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ID PMID Title PublicationDate abstract
17637600 Malnutrition in women with rheumatoid arthritis is not revealed by clinical anthropometric 2008 Oct OBJECTIVE: To evaluate diagnostic instruments for assessment of nutritional status in patients with rheumatoid arthritis (RA) in relation to objective body composition data. SUBJECTS AND METHODS: Study subjects include 60 in-ward patients (83% women, median age 65 years). Anthropometric measures and the nutritional tools Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA), Malnutrition Universal Screening Tool (MUST) and Nutritional Risk Screening tool 2002 (NRS-2002). Body composition was determined by dual-energy X-ray absorptiometry and fat-free mass index (FFMI; kg/m(2)) and fat mass index (FMI; kg/m(2)) were calculated. RESULTS: Mean body mass index (BMI) for RA women and men were 24.4 and 26.9 kg/m(2), respectively. Twelve per cent of the women and none of the few men had BMI<18.5 kg/m(2), that is, the cutoff value for malnutrition. FFMI indicated 52% of the women and 30% of the men to be malnourished. The sensitivity and specificity for BMI to detect malnutrition according to FFMI were 27 and 100%, whereas for arm muscle circumference the sensitivity was 36% and the specificity 89% and for triceps skin fold 43 and 93%, respectively. For MNA, sensitivity was 85% and specificity 39% and for SGA 46 and 82%. Both MUST and NRS-2002 had sensitivity of 45% and specificity of 19%. CONCLUSION: A large proportion of in-ward RA patients had reduced FFMI. Concurrent elevation of fat mass made BMI a non-reliable tool to detect malnutrition. Of the tested clinical evaluation tools, MNA might be used as a screening instrument, but because of its low specificity it should be followed by body composition determination.
18465450 Relationship of serum TWEAK level to cytokine level, disease activity, and response to ant 2008 May OBJECTIVES: To determine the serum concentration of tumour necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) in patients with rheumatoid arthritis (RA) and to investigate the relationship between TWEAK level and disease activity, proinflammatory cytokine levels, and response to anti-TNF treatment. METHODS: Serum samples from 40 patients with RA, 40 patients with ankylosing spondylitis (AS), and 40 healthy subjects were collected. Serum samples from 26 patients with RA who received etanercept treatment were also collected in the 12th week of etanercept therapy. Serum TWEAK, TNFalpha, and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay (ELISA), and disease activity of RA was assessed according to the 28-joint count Disease Activity Score (DAS28). RESULTS: Patients with RA had significantly higher serum levels of TWEAK, TNFalpha, and IL-6 compared with controls (p<0.05). Patients with AS also had significantly higher serum levels of TNFalpha and IL-6 (p<0.05), but their serum TWEAK levels were not different from those of the controls. In patients with RA, serum TWEAK levels correlated with DAS28 (r(2) = 0.452, p = 0.012) and TNFalpha levels (r(2) = 0.653, p<0.001) but not with IL-6 levels. Among RA patients who were treated with etanercept, responders showed a significant decrease in serum TWEAK levels at the 12th week of treatment, whereas TWEAK levels in nonresponders were not different from their baseline levels. CONCLUSIONS: Serum levels of TWEAK were significantly elevated in patients with RA, and reflected disease activity and short-term response to etanercept treatment.
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.
18556221 A tool for the assessment of hand involvement in rheumatic disorders in daily routine--the 2009 Jan OBJECTIVE: To establish a questionnaire for quantification of hand involvement in osteoarthritis (OA) of the hands and rheumatoid arthritis (RA) meeting daily routine requirements. PATIENTS AND METHODS: The smallest number of questions of the modified score for the assessment and quantification of chronic rheumatic affections of the hands (M-SACRAH) providing reasonable reliability was identified by factor analysis and calculating Cronbach's alpha, subsequently resulting in a five-item scale, the short form-SACRAH (SF-SACRAH), which was then administered to 176 RA and 71 hand-OA (HOA) patients simultaneously with the M-SACRAH. Additionally, patient's satisfaction (PatSAT) with disease status was assessed (according to the Austrian school marking system from 1 to 5). Gamma was calculated to assess the agreement of the SF-SACRAH with the M-SACRAH and between the single corresponding questions of different formats. The Wilcoxon rank test was applied to estimate the relationship between PatSAT and the SF-SACRAH. RESULTS: Alpha for the SF-SACRAH in 176 RA and 71 HOA patients amounted to 0.869 and to 0.897, respectively, indicating high internal consistency. In both patient groups the SF-SACRAH was found to be significantly correlated to the M-SACRAH (both P(s)<0.01). Agreement between the corresponding questions of both scales was significant in both patient groups by calculating gamma (average gamma 0.683 in HOA and 0.847 in RA). PatSAT and SF-SACRAH values were highly significantly correlated (P<0.001) proving the score's external validity. CONCLUSION: The SF-SACRAH proved to be a brief and practicable tool to assess hand involvement in OA and RA meeting the requirements of daily routine.
18694758 Molecular basis of recognition of human osteopontin by 23C3, a potential therapeutic antib 2008 Oct 17 Osteopontin plays an important role in the development and perpetuation of rheumatoid arthritis (RA). Antibodies targeting osteopontin have shown promising therapeutic benefits against this disease. We have previously reported a novel anti-RA monoclonal antibody, namely, 23C3, and shown it capable of alleviating the symptoms of RA in a murine collagen-induced arthritis model, restoring the cytokine production profile in joint tissues, and reducing T-cell recall responses to collagen type II. We describe here the crystal structure of 23C3 in complex with its epitope peptide. Analyses of the complex structure reveal the molecular mechanism of osteopontin recognition by 23C3. The peptide folds into two tandem beta-turns, and two key residues of the peptide are identified to be critical for the recognition by 23C3: TrpP43 is deeply embedded into a hydrophobic pocket formed by AlaL34, TyrL36, LeuL46, TyrL49, PheL91, and MetH102 and therefore has extensive hydrophobic interactions with 23C3, while AspP47 has a network of hydrophilic interactions with residues ArgH50, ArgH52, SerH53, and AsnH56 of the antibody. Besides the complementarity-determining region loops, the framework region L2 of 23C3 is also shown to interact with the epitope peptide, which is not common in the antibody-antigen interactions and thus could be exploited in the engineering of 23C3. These results not only provide valuable information for further improvement of 23C3 such as chimerization or humanization for its therapeutic application, but also reveal the features of this specific epitope of osteopontin that may be useful for the development of new antibody drugs against RA.
18576336 Association of STAT4 with rheumatoid arthritis: a replication study in three European popu 2008 Jul OBJECTIVE: This study was undertaken to investigate the previously reported association of the STAT4 polymorphism rs7574865 with rheumatoid arthritis (RA) in 3 different European populations from Spain, Sweden, and The Netherlands, comprising a total of 2,072 patients and 2,474 controls. METHODS: Three different cohorts were included in the study: 923 RA patients and 1,296 healthy controls from Spain, 273 RA patients and 285 healthy controls from Sweden, and 876 RA patients and 893 healthy controls from The Netherlands. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for the STAT4 single-nucleotide polymorphism rs7574865 using a TaqMan 5'-allele discrimination assay. The chi-square test was performed to compare allele and genotype distributions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: We observed a significantly increased frequency of the minor T allele in RA patients compared with healthy controls in the Spanish population (24.8% versus 20.8%; P = 0.001, OR 1.26 [95% CI 1.09-1.45]). This association was confirmed in both the Swedish population (P = 0.03, OR 1.35 [95% CI 1.03-1.77]) and the Dutch population (P = 0.03, OR 1.45 [95% CI 1.21-1.73]). The overall P value for all 3 populations was 9.79 x 10(-6) (OR 1.25 [95% CI 1.13-1.37]). No association between rs7574865 and the presence of rheumatoid factor or anti-cyclic citrullinated peptide autoantibodies was observed. A meta-analysis of all published STAT4 associations revealed an OR of 1.25 (95% CI 1.19-1.33) (P = 1 x 10(-5)). CONCLUSION: Our findings indicate an association between the STAT4 polymorphism rs7574865 and RA in 3 different populations, from Spain, Sweden, and The Netherlands, thereby confirming previous data.
17530706 Tumor necrosis factor alpha activates release of B lymphocyte stimulator by neutrophils in 2007 Jun OBJECTIVE: The tumor necrosis factor (TNF) family member B lymphocyte stimulator (BLyS) is an important regulator of B cell-dependent autoimmunity. Similar to other TNF family members, it is generally expressed as a transmembrane protein and cleaved from the surface to release its active soluble form. This study was undertaken to investigate the expression of BLyS and regulation of BLyS release from the surface of neutrophils infiltrating the rheumatoid joint. METHODS: BLyS expression was studied in neutrophils from the synovial fluid and peripheral blood of patients with rheumatoid arthritis (RA) and healthy controls, by flow cytometry, Western blotting, and immunofluorescence analyses. Peripheral blood neutrophils cultured with 50% RA synovial fluid were study for membrane expression of BLyS. Neutrophils were exposed to a range of proinflammatory cytokines to study the mechanisms of surface loss of BLyS. RESULTS: Expression of BLyS was detected on the surface of peripheral blood neutrophils from both RA patients and healthy controls, whereas BLyS expression on synovial fluid neutrophils was very low. Constitutive expression of BLyS was observed in neutrophils, both on the cell membrane and in intracellular stores; however, BLyS release from each of these sites was found to be regulated independently. Of the various cytokine stimuli, only TNFalpha triggered release of BLyS from the neutrophil membrane. This process led to release of physiologically relevant quantities of soluble BLyS, which was dependent on the presence of the pro-protein convertase furin. In contrast, stimulation of neutrophils with granulocyte colony-stimulating factor induced BLyS release from the intracellular stores. Incubation of peripheral blood neutrophils with RA synovial fluid led to TNFalpha-dependent shedding of BLyS from the cell surface. CONCLUSION: These findings indicate that as neutrophils enter the site of inflammation, they release surface-expressed BLyS in a TNFalpha-dependent manner, and thus may contribute to local stimulation of autoimmune B cell responses.
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.
17574895 Quality and impact of information about interventional rheumatology: a study in 119 patien 2007 Jul OBJECTIVE: To evaluate the quality of patient information about fluoroscopy-guided rheumatologic procedures, and to look for an impact on the patient's experience of the procedure. METHODS: One hundred and nineteen patients completed questionnaires before and after undergoing fluoroscopy-guided interventions. We looked for associations between the information supplied by the rheumatologist who recommended the procedure and pain, anxiety, awareness of potential complications, and the match between patient expectations and actual experience. RESULTS: 62.8% of patients reported receiving information about the procedure. Only 20.5% reported receiving specific information about potential adverse events, although 80.9% felt this information would have been useful. Most patients (74.8%) would have liked to receive additional information. Only 10.1% patients were given written information. Mean (+/-SD) anticipated pain severity as assessed in the waiting room before the procedure on a 0-10 scale was 4.5+/-2.4 in women and 4.2+/-2.3) in men. Actual pain severity during the procedure as assessed on the same scale was 2.7+/-2.6 in women and 2.2+/-1.6 in men. The level of information about the procedure did not influence anticipated or actual pain severity. Anxiety was reported by 59.8% patients and was more common in women (P<0.001), in patients given written information (P=0.05), and in patients undergoing their first intervention (P=0.05). Information was perceived as alleviating anxiety by 69.9% patients, and 77.3% of patients felt they would experience less anxiety if they had the procedure a second time. Only 21.2% patients were able to name a potential adverse event, and this proportion was not influenced by receiving written information. A mismatch between expectations about the procedure or its duration and actual experience was reported by 17 (17/69, 24.6%) and 34 (34/98, 34.7%) patients, respectively, with no significant differences across study subgroups. CONCLUSION: Information about interventional rheumatology procedures is required for ethical principles and legislation. Patients increasingly expect detailed information, which may increase the likelihood that the procedure unfolds smoothly. Our results indicate a need for optimizing patient information. Standardized written material deserves to be evaluated as a means of better meeting the informational needs of patients.
16955533 Stability analysis for drugs with multiple active ingredients. 2007 Mar 30 For every drug product on the market, the United States Food and Drug Administration (FDA) requires that an expiration dating period (shelf-life) must be indicated on the immediate container label. For determination of the expiration dating period of a drug product, regulatory requirements and statistical methodology are provided in the FDA and ICH Guidelines. However, this guideline is developed for drug products with a single active ingredient. There are many drug products consisting of multiple active ingredients, especially for most traditional Chinese medicine. In this article, we propose a statistical method for determining the shelf-life of a drug product with multiple active ingredients following similar idea as suggested by the FDA and assuming that these active ingredients are linear combinations of some factors. Stability data observed from a traditional Chinese medicine were analysed to illustrate the proposed method.
18772121 Effect of intra-articular injection of hyaluronic acid in rheumatoid arthritis patients wi 2008 Aug BACKGROUND: Intra-articular injection of hyaluronic acid (HA) is a well-documented treatment for knee osteoarthritis (OA). One of the multifactorial mechanisms is that exogenous HA can stimulate endogenous HA production. HA can regulate the growth and function of chondrocytes by binding to CD44 receptors on the chondrocytes. Synovitis is often found in patients with rheumatoid arthritis (RA) and is supposed to result from CD44 activity. The aim of this study was to investigate the effect of intra-articular injection of HA in patients with RA combined with knee OA. METHODS: Twenty RA patients with OA knees were enrolled; 11 patients were placed into a stage II group and 9 into a stage III group, in accordance with the Kellgren-Lawrence classification of knee OA. All patients received intra-articular injection of HA (ARTZ) once a week for 5 weeks, and were evaluated with the WOMAC index (including the pain, stiffness and physical function subscales) at baseline, week 5 and week 9. The Friedman test and Wilcoxon signed rank test with Bonferroni correction method were used for statistical analysis. RESULTS: The effect of intra-articular injection of HA was significant at week 5 (p < 0.0167) and persisted to week 9 (p < 0.0167). This therapy was equally efficacious with stage II and stage III patients, with no difference between the 2 groups. CONCLUSION: Intra-articular injection of HA was beneficial in patients with RA combined with knee OA.
18082407 Factors affecting anteroposterior instability following cruciate-retaining total knee arth 2008 Jan Controversy persists concerning around posterior cruciate ligament (PCL) retention in total knee arthroplasty (TKA) for patients with rheumatoid arthritis (RA). This study investigated factors affecting anteroposterior (AP) instability following cruciate-retaining (CR)-TKA. In a consecutive series of 70 knees from 52 RA patients, total displacement (TD) was measured using a KT-2000 arthrometer before and after CR-TKA under anesthesia, and changes in TD were defined as DeltaTD. TD was also measured under anesthesia in 65 knees from 48 RA patients at a mean of 7.5 years after CR-TKA. Mean postoperative TD was 9.4+/-0.95 mm, representing an increase of about 1.5-1.8 mm compared to preoperative TD, and possibly reflecting resection of the anterior cruciate ligament. Correlation analysis revealed significant negative correlations between DeltaTD and both preoperative flexion angle (r=-0.67, p<0.001) and preoperative extension angle (r=-0.63, p<0.001), suggesting that TD in knees with flexion contracture increased postoperatively. At medium-term follow-up, no patients displayed AP instability, and mean TD was 8.3+/-0.48 mm. A significant correlation was found between TD and permissible flexion angle (r=0.61, p<0.001). These results indicate that TD is basically maintained during the course of CR-TKA in RA, but may be slightly affected by factors other than the PCL itself.
17278020 Ten years results of bucillamine in the treatment of rheumatoid arthritis. 2007 A 10-year cohort study was performed, involving all of the 118 patients treated with bucillamine in our hospital between 1988 and 1990. Evaluation was made on the basis of erythrocyte sedimentation rate, grip strength, joint score, duration of morning stiffness, and Lansbury index consisting of the above four parameters. Eleven patients were male and 107 were female, with a mean age of 53 years (range: 20-79 years) and a mean duration of illness of 8.2 years (range: 2-31 years). Lansbury index remained significantly suppressed throughout the 10-year period of treatment. Continuous treatment was possible for 10 years in 18 patients (15%: 2 men and 16 women). Stage of disease did not advance in 14 patients. Six patients met the criteria for remission. Of all patients, 50% dropped out of treatment at 2.4 years after the start of treatment and 75% at 5 years. The 100 patients who dropped out could be roughly divided into three groups. One third of them dropped out because of lack of or attenuation of response. Another third dropped out because of referral to other medical facilities or discontinuation of visits to our hospital, and the remaining third dropped out because of adverse reactions to treatment. There was no particular trend in terms of sex, age, duration of sickness, drugs used before bucillamine, or level of activity of rheumatoid arthritis. There were no significant difference in the stage and class of the disease, and other backgrounds between 10-year treatment group and dropout group.
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.
18261936 A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II a 2008 Sep OBJECTIVE: Recent studies revealed a close connection between adipose tissue, adipokines and articular degenerative inflammatory diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). The goal of this work was to investigate the activity of adiponectin in human and murine chondrocytes and to study its functional role in the modulation of nitric oxide synthase type II (NOS2). For completeness, interleukin (IL)-6, IL-1beta, matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, prostaglandin E2 (PGE2), leukotriene B4 (LTB4), tumor necrosis factor alpha (TNF)-alpha and monocyte chemoattractant protein-1 (MCP-1) accumulation have been evaluated in adiponectin-stimulated chondrocytes cell culture supernatants. METHODS: Murine ATDC5 cell line, C28/I2, C20A4, TC28a2 human immortalized chondrocytes, and human cultured chondrocytes were used. Nitrite accumulation was determined by Griess reaction. Adiponectin receptors (AdipoRs) expression was evaluated by immunofluorescence microscopy and confirmed by reverse transcriptase-polymerase chain reaction. NOS2 expression was evaluated by Western blot analysis whereas cytokines, prostanoids and metalloproteinases production was evaluated by specific enzyme-linked immunosorbent assays. RESULTS: Human and murine chondrocytes express functional AdipoRs. Adiponectin induces NOS2. This effect is inhibited by aminoguanidine, dexamethasone and by a selective inhibitor of phosphatidylinositol 3-kinase. In addition, adiponectin is able to increase IL-6, MMP-3, MMP-9 and MCP-1 by murine cultured chondrocytes whereas it was unable to modulate TNF-alpha, IL-1beta, MMP-2, TIMP-1, PGE2 and LTB4 release. CONCLUSIONS: These results bind more closely the interactions between fat-derived adipokines and articular inflammatory diseases, and suggest that adiponectin is a novel key element in the maintenance of cartilage homeostasis which might be considered as a potential therapeutical target in joint degenerative diseases.
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.
18450367 The role of cortistatin in the human immune system. 2008 May 14 Cortistatin (CST) is a recently described neuropeptide that shares high homology with somatostatin (somatotropin release-inhibiting factor, SRIF) and binds with high affinity to all somatostatin (sst) receptor subtypes. CST is currently known to have a widespread distribution in many human organs including the immune system. The activities specific to CST may be partially attributable to its binding to the growth hormone secretagogue (GHS)-receptor (GHS-R) and the orphan G-protein-coupled receptor MrgX2. Human immune cells produce CST, whereas macrophage lineage and activated endothelium express sst2, and human lymphocytes express sst3. The human thymus expresses sst1, 2, 3, MrgX2 and almost all immune cells express GHS-R. Moreover, at this very moment promising research with CST in experimental animal models is being performed. On the basis of these promising results, studies aiming to further evaluate the possibilities of CST as a therapeutic agent in human immune-mediated inflammatory diseases are warranted.
17127456 Anti-CD20 therapy and autoimmune disease: therapeutic opportunities and evolving insights. 2007 Jan 1 Based on the successful clinical experience with the anti-CD20 antibody, rituximab, for the treatment of B-cell non-Hodgkins lymphoma, there is a rapidly growing literature on the treatment of patients with autoimmune diseases with this therapeutic agent. However, the pathogenetic mechanisms responsible for these diseases may differ greatly from those in B cell malignancies. Herein, I provide an overview on recently published clinical experience, and discuss immunobiologic perspectives that are most relevant to understanding the special opportunities and challenges posed by these diseases. Of special importance, there is emerging evidence that the same inherited genetic variations and acquired immunodefects that underlie autoimmune disease pathogenesis may in some patients also interfere with the efficacy of anti-CD20 antibody-based therapy.
18632310 Heart rate variability predicts anti-tumor necrosis factor therapy response for inflammato 2008 Dec 5 To consider autonomic status as a predictor of anti-tumor necrosis factor (TNF) treatment response for inflammatory arthritis, we conducted an exploratory, double-blind, 52-week study with 33 patients with rheumatoid (25) or psoriatic (8) arthritis using heart rate variability (HRV). All were assessed for parasympathetic, sympathetic, total power and tension index measures of autonomic reactivity at initiation of anti-TNF therapy with etanercept (15) or adalimumab (18). Clinical response was assessed at 6, 12, 26 and 52 weeks by internationally accepted outcome criteria (ACR20/50/70 and DAS28 response). Predictive value was demonstrated for all HRV assessments (p-value range 0.001-0.032), except sympathetic (p-value range 0.06-0.22), for ACR20, ACR50 and ACR70 at 52 weeks and at as early as 6 weeks for some measures. Only parasympathetic and tension index predicted DAS28 outcome (p-value range 0.009-0.024). Poor anti-TNF response was associated with low parasympathetic, low total power, high sympathetic and high tension index measures, a profile also predominant in the prior anti-TNF failure subset (12). In conclusion, this unique, exploratory study suggests that HRV may be a novel, useful predictor of response to anti-TNF therapy in patients with inflammatory arthritis, and emphasizes the importance of autonomic influence of autoimmune disease expression.
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.