Biomedical subjects

Simon P L Travis

Publications and source records attributed to Simon P L Travis.

8 recordsLinked to original sources

PubMed2006

TUCAN (CARD8) genetic variants and inflammatory bowel disease.

BACKGROUND & AIMS: The identification of the association between Crohn's disease (CD) and NOD2 (CARD15) confirmed both the heritability of CD and highlighted the role of the nuclear factor kappaB (NFkappaB) pathway in disease pathogenesis. Other susceptibility loci exist. TUCAN (CARD8) is located beneath a CD peak of linkage on chromosome 19q. TUCAN is expressed in the gut and is a negative regulator of NFkappaB, making it an excellent candidate gene for gastrointestinal inflammation. METHODS: Ten single nucleotide polymorphisms (SNP) across TUCAN were genotyped in 365 controls, 372 patients with CD, and 373 patients with ulcerative colitis. A diagnostic panel for CD was constructed using smoking status and TUCAN, NOD2, IBD5, NOD1, and TNFSF15 data. RESULTS: We demonstrate significant association between a TUCAN SNP and CD (OR 1.35, P = .0083). The association was more pronounced with disease affecting sites other than the colon (odds ratio, 1.52) and NOD2-negative CD (odds ratio, 1.50). Combination of these data with smoking and NOD2, IBD5, NOD1, and TNFSF15 status demonstrated very strong associations with CD and high sensitivities (96.3%), specificities (99.4%), and likelihood ratios (12.8) for CD, although further work will be needed before this model can be translated into direct clinical utility. CONCLUSIONS: We have shown an association between a likely functional polymorphism in TUCAN and CD. The combination of these data in a genetic panel suggests that clinicians may soon be able to translate genetic advances into direct benefits for patients.

CARD Signaling Adaptor Proteins↗

PubMed2006

Fistulating anal Crohn's disease: results of combined surgical and infliximab treatment.

INTRODUCTION: Infliximab is a monoclonal antibody against tumor necrosis factor-alpha, which has been shown to be effective in fistulating Crohn's disease. The safety of infliximab in patients with potential perianal sepsis is uncertain. This study was designed to assess the safety and outcome of infliximab therapy combined with surgery for patients with fistulating anal Crohn's disease. METHODS: All patients receiving infliximab for fistulating anal Crohn's disease between 2000 and 2004 were studied. Patients' demographics, clinical findings, magnetic resonance imaging, and examination under anesthesia were recorded. Perianal Crohn's disease activity index before and 8 to 12 weeks after three infusions of infliximab (5 mg/kg) were recorded. Routine policy was to insert drainage seton sutures at the time of preinfliximab examination under anesthesia and then remove it after the second infusion. Complications of treatment and outcome at the last clinic follow-up were recorded. RESULTS: Twenty-two patients underwent infliximab treatment (6 males; median age, 35 (range, 16-60) years). Twenty-one patients had preinfliximab examination under anesthesia: 12 required abscess drainage; 17 had at least one drainage seton suture inserted. Fourteen patients underwent pretreatment magnetic resonance imaging to identify clinically occult collections. All but one patient were established on immunomodulator therapy before infliximab treatment. Perianal Crohn's disease activity index improved significantly after infliximab infusion (preinfusion: median, 11, range, 8-17; postinfusion: median, 8, range, 5-16; P<0.001). There were no serious complications of infliximab treatment. At median follow-up of 21 (range, 4-31) months, only four patients achieved sustained fistula healing. Five patients have required defunctioning or proctectomy. Four patients have required repeated infusions of infliximab. CONCLUSIONS: Infliximab therapy in combination with examination under anesthesia/seton drainage is a safe and effective short-term treatment for fistulating anal Crohn's disease. Long-term fistula healing rates are low.

Adolescent↗

PubMed2006

Weight loss at high altitude: pathophysiology and practical implications.

Climbers at high altitude (>5000 m) lose weight. This impairs performance and safety, but the mechanisms are not entirely due to an imbalance between energy intake and expenditure. There is some evidence of carbohydrate malabsorption, but there are also changes in fat metabolism and total body water. This paper considers the physiological control of weight and then discusses the changes in each parameter before addressing the practical implications.

Altitude↗

PubMed2005

A common CTLA4 haplotype associated with coeliac disease.

Coeliac disease is a common enteropathy with a strong inherited risk characterised by dietary wheat, rye and barley induced T-cell activation. Although there is replicated linkage to 2q33, results are inconsistent from association studies of the most promising candidate genes: the CD28/CTLA4/ICOS cluster. CTLA4 plays a key role in regulating T lymphocyte mediated inflammatory responses, and variants in the 3' region influence development of diabetes and thyroid disease. We genotyped CTLA4 variants (-1722 C/T, -658 T/C, -318 C/T, +49 A/G, +1822 C/T, CT60 A/G) to tag all common haplotypes (>5% frequency) and an ICOS variant (IVS+173 C/T) in 340 white UK Caucasian coeliac disease cases. Strict ascertainment criteria for coeliac cases required both villous atrophy at diagnosis and positive serology. In total, 973 healthy controls were available for SNP, and 705 for CTLA4 haplotype, based association analyses. Coeliac disease showed weak association with the CTLA4 +1822T (P=0.019) and CT60 G (P=0.047) alleles. Strong association was seen with a common CTLA4 haplotype (P=0.00067, odds ratio 1.41) of frequency 32.7% in coeliac disease and 25.5% in healthy controls. A common CTLA4 haplotype shows strong association with coeliac disease, and contains multiple alleles reported to affect immunological function. Loss of tolerance to dietary antigens in coeliac disease may be mediated in part by heritable variants in co-signalling genes regulating T-cell responses.

Antigens, CD↗

PubMed2005

Comparison between prospective and retrospective evaluation of Crohn's disease activity index.

The Crohn's disease activity index (CDAI) is the most widely used measure of clinical disease activity in patients entered into clinical trials. The prospective nature of the CDAI calculation precludes its use as a clinical assessment tool. We compared the retrospective evaluation of the CDAI with the prospective evaluation in a heterogeneous patient population of 100 patients with Crohn's disease. The correlation between the two assessment methods was good with an r-value of 0.84 (p < 0,0001). There was a tendency of patients with a high retrospective CDAI to have a lower prospective CDAI which is explained by intention to treat. This study shows that a retrospective assisted evaluation of the CDAI is as accurate as the traditional prospective evaluation.

Abdominal Pain↗

PubMed2003

Thiopurine therapy: when to start and when to stop.

The thiopurines azathioprine and 6-mercaptopurine are effective both for active disease and for maintaining remission in both Crohn's disease and ulcerative colitis. This review describes criteria for starting thiopurines (two or more courses of steroids in a calendar year, relapse as prednisolone is reduced below 15 mg/day, within 6 weeks of stopping steroids) and the benefits of continuing treatment for up to 5 years. Challenging issues, such as thiopurine intolerance, relative merits of azathioprine, 6-mercaptopurine, monitoring therapy and thiopurines in pregnancy are addressed.

Azathioprine↗

PubMed2002

Role of tumor necrosis factor in Crohn's disease.

Tumor necrosis factor-alpha (TNF alpha) is one of several pro-inflammatory cytokines that have been implicated in the pathogenesis of Crohn's disease (CD). Treatment with antibodies to TNF alpha has been shown to reduce mucosal inflammation in the disease, promote tissue healing, achieve and maintain remission, improve the CD activity index (CDAI) and improve the quality of life. The first part of this article reviews the role of TNF alpha in CD.

Animals↗

PubMed2002

Therapeutic inhibitors of tumor necrosis factor in Crohn's disease.

Therapeutic options for patients with refractory ulcerative colitis or Crohn's disease have recently been augmented by the introduction of biological therapies. The pro-inflammatory cytokine, tumor necrosis factor (TNF)-alpha is present in elevated concentrations in patients with inflammatory bowel disease and inhibitors of TNF alpha have proved effective as treatment. Strategies aimed at reducing TNF in patients with Crohn's disease, include the mouse/human chimeric monoclonal antibody, infliximab (Centocor Inc), the humanized monoclonal antibody, CDP-571 (Celltech Group plc), the human recombinant TNF receptor fusion protein, etanercept (Immunex Corp), and thalidomide. New approaches, including the use of soluble TNF receptors, appear promising. This article reviews the evidence of therapeutic inhibition of TNF.

Animals↗