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ID PMID Title PublicationDate abstract
15743469 Rheumatoid arthritis synovium contains plasmacytoid dendritic cells. 2005 We have previously described enrichment of antigen-presenting HLA-DR+ nuclear RelB+ dendritic cells (DCs) in rheumatoid arthritis (RA) synovium. CD123+HLA-DR+ plasmacytoid DCs (pDCs) and their precursors have been identified in human peripheral blood (PB), lymphoid tissue, and some inflamed tissues. We hypothesized recruitment of pDCs into the inflamed RA synovial environment and their contribution as antigen-presenting cells (APCs) and inflammatory cells in RA. CD11c+ myeloid DCs and CD123+ pDCs were compared in normal and RA PB, synovial fluid (SF), and synovial tissue by flow cytometry, immunohistochemistry, and electron microscopy and were sorted for functional studies. Nuclear RelB-CD123+ DCs were located in perivascular regions of RA, in a similar frequency to nuclear RelB+CD123- DCs, but not normal synovial tissue sublining. Apart from higher expression of HLA-DR, the numbers and phenotypes of SF pDCs were similar to those of normal PB pDCs. While the APC function of PB pDCs was less efficient than that of PB myeloid DCs, RA SF pDCs efficiently activated resting allogeneic PB T cells, and high levels of IFN-gamma, IL-10, and tumor necrosis factor alpha were produced in response to incubation of allogeneic T cells with either type of SF DCs. Thus, pDCs are recruited to RA synovial tissue and comprise an APC population distinct from the previously described nuclear RelB+ synovial DCs. pDCs may contribute significantly to the local inflammatory environment.
16569685 Serum immunoglobulin free light chain assessment in rheumatoid arthritis and primary Sjogr 2007 Jan BACKGROUND: B cell activation may result in an increased secretion of immunoglobulin free light chains (FLCs) in autoimmune diseases. OBJECTIVE: To analyse serum FLC levels in patients with rheumatoid arthritis and in those with primary Sjögren's syndrome (pSS). PATIENTS AND METHODS: Blood samples were collected from 80 healthy blood donors, 50 patients with rheumatoid arthritis and 139 patients with pSS. Serum FLC level was measured using a new quantitative immunoassay. RESULTS: Mean (standard error (SE)) serum kappa and lambda FLC levels were significantly higher in patients with rheumatoid arthritis and in those with pSS than in controls (kappa : 18.9 (1.1) and 16.3 (1.4) v 10.5 (0.4) mg/l, p<0.001 and p = 0.001, respectively; lambda: 16.7 (1.2) and 19.3 (1.5) v 11.6 (0.6) mg/l, p<0.001 for both). 18 (36%) patients with rheumatoid arthritis and 31 (22.3%) patients with pSS had abnormal serum FLC levels (increased kappa or lambda levels and abnormal ratio of kappa:lambda). Serum kappa and lambda levels were correlated with other B cell activation markers in both diseases. FLC levels increased with disease activity, because, unlike total gammaglobulin and immunoglobulin G levels, they were significantly correlated with Disease Activity Score 28 in patients with rheumatoid arthritis (p = 0.004 for kappa, p = 0.05 for lambda) and with extraglandular involvement in pSS (p = 0.01 for kappa, p = 0.04 for lambda). CONCLUSION: FLC levels are increased and correlate with disease activity in patients with rheumatoid arthritis and in those with pSS, two diseases in which increased risk of lymphoma could result from persistent B cell activation and disease activity. Further studies are required to determine whether FLC assessment could represent a relevant biomarker for response to treatment (especially B cell depletion) and for the risk of lymphoma in autoimmune diseases.
15743888 Involvement of poly(ADP-ribose) polymerase 1 in ERBB2 expression in rheumatoid synovial ce 2005 Jul Hyperplasia of synovial lining cells is one of the main features of rheumatoid arthritis (RA). We previously reported that ERBB2 is highly expressed in RA synovial cells and that it plays an important role in their hyperproliferative growth. Recent findings have suggested that poly(ADP-ribose) polymerase-1 (PARP-1) is involved in the transactivation of NF-kappaB-dependent genes such as ERBB2. In the present study, we investigated the role of PARP-1 in ERBB2 transcription in RA synovial cells. The expression level of PARP-1 was significantly high in synovial cells derived from three patients with RA, compared with three patients with osteoarthritis (OA). Luciferase assays revealed that PARP-1 augments the transcription of the ERBB2 gene and that a region between -404 and -368 is responsible for this activation. A protein with an apparent molecular mass of 115 kDa was isolated mainly from nuclear extracts of RA synovial cells with an affinity matrix harboring a DNA fragment identical to the above region. Mass spectrometric analysis demonstrated this protein to be PARP-1. Southwestern blot analysis showed that PARP-1 binds to this region, but not to adjacent regions. PARP-1 associates directly with NF-kappaB, and a chromatin immunoprecipitation assay indicated that these proteins interact with this enhancer region in the ERBB2 gene. Treatment of RA synovial cells with PARP-1 small interfering RNA attenuated their ERBB2 expression, while an inhibitor of the polymerase activity of PARP-1 had no effect. PARP-1 DNA binding is not required for transcriptional activation. These findings suggest that PARP-1 is involved in the expression of ERBB2 in concert with NF-kappaB, which might be associated with the proliferation of RA synovial cells.
16412378 Identification of citrullinated eukaryotic translation initiation factor 4G1 as novel auto 2006 Mar 3 Antibodies against citrullinated proteins are highly specific for rheumatoid arthritis. We previously reported that functional variants of the gene encoding peptidylarginine deiminase type 4 were closely associated with RA. The purpose of this study was to investigate the citrullinated autoantigens recognized by serum samples from patients with RA. The human chondrocyte cDNA expression library was citrullinated by PADI4 and was immunoscreened with anti-modified citrulline antibodies and sera from patients with rheumatoid arthritis. One immunoreactive cDNA clone containing a 2480-base pair insert was isolated and sequence analysis revealed that the cDNA included a part of the eukaryotic translation initiation factor 4G1. Immunoreactivity against a recombinant citrullinated eIF4G1 fragment was observed with high specificity in 50.0% of RA patients. The levels of antibodies against citrullinated eIF4G1 were correlated with those of anti-CCP antibodies. Citrullinated eIF4G1 was identified as a candidate citrullinated autoantigen in RA patients. Citrullination of eIF4G1 may thus be involved in the pathogenesis of RA.
16557465 Suppression of collagen-induced arthritis by oral administration of the citrus flavonoid h 2006 Apr The preventive and therapeutic effects of the Citrus flavonoid hesperidin (HES) on the development of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA), were investigated. Mice were administered orally HES three times a week starting from either the onset (day 21) of secondary immunization or on day 31, when the CIA development had reached a plateau. In both cases, treatment with HES resulted in a significant suppression of clinical scores and improvement of histological features. These results suggest that oral administration of HES could be effective for treating human RA patients.
15789884 The ability of disease modifying antirheumatic drugs to induce and maintain improvement in 2005 Jan OBJECTIVE: The effectiveness of the disease-modifying antirheumatic drugs (DMARDs) methotrexate (MTX), bucillamine (BUC), salazosulphapyridine (SASP) and gold sodium thiomalate (GST) over two courses of treatment with a follow-up period of at least 12 months was evaluated in 425 patients with rheumatoid arthritis. METHODS: Clinical efficacy was evaluated on the basis of the numbers of painful and swollen joints, morning stiffness, grip strength, erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor levels before and after treatment. Results were evaluated on the basis of the survival rate (Kaplan-Meier method) and the incidence and types of adverse drug reactions (ADR) following single and combined therapies. RESULTS: In the first course of treatment, the survival rates for MTX, GST, BUC and SASP were 52.3%, 40.4%, 33.0% and 24.8%, respectively. The rates of development of ADR were 22.9%, 23.5%, 26.3% and 30.0% for BUC, SASP, GST and MTX, respectively. In the second course, the survival rates for MTX, BUC and SASP were 36.6%, 14.1% and 10%, respectively. CONCLUSION: DMARDs used in the first course of treatment improved the clinical parameters until the 6th month after initiation of treatment. Combination treatments showed some effectiveness, but because of the high incidence of ADR the survival rate was low. DMARDs used in the second course of treatment were not efficacious and there was no improvement in the survival rate compared to the first course of treatment.
16207339 Rheumatoid arthritis is an independent risk factor for multi-vessel coronary artery diseas 2005 The risk for cardiovascular (CV) disease is increased in rheumatoid arthritis (RA) but data on the burden of coronary atherosclerosis in patients with RA are lacking. We conducted a retrospective case-control study of Olmsted County (MN, USA) residents with RA and new-onset coronary artery disease (CAD) (n = 75) in comparison with age-and sex-matched controls with newly diagnosed CAD (n = 128). Angiographic scores of the first coronary angiogram and data on CV risk factors and CV events on follow-up were obtained by chart abstraction. Patients with RA were more likely to have multi-vessel coronary involvement at first coronary angiogram compared with controls (P = 0.002). Risk factors for CAD including diabetes, hypertension, hyperlipidemia, and smoking history were not significantly different in the two cohorts. RA remained a significant risk factor for multi-vessel disease after adjustment for age, sex and history of hyperlipidemia. The overall rate of CV events was similar in RA patients and controls; however, there was a trend for increased CV death in patients with RA. In a nested cohort of patients with RA and CAD (n = 27), we measured levels of pro-inflammatory CD4+CD28null T cells by flow cytometry. These T cells have been previously implicated in the pathogenesis of CAD and RA. Indeed, CD4+CD28null T cells were significantly higher in patients with CAD and co-existent RA than in controls with stable angina (P = 0.001) and reached levels found in patients with acute coronary syndromes. Patients with RA are at increased risk for multi-vessel CAD, although the risk of CV events was not increased in our study population. Expansion of CD4+CD28null T cells in these patients may contribute to the progression of atherosclerosis.
16207346 DAS28: a useful instrument to monitor infliximab treatment in patients with rheumatoid art 2005 The Disease Activity Score using 28 joint counts (DAS28) has been developed in a cohort of patients with rheumatoid arthritis in which only conventional anti-rheumatic treatments were used. It has extensively been validated to monitor disease activity in daily clinical practice as well as in clinical trials. The study of Vander Cruyssen and colleagues showed that the DAS28 correlated best with the decisions of rheumatologists to increase the infliximab dose because of insufficient response. This result once more confirms the validity of the DAS28 to monitor disease activity in patients with rheumatoid arthritis and to titrate treatment with biologicals.
16377229 Rheumatoid nodulosis. Two cases with destructive polyarthritis after 20 years. 2006 Mar The term "rheumatoid nodulosis" was coined by Ginsberg in 1975 to designate a rare and distinctive form of rheumatoid disease. Anecdotal case reports suggest a benign nondestructive course, although prolonged follow-up data are usually unavailable. We describe two cases of typical rheumatoid nodulosis with follow-ups exceeding 25 years. Onset occurred at 14 and 22 years of age, respectively. Both patients presented with palindromic rheumatism, positive tests for rheumatoid factors, negative tests for other biological markers, and normal radiographs. Multiple subcutaneous nodules developed after 4 and 6 years with palindromic flares, respectively. Functional impairments and disfigurement required several surgical procedures to remove nodules. Histology was typical for rheumatoid nodules. Neither patient responded to disease-modifying anti-rheumatic drugs (gold, antimalarials, and D-penicillamine). Treatment consisted of nonsteroidal anti-inflammatory drugs combined with prednisone as needed. After 20 and 22 years of follow-up, respectively, both patients had typical rheumatoid arthritis with deformities and radiological joint destruction. In conclusion, these two cases establish that rheumatoid nodulosis can occur as a presentation of rheumatoid arthritis with a potential for severe joint damage after many years.
15692992 The risk of congestive heart failure in rheumatoid arthritis: a population-based study ove 2005 Feb OBJECTIVE: It is hypothesized that the systemic inflammation associated with rheumatoid arthritis (RA) promotes an increased risk of cardiovascular (CV) morbidity and mortality. We examined the risk and determinants of congestive heart failure (CHF) in patients with RA. METHODS: We assembled a population-based, retrospective incidence cohort from among all individuals living in Rochester, Minnesota, in whom RA (defined according to the American College of Rheumatology 1987 criteria) was first diagnosed between 1955 and 1995, and an age- and sex-matched non-RA cohort. After excluding patients in whom CHF occurred before the RA index date, all subjects were followed up until either death, incident CHF (defined according to the Framingham Heart Study criteria), migration from the county, or until January 1, 2001. Detailed information from the complete medical records (including all inpatient and outpatient care provided by all local providers) regarding RA, ischemic heart disease, and traditional CV risk factors was collected. Cox models were used to estimate the effect of RA on the development of CHF, adjusting for CV risk factors and/or ischemic heart disease. RESULTS: The study population included 575 patients with RA and 583 subjects without RA. The CHF incidence rates were 1.99 and 1.16 cases per 100 person-years in patients with RA and in non-RA subjects, respectively (rate ratio 1.7, 95% confidence interval [95% CI] 1.3-2.1). After 30 years of followup, the cumulative incidence of CHF was 34.0% in patients with RA and 25.2% in non-RA subjects (P< 0.001). RA conferred a significant excess risk of CHF (hazard ratio [HR] 1.87, 95% CI 1.47-2.39) after adjusting for demographics, ischemic heart disease, and CV risk factors. The risk was higher among patients with RA who were rheumatoid factor (RF) positive (HR 2.59, 95% CI 1.95-3.43) than among those who were RF negative (HR 1.28, 95% CI 0.93-1.78). CONCLUSION: Compared with persons without RA, patients with RA have twice the risk of developing CHF. This excess risk is not explained by traditional CV risk factors and/or clinical ischemic heart disease.
16947381 Dysregulation of interleukin-10-dependent gene expression in rheumatoid arthritis synovial 2006 Sep OBJECTIVE: The inflammatory cytokines tumor necrosis factor alpha (TNFalpha) and interleukin-1 (IL-1) are produced by activated macrophages, are key mediators of pathogenesis, and are validated therapeutic targets in rheumatoid arthritis (RA) and seronegative spondylarthritis (SpA). IL-10 is a potent antiinflammatory cytokine that suppresses macrophage TNFalpha and IL-1 production, yet is not effective in suppressing inflammatory arthritis. To gain insight into IL-10 responses in inflammatory arthritis, we used microarray analysis to determine the patterns of IL-10-inducible gene expression in freshly isolated RA and seronegative SpA synovial macrophages. METHODS: Macrophages from the synovial fluid of 5 patients with RA and 3 with seronegative SpA (2 with psoriatic arthritis and 1 with ankylosing spondylitis) were isolated by positive selection and stimulated ex vivo with IL-10 or interferon-gamma (IFNgamma). Gene expression was analyzed using Affymetrix microarrays and protocols. Real-time polymerase chain reaction was used to confirm changes in gene expression. RESULTS: The number of genes induced by IL-10 in arthritic macrophages was markedly smaller than that induced in control macrophages, and the strength of induction was lower in arthritic macrophages for most genes. The residual response of arthritic macrophages to IL-10 stimulation was qualitatively altered, such that IL-10 preferentially increased expression of IFNgamma-inducible genes. In contrast, arthritic macrophages expressed many IFNgamma-inducible genes prior to stimulation, and their response to IFNgamma remained mostly intact. CONCLUSION: These results demonstrate that IL-10 responses are dysregulated in RA synovial macrophages. An altered biologic response to IL-10, with attenuation of its antiinflammatory function and a concomitant retention of IFNgamma-like activating functions, provides a basis for the lack of efficacy of IL-10 in suppressing inflammatory arthritis.
17022715 [Effectiveness and safety of adalimumab and etanercept for rheumatoid arthritis in a third 2006 Jul OBJECTIVE: To assess the effectiveness of adalimumab and etanercept at 6 and 12 months after therapy onset using DAS28, EULAR (European League Against Rheumatism), and ACR (American College of Rheumatology) criteria, and to analyze safety. METHOD: A prospective, 12-month, observational study of a patient cohort diagnosed with rheumatoid arthritis who were started on adalimumab or etanercept at the Rheumatology Department between January 2003 and December 2004. DAS28, EULAR, and ACR criteria were examined at 6 and 12 months. An intention-to-treat analysis was performed, and adverse reactions were quantitized. RESULTS: Ninety-nine patients were included - 50 on adalimumab and 49 on etanercept. Of these, 30 and 20%, respectively, received monotherapy. No differences in effectiveness were seen between both drugs during the studied periods of time according to DAS28. EULAR response to adalimumab at 6 and 12 months was: good 28 and 38%; moderate 40 and 36%; nil 10 and 4%; regarding etanercept at 6 and 12 months: good 29 and 43%; moderate 31 and 24%; nil 18 and 10%. As regards adalimumab at 6 and 12 months: ACR20: 64 and 62%; ACR50: 44 and 46%; ACR70: 22 and 26%; as regards etanercept at 6 and 12 months: ACR20: 61 and 65%; ACR50: 41 and 45%; ACR70: 16 and 24%. Eleven patients discontinued therapy in each group. CONCLUSIONS: Adalimumab and etanercept had a similar effectiveness in our population. Criteria of use may condition results, and thus awareness of other hospitals experience is encouraged.
16329091 Immune modulation of collagen-induced arthritis by intranasal cytokine gene delivery: a mo 2005 Dec OBJECTIVE: To develop a passively targeted, patient-compliant, intranasal interleukin-10 (IL-10) gene therapy delivery system and to investigate its therapeutic benefit in experimental collagen-induced arthritis, a model of rheumatoid arthritis. METHODS: Arthritis was induced in DBA/1 mice and monitored following intranasal administration of an IL-10 plasmid (pG-IL-10) or the empty vector 2 days (days -2 and 19) prior to collagen injection (prophylactic group, as a single dose after collagen boost on day 21 (early therapy group, or as a single dose upon acquisition of a disease score of 3 (late therapy group. IL-10-induced alterations in cytokine secretion and proliferation by spleen and lymph node cells were assessed on days 31 and 65 and correlated with histologic changes and bone erosions assessed on day 65. RESULTS: Intranasal delivery of pG-IL-10 significantly delayed arthritis onset and reduced disease severity in the prophylactic group and early therapy group, reduced cellular infiltration and bone loss in the early therapy group, and reduced T cell proliferation in response to collagen on days 31 and 65 in these two groups, with a significant reduction in tumor necrosis factor alpha production on day 65. Within the late therapy group, disease progression was arrested for the rest of the study. The intranasally administered pG-IL-10 targeted monocytes and macrophages and showed dissemination to inflamed joints and draining lymph nodes in vivo. Importantly, systemic levels of IL-10 (in serum) were transient (peaking on day 2) and undetectable by day 4. CONCLUSION: Intranasal IL-10 gene delivery significantly reduces bone destruction, shows evidence of reducing joint inflammation, and may be mediated by high local levels of IL-10 produced by transfected monocytes trafficking to inflamed joints and draining lymph nodes.
16507130 Radiographic joint damage in rheumatoid arthritis is associated with differences in cartil 2006 INTRODUCTION: The objective of this study was to determine whether serum biomarkers for degradation and synthesis of the extracellular matrix of cartilage are associated with, and can predict, radiographic damage in patients with rheumatoid arthritis (RA). METHODS: Clinical and radiographic data of 87 RA patients were recorded 1 year after disease onset and then annually up to four years. Serum concentrations of four cartilage biomarkers were determined at these time points: a neoepitope formed by collagenase cleavage of type II collagen (C2C), a neoepitope formed by collagenase cleavage of type II collagen as well as type I collagen (C1,2C), a carboxy propeptide of type II procollagen formed during synthesis (CPII), and a cartilage proteoglycan aggrecan turnover epitope (CS846-epitope). Biomarker concentrations between patients with rapid radiographic progression (>7.3 Sharp/van der Heijde units per year) and those with slow radiographic progression (<2.3 units per year) were compared. In addition, we evaluated the long-term and short-term predictive value of each biomarker for progression of radiographic damage. RESULTS: Patients with rapid radiographic progression had higher C2C, higher C1,2C, and higher CS846-epitope levels than slow progressors. CPII levels showed no differences. Most importantly, the long-term radiographic progression for C2C, for C1,2C, and for CS846-epitope can be predicted by the biomarker value at year 1 after disease onset. C2C was also a predictor for joint space narrowing and annual radiographic damage during the subsequent year. CONCLUSION: This study shows that the concentration of serum biomarkers of cartilage collagen breakdown and proteoglycan turnover, but not of collagen synthesis, are related to joint destruction in RA. The use of these biomarkers may be of value when studying progression of joint damage in patients with RA.
15705630 Are clinical trials in rheumatoid arthritis generalizable to routine practice? A re-evalua 2005 May OBJECTIVE: Trials of disease-modifying anti-rheumatic drugs (DMARDs) enrol active rheumatoid arthritis patients identified using standard criteria (three out of four of: >/=6 tender joints, >/=6 swollen joints, ESR >/= 28 mm/h, >/=45 min morning stiffness). Concern has been expressed about generalizability, as many patients in routine practice have less active disease. Furthermore, these criteria do not map onto standard disease activity and treatment response measures. We examined how many routine patients were sufficiently active to meet trial recruitment criteria and whether alternative definitions of active disease were more appropriate. METHODS: We studied 504 patients in a cross-sectional study, 156 in a longitudinal study and 94 starting new DMARDs or biologics. Patients were classified as 'trial active' (met entry criteria), in remission or 'intermediately active' (between the two). We also evaluated the effect of amendments to criteria. RESULTS: Cross-sectionally only 38% patients were 'trial active', but longitudinally 68% were 'trial active' at least once. Thus, many clinic patients do have disease activity below the level required for trial entry, but over time most reach eligibility levels. More (62%) of the cohort starting new treatment were 'trial active', suggesting that recruitment criteria relate to clinical decisions. Criteria omitting morning stiffness and a disease activity score (DAS28) >/=5.4 replicated the classification given by current criteria. CONCLUSIONS: Trial results can be generalized to routine practice because most clinic patients are 'trial active' when their therapy is changed and most become 'trial active' over time. As DAS-based criteria are simpler and relate directly to response measures, their use should be considered in future.
16264061 Optic neuritis with concurrent etanercept and isoniazid therapy. 2005 Dec OBJECTIVE: To report a case of optic neuritis associated with concurrent etanercept and isoniazid therapy. CASE SUMMARY: A 55-year-old man diagnosed as having rheumatoid arthritis had received treatment with nonsteroidal antiinflammatory drugs, sulfasalazine, oral methotrexate, leflunomide, and deflazacort. Four months prior to admission, he had a Disease Activity Score of 6.06; treatment with etanercept was considered. Three months prior to admission, because of evidence of latent tuberculosis, isoniazid 300 mg once daily and pyridoxine 50 mg once daily were prescribed. Treatment with subcutaneous etanercept 25 mg twice weekly was started 5 days after isoniazid was initiated. Two weeks prior to admission, the patient developed blurred vision in his left eye. Ten days later, his vision worsened and he was hospitalized. The visual acuity in both eyes was 0.7, and a campimetric examination was compatible with optic neuritis. Magnetic resonance imaging of the brain revealed lesions suggesting demyelinating lesions. The clinical course was consistent with bilateral optic neuritis. Etanercept was stopped, and isoniazid was replaced with rifampin 600 mg once daily. The patient was treated with intravenous methylprednisolone hemisuccinate 1 g/day for 5 days followed by oral prednisolone, resulting in a minor subjective improvement in left eye visual acuity. He then received oral prednisone for 3 weeks, slowly tapering to discontinuation. DISCUSSION: No physiologic factors could have predisposed this patient to develop optic neuritis. He was not diagnosed with a demyelinating disease or underlying systemic condition. The optic neuritis was unlikely to be an early manifestation of multiple sclerosis based on the clinical course and the negative results of the imaging tests. Furthermore, there was a close temporal correlation between the drug exposure and the onset of symptoms. After discontinuation of etanercept and isoniazid therapy, the patient's general condition improved. Use of the Naranjo probability scale indicated a possible relationship between optic neuritis and combined etanercept-isoniazid therapy. CONCLUSIONS: Patients initiated on etanercept and isoniazid should be closely monitored for the development of adverse neurologic signs and effects. If optic neuritis is determined, etanercept and isoniazid should be discontinued immediately.
15909726 Lung cancer associated with rheumatoid arthritis does not shorten life expectancy. 2005 May BACKGROUND: The incidence of lung cancer (LC) is reported to be higher in patients with rheumatoid arthritis (RA). The present study investigated whether or not RA altered the clinical manifestation of LC. METHODS: In this retrospective, cohort study, a total of 23 patients with both RA and LC (RA + LC group), and 6,570 patients with primary LC alone (LCA group), were identified from records at Taipei Veterans General Hospital between 1993 and 2002. Data about clinical characteristics, smoking habit, tumor location, LC histology, staging, and survival, were compared between the 2 groups. RESULTS: There was no significant difference in mean age at LC diagnosis between the RA + LC and LCA groups (70.2 vs 67.6 years; p = 0.154). Adenocarcinoma was the major histologic type in both groups, especially among women. There was no significant difference in histology, location, or staging of LC between the RA + LC and LCA groups. In the RA + LC group, all patients had RA before LC was diagnosed; pulmonary fibrosis was noted in 3 patients, 1 of whom had secondary Sjogren's syndrome. Median survival in the LCA group was not significantly different from that in the RA + LC group (10 [95% confidence interval, CI, 9.6, 10.4] vs 11 [95% CI, 3.7, 18.3] months; p = 0.69); the relative risk of LCA compared with RA + LC for survival was 0.938 (95% CI, 0.555, 1.585). The incidence of LC in RA patients in our hospital was 1.32% (23 of 1,740 patients). CONCLUSION: RA has no influence on LC stage and does not shorten the survival of LC patients.
16770449 Exposure to a specific pulsed low-frequency magnetic field: a double-blind placebo-control 2006 Summer BACKGROUND: Specific pulsed electromagnetic fields (PEMFs) have been shown to induce analgesia (antinociception) in snails, rodents and healthy human volunteers. OBJECTIVE: The effect of specific PEMF exposure on pain and anxiety ratings was investigated in two patient populations. DESIGN: A double-blind, randomized, placebo-controlled parallel design was used. METHOD: The present study investigated the effects of an acute 30 min magnetic field exposure (less than or equal to 400 microTpk; less than 3 kHz) on pain (McGill Pain Questionnaire [MPQ], visual analogue scale [VAS]) and anxiety (VAS) ratings in female rheumatoid arthritis (RA) (n=13; mean age 52 years) and fibromyalgia (FM) patients (n=18; mean age 51 years) who received either the PEMF or sham exposure treatment. RESULTS: A repeated measures analysis revealed a significant pre-post-testing by condition interaction for the MPQ Pain Rating Index total for the RA patients, F(1,11)=5.09, P<0.05, estimate of effect size = 0.32, power = 0.54. A significant pre-post-effect for the same variable was present for the FM patients, F(1,15)=16.2, P<0.01, estimate of effect size = 0.52, power =0.96. Similar findings were found for MPQ subcomponents and the VAS (pain). There was no significant reduction in VAS anxiety ratings pre- to post-exposure for either the RA or FM patients. CONCLUSION: These findings provide some initial support for the use of PEMF exposure in reducing pain in chronic pain populations and warrants continued investigation into the use of PEMF exposure for short-term pain relief.
16002730 A non-glycosaminoglycan-binding variant of CC chemokine ligand 7 (monocyte chemoattractant 2005 Jul 15 A non-glycosaminoglycan (GAG)-binding variant of the pleiotropic chemokine CCL7 was generated by mutating to alanine the basic (B) amino acids within an identified (44)BXBXXB(49) GAG-binding motif. Unlike wild-type (wt) CCL7, the mutant sequence had no affinity for heparin. However, the mutant retained a normal affinity for CCR1, CCR2b, and CCR3, and produced a normal calcium flux in mononuclear leukocytes. Both the wt and mutant proteins elicited an equal leukocyte chemotactic response within a solute diffusion gradient but, unlike the wt protein, the mutant failed to stimulate cell migration across a model endothelium. The number of leukocytes recruited to murine air pouches by the mutant sequence was lower than that recruited by wt CCL7. Furthermore, the presence of a mixture of a mutant and wt CCL7 within the air pouch elicited no significant cell accumulation. Cell recruitment also failed using a receptor-sharing mixture of mutant CCL7 and wt CCL5 or a nonreceptor sharing mixture of mutant CCL7 and wt CXCL12. The potential of the mutant sequence to modulate inflammation was confirmed by demonstration of its ability to inhibit the chemotactic response generated in vitro by synovial fluid from patients with active rheumatoid arthritis. A further series of experiments suggested that the non-GAG-binding mutant protein could potentially induce receptor desensitization before, and at a site remote from, any physiological recognition of GAG-bound chemokines. These data demonstrate that GAG binding is required for chemokine-driven inflammation in vivo and also suggest that a non-GAG-binding chemokine receptor agonist can inhibit the normal vectorial leukocyte migration mediated by chemokines.
15846842 Chronically inflamed synovium from spondyloarthropathy and rheumatoid arthritis investigat 2005 May We investigated the cytosolic proteome of inflamed synovial tissue by hierarchical clustering analysis and validated the feasibility of this proteome analysis by identifying proteins that were differentially expressed between rheumatoid arthritis (RA), spondyloarthropathy (SpA), and osteoarthritis (OA). Synovial biopsy samples were obtained from 18 patients undergoing needle arthroscopy for knee synovitis associated with RA (n = 6) and SpA (n = 6), and for joint effusion of the knee associated with OA (n = 6). Cytosolic proteins were extracted from the tissue and subjected to two-dimensional gel electrophoresis. Protein expression patterns were statistically analyzed and used for hierarchical cluster analysis. Proteins of interest were independently identified by matrix-assisted laser desorption/ionization- and electrospray ionization-mass spectrometry. Hierarchical cluster analysis of the complete match set, containing 640 spots, remarkably segregated SpA from RA and OA. Next, we used a subset of spots that was statistically, differentially expressed (P < 0.01), between RA and SpA, SpA and OA, or RA and OA, in both Student's t-test and Mann-Whitney U-test. The dendrograms revealed distinct clustering of RA versus SpA and RA versus OA. Spots that were differentially expressed between the groups were identified by tandem mass spectrometry. Fructose bisphosphate aldolase A and alpha-enolase showed higher expression levels in SpA than in OA (P < 0.01). Calgranulin A myeloid related protein-8 (MRP-8) was markedly up-regulated in RA and SpA patients in comparison to OA patients where this spot was below detection limit. The analysis of the cytosolic proteome of synovial tissue is a useful approach to identify disease-associated proteins in chronic inflammatory arthritis.