoscopic ultrasonography evaluation of gastric mucosa‐associated lymphoid tissue lymphoma plays a pivotal role in the initial staging and post‐treatment follow‐up evaluation of these lesions. Accurate staging is essential in the determination of the optimal treatment modality.
Impact of supplement with Lactobacillus‐ and Bifidobacterium‐containing yogurt on triple therapy for Helicobacter pylori eradication
Authors: Sheu B.‐S. , Wu J. ‐J. , Lo C. ‐Y. , Wu H. ‐W. , Chen J. ‐H. , Lin Y. ‐S. , Lin M. ‐D.
Published: March 2003

Aim : To test whether supplements of Lactobacillus‐ and Bifidobacterium‐containing yogurt (AB‐Yogurt) affect the success of Helicobacter pylori eradication.

Methods : One hundred and sixty H. pylori‐infected patients were randomized into a triple‐plus‐yogurt group or a triple‐only group, receiving 1 week of triple therapy with and without supplements of AB‐Yogurt, respectively. In the triple‐plus‐yogurt group, AB‐Yogurt was continued for 4 weeks after triple therapy. Eight weeks later, patients were assessed for the success of H. pylori eradication. The stool samples of 22 randomly selected patients, 11 from each group, were provided on enrolment, at the first week and at the fifth week for evaluation of the percentage of Bifidobacterium in anaerobes.

Results : By intention‐to‐treat analysis, the triple‐plus‐yogurt group had a higher H. pylori eradication rate than the triple‐only group (91% vs. 78%, P < 0.05). The per protocol H. pylori eradication rates were similar for both groups (93.5% vs. 89%, P = N.S.). Only patients supplemented with AB‐Yogurt showed restoration of the percentage of Bifidobacterium in the anaerobes of stools at the fifth week to the level in the stools on enrolment.

Conclusions : Supplement with AB‐Yogurt can improve the intention‐to‐treat eradication rates of H. pylori, and can restore the depletion of Bifidobacterium in stools after triple therapy.
Long‐term safety of tegaserod in patients with constipation‐predominant irritable bowel syndrome
Authors: Tougas G. , Snape W. J. , Otten M. H. , Earnest D. L. , Langaker K. ‐E. , Pruitt R. E. , Pecher E. , Nault B. , Rojavin M. A.
Published: March 2003

Background : Tegaserod is a 5‐hydroxytryptamine‐4 receptor partial agonist. Oral administration causes gastrointestinal effects resulting in increased gastrointestinal motility and attenuation of visceral sensation.

Aim : To determine the long‐term safety and tolerability of tegaserod in patients suffering from irritable bowel syndrome with constipation as the predominant symptom of altered bowel habits.

Method : A multicentre, open‐label study with flexible dose titration of tegaserod in out‐patients suffering from constipation‐predominant irritable bowel syndrome.

Results : A total of 579 patients with constipation‐predominant irritable bowel syndrome were treated with tegaserod. Of these, 304 (53%) completed the trial. The most common adverse events, classified as related to tegaserod for any dose, were mild and transient diarrhoea (10.1%), headache (8.3%), abdominal pain (7.4%) and flatulence (5.5%). Forty serious adverse events were reported in 25 patients (4.4% of patients) leading to discontinuation in six patients. There was one serious adverse event, acute abdominal pain, classified as possibly related to tegaserod. There were no consistent differences in adverse events between patients previously exposed to tegaserod and those treated de novo. No pattern‐forming tegaserod‐related abnormalities in haematological and biochemical laboratory tests, urinalysis, blood pressure, pulse rate or electrocardiograms were found.

Conclusions : Tegaserod appears to be well tolerated in the treatment of patients with constipation‐predominant irritable bowel syndrome. The adverse event profile, clinical laboratory evaluations, vital signs and electrocardiogram recordings revealed no evidence of any unexpected adverse events, and suggest that treatment is safe over a 12‐month period.
Gabexate mesilate and/or octreotide in human immunodeficiency virus‐associated pancreatic abnormalities
Authors: Manfredi R. , Calza L. , Chiodo F.
Published: March 2003

Background : Human immunodeficiency virus (HIV)‐associated pancreatic alterations are frequent, but poorly investigated, notwithstanding their potential consequences on the course and management of HIV infection. No epidemiological or clinical data on pancreatic alterations have been published since the introduction of highly active antiretroviral therapy, and no indications of the pharmacological management of symptomatic or prolonged laboratory pancreatic abnormalities have been reported.

Aim : To investigate the therapeutic role of gabexate mesilate and octreotide in HIV‐infected patients with elevated, symptomatic or instrumentally confirmed pancreatic anomalies persisting for more than 3 months.

Methods and results : An open‐label, prospective, 5‐year case–control study was conducted involving 185 consecutive patients with pancreatic alterations. Treatment of patients with severe laboratory and/or clinical involvement with low‐dose gabexate mesilate and/or somatostatin was effective and safe and led to a lower recurrence rate and a better tolerability of concomitant drug regimens compared with supportive therapy taken by control patients. Combined gabexate–octreotide proved to be more active than single drug administration.

Conclusions : Epidemiological and therapeutic data on the frequency, risk factors and clinical significance of pancreatic abnormalities during HIV infection are required, as are studies investigating the need for and choice of antisecretory and/or antiprotease compounds.
Risk of upper gastrointestinal bleeding in patients taking low‐dose aspirin for the prevention of cardiovascular diseases
Authors: Serrano P. , Lanas A. , Arroyo M. T. , Ferreira I. J.
Published: March 2003

Background : Most patients with vascular‐occlusive diseases benefit from low‐dose aspirin (75–325 mg/day). However, they have an increased risk of upper gastrointestinal bleeding (UGIB).

Aims : To analyse the incidence and factors influencing the occurrence of UGIB in patients taking low‐dose aspirin for the prevention of cardiovascular diseases outside clinical trials.

Methods : We studied 903 consecutive patients discharged on low‐dose aspirin from the Cardiology Department of a general hospital. Data were collected from medical charts and structured telephone interviews.

Results : Forty‐one patients (4.5%) presented with UGIB requiring hospitalization during follow‐up (45 ± 22 months). The incidence of UGIB was uniform during follow‐up (1.2 UGIB per 100 patient years). Multivariate analysis showed that a history of peptic ulcer or UGIB [risk ratio: 3.1, 95% CI: (1.5–6.5)] and aspirin dose (per 100 mg/day) [1.8 (1.5–2.9)] was associated with higher risk of UGIB. On the other hand, antisecretory [0.22 (0.07–0.75)] and nitrovasodilator drugs [0.73 (0.55–0.96)] were associated with a decreased risk.

Conclusions : Cardiovascular patients on long‐term low‐dose aspirin have a stable risk of major UGIB, which is higher than published controlled clinical trials. Antisecretory and nitrovasodilator drugs protect from UGIB, whereas previous peptic ulcer or UGIB and higher doses of aspirin increase the risk.
Long‐term prospective follow‐up of endoscopic oesophagitis in southern Chinese — prevalence and spectrum of the disease
Authors: Wong W.‐M. , Lam S. K. , Hui W. M. , Lai K. C. , Chan C. K. , Hu W. H. C. , Xia H. H. X. , Hui C. K. , Yuen M. F. , Chan A. O. O. , Wong B. C. Y.
Published: March 2003

Aims : To study the prevalence, clinical characteristics and long‐term outcome of oesophagitis in Chinese patients.

Methods : Clinical and endoscopic data were collected prospectively from consecutive patients who underwent upper endoscopy between 1997 and 2001. Patients with endoscopic oesophagitis were graded according to the Los Angeles system and analysed according to their clinical presentation, endoscopic details, Helicobacter pylori status, non‐steroidal anti‐inflammatory drug history, co‐morbidity and mortality.

Results : A total of 22 628 upper endoscopies were performed in 16 606 patients. Of these, 631 (3.8%) had endoscopic oesophagitis, 14 had benign oesophageal stricture (0.08%) and 10 had Barrett's oesophagus (0.06%). Most patients (94%) had either Los Angeles grade A or grade B oesophagitis. Patients who died during follow‐up had a significantly higher incidence of co‐morbid illness (100% vs. 63%, P < 0.001). By Cox regression analysis, the presence of gastrointestinal bleeding (P = 0.008), advanced age (P = 0.004) and the use of Ryle's tube (P = 0.043) were identified to be independent factors associated with mortality.

Conclusions : Complicated gastro‐oesophageal reflux disease is uncommon in the Asian population. Advanced age, use of Ryle's tube and the presence of gastrointestinal bleeding are associated with a poor long‐term outcome, which is a reflection of the severe underlying co‐morbidity.
Diagnosis of Helicobacter pylori infection
Authors: Vaira D. , Gatta L. , Ricci C. , Miglioli M.
Published: March 2003

Helicobacter pylori (H. pylori) infection can be diagnosed by invasive techniques requiring endoscopy and biopsy (histological examination, culture, polymerase chain reaction) and by noninvasive techniques (serology, urea breath test, urine or blood, detection of H. pylori antigen in stool specimen). At present, no single test can be absolutely relied upon to detect colonization by H. pylori, and a combination of two tests is recommended if feasible. The tests used should depend on the clinical circumstances, the likelihood ratio of positive and negative tests, the cost‐effectiveness of the testing strategy, and the availability of the tests. Some clinical circumstances warrant invasive studies, principally patients with alarm symptoms (bleeding, weight loss, etc.) as well as older patients with new‐onset dyspepsia. Endoscopy may also be advisable in patients who have failed eradication therapy and need culture and antimicrobial sensitivity testing to determine an appropriate regimen. Recent studies have also demonstrated that a strategy to `test and treat' for H. pylori in uninvestigated, young (< 50 years), dyspeptic patients in primary care is safe and reduces the need for endoscopy. Indeed, a number of clinical guidelines recommend noninvasive testing followed by treatment of H. pylori for dyspeptic patients in primary care based on clinical and economic analyses.
Comparison of efficacy and safety of two doses of two different polyethylene glycol‐based laxatives in the treatment of constipation
Authors: Chaussade S. , Minić M.
Published: March 2003

Aim : To compare standard and maximum daily doses of polyethylene glycol 3350 plus electrolytes (Transipeg) and polyethylene glycol 4000 (Forlax) in a multicentre, double‐blind, randomized, parallel‐group study.

Methods : Ambulatory patients with idiopathic chronic constipation were randomized to receive Forlax (10 or 20 g) or Transipeg (5.9 or 11.8 g) for 1 month. The primary efficacy end‐point was stool frequency. Secondary efficacy parameters included stool consistency, date of occurrence of first motion, straining on defecation, rectal evacuation, abdominal pain and distension. Adverse events were recorded.

Results : Stool frequency was significantly increased compared with baseline in all treatment groups (P = 0.0001). Most patients (≥ 67.3%) had their first stool within 1 day of starting treatment. Stool consistency significantly improved compared with baseline in all treatment groups (P = 0.0001). The percentage of patients with normal stool consistency was significantly higher for standard‐dose Transipeg vs. both maximum‐dose treatments (P < 0.01). Other secondary parameters were also significantly improved compared with baseline in all treatment groups (P = 0.0001). All medications were well tolerated.

Conclusions : Standard‐dose Transipeg (5.9 g) normalized stool consistency with less semi‐liquid or liquid stools than maximum‐dose Transipeg and Forlax, with a non‐significant trend towards less semi‐liquid or liquid stools than standard‐dose Forlax.
Mercaptopurine metabolite results in clinical gastroenterology practice
Authors: Bloomfeld R. S. , Onken J. E.
Published: March 2003

Background : Azathioprine (AZA) and its active metabolite mercaptopurine (MP) are frequently used in the management of inflammatory bowel disease. Measurement of the AZA/MP metabolites, thioguanine (TG) and methylmercaptopurine (MMP), has been suggested as a means to optimize therapy with AZA/MP in inflammatory bowel disease.

Aim : To evaluate the results of initial AZA/MP metabolite panels sent by gastroenterologists during the first year of its widespread availability.

Methods : Initial AZA/MP metabolite panels sent by gastroenterologists to a single laboratory were reviewed and the metabolite panels were interpreted.

Results : Initial metabolite levels were reviewed for 9187 patients. Noncompliance was detected in 263 patients (3%) and under‐dosing in 4260 patients (46%). 534 patients (6%) had levels that were consistent with preferential metabolism via the TPMT pathway. The therapeutic goal was achieved in 2444 patients (27%) and an additional 552 patients (6%) had appropriate TG levels but potential hepatotoxicity. 936 patients (10%) had potential TPMT deficiency, and 58 patients (1%) had potential TPMT absence and were at risk for leukopenia. 140 patients (2%) had too high a dose.

Conclusions : Measurement of AZA/MP metabolites can be used by practising gastroenterologists to identify potential reasons for nonresponse to AZA or MP, and to identify patients at risk for certain drug‐related toxicities.
Risk factors for failure of Helicobacter pylori therapy — results of an individual data analysis of 2751 patients
Authors: Broutet N. , Tchamgoué S. , Pereira E. , Lamouliatte H. , Salamon R. , Mégraud F.
Published: March 2003

Aim : To study risk factors for failure of Helicobacter pylori eradication treatment.

Methods : Individual data from 2751 patients included in 11 multicentre clinical trials carried out in France and using a triple therapy, were gathered in a unique database. The 27 treatment regimens were regrouped into four categories.

Results : The global failure rate was 25.8%[95% CI: 24–27]. There was a difference in failure rate between duodenal ulcer patients and non‐ulcer dyspeptic patients, 21.9% and 33.7%, respectively (P < 10−6). In a random‐effect model, the risk factors identified for eradication failure in duodenal ulcer patients (n = 1400) were: to be a smoker, and to have received the group 4 treatment, while to receive a 10 day treatment vs. 7 days protected from failure. In non‐ulcer dyspeptic patients (n = 913), the group 2 treatment was associated with failure. In both groups, age over 60 was associated with successful H. pylori eradication. There were less strains resistant to clarithromycin in duodenal ulcer patients than in non‐ulcer dyspeptic patients. Clarithromycin resistance predicted failure almost perfectly.

Conclusion : Duodenal ulcer and non‐ulcer dyspeptic patients should be managed differently in medical practice and considered independently in eradication trials.
Is eradication sufficient to heal gastric ulcers in patients infected with Helicobacter pylori? A randomized, controlled, prospective study
Authors: Higuchi K. , Fujiwara Y. , Tominaga K. , Watanabe T. , Shiba M. , Nakamura S. , Oshitani N. , Matsumoto T. , Arakawa T.
Published: March 2003

Background : In Helicobacter pylori infection, the effect of short‐term triple therapy with proton pump inhibitor plus two antibiotics on gastric ulcer healing is not well known.

Aim : To compare 1‐week triple therapy with 8‐week proton pump inhibitor therapy on gastric ulcer healing in infected patients.

Patients and methods : We randomly assigned 120 patients with H. pylori and gastric ulcers to proton pump inhibitor plus amoxicillin and clarithromycin for 1 week (n = 61) or proton pump inhibitor alone for 8 weeks (n = 59), with endoscopic assessment of ulcer healing 8 weeks after the start of treatment.

Results : Triple therapy eradicated H. pylori in 51 patients [intention‐to‐treat, 84%; 95% confidence interval (CI), 75–93%]. At 8 weeks, gastric ulcers were healed in 30 patients given triple therapy (49%; 95% CI, 37–62%) and in 49 patients given proton pump inhibitor (83%; 95% CI, 73–93%, P < 0.001). Healing rates in the triple therapy and proton pump inhibitor‐only groups were 89% and 100%, respectively, for ulcers of < 1.0 cm in diameter, 54% and 77% for ulcers of 1.0 to < 1.5 cm in diameter, and 5% and 77% (P < 0.001) for ulcers of ≥ 1.5 cm in diameter.

Conclusions : One‐week triple therapy healed most ulcers of < 1.0 cm, but not ulcers of ≥ 1.5 cm. Short‐term therapy is effective for gastric ulcers of < 1.0 cm, but, for larger ulcers, follow‐up therapy to suppress acid is needed.
Double‐blind, randomized, placebo‐controlled study of nitazoxanide in the treatment of fascioliasis in adults and children from northern Peru
Authors: Favennec L. , Jave Ortiz J. , Gargala G. , Lopez Chegne N. , Ayoub A. , Rossignol J. F.
Published: March 2003

Background : Human fascioliasis is a significant world‐wide health problem, and massive or repeated infections by Fasciola hepatica can lead to considerable morbidity.

Aim : To evaluate the safety and efficacy of nitazoxanide, when compared with placebo, in the treatment of fascioliasis in adults and children from northern Peru.

Methods : A double‐blind, placebo‐controlled study was carried out in 50 adults and 50 children infected with F. hepatica. The diagnosis of infection was based on the presence of F. hepatica eggs in one stool sample obtained before inclusion in the study. Patients were randomized to receive treatment with either a 7‐day course of nitazoxanide (100 mg b.d., age range 2–3 years; 200 mg b.d., age range 4–11 years; 500 mg b.d., age > 12 years) or matching placebo. Three post‐treatment stool examinations were carried out between 30 and 90 days after initiation of treatment.

Results : The parasite was eliminated in 18 of 30 (60%) adults completing the study who received nitazoxanide vs. one of eight adults in the placebo group (P = 0.042), and similarly in 14 of 35 (40%) children completing the treatment vs. none of eight in the placebo group (P = 0.038). Only mild, transient adverse events were reported.

Conclusions : A 7‐day course of nitazoxanide was effective in adults and children in the treatment of F. hepatica, when compared with placebo.
Sandostatin LAR (long‐acting octreotide acetate) for malignant carcinoid syndrome: a 3‐year experience
Authors: Garland J. , Buscombe J. R. , Bouvier C. , Bouloux P. , Chapman M. H. , Chow A. C. , Reynolds N. , Caplin M. E.
Published: March 2003

Background : Somatostatin analogues are the best therapy for controlling the symptoms of malignant carcinoid syndrome. Octreotide acetate given as subcutaneous injection up to three times daily, intramuscular Lanreotide injection given once per 1–2 weeks and monthly intramuscular Sandostatin LAR have demonstrated similar efficacy in short‐term studies.

Aim : To assess the long‐term effect of Sandostatin LAR on the management of patients with malignant carcinoid syndrome.

Methods : This was a 3‐year retrospective study. Twenty‐seven patients were assessed with a median follow‐up of 23 months. Thirteen patients were switched from subcutaneous octreotide and 14 patients were octreotide naive. All patients showed avid uptake on indium‐111 octreotide imaging.

Results : Ten of the 13 patients previously on subcutaneous octreotide and 13 of the 14 patients who were octreotide naive had good symptom control on Sandostatin LAR. Over the period of follow‐up, many patients showed progression of their tumour and required additional therapies. Patients expressed a preference for monthly intramuscular Sandostatin LAR as opposed to daily subcutaneous injections of octreotide. Although Sandostatin LAR was difficult to administer in certain instances, overall it was well tolerated.

Conclusions : Sandostatin LAR provides good long‐term symptomatic control in patients with malignant carcinoid syndrome; it is well tolerated and patients expressed improved satisfaction in their management.
Helicobacter DNA in bile: correlation with hepato‐biliary diseases
Authors: Fallone C. A. , Tran S. , Semret M. , Discepola F. , Behr M. , Barkun A. N.
Published: March 2003

Background : Helicobacter has been identified in isolated cases of hepato‐biliary diseases, but its role in the pathogenesis of these conditions remains unclear.

Aim : To determine whether Helicobacter could be detected in bile obtained at endoscopic retrograde cholangiopancreatography, and to evaluate the prevalence of this infection in patients with hepato‐biliary diseases.

Methods : Bile was collected from 125 patients with various hepato‐biliary diseases undergoing endoscopic retrograde cholangiopancreatography. Among them, 75 were diagnosed with biliary stones, 15 with pancreatico‐biliary malignancies and four with primary sclerosing cholangitis. The detection of Helicobacter in DNA extracted from these bile samples was performed using Helicobacter genus‐specific primers (capable of detecting 100–1000 organisms/mL).

Results : Helicobacter was detected in all positive controls. Only three samples had polymerase chain reaction inhibitors. All remaining bile samples (122 patients with hepato‐biliary diseases) were negative for Helicobacter DNA.

Conclusions : Helicobacter can be detected in bile samples using polymerase chain reaction. This infection, however, was not present in any of our patients diagnosed with gallstones or hepato‐biliary malignancies, raising doubt as to the possible association between Helicobacter and these entities. Given the low sample size of patients with primary sclerosing cholangitis, more studies are required to determine whether an association exists with this condition.
Second harmonic imaging improves trans‐abdominal ultrasound detection of biliary sludge in ‘idiopathic’ pancreatitis
Authors: Ierardi E. , Muscatiello N. , Nacchiero M. , Gentile M. , Margiotta M. , Marangi S. , De Francesco V. , Francavilla R. , Barone M. , Faleo D. , Panella C. , Francavilla A. , Cuomo R.
Published: March 2003

Background : Recently, biliary sludge has been strongly correlated with ‘idiopathic pancreatitis’. It is often diagnosed by trans‐abdominal ultrasonography, despite the low sensitivity of this investigation. New scanners, using second harmonic imaging, may improve the quality of the echographic picture.

Aim : To verify the impact of this methodology on the detection of biliary sludge in patients with ‘idiopathic’ pancreatitis.

Methods : Fifty patients with ‘idiopathic’ pancreatitis observed over a 18‐month period entered the study. Exclusion criteria were gall‐bladder stones, polyps, clinical conditions related to biliary sludge development and haemolytic disorders. Patients were assessed blind by two operators using either conventional ultrasonography or second harmonic imaging. The parameters of diagnostic quality of both examinations were evaluated using, as the gold standard, microscopic examination of the gall‐bladder content collected at endoscopy after cholecystokinin infusion.

Results : An improvement in sensitivity, specificity, efficiency and negative predictive value was obtained by second harmonic imaging compared with conventional ultrasonography.

Conclusions : Second harmonic imaging, in our experience, is a reliable non‐invasive tool for the diagnosis and follow‐up of biliary sludge in the course of ‘idiopathic’ pancreatitis.
Two mesalazine regimens in the prevention of the post‐operative recurrence of Crohn's disease: a pragmatic, double‐blind, randomized controlled trial
Authors: Caprilli R. , Cottone M. , Tonelli F. , Sturniolo G. , Castiglione F. , Annese V. , Papi C. , Viscido A. , Cammà C. , Corrao G. , Latella G.
Published: March 2003

Background : The role of mesalazine in preventing the clinical recurrence of Crohn's disease after surgery has been shown in a meta‐analysis of all published studies. No clear relationship, however, has been shown between dosage and response.

Aim : To evaluate whether 4.0 g/day of mesalazine may offer therapeutic advantages over 2.4 g/day in the prevention of both endoscopic and clinical post‐operative recurrence of Crohn's disease.

Methods : The study was a double‐blind, randomized, multi‐centre, prospective, controlled clinical trial. Two hundred and six patients, submitted to first or second intestinal resection for Crohn's disease limited to the terminal ileum, with or without involvement of the caecum/ascending colon, were enrolled. Of these, 101 were randomly allocated to receive 4.0 g/day of mesalazine (Asacol, Giuliani SpA, Milan, Italy) and 105 to receive 2.4 g/day, starting 2 weeks after surgery. The primary outcome was endoscopic recurrence, at 12 months after surgery. Three different degrees of endoscopic recurrence were evaluated (endoscopic scores: > 0, > 1 and > 2). The secondary outcome was clinical recurrence, defined as a Crohn's disease activity index of more than 150 points or an increase in the Crohn's disease activity index of 100 points or more. For statistical analysis, chi‐square, Wilcoxon and Cox regression model tests were used, when appropriate.

Results : Eighty‐four patients in the 4.0 g/day group and 81 patients in the 2.4 g/day group were evaluable by endoscopy. Endoscopic recurrence of > 0 was significantly higher in the 2.4 g/day group than in the 4.0 g/day group (62% vs. 46%; P < 0.04). No difference was observed between the two groups with regard to the other two endoscopic outcomes (> 1 and > 2) or clinical recurrence.

Conclusions : A 4.0 g/day regimen of mesalazine does not offer a clinically significant advantage over a 2.4 g/day regimen in the prevention of post‐operative endoscopic and clinical recurrence of Crohn's disease at 1 year of follow‐up.
Use of the Combitube for airway maintenance during percutaneous dilatational tracheostomy
Authors: Mallick A. , Quinn A. C. , Bodenham A. R. , Vucevic M.
Published: March 2003

The Combitube airway allows short‐term ventilation during cardiopulmonary resuscitation and can be useful in the management of the difficult airway. In a prospective observational study we assessed its use during percutaneous dilatational tracheostomy (PDT). Twenty‐one intensive care patients scheduled for elective PDT had their tracheal tube replaced by a Combitube airway retaining the same ventilator settings. Arterial blood gases, airway pressures, SpO2 and end‐tidal CO2 were measured as were the transmural pressures exerted by the Combitube cuffs. Combitube placement was successful in 20 of 21 patients although adequate ventilation was possible in only 17 (85%). There was no significant change in PaO2, SpO2, end‐tidal CO2, PaCO2 or mean airway pressure during Combitube ventilation. A high mean (SD) transmural pressure of 14.7 (5) kPa was exerted by the distal cuff. The Combitube provided a satisfactory alternative airway to the tracheal tube during performance of PDT in 85% of our patients. Potential problems associated with its use in intensive care patients are outlined.
Comparison of rocuronium and suxamethonium for use during rapid sequence induction of anaesthesia
Authors: McCourt K. C. , Salmela L. , Mirakhur R. K. , Carroll M. , Mäkinen M.‐T. , Kansanaho M. , Kerr C. , Roest G. J. , Olkkola K. T.
Published: March 2003

This study was designed to compare the tracheal intubating conditions during a rapid sequence induction of anaesthesia using rocuronium 0.6 (n = 61) or 1.0 mg.kg−1 (n = 130) or suxamethonium 1.0 mg.kg−1 (n = 127) as the neuromuscular blocking drugs. Anaesthesia was induced with fentanyl 1–2 μg.kg−1 and thiopentone 5 mg.kg−1 (median dose) and intubating conditions were assessed 60 s after the administration of the neuromuscular blocking drug by an observer unaware of which drug had been given. Intubating conditions were graded on a three‐point scale as excellent, good or poor, the first two being considered clinically acceptable. The study was carried out in two parts. At the end of the first part a comparison between the two doses of rocuronium was carried out when at least 50 patients had been enrolled in each group. The results showed the intubating conditions to be significantly superior with the 1.0 mg.kg−1 dose of rocuronium (p < 0.01). Final comparison between the 1.0 mg.kg−1 doses of rocuronium and suxamethonium showed no significant difference in the incidence of acceptable intubations (96 and 97%, respectively). The incidence of excellent grade of intubations was, however, significantly higher with suxamethonium (80% vs. 65%; p = 0.02). It is concluded that rocuronium 1.0 mg.kg−1 can be used as an alternative to suxamethonium 1.0 mg.kg−1 as part of a rapid sequence induction provided there is no anticipated difficulty in intubation. The clinical duration of this dose of rocuronium is, however, 50–60 min.