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ID PMID Title PublicationDate abstract
21110115 Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid art 2011 Aug The aim of this study was to determine whether the vitamin D receptor (VDR) polymorphisms confer susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). A meta-analysis was conducted on the associations between the BsmI, TaqI, FokI, and ApaI polymorphisms of VDR and RA or SLE using: (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) additive model. A total of ten studies, six RA and four SLE studies, were considered in the meta-analysis. Meta-analysis of the VDR BsmI and TaqI polymorphisms showed no association between RA in all subjects, or in European or Asian subjects. In contrast, meta-analysis of the F allele, the FF genotype, and the FF vs. the ff genotype of the FokI polymorphism showed significant associations with RA in Europeans. The overall OR of the association between the F allele and RA was 1.502 (95% CI=1.158-1.949, P=0.002). Meta-analysis of the B allele, BB+Bb genotype, and BB genotype (additive model) of the BsmI polymorphism showed significant associations with SLE and LN in Asians. The overall ORs of the associations between the B allele and SLE and LN were 3.584 (95% CI=1.407-9.130, P=0.007) and 3.652 (95% CI=1.347-9.902, P=0.011). This meta-analysis demonstrates that the VDR FokI polymorphism may confer susceptibility to RA in Europeans. Furthermore, associations were found between the VDR BsmI polymorphism and susceptibilities to SLE and LN in Asians.
23079199 Patient self-report outcomes to guide a treat-to-target strategy in clinical trials and us 2012 Jul Patient self-report questionnaires provide an easily-implemented approach for quantitative assessment of patients with rheumatoid arthritis (RA) in usual care settings. Patient reported outcomes (PROs) on these questionnaires and an index including only patient self-report measures, RAPID3 (Routine Assessment of Patient Index Data), distinguish active from control treatments as effectively as other measures in clinical trials of methotrexate, leflunomide, adalimumab, abatacept, and certolizumab. RAPID3 is correlated significantly with indices that include formal joint counts and laboratory tests, such as disease activity score 28 (DAS28) and clinical disease activity index (CDAI), in clinical trials and clinical care, including categories for high, moderate, low severity, and remission. Patient self-report questionnaires present additional advantages that the same observer (the patient) completes quantitative scores at each encounter regardless of the setting and the patient does most of the work to provide an index. Completion of a questionnaire helps the patient prepare for the visit, and improves doctor-patient communication. This article summarises evidence concerning PROs in clinical trials and clinical care in documenting low disease activity and remission, including a meta-analysis of studies that document the value of using PROs to implement 'treat-to-target.' Patient self-report questionnaires must be complemented by a careful joint examination, and do not prevent performance of a formal joint count or any other measure by a treating physician. Patient self-report questionnaires may provide a useful, cost-effective method to implement treat-to-target in patients with RA as well as other rheumatic diseases.
22718508 Association of interleukin 23 receptor gene polymorphisms (rs10489629, rs7517847) with rhe 2012 Sep The interleukin 23 receptor (IL-23R) polymorphisms have been already discussed in rheumatoid arthritis (RA) repeatedly, but the results are conflict. The purpose of this meta-analysis was to assess whether IL-23R gene polymorphisms are associated with RA. We retrieved the available data from Pubmed, Medline, CNKI and CBM. Our study evaluated the effects of two polymorphisms (rs10489629, rs7517847) in European population. Pooling all the subjects, we found significant associations between the two polymorphisms and RA. For rs10489629, the pooled ORs (95 % CI) of C versus T, C/C+C/T versus T/T and C/C versus C/T+T/T were 1.092 (1.038-1.149), 1.146 (1.059-1.240) and 1.099 (1.008-1.199), respectively. For rs7517847, the combined ORs (95 % CI) of G versus T, G/G+G/T versus T/T and G/G versus G/T+T/T were 1.121 (1.063-1.183), 1.184 (1.092-1.283) and 1.133 (1.030-1.246), respectively. In conclusion, this meta-analysis demonstrates that the polymorphisms rs10489629 and rs7517847 of the IL-23R gene may be considered as risk factors for developing RA in European population.
22384135 A replication study of the association between rheumatoid arthritis and deletion of the la 2012 OBJECTIVE: Two recent studies, in a Spanish and a Chinese population, point to an association between rheumatoid arthritis (RA) risk and the deletion of the Late Cornified Envelope (LCE) 3B and 3C genes (LCE3C_LCE3B-del), a known risk factor for psoriasis. We aimed to replicate these studies in a large Dutch cohort. METHODS: 1039 RA cases and 759 controls were genotyped for LCE3C_LCE3B-del. Association analysis was performed for the complete cohort and after stratification for the serologic markers anti-cyclic citrullinated peptide and rheumatoid factor. A meta-analysis was performed combining our data with the Spanish and Chinese datasets, resulting in an analysis including 2466 RA cases and 2438 controls. RESULTS: In the Dutch cohort we did not observe a significant association of LCE3C_LCE3B-del (p = 0.093) with RA risk. A stratified analysis for the serologic positive and negative group did not show an association between the genetic variant and disease risk, either. The meta-analysis, however, confirmed a significant association (p<0.0001, OR = 1.31, 95% confidence interval 1.16-1.47). CONCLUSION: Our meta-analysis confirms the association of the LCE3 deletion with RA, suggesting that LCE3C_LCE3B-del is a common risk factor for (auto)immune diseases.
23094901 Is there an association between serum 25-hydroxyvitamin D concentrations and disease activ 2012 BACKGROUND: Recently, it has been recognized that vitamin D not only is important for calcium metabolism and maintenance of bone healthy, but also plays an important role in reducing risk of many chronic diseases including rheumatoid arthritis (RA), systemic lupus erythematosus, insulin-dependent diabetes mellitus, multiple sclerosis, several cancers, heart and infectious diseases. In RA, the role of vitamin D is undefined. METHODS: The objective of this present study was to determine serum 25-hydroxyvitamin D (25(OH)D) concentrations in patients with RA and to establish its correlation with disease activity. This study was performed on fifty-five consecutive patients RA fulfilling the American Collage of Rheumatology (ACR) criteria for the classification of RA and forty-five healthy subjects. Serum 25(OH)D levels were measured using Elecsys 25(OH)D reactive kit. Disease activity was assessed according to DAS28, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The association between serum levels of 25(OH)D and age, gender, disease duration and disease activity parameters were established. RESULTS: The mean serum 25(OH)D levels were significantly decreased in RA patients compared to healthy controls (p < 0.01) and were associated with higher levels of parathyroid hormone. Vitamin D deficiency (i.e. < 30 ng/ml) was found in 50 patients (90.9 %). Serum levels of vitamin D lower than 20 ng/ml were found in 72 % of patients. We did not find the correlation between serum 25(OH)D levels and disease activity parameters. CONCLUSIONS: Our findings have demonstrated that serum 25(OH)D levels is highly prevalent in patient with RA. We believe that it will be helpful to investigate the vitamin D levels in order to determine the osteomalacia risk of RA patients (Tab. 2, Ref. 11).
22249931 Bosentan, an endothelin receptor antagonist, ameliorates collagen-induced arthritis: the r 2012 Apr OBJECTIVE: Endothelins (ETs) are involved in several inflammatory events. The present study investigated the efficacy of bosentan, a dual ETA/ETB receptor antagonist, in collagen-induced arthritis (CIA) in mice. TREATMENT: CIA was induced in DBA/1J mice. Arthritic mice were treated with bosentan (100 mg/kg) once a day, starting from the day when arthritis was clinically detectable. METHODS: CIA progression was assessed by measurements of visual clinical score, paw swelling and hypernociception. Histological changes, neutrophil infiltration and pro-inflammatory cytokines were evaluated in the joints. Gene expression in the lymph nodes of arthritic mice was evaluated by microarray technology. PreproET-1 mRNA expression in the lymph nodes of mice and in peripheral blood mononuclear cells (PBMCs) was evaluated by real-time PCR. The differences were evaluated by one-way ANOVA or Student's t test. RESULTS: Oral treatment with bosentan markedly ameliorated the clinical aspects of CIA (visual clinical score, paw swelling and hyperalgesia). Bosentan treatment also reduced joint damage, leukocyte infiltration and pro-inflammatory cytokine levels (IL-1β, TNFα and IL-17) in the joint tissues. Changes in gene expression in the lymph nodes of arthritic mice returned to the levels of the control mice after bosentan treatment. PreproET mRNA expression increased in PBMCs from rheumatoid arthritis (RA) patients but returned to basal level in PBMCs from patients under anti-TNF therapy. In-vitro treatment of PBMCs with TNFα upregulated ET system genes. CONCLUSION: These findings indicate that ET receptor antagonists, such as bosentan, might be useful in controlling RA. Moreover, it seems that ET mediation of arthritis is triggered by TNFα.
21675377 Inflammatory diseases of the bones and joints. 2011 Feb The inflammatory diseases of the bones and joints encompass infections and the consequences of immunologically mediated local and systemic disease. Infections involve bones (osteomyelitis) and joints (septic arthritis) separately as well as together and result in necrosis with inflammatory features determined by the duration of the infection. In many cases, the infecting organism, whether bacterial, fungal or mycobacterial, is present within the infected site, but occasionally is no longer identifiable locally despite the persistence of infection-related phenomena. Granulomatous infections in bones and joints require distinction from Sarcoidosis. The diagnosis of the immunologically mediated inflammatory diseases, such as RA, depends as much on the clinical features as on the histologic ones, with a few findings that might point to one or the other in ambiguous cases. Any discussion of inflammatory arthropathies should at least mention Osteoarthritis, if for no other reason than to compare it with the traditionally regarded inflammatory diseases. However, there has been increasing interest on the potential role that synovial inflammation may play in the pathogenesis of this vary common arthritis. Ultimately, the diagnosis of the inflammatory diseases of the bones and joints requires the synthesis of information from many sources: clinical, serological, microbiological, radiographic, and pathological.
22472928 Patients' satisfaction with the rheumatology day care unit. 2011 Oct BACKGROUND: Patients receiving biological therapies are regularly evaluated and monitored at rheumatology day care units (RDCU). Despite patients' satisfaction with the delivered care and the relationship between the patient and the multidisciplinary team being acknowledged as important aspects to ensure adherence to therapy, factors associated with them have not been investigated so far. OBJECTIVES: To evaluate patients' satisfaction with the functioning of the RDCU and to identify the factors associated with the level of satisfaction. METHODS: An anonymous questionnaire was administered to all patients with rheumatoid arthritis (RA) or spondyloarthritis treated with biological drugs and followed at the RDCU at Hospital Garcia de Orta, Almada, Portugal. Satisfaction was measured using a visual analogue scale (0-100, 0 meaning completely unsatisfied, 100 meaning completely satisfied). Further information was collected on socio-demographic variables, physical conditions of the RDCU, waiting time, satisfaction with the role of medical, nursing and administrative staff (satisfaction level with their friendliness, question answering, care delivery, privacy during consultation, clarity in the information given, which was then transformed into a composite score, 0-20). Factors associated with satisfaction were studied by univariable followed by multiple linear regression to adjust for potential confounders. RESULTS: In total, 150 patients were included in the study (mean age 50.6 ± 13.7 years, 64% female, 62% RA, mean disease duration 10.6 ± 6.1 years). The majority of patients attended the RDCU for more than three years and 57% received subcutaneous therapy. The mean level of satisfaction with the RDCU was 81.9 ± 17.9. Multivariable analysis showed that intravenous therapy (β 6.13, 95% confidence interval - CI 0.71-11.55), physician score (β 2.28, 95%CI 1.20-3.35) and increasing levels of satisfaction with the room temperature (β 5.64, 95%CI 3.06-8.21) and waiting time (β 25.53, 95%CI 8.17-42.89, for a very good vs non-acceptable waiting time) were positively associated with the level of satisfaction, while the nursing score was inversely associated. CONCLUSIONS: Patients were overall very satisfied with the functioning of the RDCU. Waiting time, satisfaction with the physician role, room temperature and intravenous therapy were the main factors positively associated with the level of satisfaction.
21538312 A detailed comparative study of high-resolution ultrasound and micro-computed tomography f 2011 May OBJECTIVE: To test whether bony lesions appearing on ultrasound (US) imaging are cortical breaks detectable by micro-computed tomography (micro-CT). METHODS: Twenty-six subjects (14 with rheumatoid arthritis, 6 with psoriatic arthritis, and 6 healthy controls) were assessed for bone erosions at the radial, palmar, and dorsal regions of the second metacarpophalangeal (MCP) joint and the palmar and dorsal regions of the third and fourth MCP joints. All patients underwent US and, for validation of the results, micro-CT scanning. The prevalence and severity of bone erosions as determined by US and by micro-CT were recorded and compared. RESULTS: Overall there was a good correlation between the severity of erosions as assessed by US and by micro-CT (r = 0.463, P < 0.0001). False-negative results (US negative/micro-CT positive) were obtained in only 9.9% of the joint regions and were mostly due to small erosive lesions at the dorsal sides of the MCP joints. False-positive results (US positive/micro-CT negative) were more frequent (28.6%) and were primarily based on vascular bone channels at the palmar sides of the MCP joints as well pseudo-erosions created by osteophytes. CONCLUSION: These data show that the majority of bone lesions appearing on US are indeed bone erosions with a cortical break. The sensitivity of US for detecting bone erosions was high and there was a good correlation between the severity of bone erosions as assessed by US and as assessed by micro-CT. Specificity of US for bone erosions was substantially lower, suggesting that smaller lesions seen on US do not always represent breaks in the cortical bone surface.
21113169 Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. 2011 Jan Bruton's tyrosine kinase (Btk) is a therapeutic target for rheumatoid arthritis, but the cellular and molecular mechanisms by which Btk mediates inflammation are poorly understood. Here we describe the discovery of CGI1746, a small-molecule Btk inhibitor chemotype with a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation. CGI1746 has exquisite selectivity for Btk and inhibits both auto- and transphosphorylation steps necessary for enzyme activation. Using CGI1746, we demonstrate that Btk regulates inflammatory arthritis by two distinct mechanisms. CGI1746 blocks B cell receptor-dependent B cell proliferation and in prophylactic regimens reduces autoantibody levels in collagen-induced arthritis. In macrophages, Btk inhibition abolishes FcγRIII-induced TNFα, IL-1β and IL-6 production. Accordingly, in myeloid- and FcγR-dependent autoantibody-induced arthritis, CGI1746 decreases cytokine levels within joints and ameliorates disease. These results provide new understanding of the function of Btk in both B cell- or myeloid cell-driven disease processes and provide a compelling rationale for targeting Btk in rheumatoid arthritis.
21878134 More than just B-cell inhibition. 2011 Aug 30 Despite tremendous advances in the therapy of rheumatoid arthritis (RA), there remains interest in oral agents that may offer benefits that are similar to, or better than, those of biologic therapies. In their paper, Chang and colleagues demonstrate the effectiveness of a Bruton tyrosine kinase (Btk) inhibitor in two models of RA. Btk inhibition impacts several pathways affecting both B-cell and macrophage activation, making it a promising target in RA. However, other kinase inhibitors have failed to transition from animal models to human therapy, so it remains to be seen whether a Btk inhibitor will have a role in the RA treatment armamentarium.
21979446 The diagnostic value of the proposal for clinical gout diagnosis (CGD). 2012 Mar The purpose of this study is to determine the diagnostic properties of the clinical gout diagnosis (CGD) proposal in patients with gout and other rheumatic diseases. We investigated the presence of current or past history of the previously published CGD criteria: (1) >1 attack of acute arthritis, (2) mono/oligoarthritis attacks, (3) rapid progression of pain and swelling (<24 h), (4) podagra, (5) erythema, (6) unilateral tarsitis, (7) probable tophi, and (8) hyperuricemia. CGD was established in patients with greater than or equal to four out of eight of these criteria. Demographic data and comorbidities were also considered. Statistical analysis included diagnostic test evaluation (sensitivity, specificity, likelihood ratios, positive predictive values and receiving operating characteristic curves). One hundred and sixty-seven patients with the following diagnoses were included: gout (most in intercritical period, n = 75), rheumatoid arthritis (RA, n = 30), osteoarthritis (OA, n = 31) and spondyloarthritis (SpA, n = 31). All gout patients had MSU crystal demonstration and constituted the gold standard for diagnostic test evaluation. There were significant differences across diagnostic groups in most demographic variables and comorbidity. The presence of greater than or equal to four out of eight of the CGD criteria were found in 97% patients with gout, in two patients with SpA, and one each with RA and OA. The sensitivity, specificity, and LR+ of greater than or equal to four out of eight of the CGD criteria were 97.3%, 95.6%, and 22.14, respectively. The presence of more than or equal to four out of eight items from the CGD proposal is highly suggestive of gout.
23179138 Anti-inflammatory and antioxidant potential of alginic acid isolated from the marine algae 2013 Jun The present study evaluated the anti-inflammatory and antioxidant potential of alginic acid isolated from brown algae Sargassum wightii in arthritic rats. Arthritis was induced in male Sprague-Dawley rats by intradermal injection of complete Freund's adjuvant into the right hind paw, produce inflammation of the joint tissue. Paw edema volume, enzymes linked to inflammation such as cyclooxygenase, lipoxygenase and myeloperoxidase, and the level of ceruloplasmin, C-reactive protein and rheumatoid factor were evaluated in all the experimental groups. Oxidative stress during inflammation was analyzed by estimating lipid peroxidation and the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and non-enzymatic antioxidant, reduced glutathione. Alginic acid treatment (100 mg/kg) in arthritic rats exhibited reduced paw edema volume along with reduced activities of enzymes such as cyclooxygenase, lipoxygenase and myeloperoxidase. Reduction in the level of C-reactive protein, ceruloplasmin and rheumatoid factor were also observed in arthritic rats treated with alginic acid along with reduced lipid peroxidation and enhanced activities of antioxidant enzymes, which suggest the antioxidant potential of the compound. Histopathological analysis of paw tissue showed that alginic acid treatment reduced paw edema and inflammatory infiltration in arthritic rats. Overall results suggest that alginic acid isolated from Sargassum wightii exhibits potent anti-inflammatory and antioxidant activity, and can develop this marine alga as an alternative source for therapy and can be used as a drug candidate for the development of anti-inflammatory agent.
22933315 Comparison of long-term clinical outcome with etanercept treatment and adalimumab treatmen 2012 Dec OBJECTIVE: To compare rates of sustained low and minimal disease activity and remission according to the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria during 3-year followup in rheumatoid arthritis (RA) patients treated with etanercept and adalimumab in routine care. METHODS: Four hundred seven RA patients previously unexposed to tumor necrosis factor antagonists were treated with etanercept (n = 203) or adalimumab (n = 204) and assessed at 3- and later 6-month intervals. Treatment allocation was at the discretion of the treating rheumatologist. Clinical parameters were measured at each time point, as were anti-adalimumab antibodies in adalimumab-treated patients. Achievement of clinical outcome was defined as the occurrence of sustained (at least 12 consecutive months) low disease activity (28-joint Disease Activity Score [DAS28] <3.2), minimal disease activity (DAS28 <2.6), or ACR/EULAR remission based on the Simplified Disease Activity Index (SDAI). Non-overlapping response rates were calculated. RESULTS: Among the adalimumab group, 13% reached sustained low disease activity but not sustained minimal disease activity, 15% reached sustained minimal disease activity but not sustained remission according to the SDAI, and 16% reached sustained ACR/EULAR remission. In the etanercept group the corresponding rates were 16%, 11%, and 12%, respectively (P = 0.42, overall test for linear trend). Adalimumab-treated patients without anti-adalimumab antibodies (n = 150 [74%]) had the best outcomes, and adalimumab-treated patients with anti-adalimumab antibodies the worst, with outcomes in etanercept-treated patients in between (P < 0.0001). Differences were most apparent in the sustained SDAI remission and sustained minimal disease activity categories. For example, 40% of anti-adalimumab antibody-negative patients, 23% of etanercept-treated patients, and 4% of anti-adalimumab antibody-positive patients achieved at least sustained minimal disease activity. CONCLUSION: Overall, etanercept and adalimumab treatment appear similar in inducing a good long-term clinical outcome. However, in the case of adalimumab this is strongly dependent on the presence or absence of anti-adalimumab antibodies.
22006178 The CD14(bright) CD16+ monocyte subset is expanded in rheumatoid arthritis and promotes ex 2012 Mar OBJECTIVE: Circulating monocytes contain a subpopulation of CD14+CD16+ cells; this subpopulation of cells has been described to be proinflammatory and to have an increased frequency in rheumatoid arthritis (RA). New evidence suggests that this subpopulation can be further subdivided into CD14(dim) CD16+ and CD14(bright) CD16+ cells. The aim of this study was to determine which of the two CD16+ monocyte subpopulations is expanded in patients with RA and to investigate their possible role in disease pathogenesis. METHODS: The frequencies of monocyte subpopulations in the peripheral blood of healthy donors and patients with RA were determined by flow cytometry. Monocyte subpopulations were sorted and cocultured with CD4+ T cells. Cytokines were determined in the supernatant, and Th17 cell frequencies were measured by flow cytometry. RESULTS: In comparison with the other monocyte subpopulations, CD14(bright) CD16+ cells showed higher HLA-DR and CCR5 expression and responded with higher tumor necrosis factor production to direct cell contact with preactivated T cells. They were observed at increased frequencies in the peripheral blood of patients with RA, while CD14(dim) CD16+ monocyte frequencies were not increased. CD14(bright) CD16+ cells were extremely potent inducers of Th17 cell expansion in vitro. Their frequency in the peripheral blood of patients with RA correlated closely with Th17 cell frequencies determined ex vivo. CONCLUSION: This study is the first to provide a link between the increased frequency of the CD14(bright) CD16+ monocyte subpopulation in RA and the expansion of Th17 cells, which are likely to have a role in the pathogenesis of autoimmunity.
21246742 Proteome analysis of biological fluids from autoimmune-rheumatological disorders. 2011 Feb Autoimmune-rheumatological diseases are worldwide distributed disorders and represent a complex array of illnesses characterized by autoreactivity (reactivity against self-antigens) of T-B lymphocytes and by the synthesis of autoantibodies crucial for diagnosis (biomarkers). Yet, the effects of the autoimmune chronic inflammation on the infiltrated tissues and organs generally lead to profound tissue and organ damage with loss of function (i.e., lung, kidney, joints, exocrine glands). Although progresses have been made on the knowledge of these disorders, much still remains to be investigated on their pathogenesis and identification of new biomarkers useful in clinical practice. The rationale of using proteomics in autoimmune-rheumatological diseases has been the unmet need to collect, from biological fluids that are easily obtainable, a summary of the final biochemical events that represent the effects of the interplay between immune cells, mesenchymal cells and endothelial cells. Proteomic analysis of these fluids shows encouraging results and in this review, we addressed four major autoimmune-rheumatological diseases investigated through proteomic techniques and provide evidence-based data on the highlights obtained in systemic sclerosis, primary and secondary Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis.
22886439 Do bugs control our fate? The influence of the microbiome on autoimmunity. 2012 Dec Autoimmune disease has traditionally been thought to be due to the impact of environmental factors on genetically susceptible individuals causing immune dysregulation and loss of tolerance. However, recent literature has highlighted the importance of the microbiome, (a collective genome of microorganisms in a given niche) in immune homeostasis. Increasingly, it has been recognized that disruptions in the commensal microflora may lead to immune dysfunction and autoimmunity. This review summarizes recent studies investigating the interplay between the microbiome and immune-mediated organ-specific diseases. In particular, we review new findings on the role of the microbiome in inflammatory bowel disease, celiac disease, psoriasis, rheumatoid arthritis, type I diabetes, and multiple sclerosis.
22823390 Sympathetic nerve fiber repulsion: testing norepinephrine, dopamine, and 17β-estradiol in 2012 Jul Loss of sympathetic nerve fibers (SNFs) occurs in inflamed tissue; and select semaphorins, upregulated during inflammation, stimulate repulsion/loss of SNFs. However, it is unknown whether other factors released locally in inflamed tissue, such as norepinephrine, dopamine, and 17β-estradiol, are also repellent. In order to study the effects of hormones on SNF repulsion, an SNF outgrowth assay was used. The repellent activity of semaphorins 3C was weaker than of semaphorin 3F. Tumor necrosis factor α (TNF-α) repelled nerve fibers with moderate to strong effects (from 0-100% repulsion). High concentrations of dopamine and norepinephrine (10(-6) M) induced weak but significant nerve fiber repulsion (up to 20%). Norepinephrine at 10(-8) M was comparable with 10(-6) M at inducing nerve fiber outgrowth. Stimulation with low concentrations of 17β-estradiol (10(-10) M, but not 10(-8) M) repelled SNFs. These results demonstrate that not only specific axon guidance molecules, such as semaphorins 3F and 3C, but also hormonal factors and TNF-α influence SNF repulsion and outgrowth.
22723498 Bilateral MR imaging of the hand and wrist in early and very early inflammatory arthritis: 2012 Sep PURPOSE: To identify bilateral hand and wrist findings of synovial inflammation associated with progression to rheumatoid arthritis (RA) in very-early-RA cohort (VERA) (duration, <3 months) and early-RA cohort (ERA) (duration, <12 but >3 months), to test tenosynovitis as a magnetic resonance (MR) imaging additional parameter for improving diagnostic accuracy of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) RA classification criteria, and to evaluate the symmetry of joint and tendon involvement. MATERIALS AND METHODS: With institutional review board approval and informed consent, 32 women and three men (mean age, 45 years) with untreated recent-onset inflammatory arthritis participated in this prospective study and underwent MR imaging of both wrists and hands. After 12-month follow-up, 25 patients fulfilled the criteria for RA (10 VERA and 15 ERA patients). Ten patients did not fulfill the criteria for RA (non-RA [control] group). Possible associations between synovitis for each joint and tendon and RA diagnosis at 12 months were tested (univariate logistic regression analysis). Diagnostic performance of the ACR/EULAR RA classification criteria was evaluated (receiver operating characteristic curve analysis). Asymmetry prevalence (all joints and tendons in the analysis) was calculated. RESULTS: Tenosynovitis of the extensor carpi ulnaris (odds ratio, 3.21) and flexor tendons of the second finger (odds ratio, 14.61) in VERA group and synovitis of the radioulnar joint (odds ratio, 8.79) and tenosynovitis of flexor tendons of the second finger (odds ratio, 9.60) in ERA group were significantly associated with progression to RA (P < .05). Consideration of tenosynovitis improved areas under the receiver operating characteristic curve of ACR/EULAR criteria performance for the diagnosis of RA from 0.942 (P < .0001; sensitivity, 52%; specificity, 100%) to 0.972 (P < .0001; sensitivity, 76%; specificity, 100%), with cutoff score of 6 or greater. Asymmetry was found in 80.0% (62 of 77) (VERA patients) and 69.3% (106 of 153) (ERA patients) of joint or tendon pairs (P < .05). CONCLUSION: Tenosynovitis is an imaging finding in early RA, and its inclusion as a scoring criterion might contribute for a better diagnostic performance of the 2010 ACR/EULAR classification; early RA is an asymmetric disease.
23352953 [Disease-modifying treatment for inflammatory rheumatism in sub-Saharan Africa: outcome at 2012 Oct RATIONALE: Few data are available on the treatment of rheumatoid arthritis (RA) in sub-Saharan Africa, where the diagnosis is often substantially delayed. Disease-modifying antirheumatic drugs (DMARDs) are more effective when started early. Biotherapies are not available. Given the socioeconomic constraints in sub-Saharan Africa, treatments must be selected based on locally available resources. The objective of this study was to evaluate outcomes 6 months after initiation of conventional DMARDs in Senegalese patients with RA. METHODS: We retrospectively studied consecutive RA patients seen at the rheumatology outpatient clinic of the Le Dantec Teaching Hospital, Dakar, Senegal, from January 2005 through June 2009. All patients met the ACR criteria for RA. ACR and EULAR response criteria were evaluated 6 months after treatment initiation. RESULTS: The study included 205 patients. Corticosteroids were used in 205 patients, hydroxychloroquine in 190, methotrexate in 137, and sulfasalazine in 11. Combined corticosteroid, methotrexate, and hydroxychloroquine therapy was used in 122 patients and combined corticosteroid and hydroxychloroquine therapy in 63. DMARD treatment was interrupted for at least 5 days per month for 26% of the patients, either because the drugs were out of stock at the local pharmacies and/or because the patients could not afford to purchase them. During the first 6 months of treatment, patients had a mean of 4 clinic visits, and 48% of patients missed at least one scheduled visit. After 6 months, all clinical variables had improved significantly, except the swollen joint count. The ACR20, 50, and 70 response criteria were met in 50%, 31%, and 6.9% of patients, respectively. The EULAR response was good in 53.9% of patients, moderate in 12.7%, and poor in 23.1%. DMARD therapy failed in 10.3% of patients. Half the patients had their treatment modified during the 6-month study period. DMARD therapy was discontinued in 10 patients for the following reasons: plans to become pregnant, n = 5; pregnancy during treatment, n = 2; and tuberculosis, n = 3. CONCLUSION: In Senegal, the treatment of RA relies chiefly on variable combinations of methotrexate, hydroxychloroquine, and corticosteroids. The six-month outcomes are satisfactory. Biotherapy is required in 7% to 10% of patients, a rate that could be decreased by optimizing patient follow-up. The management of chronic inflammatory joint disease couple be improved despite the limited financial resources in sub-Saharan Africa with better physician training and the incorporation of osteoarticular diseases within a vast information and education program for the general population.