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ID PMID Title PublicationDate abstract
20173777 Blockade of interleukin 1 in type 1 diabetes mellitus. 2010 Mar Interleukin 1 (IL-1) is a 17 kDa protein highly conserved through evolution and is a key mediator of inflammation, fever and the acute-phase response. IL-1 has important functions in the innate immune defense against microbes, trauma and stress, and is also an effector molecule involved in tissue destruction and fibrosis. The inhibition of IL-1 action has clinical efficacy in many inflammatory diseases, such as hereditary autoinflammatory disorders, familial hereditary fever, gout, rheumatoid arthritis and type 2 diabetes mellitus (T2DM). The latter is a common metabolic condition caused by insulin resistance and pancreatic beta-cell failure, the causes of both of which have inflammatory components. IL-1 signaling has roles in beta-cell dysfunction and destruction via the NFkappaB and mitogen-activated-protein-kinase pathways, leading to endoplasmic reticulum and mitochondrial stress and eventually activating the apoptotic machinery. In addition, IL-1 acts on T-lymphocyte regulation. The modulating effect of IL-1 on the interaction between the innate and adaptive immune systems and the effects of IL-1 on the beta-cell point to this molecule being a potential interventional target in autoimmune diabetes mellitus. Genetic or pharmacological abrogation of IL-1 action reduces disease incidence in animal models of type 1 diabetes mellitus (T1DM) and clinical trials have been started to study the feasibility, safety and efficacy of IL-1 therapy in patients with T1DM. Here, we review the rationale for blocking IL-1 in patients with T1DM.
20166849 Serum peptidome patterns of human systemic lupus erythematosus based on magnetic bead sepa 2010 May OBJECTIVES: Currently few studies have been reported to utilize matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in rheumatic disease, especially in systemic lupus erythematosus (SLE). Our aim was to find differentially expressed disease-related and condition-specific peptides in sera from patients with SLE, as well as to develop and validate the peptide classification model for the diagnosis of SLE. METHODS: Based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000, 50 SLE patients were divided into two subgroups: 25 were defined as stable SLE (SLEDAI < or = 8) and 25 as active SLE (SLEDAI > 8). Twenty-five patients with rheumatoid arthritis (RA) and 24 healthy donors were also included and underwent analysis. We performed magnetic beads-based weak cation exchange chromatography (MB-WCX) for sample processing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for peptide profiling. ClinProt software 2.1 was used for data analysis and a genetic algorithm was modelled for class prediction. RESULTS: A series of significant short peptides was detected. Classification models were developed to classify samples across normal controls, active SLE patients, and stable SLE patients, and achieved high capability of prediction and cross-validation. Blinded verification of the classification model showed 91.7% sensitivity in active SLE, 83.3% sensitivity in stable SLE, and 86.7% specificity in normal controls. CONCLUSION: We have completed a preliminary study to describe the serum peptide profile of SLE and improve the diagnosis of SLE from an integrated perspective of peptide mass patterns.
20038389 [Study of rituximab efficacy, cost, safety, and compliance of its package leaflet in a ter 2009 Nov INTRODUCTION: The appearance of monoclonal antibodies, and specifically, rituximab, has provided a new approach to treating non-Hodgkin's lymphomas and rheumatoid arthritis. The purpose of this study is to analyse whether this drug is used according to its package leaflet in clinical practice, evaluate the treatment's efficacy and determine its cost. METHODS: Ambispective, observational single-centre study of medication use set up as a prescription evaluation for the indication of rituximab in a tertiary hospital between March 2003 and 31 December 2007. RESULTS: 82 of the 221 patients who were treated (37.1 %) received the drug for a condition that does not appear in the package leaflet. 51.1 % and 27.5 % of response and progression were registered for approved diagnoses and 34.9 % and 47 % for non-approved diagnoses; the death rate was 25.3 % and 41.5 % respectively. The mean cost per treatment episode was the highest for idiopathic thrombocytopenic purpura (11,683 euro), whilst the highest treatment cost per patient was associated with follicular lymphoma (15,940 euro). DISCUSSION: We found that the main cause of the high rate of non-compliance with the package leaflet is patient lack of response to standard treatments, together with clinical practice guides that support the use of rituximab for conditions other than those for which it is indicated. Nevertheless, most of the clinical trials evaluating the efficacy of rituximab for these unauthorized diagnostic profiles have poor methodology, are in phase II, are open studies, have low patient numbers, or in some cases, are not comparative.
19941948 Apolipoprotein E and its role in aging and survival. 2010 Feb The study of biological aging has seen spectacular progress in the last decade and markers are increasingly employed for understanding physiological processes that change with age. Recently, it has been demonstrated that apolipoprotein E (apoE) has a major impact on longevity, but its mechanisms are still not fully understood. ApoE-deficient (E(o)) mice have proved to be a very popular model for studying spontaneous hypercholesterolemia and the subsequent development of atherosclerotic lesions, but only limited data are available with regard to aging and aging changes. We used this murine model to better characterize the involvement of apoE in aging and to evaluate its role in the maintenance of normal organ morphology. Our results show that E(0) mice at different ages (6, 12, 20 weeks old) developed age-dependent morphological and biochemical alterations, including fibrosis (newly formed collagen), pro-inflammatory cytokine (IL-6 and iNOS), lipofuscin accumulation, and decrease of antioxidant enzymes (superoxide dismutase and catalase) in several organs (kidney, liver and heart). It is significant that the observed degenerative findings in E(0) mice at different ages (6, 12, 20 weeks old) were not identified in control mice (C57BL), at 6, 12 and 20 weeks of age. Consequently, since these mice showed enzymatic and structural alterations, normally linked to the age, such as increase of lipofuscin, pro-inflammatory cytokines and decrease of antioxidant enzymes, we can conclude that apoE is a useful player in studies of longevity and age-related diseases, such as inflammatory status and atherosclerosis that are known risk factors for functional decline and early mortality. Moreover, it is possible that apoE may also play a role in other pathological conditions including, for example, cancer, rheumatoid arthritis and macular degeneration.
19940425 Understanding omega-3 polyunsaturated fatty acids. 2009 Nov Current intakes of very long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are low in most individuals living in Western countries. A good natural source of these fatty acids is seafood, especially oily fish. Fish oil capsules contain these fatty acids also. Very long-chain omega-3 fatty acids are readily incorporated from capsules into transport (blood lipids), functional (cell and tissue), and storage (adipose) pools. This incorporation is dose-dependent and follows a kinetic pattern that is characteristic for each pool. At sufficient levels of incorporation, EPA and DHA influence the physical nature of cell membranes and membrane protein-mediated responses, lipid-mediator generation, cell signaling, and gene expression in many different cell types. Through these mechanisms, EPA and DHA influence cell and tissue physiology and the way cells and tissues respond to external signals. In most cases the effects seen are compatible with improvements in disease biomarker profiles or health-related outcomes. As a result, very long-chain omega-3 fatty acids play a role in achieving optimal health and in protection against disease. Long-chain omega-3 fatty acids not only protect against cardiovascular morbidity but also against mortality. In some conditions, for example rheumatoid arthritis, they may be beneficial as therapeutic agents. On the basis of the recognized health improvements brought about by long-chain omega-3 fatty acids, recommendations have been made to increase their intake. The plant omega-3 fatty acid, alpha-linolenic acid (ALA), can be converted to EPA, but conversion to DHA appears to be poor in humans. Effects of ALA on human health-related outcomes appear to be due to conversion to EPA, and since this is limited, moderately increased consumption of ALA may be of little benefit in improving health outcomes compared with increased intake of preformed EPA + DHA.
19845719 Is there truly a risk of lymphoma from biologic therapies? 2009 Sep The treatment of psoriasis has undergone a revolution with the advent of biologic therapies, including infliximab, etanercept, adalimumab, efalizumab, and alefacept. Biologics are generally safe and well tolerated. However, there has been concern over the risk of lymphoma with use of these agents because of their immunosuppressive properties. This review summarizes the current evidence in regards to lymphoma risk with biologic therapy obtained from case reports and case series, observational studies, clinical trials, and meta-analyses. The majority of data for T-cell inhibitors comes from case reports and relatively small, short-term clinical trials. In addition to published case reports and case series, TNF-alpha inhibitors have also been studied extensively in large cohort studies and meta-analyses of clinical trials derived primarily from the rheumatoid arthritis population. Current data are neither sufficient to completely rule out an increased risk of lymphoma associated with biologics, nor to firmly establish a causal relationship between biologics and lymphoma. Short- to intermediate-term treatment with biologics (e.g., up to 4 years) appears to be very safe with respect to lymphoma risk, especially with TNF-alpha inhibitors in which their potential risks appear to be well defined. Continued vigilance is warranted; however, in the appropriate patient, the risk-to-benefit profile of psoriasis treatment with respect to lymphoma risk appears highly favorable.
19758114 The rationale for comparative studies of accelerated atherosclerosis in rheumatic diseases 2010 Jul The inflammatory pathogenesis of atherosclerosis is now well-established, owing to in vitro and in vivo studies and the application of high sensitivity assays for C-reactive protein (CRP) in the general population and specific groups at risk for cardiovascular disease (CVD). In view of the complexity of inflammation-induced atherosclerosis, the rationale for comparative studies of atherogenesis in rheumatic diseases with diverse inflammatory pathogenesis seems obvious; they are human in vivo models to study inflammatory mechanisms involved in atherosclerosis and the impact of treatment. Factors implicated in atherogenesis in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), familial Mediterranean fever (FMF) and Behçet's disease (BD) are discussed in this review. Evidence suggests that enhanced atherosclerosis causes premature cardiovascular events in the autoimmune disease, SLE, and the "high-grade" inflammatory rheumatic disease, RA. Preliminary data suggest that enhanced atherogenesis may accompany FMF in the absence of sufficient suppression of inflammation by colchicine. In the setting of BD, the role of atherosclerosis in the premature manifestation of coronary pathology has not been confirmed; coronary vasculitis and aneurysms appear to constitute the basis of myocardial infarction (MI) in BD. A variety of established and novel risk factors are believed to influence enhanced atherogenesis in rheumatic diseases. Antiphospholipid antibodies are thought to be intimately involved in atherogenesis in SLE and to a lesser extend in RA. CRP may play a more universal role in all rheumatic diseases. The application of high resolution ultrasound of peripheral arteries and other non-invasive techniques may allow targeted use of statins, ACE inhibitors, antiplatelet agents and other cardioprotective drugs in patients with rheumatic diseases, but this needs to be evaluated specifically in prospective studies.
19675559 Regulation of skin pigmentation and thickness by Dickkopf 1 (DKK1). 2009 Aug Dickkopf 1 (DKK1), an inhibitor of Wnt signaling, not only functions as a head inducer during development, but also regulates joint remodeling and bone formation, which suggests roles for DKK1 in the pathogenesis of rheumatoid arthritis and multiple myeloma. We recently demonstrated that levels of DKK1 in palmoplantar dermal fibroblasts are physiologically higher than those observed in non-palmoplantar dermal fibroblasts. Thus, the DKK1-rich mesenchyme in palmoplantar dermis affects the overlying epithelium and induces a palmoplantar phenotype in the epidermis. More specifically, DKK1 suppresses melanocyte function and growth through the regulation of microphthalmia-associated transcription factor (MITF) and beta-catenin. Furthermore, DKK1 induces the expression of keratin 9 and alpha-Kelch-like ECT2-interacting protein (alphaKLEIP) but downregulates the expression of beta-catenin, glycogen synthase kinase 3beta, protein kinase C, and proteinase-activated receptor-2 (PAR-2) in keratinocytes. Treatment of reconstructed skin with DKK1 reproduces the hypopigmentation and thickening of skin through Wnt/beta-catenin signaling. These studies elucidate why human palmoplantar skin is thicker and paler than non-palmoplantar skin through the secretion of DKK1 by fibroblasts that affect the overlying epidermis. Thus, DKK1 may be useful for reducing skin pigmentation and for thickening photo-aged skin and palmoplantar wounds caused by diabetes mellitus and rheumatic skin diseases.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 73-75; doi:10.1038/jidsymp.2009.4.
19572256 Suppression of the antigen-stimulated RBL-2H3 mast cell activation by Artekeiskeanol A. 2009 Nov Effects of artekeiskeanol A, a newly isolated coumarin derivative from Artemisa keiskeana Miq. (Compositae), the extract of which is used for treatment of rheumatoid arthritis as a folk medicine, on the antigen-induced activation of RBL-2H3 cells were examined. RBL-2H3 cells were sensitized with dinitrophenol (DNP)-specific IgE, and then stimulated with the antigen DNP-conjugated human serum albumin (DNP-HSA). Artekeiskeanol A at 10 to 100 microM inhibited the antigen-induced degranulation in a concentration-dependent manner, the IC(50) value being 38.0 + or - 0.2 microM. Degranulation induced by thapsigargin or A23187 also was inhibited by artekeiskeanol A at 10 to 100 microM. The antigen-induced increase in the levels of mRNA for tumor necrosis factor (TNF)-alpha and interleukin (IL)-13 and phosphorylations of Akt, p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and p44/42 MAPK were also suppressed by artekeiskeanol A. Our findings suggested that the effectiveness of the extract of A. keiskeana might partly be due to the inhibition of mast cell activation by artekeiskeanol A.
19342253 Role of a LIF antagonist in LIF and OSM induced MMP-1, MMP-3, and TIMP-1 expression by pri 2009 Jun Cartilage degradation is mediated by matrix metalloproteinases (MMPs) and their inhibitors, tissue metalloproteinases (TIMPs), which are transcriptionally regulated by a variety of growth factors and cytokines. The levels of various MMPs as well as TIMPs have been shown to increase in response to certain cytokines. These include leukaemia inhibitory factor (LIF) and Oncostatin M (OSM), both of which have been detected in the synovial fluids of patients with rheumatoid arthritis (RA). However, the role of LIF and OSM in the regulation of various MMPs and TIMPs is still incompletely understood. The aims of this study were to examine the effects of LIF and OSM on MMP-1, MMP-3, and TIMP-1 production. In addition, the capacity of the LIF antagonist, MH35-BD, to block LIF and OSM induced MMP expression was examined. Primary chondrocytes, isolated from porcine metacarpophalangeal cartilage, were cultured in the presence and absence of LIF and OSM, with and without a predetermined concentration of the LIF antagonist. We analysed the levels of MMP-1, MMP-3 and TIMP-1 expression using qRT-PCR, Northern blot, and ELISA assays. The results indicate that LIF and OSM increase the expression of MMP-1, MMP-3, and TIMP-1 several fold. Furthermore their expression is reduced to basal levels in the presence of the LIF antagonist MH35-BD.
19137064 Interleukin-32 promotes osteoclast differentiation but not osteoclast activation. 2009 BACKGROUND: Interleukin-32 (IL-32) is a newly described cytokine produced after stimulation by IL-2 or IL-18 and IFN-gamma. IL-32 has the typical properties of a pro-inflammatory mediator and although its role in rheumatoid arthritis has been recently reported its effect on the osteoclastogenesis process remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we have shown that IL-32 was a potent modulator of osteoclastogenesis in vitro, whereby it promoted the differentiation of osteoclast precursors into TRAcP+ VNR+ multinucleated cells expressing specific osteoclast markers (up-regulation of NFATc1, OSCAR, Cathepsin K), but it was incapable of inducing the maturation of these multinucleated cells into bone-resorbing cells. The lack of bone resorption in IL-32-treated cultures could in part be explain by the lack of F-actin ring formation by the multinucleated cells generated. Moreover, when IL-32 was added to PBMC cultures maintained with soluble RANKL, although the number of newly generated osteoclast was increased, a significant decrease of the percentage of lacunar resorption was evident suggesting a possible inhibitory effect of this cytokine on osteoclast activation. To determine the mechanism by which IL-32 induces such response, we sought to determine the intracellular pathways activated and the release of soluble mediators in response to IL-32. Our results indicated that compared to RANKL, IL-32 induced a massive activation of ERK1/2 and Akt. Moreover, IL-32 was also capable of stimulating the release of IL-4 and IFN-gamma, two known inhibitors of osteoclast formation and activation. CONCLUSIONS/SIGNIFICANCE: This is the first in vitro report on the complex role of IL-32 on osteoclast precursors. Further clarification on the exact role of IL-32 in vivo is required prior to the development of any potential therapeutic approach.
18564343 Increased proportion of CD56bright natural killer cells in active and inactive systemic lu 2009 Jan Natural killer (NK) cells belong to the innate immune system but can also affect adaptive immune reactions. This immune regulatory function is often ascribed to the CD56(bright) subpopulation of NK cells that is prevalent in secondary lymphoid tissues and has potent cytokine-producing ability. The NK cells have been described as affecting autoimmune disease and stimulating B-cell production of antibodies, but their role in systemic lupus erythematosus (SLE) pathology has not been extensively studied. We have studied NK cells in SLE, a B-cell-driven systemic autoimmune disease, and phenotypically characterized peripheral blood NK cells in comparison to NK cells from patients with immunoglobulin A nephritis, rheumatoid arthritis and healthy individuals. We have found an increased proportion of CD56(bright) NK cells in SLE, regardless of disease activity. We detected a somewhat increased expression of the activating receptor NKp46/CD335 on NK cells from SLE patients, although neither the percentage of NK cells of all lymphocytes nor the expression of other NK receptors analysed (LIR-1/CD85j, CD94, NKG2C/CD159c, NKG2D/CD314, NKp30/CD337, NKp44/CD336, CD69) differed between patient groups. We show that type I interferon, a proinflammatory cytokine known to be abundant in SLE, can cause increases of CD56(bright) NK cells in vitro. We confirmed that serum levels of interferon-alpha were increased in active, but not in inactive, disease in the SLE patient group. In conclusion, we found an increased proportion of CD56(bright) NK cells in the blood of SLE patients, although it remains to be examined whether and how this relates to the disease process.
19707721 Human complement activation by smooth and rough Proteus mirabilis lipopolysaccharides. 2009 Sep INTRODUCTION: Proteus mirabilis bacilli play an important role in human urinary tract infections, bacteremia, and rheumatoid arthritis. The authors previously studied human complement C3 conversion by smooth-form P. mirabilis O10, O23, O30, and O43 lipopolysaccharides (LPSs) and showed that smooth Proteus LPSs fragmented C3 in a dose- and time-dependent manner. In the present study, one smooth P. mirabilis S1959 and its two polysaccharide-truncated LPSs isolated from an R mutant strain were used to study the C3 conversion. MATERIALS AND METHODS: The conversion of C3 to C3c by smooth and rough P. mirabilis LPSs was studied by capture ELISA and crossed immunoelectrophoresis. Proteins isolated from the outer membrane were analyzed by discontinuous sodium dodecyl sulfate gel electrophoresis. RESULTS: The smooth P. mirabilis S1959 (O3) strain was resistant to the bactericidal activity of human serum, in contrast to the Ra and Re mutant strains. The presence of an exposed core oligosaccharide in R110 LPS was not sufficient to protect the strain from serum-dependent killing. In addition to LPS structure, the outer-membrane proteins may also play roles in protecting the smooth P. mirabilis S1959 (O3) strain from the bactericidal action of serum. It was shown that the Ra P. mirabilis R110 and the Re P. mirabilis R45 mutants possess very different OMP compositions from that of the P. mirabilis S 1959 strain. CONCLUSION: Regardless of the complement resistance of the P. mirabilis strains, the S1959, R110, and R45 LPSs fragmented C3 and induced C3c neo-antigen exposure. The use of complement-deficient human serum allows the conclusion that the Re-type P. mirabilis R45 LPS fragmented C3 by the antibody-independent classical pathway.
19703281 Integrative modeling of transcriptional regulation in response to antirheumatic therapy. 2009 Aug 24 BACKGROUND: The investigation of gene regulatory networks is an important issue in molecular systems biology and significant progress has been made by combining different types of biological data. The purpose of this study was to characterize the transcriptional program induced by etanercept therapy in patients with rheumatoid arthritis (RA). Etanercept is known to reduce disease symptoms and progression in RA, but the underlying molecular mechanisms have not been fully elucidated. RESULTS: Using a DNA microarray dataset providing genome-wide expression profiles of 19 RA patients within the first week of therapy we identified significant transcriptional changes in 83 genes. Most of these genes are known to control the human body's immune response. A novel algorithm called TILAR was then applied to construct a linear network model of the genes' regulatory interactions. The inference method derives a model from the data based on the Least Angle Regression while incorporating DNA-binding site information. As a result we obtained a scale-free network that exhibits a self-regulating and highly parallel architecture, and reflects the pleiotropic immunological role of the therapeutic target TNF-alpha. Moreover, we could show that our integrative modeling strategy performs much better than algorithms using gene expression data alone. CONCLUSION: We present TILAR, a method to deduce gene regulatory interactions from gene expression data by integrating information on transcription factor binding sites. The inferred network uncovers gene regulatory effects in response to etanercept and thus provides useful hypotheses about the drug's mechanisms of action.
19433409 Overproduced interleukin 6 decreases blood lipid levels via upregulation of very-low-densi 2010 Apr BACKGROUND: Interleukin 6 (IL6) blockade raises blood lipid levels in patients with rheumatoid arthritis. OBJECTIVE: To examine the influence of IL6 on lipid metabolism. METHODS: Vascular smooth muscle cells (VSMC) were cultured in the presence of IL6, soluble IL6 receptor (sIL6R), IL6+sIL6R or tumour necrosis factor alpha (TNFalpha) for 24 h. After culture, the expression of very-low-density lipoprotein receptor (VLDLR), low-density lipoprotein receptor (LDLR) and low-density lipoprotein-related protein-1 (LRP-1) were measured by real-time PCR. Human IL6 was injected into mice twice a day for 2 weeks and then VLDLR expression in several tissues and the change of total cholesterol (TC) and triglyceride (TG) levels were investigated. Finally, the effect of anti-IL6 receptor (IL6R) antibody injection on blood lipid levels was examined. RESULTS: IL6+sIL6R significantly induced expression of VLDLR mRNA in VSMC (8.6-fold, p<0.05), but IL6 or sIL6R alone and TNFalpha did not do so. None of these cytokines induced LDLR and LRP-1 mRNA expression. IL6 injection into mice increased the expression of VLDLR in heart, adipose tissue and liver and decreased TC and TG levels. The injection of anti-IL6R antibody normalised the reduced levels of TC and TG caused by IL6 injection, whereas it had no influence on the levels of TC and TG in normal mice. CONCLUSIONS: Overproduced IL6 decreased blood lipid levels by increasing VLDLR expression in several tissues. It is concluded that IL6 blockade normalises reduced lipid levels caused by IL6, but does not affect normal lipid metabolism.
20530046 The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET c 2010 Nov Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB). Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-γ release assays or, as an alternative in individuals without a history of bacille Calmette-Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis. Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test and an interferon-γ release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistent M. tuberculosis-specific immune responses undergoing TNF antagonist therapy as it significantly reduces the risk of progression to TB. This TBNET consensus statement summarises current knowledge and expert opinions and provides evidence-based recommendations to reduce the TB risk among candidates for TNF antagonist therapy.
20488620 Development and validation of the Fibromyalgia Rapid Screening Tool (FiRST). 2010 Aug The goal of this study was to develop and validate a self-completed questionnaire, the Fibromyalgia Rapid Screening Tool (FiRST), for the detection of fibromyalgia syndrome in patients with diffuse chronic pain. Items requiring "yes/no" responses and relating to the most relevant clinical characteristics of fibromyalgia were compiled by a group of rheumatologists and pain experts. The provisional questionnaire was tested in a prospective multicenter study of 162 patients with chronic pain due to fibromyalgia (according to ACR criteria) (n=92) compared with a group of patients with chronic diffuse pain due to other rheumatic conditions, including rheumatoid arthritis (n=32), ankylosing spondylitis (n=25) and osteoarthritis (n=13). Identification of the most discriminant combinations of items for fibromyalgia and the calculation of their sensitivity and specificity were based on both univariate and multivariate (stepwise logistic regression) analyses. The assessment of the psychometric properties of the questionnaire also dealt with face validity, content validity, test-retest reliability and convergent/divergent validity. Based on univariate and multivariate analyses, we retained only six items in the final version of FiRST. These items were used to calculate the sensitivity, specificity and predictive accuracy of the questionnaire. A cut-off score of 5 (corresponding to the number of positive items) gave the highest rate of correct identification of patients (87.9%), with a sensitivity of 90.5% and a specificity of 85.7%. In conclusion, FiRST is a brief, simple and straightforward self-administered questionnaire with excellent discriminative value, of potential value for the detection of fibromyalgia in both daily practice and clinical research.
20486378 [A review of diagnosis and causes of synovial cyst of the hip joint]. 2010 Apr OBJECTIVE: To analyze the clinical and radiological characteristics of hip joint synovial cyst, and to study the main causes and the early economical effective ways for diagnosis. METHODS: Twenty-five patients with hip joint synovial cyst were studied in this research, including 16 males and 9 females aged from 14 to 76 with an average age of 52.8 years old (4 cases from clinical treatment from 1999 to 2007; 1 case searched with keyword "synovial cyst" and "hip" on CNKI form 1978 to 2002, 20 cases searched with keyword synovial cyst and hip on the Medline. The clinical manifestation of 25 cases were painless mass at medial of groin middle point and lower limb venous insufficiency. Synovial cysts of the hip joint were diagnosed by ultrasonography, computer tomography (CT) or nuclear magnetic resonance (MRI). All cases were analyzed retrospectively on the cause of a diseace, clinical features and radiological examinations. RESULTS: The possible causes of this disease included rheumatoid arthritis in 8 cases, osteoarthritis in 1, total hip replacement in 3, hip tramatic in 3, femoral head necrosis in 2 and unknown origin in 9. The main clinical features included painless groin mass in 9 cases; compression of the common femoral and external iliac veins (lead to outflow obstruction and leg swelling) in 7 cases; inguinal swelling in 5 cases; deep vein thrombosis (DVT) in 3 cases; compression of artery in 1 case. The correct preoperative diagnosis were made by ultrasonography or combined with colour duplex Doppler ultrasonography (CDDS) in 13 cases; CDDS combined with CT in 8 cases; CDDS combined with CT and MRI in 2 cases; articular cavity visualization in 1 case; puncture herniography in 1 case. CONCLUSION: The hip joint synovial cyst is mainly caused by the chronic inflammation of the hip joint. As the disease is extremely rare and asymptomatically, precise diagnoses are difficult and and often delayed. More attentions should be paid because of its severe complications. CDDS is an economical effective way for early diagnosis.
20465571 Proviral integration site 2 is required for interleukin-6 expression induced by interleuki 2010 Oct PIM (proviral integration site) kinases are a distinct class of serine/threonine-specific kinases consisting of PIM1, PIM2 and PIM3. PIM2 is known to function in apoptosis pathways. Expression of PIM2 is highly induced by pro-inflammatory stimuli but the role of PIM2 in the expression of pro-inflammatory cytokines is unclear. In this study, we showed that over-expression of PIM2 in HeLa cells as well as in human umbilical vein endothelial cells enhanced interleukin-1β (IL-1β) -induced and tumour necrosis factor-α-induced IL-6 expression, whereas over-expression of a kinase-dead PIM2 mutant had the opposite effect. Studies with small interfering RNA specific to PIM2 further confirmed that IL-6 expression in HeLa cells requires PIM2. To investigate the function of PIM2 further, we generated PIM2-deficient mice. It was found that IL-6 production was significantly decreased from PIM2-deficient spleen cells after stimulation with lipopolysaccharide. Taken together, we demonstrated an important function of PIM2 in controlling the expression of the pro-inflammatory cytokine IL-6. PIM2 inhibitors may be beneficial for IL-6-mediated diseases such as rheumatoid arthritis.
20463037 Autoimmune diseases prior to the diagnosis of multiple sclerosis: a population-based case- 2010 Jul The objective of this study was to determine whether patients with multiple sclerosis (MS) are more likely to have other autoimmune disorders particularly prior to the diagnosis of MS. We conducted a population-based case-control study of patients enrolled in the Northern California Kaiser Permanente Medical Care Program. Electronic clinical records through 2005 were used to ascertain incident and prevalent MS cases and identify the presence and timing of 44 other diagnoses. Controls were matched 5:1 for gender, age, and Kaiser membership characteristics. We identified 5296 MS cases (including 924 diagnosed between 2001 and 2004) and 26,478 matched controls. Prior to MS diagnosis, cases were more likely than controls to have uveitis (OR = 3.2, 95%; CI 1.7-5.7), inflammatory bowel disease (IBD, OR = 1.7; 95%CI 1.2-2.5), and Bell's palsy (OR = 3.2; 95%CI 1.2-8.3). Cases were also more likely to develop Guillain- Barré syndrome (GBS, OR = 5.0; 95%CI 1.6-15.4) and bullous pemphigoid (OR = 6.7; 95%CI 1.5-29.9). Cases were not more likely than controls to have or to develop rheumatoid arthritis, lupus or thyroiditis. MS may share environmental triggers, genetic susceptibilities and/or alterations in immune homeostasis with IBD and uveitis, but not with other autoimmune disorders.