Comprehensive Biomedical Research Center

London, United Kingdom

Comprehensive Biomedical Research Center

London, United Kingdom
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Campbell H.E.,King's College London | Campbell H.E.,Guys and St Thomas NHS Foundation Trust GSTFT | Campbell H.E.,Comprehensive Biomedical Research Center | Escudier M.P.,King's College London | And 5 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2011

Background Orofacial granulomatosis is a rare chronic granulomatous inflammatory disease of the lips, face and mouth. The aetiology remains unclear but may involve an allergic component. Improvements have been reported with cinnamon- and benzoate-free diets. Aims To explore the prevalence of compound and food sensitivity and examine the dietary treatments used in orofacial granulomatosis. Methods A comprehensive literature search was carried out and relevant studies from January 1933 to January 2010 were identified using the electronic database search engines; AGRIS 1991-2008, AMED 1985-2008, British Nursing and Index archive 1985-2008, EMBASE 1980-2008, evidence based medicine review databases (e.g. Cochrane DSR), International Pharmaceutical and Medline 1950-2008. Results Common sensitivities identified, predominantly through patch testing, were to benzoic acid (36%) food additives (33%), perfumes and flavourings (28%), cinnamaldehyde (27%), cinnamon (17%), benzoates (17%) and chocolate (11%). The cinnamon- and benzoate-free diet has been shown to provide benefit in 54-78% of patients with 23% requiring no adjunctive therapies. A negative or positive patch test result to cinnamaldehyde, and benzoates did not predict dietary outcome. The most concentrated source of benzoate exposure is from food preservatives. Use of liquid enteral formulas can offer a further dietary therapy, particularly in children with orofacial granulomatosis. Conclusion Management of orofacial granulomatosis is challenging but cinnamon- and benzoate-free diets appear to have a definite role to play. © 2011 Blackwell Publishing Ltd.

Briscoe S.,London Bridge Sleep Center | Hardy E.,King's College London | Pengo M.F.,London Bridge Sleep Center | Kosky C.,London Bridge Sleep Center | And 8 more authors.
Chronobiology International | Year: 2014

Wrist actigraphy is a valid measure to assess sleep and circadian rhythm abnormalities. It is listed in the diagnostic criteria for sleep disorders where single night polysomnography is insufficient (ICSD-2). However, an optimal recording time remains unclear. We hypothesised that seven days would provide sufficient data for analysis, similar to recordings for 14 days. We analysed three consecutive years of actigraphy data obtained within a tertiary sleep referral centre. Data were recorded continuously for two weeks using an AW4 actiwatch (Cambridge NeuroTechnology, Cambridge, UK; Mini Mitter Co, Sunriver, OR). Parameters, including sleep efficiency (SE), sleep latency (SL), sleep fragmentation index (SFI), total sleep time (TST) and wake after sleep onset (WASO) were analysed using GraphPad Prism (Version 5.02, GraphPad Software Inc, San Diego, CA) and classified into week one, week two and an overall average for the duration of 14 days. In addition, two experienced consultants working in the sleep laboratory compared the results of week one versus week two independently, visually analysing the data for circadian rhythmicity and fragmentation of the pattern, allowing calculation of the intraclass correlation coefficient (ICC), κ. The actigraphies of 239 patients (51.9% male; age 42 (16) years) were analysed. There was no difference in SE, SL, SFI or WASO between week one, week two and 14 days average recording. A small difference was found between TST week one (399.9 minutes, 95% CI 389.9-409.9 minutes) and TST week two (388.7 minutes, 95% CI 378.3-399.1 minutes), but not between TST for 14 days average recording (394.3 minutes, 95% CI 384.7-403.9 minutes) and either week. Independent scorers achieved a good agreement in the rhythmicity of the sleep pattern (ICC κ 0.734, p < 0.001) and a low agreement for the fragmentation of the pattern (ICC κ 0.380, p < 0.001). One week of wrist actigraphy recording provides similar data to two week actigraphies, despite subtle differences between the weeks. One week wrist actigraphy could be recommended as standard compared to longer recordings to maximise efficiency of the clinical service. Further studies are required to validate our results in specific clinical subgroups. © 2014 Informa Healthcare USA, Inc.

Campbell H.,King's College London | Campbell H.,Guys and St Thomas NHS Foundation Trust GSTFT | Campbell H.,Comprehensive Biomedical Research Center | Escudier M.,King's College London | And 14 more authors.
Inflammatory Bowel Diseases | Year: 2011

Background: Orofacial granulomatosis (OFG) is a rare chronic inflammatory disease of unknown etiology sharing histological features with Crohn's disease (CD). This study aimed to 1) define the clinical presentation of OFG, 2) establish differentiating features for those with CD, 3) examine if onset of OFG is predictive of CD, and 4) establish differentiating features for children. Methods: Data were extracted from medical notes (n = 207) for demographics, clinical features, blood parameters, diagnosis of CD, and treatment's for patients with OFG. Results: Ninety-seven patients (47%) were female. The lips (184/203; 91%) and buccal mucosa (151/203; 74%) were mainly affected. Forty-six (22%) had intestinal CD. Ulcers (24/46; 46% versus 29/159; 15%, P = <0.001) were more common in patients with CD as was a raised C-reactive protein (24/33; 73% versus 60/122; 49%, P = 0.016) and abnormal full blood count (19/41; 46% versus 35/150; 23%). The buccal-sulcus (12/44; 27% versus 20/158; 13%, P = 0.019) was more often affected in those with CD. Half the patients with CD were diagnosed prior to onset of OFG. The remainder were diagnosed after. The incidence of CD is similar for children (16/69; 23%) and adults (29/132; 22%), although oral onset in childhood is more likely to occur prior to diagnosis of CD. Conclusions: OFG mainly presents in young adults with lip and buccal involvement. Abnormalities in inflammatory markers, hematology and oral features of ulceration, and buccal-sulcal involvement are factors more commonly associated with CD. Initial presentation of OFG does not necessarily predict development of CD, although this is more likely in childhood. (Inflamm Bowel Dis 2011;) Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Palles C.,University of Oxford | Cazier J.-B.,University of Oxford | Howarth K.M.,University of Oxford | Domingo E.,University of Oxford | And 84 more authors.
Nature Genetics | Year: 2013

Many individuals with multiple or large colorectal adenomas or early-onset colorectal cancer (CRC) have no detectable germline mutations in the known cancer predisposition genes. Using whole-genome sequencing, supplemented by linkage and association analysis, we identified specific heterozygous POLE or POLD1 germline variants in several multiple-adenoma and/or CRC cases but in no controls. The variants associated with susceptibility, POLE p.Leu424Val and POLD1 p.Ser478Asn, have high penetrance, and POLD1 mutation was also associated with endometrial cancer predisposition. The mutations map to equivalent sites in the proofreading (exonuclease) domain of DNA polymerases ε and δ and are predicted to cause a defect in the correction of mispaired bases inserted during DNA replication. In agreement with this prediction, the tumors from mutation carriers were microsatellite stable but tended to acquire base substitution mutations, as confirmed by yeast functional assays. Further analysis of published data showed that the recently described group of hypermutant, microsatellite-stable CRCs is likely to be caused by somatic POLE mutations affecting the exonuclease domain. © 2013 Nature America, Inc. All rights reserved.

Shrikrishna D.,UK National Heart and Lung Institute | Shrikrishna D.,Imperial College London | Tanner R.J.,UK National Heart and Lung Institute | Lee J.Y.,Imperial College London | And 10 more authors.
Chest | Year: 2014

BACKGROUND: Skeletal muscle impairment is a recognized complication of COPD, predicting mortality in severe disease. Increasing evidence implicates the renin-angiotensin system in control of muscle phenotype. We hypothesized that angiotensin-converting enzyme (ACE) inhibition would improve quadriceps function and exercise performance in COPD.METHODS: Th is double-blind, randomized placebo-controlled trial investigated the effect of the ACE inhibitor, fosinopril, on quadriceps function in patients with COPD with quadriceps weakness. Primary outcomes were change in quadriceps endurance and atrophy signaling at 3 months. Quadriceps maximum voluntary contraction (QMVC), mid-thigh CT scan of the cross-sectional area (MTCSA), and incremental shuttle walk distance (ISWD) were secondary outcomes.TRIAL REGISTRY: Current Controlled Trials; No.: ISRCTN05581879; URL: Www.controlledtrials. com.RESULTS: Eighty patients were enrolled (mean [SD], 65 [8] years, FEV 1 43% [21%] predicted, 53% men). Sixty-seven patients (31 fosinopril, 36 placebo) completed the trial. The treatment group demonstrated a significant reduction in systolic BP ( Δ - 10.5 mm Hg; 95% CI, - 19.9 to - 1.1; P = .03) and serum ACE activity (Δ - 20.4 IU/L; 95% CI, - 31.0 to - 9.8; P < .001) compared with placebo. No significant between-group differences were observed in the primary end points of quadriceps endurance half-time (Δ - 0.5 s; 95% CI, - 13.3-14.3; = 5 .94) or atrogin-1 messenger RNA expression (Δ - 0.03 arbitrary units; 95% CI, - 0.32-0.26; P = .84). QMVC improved in both groups (fosinopril: δ 1.1 kg; 95% CI, 0.03-2.2; P = .045 vs placebo: Δ - 3.6 kg; 95% CI, 2.1-5.0; P < .0001) with a greater increase in the placebo arm (between-group, P = .009). No change was shown in the MTCSA ( P = .09) or ISWD ( P = .51).CONCLUSIONS: Th is randomized controlled trial found that ACE inhibition, using fosinopril for 3 months, did not improve quadriceps function or exercise performance in patients with COPD with quadriceps weakness. © 2014 American College of Chest Physicians.

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