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ID PMID Title PublicationDate abstract
21575793 Post damage in contemporary posterior-stabilized tibial inserts: influence of implant desi 2011 Jun The mechanisms of damage at the polyethylene post in 3 contemporary tibial insert designs were evaluated and compared with a historical standard (Insall-Burstein II; Zimmer, Warsaw, Ind). One hundred five gamma sterilized posterior-stabilized tibial inserts were revised after an average of 4.7 years (0.05-13.6 years). Retrievals were classified according to their designs: Insall-Burstein II (n = 28); PFC (Johnson & Johnson, Raynham, Mass; n = 30); NexGen (Zimmer; n = 32); and Scorpio (Stryker Orthopaedics, Mahwah, NJ; n = 15). Reasons for revision and patient details were available. Surface damage scoring and photogrammetry were performed on all the retrieved tibial inserts. Oxidation analysis was carried out for traceable historical, gamma air-sterilized and conventional, gamma inert-sterilized tibial inserts (n = 61) with the use of infrared spectroscopy. The posts for all 3 contemporary designs exhibited damage similar to the historical controls. Articular, post, and backside damage scores significantly increased with implantation time. Post damage was insensitive to design and patient factors but was exacerbated by oxidation. An association between damage at the post and articular surface was also confirmed. Logistic models suggested an interaction between post damage, backside surface damage, and implant loosening.
22867931 Musculoskeletal conditions of the foot and ankle: assessments and treatment options. 2012 Jun Musculoskeletal conditions of the foot and ankle are an important public health challenge due to their increasing incidence combined with their substantial negative impact on patients' quality of life. Non-pharmacological treatments serve as the first line of treatment and are frequently used for patients with musculoskeletal conditions of the foot and ankle. This review provides a summary of the assessments and non-invasive treatment options based upon available evidence. Recent studies show that individuals with foot and ankle pain have multiple co-existing impairments in alignment, motion, load distribution and muscle performance that may be evident in static and/or dynamic tasks. In addition, both clinical and epidemiological studies support the inter-dependence between the foot and proximal joints. For instance, aberrant foot structure has been linked to foot osteoarthritis (OA), as well as OA and pain at the knee and hip. Most recently, advances in motion capture technology and plantar load distribution measurement offer opportunities for precise dynamic assessments of the foot and ankle. In individuals with musculoskeletal conditions of the foot and ankle, the chief objectives of treatment are to afford pain relief, restore mechanics (alignment, motion and/or load distribution) and return the patient to their desired level of activity participation. Given that most patients present with multiple impairments, combinational therapies that target foot-specific as well as global impairments have shown promising results. In particular, in individuals with rheumatoid arthritis and other rheumatic diseases, comprehensive rehabilitation strategies including early detection, foot-based interventions (such as orthoses) and wellness-based approaches for physical activity and self-management have been successful. While significant improvements have been made in the last decade to the assessment and treatment of foot and ankle conditions, few randomised clinical trials specifically have investigated patients with foot or ankle conditions to provide global insights into this area. Consequently, current recommendations vary based upon the scope of studies presented in this review as well as the strength of studies. This review indicates a need for more in-depth investigations into the components of assessment and treatment options for foot and ankle musculoskeletal conditions.
21881327 Adalimumab-associated pulmonary cryptococcosis. 2011 This is the first report of adalimumab-associated pulmonary cryptococcosis. A 56-year-old female with rheumatoid arthritis without a history of pulmonary disease was simultaneously administered adalimumab (40 mg/2 wks), methotrexate (4 mg/wk), and isoniazid (200 mg/day). Five months later, chest radiography revealed a small spiculated pulmonary nodule, and the laboratory test results, including levels of tumor markers and plasma β-D-glucan, were within normal ranges. Since the lesion continued to grow, even after discontinuing adalimumab, it was surgically resected. Grocott staining of the tissue sample revealed black-brown fungi, identified as Cryptococcus neoformans in culture. The patient now remains well, without adalimumab therapy.
22372158 T. asahii pulmonary infection as a complication of TNF-inhibitor and steroids: posaconazol 2011 Nov We report the first documented Trichosporon asahii infection in a patient with connective tissue disease treated with a Tumor Necrosis Factor (TNF) inhibitor and describe an institutional root cause analysis for TNF inhibitor-associated infections. Fourteen patients with incident fungal infections during TNF inhibitor treatment were identified. They were matched with uncomplicated patients receiving TNF inhibitors or with rheumatoid arthritis (RA) patients managed without TNF inhibitors. We found that patients acquiring fungal infections were more likely to have graft versus host disease (GVHD) (p<0.05). Furthermore, infected patients were more likely (OR=24.4) to have multiple immunosuppressive therapies over the controls as well as several risk factors identified by the Infectious Disease Society ofAmerica (IDSA). The 3 patient deaths in our study were associated with GVHD and infliximab. Trichosporon was isolated in 1 patient receiving adalimumab. Our results suggest that these high risk patients be monitored closely for fungal infection.
21914545 Phytochemical and pharmacological evaluation of prop roots of Pandanus fascicularis Lam. 2011 Aug OBJECTIVE: To evaluate the anti-inflammatory and analgesic activities of the ethanol and aqueous extracts of prop roots of Pandanus fascicularis (P. fascicularis) Lam (pandanaceae). And provide experimental evidence for its traditional use such as rheumatoid arthritis and spasmodic. METHODS: The anti-inflammatory activity was observed by carrageenan-induced edema of the hind paw of rats. Analgesic activities of prop roots of P. fascicularis were determined using acetic acid induced writhing model and tail clip method in mice and rat, respectively. The ethanol fraction was then subjected to chromatographic analysis and a compound has been isolated and characterized by IR, (1)H-NMR and mass spectroscopy. RESULTS: Edema suppressant effect of ethanol extract was found to be 37.03% inhibition whereas aqueous extract was found to be 63.22% inhibition after 3 h which was nearly equivalent to that of 10 mg/kg of indomethacin (67.81%). Percentage inhibition of writhing compared to control were 63.15%, 54.38%, 14.90% for aspirin, aqueous extract and ethanolic extract, respectively. Both ethanol and aqueous extracts show significant activity against appropriate controls after 60 min of treatment on tail clip method. The structure of the isolated compound is may be characterized as Hepta deca-5-ene-1-ol by analysis it's IR, (1)H-NMR and mass spectroscopy data. CONCLUSIONS: The extracts of prop roots of P. fascicularis produce significant analgesic and anti-inflammatory activities, supporting the traditional application of this herb in treating various diseases associated with inflammation and pain.
21293383 HLA-DPB1-COL11A2 and three additional xMHC loci are independently associated with RA in a 2011 Apr The aim of this study was to investigate the complex association pattern of the extended major histocompatibility complex (xMHC) region with rheumatoid arthritis (RA) susceptibility to identify effects independent of HLA-DRB1. A total of 1804 RA cases and 1474 controls were included. High-resolution HLA-DRB1 typing was performed. Subjects were genotyped for 1546 single-nucleotide polymorphisms (SNPs) using Affymetrix GeneChip 500 K (Santa Clara, CA, USA) as part of the Wellcome Trust Case Control Consortium Study. Statistical analysis was carried out using PLINK. To avoid confounding by RA-associated HLA-DRB1 alleles, we analyzed xMHC SNPs using a data set with pairwise matching of cases and controls on DRB1 genotypes. A total of 594 case-control pairs with identical DRB1 genotypes were identified. After this adjustment, 104 SNPs remained significantly associated with RA (P<0.05), suggesting that additional RA loci independent of HLA-DRB1 can be found in the xMHC region. Of these, four loci showed the strongest associations with RA (P<0.005): ZNF391, the olfactory receptor (OR) gene cluster, C6orf26-RDBP and HLA-DPB1-COL11A2. An additional locus mapping to the BTN (butyrophilin) cluster showed independent association with RA in anti-cyclic citrullinated peptide-positive patients exclusively. We have validated the previously described independent association of the HLA-DPB1-COL11A2 locus with RA. In addition, association with three novel independent RA loci in the xMHC region (ZNF391, OR2H1 and C6orf26-RDBP) has been detected.
21859685 Ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, rheumatoid a 2011 Dec OBJECTIVES: To evaluate the efficacy and safety of intravenous ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, active rheumatoid arthritis (RA) patients despite methotrexate treatment. METHODS: In this double-blind, placebo-controlled, phase III study, active RA patients on stable methotrexate were randomly assigned to one course of two infusions of ofatumumab 700 mg (n=130) or placebo (n=130), 2 weeks apart. The primary endpoint was the ACR20 response at week 24. Secondary endpoints included ACR50/70, EULAR response, disease activity score based on 28 joints using C-reactive protein, adverse events (AE) and immunogenicity. RESULTS: At week 24, a greater proportion of patients on ofatumumab compared with placebo achieved an ACR20 response (50% vs 27%, p<0.001) and a good or moderate EULAR response (67% vs 41%, p<0.001). All other key secondary efficacy endpoints were significantly improved on ofatumumab. Efficacy observed by 8 weeks was sustained throughout the study. The most common AE for ofatumumab versus placebo were rash (21% vs <1%) and urticaria (12% vs <1%), mostly occurring on the first infusion day. Overall, first-dose infusion reactions were 68% for ofatumumab and 6% for placebo, mostly mild to moderate; second-dose infusion reactions markedly declined (<1% and 0%). Serious AE were reported in 5% of ofatumumab versus 3% of placebo patients. Infection rates were 32% and 26% (serious infections <1% and 2%), respectively. One death (interstitial lung disease), unrelated to study drug, was reported on ofatumumab. No antidrug antibodies were detected in ofatumumab patients. CONCLUSIONS: Ofatumumab significantly improved all clinical outcomes in biological-naive, active RA patients with no detectable immunogenicity at week 24. No unexpected safety findings were identified. Trial Registry clinical trials.gov registration number NCT00611455.
21369647 Clinical trial safety and mortality analyses in patients receiving etanercept across appro 2011 Mar OBJECTIVES: Assessment of associations between etanercept treatment and rare adverse events has been limited by the size of clinical trial populations. The authors examined the collective safety of etanercept in clinical trials across approved indications. PATIENTS AND METHODS: Forty-nine U.S. and non-U.S. trials of etanercept, involving up to 13,977 patients for approved indications, with final trial reports as of May 2006, were selected from the Amgen Inc. clinical trials database. Exposure-adjusted rates of serious infections, opportunistic infections, malignancies, and deaths were reported by trial, indication, and dosage. RESULTS: Rates of serious infections were generally similar between etanercept and controls. Overall rates of opportunistic infections and tuberculosis were low. The standardized incidence ratio (SIR) (95% CI) for malignancy was 1.00 (0.83-1.19) for all etanercept patients across all indications. The SIR for lymphoma for patients with rheumatoid arthritis was 3.45 (1.83-5.89); all other indications reported SIRs similar to those observed in the general population. The SIRs for cutaneous squamous cell carcinoma in patients with psoriasis relative to the general population with high or low sun exposure were 2.09 (1.27-3.22) and 4.96 (3.03-7.66), respectively. SIRs were less than 1.0 for all other indications regardless of sun exposure. Rates of melanoma and basal cell carcinoma were not significantly different from those in the general population. There was no increase in mortality associated with etanercept use relative to control populations. CONCLUSION: These data support the overall tolerability of etanercept across approved indications.
21233087 Numerous IgG4-positive plasma cells are ubiquitous in diverse localised non-specific chron 2011 Mar BACKGROUND: IgG4-related systemic fibrosclerosis is a recently defined disorder characterised by a diffuse or tumefactive inflammatory reaction rich in IgG4-positive plasma cells associated with sclerosis and obliterative phlebitis. Although characteristic histopathological features are essential for the diagnosis of these disorders, to date there exists no consensus regarding the cut-off values used to define a 'significant IgG4-positive plasma cell count,' and data regarding the distribution of IgG4-positive plasma cells under common (non-specific) inflammatory conditions are lacking. METHODS: The authors analysed 121 randomly selected histopathological specimens containing prominent lymphoplasmacytic infiltrates (11 obstructive sialadenitis, 27 inflammatory lesions of the oral cavity, 24 inflammatory gastrointestinal lesions, 15 rheumatoid synovitis, 15 non-specific synovitis, eight non-specific dermatitis and 21 primary carcinomas with a peritumoral inflammatory response). For comparison, seven cases of sclerosing sialadenitis (Küttner tumour) were examined. RESULTS: High counts of IgG4 plasma cells were found in sclerosing sialadenitis (mean 40/high-power field (hpf)), contrasting sharply with sialadenitis caused by sialolithiasis (mean 3/hpf). Greatly varied but generally high counts of IgG4-positive plasma cells were also seen in several of the other lesions, particularly in rheumatoid synovitis (mean 55/hpf), oral cavity lesions (mean 79/hpf) and carcinoma-associated inflammatory response (mean 24/hpf). The mean IgG4/IgG ratios for all lesions varied between 0 and 0.4. CONCLUSIONS: The results demonstrate the ubiquitous occurrence of variably high numbers of IgG4-positive plasma cells under diverse non-specific inflammatory conditions, indicating that high IgG4-positive plasma cell counts and high IgG4/IgG ratios per se do not reliably distinguish IgG4-associated systemic disease from non-specific conditions, and that the IgG4 counts must be cautiously interpreted in the context of appropriate clinical and histopathological features.
22974785 Influence on effectiveness of early treatment with anti-TNF therapy in rheumatoid arthriti 2012 PURPOSE: To evaluate the association between starting early treatment with anti-TNF and effectiveness as well as the possibility of applying therapeutic spacing in daily practice in patients with rheumatoid arthritis (RA). METHODS: Observational, retrospective study conducted in two universitary hospitals in Spain. RA patients who received the first anti-TNF (adalimumab: ADA, etanercept: ETN or infliximab: IFX) during the study period (October 2006-2010) were included. Demographic data, time since diagnosis, disease activity (DAS28-ESR) and anti-TNF dosage were analyzed. Therapeutic objective was defined as DAS28 DAS28 < 2.6. Also the response related to criteria of the European League Against Rheumatism (EULAR) was evaluated. Therapeutic spacing was defined as the use of a lower dose or a higher interval according to label doses. The main endpoint was to assess the association between the effectiveness and the moment when the anti-TNF therapy begins. The secondary target was to evaluate the association between RA activity at the beginning of treatment with anti-TNF and dose used. Results. 82 patients were included. The prescription profile was: ADA (48.8%), ETN (31.7%) and IFX (19.5%). 71.4% of patients treated with anti-TNF during the first year since diagnosis, 57.1% of those who started after 1-5 years and 30.6% of patients who started after 5 years were in remission when the study ended. De-escalation strategy was performed in 25.6% of patients: ETN (38.5%), ADA (20.0%) and IFX (18.8%). The patients treated with a higher dose according to label doses were: IFX (81%), ADA, (12.5%) and ETN (7.7%). CONCLUSIONS: Results suggest that early treatment with anti-TNF can achieve a higher percentage of remissions. Therapeutic spacing is established as a strategy that improves the efficiency in those patients in remission, being the ETN the anti-TNF most susceptible for spacing, although a relation between the early beginning with anti-TNF and the used dose was not found.
22466401 Does searching for antineutrophil cytoplasmic antibodies help with the diagnosis of Adult- 2013 Mar Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology. It is a seronegative disease with multisystemic manifestations. One of the important laboratory findings in AOSD is negative results for rheumatoid factor and antinuclear antibody. Because there is no specific, pathognomonic test for AOSD, diagnosis is based on a set of clinical and laboratory criteria and exclusion of other diseases like infections, malignancies, and vasculitis. It is obvious that antineutrophil cytoplasmic antibodies (ANCAs) are specific for vasculitis; however, few studies detected some types of these antibodies in rheumatoid arthritis, juvenile chronic arthritis, and still's disease. The aim of this study was to investigate whether or not ANCAs exist in sera of patients with AOSD. Forty-one AOSD patients were enrolled in this prospective study; patients were diagnosed according to Yamaguchi criteria and exclusion of other diseases by at least 6-months follow-up. Sera from all patients were tested for p-ANCA and c-ANCA by indirect immunofluorescence assay. Confirmatory antigenic testing for proteinase 3 (PR3) and myeloperoxidase (MPO) ANCA subtypes then were performed on positive sera. Only one patient with AOSD in this study showed low titer of MPO-ANCA in her sera. In a 1-year follow-up, ANCA did not predict vasculitis in this patient. This study suggested that patients with AOSD are mostly seronegative for ANCAs too. Positive ANCA appears to be an epiphenomenon and has not any association with vasculitis in AOSD.
21316910 The incidence of venous thromboembolism before and after total knee arthroplasty using 16- 2011 Dec We performed a prospective study to determine the incidence of venous thromboembolism (VTE) using 16-row multidetector computed tomography (MDCT). The study included 71 patients who underwent total knee arthroplasty between September 2004 and March 2009. Multidetector computed tomography was performed 4 days before and after surgery. No patient had any presurgical symptoms of VTE. Presurgical and postsurgical incidences of pulmonary thromboembolism plus deep vein thrombosis were 0% and 13%, respectively; pulmonary thromboembolism alone, 1% and 3%, respectively; and deep vein thrombosis alone, 8% and 34%, respectively. Because asymptomatic VTE was noted in 9% of patients before surgery and 51% after surgery, we conclude that performing MDCT before and after total knee arthroplasty may be useful to clarify the incidence of VTE and to develop appropriate strategies for treatment and prevention.
22126384 Epstein-Barr virus-associated lymphoproliferative disorder presenting with classical Hodgk 2011 Dec We describe a patient who was diagnosed with classical Hodgkin lymphoma (CHL) at 67-years-old and peripheral T-cell lymphoma, not otherwise specified (PTCL) at 76-years-old, and died 5 months later. Both tumors showed prominent epithelioid cell reaction admixed with neoplastic cells. Hodgkin and Reed-Sternberg cells in the swollen lymph node were positive for CD30 and EBV-encoded RNA (EBER). PTCL cells in the skin tumor were positive for cytoplasmic CD3ε, CD4 and EBER. A rearrangement band of the T-cell receptor gene was detected in the skin tumor. This case is the first documented EBV-associated composite lymphoma composed of CHL and PTCL. The patient may show the possibility that both EBV infection and/or immunodeficiency induce the development of CHL and PTCL.
21785279 Therapeutic Fc-fusion proteins and peptides as successful alternatives to antibodies. 2011 Sep Therapeutic antibodies have captured substantial attention due to the relatively high rate at which these products reach marketing approval, and the subsequent commercial success they frequently achieve. In the 2000s, a total of 20 antibodies (18 full-length IgG and 2 Fab) were approved by the Food and Drug Administration (FDA) or European Medicines Agency (EMA). In the 2010s to date, an additional 3 antibodies (denosumab, belimumab, ipilimumab) have been approved and one antibody-drug conjugate (brentuximab vedotin) is undergoing regulatory review and may be approved in the US by August 30, 2011. However, a less heralded group of antibody-based therapeutics comprising proteins or peptides fused with an Fc is following the success of classical antibodies.
21972242 Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and lef 2012 Mar OBJECTIVES: To compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide. METHODS: 10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab. RESULTS: 1195 patients were treated with rituximab plus methotrexate, 177 with rituximab plus leflunomide and 505 with rituximab alone. Significantly more patients achieved a European League Against Rheumatism good response at 6 months when treated with rituximab plus leflunomide (29.1%) compared with rituximab plus methotrexate (21.1%) and rituximab alone (19.3%; p=0.02 and p=0.01, respectively). Similar results were observed at 12 months. Adverse events occurred in 10.2%, 13.2% and 13.9% of patients on rituximab plus leflunomide, rituximab plus methotrexate and rituximab alone, respectively. CONCLUSIONS: Leflunomide is an effective and safe alternative to methotrexate as concomitant treatment with rituximab. Slightly better results were obtained by the combination of rituximab and leflunomide than rituximab and methotrexate, raising the possibility of a synergistic effect of leflunomide and rituximab.
22184719 Calcinosis cutis occurring in association with autoimmune connective tissue disease: the M 2012 Apr OBJECTIVE: To describe characteristics and treatment of patients with calcinosis cutis in the clinical setting of autoimmune connective tissue disease (ACTD). DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: Seventy-eight patients with calcinosis cutis and ACTD between 1996 and 2009. MAIN OUTCOME MEASURES: Clinical features, treatments, and outcomes of patients with calcinosis cutis in the clinical setting of ACTD. RESULTS: Of 78 patients (mean age at onset of calcinosis cutis, 40.1 years), 64 (82%) were female. The following diseases were associated with calcinosis cutis: dermatomyositis (n = 30) with classic (n = 15), juvenile (n = 14), and amyopathic (n = 1) subtypes; systemic sclerosis with limited cutaneous scleroderma (n = 24); lupus panniculitis (n = 4); systemic lupus erythematosus (n = 2); mixed connective tissue disease (n = 4); overlap connective tissue disease (n = 6); undifferentiated connective tissue disease (n = 6); polymyositis (n = 1); and rheumatoid arthritis (n = 1). Therapy for calcinosis cutis consisted of medical treatment alone (n = 19), surgical therapy alone (n = 11), combined medical and surgical treatment (n = 17), no treatment (n = 30), and unknown (n = 1). Diltiazem hydrochloride was the most commonly used medical therapy, with 9 of 17 patients having a partial response. Twenty-eight patients had surgical excision of 1 or more lesions of calcinosis cutis: 22 had a complete response, 5 had a partial response, and 1 had no response. CONCLUSIONS: Dermatomyositis and systemic sclerosis were the most common ACTDs associated with calcinosis cutis. Although no treatment was uniformly effective, surgical excision of symptomatic lesions and medical treatment with diltiazem provided benefit for some patients.
22518822 Arthritogenic T cells drive the recovery of autoantibody-producing B cell homeostasis and 2012 Aug T cells orchestrate joint inflammation in rheumatoid arthritis (RA), but B cells/B cell-derived factors are also involved in disease pathogenesis. The goal of this study was to understand the role of antigen-specific T and B cells in the pathological events of arthritis, which is impossible to study in humans due to the small number of antigen-specific cells. To determine the significance of antigen-specific lymphocytes and antibodies in the development of an autoimmune mouse model of RA, we generated TCR transgenic (TCR-Tg) mice specific for the dominant arthritogenic epitope of cartilage proteoglycan (PG) and performed a series of combined transfers of T cells, B cells and autoantibodies into BALB/c.Scid mice. The adoptive transfer of highly purified T cells from naive TCR-Tg, arthritic TCR-Tg or arthritic wild-type mice induced arthritis in SCID recipients, but the onset and severity of the disease were dependent on the sequential events of the T cell-supported reconstitution of PG-specific B cells and autoantibodies. The presence of activated PG-specific T cells was critical for disease induction, establishing a unique milieu for the selective homeostasis of autoantibody-producing B cells. In this permissive environment, anti-PG autoantibodies bound to cartilage and induced activation of the complement cascade, leading to irreversible cartilage destruction in affected joints. These findings may lead to a better understanding of the complex molecular and cellular mechanisms of RA.
22401175 Gene expression analysis of rheumatoid arthritis synovial lining regions by cDNA microarra 2012 May OBJECTIVES: The main histological change in rheumatoid arthritis (RA) is the villous proliferation of synovial lining cells, an important source of cytokines and chemokines, which are associated with inflammation. The aim of this study was to evaluate gene expression in the microdissected synovial lining cells of RA patients, using those of osteoarthritis (OA) patients as the control. METHODS: Samples were obtained during total joint replacement from 11 RA and five OA patients. Total RNA from the synovial lining cells was derived from selected specimens by laser microdissection (LMD) for subsequent cDNA microarray analysis. In addition, the expression of significant genes was confirmed immunohistochemically. RESULTS: The 14 519 genes detected by cDNA microarray were used to compare gene expression levels in synovial lining cells from RA with those from OA patients. Cluster analysis indicated that RA cells, including low- and high-expression subgroups, and OA cells were stored in two main clusters. The molecular activity of RA was statistically consistent with its clinical and histological activity. Expression levels of signal transducer and activator of transcription 1 (STAT1), interferon regulatory factor 1 (IRF1), and the chemokines CXCL9, CXCL10, and CCL5 were statistically significantly higher in the synovium of RA than in that of OA. Immunohistochemically, the lining synovium of RA, but not that of OA, clearly expressed STAT1, IRF1, and chemokines, as was seen in microarray analysis combined with LMD. CONCLUSIONS: Our findings indicate an important role for lining synovial cells in the inflammatory and proliferative processes of RA. Further understanding of the local signalling in structural components is important in rheumatology.
22155498 Prenatal alcohol exposure alters the course and severity of adjuvant-induced arthritis in 2012 Mar Prenatal alcohol exposure (PAE) has adverse effects on the development of numerous physiological systems, including the hypothalamic-pituitary-adrenal (HPA) axis and the immune system. HPA hyper-responsiveness and impairments in immune competence have been demonstrated. The present study investigated immune function in PAE females utilizing an adjuvant-induced arthritis (AA) model, widely used as a model of human rheumatoid arthritis. Given the effects of PAE on HPA and immune function, and the known interaction between HPA and immune systems in arthritis, we hypothesized that PAE females would have heightened autoimmune responses, resulting in increased severity of arthritis, compared to controls, and that altered HPA activity might play a role in the immune system changes observed. The data demonstrate, for the first time, an adverse effect of PAE on the course and severity of AA in adulthood, indicating an important long-term alteration in functional immune status. Although overall, across prenatal treatments, adjuvant-injected animals gained less weight, and exhibited decreased thymus and increased adrenal weights, and increased basal levels of corticosterone and adrenocorticotropin, PAE females had a more prolonged course of disease and greater severity of inflammation compared to controls. In addition, PAE females exhibited blunted lymphocyte proliferative responses to concanavalin A and a greater increase in basal ACTH levels compared to controls during the induction phase, before any clinical signs of disease were apparent. These data suggest that prenatal alcohol exposure has both direct and indirect effects on inflammatory processes, altering both immune and HPA function, and likely, the normal interactions between these systems.
21556777 Interferon-γ release assay in the diagnosis of latent tuberculosis infection in arthritis 2011 Dec The aim of this study was to evaluate the usefulness of the interferon-γ release assay (IGRA) for the diagnosis of latent tuberculosis infection (LTBI) in arthritis patients who received tumor necrosis factor (TNF) antagonist in Korea. The study involved 107 consecutive patients: 61 (57%) with ankylosing spondylitis and 46 (43%) with rheumatoid arthritis. Screening tests were performed including the tuberculin skin test (TST), the QuantiFERON-TB Gold In-Tube (QFT-IT) test, and chest radiography. A positive QFT-IT test result, regardless of TST results, was considered an indication for LTBI treatment. If the QFT-IT results were indeterminate, a positive TST was regarded as an indication for LTBI treatment. A Bacillus Calmette-Guérin (BCG) scar was found in 63 patients (59%). LTBI treatment was performed in 37 patients (35%), including 36 with positive QFT-IT results and one with indeterminate QFT-IT and positive TST results. No patients developed tuberculosis during a median of 18 months (range, 13-26 months) of TNF antagonist therapy. In 16 patients who had positive TST and negative QFT-IT results, TNF antagonists were given without LTBI treatment. Tuberculosis did not occur, even in these patients, during a median of 24.5 months (range, 15-33.5 months) of TNF antagonist therapy. IGRA may be used instead of TST for the diagnosis of LTBI in patients before starting TNF antagonists in countries where tuberculosis prevalence is intermediate and the BCG vaccination is mandatory at birth, such as in Korea.