bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the cost of lost productivity in dyspepsia
Authors: Severens J. L. , Laheij R. J. F. , Jansen J. B. M. J. , Lisdonk E. H. Van Der , Verbeek A. L. M.
Published: March 2003

Background:

In the field of gastrointestinal disease, productivity costs are highly relevant because work loss is substantial in dyspeptic patients. Productivity costs are normally calculated by multiplying days absent valued by gross earnings. This, however, might lead to an overestimation.

Aim:

To use a conservative approach to calculating productivity costs, taking absence compensating mechanisms into account.

Methods:

Patients who visited their general practitioner for the first time with dyspeptic complaints and patients who were known to have persistent dyspeptic complaints were enrolled in two studies. In total, 136 patients completed a questionnaire about their employment situation, absence from work and absence compensating mechanisms.

Results:

Sixty‐six of the respondents had a paid job, of which 25 (38%) reported absence from work during the previous 4 weeks (average 3.0 days, 1.9 days related to dyspeptic complaints). More than 50% of the employed respondents answered that absence could be compensated for by colleagues, and only in 8% of the cases was absence compensated for by overtime. Using our conservative approach, only one‐quarter of the productivity costs remained, compared to the current approach of valuing each day absent as a loss of productivity.

Conclusions:

We suggest using both the current and the conservative approaches, analogous to the principles of sensitivity analysis, to avoid overestimation of productivity costs.
Idiopathic bile acid malabsorption: qualitative and quantitative clinical features and response to cholestyramine
Authors: Sinha L. , Liston R. , Testa H. J. , Moriarty K. J.
Published: March 2003

Background:

Idiopathic bile acid malabsorption is a poorly recognized cause of chronic diarrhoea. The SeHCAT (75Selenium HomotauroCholic Acid Test) can accurately diagnose this condition.

Aim:

To identify patients with idiopathic bile acid malabsorption, to describe their clinical features, both qualitatively and quantitatively, and to assess the response to cholestyramine.

Method:

Idiopathic bile acid malabsorption was considered in all patients complaining of chronic diarrhoea. They were included in the study if their SeHCATs were positive (< 15% retention) and secondary causes of bile acid malabsorption were excluded. The response to therapy with cholestyramine was assessed.

Results:

Nine patients were diagnosed with idiopathic bile acid malabsorption (median SeHCAT retention 8%, range 3–12.6). Their median daily faecal weight was 285 g (range 85–676) and median faecal fat output was 17 mmol/24 h (range 8.3–38.8). Six patients had an immediate response to cholestyramine. There was a marked reduction in stool frequency (median stool frequency pre‐treatment 5/day vs. 2/day post‐treatment, P = 0.03). Five patients had large volume diarrhoea (faecal weight > 200 g/day) and three had steatorrhoea.

Conclusions:

Idiopathic bile acid malabsorption, once suspected, especially by documenting true ‘large volume’ watery diarrhoea or steatorrhoea, is easily diagnosed and response to therapy is often very good. There is often a previous history of gastrointestinal infection and this condition should be considered in patients with chronic diarrhoea of undetermined origin, especially before they are labelled as having irritable bowel syndrome.
Short‐ and long‐term outcome of patients treated with cyclosporin for severe acute ulcerative colitis
Authors: Stack  , Long  , Hawkey
Published: March 2003

Background:

Recent evidence suggests that the immunosuppressive drug cyclosporin may be of benefit in treating patients with severe colitis who are steroid resistant. Although cyclosporin appears to be effective in reducing colectomy rates in the short term, few data are available on the long‐term follow‐up of such patients.

Aim:

To investigate the short‐ and long‐term outcome of patients with severe steroid‐resistant ulcerative colitis treated with cyclosporin who were otherwise being considered for colectomy.

Methods:

Twenty‐two patients with severe steroid‐resistant exacerbations of ulcerative colitis who were being considered for colectomy were treated with cyclosporin (4 mg/kg i.v.) daily for 7 days followed by oral treatment (6 mg/kg/day) if colectomy was avoided.

Results:

Twenty of 22 patients (91%) avoided colectomy during their initial hospital admission. With a mean follow‐up period of 39 months (range 31–59), eight of these patients have subsequently relapsed and required colectomy and 12 patients have avoided colectomy (53%). Of the 12 patients avoiding colectomy, seven have successfully been weaned on to azathioprine while five are maintained on an aminosalicylate alone. None of these long‐term responders require maintenance corticosteroids. The main side‐effects during treatment with cyclosporin were headaches (six patients, 27%), paraesthesia and tremors (four patients, 18%) and hypertension (four patients, 18%). Two patients developed renal impairment on cyclosporin which resolved on lowering the dose. In no case was cyclosporin discontinued because of an adverse reaction. No clinical or laboratory features could be identified that predicted which patients treated with cyclosporin would later require colectomy.

Conclusion:

This study shows that cyclosporin is a viable alternative to emergency colectomy in severe ulcerative colitis in the short term. Although these benefits are not maintained in all patients, more than half were found to avoid colectomy in the longer term.
First line treatment with omeprazole provides an effective and superior alternative strategy in the management of dyspepsia compared to antacid/alginate liquid: a multicentre study in general practice
Authors: Goves  , Oldring  , Kerr  , Dallara  , Roffe  , Powell  , Taylor
Published: March 2003

Background

Many patients who present with dyspepsia are prescribed antacid/alginates as their first line and often mainstay therapy. This multicentre study was designed to assess whether early introduction of acid inhibition is an effective strategy in dyspepsia management.

Methods

Dyspeptic patients (n = 674) were randomized to receive either omeprazole 10 mg o.m. or antacid/alginate liquid 10 mL q.d.s. for 4 weeks in an open, parallel group study.

Results

Complete relief of the most common symptom at entry, heartburn, was greater in the omeprazole‐treated group compared with the antacid/alginate‐treated group (64 vs. 30%, respectively, at 4 weeks; P < 0.0001). The percentage of patients who met the stringent health target of complete relief of overall symptoms was higher in the omeprazole‐treated group (41% at 4 weeks) compared with the antacid/alginate group (16% at 4 weeks; P < 0.0001). Comparisons of quality of life scores between treatments favoured the omeprazole group at 2 and 4 weeks for both the Psychological General Well‐Being Index and the Gastrointestinal Symptom Rating Scale (each P ≤ 0.0009). In addition, a greater proportion of patients rated omeprazole to be more effective in symptom relief and more convenient to use (each P = 0.0001) than antacid/alginate.

Conclusion

This study demonstrates that, compared to antacid/alginate liquid 10 mL q.d.s., omeprazole 10 mg o.m. is more effective in the management of dyspepsia symptoms and is the patients’ preferred treatment.
The monoethylglycinexylidide test for grading of liver cirrhosis
Authors: FABRIS  , JEMMOLO  , TOFFOLO  , PALEARI  , VIAGGI  , RIGON  , CASAGRANDE  , LIRUSSI  , STRAZZABOSCO  , COBELLI  , OKOLICSANYI
Published: March 2003

Background:

Monoethylglycinexylidide (MEGX) formation following lignocaine injection has recently been proposed as a simple dynamic liver function test based on a single measurement of its serum concentration.

Aim:

To determine the optimal sampling time for MEGX determination.

Methods:

A modelling analysis of lignocaine and MEGX kinetics was performed in seven normals and in four patients with compensated liver cirrhosis; a similar study was performed in 74 cirrhotic patients, divided into two groups according to disease severity (Pugh score).

Results:

Only the MEGX fractional formation rate (kf) and formation delay (τ) were significantly altered in cirrhotic patients compared to normals: kf = 0.15 ± 0.03 vs. 0.32 ± 0.10 min−1 (mean ± s.d.); τ = 7.7 ± 2.0 vs. 3.9 ± 2.9 min−1. A good correlation was found between kf and late (r = 0.82) but not early (r = 0.63) serum MEGX formation, suggesting that late measurements for the clinical MEGX test are preferred. In the second part of our investigation, by discriminant analysis of MEGX test data for 74 cirrhotic patients, the late MEGX concentrations gave the best discrimination between the two classes. In particular, the 60 min MEGX concentration showed the best diagnostic accuracy (81%), sensitivity (75%) and specificity (84%). The association of this with other MEGX parameters, either singly or derived from the whole curve measurements, did not improve the performance of the method.

Conclusion:

The MEGX test, based on a single determination 60 min after lignocaine injection, may be regarded as a simple and sensitive quantitative liver function test.
Ranitidine bismuth citrate, tetracycline, clarithromycin twice‐a‐day triple therapy for clarithromycin susceptible Helicobacter pylori infection
Authors: Graham  , Hoffman  , Anderson  , Qureshi  , Osato  , El‐Zimaity
Published: March 2003

Background:

Although many combination therapies have been proposed, there is still interest in identifying simple, inexpensive, effective protocols that have high rates of success.

Aim:

To investigate the role of the new soluble form of bismuth, ranitidine bismuth citrate, in twice‐a‐day therapy for Helicobacter pylori infection.

Methods:

Patients with histologically and culture proven H. pylori infection received ranitidine bismuth citrate 400 mg, tetracycline HCl 500 mg, and clarithromycin 500 mg, each b.d. for 14 days, followed by 300 mg ranitidine once a day for 4 additional weeks. Outcome was assessed 4 or more weeks after the end of antimicrobial therapy by repeat endoscopy with histology and culture (49 patients) or urea breath testing (14 patients).

Results:

Sixty‐three patients completed the therapy, 59 men and four women (average age 56.7 years; range 31–75 years). All patients had clarithromycin‐susceptible strains prior to therapy. H. pylori infection was cured in 94% (95% CI: 85–98%). There was a therapy failure in one patient who took the medicine for only 1 day and stopped because of side‐effects. Three of the isolates from treatment failures were available post‐failure; two were clarithromycin‐resistant and one was susceptible. Side‐effects were severe in two patients (3%) and moderate in three (primarily diarrhoea).

Conclusions:

Twice‐a‐day ranitidine bismuth citrate, tetracycline, clarithromycin triple therapy was well tolerated and effective for the treatment of H. pylori infection in patients with clarithromycin‐susceptible H. pylori.
The systemic load and efficient delivery of active 5‐aminosalicylic acid in patients with ulcerative colitis on treatment with olsalazine or mesalazine
Authors: STØA‐BIRKETVEDT  , FLORHOLMEN
Published: March 2003

Background:

There have been reports of nephrotoxic reactions in patients with ulcerative colitis treated with 5‐aminosalicylic acid (5‐ASA) preparations.

Aim:

To compare the efficacy in delivery of active 5‐ASA to the colon and the systemic load as the basis for potential long‐term toxicity during treatment with olsalazine or mesalazine in patients with ulcerative colitis in remission.

Patients and Methods:

Fifteen patients with ulcerative colitis were treated with olsalazine or mesalazine, each for 7 days in an open, randomized, crossover design study. 5‐ASA and acetyl‐5‐ASA (Ac‐5‐ASA) in plasma and urine were measured by high performance liquid chromatography.

Results:

The plasma concentration of 5‐ASA was 1.2 ± 0.1 μmol/L (mean ± S.E.M.) for olsalazine and 8.0 ± 1.9 μmol/L for mesalazine, while the plasma concentration of Ac‐5‐ASA was 2.8 ± 0.2 μmol/L for olsalazine and 10.8 ± 1.6 μmol/L for mesalazine. The amount of 5‐ASA excreted in the urine was 68 ± 30 μmol/24 h for olsalazine and 593 ± 164 μmol/24 h for mesalazine. The amount of Ac‐5‐ASA in the urine was 1260 ± 102 μmol/24 h for olsalazine and 3223 ± 229 μmol/24 h for mesalazine. The urinary recovery of total 5‐ASA plus Ac‐5‐ASA (as a percentage of the given dose) was 23 ± 2.1% for olsalazine and 39 ± 3.6% for mesalazine. The ratio between the plasma concentrations of mesalazine and olsalazine differed significantly both for 5‐ASA (5.1) and Ac‐5‐ASA (3.6); for 5‐ASA (9.9) and Ac‐5‐ASA (2.6) in urine, and for the urinary recovery of total 5‐ASA plus Ac‐5‐ASA (1.7). Moreover, in the mesalazine group there was a large variation in the individual plasma concentrations of 5‐ASA and Ac‐5‐ASA, with maximal values 5–6‐fold higher than that in the olsalazine group.

Conclusion:

The systemic load of active 5‐ASA is significantly higher for mesalazine than for olsalazine, when based on the dosages given and when calculated on an equimolar basis. Some of the patients in the mesalazine group showed unexpected high levels of plasma and urinary 5‐ASA concentrations, a finding which may have long‐term safety implications.
Anti‐ulcerogenic properties of endothelin receptor antagonists in the rat
Authors: PADOL  , HUANG  , HUNT
Published: March 2003

Background

: Endothelins have been implicated in gastric mucosal damage in a variety of animal models. Exogenous ET‐1 and ET‐3 are causally associated with experimental gastric ulcers. Furthermore, clinical reports also show elevated plasma and gastric mucosal endothelin‐1 levels in patients suffering from peptic ulcers.

Aim

: To study the possibility that endothelin receptor antagonists may have beneficial effects and prevent the development of gastric ulcers. We have tested in rats the orally‐active endothelin antagonist bosentan (Ro 47‐0203) and Ro 48‐5695, which is 10–30 times more potent than bosentan on endothelin receptors.

Methods

: Water immersion restrained stress (WIRS) and indomethacin were used to provoke gastric mucosal damage. Endothelin receptor antagonists were administered orally prior to the induction of gastric damage. The gastric lesion index (mm), assessed macroscopically, and myeloperoxidase (MPO) activity were used as markers of the extent of mucosal injury.

Results

: Bosentan at 100 and 30 mg/kg administered orally caused attenuation of gastric damage in the WIRS model by 58% and 42%, respectively. Bosentan also caused complete reduction of MPO activity. In indomethacin‐induced gastric damage, 100 mg/kg bosentan attenuated gastric damage by 45% and 61% as measured by the gastric lesion index and MPO activity respectively. Ro 48‐5695 was at least 30 times more potent than bosentan in reducing indomethacin‐induced mucosal damage and at 3 mg/kg, caused a decrease of 49% in the gastric lesion index and a reduction in MPO activity of 41%. Bosentan and Ro 48‐5695 possess weak antisecretory properties as tested in the mouse gastric gland assay, than cannot, alone, account for their anti‐ulcer properties.

Conclusions

: Both endothelin receptor antagonists prevented the development of gastric mucosal injury in the rat. Disturbances in the gastric microcirculation are responsible for the development of experimental gastric ulcers. The anti‐ulcer properties of these two endothelin antagonists suggest possible new therapeutic approaches to controlling gastric inflammation.
Patterns of consultation and treatment for heartburn: findings from a Singaporean community survey
Authors: Ho  , Kang  , Seow
Published: March 2003

Background

: The prevalence of reflux‐type symptoms among community individuals in Singapore is low.

Aim

: To describe the healthcare‐seeking behaviour of those subjects with heartburn.

Methods

: A cross‐sectional survey, using a reliable and valid questionnaire, was carried out on a race‐stratified random sample of residents, aged 21–95 years, in a Singaporean town; 93% responded (n=696).

Results

: The ethnic‐adjusted prevalence of heartburn for the past 1‐year was 4.6%. Sixteen (30%) of the 53 heartburn sufferers had sought consultation for their symptoms. They were more likely to have severe heartburn (P < 0.001), and to have complained of nocturnal awakening due to heartburn (P < 0.05) than those who did not present to medical attention. Ethnic origin did not influence the consultation pattern. Only 18 (34%) of the 53 heartburn sufferers received pharmacological therapy for their symptoms. The most commonly used medication was antacid. Medication use was associated with symptom severity (P < 0.05), but not ethnicity.

Conclusions

: Heartburn is uncommon in the general population of Singapore. Few heartburn sufferers seek medical attention, and most do not receive medications for symptomatic control. The decision to seek medical advice and/or to medicate was generally linked to symptom severity, but not to ethnicity.
The effect of Helicobacter pylori eradication therapy on gastric antral myoelectrical activity and gastric emptying in patients with non‐ulcer dyspepsia
Authors: Miyaji  , Azuma  , Ito  , Abe  , Ono  , Suto  , Ito  , Yamazaki  , Kohli  , Kuriyama
Published: March 2003

Background

: Dysmotility of the gastroduodenal region and delayed gastric emptying have been considered to play roles in non‐ulcer dyspepsia. In addition, it has been reported that Helicobacter pylori induced inflammation of the gastric mucosa may affect gastric motility.

Aim

: To evaluate the effects of H. pylori eradication therapy on gastrointestinal motility and symptoms in non‐ulcer dyspepsia patients.

Methods

: A total of 46 non‐ulcer dyspepsia patients were examined for gastric emptying, antral myoelectrical activity, H. pylori infection, and symptom scores. In H. pylori‐positive non‐ulcer dyspepsia patients, gastric emptying, antral myoelectrical activity, and symptom scores were also analysed 2 months after being cured of H. pylori infection.

Results

: A total of 67.4% of the non‐ulcer dyspepsia patients were H. pylori‐positive. Both abnormal gastric emptying and antral myoelectrical activity were observed in non‐ulcer dyspepsia patients. H. pylori‐positive non‐ulcer dyspepsia patients were divided into three groups according to their gastric emptying: the delayed gastric emptying group, the normal gastric emptying group, and the rapid gastric emptying group. In the delayed and rapid gastric emptying groups, the gastric emptying and symptom scores were improved significantly by the eradication therapy. However, there was no improvement in symptom scores in the normal gastric emptying non‐ulcer dyspepsia group by the eradication therapy.

Conclusions

: Disturbed gastric emptying and antral myoelectrical activity play roles in non‐ulcer dyspepsia. Helicobacter pylori infection, inducing disturbed gastric emptying, may cause some non‐ulcer dyspepsia symptoms. Gastric emptying and symptom scores are improved by H. pylori eradication therapy in non‐ulcer dyspepsia patients with disturbed gastric emptying. H. pylori eradication therapy is effective in H. pylori‐positive non‐ulcer dyspepsia patients with disturbed gastric emptying.
Salvage therapies after failure of Helicobacter pylori eradication with ranitidine bismuth citrate‐based therapies
Authors: Chan  , Sung  , Suen  , Wu  , Ling  , Chung
Published: March 2003

Background:

Salvage therapies after initial Helicobacter pylori eradication failure of ranitidine bismuth citrate (RBC)‐based regimens remain undefined.

Aim:

To test the efficacy of 1‐week omeprazole, amoxycillin and clarithromycin as a second‐line treatment and 1‐week quadruple therapy after repeated failures of RBC‐ and proton pump inhibitor‐based regimens.

Method:

Patients were recruited from a recently published prospective randomized study if confirmed to have failed H. pylori eradication with RBC‐based regimens. They were given omeprazole 20 mg, amoxycillin 1 g and clarithromycin 500 mg (OAC) b.d. for 1 week. 13C‐urea breath test was performed 4 weeks after the conclusion of medication. Those who failed to respond to OAC were given 1‐week quadruple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg and metronidazole 400 mg q.d.s. plus omeprazole 20 mg b.d.).

Results:

Among 398 patients receiving RBC‐based therapies, 40 (10%) had failed eradication (RAC=7, RC‐2=12, RMC=7, and RMT=14). OAC was prescribed to 31 patients (RAC=4, RC‐2=9, RMC=6, and RMT=12) and 68% had successful eradication. Nine out of 10 patients with failed second treatment received quadruple therapy; successful eradication occurred in 83% (5 out of 6) after repeated failures of clarithromycin‐based regimens.

Conclusion:

One‐week OAC is not an optimal second‐line therapy when RBC‐clarithromycin combinations fail. Quadruple therapy appears to be effective despite repeated failures of clarithromycin‐based RBC or proton pump inhibitor therapies.
The effects of omeprazole on healing and appearance of small gastric and duodenal lesions during dosing with diclofenac in healthy subjects
Authors: Dorta  , Nicolet  , Vouillamoz  , Margalith  , Saraga  , Bouzourene  , Häcki  , Stolte  , Blum  , Armstrong
Published: March 2003

Background:

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are associated with gastrointestinal mucosal damage. Omeprazole prevents the formation, and accelerates the healing, of NSAID‐induced ulcers.

Aim:

To test whether omeprazole accelerates healing of standardized gastroduodenal lesions in the presence of diclofenac.

Methods:

In a double‐blind, double‐dummy, placebo‐controlled, crossover study, 12 healthy volunteers received consecutive, 2‐week courses of omeprazole (40 mg o.d.) and placebo, in random order, with an intervening, 4‐week washout period; diclofenac (50 mg t.d.s.), was given for the second week of each course. Five endoscopies were performed, one at the outset and the others before and after each course of diclofenac. Biopsies were taken from the endoscopically normal mucosa of the corpus, antrum and duodenum and also from any new mucosal lesion that developed after diclofenac. The sites of biopsies taken before each course of diclofenac were evaluated endoscopically after each course to assess the extent of healing according to a predetermined healing score scale.

Results:

The healing scores observed after administration of placebo/diclofenac (median=0; range 0–6) and after omeprazole/diclofenac (median=0; range 0–6; P=0.17) did not differ. Small gastroduodenal lesions developed de novo in six subjects during placebo/diclofenac and in seven during omeprazole/diclofenac. Focal chemical gastropathy was observed only in close proximity to macroscopic lesions.

Conclusions:

In healthy subjects, omeprazole does not accelerate the healing of pre‐existing mucosal lesions or prevent the development of small diclofenac‐induced mucosal lesions.
Towards identifying optimal doses for alpha‐2 adrenergic modulation of colonic and rectal motor and sensory function
Authors: Malcolm  , Camilleri  , Kost  , Burton  , Fett  , Zinsmeister Alan R.
Published: March 2003

Rationale:

Visceral sensation and motility are important in functional gut disorders and are partly controlled by adrenergic innervation.

Objectives:

To characterize the α2‐adrenergic control of motor and sensory function of descending colon and rectum.

Methods:

In 32 healthy volunteers, we assessed compliance, fasting and postprandial tone, and sensations of gas, urgency and pain during phasic distentions. Each subject received one agent at clinically approved doses: clonidine (0.05, 0.1, 0.2 or 0.3 mg p.o.); or the α2 antagonist yohimbine (0.0125 mg, 0.05 mg, 0.125 mg or 0.2 mg intravenously and infusion over 2.5 h).

Results:

Clonidine increased colonic and rectal compliance, and reduced tone, pain, gas sensation and rectal urgency. Clonidine showed large pairwise differences in sensation and motility between 0.05 and 0.1 mg doses, which did not interfere with the colon’s motor response to feeding. Conversely, yohimbine dose‐dependently altered the compliance curve, increased tone and sensations of gas, pain and urgency. Drug effects in the colon were more marked at low distensions; α2 modulation of rectal sensation was observed at all levels of distension.

Conclusions:

α2‐adrenergic mechanisms modulate colorectal sensations and motility; at doses as low as 0.05 mg, clonidine reduced colorectal sensation while the tone response to feeding was preserved. These studies provide insight into the potential use of α2 agents in disease states.
Ulcer‐healing drugs are required after eradication of Helicobacter pylori in patients with gastric ulcer but not duodenal ulcer haemorrhage
Authors: Lai K. C. , Hui W. M. , Wong B. C. Y. , Hu W. H. C. , Lam S. K.
Published: March 2003

Aim:

To study the efficacy of a 2‐week anti‐Helicobacter therapy in the healing of H. pylori‐associated bleeding peptic ulcers.

Methods:

Omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1 g, twice daily, were given for 2 weeks to 180 patients with H. pylori‐associated bleeding peptic ulcers. Endoscopy was repeated 4 weeks after the eradication therapy to assess healing of the peptic ulcers.

Results:

Repeat endoscopies were performed in 168 patients (42 gastric ulcer and 126 duodenal ulcer) who followed the protocol. Thirty‐eight patients with bleeding gastric ulcers and 124 patients with bleeding duodenal ulcers healed 4 weeks after treatment (per protocol analysis; gastric ulcer: 91% vs. duodenal ulcer: 98%; P=0.035). No patients who were compliant to the study medications suffered from re‐bleeding. Stepwise discriminant analysis demonstrated that small ulcers (< 15 mm) and the presence of duodenal ulcers best predicted healing of the peptic ulcers.

Conclusions:

Ulcer‐healing drugs should be continued after a 2‐week course of omeprazole‐containing anti‐Helicobacter therapy for gastric ulcers and large peptic ulcers that have bled, but can be omitted in most patients with a bleeding duodenal ulcer.
Cetraxate, a mucosal protective agent, combined with omeprazole, amoxycillin, and clarithromycin increases the eradication rate of Helicobacter pylori in smokers
Authors: Kamada T. , Haruma K. , Miyoshi E. , Mihara M. , Kitadai Y. , Yoshihara M. , Sumii K. , Kajiyama G. , Tahara K. , Mukai T. , Kawamura Y. , Hattori N.
Published: March 2003

Background:

Our previous study demonstrated that Helicobacter pylori eradication was less effective in smokers than in non‐smokers. Cetraxate is an anti‐ulcer drug that increases gastric mucosal blood flow.

Aim:

To evaluate the effect of cetraxate combined with new triple therapy for the eradication of H. pylori in smokers.

Methods:

This study had a single‐centre, double‐blind, randomized non‐placebo design. A total of 106 consecutive H. pylori‐positive smoking patients were randomly allocated to one of two regimens: one group received omeprazole (20 mg), amoxycillin (1500 mg), and clarithromycin (600 mg) for 7 days (OAC, n=55). The other group recieved OAC plus cetraxate (600 mg) for 7 days (OAC + CET, n=51). The success of H. pylori eradication was evaluated by histology and the 13C‐urea breath test at 4 weeks after completion of treatment.

Results:

By intention‐to‐treat analysis, the H. pylori eradication rate was 55% in the OAC group and 92% in the OAC + CET group (P < 0.01). By per protocol analysis, the H. pylori eradication rate was 58% in the OAC group and 94% in the OAC + CET group (P < 0.01).

Conclusion:

Cetraxate combined with new triple therapy increases the eradication of H. pylori in smokers.
High‐dose ecabet sodium improves the eradication rate of Helicobacter pylori in dual therapy with lansoprazole and amoxicillin
Authors: Kagaya H. , Kato M. , Komatsu Y. , Mizushima T. , Sukegawa M. , Nishikawa K. , Hokari K. , Takeda H. , Sugiyama T. , Asaka M.
Published: March 2003

Aim:

The additive effect of ecabet sodium in combination with dual therapy on Helicobacter pylori eradication was evaluated.

Methods:

H. pylori‐positive chronic gastritis patients were randomly assigned to one of the following three groups and medicated for 2 weeks. Group LA: dual therapy (lansoprazole 30 mg o.d. plus amoxicillin 750 mg b.d.). Group LA1E: dual therapy plus ecabet sodium (1 g b.d.). Group LA2E: dual therapy plus ecabet sodium (2 g b.d.). Patients were evaluated 4 weeks after the cessation of treatment by culture and 13C‐urea breath test.

Results:

Seventy‐one patients (mean age, 56.6 years; range, 26–79 years; 40 males, 31 females) were enrolled in this prospective, single‐blind study, and 68 completed the protocol. The eradication rates per protocol patient were 43% in group LA, 62% in group LA1E, and 79% in group LA2E, and those on the intention‐to‐treat basis were 42% in group LA, 57% in group LA1E and 79% in group LA2E. The eradication rate in group LA2E was significantly higher than group LA (P=0.032 in per protocol, P=0.022 in intention‐to‐treat). Adverse effects were observed in 10 patients in this study. There were no severe adverse effects caused by ecabet sodium.

Conclusion:

High‐dose ecabet sodium increases eradication rates of H. pylori in dual therapy with lansoprazole and amoxicillin.
Hypochlorhydria induced by a proton pump inhibitor leads to intragastric microbial production of acetaldehyde from ethanol
Authors: Väkeväinen S. , Tillonen J. , Salaspuro M. , Jousimies‐Somer H. , Nuutinen H. , Färkkilä M.
Published: March 2003

Background:

Acetaldehyde, produced locally in the digestive tract, has recently been shown to be carcinogenic in humans.

Aim:

To examine the effect of iatrogenic hypochlorhydria on intragastric acetaldehyde production from ethanol after a moderate dose of alcohol, and to relate the findings to the changes in gastric flora.

Methods:

Eight male volunteers ingested ethanol 0.6 g/kg b.w. The pH, acetaldehyde level and microbial counts of the gastric juice were then determined. The experiment was repeated after 7 days of lansoprazole 30 mg b.d.

Results:

The mean (± S.E.M.) pH of the gastric juice was 1.3 ± 0.06 and 6.1 ± 0.5 (P < 0.001) before and after lansoprazole, respectively. This was associated with a marked overgrowth of gastric aerobic and anaerobic bacteria (P < 0.001), by a 2.5‐fold (P=0.003) increase in gastric juice acetaldehyde level after ethanol ingestion, and with a positive correlation (r=0.90, P < 0.001) between gastric juice acetaldehyde concentration and the count of aerobic bacteria.

Conclusions:

Treatment with proton pump inhibitors leads to hypochlorhydria, which associates with intragastric overgrowth of aerobic bacteria and microbially‐mediated acetaldehyde production from ethanol. Since acetaldehyde is a local carcinogen in the concentrations found in this study, long‐term use of gastric acid secretory inhibitors is a potential risk‐factor for gastric and cardiac cancers.
Review article: the ‘mechanical pumps' and the enterohepatic circulation of bile acids – defects in coeliac disease
Authors: Lanzini A. , Lanzarotto F.
Published: March 2003

Bile acid pool size is maintained relatively constant at about 3–5 g in healthy subjects by two mechanisms, enterohepatic circulation and de novo synthesis of bile acids. This latter mechanism compensates for the daily faecal loss (about 0.2–0.6 g) of bile acids, whereas the bulk of the pool is conserved by the former mechanism. The driving forces of the enterohepatic circulation are constituted by chemical pumps, including intestinal absorption and hepatic uptake, and by mechanical pumps, including gall‐bladder and intestinal motility. The latter provide the main propulsive forces for bile acids to reach the site of intestinal absorption, and by contrast with the very rapid chemical pumps, mechanical pumps have storage capacity for the bile acid pool and therefore comprise the slow limb of the enterohepatic circulation.
1In coeliac disease, a disease classically described as a malabsorption syndrome associated with mucosal atrophy of the small intestine, both gall‐bladder and small intestinal motor functions are impaired, and in this article we review the mechanisms involved in these defects, how they influence the enterohepatic circulation of bile acids, and the evidence supporting the concept that both the gall‐bladder and the small intestinal motor functions represent the main factors affecting the kinetics of the enterohepatic circulation.
Esomeprazole 20 mg maintains symptom control in endoscopy‐negative gastro‐oesophageal reflux disease: a controlled trial of ‘on‐demand’ therapy for 6 months
Authors: Talley N. J. , Lauritsen K. , Tunturi‐Hihnala H. , Lind T. , Moum B. , Bang C. , Schulz T. , Omland T. M. , Delle M. , Junghard O.
Published: March 2003

Background:

Most patients with gastro‐oesophageal reflux disease (GERD), regardless of endoscopic status, suffer symptomatic relapse within 6 months of stopping acid suppressant therapy.

Aim:

To assess the efficacy of ‘on‐demand’ treatment of GERD with esomeprazole, the first proton pump inhibitor developed as an optical isomer.

Methods:

In this multicentre, double‐blind study, 342 endoscopy‐negative GERD patients demonstrating complete resolution of heartburn during the final week of a 4‐week treatment period with esomeprazole 20 mg or omeprazole 20 mg once daily were randomized to receive esomeprazole 20 mg or placebo on demand (maximum of one dose per day) for a further 6 months. Use of rescue antacids was permitted.

Results:

All 342 patients (191 males), aged 19–79 (mean 49) years, were evaluable in the intention‐to‐treat analysis. The proportion of patients who discontinued treatment due to insufficient control of heartburn was significantly higher among placebo compared to esomeprazole recipients (51% vs. 14%; P < 0.0001). Patients randomized to esomeprazole on‐demand therapy remained in the study longer than those in the placebo group (mean 165 vs. 119 days). Over 50% took the study medication for periods of 1–3 consecutive days (esomeprazole) or 4–13 consecutive days (placebo). Use of antacids was > 2‐fold higher among placebo recipients. The frequency of adverse events was similar in the two groups, when adjusted for time spent in the study, as were the clinical laboratory profiles.

Conclusions:

On‐demand therapy with esomeprazole 20 mg is effective and well tolerated in maintaining symptom control in endoscopy‐negative GERD.
Nitrofurantoin quadruple therapy for Helicobacter pylori infection: effect of metronidazole resistance
Authors: Graham D. Y. , Saeed M. A. , Hoffman J. , El‐Zimaity H. M. T. , Kwon D. H. , Osato M. S.
Published: March 2003

Background:

Antibiotic resistance has increasingly been recognized as the major cause of treatment failure for Helicobacter pylori infection. New therapies for patients with metronidazole‐ or clarithromycin‐resistant H. pylori are needed.

Aim:

To investigate the role of nitrofurantoin quadruple therapy for the treatment of H. pylori.

Methods:

Patients with confirmed H. pylori infection received nitrofurantoin (100 mg t.d.s.), omeprazole (20 mg b.d.), Pepto‐Bismol (two tablets t.d.s.), and tetracycline (500 mg t.d.s.) for 14 days. Four or more weeks after the end of therapy, outcome was assessed by repeat endoscopy with histology and culture or urea breath testing.

Results:

Thirty patients were entered, including 25 men and five women; the mean age was 54.9 years. The most common diagnoses were duodenal ulcer (23%) and GERD (18%). The intention‐to‐treat cure rate was 70% (95% CI: 50.6–85%). Nitrofurantoin quadruple therapy was more effective with metronidazole‐sensitive strains (88%; 15 out of 17) than with metronidazole‐resistant strains (33%; three out of nine; P=0.008). Two of the treatment failures had pre‐treatment isolates susceptible to metronidazole, which were resistant after therapy.

Conclusions:

Because nitrofurantoin quadruple therapy performed inadequately in the presence of metronidazole resistance, we conclude that nitrofurantoin is unlikely to find clinical utility for the eradication of H. pylori.
Induction interferon therapy in naïve patients with chronic hepatitis C: increased end‐of‐treatment virological responses but absence of long‐term benefit
Authors: Hadziyannis A. S. , Papaioannou C. , Spanou F. , Manesis E. K. , Hadziyannis S. J.
Published: March 2003

Background and aims:

The low efficacy of interferon monotherapy and data from viral kinetic studies led us to evaluate the efficacy of interferon administered daily in chronic hepatitis C.

Patients and methods:

Thirty‐eight naïve patients with chronic hepatitis C and active liver disease randomly received 3 or 5 MU IFN‐α daily for 1 month, followed by the same dose three times a week for 11 months. Results were compared to a three‐times‐a‐week scheme of 3 MU IFN‐α for 1 year.

Results:

At the end of the induction period, 27 out of 38 (71%) patients had cleared HCV‐RNA with a significantly higher rate in the 5 MU than in the 3 MU group (17 out of 18 or 94% vs. 10 out of 20 or 50%, P=0.003). The end‐of‐treatment virological response rate was 66% (25 out of 38) in the induction groups and 40% (10 out of 25) in the control group (P=0.04). Six months after completion of therapy, the sustained response rate dropped to 29% (11 out of 38) compared to 28% (7 out of 25) in the standard regimen.

Conclusions:

In chronic hepatitis C, treatment with 5 or 3 MU IFN‐α daily during the first month of a standard IFN regimen leads to significantly increased end‐of‐treatment virological responses, but long‐term responses are similar to those of standard IFN monotherapy.
Economic analysis of four triple regimens for the treatment of Helicobacter pylori‐related peptic ulcer disease in in‐patient and out‐patient settings in Hong Kong
Authors: You J. H. S. , Lee K. K. C. , Ho S. S. S. , Sung J. J. Y. , Kung N. N. S. , Yung M. , Lee C. , Yee G. C.
Published: March 2003

Background:

One‐week triple regimens have been shown to be effective for the treatment of Helicobacter pylori‐related peptic ulcer disease.

Aim:

To conduct an economic analysis of four triple regimens for the treatment of H. pylori‐related peptic ulcer disease from the perspective of a public health organization in Hong Kong.

Methods:

Records of 200 patients with H. pylori‐related peptic ulcer disease, who had previously participated in a randomized comparison of ranitidine bismuth citrate (RBC) with amoxicillin and clarithromycin (RAC), omeprazole with amoxicillin and clarithromycin (OAC), RBC with metronidazole and tetracycline (RMT), or, colloidal bismuth subcitrate with metronidazole and tetracycline (BMT) in either in‐patient or out‐patient setting were reviewed.

Results:

Fifty patients were excluded because of incomplete documentation or lack of peptic ulcer. In the out‐patient group (n=72), the median direct costs of the RAC group (HK $ 5094) were lower those of the BMT (HK $ 5400), RMT (HK $ 5394), or OAC (HK $ 5440) groups, but the difference was significant only between the RAC and BMT groups (P < 0.05). In the in‐patient group (n=78), the median direct costs of the RMT group (HK $ 8524) were significantly lower than those of the OAC (HK $ 13 871) and RAC (HK $ 12 092) groups (P < 0.05), but were similar to those of the BMT group (HK $ 8758).

Conclusions:

RAC and RMT are the least costly regimens for out‐patient and in‐patient treatment, respectively, of H. pylori‐related peptic ulcer disease in Hong Kong.
Lack of efficacy of ridogrel, a thromboxane synthase inhibitor, in a placebo‐controlled, double‐blind, multi‐centre clinical trial in active Crohn’s disease
Authors: Carty E. , Rampton D. S. , Schneider H. , Rutgeerts P. , Wright J. P.
Published: March 2003

Background:

Thromboxanes are produced in excess and platelets are activated in active Crohn’s disease. Preliminary reports have suggested that ridogrel, a dual thromboxane synthase inhibitor and receptor antagonist, may have therapeutic benefit in patients with inflammatory bowel disease.

Aims:

To investigate the efficacy of ridogrel in patients with active Crohn’s disease.

Patients and methods:

This was an international, multicentre, randomized, double‐blind, placebo‐controlled trial of 5 mg/day oral ridogrel for 12 weeks in 85 patients with moderately active Crohn’s disease. Sixty patients were randomized to receive ridogrel, and 25 to placebo. The Crohn’s disease activity index (CDAI) was used to assess disease activity: remission was defined as a CDAI < 150. Changes in clinical condition, as assessed by the Harvey–Bradshaw index, global evaluation by the investigator and the patient, and blood measures of inflammation, were used as secondary outcomes.

Results:

The patients’ mean (s.d.) CDAI at recruitment was 277 (68) in the ridogrel treated group and 265 (70) in the placebo group. At their final assessment, 20 out of 60 (35%) patients who had been given ridogrel in an intention‐to‐treat analysis and seven out of 25 (28%) patients given placebo were in remission (no significant difference). No significant differences in Harvey– Bradshaw index or global evaluation were noted between patients given ridogrel and those given placebo. Adverse events were similar in both groups.

Conclusion:

A 5‐mg dose of oral ridogrel was not more effective than placebo in inducing remission in patients with moderately active Crohn’s disease. If thromboxane synthesis and platelet function are to be targeted for the treatment of Crohn’s disease, more potent agents require development and assessment.
Non‐systemic chemotherapy in the treatment of colorectal cancer—portal vein, hepatic arterial and intraperitoneal approaches
Authors: Buecher B. , Bleiberg H.
Published: March 2003

Loco‐regional chemotherapy, an alternative to systemic chemotherapy in the management of colorectal cancer, has been evaluated in both adjuvant and palliative settings. The rationale for loco‐regional delivery is to achieve higher dose concentrations of drugs at the tumour site or at the most common sites of tumour recurrence, while limiting systemic exposure and associated toxicity.

Adjuvant intraportal chemotherapy and palliative hepa‐tic arterial chemotherapy have been most extensively investigated. Intraperitoneal chemotherapy has also been studied as an adjuvant treatment after complete resection of colorectal cancer or cytoreductive surgery in patients with established peritoneal carcinomatosis. The results obtained have been disappointing, and none of these procedures can be considered as a standard therapeutic option today. However, methodological difficulties were encountered in most published studies, and the investigated schedules and doses may not have been optimal.

New combinations of cytotoxic drugs and new indications are currently under consideration. Promising results have recently been published for adjuvant intraperitoneal chemotherapy and hepatic arterial chemotherapy following surgical resection of hepatic metastases, but additional well‐designed multicentre phase III trials are needed to determine the true benefits of these treatment modalities and to address the issues of cost and quality of life.
Lack of symptom benefit following presumptive Helicobacter pylori eradication therapy in primary care
Authors: Williams D. , O'Kelly P. , Kelly A. , Feely J.
Published: March 2003

Background:

Helicobacter pylori eradication regimens have failure rates under 10%, however little information is available on the effect of treatment success in reducing the subsequent prescription of anti‐ulcer medications in primary care.

Aims:

To determine, using a large prescription database in eastern Ireland, the success of presumptive eradication therapy in improving symptoms of dyspepsia in primary care, as judged by a reduction in the subsequent prescription of anti‐ulcer medications.

Methods:

In a cross‐sectional study, we identified 3847 patients who received a prescription for eradication therapy for Helicobacter pylori, including 826 who were followed for 9–11 months. Those who subsequently received anti‐ulcer medications were deemed failures to obtain symptom relief.

Results:

For 3847 patients with a median follow‐up of 8 months, the failure rate was 49%. Of 826 patients, followed for a longer period (9–11 months), the overall failure rate was 56% (range 44–62% depending on the eradication regimen used). Age over 65 years (hazard ratio=1.57, 95% confidence interval= 1.29–1.91, P < 0.001), prior use of anti‐ulcer medications (hazard ratio=1.97, 95% confidence interval=1.63–2.37, P < 0.001) and prior use of aspirin/NSAIDs (hazard ratio=1.43, 95% confidence interval=1.18–1.73, P < 0.001) all predicted failure to obtain relief of symptoms of dyspepsia from eradication therapy.

Conclusions:

Such high failure rates of eradication therapy in reducing the subsequent consumption of anti‐ulcer medications have both clinical and economic implications for the use of eradication therapy for Helicobacter pylori in primary care.
Systematic review of proton pump inhibitors for the acute treatment of reflux oesophagitis
Authors: Edwards S. J. , Lind T. , Lundell L.
Published: March 2003

Background:

Esomeprazole is a new proton pump inhibitor, which has been compared to omeprazole for the treatment of reflux oesophagitis in clinical trials.

Aim:

To compare the effectiveness of esomeprazole with the recommended dose of proton pump inhibitors in the healing of reflux oesophagitis, using omeprazole as a common comparator.

Methods:

Systematic review of randomized controlled trials. Extraction and re‐analysis of data to provide ‘intention‐to‐treat’ results. Meta‐analysis using a Fixed Effects model.

Results:

A meta‐analysis of healing rates of esomeprazole 40 mg compared to omeprazole 20 mg gave the following results: at 4 weeks (relative risk 1.14; 95% CI: 1.10, 1.18) and 8 weeks (RR 1.08; 95%CI: 1.05, 1.10). Other proton pump inhibitors compared to omeprazole 20 mg are as follows: lansoprazole 30 mg at 4 weeks (RR 1.02; 95%CI: 0.97, 1.08) and 8 weeks (RR 1.01; 95%CI: 0.97, 1.06); pantoprazole 40 mg at 4 weeks (RR 0.99; 95%CI: 0.91, 1.07) and 8 weeks (RR 0.98; 95%CI: 0.93, 1.04); rabeprazole 20 mg at 4 weeks (RR 1.00; 95%CI: 0.87, 1.14) and 8 weeks (RR 0.98; 95%CI: 0.91, 1.05).

Conclusions:

Esomeprazole has demonstrated higher healing rates than omeprazole at 4 and 8 weeks. Other proton pump inhibitors (lansoprazole, pantoprazole and rabeprazole) have not shown higher healing rates when compared with omeprazole.
Safety and efficacy of glucagon as a premedication for upper gastrointestinal endoscopy—a comparative study with butyl scopolamine bromide
Authors: Hashimoto T. , Adachi K. , Ishimura N. , Hirakawa K. , Katsube T. , Kurotani A. , Hattori S. , Kinoshita Y.
Published: March 2003

Background:

Glucagon inhibits digestive motility and is used for endoscopic premedication; however, its effect on cardiopulmonary function during endoscopy has not yet been fully investigated.

Aim:

To clarify the efficacy and safety of glucagon compared with butyl scopolamine bromide as upper gastrointestinal endoscopy premedication.

Methods:

Two hundred and forty consecutive patients over 40 years of age, referred for upper gastrointestinal endoscopy, without any complications, were studied. These patients were randomly premedicated with butyl scopolamine bromide (SC group) or glucagon (G group). Time course changes in blood pressure, arterial oxygen saturation, heart rate and the number of retching episodes during endoscopy were examined. The efficacy of glucose tablets after upper gastrointestinal endoscopy to prevent hypoglycaemia caused by glucagon was evaluated. Cardiopulmonary parameters were also examined in 77 complicated patients with glucagon premedication (GC group).

Results:

A continuous increase in heart rate during upper gastrointestinal endoscopy was observed in the SC group, but not in the G and GC groups. Blood pressure, arterial oxygen saturation and number of retching episodes were not different between the groups. Hypoglycaemia‐related symptoms were frequent in the G group without glucose tablets, but were prevented by the administration of glucose.

Conclusions:

Glucagon has a weaker effect on cardiopulmonary function during upper gastrointestinal endoscopy than butyl scopolamine bromide. Glucose administration prevents hypoglycaemia‐related symptoms caused by glucagon.