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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
18314145 [Disappearance of retro-odontoid pseudotumor after C1-C2 transarticular fixation screw]. 2008 Feb Atlantoaxial degenerative articular cysts are described in various situations like rheumatoid arthritis, dialysis, and fractures... and in the C1-C2 subluxations of degenerative origin. The treatment of these retro-odontoid tumors does not consist in excision of the pseudotumor but in the reduction of instability by cervical fusion. The procedures are varied and comprise neurological and vascular risks. We report a case of C1-C2 subluxation associated with a pseudocyst compressing the cervical spinal cord, which was treated successfully by transarticular screwing without wiring procedure. This technique has never been used previously in this indication. However, the peroperational risks are less important and the results are similar to those of the other procedures.
18005267 Gene expression and pathway analysis of immune thrombocytopenic purpura. 2008 Jan A global expression profile of peripheral blood from patients with immune thrombocytopenic purpura (ITP) was performed that identified an ITP-specific signature, which also included interferon (IFN)-induced genes. Several genes correlated with ITP have been shown to be associated with expression signatures in systemic lupus erythematosis and rheumatoid arthritis, indicating an overlap with other autoimmune disorders. Pathway analysis demonstrated that IFN signalling, death receptor and protein ubiquitination pathways were associated with ITP. These results provide the first glimpse of the genes and pathways consistently aberrant in ITP, identifying new targets for investigations of pathogenesis and treatment of ITP.
17017973 New treatment options using 5-HT3 receptor antagonists in rheumatic diseases. 2006 In vitro studies have shown that a blockade of 5-HT3 receptors brings about a reduction of tumor necrosis factor, IL-1 beta, IL-2, IL-6 as well as a decrease in prostaglandins. Clinical trials have provided evidence of pain reduction in a subgroup of fibromyalgia syndrome and, moreover, have demonstrated that tropisetron injected locally for insertion tendinoses and myofascial syndromes with associated trigger points leads to an alleviation of pain that is comparable to injections with the combination of corticosteroids and local anesthetics. The effects achieved by intra-articular injections in cases of osteoarthritis and rheumatoid arthritis paralleled those exerted by intraarticular injection of corticosteroids. In addition, the positive effects produced by systemically administered tropisetron on scleroderma need to be considered since they suggest that this therapeutic principle can also be applied systemically in immunologic processes.
18803034 The role of inflammation, humoral and cell mediated autoimmunity in the pathogenesis of at 2008 Sep 20 The pathogenesis of atherosclerosis has not been well defined and many questions remain unanswered. Many studies have discussed the importance of inflammation as the first step in promoting endothelial dysfunction and atherosclerosis.The association of inflammatory markers such as fibrinogen and C reactive protein (CRP) with atherosclerosis and cardiovascular/cerebrovascular clinical events reinforces the pivotal role that inflammation plays in the atherosclerotic process.The humoral and cellular autoimmune response against antigens expressed in the endothelium and the greater prevalence of atherosclerosis in immune-mediated rheumatic diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) strongly suggest the involvement of autoimmunity in the atherosclerotic process. The role of inflammation and autoimmune responses in atherosclerosis are discussed in order to better understand their close link on its pathogenesis.
18604982 C-jun: pharmaceutical target for DNAzyme therapy of multiple pathologies. 2008 Jun Recent studies have demonstrated the potential of DNAzymes for therapy of various diseases via mRNA target-specific cleavage. One such target, the basic region-leucine zipper protein c-Jun, has been targeted and efficacy seen in such pathologies as cancer, ocular neovascularisation, arterial thickening, acute inflammation, and rheumatoid arthritis. This review discusses these cases in turn, and presents some new data on the applicability of a c-jun DNAzyme against a panel of cancer cells. Importantly, downregulation of c-jun is noted to cause apoptotic death of cancer cells. These studies collectively demonstrate the potential of this DNAzyme as a lead candidate for DNAzyme therapeutics.
18583356 Citrullinated fibrinogen inhibits thrombin-catalysed fibrin polymerization. 2008 Sep Citrullination is the post-translational modification of arginine residues by peptidylarginine deiminases (PADIs). Fibrinogen is one substrate of PADIs under physiological conditions. Fibrinogen is an important factor for blood coagulation and inducing inflammation. The citrullinated form of fibrinogen appears in rheumatoid arthritis synovial tissue together with the production of autoantibodies that target self-peptides containing citrulline. However, whether the function of fibrinogen changes after citrullination remains unclear. We found that citrullinated fibrinogen markedly impairs the function of thrombin-catalysed fibrin polymerization and also inhibits fibrin formation. Increased citrullinated fibrinogen might thus affect the balance between coagulation and fibrinolysis and alter antigenicity under physiological conditions. These data suggest that citrullination of proteins could physiologically change functions and subsequently generate pro-inflammatory conditions and autoimmune reactions.
17848800 [Fasting as part of a naturopathic treatment approach for polymyalgia rheumatica]. 2007 Aug A 67-year-old woman with proven diagnosis of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) was admitted to stationary treatment twice to receive a complex therapy with methods of natural medicine comprising fasting as its main treatment element. Both times, a discrepancy between the course of markers of the acute phase on the one hand, and subjective as well as objective clinical outcome on the other hand could be observed. This may point to special conditions of this chronic inflammatory disease as compared to e.g.rheumatoid arthritis, but also to specific problems in assessing possible effects of the treatments chosen, particularly fasting therapy, as compared to effects of conventional therapies.
17433490 Heart disease in psoriasis. 2007 Aug Psoriasis has been traditionally viewed as an inflammatory skin disorder of unknown origin. Recent advances in the immunopathogenesis and genetics of psoriasis have broadened our understanding of psoriasis. Psoriasis is now considered a systemic inflammatory condition analogous to other inflammatory immune disorders. Patients with other immune disorders, such as systemic lupus erythematosus or rheumatoid arthritis, are known to be at increased risk of heart disease. Similarly, patients with psoriasis may carry an excess risk of heart disease, which would represent an important previously unrecognized cause of morbidity and mortality. This review summarizes the current evidence for an increased cardiovascular risk in patients with psoriasis and outlines deficits in our knowledge in this area.
18677043 [Daily practice using guidelines for prevention and treatment of osteoporosis. Risk factor 2008 Aug In 2006, a set of guidelines was released in Japan regarding the initiation of medical treatment to prevent fragility fracture with risk factors considered. In February this year, a WHO working group announced the development of the Fracture Risk Assessment Tool (FRAX), which estimates fracture risk based on age, sex, bone density at the femoral neck (body mass index if bone density is not available), previous fragility fracture in adulthood, parental fracture history at the femoral neck, current smoking, steroid use, secondary osteoporosis/rheumatoid arthritis, and alcohol consumption. And then, the NOF released guidelines incorporating FRAX in the US. WHO recommends that the threshold of medical treatment should be set based on each country's medical circumstances and healthcare economic situation.
18510911 Giant cell tumor of the EDL tendon sheath: an unusual cause of hallux valgus. 2008 May Hallux valgus is a lateral deviation of the proximal phalanx of the first metatarsophalangeal joint. It is a common disorder in adults. The etiologic factors include modern shoes, rheumatoid arthritis, pes planus, metatarsus primus varus, and trauma. Tumors causing hallux valgus deformities are unusual. We report a 50-year-old female with a hallux valgus deformity caused by a giant cell tumor of the second EDL tendon sheath. Surgical excision of the tumor and corrective osteotomy produced a permanent cure. This unusual cause of a hallux valgus deformity should increase awareness of tumors as a possible cause of foot deformities.
18473018 Targeting CD22 as a strategy for treating systemic autoimmune diseases. 2007 Oct B-cells play an important role in the diagnosis and to some extent the pathogenesis of many autoimmune diseases. Specific B-cell directed antibodies are now gaining an increasing role in the management of these diseases. The first antibody target in this regard was CD20, with the development and introduction of rituximab in the management of B-cell malignancies as well as rheumatoid arthritis. A second candidate target is CD22, and the first antagonistic antibody to this B-cell marker is epratuzumab, which appears to function, in contrast to CD20 antibodies, more by modulation of B-cells than by their depletion capacity. Originally developed for the treatment of non-Hodgkin lymphoma, epratuzumab has now been reported to be effective, with a very good safety profile, in two prototype autoimmune diseases, systemic lupus erythematosus and primary Sjögren's syndrome. As such, this new investigational antibody may provide distinct therapeutic effects and may be complementary to the known effects and role of CD20 antibodies.
17884336 Autoimmunity and pathophysiology. 2007 Dec Several matters concerning the term "Autoimmunity" have arisen the last two decades. Most researchers agree that a degree of natural autoimmunity in the absence of disease is needed for the development of effective immune responses against infectious agents or cancer cells. Individuals, however, with suitable genetic background and after exposure to certain environmental triggers (such as UV radiation, bacteria, viruses, etc) may develop an exaggerated immune response against self leading to the development of several autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus etc. In this context, a the meeting on "Autoimmunity: Physiological and Pathophysiological Aspects" was held on May in Athens, Greece aiming to bring together and discuss different points of view of the principal investigators that have contributed in the development of this field during the last years. Several aspects of both natural and pathological autoimmunity as well as the possible links between these two states are presented by leading authorities of the field in this special issue.
17650738 Cognitive-behavioral interventions in rheumatic diseases. 2007 Jan Rheumatic diseases, like many other chronic diseases, represent an important public health burden. To reduce the social and economic impact of these pathologies, an appropriate management of these conditions should be encouraged based on the use of established intervention strategies. The aim of this article is to describe the content of Cognitive-Behavioural Therapies (CBTs) for patients with rheumatic diseases aimed at managing pain, disability and quality of life. These interventions involve education, training in various types of relaxation approaches and other coping skills, and the application of these skills in the patient's home and work environment. CBT include the teaching of life and coping skills that can assist the patient in productive problem solving and prevention or minimization of future pain episodes and stressful events. Moreover, several studies suggest that the cognitive-behavioural approach is efficacious in rheumatoid arthritis, osteoarthritis and fibromyalgia in improving not only the psychological adjustment during the course of the disease but also physical function.
17409008 Tumor necrosis factor is critical to control tuberculosis infection. 2007 Apr Tumor necrosis factor (TNF) is critical and non-redundant to control Mycobacterium tuberculosis infection and cannot be replaced by other proinflammatory cytokines. Overproduction of TNF may cause immunopathology, while TNF neutralization reactivates latent and chronic, controlled infection, which is relevant for the use of neutralizing TNF therapies in patients with rheumatoid arthritis.
17212914 Return-to-play decisions after cervical spine injuries. 2007 Jan This article summarizes the current evidence and expert opinion on making return-to-play decisions after cervical spine injuries. Injuries discussed include fractures, central cord neuropraxia, stringers, disc herniations, strains, sprains, and instability. Each of these injuries may be complicated by coexistence of other conditions making return-to-play decisions more complicated. The congenital, developmental, and disease processes discussed include spear tackler's spine, congenital and developmental stenosis, Klippel-Feil syndrome, odontoid abnormalities, rheumatoid arthritis, spina bifida, and Arnold-Chiari malformations. Postsurgical considerations are also discussed. This review represents an abundant amount of expert opinion that was overwhelmingly based on case series, case reports, and biomechanical studies to support the return-to-play guidelines.
16609823 The burden of musculoskeletal disease--a global perspective. 2006 Nov Musculoskeletal diseases are one of the major causes of disability around the world and have been a significant reason for the development of the Bone and Joint Decade. Rheumatoid arthritis, osteoarthritis and back pain are important causes of disability-adjusted-life years in both the developed and developing world. COPCORD studies in over 17 countries around the world have identified back and knee pain as common in the community and are likely to increase with the ageing population. Musculoskeletal conditions are an enormous cost to the community in economic terms, and these figures emphasise how governments need to invest in the future and look at ways of reducing the burden of musculoskeletal diseases by encouraging exercise and obesity prevention campaigns.
18952160 Anti-inflammatory effects of Z23 on LPS-induced inflammatory responses in RAW264.7 macroph 2008 Dec 8 AIM OF THE STUDY: Fissistigma oldhamii (Hemsl.) Merr, a traditional Chinese herb medicine, is used for treating rheumatoid arthritis in China. In our previous study, an effective compound, 7'-(3',4'-dihydroxyphenyl)-N-[(4-methoxyphenyl) ethyl] propenamide (Z23), from this herb has showed potent immunosuppressive effects both in vitro and in vivo. However, its anti-inflammatory effect and mechanism is still need to explore. MATERIALS AND METHODS: We examined the in vitro effects of Z23 on the production of nitric oxide (NO), prostaglandin E2 (PGE2) and cytokines by lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. RESULTS: Z23 significantly decreased the production of PGE2, NO, tumour necrosis factor alpha (TNFalpha) and IL6 production. Inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX2) gene expression were also significantly reduced. CONCLUSIONS: These results demonstrated that Z23 exerted an anti-inflammatory effect through modulating the synthesis of several mediators and cytokines involved in the inflammatory process. This study provided evidence to understand the therapeutic effects of Fissistigma oldhamii (Hemsl.) Merr and indicated that Z23 has the potential for treatment of various inflammatory diseases where the overproduction of NO, PGE2 and inflammatory cytokines has been shown to play a role, e.g. rheumatoid arthritis.
19088893 Rituximab for refractory rheumatoid arthritis: a 24-week open-label prospective study. 2007 OBJECTIVES: To study the efficacy of rituximab in active rheumatoid arthritis (RA) patients refractory to disease modifying anti-rheumatic drugs (DMARDs) including the tumor necrosis factor (TNF)-alpha antagonists. METHODS: Adult patients with active RA despite adequate therapies with conventional DMARDs or anti-TNFalpha agents for at least 3 months were recruited. Inclusion criteria were: (1) Positive RF / anti-CCP; (2) >/= 6 swollen joints and >/= 8 tender joints; (3) ESR >/= 28 mm/hr or CRP >/= 10 mg/L. Eligible patients were given intravenous rituximab infusions at a dose of 1000 mg on days 1 and 15. Assessment was performed 4-weekly thereafter and included tender joint counts (TJC), swollen joint counts (SJC), physician's and patient's global assessment, patient's pain assessment (VAS 0-100 mm), disability index (HAQ-DI), quality of life (SF36), fatigue score (FACIT-F), ESR and CRP. The DAS28, EULAR and ACR responses at week 24 were evaluated. RESULTS: 10 patients (8 women and 2 men) were studied (mean age: 49 years; mean RA duration 7.4 years). Baseline TJC and SJC were 25.1 +/- 13.2 and 12.8 +/- 5.4 respectively. The mean DAS28 score was 7.1 +/- 0.7, and the mean CRP and ESR levels were 52.3 +/- 60 mg/L and 95.8 +/- 32 mm/hr, respectively. The median number of failed DMARDs was 4 and two patients had failed anti-TNFalpha treatment. At week 24, there was a significant drop in TJC, SJC, ESR and CRP. The HAQ-DI score also decreased from 2.1 to 1.7 (p=0.04) while the total SF-36 score improved from 24.8 to 38.3 (p=0.008). Sixty percent of patients achieved EULAR moderate-to-good response. Half of the patients achieved ACR20 and two achieved ACR50 / 70 response. Only one patient experienced a minor infusion reaction. CONCLUSIONS: Rituximab is effective and well tolerated in patients with refractory RA.
19033291 Multinational evidence-based recommendations for the use of methotrexate in rheumatic diso 2009 Jul OBJECTIVES: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. METHODS: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007-8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. CONCLUSIONS: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.
17034761 Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of 2006 Dec 1 Toll-like receptors (TLRs), which are activated by invading microorganisms or endogenous molecules, evoke immune and inflammatory responses. TLR activation is closely linked to the development of many chronic inflammatory diseases including rheumatoid arthritis. Auranofin, an Au(I) compound, is a well-known and long-used anti-rheumatic drug. However, the mechanism as to how auranofin relieves the symptom of rheumatoid arthritis has not been fully clarified. Our results demonstrated that auranofin suppressed TLR4-mediated activation of transcription factors, NF-kappaB and IRF3, and expression of COX-2, a pro-inflammatory enzyme. This suppression was well correlated with the inhibitory effect of auranofin on the homodimerization of TLR4 induced by an agonist. Furthermore, auranofin inhibited NF-kappaB activation induced by MyD88-dependent downstream signaling components of TLR4, MyD88, IKKbeta, and p65. IRF3 activation induced by MyD88-independent signaling components, TRIF and TBK1, was also downregulated by auranofin. Our results first demonstrate that auranofin suppresses the multiple steps in TLR4 signaling, especially the homodimerization of TLR4. The results suggest that the suppression of TLR4 activity by auranofin may be the molecular mechanism through which auranofin exerts anti-rheumatic activity.