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ID PMID Title PublicationDate abstract
20022456 Common errors in the execution of preoperative templating for primary total hip arthroplas 2010 Dec We reviewed 75 primary total hip arthroplasty preoperative and postoperative radiographs and recorded limb length discrepancy, change in femoral offset, acetabular position, neck cut, and femoral component positioning. Interobturator line, as a technique to measure preoperative limb length discrepancy, had the least amount of variance when compared with interteardrop and intertuberosity lines (Levene test, P = .0527). The most common error in execution of preoperative templating was excessive limb lengthening (mean, 3.52 mm), primarily due to inferior acetabular cup positioning (Pearson correlation coefficient, P = .036). Incomplete medialization of the acetabular component contributed the most to offset discrepancy. The most common errors in the execution of preoperative templating resulted in excessive limb lengthening and increased offset. Identifying these errors can lead to more accurate templating techniques and improved intraoperative execution.
19208596 Six and 12 weeks treatment response predicts continuation of tumor necrosis factor blockad 2009 Mar OBJECTIVE: To investigate if treatment response predicts continuation of anti-tumor necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). METHODS: We investigated if treatment response and/or achieving a certain activity state at 6 weeks or 3 months predicts continuation of treatment in an observational cohort of 1789 anti-TNF-naive patients with established RA disease from southern Sweden. RESULTS: Response to treatment at 6 weeks at overall/American College of Rheumatology (ACR20) or good/major level (except ACR70) significantly predicted drug continuation. Response according to all criteria sets at overall/ACR20 and at good/major/ACR70 level predicted drug continuation at 3 months, as did achieving low disease activity at 3 months irrespective of activity index applied. Remaining in a high disease activity state predicted drug discontinuation at both timepoints and according to all criteria sets. CONCLUSION: Response criteria may be useful aids in deciding on continuation of TNF blockade in RA as early as after 6 weeks of treatment. The various criteria sets perform similarly.
19539101 N-of-1 double-blind, randomized controlled trial of tramadol to treat chronic cough. 2009 May BACKGROUND: Chronic cough caused by interstitial pneumopathy can present a therapeutic dilemma, and the use of tramadol in the treatment of this symptom might be an alternative to improve the quality of life in patients. The present study describes a patient with rheumatoid arthritis and interstitial lung disease lasting 11 years who developed dry cough secondary to interstitial pneumopathy but was nonresponsive to several treatments (codeine 20 mg q6h; clobutinol 240 mg/d; and dextromethorphan 10 mg q4h). OBJECTIVE: The purpose of this study was to investigate, for an individual patient, the effectiveness of tramadol 50 mg compared with placebo, and whether tramadol provided any antitussive benefit. METHODS: This was an N-of-1 double-blind, randomized controlled trial of tramadol against placebo. Treatment was administered in 3 pairs, each consisting of 2 periods in which either tramadol 50 mg BID or placebo was administered for 6 days, followed by a 2-day washout period, and then the administration of the alternate for 6 days. A 2-day washout period was also carried out after pairs 1 and 2. Per pair, the sequence of treatments was randomized. Outcome measures were: the intensity of daytime and nighttime cough, assessed by a visual analog scale (VAS) ranging from 0 to 5 (0 = no cough, 5 = distressing cough); and the patient's perception regarding her health state (better, same, or worse). RESULTS: A 55-year-old black woman (height, 153 cm; weight, 71 kg) was in the study. In all treatment pairs, cough intensity, as reported by the patient using the VAS, was significantly lower with tramadol compared with placebo (P < 0.001), both in the daytime (2 vs 5, respectively) and at nighttime (1 vs 4). Regarding the patient's health state, in all periods in which tramadol was administered, the patient reported feeling better than when placebo was administered. At the begin- ning of pair 2, the use of rescue tramadol 50 mg (un-blinded) was permitted due to cough intensity. In the remaining treatment periods in which placebo was administered, rescue tramadol was administered, whereas rescue tramadol was not needed during the periods in which tramadol was administered. CONCLUSIONS: Tramadol appeared to be effective in controlling cough in this patient. Because no similar report was found in the literature, further studies assessing the efficacy of tramadol as an antitussive agent are warranted.
20087267 Anti-cyclic citrullinated peptide antibodies and rheumatoid factor in Sjögren's syndrome. 2009 Oct OBJECTIVES: The purpose of this study was to evaluate the prevalence and clinical significance of anti-cyclic citrullinated peptide antibodies (anti-CCP-Abs), IgM and IgA rheumatoid factors (RFs) in primary Sjögren's Syndrome (pSS). MATERIALS AND METHODS: We compared clinical and serological characteristics of 31 pSS and 31 Rheumatoid Arthritis (RA) patients. Both, anti-CCP-Abs and RFs (IgM, IgA) directed against Fc determinants of IgG from humans and rabbit were detected by enzyme-linked immunosorbent assay (ELISA). We included 31 blood donors as control group for the evaluation of RFs and anti-CCP-Abs. Nine (29%) pSS patients presented arthritis, and 10 (32,3%) RA patients also had secondary Sjögren's syndrome (sSS) RESULTS: IgM and IgA RFs prevalence was similar in pSS and RA, whichever the antigene (Human or Rabbit IgG) used. However, RA patients with sSS showed a tendency to present more often RF positivity, longer disease duration and higher ESR and CRP when compared with pSS patients with arthritis. Anti-CCP-Abs were detected in 64,5% of RA patients and in only 6,9% of pSS patients (p<0,0005). Anti-CCP-Abs were more often positive in RA patients with sSS (RA/sSS) (8 patients, 80%) than in RA patients without sSS (18 patients, 58,1%), and were absent in pSS patients with arthritis. RF-positive pSS patients presented more often pulmonary involvement and higher inflammatory parameters, and less often neuropathy compared to RF-negative patients. In controls, anti-CCP-Abs were absent and RFs were negligible. CONCLUSIONS: Anti-CCP-Abs were detected in only a few pSS patients, none of whom presented arthritis, which contrasts with the high frequency of these antibodies in RA/sSS. These results suggest that anti-CCP-Abs could be useful in the distinction between pSS and RA with sSS. Although not useful for the differential diagnosis between RA and pSS, RFs may have a prognostic role in pSS.
20374328 The infectious profiles of anti-tumor necrosis factor agents in a Thai population: a retro 2009 Jul AIMS: Anti-tumour necrosis factor-alpha (anti-TNF) agents represented treatment advances in a number of rheumatologic diseases. However, adverse effects of anti-TNF agents have been identified through both clinical trials and post-marketing surveillance, especially an increased risk of serious infections. This study firstly described the infectious profiles of anti-TNF agents in a Thai population. METHODS: We retrospectively reviewed all infectious incidences from 100 consecutive medical records of patients who were treated with either etanercept or infliximab for any rheumatologic and non-rheumatologic conditions. RESULTS: Indications for anti TNF-alpha agents were mainly rheumatoid arthritis (46%) and spondyloarthropathy (SpA) (41%). Seventy-seven patients were treated with etanercept and 23 with infliximab. For those whose initial treatment was etanercept, there were two events of suspected active pulmonary tuberculosis (TB) and suspected hepatitis-B virus (HBV) reactivation. Two out of 23 patients (8.7%) who were firstly treated with infliximab had herpes zoster skin infection. Incidence of overall infection before anti-TNF treatment were significantly higher in patient who started with etanercept (0.065 vs. 0.019 cases per person-years in etanercept and infliximab respectively, P < 0.0001). Incidence of overall infection post-anti-TNF treatment were 0.122 and 0.201 cases per person-years in patients who started with etanercept and infliximab with no significant difference (P > 0.05). The overall infection rates were significantly increased after infliximab treatment (P < 0.0001). CONCLUSION: Even thought there were two new events of TB and HBV reactivation after etanercept treatment, incidence of overall infection seemed to be increased after infliximab treatment. The infectious screening and monitoring with high index of suspicion as well as the pre-emptive treatment are still important whenever either etanercept or infliximab is started.
20123959 Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmuni 2010 Feb 15 Chronic mucocutaneous candidiasis (CMC) is frequently associated with T cell immunodeficiencies. Specifically, the proinflammatory IL-17A-producing Th17 subset is implicated in protection against fungi at epithelial surfaces. In autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED, or autoimmune polyendocrine syndrome 1), CMC is often the first sign, but the underlying immunodeficiency is a long-standing puzzle. In contrast, the subsequent endocrine features are clearly autoimmune, resulting from defects in thymic self-tolerance induction caused by mutations in the autoimmune regulator (AIRE). We report severely reduced IL-17F and IL-22 responses to both Candida albicans antigens and polyclonal stimulation in APECED patients with CMC. Surprisingly, these reductions are strongly associated with neutralizing autoantibodies to IL-17F and IL-22, whereas responses were normal and autoantibodies infrequent in APECED patients without CMC. Our multicenter survey revealed neutralizing autoantibodies against IL-17A (41%), IL-17F (75%), and/ or IL-22 (91%) in >150 APECED patients, especially those with CMC. We independently found autoantibodies against these Th17-produced cytokines in rare thymoma patients with CMC. The autoantibodies preceded the CMC in all informative cases. We conclude that IL-22 and IL-17F are key natural defenders against CMC and that the immunodeficiency underlying CMC in both patient groups has an autoimmune basis.
19404952 The PRL -1149 G/T polymorphism and rheumatoid arthritis susceptibility. 2009 May OBJECTIVE: Previous studies have demonstrated that the PRL -1149 T (minor) allele decreases prolactin expression and may be associated with autoimmune disease. The aim of this study was to determine the role of the PRL -1149 G/T polymorphism (rs1341239) in rheumatoid arthritis (RA) susceptibility. METHODS: We examined the association between PRL -1149 G/T and RA risk in 4 separate study populations, consisting of a total of 3,405 RA cases and 4,111 controls of self-reported white European ancestry. Samples were genotyped using 1 of 3 genotyping platforms, and strict quality control metrics were applied. We tested for association using a 2-tailed Cochran-Mantel-Haenszel additive, fixed-effects model. RESULTS: In the individual populations, odds ratios (ORs) for an association between PRL -1149 T and RA risk ranged from 0.80 to 0.97. In a joint meta-analysis across all 4 populations, the OR for an association between PRL -1149 T and RA risk was 0.90 (95% confidence interval 0.84-0.96, P=0.001). CONCLUSION: Our findings indicate a possible association between the PRL -1149 T allele and decreased RA risk. The effect size is small but similar to ORs for other genetic polymorphisms associated with complex traits, including RA.
20617355 Etanercept-induced necrotizing crescentic glomerulonephritis in two patients with rheumato 2010 Dec We present two patients with rheumatoid arthritis (RA) who developed necrotizing crescentic glomerulonephritis (NCGN) during etanercept therapy. Both patients developed proteinuria and hematuria, and one progressed to renal failure. Renal biopsy revealed NCGN. In both patients, nephritis improved following discontinuation of etanercept and administration of prednisolone. Physicians should be aware of etanercept-induced GN in patients with RA on anti-tumor necrosis factor therapy.
19705304 Primary thyroid marginal zone B-cell lymphoma MALT-type in a patient with rheumatoid arthr 2010 Sep Autoimmune diseases are defined as specific, adapted immune reactions against self antigens. Immune mechanism deficiency is a causal factor for B-cell lymphoma in primary Sjögren's syndrome and autoimmune thyroid disease. Thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is a 67-fold and parotid lymphoma is a 44-fold increased risk in Sjögren's syndrome and thyroiditis. MALT lymphoma was not reported in rheumatoid arthritis. We herein report the case of a 56-year-old woman with maltoma of thyroid in rheumatoid arthritis patient.
19345053 A randomized controlled trial of an intervention to reduce low literacy barriers in inflam 2009 Jun OBJECTIVE: Test the efficacy of educational interventions to reduce literacy barriers and enhance health outcomes among patients with inflammatory arthritis. METHODS: The intervention consisted of plain language information materials and/or two individualized sessions with an arthritis educator. Randomization was stratified by education level. Principal outcomes included adherence to treatments, self-efficacy, satisfaction with care, and appointment keeping. Secondary outcomes included health status and mental health. Data were collected at baseline, six, and twelve months post. RESULTS: Of the 127 patients, half had education beyond high school and three quarters had disease duration greater than five years. There were no differences in the primary outcome measures between the groups. In mixed models controlling for baseline score and demographic factors, the intervention group showed improvement in mental health score at six and twelve months (3.0 and 3.7 points, respectively), while the control group showed diminished scores (-4.5 and -2.6 points, respectively) (p=0.03 and 0.01). CONCLUSION: While the intervention appears to have had no effect on primary outcomes, further studies with continued attention to literacy are warranted. Study site and disease duration must be considered as participants in this study had higher than average health literacy and had established diagnoses for years prior to this study. PRACTICE IMPLICATIONS: The study offers insight into an application of many of the protocols currently recommended to ameliorate effects of limited literacy.
20812050 [Adipocytokines in rheumatoid arthritis and obesity]. 2010 Aug In obese rheumatoid arthritis (RA) patients inflammatory mechanisms and cardiovascular secondary disorders are possibly related to changed expression of adipocytokines. Various adipocytokines and inflammatory parameters were examined in 112 patients (23.2% men; 76.8% women) suffering from RA: leptin, adiponectin, visfatin, sCD40 L, CRP, and ESR. Average BMI was 27.6 (+/-5.6). Leptin and BMI as well as visfatin and BMI correlated positively, BMI and adiponectin, however, showed a negative correlation. Significant differences between normal-weight and obese RA patients were found in both leptin and adiponectin measurements. Visfatin showed a positive correlation with CRP; sCD40 ligand which is a marker for increased T-cell activity correlated with CRP and ESR. Patients with low adiponectin levels (<10 microg/ml) more often suffered from cardiovascular diseases (28.6%) than those with enhanced adiponectin (14.3%). Increased pro-inflammatory leptin and decreased anti-inflammatory adiponectin in obese RA patients can be associated with RA activity and enhanced cardiovascular risk.
20720390 Autoimmune bullous skin diseases occurring under anti-tumor necrosis factor therapy: two c 2010 BACKGROUND: Anti-tumor necrosis factor (TNF) agents are increasingly being used for a rapidly expanding number of rheumatic and systemic diseases. As a result of this use, and of the longer follow-up periods of treatment, there are a growing number of reports of the development of autoimmune processes related to anti-TNF agents. The use of anti-TNF agents has been associated with more and more cases of autoimmune diseases, principally cutaneous vasculitis, lupus-like syndrome, systemic lupus erythematosus and interstitial lung disease. OBSERVATIONS: We report 2 cases of autoimmune bullous skin disease occurring in patients undergoing TNF-targeted therapy: a bullous pemphigoid and a pemphigus foliaceus. Both patients were treated by anti-TNF agents for rheumatoid arthritis and showed improvement following interruption of that treatment. Here, we discuss the relationship between anti-TNF therapy and the occurrence of autoimmune bullous disease. CONCLUSION: Anti-TNF agents should be considered as a potential cause of drug-induced autoimmune bullous skin disease.
20675706 Anti-TNF therapy is associated with an increased risk of serious infections in patients wi 2011 Jan OBJECTIVES: To evaluate the risk of serious infections (SIs) in patients with RA treated with anti-TNF therapy with emphasis on the risk across different ages. METHODS: Using data from the British Society for Rheumatology Biologics Register, a prospective observational study, we compared the risk of SI between 11 798 anti-TNF-treated patients and 3598 non-biologic DMARD (nbDMARD)-treated patients. RESULTS: A total of 1808 patients had at least one SI (anti-TNF: 1512; nbDMARD: 296). Incidence rates were: anti-TNF 42/1000 patient-years of follow-up (95% CI 40, 44) and nbDMARD 32/1000 patient-years of follow-up (95% CI 28, 36). The adjusted hazard ratio (adjHR) for SI in the anti-TNF cohort was 1.2 (95% CI 1.1, 1.5). The risk did not differ significantly between the three agents adalimumab, etanercept and infliximab. The risk was highest during the first 6 months of therapy [adjHR 1.8 (95% CI 1.3, 2.6)]. Although increasing age was an independent risk factor for SI in both cohorts, there was no difference in relative risk of infection in patients on anti-TNF therapy in the older population. There was no difference in hospital stay for SI between cohorts. Mortality within 30 days of SI was 50% lower in the anti-TNF cohort [odds ratio 0.5 (95% CI 0.3, 0.8)]. CONCLUSIONS: These data add to currently available evidence suggesting that anti-TNF therapy is associated with a small but significant overall risk of SI. This must be balanced against the risks associated with poor disease control or alternative treatments.
19554095 Emerging treatments for postmenopausal osteoporosis - focus on denosumab. 2009 The pathway of the receptor activator of the nuclear factor kappaB ligand (RANKL), RANK and osteoprotegerin (OPG) plays a central role in coupling bone formation and resorption during normal bone turnover and in a wide spectrum of diseases characterized by disturbed bone remodeling, increased bone resorption and bone destruction (osteoporosis, Paget's disease of bone, rheumatoid arthritis [RA], metastatic bone disease). Clinical trials indicate that denosumab, a RANKL-specific recombinant humanized monoclonal antibody, is effective in suppressing bone resorption, resulting in increase in bone mineral density (BMD) in post-menopausal women with low BMD, and has the potential to prevent progression of erosions in RA and of skeletal-related events in metastatic bone disease. The effects on fracture reduction in postmenopausal osteoporosis are awaited from the recently finished FREEDOM study. In clinical trials with denosumab, overall adverse events were similar to placebo or comparators, indicating a favorable safety profile in these diseases, which until now have been available up to 4 years, but data on long-term safety will be needed.
19074913 Efficacy of prednisone 1-4 mg/day in patients with rheumatoid arthritis: a randomised, dou 2009 Nov OBJECTIVE: A randomised double-blind placebo controlled withdrawal clinical trial of prednisone versus placebo in patients with rheumatoid arthritis (RA), treated in usual clinical care with 1-4 mg/day prednisone, withdrawn to the same dose of 1 mg prednisone or identical placebo tablets. METHODS: All patients were from one academic setting and all trial visits were conducted in usual clinical care. Patients were taking stable doses of 1-4 mg prednisone with stable clinical status, documented quantitatively by patient questionnaire scores. The protocol included three phases: (1) equivalence: 1-4 study prednisone 1 mg tablets taken for 12 weeks to ascertain their efficacy compared with the patient's usual tablets before randomisation; (2) transfer: substitution of a 1 mg prednisone or identical placebo tablet every 4 weeks (over 0-12 weeks) to the same number as baseline prednisone; (3) comparison: observation over 24 subsequent weeks taking the same number of either placebo or prednisone tablets as at baseline. The primary outcome was withdrawal due to patient-reported lack of efficacy versus continuation in the trial for 24 weeks. RESULTS: Thirty-one patients were randomised, 15 to prednisone and 16 to placebo, with three administrative discontinuations. In "intent-to-treat" analyses, 3/15 prednisone and 11/16 placebo participants withdrew (p = 0.03). Among participants eligible for the primary outcome, 3/13 prednisone and 11/15 placebo participants withdrew for lack of efficacy (p = 0.02). No meaningful adverse events were reported, as anticipated. CONCLUSION: Efficacy of 1-4 mg prednisone was documented. Evidence of statistically significant differences with only 31 patients may suggest a robust treatment effect.
19720877 Anti-inflammatory properties of a novel N-phenyl pyridinone inhibitor of p38 mitogen-activ 2009 Dec Signal transduction through the p38 mitogen-activated protein (MAP) kinase pathway is central to the transcriptional and translational control of cytokine and inflammatory mediator production. p38 MAP kinase inhibition hence constitutes a promising therapeutic strategy for treatment of chronic inflammatory diseases, based upon its potential to inhibit key pathways driving the inflammatory and destructive processes in these debilitating diseases. The present study describes the pharmacological properties of the N-phenyl pyridinone p38 MAP kinase inhibitor benzamide [3- [3-bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2- oxo-1(2H)-pyridinyl]-N,4-dimethyl-, (-)-(9CI); PH-797804]. PH-797804 is an ATP-competitive, readily reversible inhibitor of the alpha isoform of human p38 MAP kinase, exhibiting a K(i) = 5.8 nM. In human monocyte and synovial fibroblast cell systems, PH-797804 blocks inflammation-induced production of cytokines and proinflammatory mediators, such as prostaglandin E(2), at concentrations that parallel inhibition of cell-associated p38 MAP kinase. After oral dosing, PH-797804 effectively inhibits acute inflammatory responses induced by systemically administered endotoxin in both rat and cynomolgus monkeys. Furthermore, PH-797804 demonstrates robust anti-inflammatory activity in chronic disease models, significantly reducing both joint inflammation and associated bone loss in streptococcal cell wall-induced arthritis in rats and mouse collagen-induced arthritis. Finally, PH-797804 reduced tumor necrosis factor-alpha and interleukin-6 production in clinical studies after endotoxin administration in a dose-dependent manner, paralleling inhibition of the target enzyme. Low-nanomolar biochemical enzyme inhibition potency correlated with p38 MAP kinase inhibition in human cells and in vivo studies. In addition, a direct correspondence between p38 MAP kinase inhibition and anti-inflammatory activity was observed with PH-797804, thus providing confidence in dose projections for further human studies in chronic inflammatory disease.
19519466 Impact of IL-17 on cells of the monocyte lineage in health and disease. 2009 Jun Discovered in 1993, IL-17 has been the focus of intensive research during the last decade, in particular because of its neutrophil-accumulating capacity in several mammalian organs. We now know that the IL-17 family includes as a minimum 6 members, of whom at least IL-17A and IL-17F can be produced by T cells. Thus, IL-17 is positioned at the interface of acquired and innate immunity and constitutes a link between T cell activity and the accumulation of neutrophils locally in organs. Interestingly, there is now accumulating evidence that IL-17 has effects on myeloid cells other than neutrophils as well, namely on cells of the monocyte lineage. This review article scrutinizes the evidence that IL-17 exerts a functional impact on the cytokine production and functional activity in cells of the monocyte lineage in health and disease. Notably, this evidence includes data suggesting that there are conditions in which cells of the monocyte lineage are likely to play a significant pathogenic role and where IL-17 is directly controlling the activity of these key effector cells.
19132791 The minimally important difference for the health assessment questionnaire in rheumatoid a 2009 Feb OBJECTIVE: Patient-reported outcomes are used in clinical practice and trials. We studied a large clinical practice to determine the minimally important difference (MID) estimates for (1) the Health Assessment Questionnaire-Damage Index (HAQ-DI): improvement and worsening using patient global assessment anchor; and (2) pain using a patient-reported pain anchor. METHODS: Patients with rheumatoid arthritis (RA; N = 225) had clinic visits at 2 timepoints within 1 year, completed the HAQ-DI and pain visual analog scale (VAS; 0-100 mm), and answered the question, "How would you describe your overall status/overall pain since the last visit?", as much worsened, somewhat worsened, the same, somewhat improved, or much improved. If rated as somewhat improved or worsened, they were defined as the minimally changed subgroups. RESULTS: Eighty-three percent were women, mean age 60 years, with disease duration 11.7 +/- 10.7 years. The baseline HAQ-DI was 0.97 +/- SD 0.76, and at followup 1.0 +/- 0.77 (mean change +0.03 +/- 0.40). The baseline pain VAS was 42.3 +/- 28.8, and at followup 38.5 +/- 27.9 (mean change -2.8 +/- 25.9). The mean (SD) HAQ-DI change score was -0.09 (0.42) for somewhat improved and 0.15 (0.33) for somewhat worsened. The HAQ-DI change for somewhat/much better was -0.20 +/- 0.52, and for somewhat/much worse +0.21 +/- 0.33. For pain, somewhat improved changed by -11.9 mm on the VAS, and somewhat worsened by 6.8 mm. Estimates for HAQ-DI and pain were larger than the for no-change group, 0.03 (0.32) and -3.2 (20.9). CONCLUSION: The MID for HAQ-DI in clinical practice is smaller than it is in trials. This may have implications for observational studies and clinical care.
19279017 Transforming growth factor beta1 and laminin-111 cooperate in the induction of interleukin 2010 Jan OBJECTIVES: In synovial tissues of patients with rheumatoid arthritis (RA), strong expression of laminins and integrins co-localises with increased expression of inflammatory cytokines. Synovial fibroblasts (SF) contribute to the pathogenesis of RA through increased expression of cytokines and chemoattractant factors, one of which is interleukin-16 (IL16). A study was undertaken to investigate the regulatory pathways of IL16 in SF from patients with RA (RA-SF) and osteoarthritis (OA-SF). METHODS: SF were seeded in laminin-coated flasks and activated by the addition of cytokines. The expression of IL16 was investigated by quantitative RT-PCR, immunoblotting and ELISA; its biological activity was determined by a cell migration assay. Cell-matrix interactions were investigated by cell binding and attachment assays. Relevant intracellular signalling pathways were studied by immunoblotting and with pharmacological blocking reagents. RESULTS: Stimulation of SF with transforming growth factor beta(1)(TGF-beta(1)) and growth on laminin-111 (LM-111) significantly increased the expression of IL16. Binding to LM-111 induced significantly more IL16 mRNA in RA-SF than in OA-SF (p<0.05). The IL16 cytokine was detected in supernatants of TGF-beta(1)-activated and in LM-111+TGF-beta(1)-activated RA-SF (38 to 62 pg/ml), but not in supernatants of OA-SF. This IL16 regulation involved p38MAPK, ERK1/2 and SMAD2 signalling, but not NFkappaB. CONCLUSIONS: Binding of RA-SF to LM-111 in the presence of TGF-beta(1) triggers a significant IL16 response and thus may contribute to the infiltration of CD4+ lymphocytes into synovial tissues. This mode of IL16 induction represents a novel pathway leading to IL16 production in RA-SF but not in OA-SF, which operates independently of NFkappaB signalling.
19549093 Prevalence and extent of calcification over aorta, coronary and carotid arteries in patien 2009 Nov OBJECTIVE: To evaluate the prevalence and pattern of arterial calcification in patients with rheumatoid arthritis (RA). BACKGROUND: Patients with RA are prone to premature atherosclerosis; nonetheless the prevalence and extent of atherosclerosis in different vascular beds and their relationship to each other remain unknown. METHODS: We studied the distribution and extent of arterial calcification in 85 RA patients and 85 age-and sex-matched controls. Arterial calcification as determined by calcium score (CS) were measured using multi-detector computed tomography in thoracic aorta, coronary and carotid arteries. RESULTS: Compared with controls, RA patients had a significantly higher average CS and prevalence of CS > 0 in aorta, coronary and carotid arteries and overall arteries (all P < 0.05). After adjusting for age and sex, RA patients had a significantly higher relative risk of developing calcification in the aorta [Odds Ratio (OR) = 19.5, 95% Confidence Interval (CI): 8.0-47.6], followed by the carotid arteries (OR = 5.7, 95% CI:1.7-18.7) and coronary arteries (OR = 5.0, 95% CI:2.2-11.1) compared with controls (all P < 0.01). Amongst RA patients aged >60, 90% had diffuse arterial calcification, especially over the thoracic aorta, compared with 55% of controls who had arterial calcification clustered in the coronary arteries (P < 0.05). RA patients with total CS > 0 were older with a higher urea level and C-reactive protein than those without arterial calcification, no factor was found to be independently predictive for arterial calcification (all P > 0.05). CONCLUSIONS: Our results demonstrated that RA patients had earlier onset, more diffuse arterial calcification over multiple vascular beds and more preferential involvement of thoracic aorta, rather than coronary artery when compared with control.