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ID PMID Title PublicationDate abstract
16613915 Undergraduate musculoskeletal examination teaching by trained patient educators--a compari 2006 Nov BACKGROUND: To compare the core hand and knee examination skills gained by undergraduates taught either by trained patient educators (PEs) or by doctors. METHODS: A total of 50 final year medical students were randomized to receive training from PEs or doctors. Group A were taught hand examination by a PE with rheumatoid arthritis, and knee examination by a PE with osteoarthritis. Group B was taught hand and knee examination by a consultant rheumatologist plus an untrained patient with appropriate signs. All students were taught an established core skills set in small group workshops. Students then undertook two validated objective structured clinical examination (OSCE) stations with two blinded assessors. Pre- and post-teaching questionnaires established the students' self-reported levels of skills (SRS) and a student evaluation of teaching (SET). The study was analysed as an equivalence trial. A mean difference in OSCE scores of 10% was assumed to be of educational significance. RESULTS: Although the SET scores of both groups were high, the doctor-led group received higher scores. Aside from this, the two student groups did not differ significantly. There were no significant differences in mean hand OSCE (mean difference = 0.88, P = 0.28, 95% CI = -0.73 to 2.49) or knee OSCE (mean difference = 0.28, P = 0.7, 95% CI = -1.19 to 1.75) scores. Both the upper and lower confidence intervals for each mean difference fell within the 10% range (-2.8 to 2.8 for the hand, and -2.5 to 2.5 for the knee) and equivalence was assumed. CONCLUSIONS: Adequately trained PEs can deliver clearly structured undergraduate skills, teaching with equivalent learning outcomes to those of rheumatology consultants. PEs are a valuable development to augment musculoskeletal education in the face of expanding student numbers.
17166737 MIF production by dendritic cells is differentially regulated by Toll-like receptors and i 2006 Oct Macrophage migration inhibitory factor (MIF) is clearly associated with rheumatoid arthritis (RA) disease severity. However, the regulation of MIF during the course of RA has not been subjected to similar scientific scrutiny. The aim of our study was to investigate the role of various Toll-like receptors (TLRs) and inflammatory mediators on MIF production by dendritic cells (DCs) in healthy controls and RA patients. DCs were cultured from 12 healthy donors and 12 RA patients. Triggering via TLR mediated pathways was achieved using various TLR specific ligands alone or in combination: Pam3Cys for TLR2, LPS and recombinant extra domain A containing fibronectin for TLR4 and Poly(I:C) and R848 for TLR3 and TLR7, respectively. In addition, iDCs from healthy controls were incubated with various cytokines, RANKL and CD40L for 48 h. MIF levels were measured using an ELISA assay. Stimulation of DCs by TLR4 ligands resulted in higher MIF production compared to immature DCs from healthy controls (p<0.002) and RA patients (p<0.002). DCs from RA patients produced higher MIF levels than healthy controls both at the immature stage (p<0.04) as well after full maturation via TLR2 (p<0.04) and TLR4 (p<0.001) triggering. Incubation with TLR3 and TLR7 ligands resulted in a significantly decreased secretion of MIF in RA patients and controls. Simultaneous incubation of TLR4 with either TLR3 or TLR7 ligands resulted in a decrease of MIF secretion when compared to TLR4 stimulation alone. The secretion of MIF increased when DCs were stimulated with TNF-alpha, RANKL and CD40L. The secretion of MIF by dendritic cells is differentially regulated by TLRs. In addition, TNF-alpha, RANKL, and CD40L augment MIF production by DCs and thus play a potential role in the amplification of the inflammatory loop in RA.
18034252 Safety of atlantoaxial fusion using laminar and transarticular screws combined with an atl 2009 Jan OBJECTIVE AND IMPORTANCE: A disadvantage of transarticular and C2 pedicle screws is vertebral artery (VA) injury as a result of screw misplacement. If unilateral occlusion of the VA is present, VA injury of the dominant side will cause fatal complications as a result of collateral flow insufficiency. Several authors have recently reported the usefulness of C2 laminar screws because of their safety on VA injury. We used transarticular and C2 laminar screws combined with the atlas hook in a patient with C1-2 instability and unilateral VA occlusion, in order to reduce the risk of further VA injury. CLINICAL PRESENTATION: A 64-year-old woman with rheumatoid atlantoaxial subluxation complained of cervical myelopathy and neck pain. Preoperative MR angiography showed a left side VA occlusion. TECHNIQUE: The patient underwent atlantoaxial, posterior fusion using a transarticular screw on the side of the occlusion and a C2 laminar screw on the dominant side combined with a bilateral atlas hook. The transarticular screw was inserted using a navigation system and image intensifier, and the laminar screw was inserted free hand. Bone grafting from the iliac crest was performed. CONCLUSION: Transarticular and C2 laminar screws fixation combined with the atlas hook in a patient with unilateral VA occlusion is a useful technique, in order to reduce the risk of further VA injury.
17541951 PKC-zeta expression is lower in osteoblasts from arthritic patients: IL1-beta and TNF-alph 2008 Feb 1 Protein kinase C (PKC) is a family of enzymes detected in a diverse range of cell types where they regulate various cellular functions such as proliferation, differentiation, cytoskeletal remodelling, cytokine production, and receptor-mediated signal transduction. In this study we have analyzed the expression of 11 PKC isoforms (-alpha, -beta(I), -beta(II), -gamma, -delta, -eta, -theta, -epsilon, -zeta, -iota/lambda, and -micro) in osteoblasts from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) in comparison with osteoblasts from post-traumatic (PT) patients. By Western blotting analysis, nine isoforms, -alpha, -beta(I), -beta(II), -delta, -theta, - epsilon, -zeta, - iota/lambda, and -micro, were detected in osteoblasts. In RA and OA patients, PKC -theta and -micro were greater expressed whereas PKC-epsilon and -zeta decreased when compared with normal cells. The subcellular distribution and quantitative differences were confirmed by immuno-electron microscopy. Furthermore, we demonstrated that treatment with the proinflammatory cytokines, IL-1beta and TNF-alpha, significantly decreased PKC-zeta expression in PT osteoblasts. This suggests that proinflammatory cytokines can modulate the expression of this PKC isoform in osteoblasts in a way which is similar to changes detected in arthritic patients.
16546352 Genetic variations in ZFP36 and their possible relationship to autoimmune diseases. 2006 May The ZFP36 gene codes for TTP, a regulator of TNF alpha. In mice, TTP deficiency results in a systemic autoimmune inflammatory syndrome with severe arthritis. We hypothesized that genetic variations in ZFP36 are associated with autoimmune disease in humans. The primary objective of this study was to identify human ZFP36 genetic variants in autoimmune disease cases and controls, determine their frequencies in a general clinic population, and construct haplotypes. We resequenced ZFP36 in 316 individuals with autoimmune diseases and identified 28 polymorphisms and determined the frequency of all the known ZFP36 polymorphisms in 484 participants of the Environmental Polymorphism Registry, a regional registry being conducted by the NIEHS. Based on the sequence-verified ZFP36 genotypes, 34 haplotypes were constructed. As a secondary objective, we examined autoimmune disease cases and controls for potential ZFP36 genetic associations. One novel polymorphism, ZFP36*8, a C to T transition in the protein coding domain, was significantly associated with rheumatoid arthritis (RA) in African-Americans (RR=1.23, 95% CI: 1.11-1.36). The data presented here suggest a tentative association between ZFP36 and RA. This finding, as well as the ZFP36 polymorphisms and haplotypes identified here, should form the basis for future association studies in autoimmune diseases.
17266963 Prevalence of the metabolic syndrome is increased in rheumatoid arthritis and is associate 2008 Feb Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis. The metabolic syndrome, a cluster of cardiovascular risk factors, identifies cardiovascular risk. We tested the hypotheses that patients with RA have a higher prevalence of the metabolic syndrome, particularly the WHO-defined syndrome that requires insulin resistance, and that this is associated with coronary atherosclerosis. The prevalence of the metabolic syndrome was determined using the modified WHO and NCEP III criteria in 154 patients with RA (88 with early RA and 66 with long-standing RA) and 85 control subjects. Coronary-artery atherosclerosis was detected by electron beam computed tomography. The WHO-defined metabolic syndrome was present in 42% of patients with long-standing RA, 31% with early RA and 11% of controls (P<0.001); the NCEP-defined metabolic syndrome was present in 42% of patients with long-standing RA, 30% with early RA and 22% of controls (P=0.03). Patients with the WHO-defined metabolic syndrome had an increased risk of having higher coronary-artery calcification scores, independent of age and sex (OR=2.02, 95% CI: 1.03-3.97, P=0.04). In conclusion, patients with RA have a higher prevalence of the metabolic syndrome than control subjects. Inflammation-associated metabolic syndrome is a mechanism that may contribute to increased coronary-artery atherosclerosis in RA.
17148556 Association of PTPN22 haplotypes with Graves' disease. 2007 Feb CONTEXT: A recent study reported associations of a series of single nucleotide polymorphisms (SNPs) within PTPN22, including rs2476601, with rheumatoid arthritis. OBJECTIVE: Having previously reported significant association of the T allele of rs2476601 in a Graves' disease (GD) cohort, we sought to determine whether novel rheumatoid arthritis-associated SNPs were also contributing to susceptibility to GD. DESIGN: Case control and family-based studies of five PTPN22 tag SNPs were performed. SETTING: An United Kingdom academic department of medicine was the setting for the study. PATIENTS OR OTHER PARTICIPANTS: A total of 768 GD patients, 768 control subjects, and 313 families with autoimmune thyroid disease participated. MAIN OUTCOME MEASURE: Tests for association with disease were the main outcome measure. RESULTS: No association with disease of any of the individual SNPs and no correlation between genotype and clinical phenotype were seen. However, haplotype analysis of the SNP markers with addition of rs2476601 did reveal a strong association of a haplotype containing the T allele, in both the case control (chi2 = 29.13; P = 6.77 x 10(-8)) and family data sets (chi2 = 5.24; P = 0.02). Furthermore, a novel protective effect of a haplotype containing all six SNPs was observed (chi2 = 17.02; P = 3.7 x 10(-5)). CONCLUSIONS: These data suggest that the association of SNPs within the PTPN22 region differs between autoimmune diseases, occurring individually and/or as part of a haplotype, indicating that the mechanisms by which PTPN22 confers susceptibility to GD may, in part, be disease specific.
18986481 Generalized pustulosis induced by adalimumab in a patient with rheumatoid arthritis - a th 2008 Nov Tumor necrosis factor-alpha (TNF-alpha) inhibitors such as adalimumab are increasingly used in the treatment of chronic inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. In Europe, this group of drugs also has been approved for therapy of moderate to severe psoriasis recently. With increased application of adalimumab, the possible adverse effects occurring in the course of treatment steadily gained more attention. Among these, infection and localized skin eruptions are the most common. Usually, the cutaneous symptoms rapidly resolve after discontinuation of the drug. Here, however, we report on a woman with rheumatoid arthritis who developed a therapy-refractory, generalized pustular rash during treatment with adalimumab. After different unsuccessful therapeutic attempts, only a combined treatment with prednisone, methotrexate, and cyclosporinee eventually led to marked improvement. To the best of our knowledge, this is the first report on a generalized, therapy-resistant pustulosis as an adverse effect of adalimumab.
19066177 Adverse events of low- to medium-dose oral glucocorticoids in inflammatory diseases: a met 2009 Dec OBJECTIVES: To systematically analyse the literature on reported adverse events of low- to medium-dose glucocorticoids during >or=1 month for inflammatory diseases. METHODS: Data were systematically retrieved and selected from PUBMED, EMBASE and CINAHL databases (6097 hits). RESULTS: A total of 28 studies (2382 patients) met the inclusion criteria. The risk of adverse events over all studies was 150 per 100 patient-years (95% confidence interval (CI) 132 to 169). Psychological and behavioural adverse events (eg, minor mood disturbances) were most frequently reported, followed by gastrointestinal events (eg, dyspepsia, dysphagia). In 14 studies comprising 796 patients with rheumatoid arthritis the risk of adverse events was 43/100 patient-years (95% CI 30 to 55), in 4 studies of 167 patients with polymyalgia rheumatica the risk of adverse events was 80/100 patient-years (95% CI 15 to 146), and in 10 studies of 1419 patients with inflammatory bowel disease the risk of adverse events was 555/100 patient-years (95% CI 391 to 718). High rates of adverse events were reported in high-quality studies with short follow-up, notably in studies of patients with inflammatory bowel disease. CONCLUSIONS: The risk of adverse events depends on study design and disease. Studies on inflammatory bowel disease were often of short duration with frequent documentation of adverse events which resulted in higher adverse event rates whereas, in studies of rheumatoid arthritis, the longer follow-up may have resulted in lower adverse event rates. In most studies aimed at efficacy of glucocorticoids or other drugs, adverse events were not systematically assessed. Clear guidelines on assessment of adverse events are lacking.
19019889 Etanercept therapy in rheumatoid arthritis and the risk of malignancies: a systematic revi 2009 Jul PURPOSE: Tumour necrosis factor (TNF) plays an important role in inflammation and may affect tumour growth control. To assess the risk of malignancy with etanercept, a fusion protein that inhibits TNF action, a meta-analysis was performed using individual patient data from randomised controlled trials (RCT) in patients with rheumatoid arthritis (RA). METHODS: A search was conducted of bibliographic databases, abstracts from annual meetings and any unpublished studies on file with manufacturers of etanercept to December 2006. Only RCT of etanercept used for 12 weeks or more in patients with RA were included. Nine trials met the inclusion criteria. To adjudicate endpoints, the case narratives of potential cases were reviewed. Patient-level data were extracted from the clinical trials databases. RESULTS: The nine trials included 3316 patients, 2244 who received etanercept (contributing 2484 person-years of follow-up) and 1072 who received control therapy (1051 person-years). Malignancies were diagnosed in 26 patients in the etanercept group (incidence rate (IR) 10.47/1000 person-years) and seven patients in the control group (IR 6.66/1000 person-years). A Cox's proportional hazards, fixed-effect model stratified by trial yielded a hazard ratio of 1.84 (95% CI 0.79 to 4.28) for the etanercept group compared with the control group. CONCLUSIONS: In this analysis, the point estimate of malignancy risk was higher in etanercept-treated patients, although the results were not statistically significant. The approach of obtaining individual patient data of RCT in cooperation with trial sponsors allowed important insights into the methodological advantages and challenges of sparse adverse event data meta-analysis.
18188726 Diagnosis of rheumatoid arthritis: multivariate analysis of biomarkers. 2008 Feb OBJECTIVE: To test if a combination of biomarkers can increase the classification power of autoantibodies to cyclic citrullinated peptides (anti-CCP) in the diagnosis of rheumatoid arthritis (RA) depending on the diagnostic situation. METHODS: Biomarkers were subject to three inclusion/exclusion criteria (discrimination between RA patients and healthy blood donors, ability to identify anti-CCP-negative RA patients, specificity in a panel with major non-rheumatological diseases) before univariate ranking and multivariate analysis was carried out using a modelling panel (n = 906). To enable the evaluation of the classification power in different diagnostic settings the disease controls (n = 542) were weighted according to the admission rates in rheumatology clinics modelling a clinic panel or according to the relative prevalences of musculoskeletal disorders in the general population seen by general practitioners modelling a GP panel. RESULT: Out of 131 biomarkers considered originally, we evaluated 32 biomarkers in this study, of which only seven passed the three inclusion/exclusion criteria and were combined by multivariate analysis using four different mathematical models. In the modelled clinic panel, anti-CCP was the lead marker with a sensitivity of 75.8% and a specificity of 94.0%. Due to the lack in specificity of the markers other than anti-CCP in this diagnostic setting, any gain in sensitivity by any marker combination is off-set by a corresponding loss in specificity. In the modelled GP panel, the best marker combination of anti-CCP and interleukin (IL)-6 resulted in a sensitivity gain of 7.6% (85.9% vs. 78.3%) at a minor loss in specificity of 1.6% (90.3% vs. 91.9%) compared with anti-CCP as the best single marker. CONCLUSION: Depending on the composition of the sample panel, anti-CCP alone or anti-CCP in combination with IL-6 has the highest classification power for the diagnosis of established RA.
17488751 Regression to the mean using the disease activity score in eligibility and response criter 2007 Jul OBJECTIVES: When patients with rheumatoid arthritis (RA) are selected to start TNF-alpha inhibitors on the basis of high disease activity scores (DAS), some of the fall in DAS will be due to regression to the mean (RTM). We have assessed the extent to which such RTM explains DAS improvements on TNF-alpha inhibitors in routine clinical practice. METHODS: We retrospectively evaluated DAS28 scores that had been recorded as part of routine assessment for two RA cohorts. (i) Thirty-five patients receiving TNF-alpha inhibitors who had been assessed when starting TNF-alpha inhibitors, 9-21 months prior and 1.5-6 months post-treatment. (ii) One hundred and seventy-seven clinic patients assessed twice, a year apart in the years immediately before the introduction of TNF-alpha inhibitors. RESULTS: In patients receiving TNF-alpha inhibitors, mean DAS fell 1.8 (95% confidence interval [CI] 1.3, 2.3) from baseline but only 0.9 (95% CI 0.4, 1.4) from the previous routine assessment. Twenty-four (69%) patients showed a fall in DAS of >1.2 from baseline but only 17 (49%) from the previous assessment. Regression analysis of results from the pre-biological era estimated that as much as 0.6 of the 1.8 apparent DAS response to TNF-alpha inhibitors might be accounted for by RTM. CONCLUSIONS: Assessing change in DAS from commencement of biological therapy may overestimate response, due to the impact of RTM and fluctuation in disease. Adequacy of response might be better assessed by serial assessments and a wider range of patient-centred outcomes.
16705477 Right ventricular diastolic abnormalities in rheumatoid arthritis and its relationship wit 2006 Dec OBJECTIVES: To investigate right ventricular diastolic function in rheumatoid arthritis (RA) and its relationship with left ventricular and pulmonary involvement. METHODS: Thirty-five RA patients and 30 healthy subjects were submitted to conventional Doppler (CE) and tissue Doppler echocardiography (TDE) to assess left and right systolic and diastolic function and to estimate maximal arterial systolic pulmonary pressure (PAP). To detect pulmonary involvement, pulmonary function tests and high-resolution computed tomography (HRCT) scans were performed in all RA patients. RESULTS: An abnormal RV filling, as expressed byan inverted tricuspid (Tr.) E/A ratio, was detected in 12 (34%) of the 35 RA patients and in 2 (7%) of the 30 controls (P<0.004). If compared to CE findings, prevalence of RV diastolic abnormalities were found higher in patients with RA by TDE (RV annulus Em/Am ratio <1 (in 31 (89%) of 35 patients) (P = 0.002). Twenty-two (63%) of 35 patients had abnormal HRCT findings. Pulmonary involvement with pulmonary hypertension (PHT) (36+/-5 mmHg) was detected in 10 (29%) of 35 RA. In this group, increase of RV annulus and basal Am wave, decrease of Tr. E/A ratio and RV annulus Em/Am ratio were statistically significant compared to RA (12 (34%) of 35) patients with pulmonary involvement who had normal PAP (19+/-5 mmHg), (P = 0.014, P = 0.006, P = 0.015, P = 0.049, respectively). CONCLUSIONS: This study points out an impaired RV filling in a significant part of RA patients without overt heart failure. Impairment of RV diastolic function may be a predictor of subclinic myocardial and pulmonary involvement in patients with RA.
16766365 The activity of exoglycosidases in the synovial membrane and knee fluid of patients with r 2006 May OBJECTIVE: To determine the activities of the five exoglycosidases that catabolize glycoconjugates (proteoglycans, glycoproteins, and glycolipids) in the synovial membrane and knee joint fluid of patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). METHODS: The following exoglycosidases were analysed with the p-nitrophenyl derivatives of appropriate sugars as substrates: hexosaminidase (HEX) and its isoenzymes A and B, beta-glucuronidase, beta-galactosidase, alpha-mannosidase, and alpha-fucosidase. RESULTS: Our results show that the activity of all exoglycosidases tested in the synovial membrane of patients with RA and JIA was significantly higher than in synovial fluid. We demonstrated that only the enzymatic activity of HEX was significantly higher in the tissue of patients with inflammatory diseases in comparison to the activity in the control group. CONCLUSION: These data support the concept that the synovial cells of patients with RA and JIA are the main source of exoglycosidases, which catabolize glycoconjugates of cartilage.
16287919 Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumoco 2006 Jan OBJECTIVE: To compare antibody responses to 23-valent pneumococcal vaccine (Pneumovax) in controls and patients with established rheumatoid arthritis (RA) treated with TNF blockers, methotrexate (MTX) or a combination of both. METHODS: Patients with RA (n = 149) and healthy controls (n = 47) were vaccinated. Treatment with TNF blockers (etanercept or infliximab) and MTX was given to 50 patients, and 62 patients were treated with TNF blockers alone or with other DMARDs. MTX alone was given to 37 patients. Concentrations of immunoglobulin G (IgG) antibodies against pneumococcal capsular polysaccharides 23F and 6B were measured by enzyme-linked immunoassay before and 4-6 weeks after vaccination. An immune response was defined as a twofold or higher increase in antibody concentration following vaccination. RESULTS: Prevaccination antibody levels for both 23F and 6B were similar in the patient groups. Antibody concentrations after vaccination increased significantly in all groups. Patients treated with TNF blockers without MTX showed better immune responses than those treated with TNF blockers in combination with MTX (P = 0.037 for 23F and P = 0.004 for 6B) or MTX alone (P<0.001 for both 23F and 6B). RA patients given MTX alone had the lowest immune responses. Prednisolone treatment did not influence the responses. CONCLUSIONS: Patients treated with TNF blockers and controls showed similar responses to vaccination. In contrast, patients treated with MTX had reduced responses regardless of anti-TNF treatment. The findings do not argue against the use of pneumococcal vaccination in RA patients undergoing treatment with TNF blockers.
16723942 Diagnosis of early arthritis: outcomes of a nurse-led clinic. 2006 Apr 13 Recent data suggest that early treatment of inflammatory arthritis can improve patient outcomes. While rheumatologists recognized this need for early evaluation and treatment, the current load on the rheumatology service nationwide may limit the capacity for timely evaluation. The authors developed a protocol to be applied through a specialized early arthritis clinic that is able to discriminate between different categories of early arthritis, to shortening the time taken to reach the correct diagnosis and provide the appropriate management. A total of 108 patients have been reviewed in the early arthritis clinic over 12 months. It took 3 weeks for the patients to be fully assessed in the rheumatology clinic instead of 16 weeks. Completing the clinic proforma helped the assessor to cover all causes of arthritis/arthralgia. Disease-modifying antirheumatic drug (DMARD) therapy was initiated within a few weeks (2 to 5 weeks) once diagnosis was confirmed, instead of 8 to 10 months previously. This early arthritis clinic model helped to shorten the referral lag time (duration between symptoms onset and first rheumatologist assessment) as well as lag time to DMARD therapy (duration between symptom onset and the institution of DMARD therapy).
19104820 Predictors of bone density testing in patients with rheumatoid arthritis. 2009 Jun Patients with rheumatoid arthritis (RA) are at increased risk of low bone density and fractures. This study identifies predictors of initiation of dual energy X-ray absorptiometry (DXA) testing in RA. We identified RA patients from the CORRONA registry with >or=1 year follow-up without reported DXA at study entry. The primary outcome was report of DXA in the first year of follow-up (DXA initiation). Variables associated with DXA initiation were considered for the multivariate model. Stepwise logistic regression identified independent predictors. Of the 2,717 RA patients without DXA documented at enrollment, 297 (11%) reported DXA initiation. Independent predictors of DXA initiation included age, female sex, history of fracture, steroid use, and physician's assessment of RA activity. In conclusion, DXA initiation in RA patients in the CORRONA cohort is low despite increased risk of osteoporosis. Predictors of DXA initiation include fracture, common risk factors for osteoporosis, and RA-associated factors.
18496682 Genetic polymorphism of CYP1A2 and the toxicity of leflunomide treatment in rheumatoid art 2008 Sep OBJECTIVE: Leflunomide is a disease-modifying antirheumatic drug used for treating rheumatoid arthritis (RA). In vitro studies demonstrated that cytochromes P450 (CYPs), mainly CYP1A2 and CYP2C19, might be involved in leflunomide activation. The aim of our study was to investigate whether genetic polymorphisms of CYP1A2, CYP2C19, and CYP2C9 influence leflunomide toxicity. METHODS: A genotyping approach was used to determine CYP1A2*1F, CYP2C19*2, CYP2C19*17, CYP2C9*2, and CYP2C9*3 alleles in 105 RA patients. RESULTS: Leflunomide treatment was well tolerated by 62 patients, whereas 43 patients discontinued the treatment within the first year due to toxicity. Patients with CYP1A2*1F CC genotype had a 9.7-fold higher risk for overall leflunomide-induced toxicity than did the carriers of CYP1A2*1F A allele [P = 0.002, odds ratio = 9.708, 95% confidence interval = 2.276-41.403]. No significant association between the CYP2C19 and CYP2C9 genotypes and the leflunomide toxicity was observed. CONCLUSION: Our results suggest that the CYP1A2*1F allele may be associated with leflunomide toxicity in RA patients.
18758793 Primary total hip arthroplasty with a flattened press-fit acetabular component in osteoart 2008 Dec INTRODUCTION: A flattened cup was designed to create a more physiological load transfer to the pelvic bone compared to hemispherical cups, and to allow more bone contact compared to low-profile' spherical cups. To investigate these theoretical advantages and the potential influence of the quality of the acetabular bone, a clinical study was performed in patients with osteoarthritis (OA) and inflammatory arthritis (IA). The aims of the study were (1) to evaluate the fixation of the cup, postoperatively and later when osseous integration should have taken place, (2) to assess perioperative complications such as acetabular fractures and (3) to monitor the polar gap, a potential risk factor for osteolysis. PATIENTS AND METHODS: A prospective study was performed on all consecutive OA and IA patients with an indication for primary total hip arthroplasty (THA). Three hundred and nine OA patients (340 hips) and 65 IA patients (76 hips) were included. The acetabular component was the flattened press-fit EPF-PLUS cup, the femoral component the tapered cementless Zweymueller SL-PLUS stem. All revisions and complications were recorded. Clinical and radiographical evaluation was performed on regular basis during 6-10 years. RESULTS: The incidence of early loosening of the cup was 0 out of 340 in the OA group and 1 out of 76 in the IA group. The incidence of acetabular fractures was 7 out of 340 in the OA group and 3 out of 76 in the IA group. Failure rate for the acetabular component due to aseptic loosening or osteolysis after 6-10 years was 0% in the OA group and 4.8% in the IA group. In all cases available for follow-up the polar gap had disappeared and full osseous integration had taken place in both the groups. INTERPRETATION: This study shows that the flattened press-fit acetabular component creates adequate initial mechanical stability to allow osseous integration and that the cup can be safely used in both OA and IA patients. However, after 6-10 years, in the IA group failure of the cup due to aseptic loosening occurred once and failure due to osteolysis occurred three times, while these type of failures did not occur in the OA group.
17907214 Absence of histologic evidence of synovitis in patients with Gulf War veterans' illness wi 2007 Oct 15 OBJECTIVE: An unexplained multisymptom illness, Gulf War veterans' illness (GWVI), has been described among allied force veterans of the first Gulf War (1990-1991). It has been proposed that some of its symptoms reflect an immune dysfunction, and rheumatologic symptoms including joint pain and stiffness are reported frequently. However, it is unknown whether synovial inflammation causes the articular symptoms. We examined synovial tissue from individuals with GWVI and joint pain for evidence of inflammation. METHODS: We compared synovial biopsy samples from 6 individuals with GWVI and joint pain with samples from 9 clinically asymptomatic controls (hematoxylin and eosin [H&E] stains only) and biopsy samples or surgically obtained specimens from 10 patients with rheumatoid arthritis (RA) and 12 with osteoarthritis (OA). Inflammatory changes were quantified in H&E stained sections with a modified synovitis score by immunostaining for CD3, CD20, CD38, CD68, Ki-67, and von Willebrand factor, and with a composite inflammation score based on these markers. RESULTS: Normal histology was seen in the GWVI specimens, except for mild focal lining hyperplasia and rare low-grade perivascular infiltrates in 1 specimen each. Mean +/- SEM synovitis scores were lowest and nearly identical in control (1.38 +/- 0.30) and GWVI specimens (1.41 +/- 0.29), intermediate in OA specimens (2.64 +/- 0.39), and highest in RA specimens (6.0 +/- 0.19). Likewise, inflammatory cells, cell division, vascular density, and composite inflammation score were lowest in the GWVI specimens. CONCLUSION: Despite significant joint pain, the GWVI synovia did not differ from normal controls. These results agree with other studies that have failed to document inflammatory or immunologic etiologies in GWVI.