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ID PMID Title PublicationDate abstract
17985419 Optimizing treatment with biologics. 2007 Nov Disability and joint damage in rheumatoid arthritis (RA) occur rapidly and early in the course of the disease. Disease activity is predominantly responsible for the disability in the early stages of RA. Nonreversible joint damage increases disability later in the course of RA. In recent years, several strategies that employed combination therapies with conventional disease modifying antirheumatic drugs (DMARD) were studied with the aim of rapidly bringing the disease under control. The ultimate goal was to alleviate symptoms and slow or halt the progression of joint damage. The introduction of highly efficient biologic agents allows introduction of a number of new strategies, including early administration of a biologic agent alone or in combination with high-dose methotrexate. Other options for the use of biologic therapies include the use of biologic agents for moderate disease, and early use of a biologic agent for induction of remission and subsequent treatment with a conventional DMARD. A strategy for tight control of disease with targeted outcomes for decision-making may offer further improvement in disease control irrespective of the treatment approach. The remarkably improved outcomes that can be achieved by initiating aggressive therapy early, with close monitoring of disease progression and modification of ineffective therapeutic strategies, support the use of biologics in the optimal management of RA.
17974596 Duration of preclinical rheumatoid arthritis-related autoantibody positivity increases in 2008 Jun OBJECTIVES: To investigate factors that may influence the prevalence and timing of appearance of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies during the preclinical phase of rheumatoid arthritis (RA) development. METHODS: 243 serial prediagnosis serum samples from 83 subjects with RA were examined for the presence of RF and anti-CCP antibodies. RESULTS: Of the 83 cases, 47 (57%) and 51 (61%) subjects had at least one prediagnosis sample positive for RF or anti-CCP, respectively. Gender and race were not significantly associated with the prevalence or timing of preclinical antibody appearance. Preclinical anti-CCP positivity was strongly associated with the development of erosive RA (odds ratio = 4.64; 95% confidence interval 1.71 to 12.63; p<0.01), but RF was not (p = 0.60). Additionally, as age at the time of diagnosis of RA increased the duration of prediagnosis antibody positivity for RF and anti-CCP increased, with the longest duration of preclinical antibody positivity seen in patients diagnosed with RA over the age of 40. In no subjects did symptom onset precede the appearance of RF or anti-CCP antibodies. CONCLUSIONS: The period of time that RF and anti-CCP are present before diagnosis lengthens as the age at the time of diagnosis of RA increases. This finding suggests that factors such as genetic risk or environmental exposure influencing the temporal relationship between the development of RA-related autoantibodies and clinically apparent disease onset may differ with age.
17569744 Synovial fluid expression of autoantibodies specific for RAGE relates to less erosive cour 2007 Aug OBJECTIVES: The receptor for advanced glycation end products (RAGE) is expressed by many cells in joints of rheumatoid arthritis (RA) patients and interacts with a variety of pro-inflammatory ligands that are enriched in inflamed joint. The RAGE-ligand interaction leads to a sustained inflammatory response. Also, secreted form of the receptor, called soluble RAGE (sRAGE), the levels of which are decreased in RA patients, modulates inflammatory responses. We sought to determine whether RA patients display increased occurrence of autoantibodies against RAGE and whether such an autoantibody production is related to disease characteristics. METHODS: Matching samples of blood and synovial fluid were collected from 50 patients with RA with acute joint effusion. Blood from 43 healthy individuals and synovial fluid samples from 32 patients with non-inflammatory joint diseases were used for comparison. Anti-RAGE antibody levels were analysed using an ELISA. RESULTS: RA patients displayed significantly higher blood and synovial fluid levels of anti-RAGE antibodies, both of IgG as well as of IgM class as compared with healthy controls and with patients with non-inflammatory joint diseases. Patients with seropositive RA had significantly less IgG antibodies in their synovial fluid as compared to seronegative patients. Furthermore, the presence of IgG class of anti-RAGE antibodies locally in the joint was found to be related to less aggressive, i.e. non-erosive disease. CONCLUSION: These results suggest that RAGE-specific B cell response protect patients with RA from destructive course of the disease.
17934094 Joint remodelling in inflammatory disease. 2007 Nov Bone and the immune system share multiple interactions. The skeleton harbours the bone marrow and provides the niche for development of haematopoietic cells including the immune system. The immune system provides cells as well as molecular signals, which regulate bone homeostasis. Understanding the cellular and molecular regulation of the tight interaction between bone and the immune system is crucial for understanding the changes of skeletal architecture during inflammation. Whereas a short and self-limited activation of the immune system has no clinically meaningful effect on bone, prolonged immune activation as found in chronic inflammatory disease inevitably leads to bone wasting.
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.
18330029 [Anemia in the elderly]. 2008 Mar In the elderly, non-specific symptoms tend to come to the fore in addition to the symptoms resulted directly from anemia. Moreover, mild anemia could give the excessive effects to the heart and the lungs because of less function of organs. There is no great difference in the epidemiology of anemia in the elderly and the youth. However, the anemia associated with chronic illness, especially due to malignancy, is frequent in the elderly. The research for the original disease and its treatment should take priority in the anemia of chronic disorder.
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.
17284242 The use of recombinant adeno-associated virus for skeletal gene therapy. 2007 Feb OBJECTIVES: To provide a comprehensive literature review describing recent developments of the recombinant adeno-associated virus (rAAV) vector and exploring the therapeutic application of rAAV for bone defects, cartilage lesions and rheumatoid arthritis. DESIGN: Narrative review. RESULT: The review outlines the serotypes and genome of AAV, integration and life cycle of the rAAV vectors, the immune response and regulating system for AAV gene therapy. Furthermore, the advancements of rAAV gene therapy for bone growth together with cartilage repair are summarized. CONCLUSION: Recombinant adeno-associated virus vector is perceived to be one of the most promising vector systems for bone and cartilage gene therapy approaches and further investigations need to be carried out for craniofacial research.
19066176 Golimumab, a human antibody to tumour necrosis factor {alpha} given by monthly subcutaneou 2009 Jun OBJECTIVE: The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy. METHODS: Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24. RESULTS: The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively. CONCLUSION: The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.
18473901 Molecular targets of rheumatoid arthritis. 2008 Mar Rheumatoid arthritis (RA) is a multifactorial disease characterized by chronic inflammation of the joints. Both genetic and environmental factors are involved in the pathogenesis of joint destruction and disability. In the inflamed RA joint, the synovium is highly infiltrated by CD4+ T cells, B cells, and macrophages. Furthermore, the intimal lining becomes hyperplastic due to the increased numbers of macrophage-like and fibroblast-like synoviocytes. This hyperplastic intimal synovial lining forms an aggressive front, called pannus, which invades cartilage and bone structures, leading to compromised function and/or destruction of affected joints. RA pathology is mediated by a number of cytokines (TNF-alpha, IL-1, IL-6, IL-17, IFN gamma, etc.), chemokines (MCP-1, MCP-4, CCL18, etc.), cell adhesion molecules (ICAM-1, VCAM-1, etc.) and matrix metalloproteinases. Currently, treatment strategies targeted against TNF-alpha, IL-1 and IL-6 are available. In this review, we will summarize the use of biologics, the pros and cons of the use of biologics, and discuss on the potential molecular targets of RA.
17533629 Antiinflammatory effect of the Indian Ayurvedic herbal formulation Triphala on adjuvant-in 2007 Sep In the present study, attempts have been made to evaluate the antiarthritic effect of the Indian Ayurvedic herbal formulation Triphala on adjuvant-induced arthritis in mice and to compare it with that of the non-steroidal antiinflammatory drug indomethacin. Arthritis was induced by intradermal injection of complete Freund's adjuvant (0.1 mL) into the right hind paw of Swiss albino mice. Triphala (1 g/kg/bxwt) and indomethacin (3 mg/kg/bxwt) were administered orally for 8 days (from day 11 to 18) after adjuvant injection. The levels of lysosomal enzymes, tissue marker enzymes, glycoproteins and paw thickness were increased in adjuvant-induced arthritic animals. The body weight was found to be reduced when compared with the control animals. These physical and biochemical changes observed in arthritic animals were altered significantly to near normal conditions after oral administration of Triphala (1 g/kg/bxwt). The results obtained clearly indicate the fact that the Indian Ayurvedic herbal formulation Triphala has promising antiinflammatory activity.
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
17543722 Male hypogonadism in systemic disease. 2007 Jun Hypogonadism is often observed in the presence of common acute and chronic illnesses in men. Low testosterone levels in these patients can be associated with loss of lean body mass and bone mass density, decline in mood, loss of energy, and sexual dysfunction. The mechanisms explaining hypogonadism and various systemic diseases are not completely understood, but these conditions are likely caused by a combination of stress, nonspecific weight loss, inflammation, and medication. Testosterone replacement can be considered in this population to improve lean body mass, bone mass density, and quality of life. More information is needed regarding the risk benefits of testosterone treatment on health outcomes in men who have systemic illness.
17982129 CCL21 expression pattern of human secondary lymphoid organ stroma is conserved in inflamma 2007 Nov CCL21 is a homeostatic lymphoid chemokine instrumental in the recruitment and organization of T cells and dendritic cells into lymphoid T areas. In human secondary lymphoid organs (SLOs), CCL21 is produced by cells distributed throughout the T zone, whereas high endothelial venules (HEVs) lack CCL21 mRNA. A critical question remains whether the development of ectopic lymphoid tissue (ELT) in chronic inflammation recapitulates the features of SLOs. Thus, we systematically investigated in situ the cellular sources of CCL21 in SLOs and ELTs in several human diseases characterized by lymphoid neogenesis. By in situ hybridization and the use of combinatorial cell markers, we show that CCL21-producing vessels in inflamed tissues systematically display typical markers of lymphatic vessels, whereas, as in SLOs, ectopic HEVs do not synthesize detectable levels of CCL21. We also provide first-time evidence that a common pattern of CCL21 expression by CD45-negative myofibroblast-like cells localized in extra-HEV position and organized in a fibroblastic reticular network similarly characterizes human SLOs and organized ELTs. Altogether, our results demonstrate that in humans the pattern of CCL21 production in SLOs is maintained during inflammation and that the phenotypic and functional properties of stromal cells, found in SLO T-cell areas, are reproduced at ectopic sites.
18751703 The effect of tourniquet use on hidden blood loss in total knee arthroplasty. 2009 Oct The objective of this study was to examine the characteristics of hidden blood loss and assess the effects of using a tourniquet on postoperative hidden loss in patients undergoing primary total knee arthroplasty. Eighty patients were randomised into two groups: one group underwent operation with a tourniquet and one without. Operating time, perioperative blood loss, hidden blood loss, free haemoglobin, swelling, ecchymosis, straight leg raising action and knee flexion were measured. There were significant differences in the hidden blood loss, free haemoglobin, postoperative swelling, extent of ecchymosis, straight leg raising and postoperative knee flexion in the early period after operation between the two groups. Our results indicate that knee arthroplasty operations with a tourniquet might promote postoperative hidden blood loss and hinder patients' in early postoperative rehabilitation exercises.
17929132 Methotrexate reduces the levels of pentosidine and 8-hydroxy-deoxy guanosine in patients w 2007 This study was performed to investigate whether methotrexate (MTX) affects the levels of oxidative stress markers, including pentosidine one of the glycation end products (AGEs) or 8-hydroxy-deoxy guanosine (8-OHdG). These stress markers represent DNA damage; 19 rheumatoid arthritis (RA) patients underwent MTX treatment. The levels of serum total, urinary total, urinary-free pentosidine and also urinary 8-OHdG, as well as clinical parameters, including disease activity scores for 28 joints (DAS28) were measured at baseline and at 3 and 6 months after the initial treatment with MTX. After the initial treatment with MTX, serum total and urinary total pentosidine levels were reduced at 6 months, and urinary-free pentosidine levels were reduced at 3 and 6 months. Urinary 8-OHdG levels also were significantly reduced at 6 months after the initial treatment with MTX. This study demonstrated that MTX plays a role as a regulator against pentosidine formation and oxidative DNA damage in RA patients.
17570271 Correcting varus deformity. 2007 Jun We report our technique and the results of treating severe intra- and extra-articular varus deformity using posterior stabilized fixed-bearing implants. We used a technique of selective posteromedial release and reduction osteotomy of posteromedial tibial flare in 173 knees in 117 patients. Proximal tibial osteotomy was used to correct severe extra-articular deformity. Mean tibiofemoral varus of 22 degrees preoperatively was corrected to 5.3 degrees valgus postoperatively. A total of 86% knees were in 4 degrees to 10 degrees valgus postoperatively. Mean Knee Society score improved from 22.8 to 91.1, and function score from 22.8 to 72.1 at 2 to 9 years. Of 30 bone grafts for tibial defects, 28 were successfully incorporated. No patient reported significant instability. Three knees showed tibial component loosening. Our technique restored alignment and stability without the need for constrained implants.
17330287 Relationship between appearance and psychological distress in rheumatic diseases. 2007 Mar 15 OBJECTIVE: To examine the relationship between physical appearance concerns and psychological distress in patients with rheumatic diseases. METHODS: A total of 60 patients with systemic lupus erythematosus (SLE), 44 with chronic rheumatoid arthritis (RA), and 53 with recent-onset RA were evaluated for levels of appearance concern and a range of illness-specific measures to determine how these demographic and clinical variables were related to the dependent variable psychological distress. RESULTS: Using hierarchical multiple regression analyses, we found that both appearance concerns and levels of disability were predictive of depression in patients with RA. In the SLE sample, physical disability was predictive of depression when appearance concerns were not included in the analysis. However, disability did not predict depression when appearance concerns were entered into the analysis. This indicates that appearance concerns mediated the relationship between disability and depression in SLE. There was no association between appearance concerns and anxiety in either sample. CONCLUSION: The results suggest that appearance concerns are strongly related to depression in patients with rheumatic diseases and should be routinely assessed.