bluuebunny/crossref_metadata_2025 huggingface dataset:
Helicobacter pylori testing in the primary care setting: which diagnostic test should be used?
Authors: Weijnen C. F. , De Wit N. J. , Numans M. E. , Kuipers E. J. , Hoes A. W. , Verheij T. J. M.
Published: March 2003

Aim

: To identify the most accurate and efficient test for diagnosing Helicobacter pylori infection in primary care patients.

Study design

: A whole blood test, an ELISA, and carbon13 urea breath test (CUBT) were evaluated in a primary care setting and validated against two different gold standards that used gastric biopsies.

Population

: Primary care patients who had dyspeptic complaints lasting at least 2 weeks and were referred for endoscopy.

Outcomes measured

: Positive and negative predictive values, sensitivity and specificity were determined for all three noninvasive H. pylori tests.

Results

: Data from the three non‐invasive H. pylori tests were available for 136 primary care dyspeptic patients referred for endoscopy. They were compared with data from the gold standards. The positive predictive value of the whole blood test was in the range 71–75%, the ELISA 83–86%, and the CUBT 88–92%, while the negative predictive values were in the ranges 72–77%, 96–100%, and 95–98%, respectively. The sensitivity of the whole blood test was in the range 36–42%, the ELISA 93–100%, and the CUBT 92–97%, while the specificities were in the ranges 92–93%, 90–91% and 93–95%, respectively. The positive predictive value of the ELISA dropped significantly at lower H. pylori infection rates.

Discussion

: Both the ELISA and CUBT are effective in the primary care setting, while the whole blood tests produces inferior results. ELISA might, however, be less suitable for detecting H. pylori infection in a population with a low rate of infection.
Synergy between low‐dose ranitidine and antacid in decreasing gastric and oesophageal acidity and relieving meal‐induced heartburn
Authors: Robinson M. , Rodriguez‐Stanley S. , Ciociola A. A. , Filinto J. , Zubaidi S. , Miner P. B. , Gardner J. D.
Published: March 2003

Background:

The pathophysiology of recurrent postprandial heartburn and the basis for the effectiveness of antacids or low doses of histamine H2‐receptor antagonists have not been well studied.

Methods:

The selected subjects (n=26) had heartburn more than four times a week for at least 2 months, which was responsive to antacids. Gastric pH and oesophageal pH were measured for 1 h before, during, and 4.5 h after ingestion of a meal over 0.5 h. Heartburn severity was assessed at 15‐min intervals beginning at the end of the meal. Each subject randomly received placebo, 75 mg ranitidine, 420 mg calcium carbonate, and ranitidine plus calcium carbonate. Values for pH were converted to acid concentration (mM) and integrated acidity was calculated from the cumulative, time‐weighted means of the acid concentrations for every second of the postprandial recording period.

Results:

There was a close temporal relationship between heartburn and oesophageal acidity. Most oesophageal acid exposure occurred over a 90‐min period that began approximately 45 min after the end of the meal. During this period the gastric acid concentration was less than 5% of maximal. Ranitidine significantly decreased gastric but not oesophageal acidity, whilst antacid significantly decreased oesophageal but not gastric acidity. Ranitidine plus antacid significantly decreased both gastric and oesophageal acidity. Antacid alone and ranitidine plus antacid significantly decreased heartburn severity.

Conclusions:

Determining integrated gastric and oesophageal acidity provides novel information regarding the pathophysiology of meal‐induced heartburn as well as the actions of low‐dose ranitidine and antacid. For subjects with meal‐induced heartburn, treatment with low‐dose ranitidine plus antacid is particularly effective in decreasing gastric and oesophageal acidity as well as heartburn severity.
Glicentin, an active enteroglucagon, has a significant trophic role on the small intestine but not on the colon in the rat
Authors: Sasaki M. , Fitzgerald A. J. , Mandir N. , Sasaki K. , Wright N. A. , Goodlad R. A.
Published: March 2003

Background:

Many experiments have indicated that the gut glucagons (enteroglucagons) are associated with cell proliferation in the small intestine. However, recent studies have failed to show trophic effects of glicentin (enteroglucagon) on the intestine.

Aims:

To examine the effects of glicentin on intestinal proliferation in vivo in the rat.

Methods:

Rats were established on total parenteral nutrition for 6 days. Four experimental groups were given daily doses of 1, 4, 20 and 80 μg/rat of glicentin via the jugular vein. Rats fed by total parenteral nutrition and rats fed chow ad libitum were used as controls. Tissues taken from the duodenum, jejunum, ileum and colon were fixed in Carnoy’s fluid and microdissected to determine the metaphase arrest scores and crypt fission ratios.

Results:

The mean metaphase arrest scores per crypt of the small intestine were significantly increased in the rats given 4, 20 and 80 μg of glicentin. These responses were dose‐dependent, and were most prominent in the ileum. Crypt fission of the ileum was significantly decreased in the 20 and 80 μg glicentin groups. Glicentin had no effects on proliferation or fission in the colon.

Conclusions:

Glicentin is trophic to the rat small intestine, but not the colon.
Antiretroviral hepatotoxicity in human immunodeficiency virus‐infected patients
Authors: Hernandez L. V. , Gilson I. , Jacobson J. , Affi A. , Puetz T. R. , Dindzans V. J.
Published: March 2003

Background:

Drug hepatotoxicity is a potentially serious adverse reaction of antiretroviral therapy in human immunodeficiency virus‐infected patients. The impact of this problem in the routine treatment of patients with human immunodeficiency virus infection is poorly defined.

Objectives:

Our aim was to determine what clinical features are associated with hepatotoxicity in human immunodeficiency virus‐infected patients receiving antiretroviral therapy.

Methods:

Consecutive patients in a primary care‐based human immunodeficiency virus clinic were evaluated for hepatotoxicity. Clinic records were used to obtain patient characteristics, as well as independent variables including CD4+ count, coexisting hepatitis C and current alcohol use.

Results:

Sixty‐five patients taking antiretroviral therapy were evaluated. Twenty‐four were identified to have antiretroviral hepatotoxicity. An age over 40 years (P=0.019), an absolute CD4+ count of less than 310 cells/mL (P=0.002) and coexisting hepatitis C infection (P=0.035) were significantly associated with hepatotoxicity. Patients older than 40 years had a sevenfold increased risk (risk ratio, 6.9; 95% confidence interval, 1.7–27.3) and those with an absolute CD4+ count of less than 310 cells/mL had a tenfold increased risk (risk ratio, 10.2; 95% confidence interval, 2.5–41.9) for antiretroviral hepatotoxicity, in comparison with those who were younger or who had a greater absolute CD4+ count. Of the eight patients documented to have coexisting hepatitis C infection, six (75%) were in the antiretroviral hepatotoxicity group.

Conclusions:

An age older than 40 years and an absolute CD4+ count of less than 310 cells/mL were significantly associated with antiretroviral‐induced hepatotoxicity. The majority of our patients with chronic hepatitis C had hepatotoxicity from antiretroviral therapy.
Tegaserod, a 5‐HT4 receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation
Authors: Müller‐Lissner S. A. , Fumagalli I. , Bardhan K. D. , Pace F. , Pecher E. , Nault B. , Rüegg P.
Published: March 2003

Aim:

To investigate the efficacy and safety of tegaserod, a novel 5‐HT4 receptor partial agonist, in a randomized, double‐blind, placebo‐controlled, 12‐week treatment, multicentre study.

Methods:

Eight hundred and eighty‐one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks.

Results:

Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self‐administered questionnaire. At end‐point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of tegaserod was noted as early as week 1, and was sustained over the 12‐week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with tegaserod than placebo.

Conclusions:

Based upon the results of this study, tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated.
A randomized comparison of four omeprazole‐based triple therapy regimens for the eradication of Helicobacter pylori in patients with non‐ulcer dyspepsia
Authors: Laurent J. , Mégraud F. , Fléjou J. F. , Caekaert A. , Barthélemy P.
Published: March 2003

Background:

Helicobacter pylori eradication rates in France after therapy with omeprazole, amoxicillin and clarithromycin are among the lowest in Europe. This study evaluated alternative eradication regimens.

Methods:

Helicobacter pylori‐positive patients (n=323) with non‐ulcer dyspepsia were randomized to receive one of four 1‐week regimens consisting of omeprazole, 20 mg b.d., plus either: amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d. (OAC); bacampicillin, 1200 mg b.d., and clarithromycin, 500 mg b.d. (OBC); clarithromycin, 250 mg b.d., and metronidazole, 500 mg b.d. (OCM); or amoxicillin, 1000 mg b.d, and azithromycin, 500 mg on day 1 and 250 mg on days 2–5 (OAAz). Eradication was confirmed by urea breath test 4–6 weeks after treatment. Susceptibility testing was performed in the case of eradication failure.

Results:

The eradication rate with OAAz was 38% (95% CI, 25.6–49.4) on intention‐to‐treat analysis, which was lower (P < 0.05) than with the other regimens [OCM, 61% (50.0–72.8); OBC, 65% (54.0–76.5); OAC, 72% (61.8–81.8)]. Of the strains isolated following treatment failure with OAC, OBC or OCM, 84% were clarithromycin resistant.

Conclusions:

OAC remains the reference treatment for H. pylori eradication in France, although bacampicillin offers a useful alternative to amoxicillin. Susceptibility testing should be considered after unsuccessful eradication therapy.
Pharmacokinetics and biochemical effects of hepapoietin in patients with chronic liver disease
Authors: Marino G. , Rustgi V. K. , Salzberg G. , Johnson L. B. , Kuo P. C. , Plotkin J. S. , Flockhart D. A.
Published: March 2003

Background:

Hepapoietin is a naturally occurring cytokine that promotes hepatocyte growth. Animal studies have suggested that hepapoietin and hepatocyte growth factor have a potential role in the prevention and management of liver diseases. However, human studies have been lacking.

Aim:

To evaluate the safety and pharmacokinetics of single escalating doses of hepapoietin in patients with chronic liver disease.

Methods:

An open‐label, single escalating dose trial with five different doses of hepapoietin (1, 3, 10, 30 and 100 mg) was performed. Adults with chronic, compensated, non‐viral liver disease were included. Liver function tests were obtained before dosing, 24 h after hepapoietin administration and on days 4, 7, 30 and 45. All patients were followed for 45 days.

Results:

Twenty‐five subjects received hepapoietin, with five subjects each at 1, 3, 10, 30 and 100 mg of hepapoietin. Significant decreases occurred in total bilirubin, ammonia, partial thromboplastin time and cholesterol levels overall, and both high‐density and low‐density lipoprotein cholesterol showed a downward trend. An increase in albumin was observed at the 30 mg dose level. Slight decreases in haemoglobin and red blood cell levels were observed at day 4, but returned to normal levels immediately thereafter. Child–Pugh scores from day 0 to day 7 were improved in 24%, stable in 64% and worse in 12% of patients. Hepatic encephalopathy displayed changes from day 0 to day 45 with improvement in 16%, no change in 80% and worsening in 4%.

Conclusions:

Hepapoietin in doses up to 100 mg is safe for use in humans. Potential benefits are suggested by significant decreases in bilirubin, ammonia, partial thromboplastin time and cholesterol levels and an increase in albumin. Further studies with multiple dosing regimens are needed to identify the clinical utility of hepapoietin in the management of chronic liver disease.
Dose‐related effects of motilin on proximal gastrointestinal motility
Authors: Kamerling I. M. C. , Van Haarst A. D. , Burggraaf J. , Schoemaker H. C. , Biemond I. , Jones R. , Cohen A. F. , Masclee A. A. M.
Published: March 2003

Aim:

To assess non‐invasively the dose–response relations for the effects of exogenous motilin on antrum contraction frequency, gall‐bladder volume and gastric myoelectrical activity.

Methods:

In a double‐blind, randomized, placebo‐controlled, five‐way crossover study, 10 fasted healthy volunteers were infused intravenously with synthetic human motilin (0.5, 1, 2 and 4 pmol.min/kg) or placebo for 60 min. Gall‐bladder volume and antrum contractions were assessed by ultrasonography and gastric myoelectrical activity by electrogastrography. Motilin concentrations were measured using a radioimmunoassay.

Results:

Baseline plasma motilin levels (60 pmol/L) were similar for all treatments. Motilin levels increased upon the start of infusion and rapidly returned to baseline after cessation of the infusion. At motilin doses of 2 and 4 pmol.min/kg, the antrum contraction frequency was significantly augmented, with maximum differences of two contractions per 2‐min interval compared to placebo, while no changes in gastric myoelectrical activity were observed. Changes in gall‐bladder volume were not significantly different for any of the motilin doses compared to placebo.

Conclusions:

Motilin increased antrum contraction frequency, whereas no effect on gastric myoelectrical activity was observed. Antrum contraction frequency appears to be a useful biomarker for motilin efficacy, and motilin doses of 2 and 4 pmol.min/kg were equally effective.
Treatment with a proton pump inhibitor promotes corpus gastritis in patients with Helicobacter pylori‐infected antrum‐predominant gastritis
Authors: Suzuki M. , Suzuki H. , Kitahora T. , Miyazawa M. , Nagahashi S. , Suzuki K. , Ishii H.
Published: March 2003

Background:

Proton pump inhibitors have been reported to modify the level of Helicobacter pylori gastritis.

Aim:

To quantitatively investigate the effect of a proton pump inhibitor on the mucosal neutrophil reaction.

Methods:

Forty‐six H. pylori‐infected patients (17 duodenal ulcer, 29 gastric ulcer) were enrolled. During endoscopic examination, biopsy samples were obtained from the antrum and the corpus. The tissue content of neutrophil myeloperoxidase was measured by enzyme‐linked immunoabsorbent assay, and H. pylori infection was histologically assessed. A proton pump inhibitor was administered orally for 8 weeks.

Results:

In the patients as a whole, antral myeloperoxidase decreased significantly after proton pump inhibitor treatment, but corpus myeloperoxidase remained largely unchanged. In duodenal ulcer patients, myeloperoxidase significantly decreased in the antrum, but increased in the corpus. In gastric ulcer patients, a significant reduction was observed in antral myeloperoxidase, but corpus myeloperoxidase remained unchanged. In the antral myeloperoxidase > corpus myeloperoxidase subgroup (n=24), antral myeloperoxidase significantly decreased, whereas corpus myeloperoxidase increased. No changes were observed at either site in the corpus myeloperoxidase > antral myeloperoxidase subgroup. Histology showed that the antral bacterial load of H. pylori decreased in all subgroups, but that it was mostly unchanged in the corpus.

Conclusions:

Proton pump inhibitor treatment stimulated the neutrophil reaction in the corpus mucosa of duodenal ulcer patients and of patients in whom antral neutrophil accumulation was more predominant than that of the corpus. This phenomenon may not be caused by increased bacterial density.
Expression of cyclooxygenase‐2 in chronic hepatitis B and the effects of anti‐viral therapy
Authors: Cheng A. S. L. , Chan H. L. Y. , Leung N. W. Y. , Liew C. T. , To K. F. , Lai P. B. S. , Sung J. J. Y.
Published: March 2003

Backgound:

Cyclooxygenase‐2 may play a role in the development of hepatocellular carcinoma, but the relationship between cyclooxygenase‐2 and chronic hepatitis B is unknown.

Aim:

To investigate the expression and cellular localization of cyclooxygenase‐2 in chronic hepatitis B patients and the effects of anti‐viral therapy.

Methods:

Using immunohistochemistry, in situ hybridization, Western blot and reverse transcription polymerase chain reaction, protein and messenger RNA expression and cellular localization of cyclooxygenase‐2 in 35 chronic hepatitis B patients were assessed. Fourteen histologically normal and non‐viral‐infected livers were used as controls. The cyclooxygenase‐2 immunoreactivities of paired liver biopsies from 12 patients receiving anti‐viral therapy were compared.

Results:

Immunohistochemistry and in situ hybridization revealed that cyclooxygenase‐2 expression was confined to hepatocytes. Patients with chronic hepatitis B had significantly higher cyclooxygenase‐2 expression compared with controls. The cyclooxygenase‐2 expression of hepatitis B e antigen‐positive and ‐negative chronic hepatitis B patients was not significantly different, although the necro‐inflammatory activity of the latter group was significantly lower. Over‐expression of cyclooxygenase‐2 in patients with chronic hepatitis B was further confirmed by Western blot and reverse transcription polymerase chain reaction. Twelve hepatitis B e antigen‐positive chronic hepatitis B patients received anti‐viral therapy: lamivudine in seven and interferon in five. Despite hepatitis B e antigen seroconversion, disappearance of hepatitis B virus DNA in serum, normalization of liver enzymes and a significant reduction in necro‐inflammatory activity in all 12 patients, no significant change in cyclooxygenase‐2 expression was found.

Conclusions:

Chronic hepatitis B is associated with elevated cyclooxygenase‐2 levels in hepatocytes, and the over‐expression of this enzyme does not reflect inflammatory activity. Up‐regulation of cyclooxygenase‐2 persists after successful anti‐viral therapy.
Single subject trials as a research instrument in gastrointestinal pharmacology
Authors: Madsen L. G. , Bytzer P.
Published: March 2003

The single subject trial is a randomized controlled trial carried out in the individual patient, and the result obtained is specific to the individual patient and the drug being investigated. This type of trial offers a supplement to traditional parallel group trials, especially in patients with heterogeneous disorders, often characterized by varying treatment responses and/or high placebo response rates. Pooled results from several individual single subject trials could extend the conclusions beyond the individual patient, and help to characterize a subset of responders to a specific treatment or clarify the heterogeneity of the disease.

The basic principles of the different single subject trial designs are described. Advantages and limitations are reviewed with a special focus on published trials in functional gastrointestinal disorders.

The single subject trial may be a valuable supplement to traditional drug treatment trials, either used as isolated trials in individual patients to determine optimal therapy, or in groups of patients to identify those with a uniform response to treatment. However, the lack of validation and reliability studies limits the value of the single subject trials presented so far.
Effect of Helicobacter pylori eradication on duodenal ulcer scar in patients with no clinical history of duodenal ulcer
Authors: Kim J. S. , Kim S. G. , Choi I. J. , Park M. J. , Kim B. G. , Jung H. C. , Song I. S.
Published: March 2003

Background:

Helicobacter pylori eradication has become the standard treatment for duodenal ulcer. However, there is no relevant evidence for antibacterial treatment of the white scar stage of duodenal ulcer (duodenal ulcer scar) in patients with no past history of duodenal ulcer.

Aim:

To investigate whether H. pylori eradication could decrease duodenal ulcer recurrence in patients with duodenal ulcer scar and no past history of duodenal ulcer.

Patients and methods:

We prospectively enrolled 66 patients with duodenal ulcer scar: 53 were H. pylori‐positive and 13 were H. pylori‐negative. H. pylori‐positive patients were randomly assigned into two groups (two‐to‐one allocation): 36 patients were assigned to the treatment group and 17 to the follow‐up group. Thirteen H. pylori‐negative patients were followed up according to the study protocol. Follow‐up endoscopy was performed to evaluate ulcer scar changes and H. pylori status 6 weeks after anti‐H. pylori treatment and then every 6 months for up to 30 months.

Results:

Active duodenal ulcer recurrence was identified in seven of 23 H. pylori‐positive/non‐cured patients (30%). There was no duodenal ulcer recurrence in 43 H. pylori‐negative/cured patients (0%), which was significantly different in terms of duodenal ulcer recurrence (P=0.001).

Conclusions:

H. pylori eradication is effective at preventing active duodenal ulcer recurrence in patients with duodenal ulcer scar and no past history of duodenal ulcer.
Influence of Helicobacter pylori infection and eradication on blood lipids and fibrinogen
Authors: Elizalde J. I. , Piqué J. M. , Moreno V. , Morillas J. D. , Elizalde I. , Bujanda L. , De Argila C. M. , Cosme A. , Castiella A. , Ros E. ,   (FOR THE GROUP OF STUDY OF OESOPHAGEAL GASTRIC DISEASES FROM THE SPANISH GASTROENTEROLOGICAL ASSOCIATION)
Published: March 2003

Background:

An association between Helicobacter pylori infection and heart disease has been suggested. A potential mechanism may be inflammation‐induced atherogenic changes of lipoproteins, but epidemiological studies have provided conflicting results.

Methods:

In a prospective multicentre study, 830 patients submitted for endoscopy and H. pylori testing were evaluated. Of the 686 H. pylori‐positive patients, 487 received and 199 did not receive eradication treatment. Serum lipids and plasma fibrinogen were measured at baseline in all patients and 3 months later in those initially positive for H. pylori.

Results:

H. pylori had no influence on baseline lipid or fibrinogen levels. Increases in high‐density lipoprotein cholesterol were observed in 368 patients who received eradication treatment and in 193 untreated patients: 0.06 mmol/L (P=0.000) and 0.07 mmol/L (P=0.009), respectively. Similar minor increases in total cholesterol and triglycerides occurred in both groups. Lipid changes were related to symptom relief and a reduction in smoking. Eradication therapy was associated with a minor decrease in plasma fibrinogen irrespective of the resolution of infection.

Conclusions:

H. pylori has no influence on blood lipids or fibrinogen. Both the eradication of infection and symptomatic treatment without eradication are associated with minor lipid changes related to symptom relief and lifestyle modifications. Thus, the inflammatory changes associated with H. pylori are unlikely to affect lipoprotein or fibrinogen metabolism.
A randomized, double‐blind, comparative study of standard‐dose rabeprazole and high‐dose omeprazole in gastro‐oesophageal reflux disease
Authors: Holtmann G. , Bytzer P. , Metz M. , Loeffler V. , Blum A. L.
Published: March 2003

Background:

Rabeprazole has a faster onset of antisecretory action than omeprazole, and it is of interest to determine whether this translates into faster symptom relief in patients with gastro‐oesophageal reflux disease.

Aims:

To assess the relief from heartburn after 3 days of treatment with standard‐dose rabeprazole or high‐dose omeprazole (primary end‐point). Secondary end‐points included the decrease in score for other symptoms of gastro‐oesophageal reflux disease, healing rates and quantification of antacid use.

Methods:

Patients with endoscopically confirmed erosive oesophagitis were randomized to receive 4 weeks of double‐blind treatment with rabeprazole (20 mg) or omeprazole (40 mg). Patients who were not healed after 4 weeks received a further 4 weeks of treatment.

Results:

Two hundred and seventy‐four patients were screened, 251 patients were randomized and 230 patients completed the trial. The numbers of patients with relief from heartburn on day 4 were similar in the two groups (84% for rabeprazole; 95% confidence interval, 76–90%; 83% for omeprazole; 95% confidence interval, 75–89%). There were no significant differences between the treatments in the relief from other gastro‐oesophageal reflux disease symptoms or in healing rates. The number of reports of severe heartburn during the first 3 days was higher in the omeprazole group (daytime heartburn: 4.7% for rabeprazole vs. 10.3% for omeprazole, P=0.005; night‐time heartburn: 4.7% for rabeprazole vs. 9.8% for omeprazole, P=0.01; statistical comparisons defined post hoc).

Conclusions:

Standard‐dose rabeprazole was as effective as high‐dose omeprazole in relieving symptoms by day 4 of treatment and in healing oesophageal lesions, but had a faster onset of action in patients with severe heartburn. This suggests that the improved pharmacological properties of rabeprazole translate into a clinically relevant advantage.
Effectiveness of two quadruple, tetracycline‐ or clarithromycin‐containing, second‐line, Helicobacter pylori eradication therapies
Authors: Georgopoulos S. D. , Ladas S. D. , Karatapanis S. , Triantafyllou K. , Spiliadi C. , Mentis A. , Artikis V. , Raptis S. A.
Published: March 2003

Background:

There are no guidelines on second‐line therapies for Helicobacter pylori eradication failures of omeprazole–clarithromycin–amoxicillin triple therapy.

Aim:

To compare the efficacy of two second‐line therapies for persistent H. pylori infection.

Methods:

Over a 6‐year period, patients with persistent H. pylori infection following omeprazole–clarithromycin–amoxicillin eradication therapy were randomized to receive omeprazole, 20 mg twice daily, bismuth, 120 mg four times daily, metronidazole, 500 mg twice daily, and either tetracycline, 500 mg four times daily, or clarithromycin, 500 mg twice daily, given for 7 days. Before therapy, patients underwent endoscopy with biopsies for histology, culture and antibiotic susceptibility tests. H. pylori infection was confirmed by histology.

Results:

Of the 95 randomized patients, 88 (93%) completed the study. Age, sex, smoking, ulcer/non‐ulcer dyspepsia ratio and antibiotic resistance were not significantly different between the treatment groups. On intention‐to‐treat analysis, eradication was achieved in 41 of the 49 patients (84%; 95% confidence interval, 70.4–92.7%) and 27 of the 46 patients (59%; 95% confidence interval, 43.3–73.0%) of the tetracycline‐ and clarithromycin‐containing groups, respectively (P=0.007). On multivariate regression analysis, the sensitivity of H. pylori to metronidazole had a likelihood ratio of 5.2 (P=0.022), followed by the type of quadruple therapy (likelihood ratio, 4.4; P=0.036).

Conclusions:

Tetracycline‐containing quadruple rescue therapy is highly effective in treating H. pylori eradication failures of the omeprazole–amoxicillin–clarithromycin regimen.
The efficacy of methotrexate for maintaining remission in inflammatory bowel disease
Authors: Fraser A. G. , Morton D. , McGovern D. , Travis S. , Jewell D. P.
Published: March 2003

Background:

The management of patients with inflammatory bowel disease who are resistant to or intolerant of azathioprine remains a challenge. Low‐dose methotrexate has been shown to be effective in inducing remission in Crohn's disease.

Aim:

This review was conducted because there are limited long‐term follow‐up data during and after stopping treatment. There are also limited data on the use of methotrexate in ulcerative colitis.

Methods:

The study was a retrospective review of clinical notes. Remission was defined as minimal bowel symptoms without the need for oral steroids for 3 months. Relapse was defined as bowel symptoms that required steroid treatment or surgery.

Results:

Seventy patients were reviewed; 48 had Crohn's disease and 22 had ulcerative colitis. The mean duration of treatment was 17.1 months; the mean maintenance dose was 20 mg weekly. Remission was achieved in 34 of 55 patients who completed more than 3 months of treatment (62%). Life‐table analysis showed that the chances of remaining in remission at 12, 24 and 36 months (if treatment was continued) were 90%, 73% and 51%, respectively. The chances of remaining in remission after stopping treatment at 6, 12 and 18 months were 42%, 21% and 16%, respectively. The dose of methotrexate (mg/kg) was associated with the induction of remission (P=0.02). Treatment was equally effective for Crohn's disease and ulcerative colitis.

Conclusions:

Maintenance methotrexate treatment gives acceptable remission rates for treatment periods up to 3 years. After stopping treatment, relapse is frequent and occurs early (usually within 1 year).
An evaluation of a rapid urine test for the diagnosis of Helicobacter pylori infection in the Chinese population
Authors: Wong W. M. , Wong B. C. Y. , Xia H. H. X. , Tang V. S. Y. , Lai K. C. , Hu W. H. C. , Yuen M. F. , Chan C. K. , Lam S. K.
Published: March 2003

Background:

A new rapid urine test was developed to detect anti‐Helicobacter pylori antibody in urine using the principle of immunochromatography. The accuracy of this test in the Chinese population remains to be defined.

Aim:

To evaluate a new rapid urine test for the diagnosis of H. pylori infection in the Chinese population.

Methods:

Eligible patients without previous treatment of H. pylori were recruited. In‐house rapid urease test and histology were used as the gold standard. The rapid urine test (RAPIRUN H. pylori antibody) was performed and the results were compared with the gold standard.

Results:

One hundred and twenty‐three patients were eligible for analysis and 61 (50%) were H. pylori positive by the gold standard. The rapid urine test showed a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 96.7%, 95.2%, 95.2%, 96.7% and 95.9%, respectively. Results were obtained within 20 min and no special laboratory support was required.

Conclusions:

The rapid urine test by immunochromatography is highly accurate for the diagnosis of H. pylori infection in untreated Chinese patients.
Alverine citrate fails to relieve the symptoms of irritable bowel syndrome: results of a double‐blind, randomized, placebo‐controlled trial
Authors: Mitchell S. A. , Mee A. S. , Smith G. D. , Palmer K. R. , Chapman R. W.
Published: March 2003

Background : Alverine citrate has been used in the treatment of irritable bowel syndrome for many years.

Aims : To compare the efficacy and safety of a new formulation of alverine citrate, a 120‐mg capsule, with placebo given three times daily for 12 weeks.

Methods : One hundred and seven patients with irritable bowel syndrome were entered into this three‐centre, double‐blind, randomized, placebo‐controlled, parallel group trial. The primary end‐point was relief of abdominal pain indicated by improvement in the scores for severity and frequency. Secondary efficacy variables included scores for other clinical symptoms and for overall well‐being.

Results : The severity and frequency of abdominal pain improved in 66% and 68% of patients treated with alverine citrate vs. 58% and 69% of the placebo group, but these differences were not significant. The mean percentage reduction in the scores for abdominal pain from baseline to the final assessment, although greater in the alverine citrate group (43.7%) compared with the placebo group (33.3%), was not statistically significant.

Conclusions : Alverine citrate is no better than placebo at relieving the symptoms of irritable bowel syndrome. Future trials should be designed to take into account the high and persistent placebo response seen in this condition.
The effect of the 5‐HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients
Authors: Mayer E. A. , Berman S. , Derbyshire S. W. G. , Suyenobu B. , Chang L. , Fitzgerald L. , Mandelkern M. , Hamm L. , Vogt B. , Naliboff B. D.
Published: March 2003

Aim : To conduct a placebo‐controlled functional brain imaging study to assess the effect of the 5‐hydroxytryptamine‐3 receptor antagonist, alosetron, on irritable bowel syndrome symptoms, regional brain activation by rectosigmoid distension and associated perceptual and emotional responses.

Methods : Fifty‐two non‐constipated irritable bowel syndrome patients (28 female) were enrolled in a randomized, placebo‐controlled trial with alosetron (1–4 mg b.d.). Thirty‐seven patients completed both brain scans following randomization. Rectosigmoid stimulation was performed with a computer‐controlled barostat. Changes in regional cerebral blood flow were assessed using H215O positron emission tomography. Stimulus ratings and changes in gastrointestinal symptoms were assessed using verbal descriptor scales.

Results : Alosetron, but not placebo, treatment was associated with a decrease in symptom ratings, and reductions in emotional stimulus ratings. Compared to baseline, alosetron treatment was associated with reduced regional cerebral blood flow in bilateral frontotemporal and various limbic structures, including the amygdala. Compared to placebo, decreases in activity of the amygdala, ventral striatum, hypothalamus and infragenual cingulate gyrus were significantly greater after alosetron.

Conclusions : In non‐constipated irritable bowel syndrome patients, 3 weeks of treatment with a 5‐hydroxytryptamine‐3 receptor antagonist decreases brain activity in response to unanticipated, anticipated and delivered aversive rectal stimuli in structures of the emotional motor system, and this is associated with a decrease in gastrointestinal symptoms.
Pathogenesis of sporadic and familial gastric cancer – implications for clinical management and cancer prevention
Authors: Ebert M. P. A. , Malfertheiner P.
Published: March 2003

Gastric cancer remains a great clinical challenge despite its decreasing incidence. While major progress has been achieved in the understanding of the pathogenesis and molecular biology of sporadic gastric cancer, only recently has the role of familial aggregation of gastric cancers been rediscovered. The genetic changes underlying sporadic and familial gastric cancer have been revealed, and recent studies indicate that this familial aggregation combines genetic and microbiological aspects. Thus, for the prevention of gastric cancers these findings might be helpful for the early diagnosis and for the screening of risk groups and family members.
Percutaneous ethanol injection vs. resection in patients with small single hepatocellular carcinoma: a retrospective case–control study with cost analysis
Authors: Gournay J. , Tchuenbou J. , Richou C. , Masliah C. , Lerat F. , Dupas B. , Martin T. , Nouel J. F. , Schnée M. , Montigny P. , D'Alincourt A. , Hamy A. , Paineau J. , Le Néel J. ‐C. , Le Borgne J. , Galmiche J. P.
Published: March 2003

Background : Percutaneous ethanol injection and hepatic resection are the most widely used curative therapeutic options for patients with compensated liver disease and small hepatocellular carcinoma.

Aim : To compare percutaneous ethanol injection and hepatic resection in a selected group of consecutive French patients with a single hepatocellular carcinoma, smaller than or equal to 50 mm, in terms of survival, recurrence rate of malignancy and direct costs.

Methods : The analysis of two contemporary cohorts of Child–Pugh A or B patients with a single hepatocellular carcinoma of ≤ 50 mm treated by percutaneous ethanol injection (n=55) or hepatic resection (n=50).

Results : Long‐term survival was not significantly different between the two groups when the size of hepatocellular carcinoma was less than 30 mm. However, the survival of patients with hepatocellular carcinoma larger than 30 mm was higher after hepatic resection than after percutaneous ethanol injection (P=0.044). The cumulative direct costs were significantly higher in patients treated by hepatic resection than in those treated by percutaneous ethanol injection regardless of the tumour size. The calculated costs per month of survival in patients treated with percutaneous ethanol injection and hepatic resection were 999 vs. 3865 euros, respectively (P < 0.001).

Conclusions : Percutaneous ethanol injection is more cost effective than hepatic resection in patients with a single hepatocellular carcinoma smaller than 30 mm. However, in patients with a larger tumour, long‐term survival is higher after hepatic resection.
Helicobacter pylori and gastric adenocarcinoma
Authors: Peterson W. L.
Published: March 2003

Gastric adenocarcinoma is still the second most common cause of death from cancer, even though it is on the decline in developed countries. Although H. pylori gastritis appears to be a necessary antecedent to the development of gastric adenocarcinoma, it is not a sufficient factor in and of itself. Other required factors for the progression of this disease are poorly understood. Patients with antral predominant gastritis seem protected from the disease, while patients with pangastritis are predisposed to both diffuse‐ and intestinal‐type adenocarcinoma. Development of a vaccine against H. pylori might yield promising results in decreasing the incidence of gastric adenocarcinoma.
Effect of different proton pump inhibitors, differences in CYP2C19 genotype and antibiotic resistance on the eradication rate of Helicobacter pylori infection by a 1‐week regimen of proton pump inhibitor, amoxicillin and clarithromycin
Authors: Kawabata H. , Habu Y. , Tomioka H. , Kutsumi H. , Kobayashi M. , Oyasu K. , Hayakumo T. , Mizuno S. , Kiyota K. , Nakajima M. , Kimoto K. , Inokuchi H. , Kawai K.
Published: March 2003

Aim : To investigate the effect of different proton pump inhibitors, S‐mephenytoin 4′‐hydroxylase (CYP2C19) genotype and antibiotic susceptibility on the eradication rate of Helicobacter pylori.

Methods : One hundred and eighty‐seven H. pylori‐infected peptic ulcer patients were randomly treated with either rabeprazole (10 mg b.d.) or lansoprazole (30 mg b.d.) plus amoxicillin (750 mg b.d.) and clarithromycin (400 mg b.d.) for 1 week. The antibiotic susceptibility and CYP2C19 genotype (extensive or poor metabolizer) were investigated.

Results : The eradication rates in the rabeprazole–amoxicillin–clarithromycin (RAC) and lansoprazole–amoxicillin–clarithromycin (LAC) groups were 75% and 69%, respectively, on an intention‐to‐treat basis, and 80% and 75%, respectively, on a per protocol basis. The eradication rate for clarithromycin‐resistant strains was significantly lower than that for clarithromycin‐sensitive strains (24% vs. 86%, P < 0.05). For clarithromycin‐sensitive strains in the LAC group, there was a tendency for a lower eradication rate in extensive than poor metabolizers. The eradication rate in extensive metabolizers in the RAC group tended to be higher than that in extensive metabolizers in the LAC group (89% vs. 78%, P = 0.079726).

Conclusions : The success of the 1‐week proton pump inhibitor–amoxicillin–clarithromycin regimen depends on the susceptibility of H. pylori to clarithromycin. Moreover, differences in CYP2C19 genotype influence the eradication rates of lansoprazole‐based therapy, and the rabeprazole‐based regimen has an advantage especially in extensive metabolizers.
Response of fistulating Crohn's disease to infliximab treatment assessed by magnetic resonance imaging
Authors: Bell S. J. , Halligan S. , Windsor A. C. J. , Williams A. B. , Wiesel P. , Kamm M. A.
Published: March 2003

Aims : To assess fistula track healing after infliximab treatment using magnetic resonance imaging.

Methods : Magnetic resonance imaging and clinical evaluation were performed before and after three infliximab infusions given over a 6‐week period. Magnetic resonance images were evaluated for abscesses and fistula tracks. Paired magnetic resonance image examinations were rated ‘better’, ‘unchanged’ or ‘worse’. Magnetic resonance imaging and clinical outcomes were then compared.

Results : Of the 12 referred patients, pre‐treatment magnetic resonance imaging detected abscesses in three (two not treated). Of the 10 treated patients, seven had peri‐anal fistulas, two of whom also had recto‐vaginal fistulas, and three had abdominal wall entero‐cutaneous fistulas. After infliximab, four were in remission, one had a response and five were non‐responders. One developed a peri‐anal abscess. Magnetic resonance imaging improved in six, was unchanged in two and was worse in two. In four of the six with improvement in magnetic resonance imaging, the fistula track resolved, but two of these had clinically persistent entero‐cutaneous fistulas. The clinical outcome and magnetic resonance imaging correlated in seven of the 10 patients; in three (two entero‐cutaneous and one peri‐anal), there was discordance.

Conclusions : Magnetic resonance imaging identifies clinically silent sepsis. Fistulas may persist despite clinical remission. Clinical response to infliximab and clinical correlation with magnetic resonance imaging were poor in patients with abdominal entero‐cutaneous fistulas.
The effect of ketamine pretreatment on propofol injection pain in 100 women
Authors: Tan C. H. , Onsiong M. K. , Kua S. W.
Published: March 2003

A controlled, randomised double‐blind study was performed to compare the prior intravenous administration of ketamine 10 mg (1 ml) or 0.9% saline (1 ml) on propofol injection pain. One hundred patients of ASA status 1 or 2 presenting for gynaecological surgery were studied. Following an initial 5‐ml bolus of propofol into a dorsal hand vein, 30 s after the treatment, 84% of the saline control patients experienced mild or severe pain compared to 26% of those who were given ketamine pretreatment (p < 0.05).
Requirements for target‐controlled infusion of propofol to insert the laryngeal mask airway
Authors: Taylor I. N. , Kenny G. N. C.
Published: March 2003

The success rate for insertion of the laryngeal mask airway was assessed in 60 patients using a target‐controlled infusion of propofol. Eleven of 15 patients who received a target propofol concentration of 5 μgml−1 had the laryngeal mask inserted successfully within 3 min of induction of anaesthesia. Fourteen of 15 patients who received 6 μgml−1 had successful insertion within 3 min and all 15 patients who received 7 μgml−1 had successful insertion within 3 min. Patients who received 8 μgml−1 had successful insertion within 90 s of induction of anaesthesia. The increased success rate of LMA insertion with the higher target propofol concentrations was achieved without major haemodynamic effects in this group of fit patients. However, adverse cardiovascular effects may occur with these doses in elderly or unfit patients. It is important in individual patients to titrate the target propofol concentration to achieve the required clinical end‐point.
The influence of premedication on heart rate variability
Authors: Michaloudis D. , Kochiadakis G. , Georgopoulou G. , Fraidakis O. , Chlouverakis G. , Petrou A. , Pollard B. J.
Published: March 2003

Analysis of heart rate variability has been used to study the effects of midazolam, morphine and clonidine on the autonomic nervous system, when administered to patients for premedication. Ninety‐five patients were studied 60 min before and 60 min after premedication. Normal saline (n = 25), midazolam 0.08 mgkg−1 (n = 24), morphine 0.15 mgkg−1 (n = 23), or clonidine 2 μgkg−1 (n = 23) were administered intramuscularly by random allocation. A Holter device was connected to the patient during the study period. Using power spectral analysis the low‐frequency and high‐frequency components were calculated from the Holter recordings. These are markers for sympathetic and parasympathetic activity respectively; the low‐ to high‐frequency ratio was also calculated, a ratio of >1 signifying sympathetic dominance. A significant reduction was noticed in both low‐frequency and high‐frequency power in the three premedicated groups, whereas no changes were observed in the normal saline group. In the case of midazolam, both the low and high frequencies were decreased but the low‐ to high‐frequency ratio did not change significantly. Morphine and clonidine depressed the low‐frequency component more than the high‐frequency component and the low‐ to high‐frequency ratio was decreased, suggesting parasympathetic dominance. We conclude that heart rate variability may be a useful tool for investigating the effect of drugs on the autonomic nervous system.
Comparison of pain from insertion of venous cannulae; a volunteer study
Authors: Brown J. M.
Published: March 2003

The pain from insertion of two small cannulae was compared in 26 volunteers. Each subject was blindfolded and had both a 22G and a 20G cannula inserted in random order. One subject was rejected as cannulation was unsuccessful. Of the remaining 25 subjects, 12 found the 22G more painful and 13 the 20G. This difference was not significant (chi squared p > 0.1).
Retracted: Recovery of post‐tetanic count and train‐of‐four responses at the great toe and thumb
Authors: Saitoh Y. , Fujii Y. , Takahashi K. , Makita K. , Tanaka H. , Amaha K.
Published: March 2003

We have studied the recovery of post‐tetanic count and train‐of‐four responses at the great toe and thumb accelerographically after the administration of vecuronium 0.2 mgkg−1. Sixty adult patients scheduled for anaesthesia with nitrous oxide and isoflurane were studied. The times to the return of the first post‐tetanic twitch were comparable at the great toe and thumb (mean (SD) times: 30.0 (6.5) min and 35.0 (8.5) min, respectively). Recovery of post‐tetanic count followed similar time courses at the great toe and thumb. Also, time to the return of the first twitch of the train‐of‐four did not differ significantly at the great toe and thumb (47.5 (9.6) min vs. 49.7 (10.5) min). Similarly, time to the return of the second, third and fourth twitches of the train‐of‐four did not significantly differ at the great toe and the thumb. However, the value of the first twitch of the train‐of‐four, expressed as a proportion of control twitch, was significantly higher than that at the thumb between 50 min and 110 min after the vecuronium injection, and the train‐of‐four ratio at the great toe was significantly higher than that at the thumb between 60 min and 100 min after the vecuronium injection.