bluuebunny/crossref_metadata_2025 huggingface dataset:
Review article: chronic inflammation and reactive oxygen and nitrogen metabolism – implications in DNA damage and mutagenesis
Authors: Grisham M. B. , Jourd'Heuil D. , Wink D. A.
Published: March 2003

It is well known that chronic inflammation of the digestive tract is associated with an increased risk of malignant transformation. Because phagocytic leukocytes and cytokine‐activated parachymal cells produce large amounts of reactive metabolites of oxygen and nitrogen, there has been substantial interest in ascertaining whether these reactive intermediates may mediate mutagenesis and malignant transformation in vivo. However, very little information is available regarding the basic chemistry of how these oxygen and nitrogen‐derived species may interact to yield potentially carcinogenic agents. This review will discuss our present understanding of the chemical and biochemical interactions between superoxide and nitric oxide and provide a model by which these reactive species may damage DNA and mediate mutagenesis.
A new mechanism for anti‐inflammatory actions of proton pump inhibitors – inhibitory effects on neutrophil–endothelial cell interactions
Authors: Yoshida N. , Yoshikawa T. , Tanaka Y. , Fujita N. , Kassai K. , Naito Y. , Kondo M.
Published: March 2003

Background: Neutrophil–endothelial cell interactions mediated by adhesion molecules may be involved in gastric mucosal inflammation associated with Helicobacter pylori or nonsteroidal anti‐inflammatory drugs.

Aim: To investigate the effects of proton pump inhibitors and histamine‐2 receptor antagonists (HRA) on neutrophil‐endothelial cell adhesive interactions induced by H. pylori water extract (HPE) or interleukin‐1β (IL‐1β).

Methods: Human peripheral neutrophils and umbilical vein endothelial cells were incubated with either proton pump inhibitors (lansoprazole and omeprazole) or HRA (famotidine and ranitidine). Neutrophil surface expression of CD11b and CD18 and endothelial cell intercellular adhesion molecule‐1 (ICAM‐1) and vascular adhesion molecule‐1 (VCAM‐1) were assessed by flow cytometry and an enzyme immunoassay, respectively. Neutrophil adherence was defined as the ratio of exogenous neutrophils that adhered to the endothelial monolayers.

Results: The expression of CD11b and CD18 on neutrophils and neutrophil‐dependent adhesion to endothelial cells elicited by HPE were inhibited by lansoprazole and omeprazole at clinical relevant doses, and the expression of ICAM‐1 and VCAM‐1 on endothelial cells and endothelial‐dependent neutrophil adherence induced by IL‐1β were also inhibited by lansoprazole and omeprazole at similar doses. Famotidine and ranitidine had no effect on neutrophil–endothelial cell interactions.

Conclusions: These results indicate that proton pump inhibitors can attenuate neutrophil adherence to endothelial cells via inhibiting the expression of adhesion molecules, suggesting that proton pump inhibitors may have anti‐inflammatory activity.
Oesophageal transit, disintegration and gastric emptying of a film‐coated risedronate placebo tablet in gastro‐oesophageal reflux disease and normal control subjects
Authors: Perkins A. C. , Wilson C. G. , Frier M. , Blackshaw P. E. , Juan D. , Dansereau R. J. , Hathaway S. , Li Z. , Long P. , Spiller R. C.
Published: March 2003

Background:

Risedronate sodium is a pyridinyl bisphosphonate, proven effective for the treatment and prevention of postmenopausal osteoporosis and glucocorticoid‐induced osteoporosis and Paget’s disease of the bone.

Aim:

To compare the oesophageal transit, disintegration and gastric emptying of the commercial film‐coated risedronate tablet in subjects with gastro‐oesophageal reflux disease (GERD) and normal control subjects.

Methods:

A total of 30 subjects, 15 patients with GERD and 15 age‐ and sex‐matched, normal control subjects, participated in a single‐centre, open‐label, comparative gamma scintigraphy study. The GERD subjects had active erosive oesophagitis within 4 weeks prior to dosing.

Results:

The mean oesophageal transit (GERD, 4.4 s; controls, 3.1 s), mean disintegration (GERD, 21.8 min; controls, 19.2 min) and mean gastric emptying (GERD, 15.9 min; controls, 15.0 min) were similar in the two subject groups. The oesophageal transit is rapid and given the rapid disintegration and gastric emptying, oesophageal contact occurring via reflux of risedronate was unlikely since most, if not all, of the dosage form exited from the stomach within 30 min.

Conclusions:

The oval shape and film‐coating on the commercial risedronate tablet promotes rapid oesophageal transit and minimizes oesophageal contact, even in the high‐risk GERD population.
Effect of caloric density of a meal on lower oesophageal sphincter motility and gastro‐oesophageal reflux in healthy subjects
Authors: Pehl C. , Pfeiffer A. , Waizenhoefer A. , Wendl B. , Schepp W.
Published: March 2003

Background:

Patients with gastro‐oesophageal reflux disease are advised to avoid the ingestion of large meals. In healthy volunteers, a relationship between the amount of postprandial gastro‐oesophageal reflux and the volume of a liquid meal has been demonstrated.

Aim:

To evaluate whether the amount of postprandial gastro‐oesophageal reflux is also related to the calorie content of a meal, a second parameter that will be reduced by avoidance of the ingestion of large meals.

Methods:

Twelve healthy volunteers (six female, 19–31 years) received two solid–liquid meals with either 842 kcal (solid 582 kcal, liquid 260 kcal) or 582 kcal (31% reduction) in a randomized order. The nutritional components (10% fat, 76% carbohydrates, 14% protein) and the volume of the meals were identical in both meals. The lower oesophageal sphincter pressure was measured continuously in the first postprandial hour with a Dent sleeve, and pH‐metry was performed for 3 h postprandially with a glass electrode in the distal oesophagus. Blinded to the type of ingested meal, we calculated the mean lower oesophageal sphincter pressure, the frequency of transient lower oesophageal sphincter relaxations, the number of reflux episodes, and the fraction of time for which pH < 4.

Results:

A similar decrease in lower oesophageal sphincter pressure was observed after ingestion of the high calorie meal (median 10.9 mmHg, range 4.8–16.7 mmHg) and low calorie meal (median 9.9 mmHg, range 3.9–18.4 mmHg). No difference in the number of transient lower oesophageal sphincter relaxations (high calorie: median 9 per hour, range 5–13 per hour; low calorie: median 7 per hour, range 0–14 per hour) and of reflux episodes (high calorie: median 12 in 3 h, range 3–22 in 3 h; low calorie: median 12 in 3 h, range 3–30 in 3 h) was registered after intake of both types of meal. Additionally, no difference was identified regarding the fraction of time for which pH < 4 between the high calorie (mean 2.3%, 0.2–23.7%) and low calorie meal (3.3%, 0.5–17.8%).

Conclusion:

Reducing the caloric density of a meal neither influences postprandial lower oesophageal sphincter pressure nor decreases gastro‐oesophageal reflux in healthy volunteers. Thus, the amount of gastro‐oesophageal reflux induced by ingestion of a meal seems to depend on the volume but not on the caloric density of a meal.
Barrett’s oesophagus, dysplasia and pharmacologic acid suppression
Authors: Fitzgerald R. C. , Lascar R. , Triadafilopoulos G.
Published: March 2003

Barrett’s oesophagus, a significant complication of gastro‐oesophageal reflux disease (GERD), is the single most important risk factor for oesophageal adenocarcinoma. The strong association between Barrett’s oesophagus and chronic GERD suggests that abnormal oesophageal acid exposure plays an important role in this condition. The progression of Barrett’s oesophagus from specialized intestinal metaplasia to dysplasia and finally invasive carcinoma is incompletely understood, but increased and disordered proliferation is a key cellular event. In ex vivo organ culture experiments, cell proliferation is increased after exposure to short pulses of acid, whilst proliferation is reduced in Barrett’s oesophagus specimens taken from patients with oesophageal acid exposure normalized by antisecretory therapy.

In long‐term clinical studies, consistent and profound intra‐oesophageal acid suppression with proton pump inhibitors decreases cell proliferation and increases differentiation in Barrett’s oesophagus, but the clinical importance of such favourable effects on these surrogate markers is not clear. In clinical practice, proton pump inhibitors relieve symptoms and induce partial regression to squamous epithelium, but abnormal oesophageal acid exposure and the risk for dysplasia or adenocarcinoma persist in many patients. The ability of proton pump inhibitors to suppress acid profoundly and consistently may be critical in the long‐term management of Barrett’s oesophagus.
A 10‐year survey of inflammatory bowel diseases—drug therapy, costs and adverse reactions
Authors: Blomqvist P. , Feltelius N. , Löfberg R. , Ekbom A.
Published: March 2003

Background:

Drug therapy for Crohn’s disease and ulcerative colitis is based on anti‐inflammatory and immunodulating drugs, nutritional support and surgical resection. Recently, new drugs have been introduced.

Aim:

To report drug prescriptions, costs and adverse reactions among inflammatory bowel disease patients in Sweden between 1988 and 1997.

Methods:

Drug use was calculated from the national Diagnosis and therapy survey and drug costs from prescriptions and drug sales. Adverse drug reactions were obtained from the Medical Products Agency’s National Pharmacovigilance system.

Results:

The annual drug exposure for Crohn’s disease was 0.55 million daily doses per million population, mainly supplementation and aminosalicylic acids. Mesalazine and olsalazine had 61% within this group. For ulcerative colitis patients, drug exposure was 0.61 million daily doses per million per year and aminosalicylic acids fell from 70% to 65%. For inflammatory bowel disease patients, corticosteroids and nutritional supplementation were common. The annual average cost for inflammatory bowel disease drugs was 7.0 million US dollars. Anually, 32 adverse drug reactions were reported, mainly haematological reactions such as agranulocytosis and pancytopenia (60%), followed by skin reactions. Only two deaths were reported. Aminosalicylic acids were the most commonly reported compounds.

Conclusions:

Drug use for inflammatory bowel disease in the pre‐biologic agent era rested on aminosalicylic acid drugs and corticosteroids with stable levels, proportions and costs. The level of adverse drug reactions was low but haematological reactions support the monitoring of inflammatory bowel disease patients.
An evaluation of invasive and non‐invasive tests for the diagnosis of Helicobacter pylori infection in Chinese
Authors: Wong B. C. Y. , Wong W. M. , Wang W. H. , Tang V. S. Y. , Young J. , Lai K. C. , Yuen S. T , Leung S. Y. , Hu W. H. C. , Chan C. K. , Hui W. M. , Lam S. K.
Published: March 2003

Background:

Different tests are available for diagnosing Helicobacter pylori infection.

Aim:

To compare the most commonly used tests either alone or in combination in Chinese patients with respect to routine clinical use or research purpose.

Methods:

A total of 294 consecutive dyspeptic patients without previous H. pylori treatment were recruited. During upper endoscopy, biopsies were taken from the antrum and corpus, for a commercially available CLO‐test, an in‐house rapid urease test, culture, polymerase chain reaction and histological examination. Patients then received a 13C‐urea breath test. The H. pylori status of each patient was determined by a concordance of test results.

Results:

For routine clinical use, histology (antral plus corpus biopsies) had an accuracy of 100%, whilst the rapid urease test had an accuracy of 99.7%. The 13C‐urea breath test was equally reliable, with an accuracy of 94.5%. Combinations of two tests did not confer additional advantage over the most accurate single test. For research purposes, the accuracy of using the criteria of two positives out of three diagnostic tests was 100% and equivocal results were not found.

Conclusion:

Histology with or without a rapid urease test was highly accurate for routine clinical use. Alternatively, the 13C‐urea breath test was an equally reliable non‐invasive test. The two positives out of three tests approach was highly reliable in predicting H. pylori status of untreated Chinese patients in a research setting.
Evaluation of five commercial serological tests for the detection of Helicobacter pylori infection in Chinese
Authors: Szeto M. L. , Lee C. K. , Yee Y. K. , Li K. F. , Lee W. K. , Lee C. C. , Que T. L. , Wong B. C. Y.
Published: March 2003

Background:

Commercial serological tests for the detection of Helicobacter pylori infection must be locally validated. We evaluated the accuracy of five commercial tests in the Chinese population.

Methods:

Serum samples were collected from patients referred for upper endoscopy. Antral biopsies were taken for histological examination and culture of H. pylori. The gold standard for diagnosing H. pylori infection was positive histological staining and/or positive H. pylori culture. The serum samples were tested for H. pylori antibodies using the following tests: (i) Cobas Core Anti‐H. pylori EIA; (ii) GAP IgG; (iii) GAP IgM; (iv) H. pylori microwell EIA (Quidel); and (v) Premier H. pylori. The sensitivity, specificity and accuracy of each test was calculated according to the manufacturers’ instructions or according to a new cut‐off value.

Results:

A total of 158 patients were recruited amongst whom 114 (72%) were H. pylori‐positive. Indeterminate results varied from 7% to 19%. The accuracy of the tests varied from 57% to 85%. By using new cut‐off values, the accuracy was much improved, ranging from 73.4% to 86.7%.

Conclusions:

By defining new cut‐off values for the Chinese population, we were able to improve the performance of some of the serology tests. This illustrates the importance of local validation.
Double gastric infection with Helicobacter pylori and non‐Helicobacter pylori bacteria during acid‐suppressive therapy: increase of pro‐inflammatory cytokines and development of atrophic gastritis
Authors: Sanduleanu S. , Jonkers D. , De Bruïne A. , Hameeteman W. , Stockbrügger R. W.
Published: March 2003

Background:

Long‐term acid suppression may accelerate the development of atrophic gastritis in Helicobacter pylori‐positive subjects. The pathogenetic mechanism remains unclear.

Aim:

To test the hypothesis that gastric double infection with H. pylori and non‐H. pylori bacterial species—during acid suppression—may result in an enhanced inflammatory response, contributing to the development of atrophic gastritis.

Patients and methods:

A consecutive series of patients with gastro‐oesophageal reflux disease undergoing treatment with proton pump inhibitors (n=113) or histamine2‐receptor antagonists (H2‐RAs) (n=37), and 76 non‐treated dyspeptic controls were investigated. Gastric mucosal H. pylori and non‐H. pylori bacteria, histological gastritis, H. pylori serology, and circulating interleukin (IL)‐1β, IL‐6, and IL‐8 were examined.

Results:

Patients on acid suppression with either proton pump inhibitors or H2‐RAs had a similar prevalence of H. pylori infection to the controls, but a higher prevalence of non‐H. pylori bacteria (61% and 60% vs. 29%, P < 0.0001 and P < 0.002). Both the presence of H. pylori and non‐H. pylori bacteria were independent risk factors of atrophic gastritis (antrum: relative risks (RRs), 10.1 and 5.07; corpus: RRs, 11.74 and 6.38). A simultaneous presence of H. pylori and non‐H. pylori bacteria was associated with a markedly increased risk of atrophic gastritis (antrum: RR, 20.25; corpus: RR, 20.38), compatible with a synergistic effect. Furthermore, the simultaneous presence of both types of bacteria was associated with higher cytokine levels than in patients without any type of bacteria. This increase was also greater than in patients with H. pylori infection alone (P < 0.001, for both IL‐1β and IL‐8).

Summary and conclusions:

H. pylori‐positive patients on long‐term acid inhibition displayed three features: non‐H. pylori bacterial growth; increased cytokine levels; and a higher risk of atrophic gastritis. We suggest that double infection with H. pylori and non‐H. pyloribacteria is a major factor in the development of atrophic gastritis during gastric acid inhibition.
Renal tubular injury is present in acute inflammatory bowel disease prior to the introduction of drug therapy
Authors: Fraser J. S. , Muller A. F. , Smith D. J. , Newman D. J. , Lamb E. J.
Published: March 2003

Background

: 5‐aminosalicylic acid (5‐ASA) has been associated with renal complications in inflammatory bowel disease. Renal function is typically monitored using serum creatinine; however, significant disease may predate increases in creatinine.

Aims

: To identify whether markers of early renal disease (urinary albumin, α‐1‐microglobulin [α‐1‐M] and N‐acetyl‐β‐D‐glucosaminidase [NAG], and serum cystatin C) are useful in the assessment of renal function in inflammatory bowel disease patients receiving 5‐ASA.

Methods

: Twenty‐one patients with a new diagnosis of inflammatory bowel disease were investigated. Samples were taken at diagnosis, and at 3‐monthly intervals after the commencement of 5‐ASA, for 1 year.

Results

: Mean creatinine clearance was 100 mL/min and did not change following treatment. Inflammatory bowel disease was not associated with albuminuria. Urinary N‐acetyl‐β‐D‐glucosaminidase and α‐1‐microglobulin at diagnosis were increased in 10 (48%) and 11 (52%) patients, respectively: treatment was not associated with consistent changes in urinary protein excretion. There was a significant correlation between cystatin C and creatinine clearance both at diagnosis (r=–0.533, P=0.0275) and combining the initial and follow‐up data (r=–0.601, P < 0.01), but not between creatinine and creatinine clearance (P > 0.05).

Conclusions

: Tubular proteinuria is an extra‐intestinal manifestation of inflammatory bowel disease irrespective of 5‐ASA treatment. Tubular proteins are not useful predictors of an adverse renal response to 5‐ASA. Serum cystatin C may be an improved marker of glomerular filtration rate in this setting.
Review article: a conceptual approach to understanding the molecular mechanisms of cancer development in Barrett’s oesophagus
Authors: Souza R. F. , Morales C. P. , Spechler S. J.
Published: March 2003

Oesophageal adenocarcinoma is one of the most deadly human malignancies. Gastro‐oesophageal reflux disease (GERD) has been established as a strong risk factor for oesophageal adenocarcinoma, and more than 40% of adult Americans experience regular GERD symptoms. GERD can be complicated by oesophagitis, and by replacement of oesophageal squamous mucosa with metaplastic, intestinal‐type epithelium (Barrett’s oesophagus) that is predisposed to malignancy.

Cancers in Barrett’s oesophagus arise through a sequence of genetic alterations which endow unlimited proliferative capacity upon the cells by affecting components of the cell cycle clock apparatus—the pivotal molecular machinery in the cell nucleus that controls whether a cell will proliferate, differentiate, become quiescent or die.

This report describes how the genetic abnormalities that have been recognized in Barrett’s oesophagus might promote carcinogenesis through effects on the cell cycle clock machinery. The goal of this review is to provide the clinician with a useful conceptual basis for evaluating studies on the molecular mechanisms underlying the progression from metaplasia to carcinoma in Barrett’s oesophagus.
Chronic use of non‐steroidal anti‐inflammatory drugs does not alter colonic mucosa of patients without diarrhoea
Authors: Beaugerie L. , Berenbaum F. , Berrebi D. , Gendre J. P. , Prier A. , Kaplan G. , Chatelet F. P.
Published: March 2003

Background:

Several types of colitis can be NSAID‐induced, but whether chronic use of NSAIDs alters colonic mucosa in patients without diarrhoea is not known.

Patients and methods:

Biopsy specimens of rectal mucosa were taken in six patients with rheumatoid arthritis without diarrhoea receiving NSAIDs (group 1, n=6). Patients with rheumatoid arthritis without diarrhoea not receiving NSAIDs (group 2, n=9), and patients undergoing surveillance colonoscopy (group 3, n=23) served as controls. In all patients from the three study groups, intraepithelial lymphocyte count and apoptotic cell count were assessed, and sub‐epithelial collagen band thickness was measured. Leucocyte population of lamina propria was evaluated semi‐quantitatively. HLA‐DR and CD25 expression of mucosal cells was appreciated by immunohistochemistry.

Results:

Intraepithelial lymphocyte count was in the normal range in all three group patients, and not statistically different between groups. Apoptotic epithelial cell count was not different between groups. Sub‐epithelial collagen band thickness was normal in all the patients. No patient had a marked infiltration of lamina propria by leucocytes, and HLA‐DR and CD25 were normally expressed in all patients.

Conclusion:

These results from a small sample of patients suggest that patients without diarrhoea receiving NSAIDs on a long‐term basis do not develop microscopic or inflammatory colitis.
Randomized clinical study of nitazoxanide compared to metronidazole in the treatment of symptomatic giardiasis in children from Northern Peru
Authors: Ortiz J. J. , Ayoub A. , Gargala G. , Chegne N. L. , Favennec L.
Published: March 2003

Background:

Enteric infection by Giardia intestinalis is a common cause of diarrhoea world‐wide and a significant cause of morbidity in children.

Aim:

To compare the efficacy and safety of nitazoxanide and metronidazole in the treatment of diarrhoea caused by G. intestinalis in children.

Methods:

A total of 110 children presenting with diarrhoea caused by G. intestinalis were randomized to treatment with either a 3‐day course of nitazoxanide (100 mg b.d., age range 2–3 years; 200 mg b.d., age range 4–11 years) or a 5‐day course of metronidazole (125 mg b.d., age range 2–5 years; 250 mg b.d., age range 6–11 years). The patients were followed‐up for a determination of clinical response 7 days after the initiation of treatment, and two subsequent stool samples were collected for parasitological examination.

Results:

Diarrhoea had resolved in 47 children out of 55 (85%) in the nitazoxanide treatment group before the day 7 follow‐up visit, compared to 44 out of 55 (80%) for metronidazole. Diarrhoea resolved within 4 days in most cases. Only mild, transient adverse events were reported.

Conclusions:

A 3‐day course of nitazoxanide suspension is as efficacious as a standard 5‐day course of metronidazole suspension in treating giardiasis in children.
Twenty‐minute 50 mg 13C‐urea breath test without test meal for the diagnosis of Helicobacter pylori infection in Chinese
Authors: Wong W. M. , Wong B. C. Y. , Li T. M. , Wong K. W. , Cheung K. L. , Fung F. M. Y. , Xia H. H. X. , Lam S. K.
Published: March 2003

Background:

We have previously shown that the 75 mg 13C‐urea breath test without citrate test meal is highly accurate for the diagnosis of Helicobacter pylori infection in Chinese subjects. A lower dose 50 mg 13C‐urea breath test protocol with a sampling time at 20 min has not been validated previously.

Aim:

To investigate the accuracy of a 20‐min 50 mg 13C‐urea breath test protocol in Chinese subjects.

Methods:

Consecutive dyspeptic patients referred for upper endoscopy were recruited. 13C‐urea breath test was performed using (a) 75 mg and 50 mg of 13C‐urea on two separate days without a test meal, and (b) 50 mg of 13C‐urea with 2.4 g citrate as test meal, and compared with the gold standard [rapid urease test (CLO test) and histology]. Baseline, 20‐min and 30‐min breath samples were collected in all cases.

Results:

Two hundred and six patients were tested. The accuracy of the 50 mg 13C‐urea breath test (no citrate) at 20 min and 30 min was 98%, comparable to that of the 50 mg 13C‐urea breath test with citrate (99.1%) and the 75 mg 13C‐urea breath test without citrate (100%).

Conclusions:

A 20‐min 50 mg 13C‐urea breath test without citrate produced highly accurate results for the diagnosis of Helicobacter pylori infection and is more economical and convenient for the Chinese population.
A double‐blind placebo‐controlled study of buspirone‐stimulated prolactin release in non‐ulcer dyspepsia—are central serotoninergic responses enhanced?
Authors: Dinan T. G. , Mahmud N. , Rathore O. , Thakore J. , Scott L. V. , Carr E. , Naesdal J. , O'Morain C. A. , Keeling P. W. N.
Published: March 2003

Background:

Dyspepsia is a common symptom for which an organic cause is found in only 40% of patients. When no cause is apparent and the dyspepsia is considered to be idiopathic, a diagnosis of non‐ulcer dyspepsia is made. The pathophysiology of non‐ulcer dyspepsia is poorly understood and numerous theories have been put forward, including a theory of enhanced central serotoninergic receptor sensitivity.

Aim:

To determine the sensitivity of serotonin receptors in non‐ulcer dyspepsia.

Methods:

Using a randomized, double‐blind, placebo‐controlled design, we compared buspirone (a serotonin type 1a partial agonist)‐stimulated prolactin release in 50 patients and 59 healthy comparison subjects. Buspirone, 30 mg, or matching placebo was administered on two separate occasions and prolactin release over 180 min was monitored. Patients and healthy subjects received both treatments in random order, 1 week apart.

Results:

Overall, patients with non‐ulcer dyspepsia had greater prolactin release in response to the buspirone challenge than the healthy comparison subjects, with differences most significant at 90 min following the challenge. Enhancement occurred in patients both with and without Helicobacter pylori infection. Female subjects, both patients and healthy volunteers, showed a greater response to buspirone than male subjects, and the augmentation of response observed in male and female patients was greater in females.

Conclusions:

Patients with non‐ulcer dyspepsia have enhanced central serotoninergic responses and such responses are independent of H. pylori infection. Blockade of such receptors might be an appropriate therapeutic strategy.
A meta‐analysis comparing eradication, healing and relapse rates in patients with Helicobacter pylori‐associated gastric or duodenal ulcer
Authors: Leodolter A. , Kulig M. , Brasch H. , Meyer‐Sabellek W. , Willich S. N. , Malfertheiner P.
Published: March 2003

Aim:

To compare the effectiveness of Helicobacter pylori eradication in curing peptic ulcer disease in trials involving both gastric ulcer and duodenal ulcer.

Methods:

Twenty‐four relevant randomized controlled trials and randomized comparative trials met the predefined selection criteria. Only proton pump inhibitor‐based eradication trials were considered for the evaluation of eradication efficacy and ulcer healing. For the determination of relapse rates, all trials independent of the eradication therapy regimen were considered.

Results:

Data from 2102 patients were analysed comparing gastric ulcer with duodenal ulcer. No statistical differences between gastric ulcer and duodenal ulcer patients were found with regard to eradication rates (summarized odds ratio, 1.23; 95% confidence interval, 0.98–1.55) or ulcer relapse rates, whether in successfully H. pylori eradicated patients (summarized odds ratio, 0.69; 95% confidence interval, 0.26–1.84) or unsuccessfully H. pylori eradicated patients (summarized odds ratio, 1.48; 95% confidence interval, 0.85–2.56). Owing to heterogeneity, healing rates were not comparable.

Conclusions:

The eradication of H. pylori infection cures both gastric and duodenal ulcer, and the cure rates are similar. This suggests that H. pylori is the key factor in peptic ulcer disease independent of the ulcer site.
Reflux symptoms are associated with psychiatric disease
Authors: Avidan B. , Sonnenberg A. , Giblovich H. , Sontag S. J.
Published: March 2003

Methods:

To evaluate the frequency of reflux symptoms in patients with a diagnosed psychiatric disorder and to assess potential risk factors for symptom occurrence.

Methods:

The presence of reflux symptoms was compared between a case population of 94 psychiatric patients and a control population of 198 non‐psychiatric patients.

Results:

Heartburn, exercise‐induced heartburn, cough and dysphagia were all reported significantly more frequently by subjects with psychiatric disorders than by control subjects. The presence of any psychiatric diagnosis exerted an increased risk for both heartburn (odds ratio, 2.71; 95% confidence interval, 1.01–7.30) and exercise‐induced heartburn (3.34; 1.12–9.96). The type of psychiatric disorder, the type of psychotropic medication and the lifestyle did not influence the presence of reflux symptoms.

Conclusions:

Reflux symptoms occur more frequently in patients with than without a diagnosed psychiatric disorder. The reflux symptoms are not associated with any specific type of medication and may reflect a generally reduced threshold for or distorted perception of symptoms.
Budesonide enema in pouchitis—a double‐blind, double‐dummy, controlled trial
Authors: Sambuelli A. , Boerr L. , Negreira S. , Gil A. , Camartino G. , Huernos S. , Kogan Z. , Cabanne A. , Graziano A. , Peredo H. , Doldán I. , Gonzalez O. , Sugai E. , Lumi M. , Bai J. C.
Published: March 2003

Background:

Pouchitis has been suggested to be a recurrence of ulcerative colitis in a colon‐like mucosa. Topical steroids are a valid therapeutic alternative for distal forms of ulcerative colitis.

Aim:

To investigate the efficacy and tolerability of budesonide enema in the treatment of pouchitis compared with oral metronidazole.

Materials and methods:

Twenty‐six patients with an active episode of pouchitis (defined as a pouchitis disease activity index score ≥ 7) and no treatment during the previous month were randomized to receive either budesonide enema (2 mg/100 mL at bedtime) plus placebo tablets or oral metronidazole (0.5 g b.d.) plus placebo enema in a prospective, double‐blind, double‐dummy, 6‐week, controlled trial.

Results:

Based on the intention‐to‐treat principle, we detected a significant improvement in disease activity at the end of the first week with both drugs (P < 0.01). After that, improvement was moderated until stabilization at 4 weeks in both treatments. The per protocol analysis showed that both drugs had similar efficacy in terms of disease activity, clinical and endoscopic findings. Fifty‐eight per cent and 50% of patients improved (decrease in pouchitis disease activity index ≥ 3) with budesonide enema and metronidazole, respectively (odds ratio, 1.4; confidence interval, 0.2–8.9). Adverse effects were observed in 57% of patients given metronidazole and in 25% of patients given budesonide.

Conclusions:

Budesonide enemas are an alternative treatment for active pouchitis, with similar efficacy but better tolerability than oral metronidazole.
Evaluation of renal function following treatment with 5‐aminosalicylic acid derivatives in patients with ulcerative colitis
Authors: Mahmud N. , O'Toole D. , O'Hare N. , Freyne P. J. , Weir D. G. , Kelleher D.
Published: March 2003

Background:

A number of cases of nephrotoxicity have been reported in patients with inflammatory bowel disease taking oral 5‐aminosalicylic acid (5‐ASA).

Aim:

To evaluate the effects of 9 months of therapy with mesalazine or olsalazine on renal function in patients with ulcerative colitis in remission.

Methods:

Forty patients with ulcerative colitis in complete remission for 6 months were randomized to either olsalazine (n=20) or mesalazine (n=20 for nine months). Thirty‐six of the 40 patients were on prior salicylate therapy. Disease activity was the measure ofclinical efficacy and was assessed by the Harvey‐Bradshaw Index (HBI). Laboratory efficacy measurements included glomerular filtration rate (GFR), microalbuminuria, urinary gluthathione S‐transferase (GST) and serum C‐reactive protein (CRP). Safety analysis consisted of documentation of adverse events and laboratory values.

Results:

There was no significant reduction in the GFR overall on therapy. The levels of GFR adjusted for baseline were similar in the two treatment groups after 3, 6 and 9 months. A significantly higher percentage of mesalazine‐treated patients experienced drug related adverse events, all of a minor nature. The incidence of adverse events causing early withdrawal was similar in the two treatment groups.

Conclusion:

Treatment with mesalazine or olsalazine for 9 months had no significant impact on GFR.
The non‐inherited gastrointestinal polyposis syndromes
Authors: Ward E. M. , Wolfsen H. C.
Published: March 2003

The non‐inherited gastrointestinal polyposis syndromes represent a group of rare disorders characterized by the presence of multiple, non‐adenomatous polyps on the gastrointestinal mucosa occurring in unrelated patients. We present here a review of the clinical and histo‐ pathological aspects of the syndromes to include the Cronkhite–Canada syndrome, hyperplastic polyposis and lipomatous polyposis. While infrequently encoun‐ tered, these diseases can have devastating clinical effects that may be aggravated by delays in diagnosis and treatment. Prompt accurate diagnosis and treatment of these uncommon disorders depend on a sound working knowledge of the distinct clinical and pathological features described herein.
Flumazenil vs. placebo in hepatic encephalopathy in patients with cirrhosis: a meta‐analysis
Authors: Goulenok C. , Bernard B. , Cadranel J. F. , Thabut D. , Di Martino V. , Opolon P. , Poynard T.
Published: March 2003

Background:

Randomized controlled trials testing flumazenil in hepatic encephalopathy have shown conflicting results.

Aim:

To compare flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis.

Methods:

An overview of randomized controlled trials comparing flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis was performed. For each end‐point, heterogeneity and treatment efficacy were assessed by Peto and Der Simonian methods. As most trials were crossover in nature, a sensitivity analysis was performed including the two treatment periods.

Results:

Six double‐blind randomized controlled trials, including 641 patients (326 treated with flumazenil and 315 with placebo), were identified. The treatment duration ranged from 5 min to 3 days. Heterogeneity tests between control groups were not significant. The mean percentages of patients with clinical improvement (five trials) were 27% in treated groups and 3% in placebo groups. This difference was significant by both methods (Peto: odds ratio=6.15; 95% confidence interval, 4.0–9.5; P < 0.001; Der Simonian: mean rate difference, 29%; 95% confidence interval, 17–41; P < 0.001). The mean percentages of patients with electroencephalographic improvement were 19% in treated groups and 2% in placebo groups. This difference was significant only with the Peto method (odds ratio=5.8; 95% confidence interval, 3.4–9.7; P < 0.001). The sensitivity analysis showed similar results.

Conclusions:

This meta‐analysis shows that flumazenil induces clinical and electroencephalographic improvement of hepatic encephalopathy in patients with cirrhosis.
Faecal markers in the assessment of activity in inflammatory bowel disease
Authors: Poullis A. , Foster R. , Northfield T. C. , Mendall M. A.
Published: March 2003

The fundamental pathological process behind ulcerative colitis and Crohn's disease is intestinal inflammation. As the precise cause of this is not yet completely understood, current treatment strategies are aimed at reducing or eliminating the inflammation. Endoscopic examination and histological analysis of biopsy specimens remain the `gold standard' methods for detecting and quantifying bowel inflammation; however, these techniques are costly, invasive, and repeated examinations are unpopular with patients. Disease activity questionnaires and laboratory `inflammatory markers', although widely used, show an unreliable correlation with endoscopy and histology. New markers need to be developed to detect and quantify bowel inflammation. These would be of use diagnostically and also an aid to pharmacological treatment.
Role of Helicobacter pylori serology in atrophic body gastritis after eradication treatment
Authors: Lahner E. , Bordi C. , Di Giulio E. , Caruana P. , D'Ambra G. , Milione M. , Grossi C. , Delle Fave G. , Annibale B.
Published: March 2003

Background:

It has been reported that 50% of patients with atrophic body gastritis have positive Helicobacter pylori antibody titres only. In atrophic body gastritis, a decrease in H. pylori antibodies after eradication treatment has been reported, suggesting that serology may indicate an active H. pylori infection.

Aim:

To investigate the time course of H. pylori antibodies and gastric inflammation after eradication treatment in patients with atrophic body gastritis, and to determine whether serology alone can be considered as a valid tool to assess the efficacy of eradication treatment in patients with atrophic body gastritis.

Methods:

Twenty‐seven patients with atrophic body gastritis (12 serologically H. pylori‐positive only, ABG‐S+; 15 H. pylori‐positive at histology and serology, ABG‐H+) were included in the treatment group, and 17 patients (all ABG‐S+) in the no treatment group. All patients had gastroscopy plus biopsies evaluated according to the updated Sydney system and H. pylori immunoglobulin G determination: in the treatment group, at baseline and 6 and 24 months after eradication (bismuth‐based triple regimens); in the no treatment group, at baseline and after 3 years.

Results:

In the treatment group, in ABG‐S+ patients, H. pylori antibodies decreased significantly 6 months after treatment [37.5 U/mL (16–100 U/mL) vs. 15 U/mL (0–100 U/mL), P < 0.01], but 2 years after treatment no further decrease occurred. In addition, in ABG‐H+ patients, a significant decrease in H. pylori antibodies occurred 6 months after treatment [45 U/mL (12.5–100 U/mL) vs. 31 U/mL (0–65 U/mL), P < 0.01], but a further decrease was also observed 2 years after treatment [20 U/mL (0–56 U/mL), P < 0.01]. In ABG‐S+ patients, no correlation was observed between the H. pylori antibodies and gastric inflammation score, whereas, in the ABG‐H+ group, this correlation was extremely significant (r=0.5991, P < 0.0001). In the no treatment group, at follow‐up, a significant decrease in H. pylori antibodies was observed [26 U/mL (15–100 U/mL) vs. 22 U/mL (0–53 U/mL), P < 0.05], but the gastric body inflammation remained unchanged.

Conclusions:

This study shows that, in ABG‐S+ patients after eradication treatment, serology does not keep in step with gastric inflammation. This suggests that, in patients with atrophic body gastritis, serology alone may not be valid for the assessment of the efficacy of eradication treatment.
The effect of Helicobacter pylori eradication on the natural course of atrophic gastritis with dysplasia
Authors: Kokkola A. , Sipponen P. , Rautelin H. , Härkönen M. , Kosunen T. U. , Haapiainen R. , Puolakkainen P.
Published: March 2003

Background:

There are few data on the natural course of Helicobacter pylori‐related atrophic gastritis.

Aim:

To investigate the effect of H. pylori eradication on advanced atrophic gastritis in the corpus.

Methods:

Twenty‐two elderly men with H. pylori infection and moderate or severe atrophic corpus gastritis formed the study population. These men were under endoscopic surveillance because of the presence of indefinite or definite dysplastic gastric lesions in addition to atrophic corpus gastritis. The men were gastroscopically and bioptically examined four times before they received H. pylori eradication therapy (mean follow‐up time, 7.5 years), and once again 2.5 years after eradication therapy. Serum levels of pepsinogen I and H. pylori antibodies were analysed at baseline, immediately before and 2.5 years after eradication therapy.

Results:

During the 7.5‐year period prior to eradication therapy, no significant changes were observed in the mean atrophy and intestinal metaplasia scores or in the mean serum level of pepsinogen I. However, a significant improvement occurred in the mean histological scores of inflammation (from 2.2 to 0.5), atrophy (from 2.2 to 1.2) and intestinal metaplasia (from 1.6 to 1.1) in the corpus mucosa after H. pylori eradication. In addition, the mean serum level of pepsinogen I increased from 16.3 to 25.7 μg/L (P=0.0071, Wilcoxon signed rank test) after eradication therapy.

Conclusions:

The results suggest that advanced atrophic corpus gastritis (and intestinal metaplasia) improves and may even heal after the eradication of H. pylori.
Dose‐dependent control of intragastric pH by pantoprazole, 10, 20 or 40 mg, in healthy volunteers
Authors: Tutuian R. , Katz P. O. , Bochenek W. , Castell D. O.
Published: March 2003

Background:

Proton pump inhibitors have emerged as the most effective class of drugs for the treatment of gastro‐oesophageal reflux. Pantoprazole is a proton pump inhibitor that has demonstrated high clinical efficacy.

Aim:

To evaluate the effect of once‐daily doses of pantoprazole, 10, 20 and 40 mg, on gastric acidity in healthy volunteers.

Methods:

Thirty‐six subjects received pantoprazole in a three‐way crossover design study. Ambulatory 24‐h intragastric pH and distal oesophageal pH were monitored at baseline and on the last day of each treatment period. The measured endpoints were the median intragastric and oesophageal pH, the percentage of time the intragastric pH < 4 and oesophageal pH < 4 and the area under the curve for gastric acidity over 24 h. Safety was evaluated by incidence and severity of adverse events.

Results:

Pantoprazole demonstrated a linear dose‐ dependent suppression of gastric acidity over the dose range 10–40 mg. The dose of 40 mg demonstrated a significantly greater response than the lower doses, particularly at night. All pantoprazole doses were well tolerated.

Conclusions:

Pantoprazole demonstrates a dose‐related effect in the range 10–40 mg once daily. The once‐daily dose of 40 mg provides the highest and most consistent control of gastric pH, especially at night.
Blood antioxidant levels in patients with alcoholic liver disease correlate with the degree of liver impairment and are not specific to alcoholic liver injury itself
Authors: Van De Casteele M. , Zaman Z. , Zeegers M. , Servaes R. , Fevery J. , Nevens F.
Published: March 2003

Background:

Enhanced production of reactive oxygen species may play a pathogenic role in alcoholic liver injury.

Aims:

To investigate whether various antioxidant parameters in blood are affected in different stages of alcoholic liver disease and how specific the changes are relative to non‐alcoholic cirrhosis.

Methods:

Patients with alcohol abuse without cirrhosis (n=14), with alcoholic cirrhosis [Child–Pugh scores A (n=9), B (n=5) and C (n=18)] and with non‐alcoholic cirrhosis [Child–Pugh score C (n=6)] and healthy controls (n=13) were studied. Levels of reduced glutathione and glutathione peroxidase activity in blood, erythrocytic superoxide dismutase activity and carotenoids, α‐tocopherol and malondialdehyde in plasma were measured.

Results:

Levels of reduced glutathione were significantly decreased in Child–Pugh score C cirrhotics, alcoholic or not in origin, whereas oxidized glutathione and glutathione peroxidase activity were not affected. Superoxide dismutase activity and α‐tocopherol levels were not significantly different in the various groups. Carotenoid levels were significantly lower in alcoholic cirrhotics (Child–Pugh score C) vs. controls. Malondialdehyde levels were elevated only in cirrhotics Child–Pugh score C, alcoholic or non‐alcoholic.

Conclusions:

Levels of reduced glutathione and malondialdehyde reflect the degree of liver impairment, more than the relation with alcohol intake. Decreases in several antioxidant levels are not specific to alcoholic liver injury.
Intestinal metaplasia and gastric carcinogenesis
Authors: Leung W. K. , Sung J. J. Y.
Published: March 2003

Gastric intestinal metaplasia, an intermediate step in Correa's cascade of gastric carcinogenesis, is generally regarded as a pre‐malignant lesion. Epidemiological studies suggest that patients with intestinal metaplasia have more than a 10‐fold increased risk of developing gastric cancer. Within the subclassification of intestinal metaplasia, incomplete or type III intestinal metaplasia appears to be associated with even higher malignant potential. The topographical distribution of intestinal metaplasia may also have prognostic implications. Certain genetic and epigenetic alterations have been demonstrated in gastric intestinal metaplasia which straddle into gastric cancer. These findings suggest that genetic changes occur early in the multistep gastric carcinogenesis process. Unlike Barrett's oesophagus and colonic polyp, which have well‐defined surveillance guidelines, there is no widely accepted surveillance programme for gastric intestinal metaplasia. An annual surveillance programme may allow early detection of gastric cancer, which theoretically may improve survival. It remains elusive whether the treatment of Helicobacter pylori infection may reverse gastric intestinal metaplasia or reduce the subsequent risk of cancer development. Further controlled studies with longer follow‐up are needed to resolve this controversy. The role of chemo‐prophylactic agents, e.g. cyclo‐oxygenase‐2 inhibitor, should be investigated.
The role of the gut flora in health and disease, and its modification as therapy
Authors: Hart A. L. , Stagg A. J. , Frame M. , Graffner H. , Glise H. , Falk P. , Kamm M. A.
Published: March 2003

The gut flora is a vast interior ecosystem whose nature is only beginning to be unravelled, due to the emergence of sophisticated molecular tools. Techniques such as 16S ribosomal RNA analysis, polymerase chain reaction amplification and the use of DNA microarrays now facilitate rapid identification and characterization of species resistant to conventional culture and possibly unknown species. Life‐long cross‐talk between the host and the gut flora determines whether health is maintained or disease intervenes. An understanding of these bacteria–bacteria and bacteria–host immune and epithelial cell interactions is likely to lead to a greater insight into disease pathogenesis. Studies of single organism–epithelial interactions have revealed the large range of metabolic processes that gut bacteria may influence. In inflammatory bowel diseases, bacteria drive the inflammatory process, and genetic predisposition to disease identified to date, such as the recently described NOD2/CARD15 gene variants, may relate to altered bacterial recognition. Extra‐intestinal disorders, such as atopy and arthritis, may also have an altered gut milieu as their basis. Clinical evidence is emerging that the modification of this internal environment, using either antibiotics or probiotic bacteria, is beneficial in preventing and treating disease. This natural and apparently safe approach holds great appeal.