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ID PMID Title PublicationDate abstract
16756797 [Shoulder arthroplasty]. 2006 May 8 Every year, almost 500 shoulder arthroplasties are performed in Denmark. About two-thirds are done due to fractures of the proximal humerus. Other common indications are rheumatoid arthritis and primary or secondary arthrosis. The prosthesis is fixed with or without bone cement. If the rotator cuff is lacking, an inverse total arthroplasty can be used, and in arthrosis/arthritis with good bone stock, a resurfacing prosthesis can be used. Good pain relief can be expected, but shoulder movement will usually be permanently inhibited.
16331753 HLA-DR genotypes in familial rheumatoid arthritis: increased frequency of protective and n 2005 Dec OBJECTIVE: We describe a unique family where each of the 5 siblings in the second generation has rheumatoid arthritis (RA). Two other members of the family have RA and systemic lupus erythematosus (SLE), respectively. No members of previous generations in the family had documented inflammatory arthritis. Due to the suspected genetic predisposition, HLA-DR genotypes were determined in the affected siblings and their parents, children, and grandchildren. We investigated the possible role of various HLA-DR alleles in the evolution of RA in this multicase family. METHODS: HLA-DRB1* alleles were determined by polymerase chain reaction using the sequence-specific primer-Olerup method. RESULTS: The most common alleles in the 6 persons with RA were HLA-DRB1*07 and DRB1*15, which are known to be protective and neutral in RA. No patient or family member carried any HLA-DR4 alleles. CONCLUSION: HLA-DRB1*07 and DRB1*15 alleles are thought to be protective or neutral in RA. However, the majority of RA patients in the family and nearly half of all family members carried these alleles, suggesting a role of these genotypes in susceptibility to RA. No RA patient in this family carried HLA-DR4 alleles. Thus, in our rare family with 6 RA cases, an unexpected genetic background may be involved in the increased susceptibility to inflammatory arthritis.
16932648 B-cell targeted therapies in rheumatoid arthritis and systemic lupus erythematosus. 2006 Jan B cells appear to have a central role in the immunopathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE); both autoantibody production and B-cell anomalies are characteristic of these diseases. With the recent availability of biologic agents that can deplete B cells or block their function in vivo, it has become possible to target B cells therapeutically. Evidence strongly suggests that novel B-cell targeting agents are effective. In addition, the mechanistic specificity of B-cell targeted approaches, combined with the ability to test them in large randomized controlled trials, will provide an unprecedented opportunity to study the precise roles of B cells in the immunopathogenesis of RA and SLE. The largest volume of information is available for rituximab, a chimeric monoclonal antibody that depletes B cells by binding to the CD20 cell-surface antigen. Information from multiple investigator-sponsored trials and from off-label use suggests efficacy of this antibody in RA, SLE, and other autoimmune syndromes. Randomized controlled trials have also provided solid evidence for the efficacy of rituximab in RA and are ongoing in SLE. Other therapeutic agents supported by controlled data include cytotoxic T-lymphocyte-associated protein 4 immunoglobulin and antibodies against the interleukin-6 receptor and the B-cell survival molecule BLyS. Additional agents and targets are in earlier stages of development. The concerns about infectious complications have so far not proven to be justified. We can reasonably expect important advances in the understanding and treatment of RA and SLE in the next 5-10 years, as B-cell targeting methods become more widespread and sophisticated.
15996057 Longterm safety, efficacy, and radiographic outcome with etanercept treatment in patients 2005 Jul OBJECTIVE: To evaluate safety, efficacy, and radiographic progression in patients with early rheumatoid arthritis (RA) undergoing longterm treatment with etanercept. METHODS: Patients with early RA (disease duration of 3 years or less) who had completed a 2-year efficacy study comparing etanercept and methotrexate (MTX) were followed in an extension where they received 25 mg etanercept twice weekly. Safety was summarized descriptively and compared with data from the efficacy study. Efficacy and radiographic progression were assessed using American College of Rheumatology response criteria, disease activity scores, and Total Sharp Score (TSS). RESULTS: Rates of serious adverse events and serious infections did not increase with longterm exposure to etanercept, and were similar to rates reported for the blinded portion of the efficacy study. Efficacy was sustained in patients who completed 5 years of etanercept treatment at the time of this report (N = 201), even in those who decreased or discontinued use of MTX or corticosteroids. No radiographic progression (change in TSS < or = 0) was seen in 55% of patients with 5-year radiographs; negative change (TSS < 0) was seen in 11%. CONCLUSION: Etanercept treatment in patients with early RA was generally well tolerated for up to 5 years. The results indicate sustained efficacy and decreased rate of radiographic progression. The rate of radiographic progression was low compared with other studies, emphasizing the benefit gained in patients with early aggressive RA who undergo longterm treatment with etanercept.
17027523 Regulation of osteoclast differentiation and function by interleukin-1. 2006 Interleukin-1 (IL-1) is a multifunctional cytokine that regulates various cellular and tissue functions. Among tissues, bone is the most sensitive to IL-1. IL-1 is a potent cytokine for bone resorption and participates in the multiple steps of osteoclast recruitment, such as differentiation, multinucleation, activation, and survival. On the other hand, considerable evidence has been accumulated over the past 10 years to indicate that this cytokine plays key roles in pathological bone destruction in a variety of human diseases, including rheumatoid arthritis, osteoporosis, and periodontal disease. In this chapter, we review the history of "IL-1 in bone" and the locus of this cytokine "from laboratory bench to bedside." A better understanding of the role of IL-1 in osteoclastic bone resorption would provide opportunities for developing new therapeutics to treat diseases of the bone.
15692990 Fibroblast-like synoviocytes derived from patients with rheumatoid arthritis show the impr 2005 Feb OBJECTIVE: Given the heterogeneity of gene expression patterns and cellular distribution between rheumatoid arthritis (RA) synovial tissues, we sought to determine whether this variability was also reflected at the level of the fibroblast-like synoviocyte (FLS) cultured from RA synovial tissues. METHODS: Gene expression profiles in FLS cultured from synovial tissues obtained from 19 RA patients were analyzed using complementary DNA microarrays and hierarchical cluster analysis. To validate the subclassification, we performed prediction analysis and principal components analysis. Genes that differed significantly in their expression between FLS cultures were selected using Statistical Analysis of Microarrays software. Real-time quantitative polymerase chain reaction was performed to validate the microarray data. Immunocytochemistry was applied to study the expression of the genes of interest in FLS and synovial tissues. RESULTS: Hierarchical clustering identified 2 main groups of FLS characterized by distinctive gene expression profiles. FLS from high-inflammation synovial tissues revealed increased expression of a transforming growth factor beta/activin A-inducible gene profile that is characteristic of myofibroblasts, a cell type considered to be involved in wound healing, whereas increased production of growth factor (insulin-like growth factor 2/insulin-like growth factor binding protein 5) appeared to constitute a characteristic feature of FLS derived from low-inflammation synovial tissues. The molecular feature that defines the myofibroblast-like phenotype was reflected as an increased proportion of myofibroblast-like cells in the heterogeneous FLS population. Myofibroblast-like cells were also found upon immunohistochemical analysis of synovial tissue. CONCLUSION: Our findings support the notion that heterogeneity between synovial tissues is reflected in FLS as a stable trait, and provide evidence of a possible link between the behavior of FLS and the inflammation status of RA synovium.
16329077 Generation of neoantigenic epitopes after posttranslational modification of type II collag 2005 Dec OBJECTIVE: Collagen-induced arthritis is a commonly accepted model of rheumatoid arthritis (RA). However, it has been difficult to substantiate the involvement of autoimmunity to type II collagen (CII) in the pathogenesis of RA. The aim of this investigation was to determine if CII, modified by reactive oxidant species present within the inflamed joint, could generate neoantigenic epitopes. METHODS: Oxidants that play a role in acute and chronic inflammation and are present in the rheumatoid joint (hydroxyl radical, hypochlorous acid, and peroxynitrite) were used for modification of native CII. In addition, CII was glycated with ribose, since nonenzymatic oxidative reactions by glycation are evident in RA. Modifications were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 3-dimensional fluorescence followed by enzyme-linked immunosorbent assay (ELISA) and Western blotting, using, as probes, sera from patients with RA and from patients with other inflammatory and noninflammatory joint diseases. RESULTS: Only 1 RA serum sample showed strong binding to native CII. In contrast, binding to modified CII was increased in 14 of 31 RA sera, of which 7 were strong binders and 7 were moderate binders. Among the non-RA serum samples, only 1 yielded a strong reaction to modified CII and 5 of 41 were moderate binders. Samples that showed the strongest binding to modified CII in ELISA also showed strong binding to various fragmented or aggregated forms of CII in Western blots, as well as strong binding to fragmented CII present in RA synovial fluid. CONCLUSION: When modified by conditions found within the inflamed joint, CII acts as an autoantigen in RA.
15702101 Methotrexate and oral ulceration. 2005 Jan 22 Methotrexate is well established in the drug treatment of various neoplastic diseases. More recently it has become increasingly used as a once-weekly, low-dose treatment of disorders such as psoriasis and rheumatoid arthritis. Clinical trials have shown its effectiveness in these conditions and it is likely that dentists will encounter patients taking this drug in general dental practice. Oral ulceration can occur as a side effect of methotrexate therapy. This may be due to lack of folic acid supplementation or overdosage due to confusion regarding its once-weekly regime. Illustrations of these problems, which have initially presented in a dental setting, are given. Important drug interactions of methotrexate relevant to dentistry are discussed.
16255019 Influence of HLA-DR genes on the production of rheumatoid arthritis-specific autoantibodie 2005 Nov OBJECTIVE: Antibodies directed against citrullinated fibrinogen are highly specific for rheumatoid arthritis (RA). This study was undertaken to test whether RA-associated HLA-DR alleles are associated with anti-citrullinated fibrinogen in RA patient sera and whether replacement of arginyl by citrullyl residues on fibrinogen peptides modifies their binding to HLA-DR molecules and their recognition by T cells. METHODS: Antikeratin, antifilaggrin, and anti-citrullinated fibrinogen antibodies were assayed in RA patients who had undergone HLA-DR typing. Direct assays were performed to investigate binding of citrullinated or native fibrinogen peptides (encompassing the entire alpha- and beta-chains of fibrinogen) to purified HLA-DR molecules. T cell proliferative responses to citrullinated or native fibrinogen peptides were measured in RA patients and controls. RESULTS: HLA-DRB1*0404 was associated with anti-citrullinated fibrinogen in RA sera (P = 0.002). For the RA-associated alleles HLA-DRB1*0401 and HLA-DR1, there was a nonsignificant trend toward association (P = 0.07). Multiple peptides from the alpha- and beta-chains of fibrinogen bound many HLA-DR alleles; DRB1*0404 was the best fibrinogen peptide binder. Citrullination did not influence fibrinogen peptide binding to HLA-DR or fibrinogen peptide recognition by T cells. Peripheral blood T cells that recognized native or citrullinated fibrinogen peptides were common in RA patients but not in healthy controls. CONCLUSION: The RA-associated HLA-DRB1*0404 allele is also associated with production of antibodies to citrullinated fibrinogen. DRB1*0401 and DRB1*01 tend to be associated with anti-citrullinated fibrinogen, but this is not statistically significant. Citrullination of fibrinogen peptide does not influence peptide-DR-T cell interaction. Finally, T cell proliferation in response to citrullinated or uncitrullinated fibrinogen peptides is frequent in RA patients and very infrequent in controls.
17129076 Cost effectiveness of tumour necrosis factor-alpha inhibitors as first-line agents in rheu 2006 BACKGROUND AND OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease with an unknown aetiology that results in >9 million physician visits and >250 000 hospitalisations per year in the US. Tumour necrosis factor-alpha (TNFalpha) inhibitors are effective agents in treating RA; however, their cost effectiveness as first-line agents has not been investigated. This study aimed to examine the cost effectiveness of using TNFalpha inhibitors (both as monotherapy and in combination with methotrexate) as first-line agents versus methotrexate (monotherapy) from a payer perspective. METHODS: A Markov model was developed utilising a discount rate of 3% per annum, a cycle length of 1 year and a lifetime time-horizon for a hypothetical cohort of US females aged 55-60 years who had been diagnosed with RA. The source of data for predicted probabilities, expected mortality rates and treatment costs in year 2005 US dollars (drug, toxicity, monitoring and hospitalisation) was from the literature. These costs are assigned in 5-year cycles (calculated from initial 1-year estimates) along with the effect on quality-adjusted life-years (QALYs), which were calculated using the Health Assessment Questionnaire score. Univariate sensitivity analyses were conducted on all relevant parameters. RESULTS: Adalimumab, etanercept, adalimumab plus methotrexate and infliximab plus methotrexate had incremental cost-effectiveness ratios (ICERs) versus methotrexate monotherapy of $US63 769, $US89 772, $US194 589 and $US409 523 per QALY, respectively. When taking into consideration age at diagnosis, the ICER for etanercept ranged from $US84 129 to $US96 225 per QALY. In considering males for the base-case age at diagnosis, the ICER for etanercept versus methotrexate was $US85 100 per QALY. The average lifetime cost across all treatment arms in a woman diagnosed between 55 and 60 years of age was $US211 702. CONCLUSION: While these ICERs cannot be used to directly compare one biological agent with another since there are no comparative trials, they do provide a valid comparison versus methotrexate as first-line agents. Depending where the cost-effectiveness threshold is drawn (i.e. whether it is considered to be $US50 000 or $US100 000 per QALY), etanercept and adalimumab may be considered relatively cost-effective first-line treatments for RA compared with methotrexate monotherapy.
16869010 Increased arthritis susceptibility in cartilage proteoglycan-specific T cell receptor-tran 2006 Aug OBJECTIVE: To better understand the role of antigen (arthritogenic epitope)-specific T cells in the development of autoimmune arthritis. METHODS: A transgenic (Tg) mouse expressing the T cell receptor (TCR) Valpha1.1 and V(beta)4 chains specific for a dominant arthritogenic epitope (designated 5/4E8) of human cartilage proteoglycan (HuPG) aggrecan was generated. This TCR-Tg mouse strain was backcrossed into the PG-induced arthritis (PGIA)-susceptible BALB/c strain and tested for arthritis incidence and severity. RESULTS: CD4+ TCR-Tg T cells carried functionally active TCR specific for a dominant arthritogenic epitope of HuPG (5/4E8). T cells of naive TCR-Tg mice were in an activated stage, since the in vitro response to HuPG or to peptide stimulation induced interferon-gamma and interleukin-4 production. TCR-Tg mice uniformly, without exception, developed severe and progressive polyarthritis, even without adjuvant. Inflamed joints showed extensive cartilage degradation and bone erosions, similar to that seen in the arthritic joints of wild-type BALB/c mice with PGIA. Spleen cells from both naive and HuPG-immunized arthritic TCR-Tg mice could adoptively transfer arthritis when injected into syngeneic BALB/c.SCID recipient mice. CONCLUSION: TCR-Tg BALB/c mice display increased arthritis susceptibility and develop aggravated disease upon in vivo antigen stimulation. This model using TCR-Tg mice is a novel and valuable research tool for studying mechanisms of antigen (arthritogenic epitope)-driven regulation of arthritis and understanding how T cells recognize autoantigen in the joints. This type of mouse could also be used to develop new immunomodulatory strategies in T cell-mediated autoimmune diseases.
15809873 Comparison between mobile-bearing and fixed-bearing knees in bilateral total knee replacem 2005 Jun The purpose of this study was to compare mid-term results of mobile-bearing and fixed-bearing in bilateral total knee arthroplasty (TKA). Twenty-two patients underwent bilateral TKA with a mobile-bearing prosthesis (Rotaglide, Corin, UK) on one side and a fixed-bearing prosthesis (NexGen-CR, Zimmer, USA) on the other. There were 21 female patients, and in 18 patients, the diagnosis was rheumatoid arthritis. The average age was 59.6 (35-78) years. In all procedures, the posterior cruciate ligament was retained and patella re-surfaced. The average follow-up in the mobile-bearing group was 98 (79-107) months and 96 (79-107) months in the fixed-bearing group. At the final follow-up, the knee score was 91.8 points and 91.1 points, respectively, and the function score 65.5 points. The range of motion was similar in the two groups (1.1-106.9 degrees; 0.4-106.9 degrees). Five patients favoured the fixed-bearing prosthesis, but 16 found no difference. In patients with bilateral TKA, there was no difference in the short-term result between mobile-bearing and fixed-bearing prostheses.
16645974 Performance of an automated computer-based scoring method to assess joint space narrowing 2006 May OBJECTIVE: To compare the diagnostic performance of a computer-based method for measuring joint space width with the Sharp joint space narrowing (JSN) scoring method in patients with rheumatoid arthritis (RA). METHODS: A random sample of patients with early RA, for whom sequential hand radiographs and Sharp scores were available, was selected from the National Data Bank for Rheumatic Diseases. Hand joint space width was measured using an automated, computer-based method in random order and with blinding for clinical information. We constructed a receiver operating characteristic curve and compared the diagnostic performance of the computer-based and Sharp methods based on the areas under the curve. RESULTS: One hundred twenty-nine patients with early RA who underwent serial radiography were included. Changes in the computer-based and Sharp methods were highly correlated (r = 0.75, P < 0.001). The computer-based method was significantly more discriminant than the Sharp JSN subscale. The area under the curve of the computer-based method was 0.96 (95% confidence interval [95% CI] 0.94, 0.99) compared with 0.93 (95% CI 0.89, 0.96) for the Sharp subscale (P = 0.024). At the most discriminant cutoff, specificity of the computer-based method was 88.4% compared with 81.4% for the Sharp subscale (P = 0.11); sensitivity was 87.6% for the computer-based method compared with 82.2% for Sharp subscale (P = 0.19). The signal-to-noise ratio for the computer-based method was 83% compared with 70% for the Sharp subscale (P = 0.013). CONCLUSION: The computer-based method for measuring joint space width is more discriminant than the semiquantitative Sharp JSN subscale.
16163444 IL-17 increased the production of vascular endothelial growth factor in rheumatoid arthrit 2006 Feb Interleukin-17 (IL-17) is a proinflammatory cytokine that is expressed in the synovium T cells of rheumatoid arthritis (RA). This cytokine is implicated in the inflammation and destruction of the joint. However, the role of IL-17 on the production of vascular endothelial factor (VEGF) important to synovial proliferation has still not been identified. In this study, we investigated the effect on cultured rheumatoid fibroblast-like synoviocytes (FLS) of the IL-17 on the production and expression of VEGF, which play an important role in angiogenesis in rheumatoid synovium. IL-17 increased the production of VEGF dose dependently and the mRNA expression of VEGF. These results suggest that IL-17 might influence angiogenesis in RA by up-regulating the expression of VEGF in rheumatoid FLS.
17014017 High prevalence of thyroid autoimmunity and hypothyroidism in patients with psoriatic arth 2006 Oct OBJECTIVE: To evaluate the prevalence of thyroid disorders in a group of patients with psoriatic arthritis (PsA). METHODS: A complete thyroid investigation was carried out in 80 patients with PsA, in gender- and age-matched subjects (1:5) drawn from the general population (controls), and in 112 patients with rheumatoid arthrtitis (RA) with similar iodine intake. RESULTS: Anti-thyroid peroxidase antibodies (AbTPO), a hypoechoic thyroid, and subclinical hypothyroidism were significantly more frequent in women with PsA than in control women, and their frequency was similar to that in patients with RA (positive AbTPO titer 28%, 12%, and 31%; hypoechoic thyroid 31%, 16%, and 36%; subclinical hypothyroidism 25%, 8%, and 12%, respectively). Among men, positive AbTPO titers and a hypoechoic thyroid were found more frequently in the patients with PsA and RA than in controls (positive AbTPO titer 14%, 5%, and 2%; hypoechoic thyroid 16%, 10%, and 3%, respectively). All patients with PsA with subclinical hypothyroidism had polyarticular involvement (p
17243489 Drug evaluation: the C5a receptor antagonist PMX-53. 2006 Dec Peptech is developing PMX-53, a complement C5a inhibitor for the potential treatment of inflammatory disorders, including rheumatoid arthritis and psoriasis. Phase Ib/IIa clinical trials have been completed for both indications.
16263612 Limited influence of prosthetic position on aseptic loosening of elbow replacements: 125 e 2005 Oct BACKGROUND: Aseptic loosening of elbow replacements, seen in long-term follow-up, remains a problem. In this study, we attempted to determine the influence of cementing technique, prosthetic position, different component sizes, use of a bone plug, and intraoperative fractures on the development and progression of radiolucent lines and aseptic loosening. METHODS: We studied standard radiographs of 125 primary Souter-Strathclyde total elbow prostheses using the Wrightington method. Additionally, 104 preoperative radiographs were available for analysis. We used a Markow statistical model to detect relationships between all factors described above. RESULTS: After a mean follow-up time of 5.5 (2-19) years, 21 (17%) prostheses had loosened radiographically (10-year survival: 65%). When the humeral component was tilted more medially or more anteriorly, we found development of radiolucent lines at the medial condyle and at the posterior side of the humeral component. However, the progression of these lines was not influenced by these positions. No other prognostic factors for radiolucent lines or aseptic loosening were found. INTERPRETATION: Despite the small number of elbows studied, the weak influence of prosthetic position on aseptic loosening gives more ground for a multifactorial cause for aseptic loosening of the Souter-Strathclyde total elbow prosthesis.
15967423 Plasma and urinary carnitine and acylcarnitines in chronic fatigue syndrome. 2005 Oct Contradictory reports have suggested that serum free carnitine and acylcarnitine concentrations are decreased in patients with chronic fatigue syndrome (CFS) and that this is a cause of the muscle fatigue observed in these patients. Others have shown normal serum free carnitine and acylcarnitines in similar patients. We report here studies on free, total and esterified (acyl) carnitines in urine and blood plasma from UK patients with CFS and three control groups. Plasma and timed urine samples were obtained from 31 patients with CFS, 31 healthy controls, 15 patients with depression and 22 patients with rheumatoid arthritis. Samples were analysed using an established radioenzymatic procedure for total, free and esterified (acyl) carnitine. There were no significant differences in plasma or urinary total, free or esterified (acyl) carnitine between UK patients with CFS and the control groups or in renal excretion rates of these compounds. The data presented here show that, in the CFS patients studied, there are no significant abnormalities of free or esterified (acyl) carnitine. It is thus unlikely that abnormalities in carnitine homeostasis have any significant role in the aetiology of their chronic fatigue.
16583484 Mycobacterium marinum arthritis mimicking rheumatoid arthritis. 2006 Apr Mycobacterium marinum is an atypical mycobacterium found in salt and fresh water. M. marinum infection occurs following skin trauma in fresh or salt water and usually presents as a localized granuloma or sporotrichotic lymphangitis. It rarely affects the musculoskeletal system. We describe a patient who presented with subcutaneous nodules and an inflammatory arthritis that was thought to be rheumatoid arthritis, and was treated as such with corticosteroids, methotrexate, and anti-tumor necrosis factor-alpha therapy, with worsening of his arthritis.
16417774 A clinical study of Suogudan granule in the treatment of rheumatoid arthritis. 2005 Dec OBJECTIVE: To study the clinical efficacy of Suogudan Granule (SGDG) in the treatment of rheumatoid arthritis (RA). METHODS: Ninety patients with RA were randomly divided into the treated group and the control group. The treated group was administered orally with SGDG 6 g each time, thrice a day, while the control group with the combined therapy of Fenbid Capsules 0.3 g each time, twice a day and Tripterygium tablet 20 mg each time, thrice a day. The treatment course for both groups was 6 weeks. The changes of clinical symptoms and signs, and laboratory indices such as erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), antistreptolysin O (ASO), routine examination of blood and urine, liver and kidney function, etc. before and after treatment were observed. RESULTS: (1) The total effective rate in the treated group (88.0%) was obviously higher than that in the control group (67.5%) with significant difference (P < 0.05). (2) The improvement in arthralgia, joint swelling, time of morning stiffness, 15-meter walking, analgesia initiation and persistence in the treated group was better than that in the control group (P < 0.05, P < 0.01), but there was no obvious difference in improvement of joint tenderness, range of joint motion, grip strength, and initiating detumescence time (P > 0.05). (3) The improvement in ESR and RF in the treated group was better than that in the control group with significant difference (P < 0.05). The negative-conversion rate of ASO in the treated group was also higher than that in the control group (P < 0.01). (4) No evident abnormality in blood, urine, liver or kidney function was found in either group. CONCLUSION: SGDG is effective and safe for the treatment of RA.