[Show abstract][Hide abstract] ABSTRACT: Importance
Case reports and series suggest hematopoietic stem cell transplantation (HSCT) may benefit some patients with Crohn disease.Objective
To evaluate the effect of autologous HSCT on refractory Crohn disease.Design, Setting, and Participants
Parallel-group randomized clinical trial conducted in 11 European transplant units from July 2007 to September 2011, with follow-up through March 2013. Patients were aged 18 to 50 years with impaired quality of life from refractory Crohn disease not amenable to surgery despite treatment with 3 or more immunosuppressive or biologic agents and corticosteroids.Interventions
All patients underwent stem cell mobilization before 1:1 randomization to immunoablation and HSCT (n = 23) or control treatment (HSCT deferred for 1 year [n = 22]). All were given standard Crohn disease treatment as needed. Main Outcomes and Measures
Sustained disease remission at 1 year, a composite primary end point comprising clinical remission (Crohn Disease Activity Index (CDAI) <150 [range, 0-600]), no use of corticosteroids or immunosuppressive or biologic drugs for at least the last 3 months, and no endoscopic or radiological evidence of active (erosive) disease anywhere in the gastrointestinal (GI) tract. Secondary outcomes were individual components of the primary composite outcome and other measures of disease activity, laboratory results, quality of life and functional status, and GI tract imaging. Results
Twenty-three patients underwent HSCT and 22 received standard Crohn disease treatment (controls). Sustained disease remission was achieved in 2 patients undergoing HSCT (8.7%) vs 1 control patient (4.5%) (absolute difference, 4.2% [95% CI, −14.2% to 22.6%]; P = .60). Fourteen patients undergoing HSCT (61%) vs 5 control patients (23%) had discontinued immunosuppressive or biologic agents or corticosteroids for at least 3 months (difference, 38.1% [95% CI, 9.3% to 59.3%]; P = .01). Ten vs 2 patients had a CDAI less than 150 (remission) at the final evaluation, 8 (34.8%) vs 2 (9.1%) for 3 or more months (difference, 25.7% [95% CI, 1.1% to 47.1%]; P = .052). Eight (34.8%) vs 2 (9.1%) patients were adjudicated free of active disease on endoscopy and radiology at final assessment (difference, 25.7% [95% CI, 1.1% to 47.1%]; P = .054). There were 76 serious adverse events in patients undergoing HSCT vs 38 in controls. One patient undergoing HSCT died.Conclusions and Relevance
Among adult patients with refractory Crohn disease not amenable to surgery who had impaired quality of life, HSCT, compared with conventional therapy, did not result in a statistically significant improvement in sustained disease remission at 1 year and was associated with significant toxicity. These findings do not support the widespread use of HSCT for patients with refractory Crohn disease.Trial Registration
Full-text · Article · Dec 2015 · JAMA The Journal of the American Medical Association
[Show abstract][Hide abstract] ABSTRACT: Adverse drug effects on the gastrointestinal (GI) tract can occur as a predictable result of a drug's mode of action, by direct injury, through compromising GI defences, or as a consequence of changes in colonic bacterial flora. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common cause of gastroduodenal injury, owing to inhibition of prostaglandin synthesis, and increase the risk of serious GI complications between twofold and fourfold. Low doses of aspirin are associated with an increased risk of upper GI haemorrhage. COX-2 inhibitors largely spare the GI mucosa from injury. Advancing technology for investigating the small bowel now allows identification of subtle changes to the small bowel mucosa (such as ulceration and erosions) secondary to drugs. This can lead to occult iron deficiency anaemia, hypoalbuminaemia and protein-losing enteropathy. Drug-induced colitis is an important problem, with antibiotics the most common drug cause. Drugs can also exacerbate pre-existing inflammatory bowel disease. Strategies to minimize the adverse GI effects of drugs include drug avoidance or minimization, using lowest doses for the shortest time, selective COX-2 inhibitors for high-GI/low-cardiovascular risk patients, and upper GI mucosal protection by co-prescription of proton pump inhibitors with GI irritants.
[Show abstract][Hide abstract] ABSTRACT: Introduction
Gout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol, which has been named the Febuxostat versus Allopurinol Streamlined trial (FAST).
Methods and analysis
FAST is a cardiovascular safety study using the prospective, randomised, open, blinded endpoint design. FAST is recruiting in the UK and Denmark. Recruited patients are aged over 60 years, prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor. After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism (EULAR) urate targets (serum urate <357 µmol/L), patients are randomised to either continue optimal dose allopurinol or to use febuxostat. Patients are followed-up for an average of 3 years. The primary endpoint is first occurrence of the Anti-Platelet Trialists’ Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are all cause mortality and hospitalisations for heart failure, unstable, new or worsening angina, coronary or cerebral revascularisation, transient ischaemic attack, non-fatal cardiac arrest, venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia. The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3.
Ethics and dissemination
FAST (ISRCTN72443728) has ethical approval in the UK and Denmark, and results will be published in a peer reviewed journal.
Trial Registration number
FAST is registered in the EU Clinical Trials Register (EUDRACT No: 2011-001883-23) and International Standard Randomised Controlled Trial Number Register (ISRCTN No: ISRCTN72443728).
[Show abstract][Hide abstract] ABSTRACT: Introduction
Cyclooxygenase 2 (COX-2) inhibitors have less upper gastrointestinal toxicity than traditional non-steroidal anti-inflammatory drugs (NSAIDs). However, both COX-2 inhibitors and traditional NSAIDs may be associated with adverse cardiovascular side effects. Data from randomised and observational studies suggest that celecoxib has similar cardiovascular toxicity to traditional NSAIDs. The overall safety balance of a strategy of celecoxib therapy versus traditional NSAID therapy is unknown. The European Medicines Agency requested studies of the cardiovascular safety of celecoxib within Europe. The Standard care versus Celecoxib Outcome Trial (SCOT) compares the cardiovascular safety of celecoxib with traditional NSAID therapy in the setting of the European Union healthcare system.
Methods and analysis
SCOT is a large streamlined safety study conducted in Scotland, England, Denmark and the Netherlands using the Prospective Randomised Open Blinded Endpoint design. Patients aged over 60 years with osteoarthritis or rheumatoid arthritis, free from established cardiovascular disease and requiring chronic NSAID therapy, are randomised to celecoxib or their previous traditional NSAID. They are then followed up for events by record-linkage within their normal healthcare setting. The hypothesis is non-inferiority with a confidence limit of 1.4. The primary endpoint is the first occurrence of hospitalisation or death for the Anti-Platelet Trialists’ Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are (1) first hospitalisation or death for upper gastrointestinal ulcer complications (bleeding, perforation or obstruction); (2) first occurrence of hospitalised upper gastrointestinal ulcer complications or APTC endpoint; (3) first hospitalisation for heart failure; (4) first hospitalisation for APTC endpoint plus heart failure; (5) all-cause mortality and (6) first hospitalisation for new or worsening renal failure.
Ethics and dissemination
SCOT has been approved by the relevant ethics committees. The trial results will be published in a peer-reviewed scientific journal.
Clinical trials registration number
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The vascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors (coxibs) and traditional non-steroidal anti-inflammatory drugs (tNSAIDs), are not well characterised, particularly in patients at increased risk of vascular disease. We aimed to provide such information through meta-analyses of randomised trials. METHODS: We undertook meta-analyses of 280 trials of NSAIDs versus placebo (124,513 participants, 68,342 person-years) and 474 trials of one NSAID versus another NSAID (229,296 participants, 165,456 person-years). The main outcomes were major vascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death); major coronary events (non-fatal myocardial infarction or coronary death); stroke; mortality; heart failure; and upper gastrointestinal complications (perforation, obstruction, or bleed). FINDINGS: Major vascular events were increased by about a third by a coxib (rate ratio [RR] 1.37, 95% CI 1.14-1.66; p=0.0009) or diclofenac (1.41, 1.12-1.78; p=0.0036), chiefly due to an increase in major coronary events (coxibs 1.76, 1.31-2.37; p=0.0001; diclofenac 1.70, 1.19-2.41; p=0.0032). Ibuprofen also significantly increased major coronary events (2.22, 1.10-4.48; p=0.0253), but not major vascular events (1.44, 0.89-2.33). Compared with placebo, of 1000 patients allocated to a coxib or diclofenac for a year, three more had major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events (0.93, 0.69-1.27). Vascular death was increased significantly by coxibs (1.58, 99% CI 1.00-2.49; p=0.0103) and diclofenac (1.65, 0.95-2.85, p=0.0187), non-significantly by ibuprofen (1.90, 0.56-6.41; p=0.17), but not by naproxen (1.08, 0.48-2.47, p=0.80). The proportional effects on major vascular events were independent of baseline characteristics, including vascular risk. Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications (coxibs 1.81, 1.17-2.81, p=0.0070; diclofenac 1.89, 1.16-3.09, p=0.0106; ibuprofen 3.97, 2.22-7.10, p<0.0001; and naproxen 4.22, 2.71-6.56, p<0.0001). INTERPRETATION: The vascular risks of high-dose diclofenac, and possibly ibuprofen, are comparable to coxibs, whereas high-dose naproxen is associated with less vascular risk than other NSAIDs. Although NSAIDs increase vascular and gastrointestinal risks, the size of these risks can be predicted, which could help guide clinical decision making. FUNDING: UK Medical Research Council and British Heart Foundation.
[Show abstract][Hide abstract] ABSTRACT: Interpretation of video capsule data is time-consuming. Olympus capsule endoscopy (CE) software systems are equipped with auto-speed-adjusted and express-selected playback modes and overview function in an effort to reduce reading times. The clinical efficacy of these new playback features is unknown. Our objective was to evaluate the diagnostic yield and reading times of these new playback features.
This was a retrospective cohort study involving two experienced CE readers who analysed the CE procedures using either overview with express-selected or overview with auto-speed-adjusted modes. All CE videos were read blinded using Olympus Endocapsule software at 15 frames per second. The findings were then compared with those obtained when the CE procedures were read with conventional methods.
Seventy patients (36 male, 34 female) with a mean age of 51 ± 22 years were included in the study. Clinically significant findings were found for 40/70 (57%) patients. Use of overview function alone resulted in recognition of 32/40 (80%) clinically significant findings; when overview function was combined with express-selected or auto-speed-adjusted methods 39/40 (97.5%) clinically significant findings were recognised. The average reading time for overview with auto-speed-adjusted mode (34 ± 10 min) was significantly (p = 0.001) more than for overview with express-selected mode (19 ± 5 min).
The reading time for overview with express-selected mode was significantly lower than for overview with auto-speed-adjusted mode, with few unrecognised clinically significant lesions. These new playback systems can efficaciously reduce reading times of CE but need further evaluation in prospective multicentre studies.
No preview · Article · Feb 2012 · Digestive Diseases and Sciences
[Show abstract][Hide abstract] ABSTRACT: The serendipitous discovery of long-standing remission in patients with Crohn's disease (CD) undergoing bone marrow transplantation for other indications has led to the hope that hematopoietic stem cell transplantation (HSCT) could lead to a "cure" for this often refractory condition. Allogenic HSCT could benefit patients by replacing the genetic predisposition to CD in circulating leucocytes. Autologous HSCT would not change the genetic predisposition but might "reset" the immune system by eliminating autoreactive cells in the recipient and restoring the patient to the status quo of being predisposed to CD, but not suffering from it. Both HSCT and mesenchymal stem cell (MSC) therapy are currently under investigation as novel therapies for CD. Local inoculation of adipose tissue-derived MSC is a promising new treatment of fistulas in patients with CD and systemic infusion of MSC does not require toxic conditioning regimens and is currently being evaluated in clinical trials.
[Show abstract][Hide abstract] ABSTRACT: Ever since they were launched, proton pump inhibitors (PPIs) have been regarded as profligate prescription interventions and have become a favourite target for pharmacy advisers. Now that they are cheap, with generic omeprazole 20 mg daily costing £1.88 per month (£24.51 per annum) in the UK, it is time to ask whether this status should be reviewed, whether there are areas where the message should be reversed and whether there are any circumstances in which the extra cost of branded PPIs or combined preparations is justified. Equally, with the recognition of an extended toxicity profile, is prescribing profligacy not an economic but a safety issue?
[Show abstract][Hide abstract] ABSTRACT: IBD is a lifelong condition that can impose a substantial physical, psychological and social burden on individuals. In this article, Joanne Cooper, Jacqueline Collier, Veronica James and Christopher J Hawkey present a case study of one person's diagnosis of IBD during pregnancy. Taken from a larger qualitative research project exploring beliefs about personal control and self-management in inflammatory bowel disease (IBD), the challenges faced when developing symptoms of IBD during pregnancy are discussed. This offers new insight into the needs of pregnant women developing IBD and identifies the important role played by gastrointestinal nurses in supporting patients and educating non-IBD specialist staff.
No preview · Article · Jun 2011 · Gastrointestinal Nursing
[Show abstract][Hide abstract] ABSTRACT: Fat wrapping and mesenteric hypertrophy are characteristics of Crohn's disease (CD). In patients with CD, mesenteric adipose tissue releases higher levels of adiponectin, which could up-regulate production of tumor necrosis factor-α and increase the risk for aggressive disease. We investigated whether a higher ratio of visceral to subcutaneous fat was associated with complicated (fistulating or stricturing) CD.
We identified patients with a confirmed diagnosis of CD who had computed tomography scans of their abdomens (n = 50). Areas of subcutaneous and visceral fat were measured in 1 cross-sectional scan that was taken at the level of the umbilicus. The mesenteric fat index (MFI), defined as the ratio of areas of visceral to subcutaneous fat, was compared between patients with complicated (strictures and fistulas) and inflammatory CD.
The mean age of the patients with complications (n = 29) was 49.3 ± 15.6 years, and in patients with inflammatory CD (n = 21) it was 37.7 ± 19.1 years. The MFI was significantly higher (P = .001) in patients with complicated disease (0.67 ± 0.29) than in those with uncomplicated disease (0.23 ± 0.10) and was the only variable that remained significantly different on multivariate analysis. The area under the receiver operating curve for the MFI was 0.95 (95% confidence interval, 0.89-1.0), and an MFI of 0.29 identified patients with complicated CD with 93% sensitivity and 81% specificity.
A high ratio of areas of visceral to subcutaneous fat (MFI) is a marker of aggressive CD. Further studies are needed to determine the roles of adipose tissue in pathogenesis of CD.
No preview · Article · May 2011 · Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association
[Show abstract][Hide abstract] ABSTRACT: Background: Dysplasia in colonic inflammatory bowel disease (IBD) is often multifocal and flat. High-definition (HD) colonoscopy improves adenoma detection rates by improving the ability to detect subtle mucosal changes. The utility of HD colonoscopy in dysplasia detection in patients with IBD has not been reported so far. We aimed to compare the yield of dysplastic lesions detected by standard definition (SD) white light endoscopy with HD endoscopy. Methods: A retrospective cohort study of patients with long-standing (>7 years) colonic IBD undergoing surveillance colonoscopy at Nottingham University Hospital was studied between September 2008 and February 2010. Details of diagnosis, duration of disease, and outcomes of the colonoscopy were collected from the endoscopy database, electronic patient records, and patient notes. Results: There were 160 colonoscopies (101 ulcerative colitis [UC] and 59 Crohn's disease [CD]) in the SD group and 209 colonoscopies (147 UC and 62 CD) in the HD group. The groups were well matched for all demographic variables. Thirty-two dysplastic lesions (27 on targeted biopsy) were detected in 24 patients in the HD group and 11 dysplastic lesions (six on targeted biopsy) were detected in eight patients the SD group. The adjusted prevalence ratio of detecting any dysplastic lesion and dysplastic lesion on targeted biopsy was 2.21 (95% confidence interval [CI] 1.09–4.45) and 2.99 (95% CI 1.16–7.79), respectively, for HD colonoscopy. Conclusions: HD colonoscopy improves targeted detection of dysplastic lesions during surveillance colonoscopy of patients with colonic IBD in routine clinical practice. Randomized controlled studies are required to confirm these findings.
[Show abstract][Hide abstract] ABSTRACT: Inflammatory Bowel Disease is a collective term for two distinct long term conditions: Ulcerative Colitis and Crohn's disease. There is increasing emphasis on patients taking greater personal control and self-management of this condition, reflecting earlier research into the management of chronic illness. Nurses play a pivotal role in this process, yet how optimal personal control is self-assessed and self-managed in Inflammatory Bowel Disease is poorly understood.
This study set out to explore beliefs about personal control and self-management of Inflammatory Bowel Disease. It focused on the role of physical, psychological and socio-economic factors within the individual's life experience.
A qualitative approach was used comprising 24, one-to-one, semi-structured interviews with participants aged 30-40 years. Participants with a histological diagnosis of Inflammatory Bowel Disease for at least 12 months were eligible and recruited by gastrointestinal specialist staff from outpatient clinics at a large National Health Service Trust in the United Kingdom. Interviews were transcribed verbatim. Data analysis was informed by existing theories of personal control and used the 'systematic framework analysis' approach.
In addition to existing theories of personal control, self-discrepancy theory helped to explain how people viewed the control and self-management of Inflammatory Bowel Disease. One main theme emerged from the findings: 'Reconciliation of the self in IBD', this was supported by three sub-themes and eight basic themes. Some participants found that being unable to control and predict the course of their condition was distressing, however for others this limited control was not viewed as a negative outcome. Being able to share control of IBD with specialist health care staff was beneficial, and participants stated that other priorities in life were as equally important to manage and control. A key barrier to ensuring greater personal control and self-management was a lack of knowledge and awareness by non-specialist health care staff, employers and the wider society.
Nurses involved in the care of individuals with Inflammatory Bowel Disease should support and prepare patients for the discrepancies and uncertainties of living with the condition. Greater training about Inflammatory Bowel Disease is recommended, specifically for non-specialist health care staff and employers.
No preview · Article · Dec 2010 · International journal of nursing studies
[Show abstract][Hide abstract] ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of pain in rheumatic disorders and chronic pain syndromes. Their use is, however, limited by gastrointestinal (GI) toxicity, including upper GI symptoms, ulcers and related complications. Using data from the NASA/SPACE studies, we have reviewed the efficacy and tolerability of esomeprazole (20 or 40 mg once daily) in the management (i.e. short-term resolution plus long-term prevention of relapse) of upper GI symptoms in users of continuous daily NSAIDs.
The NASA/SPACE programme comprised four double-blind, placebo-controlled studies in NSAID users. Two studies evaluated the efficacy of esomeprazole for upper GI symptom relief over 4 weeks. Those patients with symptom relief were then enrolled into a further two studies that assessed efficacy over 6 months.
In the 4-week studies, more patients in the esomeprazole groups achieved relief from upper GI symptoms at week 4 compared with placebo (p<0.05). The proportion of patients with symptom relapse at 6 months was lower with esomeprazole 20 mg and 40 mg than with placebo (p<or=0.01).
Esomeprazole proved effective for both short-term resolution of, and sustained relief from, upper GI symptoms in long-term NSAID users, and was well tolerated.
No preview · Article · Nov 2009 · Clinical Drug Investigation
[Show abstract][Hide abstract] ABSTRACT: To evaluate the sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of 3 different techniques: high resolution white light endoscopy (WLE), Narrow Band Imaging (NBI) and Chromoendoscopy (CHR), all with magnification in differentiating adenocarcinomas, adenomatous and hyperplastic colorectal polyps.
Each polyp was sequentially assessed first by WLE, followed by NBI and finally by CHR. Digital images of each polyp with each modality were taken and stored. Biopsies or polypectomies were then performed followed by blinded histopathological analysis. Each image was blindly graded based on the Kudo's pit pattern (KPP). In the assessment with NBI, the mesh brown capillary network pattern (MBCN) of each polyp was also described. The Sn, Sp, PPV and NPV of differentiating hyperplastic (Type I & II-KPP, Type I-MBCN) adenomatous (Types III, IV-KPP, Type II-MBCN) and carcinomatous polyps (Type V-KPP, Type III-MCBN) was then compared with reference to the final histopathological diagnosis.
A total of 50 colorectal polyps (5 adenocarcinomas, 38 adenomas, 7 hyperplastic) were assessed. CHR and NBI [KPP, MBCN or the combined classification (KPP & MBCN)] were superior to WLE in the prediction of polyp histology (P < 0.001, P = 0.002, P = 0.001 and P < 0.001, respectively). NBI, using the MBCN pattern or the combined classification showed higher numerical accuracies compared to CHR, but this was not statistically significant (P = 0.625, 0.250).
This feasibility study demonstrated that this combined classification with NBI could potentially be useful in routine clinical practice, allowing the endoscopist to predict histology with higher accuracies using a less cumbersome and technically less challenging method.
[Show abstract][Hide abstract] ABSTRACT: Low-dose acetylsalicylic acid (ASA; aspirin; 75-325 mg/day) is effective for the prevention of cardiovascular events, and its use in this indication is rapidly increasing. However, the use of ASA and, indeed, other non-steroidal anti-inflammatory drugs (NSAIDs) is limited by the incidence of adverse gastroduodenal events. OBJECTIVES AND SCOPE: To review the clinical evidence for, and the pharmacodynamic basis of, ASA-induced gastroduodenal toxicity in comparison with NSAIDs, and address the question of whether low-dose ASA is 'safe' from a gastroduodenal perspective. This was a narrative, descriptive review, rather than a formal systematic review.
Adverse gastroduodenal effects, which are well known to occur with NSAIDs, are also prevalent in patients receiving low-dose ASA for cardiovascular protection even at doses as low as 75 mg/day. The risk of gastroduodenal toxicity is particularly high among 'at-risk' low-dose ASA patients (aged >70 years, previous ulcer or upper gastrointestinal bleeding and users of antiplatelets or NSAIDs). There are important differences in the mechanism of ASA-induced gastroduodenal toxicity, relative to NSAIDs. These differences include the effects on the cyclooxygenase (COX)-1 isoenzyme, local effects on the gastroduodenal mucosa specific to ASA and a reduction in platelet aggregation.
Data suggest that ASA causes significant gastroduodenal damage even at the low doses used for cardiovascular protection. These effects (both systemic and possibly local) may be pharmacodynamically distinct from the gastroduodenal toxicity seen with NSAIDs. Studies are required to establish strategies for improving the tolerability of low-dose ASA, allowing patients to continue to benefit from the cardiovascular protection associated with such therapy.
No preview · Article · Sep 2009 · Current Medical Research and Opinion
[Show abstract][Hide abstract] ABSTRACT: Campylobacter jejuni, the commonest cause of bacterial diarrhoea worldwide, can also induce colonic inflammation. To understand how a previously identified heat stable component contributes to pro-inflammatory responses we used microarray and real-time quantitative PCR to investigate the transcriptional response to a boiled cell extract of Campylobacter jejuni NCTC 11168.
RNA was extracted from the human colonocyte line HCA-7 (clone 29) after incubation for 6 hours with Campylobacter jejuni boiled cell extract and was used to probe the Affymetrix Human Genome U133A array. Genes differentially affected by Campylobacter jejuni boiled cell extract were identified using the Significance Score algorithm of the Bioconductor software suite and further analyzed using the Ingenuity Pathway Analysis program. The chemokines CCL20, CXCL3, CXCL2, Interleukin 8, CXCL1 and CXCL6 comprised 6 of the 10 most highly up-regulated genes, all with Significance Scores > or = 10. Members of the Tumor Necrosis Factor alpha/Nuclear Factor-kappaB super-family were also significantly up-regulated and involved in the most significantly regulated signalling pathways (Death receptor, Interleukin 6, Interleukin 10, Toll like receptor, Peroxisome Proliferator Activated Receptor-gamma and apoptosis). Ingenuity Pathway Analysis also identified the most affected functional gene networks such as cell movement, gene expression and cell death. In contrast, down-regulated genes were predominantly concerned with structural and metabolic functions.
A boiled cell extract of Campylobacter jejuni has components that can directly switch the phenotype of colonic epithelial cells from one of resting metabolism to a pro-inflammatory one, particularly characterized by increased expression of genes for leukocyte chemoattractant molecules.