bluuebunny/crossref_metadata_2025 huggingface dataset:
Dramatic change in local climate patterns in the Amboseli basin, Kenya
Authors: Altmann J. , Alberts S. C. , Altmann S. A. , Roy S. B.
Published: March 2003

The Amboseli basin, a semi‐arid, open savannah area of southern Kenya, has experienced extensive changes in habitat since the early 1960's. The present report documents patterns of air temperature and rainfall in Amboseli for the 25‐year period beginning 1976. Daily temperatures increased dramatically throughout this time period, at a rate almost an order of magnitude greater than that attributed to global warming. Mean daily maximum temperature increased more than did daily minimum (0.275 vs. 0.071°C per annum). Although increases in mean daily maxima were documented for all months of the year, they were greatest during the hottest months, February and March. Annual rainfall varied more than four‐fold (x = 346.5 mm, SD = 120.0, range 132.0–553.4 mm), yet did not exhibit any directional or other regular pattern of variability among years over this same 25‐year period. Empirical as well as theoretical investigation of relations between such changes in climatic conditions and habitat characteristics are needed at local and regional as well as global scales.
Coastal sponge communities of the West Indian Ocean: taxonomic affinities, richness and diversity
Authors: Barnes David K. A. , Bell James J.
Published: March 2003

Sponges assemblages were sampled in four coastal study regions (Malindi, Kenya; Quirimba Archipelago, northern Mozambique; Inhaca Island, Southern Mozambique and Anakao, Madagascar) in the west Indian Ocean. Sponge species were counted in multiple 0.5 m2 quadrats at depths of between 0 and 20 m at a number of sites within localities within each region. Despite the relatively small areas sampled, sponge samples comprised a total of 130 species and 70 genera of the classes Demospongiae and Calcarea. Sponges are clearly a major taxon in these regions in terms of numbers of species, percentage cover or biomass, although their ecology in the west Indian Ocean is virtually unknown. Nearly half of the genera, e.g. Iotrochota, found were species with a so‐called Tethyan distribution. Most of the other genera were cosmopolitan, e.g. Clathria, but some were cold water (Coelosphaera), Indo‐Australian (Ianthella) or circum‐African (Crambe). Many of the species encountered in the present study occurred in at least two study regions, many in more and could occupy large areas of substratum. Some of these, e.g. Xestospongia exigua, are commonly found throughout the Indo‐west Pacific region where they also occupy much space. The endemicity of the shallow water sponge faunas in East Africa (20–25%) seem to be high within the Indo‐Pacific realm but are lower than northern Papua New Guinea. The tropical regions (Kenya and Northern Mozambique) were more speciose than subtropical regions (southern Mozambique and Madagascar) but not significantly more diverse (Shannon H′). Although latitude was not a major influence on sponge community patterns, hard substratum assemblages did form a cline from the tropics to Southern Mozambique, linked by Madagascar. Substratum nature (habitat) was most important in influencing the suite and number of species present. Sponge assemblages of soft substrata were much more dissimilar, both within and between habitats, than those on hard substrata. There was a predictable variability in species richness between hard substratum habitats: coral reefs being speciose and caves being less so. Our findings showed that both patterns and influences on species richness may be decoupled from those influencing diversity. In our data species richness, but not diversity, showed striking regional and bathymetric trends. In addition, sponge species richness mainly split at coral reef vs. non‐reef habitats, whilst diversity divided principally into assemblages on hard and soft substrata. We consider this dichotomy of findings between species richness and diversity values to be important, as these are two principal measures used for the interpretation of biodiversity.
Review article: faecal occult blood testing for colorectal cancer
Authors: Allison
Published: March 2003

Major health organizations recommend colorectal cancer screening using faecal occult blood tests, sigmoidoscopy or both for patients 50 years of age or older who are at average risk for colorectal cancer. However, no specific recommendations have been made regarding choice of test from among the tests currently or soon to be available. Therefore, to aid clinicians in rationally choosing a particular test for faecal occult blood, published data are reviewed regarding the performance characteristics, strengths and weaknesses of the various faecal occult blood tests. New studies suggest that immunochemical tests (e.g. HemeSelect) or a combination of sensitive guaiac tests and immunochemical tests (e.g. Hemoccult Sensa and HemeSelect) are the most sensitive, specific tests for detecting colorectal carcinoma and colorectal polyps ≥ 1 cm.
Sex hormone status and bone metabolism in men with Crohn’s disease
Authors: Robinson  , Iqbal  , Al‐Azzawi  , Abrams  , Mayberry
Published: March 2003

Background:

Men with Crohn’s disease (CD) are at risk of osteoporosis, but the factors contributing to low bone mineral density and its optimum treatment have not been established.

Aim:

To investigate the sex hormone status of men with CD, and to establish the influence of sex hormones on their bone metabolism.

Methods:

Bone density was measured by dual energy X‐ray absorptiometry at the hip and lumbar spine in 48 men with CD. Total serum testosterone and gonadotrophins were measured in all subjects and the free androgen index calculated in men with low or borderline total testosterone. Serum osteocalcin, pro‐collagen carboxy‐terminal peptide, bone specific alkaline phosphatase and urinary deoxypyridinoline were measured as markers of bone turnover.

Results:

Eight (17%) men had osteoporosis, and a further 14 (29%) had osteopenia. Three (6%) men had a low free androgen index and normal gonadotrophins consistent with secondary hypogonadism, two of whom had osteopenia of the hip and spine. Age (P=0.002) and small bowel Crohn’s disease (P=0.02) were the only independent predictors of serum testosterone. There was a significant association between total testosterone and osteocalcin (r=0.53, 95% CI: 0.29–0.71, P=0.0001) which was independent of age and current steroid use (P=0.0001).

Conclusions:

Previously undiagnosed hypogonadism is an uncommon cause of low bone density in men with CD. The independent association between testosterone and the bone formation marker osteocalcin suggests sex hormone status influences bone metabolism in men with CD. The results suggest testosterone replacement might be effective treatment for some men with osteoporosis and Crohn’s disease.
Psyllium is superior to docusate sodium for treatment of chronic constipation
Authors: McRorie  , Daggy  , Morel  , Diersing  , Miner  , Robinson
Published: March 2003

Background:

Stool softening is a physician’s first step in the management of chronic constipation.

Aim:

To compare stool softening (stool water content) and laxative efficacy of psyllium hydrophilic mucilloid vs. docusate sodium.

Methods:

The multi‐site, randomized, double‐blind, parallel‐design study of 170 subjects with chronic idiopathic constipation involved a 2‐week baseline (placebo) phase followed by 2 weeks of treatment. The treatment phase compared psyllium (5.1 g b.d.) plus docusate placebo to docusate sodium (100 mg b.d.) plus psyllium placebo. Stools were collected and assessed.

Results:

Compared to baseline, psyllium increased stool water content vs. docusate (psyllium 2.33% vs. docusate 0.01%,P = 0.007). Psyllium also increased stool water weight (psyllium 84.0 g/BM; docusate 71.4 g/BM;P = 0.04), total stool output (psyllium 359.9 g/week; docusate 271.9 g/week;P = 0.005), and O’Brien rank‐type score combining objective measures of constipation (psyllium 475.1; docusate 403.9;P = 0.002). Bowel movement (BM) frequency was significantly greater for psyllium (3.5 BM/week) vs. docusate (2.9 BM/week) in treatment week 2 (P = 0.02), with no significant difference (P > 0.05) between treatment groups in treatment week 1 (3.3 vs. 3.1 BM/week).

Conclusion:

Psyllium is superior to docusate sodium for softening stools by increasing stool water content, and has greater overall laxative efficacy in subjects with chronic idiopathic constipation.
Olsalazine versus mesalazine in the treatment of mild to moderate ulcerative colitis
Authors: Kruis  , Brandes  , Schreiber  , Theuer  , Krakamp  , Schütz  , Otto  , Lorenz‐Mayer  , Ewe  , Judmaier
Published: March 2003

Aim:

To compare the efficacy and tolerability of olsalazine sodium with enteric‐coated mesalazine in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis.

Patients and methods:

Patients with mild to moderate active ulcerative colitis were randomized to receive either olsalazine sodium, 3 g/day (n = 88), or mesalazine, 3 g/day (n = 80), for up to 12 weeks.

Results:

Of the patients treated with olsalazine sodium, 52.2% achieved endoscopic remission, compared with 48.8% of patients treated with mesalazine. This difference was not significant (P = 0.67). There was a non‐significant trend for patients with left‐sided colitis or a more severe endoscopic grade to achieve remission if they were treated with olsalazine sodium than if they were treated with mesalazine. Both treatments were comparable with respect to clinical activity index and an investigator’s global assessment. Seventy patients reported one or more adverse events; adverse events were seen in 45% of olsalazine sodium‐treated patients and in 36% of mesalazine‐treated patients. Eleven patients treated with olsalazine sodium and nine patients treated with mesalazine withdrew from the study because of adverse events. One patient treated with olsalazine sodium compared with two treated with mesalazine stopped treatment because of diarrhoea. Serious adverse events occurred in three patients treated with olsalazine sodium and in four treated with mesalazine.

Conclusion:

Therapeutic effectiveness and tolerance to the treatment did not differ between olsalazine sodium, 3 g/day, and mesalazine, 3 g/day, in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis within 12 weeks of treatment.
On‐demand treatment of gastro‐oesophageal reflux symptoms: a comparison of ranitidine 75 mg with cimetidine 200 mg or placebo
Authors: Galmiche J. P. , Shi G. , Simon B. , Casset‐Semanaz F. , Slama A.
Published: March 2003

Aim:

To compare the effects of ranitidine 75 mg with those of either cimetidine 200 mg or placebo given on demand for relief of typical symptoms of gastro‐oesophageal reflux disease during a 15‐day period.

Methods:

A total of 1336 patients (aged ≥ 18 years) with heartburn episodes were recruited and randomly assigned to a ranitidine 75 mg, cimetidine 200 mg or placebo group. Depending on the occurrence or persistence of heartburn, treatment was administered as required up to three times daily, with at least 2 h between drug doses. Antacids were allowed as rescue medication if symptoms persisted for at least 2 h after the third medication on any given day. The primary end‐point was defined as the proportion of patients with relief of at least 75% of heartburn episodes during the study period (i.e. relief occurring within 2 h after drug ingestion and lasting for at least 5 h).

Results:

Analysis was performed in an intention‐to‐treat population comprising 504 subjects in the ranitidine group, 515 in the cimetidine group and 270 in the placebo group. Primary end‐point success rates were 41, 38 and 28%, respectively, for the three groups (P < 0.001 for ranitidine vs. placebo, P = 0.274 for ranitidine vs. cimetidine). Ranitidine 75 mg was significantly more effective than placebo in providing overall heartburn relief (P < 0.001). The differences between the ranitidine and cimetidine groups were not significant, except for a greater reduction in heartburn frequency in the ranitidine group at the end of the study period (P < 0.05). Drug dose was lower and less rescue medication was used in the ranitidine group than the placebo group. The three treatment groups did not differ in terms of tolerability.

Conclusion:

On‐demand ranitidine 75 mg or cimetidine 200 mg are safe and effective treatment for reflux‐related symptoms.
TNFα processing enzyme inhibitors prevent aspirin‐induced TNFα release and protect against gastric mucosal injury in rats
Authors: Fiorucci  , Antonelli  , Migliorati  , Santucci  , Morelli  , Federici  , Morelli
Published: March 2003

Background:

Although previous studies indicate that prevention of tumour necrosis factor α (TNFα) release protects against NSAID‐induced gastric mucosal injury, intracellular pathways by which aspirin causes TNFα release are unknown. TNFα is synthesized as a precursor which is proteolytically cleaved by a specific converting enzyme, TACE, to release the mature cytokine. TACE inhibitors prevent TNFα release and protect against TNFα‐mediated disease.

Aim:

To investigate: (i) molecular events that regulate TNFα secretion in response to aspirin in vivo and in vitro; (ii) whether TNFα secretion inhibitors prevent aspirin‐induced TNFα release and protect against gastric mucosal damage; and (iii) whether TNFα exerts a direct cytotoxic effect on gastric epithelial cells.

Methods:

In vitro studies were carried out on mouse macrophages and rat gastric mucosal cells. Gastric mucosal damage was induced in rats by oral administration of 300 mg/kg aspirin. TNFα cytotoxicity on gastric mucosal cells was examined by treating rats with lipopolysaccharide to release TNFα or by incubating dispersed gastric mucosal cells with increasing concentrations of TNFα.

Results:

Aspirin increases intracellular calcium (Ca2+) levels and causes a time and concentration dependent increase in macrophage TNFα mRNA accumulation and cytokine release. Agents that cause Ca2+ mobilization with a receptor‐independent mechanism, such as ionomycin and thapsigargin, stimulate TNFα release. Incubating the macrophages in a Ca2+ free medium inhibited TNFα secretion. Agents that prevent TNFα mRNA transcription, e.g. lisophylline, PGE2, interleukin‐10 and 8‐BrcAMP, or TACE inhibitors, e.g. EDTA, TAPI‐2 and BB‐3103, inhibit TNFα release and protect rats against gastric mucosal injury induced by oral administration of aspirin. TNFα exerts a direct␣cytotoxic effect on gastric epithelial cells as demonstrated by the reduced viability observed in gastric mucosal␣cells prepared from rats treated with lipopolysaccharide, or␣directly incubated with increasing concentrations of TNFα.

Conclusions:

(i) Aspirin directly stimulates TNFα gene transcription; (ii) TACE inhibitors protect against aspirin‐induced gastric mucosal injury; and (iii) TNFα exerts a direct cytotoxic effect on gastric epithelial cells.
Efficacy of omeprazole in functional dyspepsia: double‐blind, randomized, placebo‐controlled trials (the Bond and Opera studies)
Authors: Talley  , Meineche‐Schmidt  , Paré  , Duckworth  , Räisänen  , Pap  , Kordecki  , Schmid
Published: March 2003

Background:

The efficacy of H2‐receptor antagonists in functional dyspepsia is equivocal and the therapeutic place of proton pump inhibitors in functional dyspepsia is unknown.

Aim:

To evaluate the efficacy of proton pump inhibitor therapy in functional dyspepsia.

Methods:

Patients (n = 1262) with a clinical diagnosis of functional dyspepsia (persistent or recurrent epigastric pain or discomfort for at least 1 month and a normal upper gastrointestinal endoscopy) were randomized to receive omeprazole 20 mg, 10 mg or identical placebo, for 4 weeks. Symptoms were assessed using validated measures. Helicobacter pylori status was determined pre‐entry by a 13C‐urea breath test.

Results:

On an intention‐to‐treat analysis (n=1248), complete symptom relief was observed in 38% on omeprazole 20 mg, compared with 36% on omeprazole 10 mg and 28% on placebo (P = 0.002 and 0.02, respectively). Among those with ulcer‐like and reflux‐like dyspepsia, complete symptom relief was achieved in 40% and 54% on omeprazole 20 mg, and 35% and 45% on omeprazole 10 mg, respectively, compared with 27% and 23% on placebo (all P < 0.05, except omeprazole 10 mg in ulcer‐like dyspepsia, P = 0.08). There was no significant benefit of omeprazole over placebo in dysmotility‐like dyspepsia. Symptom relief was similar in H. pylori‐positive and negative cases.

Conclusions:

Omeprazole is modestly superior to placebo in functional dyspepsia at standard (20 mg) and low doses (10 mg) but not in patients with dysmotility‐like dyspepsia.
Gastro‐oesophageal reflux associated with nocturnal gastric acid breakthrough on proton pump inhibitors
Authors: Katz  , Anderson  , Khoury  , Castell
Published: March 2003

Background

Nocturnal gastric acid breakthrough, defined as intragastric pH < 4 for more than 1 h in the overnight period, is observed in up to 70% of normal subjects on proton pump inhibitors taken twice daily. The frequency of this breakthrough in patients with gastro‐oesophageal reflux and accompanying oesophageal reflux during this period has not been studied.

Aim

To examine the frequency of nocturnal breakthrough and accompanying oesophageal acid exposure in patients with gastro‐oesophageal reflux treated with proton pump inhibitors twice daily.

Methods

Prolonged ambulatory pH records from 76 patients on twice daily proton pump inhibitors between January 1991 and July 1997 were analysed for the presence of nocturnal gastric acid breakthrough and accompanying oesophageal pH < 4. Studies from 31 normal subjects on twice daily proton pump inhibitors constituted the control group.

Results

Nocturnal gastric acid breakthrough was seen in 70% of 61 patients with gastro‐oesophageal reflux, 80% of 15 patients with Barrett’s oesophagus and 67% of normal controls (P = N.S.). Oesophageal acid exposure was seen in 33% of gastro‐oesophageal reflux patients, 50% of Barrett’s oesophagus patients and 8% of normal controls (P < 0.03). No difference was found between patients taking omeprazole or lansoprazole.

Conclusion

Nocturnal acid breakthrough is frequently seen on proton pump inhibitors twice daily and is often accompanied by oesophageal reflux. This has important implications for medical therapy in patients with severe gastro‐oesophageal reflux and Barrett’s oesophagus.
Antiinflammatory actions of cat’s claw: the role of NF‐κB
Authors: Sandoval‐Chacón  , Thompson  , Zhang  , Liu  , Mannick  , Sadowska‐Krowicka  , Charbonnet  , Clark  , Miller
Published: March 2003

Background:

Uncaria tomentosa is a vine commonly known as cat’s claw or ‘uña de gato’ (UG) and is used in traditional Peruvian medicine for the treatment of a wide range of health problems, particularly digestive complaints and arthritis.

Purpose:

The aim of this study was to determine the proposed anti‐inflammatory properties of cat’s claw. Specifically: (i) does a bark extract of cat’s claw protect against oxidant‐induced stress in vitro, and (ii) to determine if UG modifies transcriptionally regulated events.

Methods:

Cell death was determined in two cell lines, RAW 264.7 and HT29 in response to peroxynitrite (PN, 300 μM). Gene expression of inducible nitric oxide synthase (iNOS) in HT29 cells, direct effects on nitric oxide and peroxynitrite levels, and activation of NF‐κB in RAW 264.7 cells as influenced by UG were assessed. Chronic intestinal inflammation was induced in rats with indomethacin (7.5 mg/kg), with UG administered orally in the drinking water (5 mg/mL).

Results:

The administration of UG (100 μg/mL) attenuated (P < 0.05) peroxynitrite‐induced apoptosis in HT29 (epithelial) and RAW 264.7 cells (macrophage). Cat’s claw inhibited lipopolysaccharide‐induced iNOS gene expression, nitrite formation, cell death and inhibited the activation of NF‐κB. Cat’s claw markedly attenuated indomethacin‐enteritis as evident by reduced myeloperoxidase activity, morphometric damage and liver metallothionein expression.

Conclusions:

Cat’s claw protects cells against oxidative stress and negated the activation of NF‐κB. These studies provide a mechanistic evidence for the widely held belief that cat’s claw is an effective anti‐inflammatory agent.
Review article: cytochrome P450 and the metabolism of proton pump inhibitors — emphasis on rabeprazole
Authors: Ishizaki  , Horai
Published: March 2003

The proton pump inhibitors rabeprazole, omeprazole, lansoprazole, and pantoprazole undergo an extensive hepatic biotransformation. In the liver, they are metabolized to varying degree by several cytochrome P450 (CYP) isoenzymes which are further categorized into subfamilies of related polymorphic gene products. The principal isoenzymes involved in the metabolism of proton pump inhibitors are CYP2C19 and CYP3A4. Of these two, minor mutations in CYP2C19 affect its activity in the liver and, in turn, the metabolic and pharmacokinetic profiles of the proton pump inhibitors. The metabolism of rabeprazole is less dependent on CYP2C19 and therefore is the least affected by this genetic polymorphism. Recent studies have brought to light the important role that this polymorphism plays in the therapeutic effectiveness of proton pump inhibitors during the treatment of acid‐related diseases.
Is maintenance therapy always necessary for patients with ulcerative colitis in remission?
Authors: ARDIZZONE  , PETRILLO  , IMBESI  , CERUTTI  , BOLLANI  , BIANCHI PORRO
Published: March 2003

Background

: The efficacy of sulphasalazine and mesalazine in preventing relapse in patients with ulcerative colitis is well known. It is less clear how long such maintenance should be continued, and if the duration of disease remission is a factor that affects the risk of recurrence.

Aim

: To determine whether the duration of disease remission affects the relapse rate, by comparing the efficacy of a delayed‐release mesalazine (Asacol, Bracco S.p.A., Milan, Italy) against placebo in patients with ulcerative colitis with short‐ and long‐duration of disease remission.

Methods

: 112 patients (66 male, 46 female, mean age 35 years), with intermittent chronic ulcerative colitis in clinical, endoscopic and histological remission with sulphasalazine or mesalazine for at least 1 year, were included in the study. Assuming that a lower duration of remission might be associated with a higher relapse rate, the patients were stratified according to the length of their disease remission, prior to randomization into Group A (Asacol 26, placebo 35) in remission from 1 to 2 years, or Group B (Asacol 28, placebo 23) in remission for over 2 years, median 4 years. Patients were treated daily with oral Asacol 1.2 g vs. placebo, for a follow‐up period of 1 year.

Results

: We employed an intention‐to‐treat analysis. In Group A, whilst no difference was found between the two treatments after 6 months, mesalazine was significantly more effective than placebo in preventing relapse at 12 months [Asacol 6/26 (23%), placebo 17/35 (49%), P = 0.035, 95% Cl: 48–2.3%]. In contrast, in Group B no statistically significant difference was observed between the two treatments, either at 6 or 12 months [Asacol 5/28 (18%), placebo 6/23 (26%), P = 0.35, 95% Cl: 31–14%] of follow‐up. Patients in group B were older, and had the disease and remission duration for longer, than those in Group A.

Conclusions

: Mesalazine prophylaxis is necessary for the prevention of relapse by patients with ulcerative colitis in remission for less than 2 years, but this study casts doubt over whether continuous maintenance treatment is necessary in patients with prolonged clinical, endoscopic and histological remission, who are at very low risk of relapse.
Prospective evaluation of ranitidine bismuth citrate‐based triple therapy for the treatment of Helicobacter pylori infection
Authors: MÖNKEMÜLLER  , HIRSCHOWITZ
Published: March 2003

Background

: There is a need for effective and inexpensive therapy for Helicobacter pylori with good patient compliance.

Aim

: To evaluate a simplified twice daily schedule for treating H. pylori.

Methods

: Patients infected with H. pylori (positive by CLO‐ and 13C‐urea breath tests [UBT]) and not previously treated with anti‐H. pylori therapy were treated with ranitidine bismuth citrate (RBC) and two inexpensive antibiotics (metronidazole, tetracycline) twice daily for 14 days in an open‐label study. Eradication was established by a negative UBT 4 weeks after ending therapy.

Results

: Twenty men and 30 women (age 54 ± 14 years, range 26–74) were included in the study. Five patients were prematurely withdrawn (side‐effects 2, took additional antibiotics 2 and surgery 1) and one patient was lost to follow‐up; therefore, 44 (88%) patients completed the H. pylori eradication protocol. Per protocol (PP) cure rate was 82% (36/44 patients, 95% CI: 68–95%), and intention‐to‐treat cure rate was 72% (36/50 patients, 95% CI: 58–82%). Five patients (10%) developed side‐effects during therapy, most commonly nausea (3 patients). Four weeks after the end of treatment, 78% (PP) of patients were symptomatically improved.

Conclusions

: A 2‐week course of twice‐daily RBC‐based triple therapy was well tolerated, eradicated H. pylori in 72% (ITT) and 82% (PP) of patients, respectively, and relieved symptoms in 78%.
Head‐to‐head comparison of 1‐week triple regimens combining ranitidine or omeprazole with two antibiotics to eradicate Helicobacter pylori
Authors: SAVARINO  , ZENTILIN  , BISSO  , PIVARI  , MELE  , MELA  , MANSI  , VIGNERI  , TERMINI  , CELLE.
Published: March 2003

Background

: Triple therapies containing omeprazole and ranitidine have been shown to be equivalent in eradicating H. pylori infection, but have been assessed either separately or head‐to‐head, only in small trials.

Aim

: To carry out a large randomized controlled study comparing omeprazole and ranitidine combined with two antibiotic combinations for 1 week.

Methods

: Three hundred and twenty H. pylori‐positive patients were randomly subdivided into four equal‐sized groups and received one of the following treatments: OAM = omeprazole 20 mg b.d. + amoxycillin 1 g b.d. + metronidazole 500 mg b.d.; RAM = ranitidine 300 mg b.d. + amoxycillin 1 g b.d. + metronidazole 500 mg b.d.; OAC = omeprazole 20 mg b.d. + amoxycillin 1 g b.d. + clarithromycin 250 mg t.d.s.; RAC=ranitidine 300 mg b.d. + amoxycillin 1 g b.d. + clarithromycin 250 mg t.d.s. The assessment of H. pylori status was performed before and 4 weeks after the end of therapy by means of CLO‐test and histology. H. pylori infection was considered to be eradicated when both tests were negative.

Results

: OAM and RAM eradicated H. pylori in 89% and 85% of cases on per protocol (P = 0.48) and in 77% and 75% of cases on intention‐to‐treat analyses (P = 0.71). OAC and RAC eradicated H. pylori in 67% and 70% of cases on per protocol (P = 0.68) and in 57% and 64% of cases on intention‐to‐treat analyses (P = 0.41). In contrast, there was significant difference between OAM and OAC (P < 0.01) and between RAM and RAC (P < 0.05). Side‐effects occurred in 15%, 10%, 17% and 16% of patients with respect to the above four subgroups.

Conclusions

: Omeprazole and ranitidine combined with two antibiotics for 1 week are equally effective in the eradication of H. pylori infection, and these results question the role of profound acid suppression in the eradication of the bacterium.
Famotidine versus omeprazole in combination with clarithromycin and metronidazole for eradication of Helicobacter pylori—a randomized, controlled trial
Authors: Gschwantler  , Dragosics  , Schütze  , Wurzer  , Hirschl  , Pasching  , Wimmer  , Klimpfinger  , Oberhuber  , Brandstätter  , Hentschel  , Weiss
Published: March 2003

Background

: One‐week low‐dose triple therapy is currently considered the gold standard regimen for treatment of Helicobacter pylori infection. However, the mechanisms involved in the synergy between antibiotics and proton pump inhibitors are controversial.

Aims

: To test the hypothesis that acid suppression represents the crucial mechanism by which the antibacterial activity of antibiotics can be enhanced, and to assess the impact of primary resistance on treatment outcome.

Methods

: One hundred and twenty patients with H. pylori infection and duodenal ulcer, gastric ulcer or non‐ulcer dyspepsia were randomly assigned to a 1 week course of either famotidine 80 mg b.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (FCM group; n = 60) or omeprazole 20 mg o.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (OCM group; n=60). Gastroscopy was performed at baseline and 5 weeks after completion of treatment. H. pylori status was assessed by biopsy urease test, histology and culture.

Results

: In the intention‐to‐treat analysis, eradication of H. pylori was achieved in 47 of 60 patients (78%; 95% CI: 66–88%) in the FCM group, compared to 44 of 60 patients (73%; 95% CI: 60–84%) in the OCM group (N.S.). Using per protocol analysis, eradication therapy was successful in 47 of 52 patients (90%; 95% CI: 79–97%) treated with FCM and 44 of 57 patients (77%; 95% CI: 64–87%) treated with OCM (N.S.). Primary metronidazole resistance was present in 27% and primary clarithromycin resistance in 8% of strains. Overall per protocol eradication rates in strains susceptible to both antibiotics and strains with isolated metronidazole resistance were 93% and 84%, respectively. No patient with clarithromycin resistance responded to treatment.

Conclusions

: High‐dose famotidine and omeprazole, combined with clarithromycin and metronidazole, are equally effective for eradication of H. pylori. In 1‐week low‐dose triple therapy, metronidazole resistance has no major impact on eradication rates whereas clarithromycin resistance is associated with a poor treatment outcome.
Review article: proteinase‐activated receptors — novel signals for gastrointestinal pathophysiology
Authors: Vergnolle
Published: March 2003

Proteinase‐activated receptors (PARs) have the common property of being activated by the proteolytic cleavage of their extracellular N‐terminal domain. The new NH2‐terminus acts as a ‘tethered ligand’ binding and activating the receptor itself. Four members of this family have been cloned, three of which are activated by thrombin (PAR‐1, PAR‐3 and PAR‐4) while the fourth (PAR‐2) is activated by trypsin or mast cell tryptase.

In physiological or pathophysiological conditions, the gastrointestinal tract is exposed more than other tissues to proteinases (digestive enzymes, proteinases from pathogens or proteinases from inflammatory cells) that can activate PARs. Since PARs are highly expressed throughout the gastrointestinal tract, the study of the role of PARs in these tissues appears to be particularly important.

It has already been shown that PAR‐2 activation induces calcium mobilization and eicosanoid production in enterocytes as well as changes in ion transport in jejunal tissue segments. PAR‐2 activation also causes calcium mobilization and stimulates amylase release from pancreatic acini. Moreover, both PAR‐1 and PAR‐2 activation can alter the gastrointestinal motility. In inflammatory or allergic conditions, the proteinases that constitute the major agonists for PARs (thrombin, trypsin and mast cell tryptase) are usually released. The activation of PARs by these proteinases might contribute to the gastrointestinal disorders associated with these pathologies.

A complete understanding of the role of PARs in the gastrointestinal tract will require the development of selective receptor antagonists that are not yet available. Nonetheless, the use of PAR agonists has already highlighted new potential functions for proteinases in the gastrointestinal tract, thus the control of PAR activation might represent a promising therapeutic target.
Predictive factors of outcome of intensive intravenous treatment for attacks of ulcerative colitis
Authors: Carbonnel  , Gargouri  , Lémann  , Beaugerie  , Cattan  , Cosnes  , Gendre
Published: March 2003

Background:

Intensive intravenous treatment remains the first line therapy of severe, uncomplicated attacks of ulcerative colitis.

Aim:

To predict the failure of intensive intravenous treatment by combining clinical and laboratory parameters with endoscopy findings.

Methods:

Retrospective study conducted in a tertiary care referral centre. Failure of intensive intravenous treatment was defined as colectomy before day 30, intravenous cyclosporin, or death. Predictive factors of outcome were assessed using univariate and multivariate prognostic analysis.

Results:

Between January 1990 and May 1997, 85 consecutive patients were treated with intensive intravenous treatment for non‐response to oral corticosteroids (n=59) and/or severe attack of ulcerative colitis (n=26). There were 41 successes and 44 failures (including 1 death, 13 cyclosporin and 30 colectomies before day 30). Multivariate prognostic analysis found that the presence of Truelove and Witts’ criteria (P=0.018), an attack that had lasted more than 6 weeks (P=0.001), and severe endoscopic lesions (P=0.007) were associated with an increased risk of failure. Patients with severe endoscopic lesions and Truelove and Witts’ criteria, or an attack of more than 6 weeks had a failure rate of 85–86%.

Conclusion:

Clinical, laboratory and endoscopic findings can predict the risk of failure of intensive intravenous treatment. A prospective study is required to confirm these results.
The omeprazole test is as sensitive as 24‐h oesophageal pH monitoring in diagnosing gastro‐oesophageal reflux disease in symptomatic patients with erosive oesophagitis
Authors: Fass  , Ofman  , Sampliner  , Camargo  , Wendel  , Fennerty
Published: March 2003

Background:

Ambulatory 24‐h oesophageal pH monitoring and a short course of high dose omeprazole can be used as diagnostic modalities for GERD. However, comparative studies of the diagnostic accuracy and reliability of both strategies have not been performed.

Aim:

To compare the omeprazole test to ambulatory 24‐h oesophageal pH monitoring in diagnosing GERD in symptomatic patients using endoscopically proven erosive oesophagitis as a gold standard.

Methods:

Patients with heartburn underwent an upper endoscopy. Only those with erosive oesophagitis were included in the study. Subsequently, patients underwent ambulatory 24‐h oesophageal pH monitoring and an ‘omeprazole test.’ Daily symptoms were recorded during the first week (baseline) and repeated during the second week on therapy (omeprazole 40 mg in the morning and 20 mg in the evening).

Results:

Thirty‐five patients were included in the study. The omeprazole test was significantly more sensitive in diagnosing GERD than total acid contact time on 24‐h oesophageal pH monitoring (83% vs. 60%; P < 0.03). However, the sensitivity of the pH test increased to 80% after adding patients with a positive symptom index, and patients with abnormal acid exposure in the supine or erect positions despite normal total acid contact time. Patients with a normal pH test were significantly younger (49 ± 2.6 years) than those with abnormal test (59 ± 1.8; P=0.002).

Conclusions:

In this study an omeprazole test was at least as sensitive as ambulatory 24‐h oesophageal pH monitoring in diagnosing GERD in patients with erosive oesophagitis.
High incidence of reflux oesophagitis after eradication therapy for Helicobacter pylori: impacts of hiatal hernia and corpus gastritis
Authors: Hamada  , Haruma  , Mihara  , Kamada  , Yoshihara  , Sumii  , Kajiyama  , Kawanishi
Published: March 2003

Background:

Although several recent studies have shown that the eradication of Helicobacter pylori provokes reflux oesophagitis, the results are conflicting.

Aim:

To investigate the prevalence of reflux oesophagitis in patients after eradication of H. pylori and consider its association with hiatal hernia and corpus gastritis.

Methods:

A total of 286 patients who underwent H. pylori eradication therapy and 286 age‐ and disease‐matched H. pylori‐positive controls who did not undergo eradication therapy were followed prospectively. All patients and controls underwent endoscopy at 1‐year intervals or when upper gastrointestinal symptoms recurred. The presence of hiatal hernia and histology of the gastric corpus were evaluated at the time of initial endoscopy.

Results:

The estimated prevalence of reflux oesophagitis within 3 years was 18% after eradication therapy and 0.3% without therapy. Patients who developed reflux oesophagitis after therapy had a greater prevalence of hiatal hernia (P=0.0008) and more severe corpus gastritis (P=0.0005) before therapy. Cumulative prevalence of reflux oesophagitis was 26% in patients with hiatal hernia, 7.7% in those without hiatal hernia, 33% in those with corpus atrophic gastritis and 13% in those without corpus atrophic gastritis. When patients had both hiatal hernia and corpus gastritis, the prevalence of reflux oesophagitis was 37%. The newly developed reflux oesophagitis was classified as mild in 35 out of 36 (97%) patients who developed reflux oesophagitis after eradication therapy.

Conclusions:

Eradication of H. pylori increased the prevalence of reflux oesophagitis in our patient group. The presence of hiatal hernia and corpus gastritis are closely related to the development of reflux oesophagitis after H. pylori eradication therapy.
Alosetron, a 5‐HT3 receptor antagonist, delays colonic transit in patients with irritable bowel syndrome and healthy volunteers
Authors: Houghton  , Foster  , Whorwell
Published: March 2003

Background:

Alosetron is a potent and selective 5‐HT3 receptor antagonist, which has been shown to be beneficial in the treatment of female patients with non‐constipated irritable bowel syndrome.

Aims:

To investigate the effect of alosetron on whole gut, small bowel and colonic transit in patients with irritable bowel syndrome (Study 1) and healthy volunteers (Study 2).

Subjects:

Thirteen patients with irritable bowel syndrome and 12 healthy volunteers.

Methods:

Both studies were randomized, double‐blind, placebo‐controlled with a two‐way crossover design, in which each subject received alosetron (2 mg b.d. administered orally) or placebo for 8 days. Mean whole gut transit was determined from the excretion of radio‐opaque markers; small bowel transit was determined from rise in breath hydrogen after a meal; and colonic transit and segmental transit were evaluated from abdominal X‐ray. In addition, colonic transit was calculated by subtracting small bowel transit time from whole gut transit time.

Results:

Alosetron increased colonic transit time by prolonging left colonic transit in both patients with irritable bowel syndrome and controls. This resulted in a tendency for the whole gut transit to be delayed in irritable bowel syndrome patients (P=0.128), which was confirmed in controls (P=0.047).

Conclusion:

Alosetron delays colonic transit by prolonging left colonic transit. These results add to the body of evidence suggesting that alosetron should have a therapeutic role in patients with non‐constipated irritable bowel syndrome.
Effects of alosetron on gastrointestinal transit time and rectal sensation in patients with irritable bowel syndrome
Authors: Thumshirn  , Coulie  , Camilleri  , Zinsmeister  , Burton  , Van Dyke
Published: March 2003

Background:

Alosetron, a 5‐HT3‐receptor antagonist, relieves abdominal pain and improves bowel function in non‐constipated, female patients with irritable bowel syndrome. 5‐HT3 antagonists delay colonic transit, increase colonic compliance, and increase small intestinal water absorption.

Aim:

To evaluate the effects of alosetron on gastrointestinal and colonic transit, rectal compliance and rectal sensation in irritable bowel syndrome.

Methods:

A double‐blind, placebo‐controlled, two‐dose study of alosetron was performed in 25 non‐constipated irritable bowel syndrome patients, with paired studies before and after 4 weeks of treatment with placebo (n=5), 1 mg alosetron (n=10) or 4 mg (n=10) alosetron b.d. Gastrointestinal and colonic transit were measured by scintigraphy. Rectal compliance and sensation were assessed by rectal balloon distention with a barostat.

Results:

There was a trend (P=0.06) for 1 mg alosetron to increase rectal compliance (median pressure at half maximum volume 11 mmHg after alosetron vs. 15.6 mmHg before alosetron). The 1 mg b.d. alosetron dose non‐significantly retarded proximal colonic transit. Alosetron and placebo reduced sensory scores relative to baseline values; none of the changes induced by alosetron was significant relative to placebo.

Conclusions:

Alosetron had no significant effect on gastrointestinal transit or rectal sensory and motor mechanisms in non‐constipated irritable bowel syndrome patients in this study. Alosetron’s effects on colonic sensorimotor function and central sensory mechanisms deserve further evaluation.
Proton pump inhibitors: better acid suppression when taken before a meal than without a meal
Authors: Hatlebakk J. G. , Katz P. O. , Camacho‐Lobato L. , Castell D. O.
Published: March 2003

Background:

Proton pump inhibitors including omeprazole and lansoprazole inhibit gastric acid secretion by selectively and non‐competitively inactivating the H+, K+ ATPase molecules of the parietal cell, but possibly only those that are actively secreting acid. This might imply that stimulation of acid secretion by a meal is necessary for optimal inhibition of gastric secretion.

Aim:

To quantify and compare the effect on daytime gastric acidity of omeprazole 20 mg or lansoprazole 30 mg daily taken 15 min before breakfast, with that of the same drug taken without a meal.

Methods:

Twenty‐one healthy volunteers were randomized to receive either omeprazole or lansoprazole. They were given the drug for two separate periods of 7 days in randomized order and at least 7 days apart. During one period the study medication was taken before breakfast; during the other it was taken at the same hour, but with no meal until 12:00 hours. Lunch was standardized. On day 7, intragastric pH‐metry was performed, starting at 08:00 hours. Tracings were analysed for the 8‐h period from 08:00 hours until 16:00 hours with regard to percentage time for which gastric pH was below 4.0 and 3.0, and median gastric pH. Tracings were also analysed after removing the 1 h breakfast period, to exclude the buffering effect of the meal.

Results:

When taking the drug with breakfast, the median percentage time for which gastric pH < 4.0 was 17.2 (interquartile range 4.6–45.5), compared with 42.0 (interquartile range 31.4–48.8) when taken without food (P=0.01). Fifteen subjects had better control of gastric acidity when the medication was taken with breakfast. A pH threshold of 3 and median pH showed similar differences. When the breakfast period was removed, the differences were no longer statistically significant.

Conclusions:

When therapy with omeprazole or lansoprazole is indicated, medication should be taken before a meal for optimal control of daytime gastric acidity.
13C‐urea breath test without a test meal is highly accurate for the detection of Helicobacter pylori infection in Chinese
Authors: Wong W. M. , Wong B. C. Y. , Wong K. W. , Fung F. M. Y. , Lai K. C. , Hu W. H. C. , Yuen S. T. , Leung S. Y. , Lau G. K. K. , Lai C. L. , Chan C. K. , Go R. , Lam S. K.
Published: March 2003

Background:

Conventional 13C‐urea breath testing (13C‐UBT) includes a test meal to delay gastric emptying, which, theoretically, improves the accuracy of the test. Citric acid has been proposed as the best test meal. However, recent studies have suggested that a test meal may not be necessary.

Aim:

To investigate a new 13C‐UBT protocol without a test meal in a Chinese population.

Methods:

Consecutive dyspeptic patients referred for upper endoscopy were recruited. 13C‐UBT was performed on two separate days with or without a test meal (2.4 Gm citric acid) and compared with the ‘gold standard’ (CLO test and histology).

Results:

Two hundred and two patients were tested. Using receiver operating characteristics (ROC) analysis, the optimal delta‐value and optimal measurement interval for UBT were 5% and 30 min, respectively, both with or without a test meal. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 13C‐UBT with citric acid (96.5%, 97.7%, 98.2%, 95.6%, 97.0%) were similar to 13C‐UBT without a test meal (94.7%, 97.7%, 98.2%, 93.5%, 96.0%).

Conclusion:

This simplified 13C‐UBT protocol without a test meal produced highly accurate and reliable results in the Chinese population.
Low serum retinol levels are associated with hepatocellular carcinoma in patients with chronic liver disease
Authors: Newsome P. N. , Beldon I. , Moussa Y. , Delahooke T. E. , Poulopoulos G. , Hayes P. C. , Plevris J. N.
Published: March 2003

Background:

Retinol and other vitamin A derivatives affect the differentiation and growth of many tissues and have anti‐tumour properties.

Aim:

To investigate serum retinol levels in patients with liver disease and hepatocellular carcinoma (HCC) and to assess its importance as a risk factor for the development of HCC.

Methods:

Serum retinol levels were measured in healthy volunteers and 175 patients (34 with chronic hepatitis C, 117 with cirrhosis, and 24 with HCC.

Results:

The serum retinol levels (mean ± s.e.) in ng/mL, were 972.1 ± 37.7 in the control group and 647 ± 41.1 in patients with chronic hepatitis C. Serum retinol levels in patients with cirrhosis and HCC were lower than in patients with cirrhosis alone (365.8 ± 43.1 vs. 438.9 ± 22.1, P < 0.04). In particular, there was a more significant difference in serum retinol levels between Child–Pugh grade A patients with cirrhosis and Child–Pugh grade A patients with cirrhosis/HCC (serum retinol levels 532.4 ± 26.7 vs. 366.1 ± 86.4, P < 0.03). There was a significant difference in serum retinol levels between normal controls and all patients’ groups (P < 0.001). There were significantly lower serum retinol levels in cholestatic Child–Pugh grade A patients with cirrhosis compared with noncholestatic Child–Pugh grade A patients with cirrhosis/HCC (411.5 ± 30.3 vs. 579.7 ± 32.7, P < 0.0004). Sixty percent of patients with Child–Pugh grade A cirrhosis/HCC had serum retinol levels below 350 ng/mL compared with only 18.4% of cirrhotics without HCC (χ2‐test, P=0.01). No correlation was found between serum retinol levels and αFP or any other liver function tests, apart from serum albumin, which showed a positive correlation (r=0.61 P < 0.018).

Conclusions:

There was a progressive reduction in serum retinol levels from controls to patients with liver cirrhosis. Those patients with cirrhosis and HCC had significantly lower values than patients with cirrhosis alone. Serum retinol levels may be a risk factor for the development of HCC.
The effect of inflammation severity and of treatment on the production and release of TNFα by colonic explants in inflammatory bowel disease
Authors: Dionne S. , Ruemmele F. M. , Laberge S. , Seidman E. G.
Published: March 2003

Background:

Despite its pivotal role in mucosal inflammation, data on TNFα levels in inflammatory bowel diseases have been contradictory.

Aim:

To examine TNFα production in relation to the type and severity of inflammation and therapy, using colonic explant cultures.

Materials and methods:

Rectal mucosal biopsies from 271 paediatric patients (178 inflammatory bowel disease, 27 inflammatory controls, 66 normal) were cultured for 4 or 18 h. Basal TNFα tissue content and release into the medium were measured by ELISA and compared to histological severity and clinical parameters.

Results:

TNFα release as well as tissue‐associated TNFα levels were significantly increased in rectal biopsies from involved inflammatory bowel disease tissue. The amount of TNFα correlated with inflammation severity scores. TNFα levels were higher at 18 compared to 4 h in all groups, whether inflamed or not. TNFα released from rectal biopsies was lower among treated patients at 18 h. The presence of proximal colonic involvement was associated with higher TNFα release by uninvolved Crohn’s disease rectal biopsies compared to patients with ileitis alone.

Conclusions:

TNFα production and release is increased in involved rectal explants from inflammatory bowel disease. Anti‐inflammatory treatment diminishes this response.