bluuebunny/crossref_metadata_2025 huggingface dataset:
Cure of Helicobacter pylori infection in elderly patients: comparison of low versus high doses of clarithromycin in combination with amoxicillin and pantoprazole
Authors: Pilotto A. , Franceschi M. , Leandro G. , Bozzola L. , Rassu M. , Soffiati G. , Di Mario F. , Valerio G.
Published: March 2003

Background:

Advancing age may influence clarithromycin’s pharmacokinetics. No studies have yet compared the effects of different dosages of clarithromycin in combination with a proton pump inhibitor and amoxicillin in elderly patients.

Aim:

To compare the efficacy and tolerability of clarithromycin 250 mg vs. clarithromycin 500 mg twice daily (b.d.) in combination with pantoprazole and amoxicillin in elderly patients.

Methods:

One hundred and fifty‐four elderly patients with H. pylori‐associated ulcer disease or chronic gastritis were consecutively randomized to receive pantoprazole 40 mg daily plus amoxicillin 1 g, and either clarithromycin 250 mg b.d. (PAC 250) or clarithromycin 500 mg b.d. (PAC 500). Two months after therapy, endoscopy and gastric biopsies were repeated.

Results:

The cure rates of H. pylori infection in the PAC 250 and PAC 500 groups were, respectively, 83% and 79% (ITT analysis) and 94% and 88% (PP analysis) (P=N.S.). Significant decreases in chronic gastritis activity both in the body (P < 0.00001) and the antrum (P < 0.0001) of the stomach were found in H. pylori‐cured patients, independently of clarithromycin dosage. Four patients in PAC 250 (5%) and seven in PAC 500 (9%) reported adverse events (P=N.S.). One patient in PAC 250 (25%) and three in PAC 500 (43%) discontinued the study because of these drug‐related side‐effects (P=N.S.).

Conclusions:

In elderly patients, 1‐week triple therapy with a proton pump inhibitor, amoxicillin and clarithromycin is a highly effective and well tolerated anti‐H. pylori treatment. With this combination, clarithromycin at the lower dose of 250 mg b.d. achieved excel‐ lent cure rates and minimized adverse events and costs.
Review article: transfusion in gastrointestinal haemorrhage—if, when and how much?
Authors: Duggan J. M.
Published: March 2003

Despite the conventional wisdom that blood transfusion is of use in acute upper gastrointestinal haemorrhage, this review proposes that there is considerable doubt about the optimal timing and intensity of transfusion of blood and crystalloids in this setting. It advocates the need for controlled trials to identify the most appropriate timing and intensity of transfusion of patients with acute gastrointestinal haemorrhage.
Review article: lymphatic vessel pumping and inflammation—the role of spontaneous constrictions and underlying electrical pacemaker potentials
Authors: Von Der Weid P.‐Y.
Published: March 2003

The lymphatic circulation is important in maintaining tissue fluid homeostasis. It removes fluid, proteins and other particles from tissue spaces and returns them to the blood stream. This function is achieved by rhythmical contractions of the collecting lymphatic vessels. The contractile mechanism is intrinsic to the smooth muscles present in the vessel wall and consequent to action potentials. The underlying electrical mechanism has been proposed to be due to rhythmic synchronization of Ca2+‐dependent spontaneous transient depolarizations. The lymphatic pumping activity adapts to changes in fluid load and has been observed to augment during inflammatory reactions to help resolve the associated oedema. This beneficial action has been generally attributed to the increase in interstitial pressure consequent to the oedema. However, little attention has been paid to the possible role inflammatory mediators that are present in the lymphatic vessel environment, could play in directly affecting the lymphatic contractile mechanism. This review article discusses our current knowledge on the mechanism and initiation of lymphatic pumping and how these events are modulated during inflammatory conditions.
The limitations of corticosteroid therapy in Crohn’s disease
Authors: Rutgeerts P. J.
Published: March 2003

Corticosteroids are highly effective in inducing clinical remission in patients with active Crohn’s disease. However, the role of corticosteroids in the treatment of this disease is primarily ameliorative because they are ineffective in maintaining remission or healing mucosal lesions. Nearly half of the patients who initially respond to corticosteroid therapy develop a dependency on corticosteroids or have a relapse within 1 year. In addition, use of these agents is often limited by a relatively high risk of serious adverse effects that can involve nearly every major body system. These effects include: bone loss, which can develop with even short‐term and low‐dose corticosteroid therapy; metabolic complications such as glucose intolerance and diabetes mellitus; increased intraocular pressure and glaucoma; and potentially lethal infections.

To minimize the risk of toxicity, corticosteroids are increasingly recommended for short‐term use only at the lowest effective dose to induce remission in patients with moderately to severely active Crohn’s disease. Corticosteroid formulations with low systemic bioavailability, such as controlled‐release budesonide, may be associated with a lower rate of dermatologic adverse effects but appear to be somewhat less effective than conventional corticosteroids in inducing remission in patients with active Crohn’s disease.

Immunosuppressive agents such as azathioprine, 6‐mercaptopurine, and methotrexate have demon‐ strated corticosteroid‐sparing effects, facilitating the withdrawal of corticosteroids when initiated as maintenance therapy. Infliximab can be used as an alternative to corticosteroids.
Double‐blind placebo‐controlled multicentre studies of rebamipide, a gastroprotective drug, in the treatment of functional dyspepsia with or without Helicobacter pylori infection
Authors: Talley N. J. , Riff D. S. , Schwartz H. , Marcuard S. P.
Published: March 2003

Background:

Functional dyspepsia is a problem that is difficult to treat in clinical practice.

Aim:

To evaluate the efficacy and safety of rebamipide (a cytoprotective drug) in functional dyspepsia.

Methods:

Patients with functional dyspepsia (n=557) were divided a priori into two studies by Helicobacter pylori status, and enrolled in a 2‐week baseline evaluation period. Ninety‐nine patients with Helicobacter pylori and 173 patients without Helicobacter pylori, continuing to have at least moderate upper abdominal pain or discomfort, were randomly assigned to rebamipide 100 mg, rebamipide 200 mg or placebo, three times a day, in a double‐blind design for 8 weeks.

Results:

There was significant improvement of individual symptom scores from baseline in all the treatment arms. No significant improvement of individual symptom scores was observed in either rebamipide group at the end of the studies compared to placebo, although the belching score was significantly reduced in the rebamipide 100 mg and 200 mg groups at week 2 (P=0.017 and P=0.012, respectively) in the Helicobacter pylori‐positive patients. The ratio of patients who requested usage of the study medication again was greater in the rebamipide 100 mg (85%) and 200 mg (96%, P=0.020) groups compared with the placebo group (72%) among Helicobacter pylori‐positive patients. There were no serious study medication related adverse events.

Conclusions:

Rebamipide was not superior to placebo in terms of individual symptoms at the end of treatment.
Control of intragastric acidity with over‐the‐counter doses of ranitidine or famotidine
Authors: Hamilton M. I. , Sercombe J. , Pounder R. E.
Published: March 2003

Background:

Histamine H2‐receptor antagonists are available over the counter for the treatment of heartburn.

Aim:

To compare the effects of low doses of ranitidine and famotidine on intragastric acidity in a three‐way crossover study.

Methods:

Healthy subjects (12 male, 12 female) were dosed on three occasions with single oral doses of placebo, ranitidine, 75 mg, and famotidine, 10 mg, 1 h after lunch. The pH of gastric aspirates was then measured for 20 h. Subjects ate standard meals and snacks. Analysis of variance was used to determine the statistical significance of differences in acidity (mmol/L) during the day (12.30–22.30 hours) and night (22.30–08.30 hours).

Results:

Ranitidine and famotidine were superior (P < 0.05) to placebo in decreasing acidity for daytime and night‐time intervals. There were no significant differences in mean gastric acidity between ranitidine and famotidine during the daytime (11.37 mmol/L vs. 13.42 mmol/L, respectively) and night‐time (23.57 mmol/L vs. 24.74 mmol/L, respectively). Intragastric acidity after ranitidine was significantly lower than that after famotidine in the first 2.5‐h period following dosing (4.32 mmol/L vs. 9.28 mmol/L; P < 0.05).

Conclusions:

Lunchtime doses of ranitidine and famotidine decreased acidity during day‐ and night‐time periods. The effect of ranitidine was significantly greater for the first 2.5 h after dosing.
Effects of NSAIDs on cryoprobe‐induced gastric ulcer healing in rats
Authors: Tibble J. , Sigthorsson G. , Caldwell C. , Palmer R. H. , Bjarnason I.
Published: March 2003

Background:

Failure of ulcer healing may be critically important to the development of serious gastrointestinal complications in patients on long‐term NSAIDs.

Aim:

To determine the effect of indometacin, celecoxib, a cyclooxygenase‐2‐specific inhibitor, and nabumetone, a pro‐drug, on ulcer healing rates in the rat.

Methods:

Gastric ulcers were induced using a cryoprobe. An NSAID or a vehicle control was administered to groups of eight rats for 3 or 6 days (2 mg/kg indometacin, 9 mg/kg celecoxib or 40 mg/kg nabumetone). The ulcer area was measured and epithelial proliferation at the ulcer margins was measured histochemically. The effect of the drugs on intestinal prostaglandin levels was also assessed.

Results:

The mean ulcer sizes in the four groups on day 3 were comparable. On day 6, control animals and those receiving nabumetone showed significant ulcer healing (P < 0.02), while the mean ulcer sizes in the indometacin (P < 0.01) and celecoxib (P < 0.02) groups were significantly larger than those in the control group. Higher doses of nabumetone (160 mg/kg), however, impaired healing. Intestinal prostaglandins were reduced (P < 0.01) only in indometacin‐treated animals. The epithelial proliferation index was significantly lower among indometacin‐ (P=0.02) and celecoxib‐treated (P=0.03) animals compared to controls at day 3.

Conclusions:

Celecoxib and indometacin both decreased the epithelial proliferative response and delayed healing of cryoprobe‐induced gastric ulcers. In contrast, nabumetone impaired ulcer healing only at very high doses.
Dysfunction of oesophageal motility in Helicobacter pylori‐infected patients with reflux oesophagitis
Authors: Wu J. C. Y. , Lai A. C. W. , Wong S. K. H. , Chan F. K. L. , Leung W.‐K. , Sung J. J. Y.
Published: March 2003

Background:

Helicobacter pylori infection has been suggested to be protective against gastro‐oesophageal reflux disease. However, a significant proportion of patients with gastro‐oesophageal reflux disease are infected by H. pylori.

Aim:

To study oesophageal motor function in H. pylori‐infected patients with reflux oesophagitis.

Methods:

Patients with erosive reflux oesophagitis were recruited prospectively for stationary oesophageal manometry and 24‐h ambulatory oesophageal pH monitoring. H. pylori status was determined by biopsy urease test. Non‐reflux volunteers were recruited as controls.

Results:

Seventy‐four patients with erosive oesophagitis (34 H. pylori‐positive, 40 H. pylori‐negative) and 48 non‐reflux patient controls (22 H. pylori‐positive, 26 H. pylori‐negative) were recruited. There was no difference in severity of oesophagitis (median grade, 1; P=0.53) or oesophageal acid exposure (total percentage time oesophageal pH < 4, 7.6% vs. 6.8%; P=0.57) between H. pylori‐positive and H. pylori‐negative groups. Compared to H. pylori‐negative patients, H. pylori‐positive patients had significantly lower basal lower oesophageal sphincter pressure (12.2 mmHg vs. 15.3 mmHg; P=0.03) and amplitude of distal peristalsis (56.9 mmHg vs. 68.4 mmHg; P=0.03). Ineffective oesophageal motility (14% vs. 7%; P=0.02) and failed oesophageal peristalsis were also significantly more prevalent in H. pylori‐positive patients.

Conclusions:

Among patients with a similar degree of reflux oesophagitis, H. pylori‐infected patients have more severe oesophageal dysmotility and lower oesophageal sphincter dysfunction. Oesophageal motor dysfunction probably plays a dominant role in the development of gastro‐oesophageal reflux disease in patients with H. pylori infection.
Appropriateness and diagnostic yield of upper gastrointestinal endoscopy in an open‐access endoscopy system: a prospective observational study based on the Maastricht guidelines
Authors: Manes G. , Balzano A. , Marone P. , Lioniello M. , Mosca S.
Published: March 2003

Aim:

To test the appropriateness of referrals for upper gastrointestinal endoscopy in Campania, Italy, using the criteria of the Maastricht Consensus.

Patients:

Patients undergoing endoscopy during a 1‐week period in 21 Endoscopy Services were considered prospectively. The reasons for endoscopy were dyspeptic symptoms, history of peptic ulcer and assessment after treatment. The age, sex, symptoms, history of peptic ulcer (previous endoscopic or radiographic examinations and treatment), endoscopic diagnosis and H. pylori status were recorded. The indications for endoscopy were evaluated according to the Maastricht guidelines.

Results:

Two hundred and sixteen of 706 patients presented with reflux symptoms, 430 with dyspeptic symptoms, 38 with alarm symptoms and 22 with atypical symptoms. Endoscopy was normal in 376 cases (53.2%); duodenal ulcer was found in 219, gastric ulcer in 45, oesophagitis in 82 and gastric cancer in six. All patients with cancer were older than 45 years, and four presented with alarm symptoms. In 398 cases (56%), endoscopy was considered not to be indicated: 250 patients with a previous diagnosis of ulcer without a change in symptoms, 38 patients in order to confirm eradication and 110 patients younger than 45 years with dyspepsia without alarm symptoms.

Conclusions:

A large number of endoscopic examinations could be avoided by following the guidelines of the Maastricht Consensus. In order to reduce endoscopic workload, strategies for educating physicians should be pursued.
A double‐blind comparison of balsalazide, 6.75 g, and sulfasalazine, 3 g, as sole therapy in the management of ulcerative colitis
Authors: Mansfield J. C. , Giaffer M. H. , Cann P. A. , Mckenna D. , Thornton P. C. , Holdsworth C. D.
Published: March 2003

Background:

Sulfasalazine is accepted therapy for active ulcerative colitis, but side‐effects and intolerance are common. Balsalazide is an azo‐bonded pro‐drug which also releases 5‐aminosalicylic acid into the colon, but uses an inert carrier molecule.

Aim:

To compare the safety and efficacy of sul‐ fasalazine, 3 g, with balsalazide, 6.75 g, in the initial daily treatment of mild to moderate ulcerative colitis.

Methods:

A randomized, multicentre, double‐blind, parallel group study was performed, with a treatment duration of 8 weeks. Patients on previous maintenance treatment were excluded. The trial medication was the sole treatment for the colitis. Efficacy was assessed by patient diaries, symptom assessment, sigmoidoscopic appearance and histology.

Results:

Fifty patients were recruited: 26 allocated to the balsalazide group and 24 to the sulfasalazine group. More patients withdrew due to adverse events in the sulfasalazine group (nine patients vs. one patient in the balsalazide group, P=0.004). Improvement occurred in both groups, with a tendency to a faster response with balsalazide. Of the patients taking balsalazide, 61% achieved clinical and sigmoidoscopic remission.

Conclusions:

Balsalazide, 6.75 g, is effective as the sole treatment for patients with mild to moderately active ulcerative colitis, with significantly fewer withdrawals due to side‐effects than in a similar group of patients taking sulfasalazine, 3 g.
Transient lower oesophageal sphincter relaxations—a pharmacological target for gastro‐oesophageal reflux disease?
Authors: Hirsch D. P. , Tytgat G. N. J. , Boeckxstaens G. E. E.
Published: March 2003

The oesophago‐gastric junction functions as an anti‐reflux barrier preventing increased exposure of the oesophageal mucosa to gastric contents. Failure of this anti‐reflux barrier results in gastro‐oesophageal reflux disease, and may lead to complications such as oesophagitis, Barrett’s oesophagus and eventually oesophageal carcinoma.

Recent studies have suggested that transient lower oesophageal sphincter relaxation is the main mechanism underlying gastro‐oesophageal reflux. It involves a prolonged relaxation of the lower oesophageal sphincter, mediated by a vago‐vagal neural pathway, synapsing in the brainstem.

Several drugs, such as atropine, baclofen and loxiglumide, have been shown to reduce the rate of transient lower oesophageal sphincter relaxations and concomitantly the number of reflux episodes. These findings illustrate that transient lower oesophageal sphincter relaxations may represent a potential new target for the pharmacological treatment of gastro‐oesophageal reflux disease.

It is possible that the reduction in the number of transient lower oesophageal sphincter relaxations may also contribute to the beneficial effect of fundoplication and new endoscopic anti‐reflux procedures. It should be emphasized, however, that other factors, such as low lower oesophageal sphincter pressure, the presence of a hiatal hernia and impaired oesophageal peristalsis, are also of great importance. Therefore, whether the targeting of transient lower oesophageal sphincter relaxations is the ‘golden bullet’ in anti‐reflux therapy remains to be proven, as evidence of an effective control of gastro‐oesophageal reflux in reflux patients is still lacking.
Effects of meal consistency and ingested fluid volume on the intragastric distribution of a drug model in humans—a magnetic resonance imaging study
Authors: Faas H. , Steingoetter A. , Feinle C. , Rades T. , Lengsfeld H. , Boesiger P. , Fried M. , Schwizer W.
Published: March 2003

Background:

Controlled delivery of drugs to the small intestine in relation to emptying of an ingested meal is important in various pathophysiological conditions. We investigated the effects of different food consistencies and the amount of co‐ingested liquid on the intragastric distribution of a contrast marker.

Methods:

Five healthy subjects received four meals (each 650 kcal: A, mashed potato with 100 mL water; B, rice with 100 mL water; C, hamburger meal with 100 mL water; D, hamburger meal with 300 mL water). A capsule filled with gadolinium tetra‐azacyclododecane tetra‐acetic acid solution (as contrast marker) was ingested following meal termination, and its intragastric distribution was assessed by magnetic resonance imaging.

Results:

Initially, marker distribution was confined to the fundus, and subsequently extended along the inner curvature of the stomach. The maximum distribution volume of the marker was lower in meal A than in meal B (P < 0.05). No differences in marker distribution were observed when the hamburger meal was given with 100 or 300 mL water.

Conclusions:

The intragastric distribution kinetics of the marker gadolinium tetra‐azacyclododecane tetra‐acetic acid appeared to depend on meal consistency, but not on the amount of water co‐ingested. Three‐dimensional magnetic resonance imaging allows detailed analysis of the intragastric distribution of a drug model in relation to meal emptying and intragastric meal distribution.
Effects of antacid formulation on postprandial oesophageal acidity in patients with a history of episodic heartburn
Authors: Robinson M. , Rodriguez‐Stanley S. , Miner P. B. , McGuire A. J. , Fung K. , Ciociola A. A.
Published: March 2003

Background:

Heartburn self‐treatment with antacids is extremely common. If the oesophagus is the primary site of antacid action, chewable antacids might raise the oesophageal pH more effectively than swallowable tablets.

Aim:

To establish a model to assess postprandial acid reflux and to compare the onset and duration of action on oesophageal pH of different antacid formulations.

Methods:

Twenty subjects with a history of episodic heartburn underwent eight pH monitoring sessions each for 5.5 h postprandially. One hour after consuming a meal consisting of chilli, cheese, raw onions and cola, subjects received 750 mg, 1500 mg and 3000 mg of either chewable or swallowable CaCO3 tablets, an effervescent bicarbonate solution or placebo. Oesophageal and gastric pH data were collected.

Results:

Mean intra‐oesophageal pH remained lower than baseline for more than 1 h (pH range 5–5.5) postprandially, indicating reflux of somewhat acidic intragastric contents into the oesophagus. The onset of action on oesophageal pH was similar for all antacids (30–35 min). The duration of action on pH varied: chewable tablets and effervescent bicarbonate had relatively long durations of action (oesophagus, 40–45 min; stomach, 100–180 min); swallowable tablets had little effect.

Conclusions:

The meal model used in this study dependably produced acidic gastro‐oesophageal reflux. Antacids increased oesophageal pH independent of gastric pH, demonstrating that chewing antacids controls oesophageal acidity more effectively than swallowing antacid tablets.
Helicobacter pylori, parietal cell antibodies and autoimmune gastropathy in type 1 diabetes mellitus
Authors: De Block C. E. M. , De Leeuw I. H. , Bogers J. J. P. M. , Pelckmans P. A. , Ieven M. M. , Van Marck E. A. E. , Van Hoof V. , Máday E. , Van Acker K. L. , Van Gaal L. F.
Published: March 2003

Background:

Fifteen to 20% of type 1 diabetic patients exhibit parietal cell antibodies (PCA), which are associated with autoimmune gastritis, hypochlorhydria, iron deficiency and pernicious anaemia.

Aim:

To examine whether Helicobacter pylori infection could explain the high prevalence of PCA and autoimmune gastropathy in diabetes. If so, H. pylori eradication could prevent autoimmune gastritis.

Methods:

In 229 type 1 diabetics (M/F: 135/94; age: 41 ± 12 years) PCA were measured. H. pylori infection was assessed by serology, urea breath test in all and by histology (updated Sydney system) in 88 subjects. Pentagastrin tests were performed in 42 patients.

Results:

Sixty‐nine patients were PCA‐positive. H. pylori infection was present in 72 patients and was negatively associated with HLA‐DQA1*0103‐B1*0603 (OR=0.12, P=0.015) and positively with DQA1*0501‐B1*0201 (OR=1.9, P=0.032). PCA‐positivity was linked to HLA‐DQA1*0501‐B1*0301 (OR=3.9, P=0.017). A link between H. pylori and PCA was observed when PCA‐positivity was defined as a titre ≥ 1/20 (OR=2.0, P=0.03), but not if ≥ 1/40 was the cut‐off point. PCA‐positivity, but not H. pylori infection, was associated with iron deficiency anaemia (OR=2.7, P=0.008), pernicious anaemia (OR= 33.5, P < 0.0001), hypochlorhydria (OR=12.1, P=0.0008) and autoimmune gastritis (OR=12.5, P < 0.0001).

Conclusions:

The HLA‐bound susceptibility of H. pylori and PCA differed. PCA‐positivity but not ongoing H. pylori infection is associated with autoimmune gastritis. Low titres of PCA might reflect H. pylori infection rather than autoimmune gastropathy.
One‐week omeprazole, furazolidone and amoxicillin rescue therapy after failure of Helicobacter pylori eradication with standard triple therapies
Authors: Wong W. M. , Wong B. C. Y. , Lu H. , Gu Q. , Yin Y. , Wang W. H. , Fung F. M. Y. , Lai K. C. , Xia H. H. X. , Xiao S. D. , Lam S. K.
Published: March 2003

Aim:

To test the efficacy of omeprazole, furazolidone and amoxicillin triple therapy for the treatment of Helicobacter pylori infection after failure of standard first‐line therapy recommended by the Asia‐Pacific Consensus on the management of H. pylori infection.

Methods:

Patients with failed H. pylori eradication received omeprazole, 20 mg, furazolidone, 100 mg, and amoxicillin, 1 g, all twice daily for 1 week. Endoscopy (CLO test, histology and culture) was performed before treatment. Post‐treatment H. pylori status was determined by 13C‐urea breath test 6 weeks later.

Results:

Fifty patients were recruited. Resistance to metronidazole, clarithromycin and both drugs was in the range of 50–64%, 60–75% and 40–50%, respectively, after failure of first‐line therapy. Amoxicillin resistance was not found. The intention‐to‐treat and per protocol H. pylori eradication rates were 52% and 53%, respectively. Patients with double resistance to metronidazole and clarithromycin showed the lowest eradication rate (38%), which was significantly lower than that of patients with sensitive strains (88%). Side‐effects were minimal and compliance was excellent (98%).

Conclusions:

One‐week omeprazole, furazolidone and amoxicillin rescue therapy achieved a high eradication rate in strains sensitive to metronidazole and clarithromycin. This is a cheap and safe rescue regimen when guided by pre‐treatment sensitivity testing.
Prospective study of the ability of histamine, serotonin or serum chromogranin A levels to identify gastric carcinoids in patients with gastrinomas
Authors: Bashir S. , Gibril F. , Ojeaburu J. V. , Asgharian B. , Entsuah L. K. , Ferraro G. , Crafa P. , Bordi C. , Jensen R. T.
Published: March 2003

Background:

Chronic hypergastrinaemia causes gastric enterochromaffin cell proliferation and carcinoid tumours. The only reliable means to diagnose enterochromaffin cell changes/carcinoids is by biopsy.

Aim:

To assess whether serum histamine, chromogranin A or serotonin and urinary N‐methylimidazoleacetic acid or 5‐hydroxyindoleacetic acid correlate with advanced enterochromaffin cell changes or gastric carcinoids in patients with gastrinomas.

Methods:

Consecutive patients (n=145) had the above assays and endoscopy with gastric biopsies.

Results:

Lower N‐methylimidazoleacetic acid and chromogranin A levels (P < 0.0001) occurred in disease‐free patients. In patients with active disease, the fasting serum gastrin levels correlated (P < 0.0001) with both chromogranin A and N‐methylimidazoleacetic acid levels. Chromogranin A (P=0.005), but not N‐methylimidazoleacetic acid, serotonin, 5‐hydroxyindoleacetic acid or histamine levels, correlated with the enterochromaffin cell index. Carcinoids, but not advanced enterochromaffin cell changes only, were associated with higher chromogranin A and N‐methylimidazoleacetic acid levels.

Conclusions:

Serum chromogranin A levels and urinary N‐methylimidazoleacetic acid levels, but not serum histamine or serotonin or urinary 5‐hydroxyindoleacetic acid, correlate with the presence of gastric carcinoids. However, no assay identified patients with advanced enterochromaffin cell changes only with high sensitivity/specificity. Thus, N‐methylimidazoleacetic acid and chromogranin A levels are unable to identify patients with advanced changes in enterochromaffin cells and therefore neither can replace routine gastric biopsies.
Sequential intravenous/oral antibiotic vs. continuous intravenous antibiotic in the treatment of pyogenic liver abscess
Authors: Ng F. H. , Wong W. M. , Wong B. C. Y. , Kng C. , Wong S. Y. , Lai K. C. , Cheng C. S. , Yuen W. C. , Lam S. K. , Lai C. L.
Published: March 2003

Aim : Pyogenic liver abscesses result in substantial morbidity and mortality. Antimicrobial regimens using sequential intravenous/oral therapy may reduce the length of hospital stay. In this retrospective analysis, the efficacy of continuous intravenous antibiotic therapy (group I) vs. sequential intravenous/oral antibiotic therapy (group II) was studied in patients with pyogenic liver abscess.

Methods : One hundred and twelve consecutive patients (55 in group I and 57 in group II) with pyogenic liver abscess were analysed. Clinical response, length of hospital stay and relapse rates were examined.

Results : Group II had a significantly shorter duration of intravenous antibiotic treatment (3.2 weeks vs. 5.9 weeks, P < 0.01) and a shorter length of hospital stay (28 days vs. 42 days, P < 0.01) when compared to group I. Oral antibiotics were prescribed for a median duration of 2.9 weeks in group II after discharge. No relapse occurred within 6 weeks after the completion of treatment in both groups. The cost of therapy was significantly lower in group II than in group I by 33%.

Conclusions : A sequential intravenous/oral antibiotic regime is a safe and effective treatment for pyogenic liver abscess. This reduces the cost of therapy and the length of hospital stay.
Helicobacter pylori eradication does not worsen quality of life related to reflux symptoms: a prospective trial
Authors: Laine L. , Dhir V.
Published: March 2003

Background:

Concern has been raised that Helicobacter pylori therapy may lead to the development of gastro‐oesophageal reflux disease. This prospective study was designed to assess reflux‐related quality of life and the symptoms of gastro‐oesophageal reflux disease in patients undergoing H. pylori therapy.

Methods:

Patients with a primary complaint of dyspepsia (upper abdominal pain or discomfort) and endoscopic biopsy positive for H. pylori received triple therapy for 2 weeks. A validated reflux‐related quality of life questionnaire sensitive to change was given at baseline, 1 month and 6 months after therapy; symptoms were also recorded. A urea breath test was performed 1 month after the end of therapy; patients and investigators were blind to the results.

Results:

H. pylori was eradicated in 48 of 61 patients. The mean scores in cured patients for each of the five domains were comparable at baseline and 6 months after therapy: differences were − 0.23 to 0.13 (P > 0.20) on a scale of 1–7. The proportion of cured patients with a large decrease in quality of life (10–17% in the five domains) was similar to the proportion with a large increase (15–21%). Heartburn was present at baseline in 22 cured patients; at 6 months, it persisted in 13 and resolved in nine, whilst nine patients developed new heartburn.

Conclusions:

A population of patients presenting with dyspepsia should have no overall increase or decrease in quality of life due to symptomatic gastro‐oesophageal reflux disease in the 6 months after H. pylori therapy.
Determination of the time of onset of action of ranitidine and famotidine on intra‐gastric acidity
Authors: Gardner J. D. , Ciociola A. A. , Robinson M. , Mcisaac R. L.
Published: March 2003

Background : No standard methods exist for determining the onset of action of gastric antisecretory agents in human subjects.

Methods : Intragastric pH was measured when placebo, ranitidine 150 mg, ranitidine 75 mg or famotidine 10 mg were administered 30 min after the end of a meal.

Results : When the onset of action was defined as the earliest time that mean gastric pH with active treatment was statistically significantly higher (P < 0.05) than the corresponding placebo value, the onsets of action of ranitidine 75 mg and 150 mg were 55 min, and of famotidine 10 mg, 90 min. When onset was defined in terms of a particular decrease in gastric acid concentration for the group as a whole or for individual subjects, there was an important variation in the relative times of onset of ranitidine 75 mg and famotidine 10 mg.

Conclusions : When administered after a meal, the onset of action of ranitidine and famotidine on gastric pH can be determined for individual subjects as well as for the group as a whole. When onset was determined for the group using statistical significance, which does not depend on arbitrary cut‐off points, ranitidine 75 mg had an earlier onset of action than did famotidine 10 mg.
Appropriateness of urea breath test: a prospective observational study based on Maastricht 2000 guidelines
Authors: Perri F. , Ricciardi R. , Merla A. , Piepoli A. , Gasperi V. , Quitadamo M. , Andriulli A.
Published: March 2003

Background : The urea breath test is routinely used for diagnosing or confirming the eradication of Helicobacter pylori.

Aim : To evaluate the appropriateness of urea breath test referrals.

Methods : The age, sex, symptoms, endoscopic findings, use of non‐steroidal anti‐inflammatory drugs, family history of gastric cancer or H. pylori infection and concomitant diseases of patients referred for urea breath testing in a 1‐year period were recorded. The appropriateness of urea breath test referrals was judged according to Maastricht guidelines.

Results : One thousand, three hundred and twenty subjects (47 ± 16 years) were referred in 2001: 578 (43.8%) for the diagnosis and 742 (56.2%) for confirmation of the eradication of H. pylori. The urea breath test was considered to be appropriate in 836 (63.3%) patients, inappropriate in 192 (14.5%) and appropriate but avoidable in 292 (22.1%). The appropriateness ratios of urea breath test referrals were 4.6 and 9.0 (P < 0.0001) for general practitioners and gastroenterologists, respectively. Of the patients (n=230) with uninvestigated dyspepsia, who underwent urea breath testing according to a ‘test and treat’ strategy, 98 (42.6%) presented at least one risk factor for organic disease.

Conclusions : In Italy, nearly 36% of urea breath test referrals are inappropriate or could be avoided if all dyspeptic patients with risk factors were referred for endoscopy or all dyspeptic patients undergoing endoscopy were tested for H. pylori infection with biopsy methods. Both general practitioners and, to a lesser extent, gastroenterologists require educational programmes to deal effectively with H. pylori.
Non‐transferrin‐bound iron in untreated and ribavirin‐treated chronic hepatitis C patients
Authors: Van Vlierberghe H. , Verdievel H. , Colle I. , Delanghe J. , Praet M. , Bernard D. , Leroux‐Roels G. , De Vos M.
Published: March 2003

Background : In patients with chronic hepatitis C, elevations in serum iron levels, hepatic iron content and oxidative stress‐related molecules have been reported. Treatment with ribavirin induces an increase in hepatic iron concentration. In situations of iron overload, non‐transferrin‐bound iron can appear. Therefore, we determined non‐transferrin‐bound iron levels in untreated chronic hepatitis C patients and in patients during interferon–ribavirin treatment.

Materials and methods : In 10 untreated and 19 interferon–ribavirin‐treated chronic hepatitis C patients, we examined non‐transferrin‐bound iron levels by a colorimetric method using nitrilotriacetic acid as a ligand and sodium triscarbonatecobalt(iii) to block free iron binding sites on transferrin.

Results : Despite the presence of high serum iron saturation and ferritin levels, non‐transferrin‐bound iron was absent in the majority of hepatitis C virus patients (25/29, 86%). There was no difference in non‐transferrin‐bound iron levels between untreated and treated patients. Four patients with high non‐transferrin‐bound iron levels were distinguished by higher serum iron levels. In two of these patients, hepatocytic iron was present on liver biopsy.

Conclusions : In the majority of chronic hepatitis C patients, non‐transferrin‐bound iron levels are normal. Treatment with ribavirin does not induce high non‐transferrin‐bound iron levels. Non‐transferrin‐bound iron levels are only higher than normal in hepatitis C patients with higher serum iron levels.
A randomized placebo‐controlled trial of simethicone and cisapride for the treatment of patients with functional dyspepsia
Authors: Holtmann G. , Gschossmann J. , Mayr P. , Talley N. J.
Published: March 2003

Aim : To compare the efficacy of simethicone with placebo and the prokinetic cisapride in patients with functional dyspepsia.

Methods : One hundred and eighty‐five patients with functional dyspepsia were randomized and treated in a double‐dummy technique with simethicone (105 mg t.d.s.), cisapride (10 mg t.d.s.) or placebo (t.d.s.). The primary outcome measure was the O'Brien global measure of the patients' rating of 10 upper gastrointestinal symptoms (graded as absent=0, moderate=1, severe=2 or very severe=3). Outcome measures were assessed at baseline and after 2, 4 and 8 weeks of treatment (intention‐to‐treat).

Results : At 2, 4 and 8 weeks, treatment with simethicone and cisapride yielded significantly (all P values < 0.0001) better improvement of symptoms compared to placebo. Simethicone was significantly better than cisapride after 2 weeks (P=0.0007), but the differences were not statistically significant after 4 and 8 weeks. Patients treated with simethicone judged the efficacy of their treatment as very good in 46% of cases, compared to 15% and 16% receiving cisapride and placebo, respectively.

Conclusions : Simethicone and cisapride were significantly better than placebo for symptom control in patients with functional dyspepsia after 2, 4 and 8 weeks of treatment. Simethicone was also superior to the prokinetic cisapride in the first 2 weeks of treatment.
Effects of ABT‐229, a motilin agonist, on acid reflux, oesophageal motility and gastric emptying in patients with gastro‐oesophageal reflux disease
Authors: Netzer P. , Schmitt B. , Inauen W.
Published: March 2003

Aim : The effect of ABT‐229, a new macrolide with no antibacterial activity, on gastro‐oesophageal reflux, oesophageal motility and gastric emptying in patients with gastro‐oesophageal reflux disease was investigated.

Methods : Twenty‐one patients were treated with a placebo and ABT‐229 (2.5, 5 or 10 mg b.d.) in a randomized, incomplete crossover study design. Ambulatory 24‐h pH manometry was performed and gastric emptying was assessed by the 13C‐octanoic acid breath test on the seventh day of treatment.

Results : A significant decrease was found in the mean (± s.e.) percentage of reflux time (intra‐oesophageal pH < 4) for ABT‐229 5 mg b.d. and 10 mg b.d., but not for 2.5 mg b.d., compared with placebo. For ABT‐229 5 mg, it was 8.5 ± 0.5% vs. 10.7 ± 0.7% (P < 0.038) and, for ABT‐229 10 mg, it was 6.6 ± 0.5% vs. 8.4 ± 0.5% (P < 0.019). There were no significant differences in any of the analysed manometric parameters. In addition, the gastric half‐emptying time for all doses of ABT‐229 did not differ significantly from that after placebo.

Conclusions : ABT‐229 is able to reduce slightly, but significantly, acid reflux in patients with gastro‐oesophageal reflux disease. This effect does not appear to be due to a measurable improvement in oesophageal motility or gastric emptying.
Prokinetic effect of indoramin, an α‐adrenergic antagonist, on human gall‐bladder
Authors: Sengupta S. , Cooney R. , Baj M. , Ni'Muircheartaigh R. , O'Donnell L. J. D.
Published: March 2003

Background : The effects of α‐ and β‐adrenergic agents on gall‐bladder motility remain undefined.

Aim : To determine the effects of α‐ and β‐antagonists on gall‐bladder motility in healthy humans.

Methods : In this single, blind, three‐way crossover study, a slow‐release formulation of propranolol 80 mg (β‐antagonist), indoramin 25 mg (post‐synaptic α1‐antagonist) and placebo were administered to 10 healthy volunteers on three separate days 8 h before the assessment of gall‐bladder volumes by ultrasonography. Gall‐bladder volumes were assessed in the fasting state and at 5‐min intervals for 50 min after a standard proprietary enteral feed (Ensure 186 mL, Abbott).

Results : The fasting gall‐bladder volumes of subjects who received placebo or indoramin were significantlydifferent (mean ± S.E.M.: 16.50 ± 2.78 mL and 13.47 ± 2.24 mL, respectively; P < 0.001, two‐way analysis of variance). The fasting gall‐bladder volume after the administration of propranolol was 17.49 ± 2.37 mL and was not significantly different from placebo (16.50 ± 2.78 mL). When the mean post‐prandial gall‐bladder volumes were compared, indoramin significantly enhanced post‐prandial gall‐bladder emptying compared to placebo (P < 0.001). There was no significant post‐prandial volume difference between placebo and propranolol.

Conclusions : Indoramin, an α‐adrenergic antagonist, acts as a prokinetic agent, enhancing post‐prandial gall‐bladder emptying in healthy individuals.
Serum pepsinogen can predict response to H2‐receptor antagonist in patients with functional dyspepsia
Authors: Yoshikawa I. , Murata I. , Kume K. , Kanagawa K. , Hirohata Y. , Nakamura H. , Otsuki M.
Published: March 2003

Background : Therapy for the relief of symptoms of functional dyspepsia is unpredictable.

Aim : To identify which patients may benefit from antisecretory therapy.

Methods : Twenty‐seven patients with functional dyspepsia were selected to receive H2‐receptor antagonist (H2RA) treatment for 4 weeks. Serum pepsinogen A, pepsinogen C and gastrin were measured, and Helicobacter pylori status was determined. Symptoms were assessed at baseline and after H2RA treatment.

Results : Fourteen patients were identified as H2RA responders and the remaining patients were non‐responders. No differences were found between responders and non‐responders with regard to serum pepsinogen A, pepsinogen C, gastrin and H. pylori status. However, the pepsinogen A/C ratio was significantly higher in responders than in non‐responders. Ten of the 13 functional dyspepsia patients (77%) with a high value of the pepsinogen A/C ratio (≥ 4.5) achieved symptom resolution by H2RA, compared with only one of the eight patients (13%) with a low value of the pepsinogen A/C ratio (≤ 3.0).

Conclusions : The serum pepsinogen A/C ratio seems to identify those functional dyspepsia patients for whom acid control provides benefit. This ratio may be a practical tool for the management of functional dyspepsia patients.
Metabolic bone disease is present at diagnosis in patients with inflammatory bowel disease
Authors: Lamb E. J. , Wong T. , Smith D. J. , Simpson D. E. , Coakley A. J. , Moniz C. , Muller A. F.
Published: March 2003

Aim : To establish whether bone disease is present at diagnosis in inflammatory bowel disease and to identify contributory metabolic abnormalities.

Methods : Newly diagnosed patients with inflammatory bowel disease (19 males, 15 females; mean age, 44 years; range, 17–79 years; 23 ulcerative colitis, 11 Crohn's disease) were compared against standard reference ranges and a control group with irritable bowel syndrome (eight males, 10 females; mean age, 40 years; range, 19–64 years). Bone mineral density (g/cm2, dual‐energy X‐ray absorptiometry: lumbar spine and femoral neck) and biochemical bone markers were measured.

Results : Femoral neck bone mineral density, T‐ and Z‐scores (mean ± s.d., respectively) were lower in inflammatory bowel disease patients than in irritable bowel syndrome controls (0.78 ± 0.12 vs. 0.90 ± 0.16, P = 0.0046; − 0.88 ± 0.92 vs. 0.12 ± 1.17, P = 0.0018; − 0.30 ± 0.89 vs. 0.61 ± 1.10, P = 0.0030). Lumbar spine bone mineral density and T‐scores were also significantly lower in patients than controls (0.98 ± 0.15 vs. 1.08 ± 0.13, P = 0.0342; − 1.05 ± 1.39 vs. − 0.14 ± 1.19, P = 0.0304). Compared with controls, the urinary deoxypyridinoline : creatinine ratio was increased (7.66 vs. 5.70 nmol/mmol, P = 0.0163) and serum 25‐hydroxy vitamin D was decreased (18.7 vs. 28.5 µg/L, P = 0.0016); plasma osteocalcin and serum parathyroid hormone did not differ (P > 0.05).

Conclusions : The bone mineral density is reduced at diagnosis, prior to corticosteroid treatment, in both Crohn's disease and ulcerative colitis. Our data suggest that this is attributable to increased resorption rather than decreased bone formation.
Breath testing for human liver function assessment
Authors: Armuzzi A. , Candelli M. , Zocco M. A. , Andreoli A. , De Lorenzo A. , Nista E. C. , Miele L. , Cremonini F. , Cazzato I. A. , Grieco A. , Gasbarrini G. , Gasbarrini A.
Published: March 2003

Carbon‐labelled breath tests were proposed as tools for the evaluation of human liver function 30 years ago, but have never become part of clinical routine. One reason for this is the complex role of the liver in metabolic regulation, making it difficult to provide essential information for the management of patients with liver disease with a single test and to satisfy the hepatology community. As a result, a battery of breath tests have been developed. Depending on the test compound administered, different metabolic pathways (microsomal, cytosolic, mitochondrial) can be examined. Most available data come from microsomal function tests, whilst information about cytosolic and mitochondrial liver function is more limited. However, breath tests have shown promise in some studies, in particular to predict the outcome of patients with chronic liver disease or to monitor hepatic function after treatment. Whilst we await new substrates that can be used to measure liver function in a more valid manner, and large prospective studies to assess the usefulness of available test compounds, the aim of this review is to describe how far we have come in this controversial and unresolved issue.
Natural history and epidemiology ofHelicobacter pyloriinfection
Authors: Go M. F.
Published: March 2003

Helicobacter pyloriis a common bacterium infecting about half the world's population. It is causally linked with a diverse spectrum of gastrointestinal clinical disorders including peptic ulcer disease, gastric cancer, and gastric MALT lymphoma. The principal reservoir is the human stomach, and transmission probably occurs by person‐to‐person passage. Prevalence rates are generally much higher in developing countries compared to developed countries, although there are subgroups within many regions with higherH. pyloriprevalence than in the general population. The prevalence ofH. pylorivaries by geographical location, ethnic background, socioeconomic conditions, and age. Recent studies suggest decreasing prevalence in developed countries or those with rapidly improving socioeconomic conditions. Comparative studies of the two fully sequencedH. pylorigenomes are providing understanding of its large genetic diversity and bacterial virulence factors. The discovery of the type IV secretion system inH. pyloriand its role in translocation of the CagA protein from the bacterial cell into the host epithelial cell provides insight into how host–bacterial interaction may lead to host disease. Cytokine promoter polymorphisms are determinants important in host gastric acid secretion status. Understanding the changing trends inH. pyloriepidemiology, details of its transmission pathways, and the bacterial and host determinants leading to gastroduodenal disease remain the challenges in this area. Global epidemiological studies, advances in technology, and medical interventions have converged to help clarify the mechanisms of interaction between this ubiquitous micro‐organism and its host that result in its diverse clinical manifestations.