bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of alverine citrate on cat intestinal mechanoreceptor responses to chemical and mechanical stimuli
Authors: ABYSIQUE  , LUCCHINI  , ORSONI  , MEI  , BOUVIER
Published: March 2003

Background:

Alverine citrate is commonly used in the treatment of painful affections of the colon.

Aim:

To determine whether alverine citrate acts on the vagal sensory endings.

Methods:

Unitary recordings were performed at the level of the vagal fibres in the nodose ganglion of anaesthetized cats using extracellular glass microelectrodes, and the patterns of response to chemical and mechanical stimuli applied to identified vagal intestinal mechanoreceptors were studied.

Results:

The intestinal mechanoreceptors located at the endings of type C vagal fibres responded mainly to mechanical stimuli (distension and contraction), but also responded to chemical substances (cholecystokinin and substance P). The most conspicuous effect of alverine (2 mg/kg) was that it significantly inhibited the pattern of vagal activity produced in response to either cholecystokinin (5–10 μg/kg), substance P (5–10 μg/kg) or phenylbiguanide (5–10 μg/kg), a 5‐HT3 receptor agonist. On the other hand, the unitary vagal response to the mechanical distension was slightly enhanced by alverine, as was any spontaneous activity present.

Conclusions:

Based on the present data, alverine citrate can be said to decrease the sensitivity of the intestinal mechanoreceptors, which is consistent with its previously established anti‐spasmodic effects.
The importance of clarithromycin dose in the management of Helicobacter pylori infection: a meta‐analysis of triple therapies with a proton pump inhibitor, clarithromycin and amoxycillin or metronidazole
Authors: Huang J.‐Q. , Hunt R. H.
Published: March 2003

Background

: It is not clear which dose of clarithromycin (500 mg b.d. or 250 mg b.d.) is more effective for Helicobacter pylori eradication in proton pump inhibitor‐based triple therapies.

Methods

: We undertook a meta‐analysis of the effect of 7‐day triple therapies consisting of a proton pump inhibitor (P), and clarithromycin (C) and amoxycillin (A) or metronidazole (M). A meta‐analysis of all clinical trials performed in an adult population and published in English up to March 1998 was undertaken. Studies with doses of clarithromycin 500 mg b.d. or 250 mg b.d. only were included.

Results

: A total of 82 studies (31 papers and 51 abstracts) involving 110 treatment arms and 6123 patients were analysed that met the predetermined inclusion and exclusion criteria. In the PAC combination, the pooled eradication rate in patients treated with clarithromycin 500 mg b.d. was 89.5% (95% CI: 86.9–92.0%) by per protocol analysis and 86.6% (95% CI: 81.0–89.3%) by intention‐to‐treat analysis. These rates are significantly higher than those achieved with clarithromycin 250 mg b.d. (83.3% by per protocol and 78.2% by intention‐to‐treat analysis, both P < 0.0001). This difference was confirmed in head‐to‐head comparative studies. In the PMC regimen, clarithromycin 500 mg b.d. eradicated 90.8% (95% CI: 87.0–94.5%) of the infections compared to 88.5% (95% CI: 85.5–91.5%) in patients treated with clarithromycin 250 mg b.d. by per protocol analysis (P = 0.082). The corresponding rates by intention‐to‐treat analysis for clarithromycin 500 mg b.d. and 250 mg b.d. was 88.3% and 86.7%, respectively (P = 0.259).

Conclusions

: Seven‐day triple therapies with a proton pump inhibitor, clarithromycin and amoxycillin or metronidazole are highly effective treatments for the eradication of H. pylori. Clarithromycin 500 mg b.d. should be used in these combinations to achieve the best first treatment results, which can minimize the subsequent development of bacterial resistance to clarithromycin and metronidazole.
Effects of ranitidine bismuth citrate on Helicobacter pylori motility, morphology and survival
Authors: Worku M. L. , Sidebotham R. L. , Karim Q. N.
Published: March 2003

Aim

: The effects of the anti‐ulcer agents ranitidine bismuth citrate (RBC), ranitidine hydrochloride (R) and colloidal bismuth citrate (BC), on Helicobacter pylori motility, morphology and survival were examined to determine whether the clinical effectiveness of RBC might be linked to a specific action that inhibits bacterial motility.

Methods

: H. pylori from patients with duodenal ulcer or non‐ulcer dyspepsia were exposed to RBC and BC at bismuth concentrations ranging from 12.5 to 50 μg/mL, and R at ranitidine concentrations ranging from 12.5 to 50 μg/mL for a brief period (< 15 min), 6 h and 24 h. Bacterial motility was assessed with a Hobson BacTracker, bacterial morphology by transmission electron microscopy, and growth inhibition by counting colony‐forming units.

Results

: H. pylori motility was diminished with RBC and BC but not R. However, the effect of RBC was markedly greater than that of BC at each bismuth concentration and time of exposure tested: (i) brief exposure to RBC/bismuth 50 μg/mL but not to BC, resulted in a significant loss of motility without loss of viability or change in cell morphology, and (ii) bacteria were immobilized, and lost viability after exposure to RBC/bismuth 50 μg/mL for 24 h but not to BC. Morphological destruction caused by RBC differed from that by BC: after 24 h exposure to the highest concentration tested, cell fragmentation and flagella detachment occurred more frequently with BC than RBC, but the latter produced greater disruption of intracellular structures.

Conclusions

: RBC suppresses growth of H. pylori, and has a specific inhibitory effect on the bacterial motor mechanism. These pharmacological actions are likely to contribute to the clinical effectiveness of the agent.
Two‐week dual vs. one‐week triple therapy for cure ofHelicobacter pyloriinfection in primary care: a multicentre, randomized trial
Authors: Calvet X. , López‐Lorente M. ‐T. , Cubells M.‐J , Barè M , Gálvez E. , Molina E. ,   for the Sabadell Primary Care Study Group
Published: March 2003

Background

: One‐week triple therapy has been suggested to be superior to two‐week omeprazole‐clarithromycin therapy for the cure ofHelicobacter pyloriinfection. However, direct comparisons of the two treatments are scarce.

Aim

: To compare triple with dual therapy forH. pyloriinfection in the primary care setting.

Methods

: One hundred and forty‐five patients with duodenal ulcer andH. pyloriinfection were randomized to receive omeprazole 20 mg b.d. and clarithromycin 500 mg t.d.s. for 14 days (OC14 group, 69 patients) or omeprazole 20 mg b.d., clarithromycin 500 mg b.d. and amoxycillin 1 g b.d. for 7 days (OCA7 group, 76 patients). Eradication was evaluated by the13C‐urea breath‐test.

Results

: Intention‐to‐treat analysis showed a cure rate of 48% (95% CI: 36–60%) in the OC14 group, and 71% (95% CI: 59–80%) in the OCA7 group (P=0.0004). Per protocol analysis showed cure rates of 51% (95% CI: 38–63%, 33/65 patients) and 82% (95% CI: 70–90%, 54/66 patients), respectively (P=0.0001). There were no significant differences in compliance or side‐effects.

Conclusion

: One‐week twice‐daily triple therapy is superior to 2‐week dual therapy, but the cure rate in primary care was far below 90%.
Post‐prandial ranitidine is superior to post‐prandial omeprazole in control of gastric acidity in healthy volunteers
Authors: Khoury  , Katz  , Castell
Published: March 2003

Background

: Episodic heartburn is a common problem, affecting over 40 million Americans. Although omeprazole provides excellent acid suppression when used daily, the use of omeprazole as on‐demand therapy for episodic symptoms has not been extensively studied.

Aim

: To compare the onset and duration of post‐prandial gastric acid suppression by omeprazole (10 and 20 mg) or ranitidine (75 and 150 mg) taken as single doses in healthy volunteers.

Methods

: Twenty‐four healthy volunteers (14 male, 10 female, mean age 33.4 years, range 18–56 years) were given ranitidine (RAN) 75 mg or 150 mg vs. omeprazole (OME) 10 mg or 20 mg when pH returned to below 2 after breakfast, in a randomized open label crossover design, with a washout of at least 2 days between medications. Intragastric pH was monitored for 6 h. The time between drug ingestion and rise of gastric pH > 3 and 4, and total time pH remained > 3 and 4 during the 6 h post drug, was compared between groups using two way ANOVA and Wilcoxon matched pairs test.

Results

: The median time needed to pH > 4 was 204.5 min for RAN 75 mg, 186 min for RAN 150 mg and > 360 min for both OME 10 and 20 mg (P < 0.001 between the four groups). The median time that pH remained > 4 was 93 min for RAN 75 mg, 143.5 min for RAN 150 mg and 0 min for both OME 10 and 20 mg (P < 0.001 between the four groups). Both doses of RAN were significantly superior to both doses of OME, although no significant difference was found between the high and the low doses of either drugs. Similar results were found for pH > 3.

Conclusion

: Ranitidine 75 or 150 mg provides more rapid increase in gastric pH to > 3 and > 4 compared to omeprazole 10 or 20 mg when taken at the end of the post‐prandial period. These data suggest that ranitidine may be more effective for episodic post‐prandial heartburn than omeprazole.
Economic analysis of step‐wise treatment of gastro‐oesophageal reflux disease
Authors: Sonnenberg  , Inadomi  , Becker
Published: March 2003

Background

: To expose patients with gastro‐oesophageal reflux disease (GERD) to the least amount of medication and to reduce health expenditures, it is recommended that their treatment is started with a small dose of an antisecretory or prokinetic medication. If patients fail to respond, the dose is increased in several consecutive steps or the initial regimen is changed to a more potent medication until the patients become asymptomatic. Although such treatment strategy is widely recommended, its impact on health expenditures has not been evaluated.

Methods

: The economic analysis compares the medication costs of competing medical treatment strategies, using two different sets of cost data. Medication costs are estimated from the average wholesale prices (AWP) and from the lowest discount prices charged to governmental health institutions. A decision tree is used to model the step‐wise treatment of GERD. In a Monte Carlo simulation, all transition probabilities built into the model are varied over a wide range. A threshold analysis evaluates the relationship between the cost of an individual medication and its therapeutic success rate.

Results

: In a governmental health care system, a step‐wise strategy saves on average $916 per patient every 5 years (range: $443–$1628) in comparison with a strategy utilizing only the most potent medication. In a cost environment relying on AWP, the average savings amount to $256 (–$206 to +$1561). The smaller the cost difference between two consecutive treatment steps, the longer one needs to follow the patients to reap the benefit of the small cost difference. However, even a small cost difference can turn into tangible cost savings, if a large enough fraction of GERD patients responds to the initial step of a less potent but also less expensive medication.

Conclusions

: The economic analysis suggests that a step‐wise utilization of increasingly more potent and more expensive medications to treat GERD would result in appreciable cost savings.
Review article: mechanisms of action and therapeutic applications of ursodeoxycholic acid in chronic liver diseases
Authors: Trauner  , Graziadei
Published: March 2003

Ursodeoxycholic acid (ursodiol) is a non‐toxic, hydrophilic bile acid used to treat predominantly cholestatic liver disorders. Better understanding of the cellular and molecular mechanisms of action of ursodeoxycholic acid has helped to elucidate its cytoprotective, anti‐apoptotic, immunomodulatory and choleretic effects. Ursodeoxycholic acid prolongs survival in primary biliary cirrhosis and it improves biochemical parameters of cholestasis in various other cholestatic disorders including primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, cystic fibrosis and total parenteral nutrition‐induced cholestasis. However, a positive effect on survival remains to be established in these diseases. Ursodeoxycholic acid is of unproven efficacy in non‐cholestatic disorders such as acute rejection after liver transplantation, non‐alcoholic steatohepatitis, alcoholic liver disease and chronic viral hepatitis. This review outlines the present knowledge of the modes of action of ursodeoxycholic acid, and presents data from clinical trials on its use in chronic liver diseases.
Interferon alfa‐2b alone or in combination with ketoprofen as treatment for interferon‐naive chronic hepatitis C patients
Authors: Fabris  , Tositti  , Negro  , Marranconi  , Infantolino  , Rassu  , De Lalla
Published: March 2003

Background

: Non‐steroidal anti‐inflammatory drugs may amplify the anti‐viral effect of α‐interferon in vitro but in vivo data are still controversial.

Aim

: To test the hypothesis that ketoprofen may increase the rate of response to α‐interferon of chronic hepatitis C patients.

Methods

: Fifty patients with chronic hepatitis C who had never received α‐interferon were randomly assigned to receive 3–8 MU of α2b‐interferon, three times weekly for 6 months, alone or in association with ketoprofen at a dose of 200 mg/day five times weekly. The virological response to treatment (undetectable HCV RNA in serum) was evaluated after 3 months and at the end of treatment, and 6 and 12 months after therapy withdrawal.

Results

: One patient under combination therapy stopped the ketoprofen for persisting epigastric pain. Complete response under treatment was observed in 15 out of 24 (62.5%) patients receiving α2b‐interferon alone and in 14 out of 26 (53.8%) patients under combination therapy (P=N.S.). One year after the end of treatment, a sustained response was seen in 4 out of 24 (16.2%) patients treated with α2b‐interferon and in 5 out of 26 (19.2%) patients having received the combination (P=N.S.).

Conclusion

: Administration of ketoprofen does not increase either the primary or the sustained response to α2b‐interferon therapy of interferon‐naive chronic hepatitis C patients.
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 (NUD). 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 NUD patients.

Methods

: Forty‐six NUD patients were examined for gastric emptying, antral myoelectrical activity, H. pylori infection, and symptom scores. In H. pylori‐positive NUD patients, gastric emptying, antral myoelectrical activity, and symptom scores were also analysed 2 months after cure of H. pylori infection.

Results

: Sixty‐seven per cent of NUD patients were H. pylori‐positive. Both abnormal gastric emptying and antral myoelectrical activity were observed in NUD patients. H. pylori‐positive NUD patients were divided into three groups according to their gastric emptying: the delayed group, the normal group, and the rapid group. In the delayed and rapid gastric emptying groups, the emptying and symptom scores were improved significantly by eradication. There was no improvement in symptom scores in the normal gastric emptying NUD group by the eradication therapy.

Conclusions

: Disturbed gastric emptying and antral myoelectrical activity play roles in NUD. H. pylori‐induced disturbed gastric emptying may cause some NUD symptoms. Gastric emptying and symptom scores are improved by H. pylori eradication therapy in NUD patients with disturbed gastric emptying; H. pylori eradication therapy is effective in H. pylori‐positive NUD patients with disturbed gastric emptying.
Management of Helicobacter pylori‐related gastrointestinal diseases by general practitioners in Italy
Authors: Maconi  , Tosetti  , Miroglio  , Parente  , Colombo  , Sainaghi  , Bianchi Porro
Published: March 2003

Aims

: To investigate the diagnostic approach to and management of Helicobacter pylori infection at primary care level in Italy 2 years after the Maastricht consensus report.

Methods

: A total of 100 randomly selected general practitioners (GPs) answered a 12‐item multiple‐choice questionnaire, personally delivered and collected by non‐medical staff.

Results

: In 25% of cases, GPs preferred a prompt referral of dyspeptic patients to the specialist. The favourite diagnostic test for H. pylori infection was gastroscopy with biopsies (55%), followed by standard and office‐based serology (24% and 18%, respectively), and 13C urea breath test (5%). H. pylori‐eradication was prescribed in patients with peptic ulcer, reflux oesophagitis and functional dyspepsia by 64%, 43% and 66% of GPs, respectively. Only 7% of GPs adopted a test‐and‐treat approach. Proton pump inhibitor‐based triple therapies were used by almost all physicians. In peptic ulcer disease, most of GPs re‐tested patients in order to confirm H. pylori eradication (50% by gastroscopy with biopsies and 30% by serology only 2 months after therapy).

Conclusions

: Uncertainty seems to persist among Italian GPs concerning the indications for H. pylori treatment, the use of diagnostic tests, and patient follow‐up. In contrast, no doubts exist regarding the first choice eradication regimens. This survey suggests that further efforts should be made to spread scientific knowledge and guidelines on H. pylori diagnosis and management in primary care in Italy.
Onset of action during on‐demand treatment with Maalox suspension or low‐dose ranitidine for heartburn
Authors: Faaij  , Van Gerven  , Jolivet‐Landreau  , Masclee  , Vendrig  , Schoemaker  , Jacobs  , Cohen
Published: March 2003

Aim:

To compare the onset of action of the local antacid Maalox and the systemic H2‐antagonist ranitidine, during ‘on demand’ ambulant treatment of a single heartburn episode, using a randomized, parallel group, double‐blind, double‐dummy design.

Methods:

Subjects with self‐perceived heartburn without known gastrointestinal disease or interfering treatments were selected with questionnaires. The study was performed unsupervised, whenever heartburn required medication. An electronic patient diary gave instructions when to take study medication, and provided visual analogue scales and five‐item relief ratings for heartburn, at frequent time intervals activated by an alarm‐clock.

Results:

After a study of the natural history of heartburn and the feasibility of the study procedures in 23 patients, 49 subjects took Maalox and 45 ranitidine. Half of these experienced meaningful heartburn relief within 19 min after Maalox, and within 70 min after ranitidine. One hour after intake, the average heartburn relief score was 3.43 in the Maalox group and 3.04 in the ranitidine group (3 means ‘slight improvement’ and 4 ‘strong improvement’). Heartburn was similar in both groups after 3 h.

Conclusions:

Maalox provides faster relief of heartburn than ranitidine. Heartburn can be assessed frequently and reliably under ambulant conditions using an electronic patient diary.
Furazolidone combination therapies for Helicobacter pylori infection in the United States
Authors: Graham  , Osato  , Hoffman  , Opekun  , Anderson  , El‐Zimaity
Published: March 2003

Background:

Antibiotic resistance has begun to impair the ability to cure Helicobacter pylori infection.

Aim:

To evaluate furazolidone as a component of combination therapies for treatment of H. pylori infection in the United States.

Methods:

Patients with active H. pylori infection received furazolidone combination therapy for 14 days (furazolidone 100 mg and tetracycline 500 mg t.d.s.; omeprazole 20 mg o.d. in the morning and, depending on the pre‐treatment antimicrobial susceptibility pattern, 500 mg of metronidazole or clarithromycin t.d.s.).

Results:

A total of 27 patients received the metronidazole containing combination (cure rate 100%) and seven received the clarithromycin combination (cure rate 86%). Overall the cure rates for intention‐to‐treat was 97% (95% CI: 85% to 100%). The single failure took the clarithromycin containing combination for only 2 days (per protocol cure rate = 100%). Side‐effects were common and led to discontinuation of therapy in 26% of patients. An attempt to eliminate metronidazole and clarithromycin and use furazolidone, tetracycline, and lansoprazole b.d. produced an unsatisfactory cure rate of 72%.

Conclusion:

Furazolidone combination therapy appears to be effective. Additional studies with different antimicrobial combinations and duration of therapy are warranted.
Efficacy of a multistep strategy for Helicobacter pylori eradication
Authors: Gasbarrini  , Ojetti  , Armuzzi  , Branca  , Canducci  , Torre E. Sanz , Candelli  , Pastorelli  , Anti  , Fedeli  , Fadda  , Pola  , Gasbarrini
Published: March 2003

Background:

Helicobacter pylori eradication therapies do not achieve 100% success rates. Antibiotic resistant strains are among the major causes of failure. Current recommendations concerning the management of treatment failures are not fully clear.

Aim:

To evaluate the efficacy of a multi‐step therapeutic strategy in a large group of infected patients.

Methods:

A total of 2606 H. pylori‐positive patients were administered tinidazole, clarithromycin and a proton pump inhibitor for 1 week. Patients with continuing infection were then given a second 1‐week course of amoxycillin, clarithromycin and ranitidine bismuth citrate. Patients still infected after the second course underwent upper gastrointestinal endoscopy with H. pylori culture, and then received a 1‐week quadruple proton pump inhibitor‐bismuth based scheme established on H. pylori antibiotic sensitivity.

Results:

After the first step, eradication was achieved in 2063 out of 2413 patients [86% per protocol analysis (PP); 79% intention‐to‐treat analysis (ITT)]. First‐step failures (350 out of 2413; 14.5% PP) showed second‐step eradication rates of 82% (271 out of 329 patients, PP; 77% ITT). The specific quadruple therapy for second‐step failures (58 out of 329, 18% PP) achieved 77% (30 out of 39 patients, PP) or 52% (ITT) success. This algorithm led to overall eradication rates of 99% (PP) or 91% (ITT).

Conclusions:

This multi‐step strategy succeeded in a high percentage of H. pylori infected patients. Given the lack of precise guidelines on treatment failures, assessing H. pylori sensitivity to antibiotics only after failure of the second treatment could be suggested in clinical practice.
A meta‐analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection
Authors: Calvet  , García  , López  , Gisbert  , Gené  , Roque
Published: March 2003

Background:

Although triple therapies with a proton pump inhibitor, clarithromycin and either amoxycillin or metronidazole are the most widely accepted treatment for Helicobacter pylori infection, there is no consensus on how long treatment should be maintained for.

Aim:

To evaluate whether increasing the length of triple therapies beyond 7 days improves treatment efficacy.

Methods:

An extensive search of the literature was performed. Reports of randomized trials comparing different lengths of therapy were selected. Short (7‐day) vs. long (10/14‐day) therapies were compared, and three‐way comparison of 7‐day vs. 10‐day, 10‐day vs. 14‐day and 7‐day vs. 14‐day therapies was performed. Meta‐analysis was conducted using conventional shareware (Review Manager 4.0). The Peto Odds Ratio using a fixed model analysis was calculated for each comparison.

Results:

Thirteen studies were identified. Pooled 10‐ to 14‐day therapies achieved better results than 7‐day schedules. In head‐to‐head comparisons, only 14‐day therapies were significantly better than 7‐day treatments. Improvement in cure rates ranged from 7 to 9%. Comparisons of 7‐day vs. 10‐day and 10‐day vs. 14‐day also showed a non‐significant trend towards better cure rates with longer therapies.

Conclusions:

Fourteen‐day, proton pump inhibitor‐based triple therapy achieves better results than 7‐day schedules. Additional data are necessary to evaluate 10‐day therapies.
Review article: alginate‐raft formulations in the treatment of heartburn and acid reflux
Authors: Mandel  , Daggy  , Brodie  , Jacoby
Published: March 2003

Alginate‐based raft‐forming formulations have been marketed word‐wide for over 30 years under various brand names, including Gaviscon. They are used for the symptomatic treatment of heartburn and oesophagitis, and appear to act by a unique mechanism which differs from that of traditional antacids. In the presence of gastric acid, alginates precipitate, forming a gel. Alginate‐based raft‐forming formulations usually contain sodium or potassium bicarbonate; in the presence of gastric acid, the bicarbonate is converted to carbon dioxide which becomes entrapped within the gel precipitate, converting it into a foam which floats on the surface of the gastric contents, much like a raft on water. Both in vitro and in vivo studies have demonstrated that alginate‐based rafts can entrap carbon dioxide, as well as antacid components contained in some formulations, thus providing a relatively pH‐neutral barrier. Several studies have demonstrated that the alginate raft can preferentially move into the oesophagus in place, or ahead, of acidic gastric contents during episodes of gastro‐oesophageal reflux; some studies further suggest that the raft can act as a physical barrier to reduce reflux episodes. Although some alginate‐based formulations also contain antacid components which can provide significant acid neutralization capacity, the efficacy of these formulations to reduce heartburn symptoms does not appear to be totally dependent on the neutralization of bulk gastric contents.

The strength of the alginate raft is dependant on several factors, including the amount of carbon dioxide generated and entrapped in the raft, the molecular properties of the alginate, and the presence of aluminium or calcium in the antacid components of the formulation. Raft formation occurs rapidly, often within a few seconds of dosing; hence alginate‐containing antacids are comparable to traditional antacids for speed of onset of relief. Since the raft can be retained in the stomach for several hours, alginate‐based raft‐forming formulations can additionally provide longer‐lasting relief than that of traditional antacids. Indeed, clinical studies have shown Gaviscon is superior to placebo, and equal to or significantly better than traditional antacids for relieving heartburn symptoms.

Alginate‐based, raft‐forming formulations have been used to treat reflux symptoms in infants and children, and in the management of heartburn and reflux during pregnancy. While Gaviscon is effective when used alone, it is compatible with, and does not interfere with the activity of antisecretory agents such as cimetidine. Even with the introduction of new antisecretory and promotility agents, alginate‐rafting formulations will continue to have a role in the treatment of heartburn and reflux symptoms. Their unique non‐systemic mechanism of action provides rapid and long‐duration relief of heartburn and acid reflux symptoms.
Metronidazole containing quadruple therapy for infection with metronidazole resistant Helicobacter pylori: a prospective study
Authors: Graham  , Osato  , Hoffman  , Opekun  , Anderson  , Kwon  , El‐Zimaity
Published: March 2003

Background:

Metronidazole remains a key component of H. pylori infection therapy. It has been suggested that despite resistance, metronidazole may be effective when given at high dose with bismuth, tetracycline, and a proton pump inhibitor (quadruple therapy).

Aim:

To prospectively evaluate metronidazole quadruple therapy for treatment of metronidazole resistant H. pylori infection in the United States.

Methods:

Patients infected with metronidazole resistant H. pylori were prospectively prescribed 14 days of quadruple therapy consisting of metronidazole 500 mg t.d.s., tetracycline 500 mg q.d.s., two bismuth subsalicylate tablets q.d.s., and omeprazole 20 mg o.d.

Results:

A total of 26 patients were entered into the study; 22 for their first treatment and four as re‐treatment for failed therapy. Of the 26 patients, 24 were cured (cure rate 92%; 95% CI: 78–99%). Both treatment failures reported full compliance to 14 days of therapy. Side‐effects were common and resulted in premature discontinuation of therapy in 31%. Premature discontinuation did not reduce the cure rate.

Conclusion:

Quadruple metronidazole combination therapy is effective despite the presence of metronidazole resistance and should be considered as either first line therapy or for failures of twice‐a‐day combination therapies.
A placebo‐controlled study to assess the effects of 7‐day dosing with 10, 20 and 40 mg rabeprazole on 24‐h intragastric acidity and plasma gastrin in healthy male subjects
Authors: Williams  , Blanshard  , Millson  , Sercombe  , Pounder
Published: March 2003

Aim:

To compare the effects of rabeprazole 10, 20 and 40 mg o.d. on 24‐h intragastric acidity and plasma gastrin concentration in a randomized, double‐blind placebo‐controlled trial.

Methods:

Twenty‐four healthy male volunteers were studied on the 7th day of morning dosing with either placebo or rabeprazole 10, 20 or 40 mg in a crossover fashion. On day 7, hourly intragastric acidity was measured for 24 h from 08.00 hours by gastric aspiration. Plasma gastrin concentrations were also measured hourly from 08.00 to 24.00 hours, and 2‐hourly thereafter.

Results:

Compared with placebo, rabeprazole 10, 20 and 40 mg produced significant dose‐related decreases in intragastric acidity (median 24‐h integrated acidity=697, 186, 129 and 82 mmol h/L, respectively). This was associated with significant elevation of plasma gastrin concentration (median 24‐h integrated gastrin=141, 1184, 1484 and 1763 pmol.h/L, respectively). Rabeprazole 40 mg resulted in significantly decreased acidity compared with both 10 and 20 mg, and in longer times for which intragastric pH was maintained at > 3 (19.2 h vs. 17.3 h and 17.5 h) and > 4 (17 h vs. 14.2 h and 15.2 h), but was accompanied by significantly increased plasma gastrin. There was a consistent trend for greater antisecretory activity for 20 mg compared with 10 mg, but these differences did not reach statistical significance. The interindividual variability in antisecretory response was greatest with 10 mg.

Conclusions:

Rabeprazole 10, 20 and 40 mg produce significant, profound dose‐related inhibition of gastric acid secretion. Taking into account reciprocal increases in plasma gastrin and the interindividual variation in antisecretory response, 20 mg appears to be the preferred dose for routine clinical use.
Review article: primary prophylaxis for portal hypertensive bleeding in cirrhosis
Authors: Vlachogiannakos  , Goulis  , Patch  , Burroughs
Published: March 2003

Variceal bleeding is a consequence of portal hypertension, which in turn is the major complication of hepatic cirrhosis. Given the high rate of mortality of the first bleeding episode, primary prophylaxis to prevent bleeding from varices and portal hypertensive gastropathy is the current optimal therapeutic approach. The difficulty in identification of patients with varices who will bleed, before they do so, can justify a strategy of treating all patients with varices prophylactically. We evaluated the various therapies that have been assessed in randomized controlled trials for prevention of first bleeding, using meta‐analysis where applicable. The current first choice treatment is non‐selective β‐blockers; it is cheap, easy to administer, and is effective in preventing the first variceal haemorrhage and bleeding from gastric mucosa. Combination drug therapy of β‐blockers and nitrates looks promising, but needs further evaluation in randomized controlled trials. The conflicting results of the randomized studies of endoscopic banding ligation and the small number of patients and clinical events, as well as the cost, do not warrant any change in current practice. However, endoscopic banding ligation may be a reasonable alternative for patients who cannot tolerate, or have contraindications to β‐blockers or no haemodynamic response to the drug therapy, but this must be proved in randomized trials.
Effects of interferon‐beta on plasma lipid and lipoprotein composition and post‐heparin lipase activities in patients with chronic hepatitis C
Authors: Andrade  , García‐Escaño  , Valdivielso  , Alcántara  , Sánchez‐Chaparro  , González‐Santos
Published: March 2003

Background:

Interferon therapy has been shown to induce lipid abnormalities.

Aim:

We assessed the effects of interferon‐β on the lipoprotein profile and post‐heparin lipase activities in 26 normolipaemic patients with chronic hepatitis C.

Methods:

Interferon‐β was administered subcutaneously at doses of 6 × 106 U (units) three times a week, over 6 months, and lipoproteins and post‐heparin lipases were measured at baseline and at the end of therapy.

Results:

Plasma triglycerides increased by 21% due to preferential enrichment in those contained in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions. The concentration of cholesterol decreased slightly in the high density lipoprotein (HDL) subfractions. Lipoprotein lipase, but not hepatic lipase activity decreased by a 36%, and this change showed a significant negative correlation with changes in plasma triglycerides. Five patients (19.5%) responded to interferon‐β therapy. The lipoprotein profile was no different between responders and non‐responders to therapy.

Conclusions:

Interferon‐β treatment in normolipaemic patients with chronic hepatitis C induced moderate disturbances in plasma lipoproteins, associated with inhibition of lipoprotein lipase activity.
Pantoprazole versus one‐week Helicobacter pylori eradication therapy for the prevention of acute NSAID‐related gastroduodenal damage in elderly subjects
Authors: Pilotto A. , Di Mario F. , Franceschi M. , Leandro G. , Battaglia G. , Germanà B. , Marin R. , Valerio G.
Published: March 2003

Aim:

To compare the efficacy of pantoprazole vs. a one‐week Helicobacter pylori eradication therapy for the prevention of NSAID‐related gastroduodenal damage.

Methods:

Patients over 60 years old with symptoms and/or a history of ulcer who needed NSAID treatment were evaluated by endoscopy. H. pylori positive subjects who had no severe gastroduodenal lesions were randomized to take, concomitantly with NSAID therapy, either: (i) pantoprazole 40 mg daily plus amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. for 1 week (35 subjects, Group PAC) or (ii) pantoprazole 40 mg daily for 1 month (34 subjects, Group P). Endoscopy was repeated after 1 month.

Results:

A significantly higher incidence of severe gastroduodenal damage was found in Group PAC than in Group P (29% vs. 9%, P < 0.05). The percentages of patients worsened, unchanged and improved after 1 month were, respectively: Group PAC: 46%, 46%, and 9% and Group P: 7%, 65%, and 29% (P < 0.0008). The percentage of H. pylori‐negative subjects was 89% in Group PAC and 52% in Group P (P=0.0009). The incidence of gastroduodenal damage was higher in Group PAC treatment failures than in cured patients (50% vs. 25.8%, P=ns).

Conclusion:

One month of pantoprazole was more effective than a proton pump inhibitor‐based triple therapy in the prevention of gastroduodenal damage in elderly H. pylori‐positive NSAID users.
Proton pump inhibitor, clarithromycin and either amoxycillin or nitroimidazole: a meta‐analysis of eradication of Helicobacter pylori
Authors: Gisbert J. P. , González L. , Calvet X. , García N. , López T. , Roqué M. , Gabriel R. , Pajares J. M.
Published: March 2003

Aim:

To perform a meta‐analysis of studies comparing twice daily, one‐week triple therapy with a proton pump inhibitor, clarithromycin (C) and amoxycillin (A) (PCA) vs. those using proton pump inhibitor, clarithromycin and a nitroimidazole (N) (PCN) for H. pylori eradication.

Review methods:

Selection criteria: Comparative randomized trials of PCA vs. PCN were included. Data sources: PubMed database and abstracts from congresses until September 1999. Statistics: Meta‐analysis was performed combining the Odds Ratios (OR) of the individual studies in a global OR (Peto method) both on an intention‐to‐treat (ITT) and on a per protocol (PP) basis.

Results:

Twenty‐two studies fulfilled the inclusion criteria. Eighteen studies reported ITT and 20 PP analysis. Mean H. pylori eradication rates were 81% (95% CI: 79–83%) ITT, and 84% (82–86%) PP with PCA, and 81% (78–83%) ITT and 84% (82–86%) PP with PCN; the odds ratio for the effect of PCA vs. PCN was 1 (0.83–1.22) on an ITT, and 0.98 (0.8–1.2) on a PP basis. Subanalysis showed that mean H. pylori eradication efficacy with PC(250 b.d.)A was 81% (78–85%) ITT, vs. 86% (83–89%) with PC(250 b.d.)N. The odds ratio for this comparison was 0.68 (0.48–0.98). Finally, when comparing PC(500 b.d.)A against PC(250 b.d.)N ITT cure rates were 77% (74–80%), and 75% (72–78%) with an odds ratio of 1.18 (0.93–1.5).

Conclusion:

Overall, one‐week combination regimens of PCA and PCN present similar H. pylori eradication efficacy. Nevertheless, the PCN regimen obtains significantly better results when using low doses of C (250 mg b.d.).
A pilot study of N‐acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease
Authors: Salvatore S. , Heuschkel R. , Tomlin S. , Davies S. E. , Edwards S. , Walker‐Smith J. A. , French I. , Murch S. H.
Published: March 2003

Background:

The breakdown of glycosaminoglycans is an important consequence of inflammation at mucosal surfaces, and inhibition of metalloprotease activity may be effective in treating chronic inflammation.

Aim:

To report an alternative approach, using the nutriceutical agent N‐acetyl glucosamine (GlcNAc), an amino‐sugar directly incorporated into glycosaminoglycans and glycoproteins, as a substrate for tissue repair mechanisms.

Methods:

GlcNAc (total daily dose 3–6 g) was administered orally as adjunct therapy to 12 children with severe treatment‐resistant inflammatory bowel disease (10 Crohn’s disease, 2 ulcerative colitis). Seven of these children suffered from symptomatic strictures. In addition, similar doses were administered rectally as sole therapy in nine children with distal ulcerative colitis or proctitis resistant to steroids and antibiotics. Where pre‐ and post‐treatment biopsies were available (nine cases), histochemical assessment of epithelial and matrix glycosaminoglycans and GlcNAc residues was made.

Findings:

Eight of the children given oral GlcNAc showed clear improvement, while four required resection. Of the children with symptomatic Crohn’s stricture, only 3 of 7 have required surgery over a mean follow‐up of > 2.5 years, and endoscopic or radiological improvement was detected in the others. Rectal administration induced remission in two cases, clear improvement in three and no effect in two. In all cases biopsied there was evidence of histological improvement, and a significant increase in epithelial and lamina propria glycosaminoglycans and intracellular GlcNAc.

Conclusions:

GlcNAc shows promise as an inexpensive and nontoxic treatment in chronic inflammatory bowel disease, with a mode of action which is distinct from conventional treatments. It may have the potential to be helpful in stricturing disease. However, controlled trials and an assessment of enteric‐release preparations are required to confirm its efficacy and establish indications for use.
The prevalence of gastro‐oesophageal reflux symptoms in a UK population and the consultation behaviour of patients with these symptoms
Authors: Kennedy T. , Jones R.
Published: March 2003

Background:

Patients consulting with gastro‐oesophageal reflux symptoms (GORS) may differ from nonconsulters.

Aim:

To describe these differences in a UK population.

Methods:

A postal questionnaire was sent to 4432 adults. Definitions used were GORS (either heartburn or acid regurgitation on more than six occasions during the previous year), dyspepsia (upper abdominal pain or discomfort on more than six occasions during the previous year) and irritable bowel syndrome (abdominal pain with three or more Manning criteria). Socio‐economic status was identified by the Standard Occupational Classification.

Results:

With a 71.7% response, GORS were reported by 28.7% of the sample, it was unaffected by gender and age but was more common among the socially disadvantaged (P < 0.005). Less than 25% of GORS patients consulted during the previous year. Increasing age (χ2 for trend; P < 0.001) and coexisting upper abdominal symptoms (χ2P < 0.001) positively influenced consultation behaviour, but it was unaffected by socio‐economic status, gender, or the coexistence of irritable bowel syndrome. Dyspepsia and nausea independently predicted consultation.

Conclusions:

GORS are especially common among the deprived. Socio‐economic variables do not affect consultation behaviour, but the patient’s age and the burden (number and type) of associated symptoms do.
Review article: healing after inflammatory injury – coordination of a regulatory peptide network
Authors: Podolsky D. K.
Published: March 2003

Intestinal epithelial cells are capable of producing a variety of cytokines and other regulatory factors that can affect functional regulation of the epithelium itself, through autocrine and paracrine mechanisms, as well as functional integration with lamina propria populations. The bi‐directional nature of this cytokine network is now apparent, with the demonstration that both rat and human intestinal epithelium‐derived cell lines possess a much greater array of cytokine receptors than previously anticipated.
The roles of prostaglandin E receptor subtypes in the cytoprotective action of prostaglandin E2 in rat stomach
Authors: Araki H. , Ukawa H. , Sugawa Y. , Yagi K. , Suzuki K. , Takeuchi K.
Published: March 2003

Aim: To investigate the EP receptor subtype involved in the gastroprotective action of prostaglandin (PG) E2 using various EP receptor agonists in rats, and using knockout mice lacking EP1 or EP3 receptors.

Methods: Male SD rats and C57BL/6 mice were used after an 18‐h fast. Gastric lesions were induced by oral administration of HCl/ethanol (150 m
m HCl in 60% ethanol). Rats were given various EP agonists i.v. 10 min before HCl/ethanol: PGE2, sulprostone (EP1/EP3 agonist), butaprost (EP2 agonist), 17‐phenyl‐ω‐trinorPGE2 (17‐phenylPGE2: EP1 agonist), ONO‐NT012 (EP3 agonist) and 11‐deoxyPGE1 (EP3/EP4 agonist). In a separate study, the effect of PGE2 on HCl/ethanol lesions was examined in EP1‐ and EP3‐receptor knockout mice.

Results: Gastric lesions induced by HCl/ethanol were dose dependently prevented by PGE2; this effect was mimicked by sulprostone and 17‐phenylPGE2 and was significantly antagonized by ONO‐AE‐829, an EP1 antagonist. Neither butaprost, ONO‐NT012 nor 11‐deoxyPGE1 exhibited any protective activity against HCl/ethanol‐induced gastric lesions. PGE2 caused an inhibition of gastric motility as well as an increase of mucosal blood flow and mucus secretion, the effects being mimicked by prostanoids activating EP1 receptors, EP2/EP3/EP4 receptors and EP4 receptors, respectively. On the other hand, although HCl/ethanol caused similar damage in both wild‐type mice and knockout mice lacking EP1 or EP3 receptors, the cytoprotective action of PGE2 observed in wild‐type and EP3‐receptor knockout mice totally disappeared in mice lacking EP1 receptors.

Conclusion: The gastric cytoprotective action of PGE2 is mediated by activation of EP1 receptors. This effect may be functionally associated with inhibition of gastric motility but not with increased mucosal blood flow or mucus secretion.
Review: pathogenesis of gallstones
Authors: Dowling R. H.
Published: March 2003

The aim of this article is to review selected aspects of the pathogenesis of cholesterol‐rich, gall‐bladder stones (GBS) – with emphasis on recent developments in biliary cholesterol saturation, cholesterol microcrystal nucleation, statis within the gall‐bladder and, particularly, on the roles of intestinal transit and altered deoxycholic acid (DCA) metabolism, in GBS development.

In biliary cholesterol secretion, transport and satura‐ tion, recent developments include evidence in humans and animals, that bile lipid secretion is under genetic control. Thus in mice the md‐2 gene, and in humans the MDR‐3 gene, encodes for a canalicular protein that acts as a ‘flippase' transporting phospholipids from the inner to the outer hemi‐leaflet of the canalicular membrane. In the absence of this gene, there is virtually no phospho‐ lipid or cholesterol secretion into bile. Furthermore, when inbred strains of mice that have ‘lith genes' are fed a lithogenic diet, they become susceptible to high rates of GBS formation.

The precipitation/nucleation of cholesterol micro‐ crystals from supersaturated bile remains a critical step in gallstone formation. methods of studying this phenomenon have now been refined from the original ‘nucleation time' to measurement of cholesterol appearance/detection times, and crystal growth assays. Furthermore, the results of recent studies indicate that, in addition to classical Rhomboid‐shape monohydrate crystals, cholesterol can also crystallize, transiently, as needle‐, spiral‐ and tubule‐shaped crystals of anhydrous cholesterol. A lengthy list of promoters, and a shorter list of inhibitors, has now been defined.

There are many situations where GB stasis in humans is associated with an increased risk of gallstone forma‐ tion – including iatrogenic stone formation in acro‐ megalic patients treated chronically with octreotide (OT). As well as GB stasis, however, OT‐treated patients all have ‘bad' bile which is supersaturated with cholesterol, has excess cholesterol in vesicles, rapid microcrystal mulceation times and a two‐fold increase in the percentage DCA in bile. This increase in the proportion of DCA seems to be due to OT‐induced prolongation of large bowel transit time (LBTT). Thus LBTT is linearly related to (i) the percentage of DCA in serum; (ii) the DCA pool size; and (III) the DCA input or ‘synthesis' rate. Furthermore, the intestinal prokinetic, cisapride, counters the adverse effects of OT on intestinal transit, and ‘normalizes' the percentage of DCA in serum/bile.

Patients with spontaneous gallstone disease also have prolonged LBTTs, more colonic Gram‐positive an‐ aerobes, increased bile acid metabolizing enzymes and higher intracolonic pH values, than stone‐free controls. Together, these changes lead to increased DCA formation, solubilization and absorption. Thus, in addition to the ‘lithogenic liver' and ‘guilty gall‐bladder' one must now add the ‘indolent intestine' to the list of culprits in cholesterol gallstone formation.