bluuebunny/crossref_metadata_2025 huggingface dataset:
Up‐regulation of TFF expression by PPARγ ligands in gastric epithelial cells
Authors: Shimada T. , Koitabashi A. , Kuniyoshi T. , Hashimoto T. , Yoshiura K. , Yoneda M. , Hiraishi H. , Terano A.
Published: August 2003

Background : Although trefoil factor family peptides (TFF peptides) are assumed to play important roles in gastric mucosal protection, the regulatory mechanism of gastric TFF expression has not been fully understood yet. Recent reports showed gastric expression of peroxisome proliferator‐activated receptor γ (PPARγ), a nuclear receptor known to be involved in the regulation of cell growth and differentiation in other cell types, such as adipocytes.

Aim : To determine whether PPARγ affects the expression of TFF in gastric epithelial cells.

Methods : MKN45 gastric cells were used as a model of gastric epithelial cells. DNA synthesis of the cells was determined by the measurement of BrdU incorporation. The effects of PPARγ ligands, 15‐deoxy‐Δ12,14‐prostaglandin J2 (15d‐PGJ2) and troglitazone (TGZ) on TFF expression were assessed by real‐time quantitative reverse transcription‐polymerase chain reaction (RT‐PCR).

Results : MKN45 cells expressed a significant amount of PPARγ. Both 15d‐PGJ2 and TGZ suppressed DNA synthesis of the cells in a dose‐dependent manner. In the control condition, MKN45 cells most abundantly expressed TFF1 and the relative expression level of TFF1, TFF2, and TFF3 mRNA was 1700:32:1. TFF1 and TFF2 mRNA levels were significantly up‐regulated by the incubation of the cells with 15d‐PGJ2 (10 µm) or TGZ (30 µm), whereas TFF3 mRNA level was not affected.

Conclusion : The results of the present study suggest a possible role of PPARγ in the regulation of TFF expression in gastric epithelial cells.
The protective effect of rebamipide on paracellular permeability of rat gastric epithelial cells
Authors: Joh T. , Takezono Y. , Oshima T. , Sasaki M. , Seno K. , Yokoyama Y. , Ohara H. , Nomura T. , Alexander J. S. , Itoh M.
Published: August 2003

Background : Barrier function in gastric epithelial cells is essential for the gastric defence mechanism against acid back‐diffusion into the mucosal layer. Our previous study indicated that trans‐epithelial resistance (TER) of rat gastric epithelial cells was rapidly increased when the cells were exposed to acid. This response to acid was diminished by indometacin.

Aim : Evaluate the effects of a mucoprotective agent, rebamipide, on the nonsteroidal anti‐inflammatory drug (NSAID)‐induced increase of gastric epithelial permeability.

Methods : Rat gastric epithelial cells were plated on tissue culture inserts. Cells were exposed to a NSAID (indometacin, 10−7 M). Trans‐epithelial permeability was measured by TER and diffusion rate of 14C‐mannitol. The effect of rebamipide was evaluated by measuring TER. Endogenous prostaglandin E2 (PGE2) production in culture medium was also measured.

Results : Indometacin gradually and significantly decreased TER and increased 14C‐manitol permeability. Rebamipide reversed the indometacin‐induced changes in epithelial permeability and induced PGE2 synthesis. This induction was blocked by either indometacin or a Cyclooxygenase (COX)‐2 specific inhibitor.

Conclusions : COX inhibitors such as indometacin inhibit regulation of epithelial permeability by reducing PGE2. COX‐1 has an important role in the gastric defense mechanism. Rebamipide suppressed an indometacin‐induced increase in gastric epithelial permeability by increasing PGE2 levels in a COX‐2 dependent manner.
Effects of antioxidative agents on apoptosis induced by ischaemia‐reperfusion in rat intestinal mucosa
Authors: Kojima M. , Iwakiri R. , Wu B. , Fujise T. , Watanabe K. , Lin T. , Amemori S. , Sakata H. , Shimoda R. , Oguzu T. , Ootani A. , Tsunada S. , Fujimoto K.
Published: August 2003

Background & aim : We have previously demonstrated that ischaemia‐reperfusion induces apoptosis in the intestinal mucosa. To evaluate that reactive oxygen species enhanced intestinal apoptosis after ischaemia‐reperfusion, we examined whether antioxidants reduced apoptosis.

Methods : Rats were infused through a duodenal tube with antioxidative agents, glutathione, rebamipide and dymethylsulfoxide during 2 h before an ischaemic insult. The superior mesenteric artery was occluded for 60 min, followed by 60 min reperfusion. Apoptosis was evaluated by percentage fragmented DNA (fragmented DNA/total DNA) and immunochemical staining.

Results : Increase in apoptosis in the intestinal mucosa after ischaemia‐reperfusion was attenuated by intraduodenal infusion of antioxidative agents, but was not completely abolished.

Conclusion : Scavenging effects of the antioxidative agents attenuated increases in intestinal apoptosis, indicating that oxidative stress after ischaemia‐reperfusion plays an important role in induction of apoptosis in the intestinal mucosa.
Review article: clinical significance of mucosal‐protective agents: acid, inflammation, carcinogenesis and rebamipide
Authors: Haruma K. , Ito M.
Published: August 2003

While a great deal of clinical evidence has been found regarding anti‐acids for the treatment of gastric disorders including peptic ulcers, not all disorders can be explained only by the hyperfunction of acid secretion. Especially in the Asian region, glandular atrophy is more prominent than in Western countries, therefore low acid output is often observed in these patients. Improvement of mucosal protection is rational therapy for these patients; this is the reason for use of these agents in Asian countries. Rebamipide has many biological activities for gastric mucosa such as increasing the blood flow and biosynthesis prostaglandins and the decrease of oxygen radicals. These suggest the possible efficacy of rebamipide in the prevention of both Helicobacter pylori‐related and nonsteroidal anti‐inflammatory drug (NSAID)‐induced gastric injury, which has been proved by human studies. Rebamipide is the only mucosal‐protective drug which can improve the histological gastritis in vivo, whereas anti‐acids have a lesser effect in influencing gastritis. Improvement of gastritis is expressed not only in quantity but also in quality of gastritis, which is shown as the reduction of iNOS expression in the gastric mucosa. Clinically, it is suggested that rebamipide has the potential to prevent gastric carcinogenesis by improvement of histological gastritis.
Comparison of the effects of rebamipide with those of cimetidine on chronic gastritis associated with Helicobacter pylori in Mongolian gerbils
Authors: Higuchi K. , Tanigawa T. , Hamaguchi M. , Takashima T. , Sasaki E. , Shiba M. , Tominaga K. , Fujiwara Y. , Oshitani N. , Matsumoto T. , Watanabe T. , Arakawa T.
Published: August 2003

Background and Aims : The effects of rebamipide on chronic gastritis associated with Helicobacter pylori have not been well‐defined. We compared these effects of rebamipide with those of cimetidine in Mongolian gerbils infected with H. pylori.

Methods : Mongolian gerbils with or without H. pylori were divided into 10 groups 6 weeks after inoculation and fed diets containing a drug (rebamipide or cimetidine) or control diet. All animals were sacrificed 4 weeks after grouping. Their stomachs were examined for histology, colonization by H. pylori, myeloperoxidase activity (myeloperoxidase), production of neutrophil chemokine (CINC/KC) and tumour necrosis factor‐α (TNF‐α), and serum gastrin levels.

Results : H. pylori colonized all of the inoculated animals. Neither rebamipide nor cimetidine decreased myeloperoxidase activity, but each reduced wet stomach weight in H. pylori‐infected animals. The amount of increase in CINC/KC and TNF‐α in gastric tissue caused by H. pylori infection was decreased by treatment with rebamipide or cimetidine. H. pylori infection increased serum gastrin levels, and this increase was significantly enhanced by cimetidine but not rebamipide.

Conclusions : Rebamipide may improve H. pylori‐infected chronic gastritis by preventing the production of inflammatory cytokines and chemokines, as does cimetidine, but may be preferable to cimetidine for long‐term administration for treatment of H. pylori‐infected chronic gastritis due to its effect on serum gastrin levels.
Gastric restitution is inhibited by dexamethasone, which is reversed by hepatocyte growth factor and rebamipide
Authors: Takahashi M. , Takada H. , Takagi K. , Kataoka S. , Soma R. , Kuwayama H.
Published: August 2003

Background : Glucocorticoids have been shown to induce peptic ulcers, especially when co‐administered with NSAIDs. Hepatocyte growth factor (HGF) plays a role in gastric ulcer repair, facilitating the restitution of gastric mucosal epithelial cells. HGF expression is induced by PGs in gastric fibroblasts. We hypothesized that dexamethasone (DEX) may inhibit PG production and HGF expression, thus inhibiting HGF‐induced gastric epithelial restitution.

Aim : To investigate the effect of DEX on gastric restitution, using cultured gastric cells, the role of HGF in the restitution inhibited by DEX, and the effect of rebamipide on DEX‐ inhibited restitution.

Methods : Human gastric fibroblasts were prepared from human stomach obtained at surgery; PGE2 and HGF is determined by ELISA; Restitution was assessed by the round wound restitution model, using coculture of gastric fibroblasts and epithelial cells; COX‐2 and HGF mRNA were quantified by TaqMan RT‐PCR system.

Results : 1. DEX inhibited HGF mRNA and COX‐2 mRNA. Accordingly, it inhibited PGE2 and HGF release. 2. DEX inhibited the restitution of gastric cells. 3. The inhibition of restitution was reversed by HGF and rebamipide to the same extent. 4. Rebamipide induced PGE2 and HGF.

Conclusion : DEX inhibits restitution via HGF depletion, and rebamipide reverses the inhibited restitution by HGF induction.
The effects of cure of Helicobacter pylori infection on the signal transduction of gastric epithelial cells
Authors: Azuma T. , Yamazaki S. , Yamakawa A. , Ito Y. , Ohtani M. , Dojo M. , Yamazaki Y. , Higashi H. , Hatakeyama M.
Published: August 2003

Background : The CagA protein of Helicobacter pylori is directly injected from the bacteria into cells via the bacterial type IV secretion system and undergoes tyrosine phosphorylation in the gastric epithelial cells. Translocated CagA forms a physical complex with the SRC homology 2 domain (SH2)‐containing tyrosine phosphatase SHP‐2, which plays an important role in mitogenic signal transduction in the host cells.

Aim : We examined the effect of eradication therapy on the signal transduction pathway of gastric epithelial cells induced by the CagA protein of H. pylori.

Methods : Gastric biopsy samples were obtained from 20 H. pylori‐positive atrophic gastritis patients before, and 3 months after, H. pylori infection eradication therapy, and subjected to immunoblot analysis to detect tyrosine phosphorylated CagA protein and CagA co‐immunoprecipitated endogenous SHP‐2.

Results : Tyrosine phosphorylated CagA protein and CagA co‐immunoprecipitated endogenous SHP‐2 were detected in the gastric mucosa from H. pylori‐positive atrophic gastritis patients. All H. pylori strains from these patients were cagA‐positive type I strains. After curing H. pylori infection, the tyrosine phosphorylated CagA protein and CagA co‐immunoprecipitated endogenous SHP‐2 disappeared from the gastric mucosa.

Conclusion : The cure of infection reduces the stimulated signal transduction of gastric epithelial cells by the translocated CagA protein of H. pylori, and may confer a beneficial effect on the reduction of cancer risk.
Effects of rebamipide, a gastro‐protective drug on the Helicobacter pylori status and inflammation in the gastric mucosa of patients with gastric ulcer: a randomized double‐blind placebo‐controlled multicentre trial
Authors: Fujioka T. , Arakawa T. , Shimoyama T. , Yoshikawa T. , Itoh M. , Asaka M. , Ishii H. , Kuwayama H. , Sato R. , Kawai S. , Takemoto T. , Kobayashi K.
Published: August 2003

Aims : To investigate the effects of rebamipide on the Helicobacter pylori eradication rate with amoxicillin and omeprazole. The trial also examined its histological effects on gastro‐mucosal inflammation after eradication.

Methods : Two hundred and six H. pylori‐positive patients with active gastric ulcer underwent 8‐week based therapy (OA) consisting of 2‐week amoxicillin with omeprazole and subsequent 6‐week omeprazole. They randomly received either rebamipide (OA‐R) or placebo (OA‐P) for 16 weeks: combined with the OA based therapy, and subsequently for another 8 weeks. Besides eradication rate, inflammatory findings of gastric mucosa after eradication were evaluated histologically.

Results : Per Protocol Set analysis showed no significant difference in eradication rate between OA‐R (64.6%; 95% confidence interval, 54.3–75.0%) and OA‐P (67.9%; 95% CI, 57.6–78.3%). Histological findings in the gastric mucosa of the ulcer region, however, indicated a significant improvement (P = 0.017) in inflammation scores in OA‐R (1.84 ± 0.41) compared with that in OA‐P (2.02 ± 0.39) after 16‐weeks of treatment. This suppressive effect on inflammation was observed even in the OA‐R patients unsuccessfully eradicated.

Conclusion : Rebamipide demonstrated a suppressive effect on the persistent and possibly chronic inflammation in the gastric mucosa of the ulcer region after eradication, but the drug did not improve the eradication rate.
Review article: inflammation‐related promotion of gastrointestinal carcinogenesis – a perigenetic pathway
Authors: Tsuji S. , Kawai N. , Tsujii M. , Kawano S. , Hori M.
Published: August 2003

Chronic inflammation has been reported to accelerate neoplasmas in gastrointestinal tract. Certain bacteria including Helicobacter pylori directly interact with host cells, induce proinflammatory cytokines and stimulate production of free radicals. Free radicals cause mutations in target cells so that neoplastic clones are established. Accumulation of such genetic alterations may cause malignant transformation of some established clones. In addition, inflammatory alterations may promote growth, expansion and invasion of gastrointestinal epithelial cells. The latter changes caused by inflammation may occur even without further genetic mutations or epigenetic alterations, and therefore may be categorized as ‘perigenetic alterations’ of neoplastic cells. For an example, tumour necrosis factor α (TNF‐α) plays pivotal roles not only in the reduction but also in the growth, invasion and metastases of certain neoplasmas. Our studies show that TNF‐α increases intracellular radical production, degradates E‐cadherin / β‐catenin complex and promotes dispersion and migration in epithelial cells transformed with an activated src oncogene (v‐src). These data indicate that an inflammatory cytokine induces the malignant potential of src‐activated neoplastic cells. Interestingly, TNF‐α also induced these phenotypic changes in nonmutated cells whose c‐Src was activated by TGF‐α, suggesting that the invasive properties of the cell were not necessarily related to gene mutation. Furthermore, certain radical scavengers suppressed the invasive phenotype of the cells. These results indicate that perigenetic alterations are an important target of pharmacological intervention of carcinogenesis.
Effect of long‐term administration of rebamipide on Helicobacter pylori infection in mice
Authors: Hahm K. B. , Kim D. H. , Lee K. M. , Lee J. S. , Surh Y. J. , Kim Y. B. , Yoo B. M. , Kim J. H. , Joo H. J. , Cho Y. K. , Nam K. T. , Cho S. W.
Published: August 2003

Background : It has been suggested that chronic, persistent, uncontrolled inflammations in the stomach could provide the basic step for the beginning of carcinogenesis. One of the potential clinical applications of rebamipide is the inhibition of the immunoinflammatory response in gastric mucosa imposed by Helicobacter pylori.

Aim : To determine the implications of long‐term rebamipide treatment in H. pylori infection, we studied the underlying moleculo‐pathological changes in gastric lesions in mice infected with H. pylori (SS1 strain), following this treatment.

Methods : C57BL/6 mice were sacrificed 24 and 50 weeks after H. pylori infection, respectively. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels of IL‐1β, TNF‐α, IFN‐γ and IL‐10, mRNA transcripts of various mouse cytokines and chemokines, and NF‐κB binding activities, and finally the presence of gastric adenocarcinoma were compared between an H. pylori infected group (HP), and an H. pylori infected group administered with long‐term rebamipide‐containing pellet diets (HPR).

Results : Serum levels of IL‐1β, IFN‐γ and TNF‐α, the gastric mucosal expression of ICAM‐1, HCAM and MMP, and transcriptional regulation of NF‐κB‐DNA binding were all significantly decreased in the HPR group compared with the HP group. An RNase protection assay showed, in the rebamipide administered group, significantly decreased mRNA levels of apoptosis‐related genes such as caspase‐8, FasL, Fas, TRAIL and various cytokines genes such as IFN‐γ, RANTES, TNF‐α, TNFR p75, IL‐1β. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not different in either group. However, long‐term administration of rebamipide showed the advantage of decreasing precancerous lesions like chronic atrophic gastritis and showed molecular evidence of attenuation of proliferation.

Conclusion : The long‐term administration of rebamipide should be considered in the treatment of H. pylori since it demonstrated molecular and biological advantages like a lessening of gastric inflammation and a possible chemopreventive effect.
Long‐term evaluation of mice model infected with Helicobacter pylori: focus on gastric pathology including gastric cancer
Authors: Kim D. H. , Kim S. W. , Song Y. J. , Oh T. Y. , Han S. U. , Kim Y. B. , Joo H. J. , Cho Y. K. , Kim D. Y. , Cho S. W. , Kim M. W. , Kim J. H. , Hahm K. B.
Published: August 2003

Background : Long‐term evaluation of gastric pathology after H. pylori infection is very important in order to reveal its clinical implications, since debate still exists on the gastric carcinogenesis provoked by H. pylori infection in animal models.

Aim : Either to evaluate the long‐term outcome of H. pylori infection or to determine how H. pylori could provoke gastric cancer in the mice model.

Methods : Four‐week‐old specific pathogen free C57BL/6 mice (n = 115) were infected with SS1, the mouse‐adapted H. pylori strain. After 4, 8, 16, 24, 36, 50 and 80 weeks of bacterial infection, the H. pylori‐infected mice were sacrificed.

Results : After 80 weeks of infection, almost all the H. pylori‐infected mice developed hyperplastic gastritis, but did not show any evidence of gastric adenoma, dysplasia or carcinoma. PCNA positive cells were most abundant after 50 weeks and tended to decrease thereafter up to 80 weeks, whereas apoptosis began to be noted 8 weeks after H. pylori infection, showing 7–8 apoptotic cells/high power field, and tending to increase as time passed. Normally observed neutral mucin decreased during the experiment, showing the most marked decrease 50 weeks after H. pylori infection. In contrast, acidic mucin was noted from 50 weeks after infection.

Conclusion : The SS1‐infected mouse seems to be a suitable animal model for H. pylori‐related research, and H. pylori itself does not induce gastric cancer in normal wild‐type mouse model following long‐term exposure, which could be explained by the balance that exists between cell proliferation and apoptosis.
The effect of rebamipide on Helicobacter pylori extract‐mediated changes of gene expression in gastric epithelial cells
Authors: Yoshida N. , Ishikawa T. , Ichiishi E. , Yoshida Y. , Hanashiro K. , Kuchide M. , Uchiyama K. , Kokura S. , Ichikawa H. , Naito Y. , Yamamura Y. , Okanoue T. , Yoshikawa T.
Published: August 2003

Background : Recent studies have shown that Helicobacter pylori affects intracellular signal transduction in host cells, leading to the activation of transcriptional factors and the induction of pro‐inflammatory cytokines. On the other hand, rebamipide, an anti‐gastritis and anti‐ulcer agent, could scavenge reactive oxygen species and reduce interleukin‐8 (IL‐8) expression in gastric epithelial cells induced by H. pylori‐stimulation through the attenuated activation of nuclear factor‐κB (NF‐κB).

Aims : In this study, we investigated the effects of rebamipide on gene expression in H. pylori‐stimulated epithelial cells using DNA chip.

Methods : H. pylori water extract (HPE) was prepared from NCTC11637, the type strain of H. pylori. Total RNA was extracted from MKN45 cells, a human gastric cancer cell line, following HPE‐stimulation with and without rebamipide for 3 h, and differences in gene expression profiles were observed using GeneChip and Human 6800 probe array.

Results : The GeneChip analysis demonstrated that 132 up‐regulated genes and 873 down‐regulated genes, such as growth factors, chemokines and transcription factors, were detected in MKN45 cells 3 h after stimulation of H. pylori. Among them, several genes, including bFGF, RANTES and MIP‐2β, were previously unknown to be expressed in H. pylori‐stimulated human gastric cells. Rebamipide reduced expression of 119 genes encoding cytokines, growth factors and their receptors and transcription factors.

Conclusions : These findings suggest that rebamipide could inhibit inflammatory reactions and tumour progression by modifying H. pylori infection‐induced gene expression in gastric epithelial cells.
Rebamipide binds to iNOS‐positive cells in acetic acid‐treated but not in ethanol‐treated rat gastric mucosa
Authors: Nakamura M. , Akiba Y. , Matsui H. , Tsuchimoto K. , Ishii H.
Published: August 2003

Background : Rebamipide is a gastroprotective agent to stimulate prostaglandin generation in gastric mucosa and attenuate the activity of neutrophils, but direct evidence for the effector sites of this agent has remained to be clarified.

Aim : The present study was undertaken to show the effector sites of rebamipide in control and ulcer‐provoked rats.

Methods : The rats were divided into control, acetic acid‐ and ethanol‐treated rats. In the acetic acid‐treated group, 100% acetic acid was attached to the serosal surface of the stomach for 30 s, 7 days before the experiments. In the ethanol‐treated group, a dose of 0.5 mL/100 g body weight of 50% ethanol was administered through orogastric intubation 2 h before the experiments. Using the unfixed cryostat sections, aqueous solution of 3H‐rebamipide was applied and the localization of the binding sites of rebamipide was investigated by autoradiography.

Results : In the control rats, rebamipide was found to bind to the surface epithelial cells. In the ethanol‐treated group, few binding sites were observed in the damaged gastric mucosa. In the acetic acid‐treated group, the marked accumulation of the binding sites of 3H‐rebamipide was observed in the mesenchymal cells in the lamina propria mucosae between the regenerated gastric epithelial cells. Combination of autoradiography and immunohistochemistry has revealed that iNOS‐immunoreactive cells had the strong binding of rebamipide in the acetic acid‐treated group. Some of these cells were CD68‐positive macrophages, while others were CD68‐negative, corresponding to polymorphonuclear leucocytes. In the ethanol‐treated acute gastric mucosal injury group, few binding sites were observed in the damaged gastric mucosa.

Conclusions : Autoradiography has made it clear that rebamipide binds to iNOS‐positive cells in the gastric mucosa 7 days after acetic acid‐treatment.
Introducing touchscreens to black and ethnic minority groups—a report of processes and issues in the Three Cities project
Authors: Jackson Margot , Peters Jean
Published: August 2003

There is a need for people to have access to health information but this may not be readily available for some black and ethnic minority groups living in England. This study aims to improve access to health information for ethnic minority groups by providing this in their own language, in an audio and visual format through a touchscreen computer. The study was led by health promotion and public health workers informed by advisory panels of representatives from local black and ethnic minority groups in the cities of Nottingham, Sheffield and Leicester. Discussion within the advisory panels and local epidemiological data helped to identify groups to be targeted and priority health issues to be addressed. Other issues covered during development included interface design, language translation and identification of accessible locations. A number of problems were addressed in establishing appropriate touchscreen facilities, mainly relating to producing information in an electronic format for multiple languages and populations not necessarily computer‐literate. Three touchscreens, containing information on 10 health topics, translated into five languages are currently installed, one in each city. They are being rotated through a series of locations including a library, GP practice, and a temple. Their use, and satisfaction with use, is being evaluated over a 2‐year period, by statistical analysis of computer logs and the collection of qualitative information by bi‐lingual interviewers with users, over an 18‐month period. Health information can be made available for ethnic minority groups even if they are unable to read their mother tongue. Touchscreens appear to be a suitable medium for achieving this.
Producing an information leaflet to help patients access high quality drug information on the Internet: a local study
Authors: Coleman Bridget
Published: August 2003

Objectives: To develop a patient information leaflet (PIL) to help local patients meet their drug information needs using the Internet, and to perform a preliminary evaluation of this tool.

Methods: Development—a cross‐sectional survey of the drug information needs of local patients using a semi‐structured questionnaire; assessment of websites offering free, consumer‐orientated medicines information using set criteria; identification of consensus criteria to evaluate the quality of health‐related on‐line information; evaluation—views on a draft patient information leaflet from a focus group.

Results: Those surveyed felt that being directed to high‐quality websites and being provided with assessment criteria for on‐line information would be useful. The three websites fulfilling most of the set quality criteria were Surgery Door (www.surgerydoor.co.uk), InteliHealth (www.intelihealth.com) and medlineplus (www.nlm.nih.gov/medlineplus). The six most frequently cited assessment criteria were currency, authorship, commerciality, relevance, links and attribution. A draft leaflet was constructed listing the above three websites and six criteria along with tips on how to search the Internet effectively. A focus group reacted favourably.

Conclusion: The Internet is a source of drug information—an information leaflet may help to guide local patients through its variable information quality.
Clinical Evidence diagnosis: developing a sensitive search strategy to retrieve diagnostic studies on deep vein thrombosis: a pragmatic approach
Authors: Vincent Sam , Greenley Sarah , Beaven Olwen
Published: August 2003

Objectives: To devise and evaluate a sensitive search strategy to retrieve diagnostic studies on specific diagnostic tests for deep vein thrombosis (DVT).

Methods: Systematic reviews on diagnostic tests for DVT were identified and the studies cited by them used to produce a reference set of search results (to be used to evaluate different search strategies). Five existing diagnosis search filters were combined to produce a sensitive search. This combined search was then refined to produce a more specific strategy, which was run on medline and the results were checked against the reference set. This search was too specific and was modified to produce a more balanced final strategy, which was again tested and the results compared with the reference set. The sensitivity of this newly created strategy was compared with the existing diagnosis searches already found. Finally, studies identified by the final search strategy were critically appraised for validity and relevance and the selected articles were compared with those found in the reference set.

Results: The final filter retrieved 124 out of 126 references from the reference set. From the search result, 227 cohort studies were selected and 147 of these were not cited in any of the systematic reviews on diagnostic tests for DVT.

Conclusions: The search strategy had 98.8% sensitivity. The precision of 8.8%, although low, compares well with other strategies with high sensitivity. Most of the systematic reviews on diagnosing a DVT have omitted a number of high quality articles.
Access to the online evidence base in general practice: a survey of the Northern and Yorkshire Region
Authors: Wilson Paul , Glanville Julie , Watt Ian
Published: August 2003

Aims: To assess the awareness and use of NHSnet within general practice. To investigate the presence of skills necessary to maximize the benefits of NHSnet connections.

Methods: Postal survey of general practice staff in the Northern and Yorkshire Region.

Results: At least one completed questionnaire was obtained from 65% of the general practices surveyed, and the individual response rate to the general practice survey was 44%. Ninety per cent of all respondents reported that their practice was connected to the NHSnet, with 59% of respondents reporting that they use NHSnet at least once a week. Although NHSnet was used to search for research information or guidance, all respondents in this survey still reported greater access to and use of paper‐based information resources. Respondents indicated that they still needed further training on how to use NHSnet (42%), how to search the Internet (31%) and how to search electronic databases such as medline (49%).

Conclusions: Since our 1999 survey, reported NHSnet connectivity has increased greatly, with a majority of respondents reporting that they use NHSnet at least once a week. Although encouraging, this level of usage suggests that using the Internet/NHSnet to find research has yet to become a core activity in general practice.
Usability evaluation of an NHS library website
Authors: Ebenezer Catherine
Published: August 2003

Objectives:  To carry out a usability evaluation of the recently launched South London and Maudsley NHS Trust library website.

Methods:  A variety of standard methodologies were employed: content and design evaluation of selected comparable sites, focus groups, a questionnaire survey of library and Web development staff, heuristic evaluation, observation testing, card sorting/cluster analysis, and label intuitiveness/category membership testing. All test participants were staff of or providers of services to the trust. Demographic information was recorded for each participant.

Results:  Test participants’ overall responses to the site were enthusiastic and favourable, indicating the scope and content of the site to be broadly appropriate to the user group. Testers made numerous suggestions for new content. Usability problems were discovered in two main areas: in the organization of the site, and in the terminology used to refer to information services and sources. Based on test results, proposals for a revised menu structure, improved accessibility, and changes to the terminology used within the site are presented.

Conclusion:  Usability evaluation methods, appropriately scaled, can be advantageously applied to NHS library websites by an individual Web editor working alone.
Conceptualizations of frailty in relation to older adults
Authors: Markle‐Reid Maureen , Browne Gina
Published: September 2003

Aim. The aim of this article is to discuss the concept of frailty and its adequacy in identifying and describing older adults as frail.

Background. Despite the dramatic increase in use of the term ‘frailty’ over the past two decades, there is a lack of consensus in the literature about its meaning and use, and no clear conceptual guidelines for identifying and describing older adults as frail. Differences in theoretical perspectives will influence policy decisions regarding eligibility for, and allocation of, scarce health care resources among older adults.

Method. The article presents a literature review and synthesis of definitions and conceptual models of frailty in relation to older adults. The first part of the paper is a summary of the synonyms, antonyms and definitions of the term frailty. The second part is a critical evaluation of conceptual models of frailty. Six conceptual models are analysed on the basis of four main categories of assumptions about: (1) the nature of scientific knowledge; (2) the level of analysis; (3) the ageing process; (4) the stability of frailty. The implications of these are discussed in relation to clinical practice, policy and research.

Conclusion. The review gives guidelines for a new theoretical approach to the concept of frailty in older adults: (1) it must be a multidimensional concept that considers the complex interplay of physical, psychological, social and environmental factors; (2) the concept must not be age‐related, suggesting a negative and stereotypical view of ageing; (3) the concept must take into account an individual's context and incorporate subjective perceptions; (4) the concept must take into account the contribution of both individual and environmental factors.
Accompanying critically ill relatives in emergency departments
Authors: Redley Bernice , Beanland Christine , Botti Mari
Published: September 2003

Background. Family members are a crucial part of the holistic approach to care in emergency departments. In particular, they are a group who are vulnerable, yet have been overlooked when considering care options.

Aim. The primary aim of this systematic review was to appraise research relevant to identifying and meeting the needs of family members who accompany a critically ill person into the Emergency Department (ED). The information was intended to inform future research into the care of these people.

Method. A quality assessment strategy was specifically developed to evaluate the various research designs used. The outcomes of the highest quality studies were used to develop evidence‐based clinical practice guidelines to inform clinicians caring for family members who accompany a critically ill person into the ED.

Results. Recommendations for family care drawn from this review provide the foundation for more rigorous methodologies in future research into this topic. Key findings concern family needs for communication, proximity, support, comfort, assurance and to locate meaning in the event.

Conclusion. The review has revealed current knowledge about the care of family members who accompany a critically ill person into the ED that provides guidelines for practice. Despite significant limitations, the knowledge can lead to recommendation to guide and inform future intervention research.
Park's Tribolium competition experiments: a non‐equilibrium species coexistence hypothesis
Authors: Edmunds Jeffrey , Cushing J. M. , Costantino R. F. , Henson Shandelle M. , Dennis Brian , Desharnais R. A.
Published: August 2003

In this journal 35 years ago, P. H. Leslie, T. Park and D. B. Mertz reported competitive exclusion data for two Tribolium species. It is less well‐known that they also reported ‘difficult to interpret’ coexistence data. We suggest that the species exclusion and the species coexistence are consequences of a stable coexistence two‐cycle in the presence of two stable competitive exclusion equilibria.

A stage‐structured insect population model for two interacting species forecasts that as interspecific interaction is increased there occurs a sequence of dynamic changes (bifurcations) in which the classic Lotka–Volterra‐type scenario with two stable competitive exclusion equilibria is altered abruptly to a novel scenario with three locally stable entities; namely, two competitive exclusion equilibria and a stable coexistence cycle. This scenario is novel in that it predicts the competitive coexistence of two nearly identical species on a single limiting resource and does so under circumstances of increased interspecific competition. This prediction is in contradiction to classical tenets of competition theory.
Diversity–stability relationships in multitrophic systems: an empirical exploration
Authors: Amarasekare Priyanga
Published: August 2003

The relationship between diversity and stability is crucial in understanding the dynamics of multitrophic interactions. There are two basic hypotheses about the causal link between diversity and stability. The first is that fluctuations in resource abundance allow consumer coexistence, thus increasing diversity at the consumer trophic level (resource variability hypothesis). The second is that interactions between coexisting consumer species reduce consumer efficiency and dampen population fluctuations, thus increasing consumer–resource stability (consumer efficiency hypothesis).

The two hypotheses lead to three comparative predictions: (i) fluctuations should be greater (resource variability) or smaller (consumer efficiency) in resource populations with coexisting consumer species, compared to those invaded only by the consumer species superior at resource exploitation; (ii) average resource abundance should be greater (resource variability) or smaller (consumer efficiency) in resource populations with greater fluctuations; and (iii) removal of the consumer species inferior at resource exploitation should increase or not affect resource population fluctuations (resource variability), or always increase them (consumer efficiency).

I tested these predictions with data from a host–multiparasitoid community: the harlequin bug (Murgantia histrionica) and two specialist parasitoids (Trissolcus murgantiae and Ooencyrtus johnsonii) that attack the bug's eggs.

Local host populations with coexisting parasitoids exhibited smaller fluctuations and greater average abundance compared to those with just Trissolcus, the species superior at host exploitation. Local populations that lost Ooencyrtus, the species inferior at host exploitation, exhibited an increase in host population fluctuations compared to those that did not.

The results contradict the expectations of the resource variability hypothesis, suggesting that host population fluctuations are unlikely to be driving parasitoid coexistence. They are consistent with the consumer efficiency hypothesis, that interactions between coexisting parasitoid species dampens host population fluctuations. I discuss the implications of these results as well as possible caveats.
Web‐location by linyphiid spiders: prey‐specific aggregation and foraging strategies
Authors: Harwood James D. , Sunderland Keith D. , Symondson William O. C.
Published: August 2003

Web‐location cannot be designed simply to optimize foraging success, but must be a compromise between competing factors, including microhabitat parameters (physical structure, microclimate) and predator avoidance.

We tested the hypothesis that, despite these compromises, linyphiid spiders managed to locate their webs within microsites with enhanced prey resources.

We tested further the ‘equilibrium’ hypothesis that spiders, within a community of species, occupy different, relatively narrow niche axes and despite being generalists do not simply aggregate to the same resources.

In the first study of its kind, prey resources at web‐sites were compared with those at matched non‐web‐sites with the same microhabitat properties. This was carried out for two subfamilies of Linyphiidae, one of which (Linyphiinae) is web‐dependent and locates its web just above the ground, and the other (Erigoninae) is less web‐dependent, locating its web on the ground and often hunting away from its web. We hypothesized that these subfamilies would locate their webs at microsites with enhanced densities of the prey most likely to be captured by their contrasting foraging strategies. We used spider weights as a surrogate for nutritional state, and compared spiders in webs with those without webs.

We found that even within a relatively uniform crop of wheat, spiders located their webs at microsites with greater prey resources. The most numerous prey, Collembola, were at significantly greater density at web‐sites of both subfamilies of spider. However, there were significantly more Collembola at web‐sites of the surface‐hunting Erigoninae. By contrast, significantly more non‐Collembola prey, especially aphids and Thysanoptera, were found at web‐sites of the Linyphiinae, whose aerial webs might be expected to intercept such prey more efficiently.

These differences were also present at matched non‐web‐sites, suggesting that microsite selection by the spiders was determined by the spectra of prey present. Comparison of the weights of web‐owning and non‐web‐owning Tenuiphantes tenuis (Linyphiinae) demonstrated the nutritional benefits of web‐owning.

The results suggested that the spiders used a combination of web‐location strategies at the microhabitat level, foraging behaviour and (known) high‐intensity intraspecific competition, to exploit prey‐rich microsites efficiently within fields in a dynamic manner.
Habitat use and feeding behaviour in two closely related fish species, the three‐spined and nine‐spined stickleback: an experimental analysis
Authors: Hart Paul J. B.
Published: August 2003

In this paper I analyse experimentally the way in which nine‐spined sticklebacks (Pungitius pungitius) and three‐spined sticklebacks (Gasterosteus aculeatus) use weeded areas and open water and how this use is influenced by food availability.

Experiments were designed to answer two questions: what preference do the two stickleback species have for weeded areas and the open water and then how is this preference changed by the presence or absence of food? Further, differences in behaviour between the two species were analysed.

Results showed differential habitat use by the two species: nine‐spined occupied the weeded area more often than three‐spined and were less likely to utilize the bottom 10 cm of the water column.

While foraging, nine‐spined swam and pointed more often than did three‐spined and modified some of these behaviours in response to the distribution of food.

The nine‐spined stickleback has a slimmer, more streamlined body than does the three‐spined and the differences in habitat use and behaviour reflected this.

The results are discussed in relation to interspecific competition and speciation through the ecological selection of different trophic morphologies.
The species–accumulation curve and estimation of species richness
Authors: Ugland Karl I. , Gray John S. , Ellingsen Kari E.
Published: August 2003

One of the general characteristics of ecological communities is that the number of species accumulates with increasing area sampled. However, it is important to distinguish between the species–area relationship and species accumulation curves. The species–area relationship is concerned with the number of species in areas of different size irrespective of the identity of the species within the areas, whereas the species accumulation curve is concerned with accumulation rates of new species over the sampled area and depends on species identity.

We derive an exact analytical expression for the expectance and variance of the species–accumulation curve in all random subsets of samples from a given area. The analytical species accumulation curve may be approximated by a semilog curve. Both the exact accumulation curve and its semilog approximation are independent of the underlying species abundance distributions, but are influenced strongly by the distribution of species among the samples and the spatial relationship of the samples that are randomized.

To estimate species richness in larger areas than that sampled we take account of the spatial relationship between samples by dividing the sampled area into subareas. First a species–accumulation curve is obtained for randomized samples of all the single subareas. Then the species–accumulation curve for all combinations of two subareas is calculated and the procedure is repeated for all subareas. From these curves a new total species (T–S) curve is obtained from the terminal point of the subarea plots. The T–S curve can then be extrapolated to estimate the probable total number of species in the area studied.

Data from the Norwegian continental shelf show that extrapolation of the traditional species–accumulation curve gave a large underestimate of total species richness for the whole shelf compared with that predicted by the T–S curve. Application of non‐parametric methods also gave large underestimates compared with actual data obtained from more extensive sampling than the data analysed here. Although marine soft sediments sampled in Hong Kong were not as variable as those from the Norwegian shelf, nevertheless here the new method also gave higher estimates of total richness than the traditional species–accumulation approaches.

Our data show that both the species–accumulation curve and the accompanying T–S curve apply to large heterogeneous areas varying in depth and sediment properties as well as a relatively small homogeneous area with small variation in depth and sediment properties.
How parasites divide resources: a test of the niche apportionment hypothesis
Authors: Mouillot David , George‐Nascimento Mario , Poulin Robert
Published: August 2003

Modelling species abundance patterns, i.e. the distribution of relative abundance among species within the same community, has become a common framework in community ecology. To describe species abundance patterns several statistical models have been proposed, e.g. the log‐normal distribution, but these do not provide an ecological explanation of the underlying processes.

Tokeshi introduced (1990) and developed (1993, 1996, 1999) a series of niche‐orientated stochastic models to fit species abundance patterns. They suggest that abundance of species are proportional to the resources they apportion. Following this hypothesis, Tokeshi defined some processes in resource partitioning to explain species abundance patterns.

To study the rules which govern species assemblages, parasite communities present advantages because each host harbours a replicate community, the total niche is limited to the body of the host and demographic processes are usually similar for all parasite species in a community. Using five Tokeshi models, we searched for common rules structuring the parasite communities of six species of marine fish from the coast of Chile. The biovolume of each parasite species was preferred as a measure of its ‘abundance’ over actual numerical abundance, to account for the considerable variation in body size among parasite species.

The random assortment model, which suggests a lack of competition and interaction and independent apportionment of resources between species in the community, was fitted successfully to the parasite communities of three fish species for both means and variances of abundance ranks using a new Monte‐Carlo method.

These results are in accordance with current knowledge on parasite coexistence rules, i.e. that most parasite communities appear non‐saturated with species, with many empty niches and with interspecific competition not playing a major structuring role.