clinical and epigenetic factors underlying treatment refractory rheumatoid arthritis

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The! Norfolk! early! arthritis! registry! examined! clinical! factors! and! basic! immunological! data! to! seek! a! responder! pattern! to! Methotrexate! (Hider! et! al.! 2008).! These! factors! ... function and role 240! Table 5-90 Paired sample t-test results (p value) between baseline and three months and three month and six month study visits for all cytokine analytes 289! ! 13! ! Table 5-91 Selected cytokines and inflammatory markers examined by autoantibody status 290! Table 5-92 Correlation between selected cytokines and mood (HADS) and fatigue 291! Table 6-93 Coping and. .. IB.! Associations! and! predictors! of! fatigue! in! severe! Rheumatoid! Arthritis. ! Oral! presentation! to! Scottish! Society! for! Rheumatology! Autumn!Meeting,!2nd!November!2012.! ! ! ! ! ! 21! ! !Chapter!1D!Introduction !and! Aims! Chapter!One!will!outline!the!relevant!background!to !rheumatoid! arthritis! as!a!disorder! including! the! epidemiology,! those! underlying! aetiological! factors! important!... permeability! and! angiogenesis! mediated! by! vascular! growth! factors! such! as! vascular! endothelial! growth! factor! (VEGF).! Hypertrophy! of! the! surface!epithelial!layer !and! deeper!interstitial!layer,!to!which!the!term!‘pannus’!is!given,! invades! and! destroys! underlying! bone! and! cartilage.! Together! with! oedema! facilitated! by!neoWangiogenesis !and! synovial!hypertrophy,!the !clinical! picture!of!a!swollen,!synovitic!... matrix! degradation! products! and! angiogenesis !factors. !Secretion!of!receptor!activator!of!nuclear!factor!kappaWB!ligand! (RANKL)! stimulates! maturation! of! osteoclast! precursors! to! osteoclasts,! which! effect! resorption!of!bone.!They!may!also!produce!reactive!oxygen !and! nitrogen!intermediates! and! prostaglandins !and! as!such!contribute!to!the!inflammatory!milieu !and! to!the!algesic! aspect!of!the!disease.!... RA!is!characterised!by!joint!swelling,!pain !and! loss!of!function!when!the!disease!enters! the!articular!phase.!Tendon !and! involvement!of!the!bursae!may!also!occur.!If!persistent,! chronic! and! irreversible! changes! appear! with! bone! and! cartilage! destruction,! ligamentous !and! tendon!rupture !and! fibrosis.!Loss!of!articular!range!of!movement!then! occurs.!Morning!stiffness !and! gelling!are!characteristic !and! relate!directly!with!disease!... poorer! prognosis! and! disease! in! RA! (abbreviations! can! be! found! in! text!or!Chapter!8.1!‘Abbreviations!used‘)! ! ! 35! ! 1.10.1!Predicting!Outcome! !In! order! that! treatment! can! be! administered! most! appropriately! and! judiciously,! attempts!have!been!made!to!predict!disease!course !and! outcome!on!the!basis!of !clinical! factors, ! biomarkers! and! genetic! profiling.! Severity! and! course!... between fatigue and clinical, biochemical variables and composite disease activity scores 137! Table 3-47 Bivariate correlation between fatigue and mood 138! Table 3-48 Selected clinical factors associated with severity of fatigue at baseline in biologic resistant RA 141! Table 3-49 Individual bivariate correlations between clinical, disease, patient outcome measures and fatigue... anxiety and depression scores at baseline study visit 154! ! 12! ! Table 3-62 Proportion of biologic resistant group with ‘possible’ and ‘probable’ mood disturbance at baseline and six months 154! Table 3-63 Correlation between fatigue and mood 156! Table 3-64 Correlation between mood and disability (HAQ) 159! Table 3-65 Correlation between mood (HADS score) and SF-36 physical and. .. Pima!Indians!(who,!with!native!Alaskan!populations,!display!a!particularly!high!incidence! and! prevalence)!to!Japan !and! Finland!(Silman!2002).! 1.2.2!Genetics !and! onset!of !Rheumatoid! Arthritis! Susceptibility,! pattern! of! onset,! course! and! response! to! therapy! might! be! expected! to! have! an! underpinning! genetic! influence.! Indeed,! this! is! suggested! in! epidemiological! studies;!RA!is!more!common!in!firstWdegree!relatives !and! monozygotic!twin!concordance! is!approximately!15%!falling!to!4%!in!dizygotic!twins!(D.!M.!Lee!&!Weinblatt!2001).!Age! . baseline and six months in biologic resistant group 132! Table 3-42 Disability (HAQ) at baseline and six months 133! Table 3-43 Bivariate analysis of disability (HAQ) and clinical and biochemical. components and HADS- D/HADS-A scores 136! Table 3-45 FACIT fatigue results at baseline and six month study visits 137! Table 3-46 Correlation between fatigue and clinical, biochemical variables and. and clinical/ biochemical variables 190! Table 4-80 Clinical variables between groups in microRNA-27b experiment 192! Table 4-81 Correlations between relative expression of microRNA-27b and clinical/ biochemical