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

ID PMID Title PublicationDate abstract
15340228 Suppressive effect of Kanzo-bushi-to, a Kampo medicine, on collagen-induced arthritis. 2004 Sep Kanzo-bushi-to (KBT) is a traditional Japanese herbal medicine (Kampo medicine), which is used in Japan to treat rheumatoid arthritis. In the present study, we investigated the suppressive effect of KBT on collagen-induced arthritis (CIA) and further studied the underlying mechanism. CIA was induced in male DBA/1J mice by immunization with bovine type II collagen, followed by a booster injection 21 d later. KBT was given at a dose of 430 mg/kg/d from three days before the first immunization to the end of the experiment. KBT suppressed CIA development effectively and further protected focal bone erosion and bone destruction as evidenced by the reduced histological score. Histochemical examination revealed that KBT decreased TRAP-positive cells at the synovium-bone interface and at the sites of focal bone erosion, coincident with the findings that RANKL/OPG mRNA ratio was significantly reduced by KBT treatment. KBT also decreased mRNA levels of M-CSF and iNOS in joints and of iNOS in peritoneal macrophages. In conclusion, KBT prevented osteoclast generation by decreasing RANKL/OPG ratio and M-CSF mRNA levels, resulting in reduction in bone erosion and destruction. In addition, KBT has anti-inflammatory effect such as the suppression of iNOS expression in peritoneal macrophages and joints of CIA mice. These finding suggests that KBT is a potential new therapeutic agent for the treatment of RA.
14579159 Gout in systemic lupus erythematosus and overlap syndrome - a hospital-based study. 2003 Oct The negative association between gout and rheumatoid arthritis is widely accepted, and gout is also speculated to be rare in systemic lupus erythematosus (SLE), as only a few sporadic cases have been reported. From 1985 to 2001 we encountered 15 lupus patients at Chang-Gung Memorial Hospital, including two with lupus-scleroderma and one with lupus-scleroderma-polymyositis overlap syndrome coexisting with gout. This study retrospectively analyses the clinical and laboratory characteristics of these patients. A lower female predominance is found, and most patients developed gout after the onset of SLE, although gout preceded SLE in two cases. Measurement of serum uric acid and 24-h urine uric acid found all of the patients to be hyperuricaemic and underexcretors of uric acid. Furthermore, most of the patients (14/15) were receiving diuretics. Also, many had hypertension and serious cardiovascular diseases. Renal impairment during gouty attacks seemed to be a predisposing factor for developing end-stage renal disease. Gouty arthritis usually occurred during relative SLE inactivity, podagra was frequent, and tophi were found in a few patients. Compared with the unselected population of SLE patients, the cases studied here had a higher incidence of chronic arthritis, malar rash, haematologic disorder, photosensitivity, serositis and neurologic disorder. Renal disease in the patients sampled was frequently membranous nephropathy.
12792223 A lupus-like syndrome associated with infliximab therapy. 2003 May Infliximab, a chimeric monoclonal antibody targeting tumor necrosis factor alpha (TNF-alpha), is efficacious in the treatment of rheumatoid arthritis and Crohn's disease. We report in detail an unusual adverse reaction to infliximab therapy, a drug-induced lupus-like clinical syndrome. A 45-year-old woman with steroid-dependent Crohn's colitis, successfully managed with maintenance infliximab infusions and methotrexate, developed a lupus-like syndrome eight months after her initial infusion. This was characterized by inflammatory arthritis and an urticarial and papulosquamous rash and was accompanied by high titers of antinuclear, double-stranded DNA, glomerular-binding, and histone antibodies and by reduced levels of the C4 component of complement. After discontinuance of infliximab infusions and treatment of symptoms with intermittent courses of prednisone, the patient's arthritis progressively improved, with accompanying decrements in autoantibody titers. One year later, she has minimal joint discomfort and no rash or gastrointestinal symptoms despite also discontinuing prednisone and methotrexate. Infliximab therapy may cause a lupus-like syndrome that is reversible upon discontinuing this agent. These findings support recent evidence identifying TNF-alpha as an inhibitor of autoantibody formation.
12718749 Aggrecanases and cartilage matrix degradation. 2003 The loss of extracellular matrix macromolecules from the cartilage results in serious impairment of joint function. Metalloproteinases called 'aggrecanases' that cleave the Glu373-Ala374 bond of the aggrecan core protein play a key role in the early stages of cartilage destruction in rheumatoid arthritis and in osteoarthritis. Three members of the ADAMTS family of proteinases, ADAMTS-1, ADAMTS-4 and ADAMTS-5, have been identified as aggrecanases. Matrix metalloproteinases, which are also found in arthritic joints, cleave aggrecans, but at a distinct site from the aggrecanases (i.e. Asn341-Phe342). The present review discuss the enzymatic properties of the three known aggrecanases, the regulation of their activities, and their role in cartilage matrix breakdown during the development of arthritis in relation to the action of matrix metalloproteinases.
15377173 Current concepts in the therapy of the spondyloarthritides. 2004 Recent success in the treatment of patients with the more severe forms of spondyloarthritides (SpA) has dramatically changed old paradigms. There is evidence that anti-tumor necrosis factor (TNF)-alpha therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis. Based on recent data on more than 1000 patients with AS and psoriatic arthritis, this treatment seems to be even more effective than in rheumatoid arthritis (RA). The currently available anti-TNFalpha agents, infliximab, etanercept, and adalimumab, are approved for the treatment of RA in the US and in Europe. TNFalpha blockers may even be considered as a first-line treatment in patients with active AS whose condition is not sufficiently controlled with NSAIDs, as in the case of axial disease. There is preliminary evidence that both agents also work in other SpA, such as undifferentiated SpA. There is hope that ankylosis may be preventable, but it remains to be shown whether patients benefit from long-term anti-TNFalpha therapy and whether radiologic progression and ankylosis can be stopped. Furthermore, it seems that anti-TNFalpha therapy can also improve clinical manifestations of other inflammatory spinal disorders, such as sciatica and back pain caused by disc herniation, or possibly even intermittent inflammatory states of degenerative disc disease. Severe adverse events from treatment with anti-TNFalpha continue to be rare. Tuberculosis can be largely prevented by appropriate screening. As it stands now, the benefits of anti-TNFalpha therapy in AS seem to outweigh the shortcomings.
15110958 [Light chain multiple myeloma revealed by an amyloid arthropathy. A report of two cases]. 2004 May INTRODUCTION: Amyloid arthropathy occurs in 5-15% of patients with multiple myeloma. It is rarely inaugural. Some cases are reported in which the articular manifestations are present many months before the diagnosis of myeloma. We report two unusual cases where the amyloid arthropathy reveals the multiple myeloma. EXEGESIS: Case 1: A 54-year-old man take medical advice for a polyarthritis evolving for 6 months. He has no evidence of multiple myeloma except a hypercalcemia and a hypoalbuminemia. The diagnosis of multiple myeloma is based on an immunobinding of plasmatic proteins. It is a light chain multiple myeloma, lambda type. Amylosis is revealed by biopsy specimens from the synovial tissue of the knee. The patient died rapidly because of an intestinal hemorrhage. Case 2: A 78-year-old woman complains from a polyarthritis evolving for 4 months. She has besides an elevated erythrocyte sedimentation rate, an anemia and a renal insufficiency, a profound hypogammaglobulinemia. There is no radiological abnormalities. The diagnosis of multiple myeloma is based on serum and urine immunoelectrophoresis. It is a light chain multiple myeloma, lambda type. The patient is at her sixth monthly course of cyclophosphamid and prednisone. As far as amyloid arthropathy is concerned, it is relatively improved by corticoid intra-articular injections. CONCLUSION: These are two case reports of a light chain multiple myeloma of lambda type, associated to an amyloid arthropathy in its polyarticular presentation, mimicking a rheumatoïd arthritis. The revelatory nature of the amyloid arthropathy is interesting to report.
12716445 COX-2: Where are we in 2003? - Be strong and resolute: continue to use COX-2 selective inh 2003 Cyclooxygenase (COX)-2 selective inhibitors have been shown to have comparable efficacy to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Large outcome studies have shown that patients with OA and RA not taking low-dose aspirin have fewer symptomatic and complicated upper GI events when treated with COX-2 selective inhibitors than with nonselective NSAIDs. When used in recommended dosages, there is no convincing evidence that patients treated with COX-2 selective inhibitors have an increased incidence of cardiovascular thrombotic events, including non-fatal myocardial infarction, than patients treated with either placebo or nonselective NSAIDs other than naproxen. Co-therapy with low-dose aspirin is recommended in patients with OA and RA at increased risk for cardiovascular events; the need for gastroprotective therapy in such patients is controversial.
12753504 Comparison of immunoglobulin heavy chain rearrangements between peripheral and glandular B 2003 May Myoepithelial sialadenitis (MESA) of the major salivary glands is a characteristic feature of primary Sjögren's syndrome (pSS). To delineate systemic and organ-specific influences on B cells in a patient with pSS and benign MESA, individual B cells were simultaneously obtained from the peripheral blood and inflamed parotid gland. Immunoglobulin variable heavy chain (VH) rearrangements in single sorted CD19+ B cells were subsequently amplified, sequenced and analysed. Despite the presence of two clonal expansions using VH1-08 and VH2-70 segments, respectively, the majority of glandular B cells were polyclonal, resembling the VH gene usage and mutational pattern of the corresponding blood population. However, striking differences were observed in the proportion of cells expressing mutated VH rearrangements (blood, 28.9% versus parotid, 80.4%; P < 0.0001). Moreover, the glandular productive VH rearrangements differed significantly from their blood counterparts by a higher mutational frequency (P < 0.0001), shorter CDR3 lengths (P = 0.001) and a less frequent usage of JH6 (P = 0.0292), indicating an accumulation of memory B cells in the inflamed parotid. Thus, both preferential influx/homing of memory B cells and local proliferation may contribute to the pattern of benign MESA in pSS. Notably, one of the glandular clonal rearrangements (using VH1-08) was also detected in the patient's peripheral repertoire.
12115224 Cyclosporine inhibition of vascular endothelial growth factor production in rheumatoid syn 2002 May OBJECTIVE: To determine the antiangiogenic effect of cyclosporin A (CSA) in rheumatoid arthritis (RA). METHODS: We investigated the effect of CSA on the production of vascular endothelial growth factor (VEGF) by rheumatoid synovial fibroblasts. Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of RA patients, and cultured in the presence of CSA. The production of VEGF by FLS was measured in culture supernatants by enzyme-linked immunosorbent assay. The VEGF messenger RNA (mRNA) expression and activator protein 1 (AP-1) binding activity for VEGF transcription were determined by polymerase chain reaction and electrophoretic mobility shift assay, respectively. RESULTS: CSA dose-dependently inhibited both constitutive and transforming growth factor beta-induced VEGF production at the protein and mRNA levels. The suppressive action of CSA on VEGF synthesis was calcineurin dependent, as evidenced by a comparable inhibition by FK-506. Agonists of cAMP, 3-isobutyl-1-methylxanthine and N-2-O-dibutyryl-cAMP, mimicked the effect of CSA on VEGF production, while a cAMP antagonist, 2',3'-dideoxyadenosine, abrogated the effect of CSA. A gel mobility shift assay showed that the inhibitory effect of CSA was associated with decreased AP-1 binding activity to the VEGF promoter, in a cAMP-dependent manner. CONCLUSION: CSA may exert an antiangiogenic effect by inhibiting AP-1-mediated VEGF expression in rheumatoid synovial fibroblasts.
12931754 Juvenile ankylosing spondylitis with uveitis. 2003 Mar A 17-year-old boy had suffered from right ankle arthralgia when he was 13 years old. He also had bilaterally congested conjunctivas and were erythematous around his right ankle joint. A soft tissue echo showed swelling of the right ankle joint. A Ga 67 scan revealed a focal elevated uptake in the right ankle, but a bone scan was negative. Reactive arthritis was suspected due to conjunctivitis, arthritis and a previous episode of watery diarrhea. An ophthalmologic examination showed no evidence of uveitis. Laboratory data were negative for rheumatoid factor, antinuclear antibody and anti-ds DNA. Erythrocyte sedimentation rate (ESR) was 40 mm/hr and a histocompatibility test was positive for antigen B27. Based on the diagnosis of cellulitis and reactive arthritis, oxacillin and naproxen were given for 14 days. During follow-up at the OPD, bilateral arthralgia of the ankle joints was noted and a sonography showed bilateral edematous ankle joints. Juvenile ankylosing spondylitis (JAS) was suspected. Two years later, he had lower back pain and arthralgia of the knee joints with uveitis of the right eye. He was treated with naproxen and prednisolone. Because few JAS cases initially present as axial arthropathy or enthesopathy and uveitis is uncommon in children, we presented the case with a review of literature and conclusion that the possibility of JAS should be considered in young adolescent boys with arthritis of the lower limbs, enthesitis, a family history of related diseases and positive HLA-B27, as well as negative rheumatoid factor (RF) and anti-nuclear antibody (ANA) results.
12759296 Sonographic training in rheumatology: a self teaching approach. 2003 Jun OBJECTIVE: To evaluate a self teaching approach to be followed by a novice without previous practical experience in musculoskeletal ultrasonography. METHODS: The novice was given short general training (two hours) by an experienced sonographer focusing on the approach to the ultrasound equipment, and asked to obtain the best sonographic images of different anatomical areas as similar as possible to the "gold standard" pictures in the online version of the guidelines for musculoskeletal ultrasonography in rheumatology (free access at http://www.sameint.it/eular/ultrasound). At the end of each scanning session, both novice and tutor scored "blindly" all the images from 0 (the lowest quality) to 10 (the highest quality), with a minimum quality score of 6 considered acceptable for standard clinical use. The tutor then explained how to improve the quality of the pictures. Fourteen consecutive inpatients (seven with rheumatoid arthritis, three with psoriatic arthritis, two with reactive arthritis, and two with osteoarthritis) and five healthy subjects were examined. Ultrasound examinations were performed with a Diasus (Dynamic Imaging Ltd, Livingston, Scotland, UK) using two broadband linear probes of 5-10 and 8-16 MHz frequency. RESULTS: Sonographic training lasted one month and included 30 scanning sessions (24 hours of active scanning). 243 images were taken of the selected anatomical areas. The mean time required to produce each image was 6 minutes (SD 4.2; range 1-30). At the end of the training, the novice scored >/=6 for each standard scan. CONCLUSION: A novice can obtain acceptable sonographic images in 24 non-consecutive hours of active scanning after an intensive self teaching programme.
15450337 Current concepts and review of alefacept in the treatment of psoriasis. 2004 Oct Alefacept is a novel biologic agent that selectively targets the memory T-cell population involved in the pathogenesis of psoriasis. Alefacept, administered by intramuscular (IM)or intravenous (IV) bolus injection, is safe and efficacious and improves quality of life ina broad spectrum of psoriasis patients. Disease remissions last approximately 7 months in responders following either IM or IV administration without further treatment. In clinical studies, treatment of patients with psoriasis with up to six courses of alefacept demonstrates the following: no evidence of an increased risk for infection or malignancy;no correlation between rates of infection, malignancy, and circulating CD4+ /CD8+ T-cell counts; and low immunogenicity. A preliminary study evaluating the use of alefacept for the treatment of active psoriatic arthritis parallels the psoriasis experience and supports the premise of targeting T cells as an intervention for this disease. Research continues to examine the use of alefacept in combination with other systemic psoriasis therapies and phototherapy and its potential as a treatment for other T-cell-mediated diseases, such as psoriatic arthritis, alopecia areata, and rheumatoid arthritis.
12083738 Alteration of gastric ulcerogenic and healing responses in rats with adjuvant-induced arth 2002 May Gastroenteropathy is the most common among patients who use non-steroidal anti-inflammatory drugs (NSAIDs) for treatment of inflammatory disorders. It is known that rheumatoid arthritic patients are more susceptible to NSAID-induced gastropathy than other NSAID users. This article reviewed our recent studies concerning the influence of arthritic conditions on gastric ulcerogenic response to NSAID and healing response of chronic gastric ulcers in rats. Gastric lesions induced by indomethacin, one of the conventional NSAIDs, were markedly aggravated in arthritic rats. This increased ulcerogenic response in arthritic rats was attributable to nitric oxide production due to up-regulation of inducible nitric oxide synthase. In arthritic rat stomachs, cyclooxygenase (COX)-2 was also up-regulated, where COX-2 selective inhibitors such as rofecoxib or celecoxib provoked gross lesions, although they caused no damage in normal rats. In addition, the healing of chronic gastric ulcers was also delayed in arthritic rats because of less expression of various growth factors such as basic fibroblast growth factors or insulin-like growth factors. Based on these findings, it is concluded that arthritic conditions alter the mucosal ulcerogenic and healing responses in the stomach. Especially, caution should be paid on the use of COX-2 selective inhibitors in rheumatoid arthritic patients.
13130488 Prevention of the onset and progression of collagen-induced arthritis in rats by the poten 2003 Sep OBJECTIVE: FR167653 is a potent inhibitor of p38 mitogen-activated protein kinase (MAPK) and inhibits tumor necrosis factor alpha (TNFalpha) and interleukin-1 beta (IL-1 beta) production in inflammatory cells. In this study we investigated the effect of FR167653 on collagen-induced arthritis (CIA). METHODS: Rats with CIA were subcutaneously injected with FR167653 (32 mg/kg/day) starting on the day of the booster injection (day 7) in the prophylactic treatment group and after the onset of arthritis (day 21) in the therapeutic treatment group. Hind-paw swelling, body weight, radiographic and histologic scores, and osteoclast number were evaluated. Cytokine levels in the serum and tissue were assessed by enzyme-linked immunosorbent assays. Flow cytometric analysis of T lymphocytes from bone marrow was performed. The effect of FR167653 on in vitro osteoclast formation induced by soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and TNFalpha was examined. RESULTS: Swelling of hind paws and loss of weight occurred in the CIA rats, but this was not evident in the prophylactic treatment group. Therapeutic treatment also significantly reduced paw swelling. The mean radiographic and histologic scores as well as the osteoclast numbers were significantly lower in the treatment group than in the CIA rats without treatment. FR167653 treatment reduced the serum levels of TNFalpha and IL-1 beta, lowered the IL-1 beta concentration in the ankle joints, and decreased the CD4-,CD8a+ T cell population in bone marrow. Furthermore, FR167653 inhibited the osteoclast-like cell differentiation induced by both sRANKL and TNFalpha in vitro. CONCLUSION: FR167653 prevents the onset of arthritis in a prophylactic treatment model and suppresses the progression of joint destruction in a therapeutic treatment model, suggesting that p38 MAPK is a potential therapeutic target for rheumatoid arthritis.
12854666 Ten-year evaluation of cementless Buechel-Pappas meniscal bearing total ankle replacement. 2003 Jun A porous-coated, cementless, congruent-contact, three-piece, meniscal-bearing total ankle replacement was developed and used clinically over a 2- to 10-year period for patients with disabling ankle arthritis. Polished titanium-nitride ceramic-coated Ti6Al4V tibial and talar components with a deep-sulcus trochlear groove and two lateral fixation fins for the talar onlay component were used. The ultra-high-molecular-weight polyethylene (UHMWPe) meniscal bearing congruently conformed to the flat upper tibial component surface and the deep sulcus and cylindrical geometry of the lower talar component surface. Fifty deep-sulcus (Buechel-Pappas) total ankle replacements were implanted in 49 patients. Diagnoses were 8 osteoarthritis (16%), 7 rheumatoid arthritis (14%), 2 avascular necrosis (4%), and 33 post-traumatic arthritis (66%). Ages ranged from 26 to 71 years (mean 49 years). Clinical results using a strict ankle scoring system demonstrated good/excellent results in 88% of cases. Postoperative ankle motion ranged from 12 degrees to 46 degrees total arc (mean 28 degrees), which was similar to the preoperative motion. Revision for malalignment was necessary in two cases (4%). Mechanical complications included one case of meniscal bearing wear (2%) in a patient with post-traumatic arthritis with component malalignment and one case of talar component subsidence (2%) in a patient with avascular necrosis of the talus. No tibial component loosening was seen. Cumulative survivorship using an end point of revision of any component for any reason was 93.5% at 10 years (confidence interval 61-100%).
18034108 Postoperative treatment and rehabilitation after total knee arthroplasty. 2002 Dec 30 Total arthroplasty is the primary surgical method used in patients with extensive deformations of the knee joint in the course of osteoarthritis or rheumatoid arthritis. Good outcome after arthroplasty depends on the proper identification of indications, good surgical technique, and the proper postoperative treatment and rehabilitation. In postoperative treatment appropriate conditions should be provided for healing of the damaged tissues and prevention of early and late complications. The aim of rehabilitation is to restore mobility in the highest possible range and full muscular control of the operated knee, i.e. to rebuild correct static and dynamic function of the joint and the entire lower limb. This study present a model of postoperative management and rehabilitation after total knee arthroplasty based on current literature and clinical experience from 597 arthroplasties performed in 530 patients between the years 1995 and 2002.
15038087 [Evaluation of diagnostic methods for Helicobacter pylori infection]. 2004 Mar In Japan, the noninvasive diagnostic tests currently approved for health insurance by the Ministry of Health are the serology test, the 13C-UBT test and the stool antigen test. The serology(antibody detection) test is useful for pretreatment screening, but because it reflects an immunologic response, false negatives are seen in patients with diseases such as rheumatoid arthritis and connective tissue diseases, and in the elderly. Furthermore, the serology test is difficult to use in the clinical setting, because 6 months or more is needed for the antibody titer to fall, after eradication therapy. For UBT, the expensive 13C-UBT is used. In view of the anticipated increase in testing, a test that is relatively inexpensive, simple, accurate and safe is needed. The stool antigen test has become available, and the test has been validated for accuracy. The stool antigen test is useful for the diagnosis of H. pylori infection before and after treatment in Japanese population.
14993360 Coming of age: anti-cytokine therapies. 2002 Feb Although cytokines are critical in maintaining normal physiology, excessive production of these proteins can lead to pathological consequences. Inhibitors of cytokine production or action are therefore widely investigated as potential therapeutic agents in a variety of immune and inflammatory diseases. Indeed, the successful application of inhibitors of tumor necrosis factor-alpha in rheumatoid arthritis and Crohn's disease heralds the great therapeutic potential of biopharmaceutical agents to counteract cytokine activities. Emerging opportunities for new therapeutics, as well as the challenges we face in their use and development, are described in this review.
12427239 Methotrexate-induced optic neuropathy. 2002 Dec A 53-year-old Caucasian woman with long-standing, well controlled, severe rheumatoid arthritis, treated with methotrexate, salazopyrin, naprosyn, prednisone and plaquenil, presented with progressive visual loss in each eye. She had a past history of non-necrotizing anterior scleritis that was treated with increased doses of prednisone. She developed left then right central scotomas, reduced vision and optic atrophy. Eventually a diagnosis of methotrexate-induced optic atrophy was made.
12192258 Impact of osteoarthritis on individuals and society: how much disability? Social consequen 2002 Sep Osteoarthritis is a major cause of disability in both the developed and developing world. With the population aging, the prevalence of osteoarthritis is increasing and its consequences are impacting significantly on society. This is one of the reasons why osteoarthritis has been adopted as a major focus (along with osteoporosis, rheumatoid arthritis, back pain, and musculoskeletal trauma) by the global initiative--the Decade of Bone and Joint Disease. Adequate studies on the costs of osteoarthritis are urgently required so that cogent arguments can be made to governments to appropriately fund prevention and treatment programs for this condition. Its recognition as a major cause of disability, particularly in the aging population, should increase community focus on this important condition.