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ID PMID Title PublicationDate abstract
17029072 Long-term outcome of patients with rheumatoid arthritis treated by multiple arthroplasty. 2005 We conducted a study of 82 patients with rheumatoid arthritis (RA) who had undergone multiple arthroplasty and investigated their clinical findings and clinical courses. We reviewed the significance of multiple arthroplasty in the treatment of RA, its problems, and measures to solve them. All patients initially regained and maintained good walking capacity. However, the walking capacity of many patients again decreased over the long term; in the tenth year, 79% of patients were capable of a practical gait. The causes of decreased walking capacity included complications of artificial joints, cervical lesions, and vertebral compression fractures. Fractures were observed in as many as nine patients, indicating that it is important to prevent and treat their cause, that is, osteoporosis. The survival rate was 71% in 10 years. In RA patients, particularly those who have undergone multiple arthroplasty, the major causes of death are infection and rheumatic disease, suggesting that prevention of such diseases should be considered paramount. Appropriate systemic treatment of RA, patient education, and measures against osteoporosis for prevention of complications may preserve the worth of multiple arthroplasty for RA patients with multiple joint destruction.
15901906 Cytokine genotypes correlate with pain and radiologically defined joint damage in patients 2005 Sep OBJECTIVES: Single nucleotide polymorphisms (SNPs) in cytokine genes have been associated with risk of a number of autoimmune diseases. Moreover, some SNPs are associated with variations in rates of in vitro gene expression, and it is therefore possible that these functional polymorphisms may differentially affect inflammatory processes and disease outcome. This project's objective was to determine whether cytokine genotypes correlate with disease outcomes in patients with juvenile rheumatoid arthritis (JRA). METHODS: Genotypes of SNPs of pro-inflammatory cytokines, tumour necrosis factor-alpha -308G -->A, interleukin-6 (IL-6) -174G -->C and interferon-gamma +874G -->A, and anti-inflammatory, immunosuppressive cytokines, interleukin-10 -1082G -->A, -819C -->T and -592A -->C and transforming growth factor-beta1 (TGF-beta1) codon 10T -->C and codon 25G -->C, were determined for patients with JRA who previously participated in a long-term outcome study. Cytokine genotypes and clinical variables showing significant correlations with clinical outcomes at the alpha = 0.100 level in univariate analyses were entered in multivariate tests. RESULTS: In multivariate tests, the IL-6 genotype -174G/G was positively correlated with pain [regression coefficient B = 0.899, 95% confidence intervals (CI) 0.185, 1.612, P = 0.014]. The homozygous TGF-beta1 codon 25G/G genotype showed a protective effect against joint space narrowing on radiographs taken within 2 yr of disease onset, but confidence intervals were wide [odds ratio (OR) 0.176, 95% CI 0.037, 0.837 P = 0.029]. CONCLUSIONS: The correlation of IL-6 genotype with pain and the possible association of the TGF-beta1 codon 25 genotype with short-term radiographic damage (G/C with greater risk and G/G with decreased risk) suggests that both these polymorphisms may be useful early prognostic indicators. Further studies of the relation between cytokine genotypes and outcomes in patients with all forms of juvenile idiopathic arthritis (JIA) are warranted.
17028815 Proposed [corrected] Japanese guidelines for the use of infliximab for rheumatoid arthriti 2005 Differences in ethnic backgrounds as well as in medical and socioeconomic status often affect both the efficacy and adverse effects of medications. Recent data suggest an increased risk of opportunistic infections, especially tuberculosis (TB), among rheumatoid arthritis (RA) patients receiving infliximab, a chimeric monoclonal anti-tumor necrosis factor alpha (TNF-alpha) antibody. In this regard, the annual incidence of TB is approximately five times higher in Japan than in the United States. Furthermore, since Bacillus Calmette-Guérin vaccination is mandatory in childhood when the skin test for purified protein derivative (PPD) is negative, a high incidence of false-positive PPD skin tests is observed among the Japanese population. In addition, the upper limit of methotrexate dosage to be used for RA is lower in Japan. We have therefore established official guidelines for the proper use of infliximab in Japanese RA patients. In this review, an algorithm for the diagnosis and management of TB in RA is presented in an evidenced-based form.
16278143 Tipping the balance towards tolerance: the basis for therapeutic immune modulation by gold 2005 Sep Gold salts have long been used in the treatment of rheumatoid arthritis. However, the basis for their therapeutic immune-modulating properties has never been satisfactorily explained. Furthermore, treatments are often marred by the development of adverse immune reactions such as hypersensitivity and even exacerbation of autoimmunity. We would like to propose a hypothesis to explain the basis for both the beneficial and adverse immune-modulating effects of gold in the treatment of rheumatoid arthritis. If accepted, this hypothesis will allow for the development of safer and more effective treatments with gold salts. The principle underlying this hypothesis also has broader implications for how immune hypersensitivity and tolerance are perceived.
17117588 Estrogen receptor ligands in the control of pathogenic inflammation. 2006 Nov Inflammation is recognized as a key component in a number of diseases, including rheumatoid arthritis, inflammatory bowel disease and atherosclerosis. Although well known for their classic effects on the reproductive tract and action by means of estrogen response elements in gene promoters, estrogens are also known to possess anti-inflammatory activity. This was originally highlighted with the observation that pregnancy ameliorates symptoms of rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. Furthermore, the antagonistic cross talk between nuclear factor kappaB and estrogen receptor signaling pathways has been well documented. Recently, novel estrogen receptor ligands, pathway-selective ligands and estrogen receptor beta-selective ligands have been identified which demonstrate potent anti-inflammatory activity; these ligands are being analyzed for their therapeutic potential in pathogenic inflammation.
17029071 Mechanisms of bone loss in rheumatoid arthritis. 2005 Rheumatoid arthritis (RA) is an autoimmune inflammatory disease in which destruction of bone in the joints causes major morbidity. Recent research has shed light on the cell and molecular mechanisms that lead to this osteolysis, all due directly or indirectly to the chronic inflammation. The aspects of this research covered in this review include the alteration of cell proliferation and survival that results in growth of the RA synovium. This process depends upon an increase in angiogenesis and local blood flow, which is also a feature of increased bone turnover. In addition, the inflammatory environment increases expression of chemokines, which are involved in the recruitment of monocytic osteoclast precursors. Chronic inflammation also promotes an overall catabolic state, with increased osteoclast differentiation and resorptive activity, driven by disregulation of receptor activator of NF-kappaB ligand (RANKL) and the synergistic activity of inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1. Osteoclast survival is increased in this environment, but osteoblast differentiation and survival are decreased, with a consequent reduction in bone formation and a net loss of bone. Recognition of these processes and the factors involved will enable more effective and targeted treatments for RA.
16816838 B cells move to centre stage: novel opportunities for autoimmune disease treatment. 2006 Jul The B-cell arm of the immune system has long been appreciated for its crucial role in pathogen resistance, but in the study of many autoimmune diseases, T cells have dominated the limelight for decades. However, the development of the B-cell-depleting antibody rituximab as a lymphoma therapy has provided a tool to probe the contribution made by B cells in several immune disorders. Recently, the success of B-cell depletion with rituximab in the treatment of rheumatoid arthritis has stimulated investigation of its effects in several other immune disorders, and considerable interest in the potential of drugs that can modulate B-cell function for the treatment of such diseases in general. This article discusses the role of B cells in a range of autoimmune disorders, including rheumatoid arthritis and systemic lupus erythematosus, and analyses approaches to therapeutic B-cell manipulation.
24783297 Biotechnologically produced drugs as second-line therapy for rheumatoid arthritis: Executi 2005 The aims of the present investigation were: ■. to assess the benefit of treatment with biotechnologically produced drugs compared with each other. ■. to assess the benefit of treatment with biotechnologically produced drugs compared with treatment with non-biotechnologically produced drugs, as well as ■. to assess the benefit of treatment with biotechnologically produced drugs compared with treatment without therapy extension (with or without placebo control); in each case as second-line therapy in patients with RA. The assessment was based on patient-relevant outcomes. In this context, “treatment extension” is understood as continued therapy initiated as a supplementation to existing therapy. For the present commission, for biotechnologically produced drugs (biologic disease modifying anti-rheumatic drugs, bDMARDs), second-line therapy, i.e. therapy after failure of previous treatment, was to be distinguished from first-line therapy, i.e. therapy in treatment-naive patients. In the present benefit assessment, the definition of second-line therapy therefore covered the use of biotechnologically produced drugs in persons who had been pretreated with at least one disease-modifying antirheumatic drug, also including biotechnologically produced ones.
16868981 RANTES and monocyte chemoattractant protein 1 as sensitive markers of disease activity in 2006 Aug OBJECTIVE: To longitudinally investigate serum and synovial fluid (SF) levels of RANTES and monocyte chemoattractant protein 1 (MCP-1) as well as in vitro migration of mononuclear cells toward SF in patients with juvenile rheumatoid arthritis (JRA). METHODS: Serum and SF levels of RANTES and MCP-1 were determined by enzyme-linked immunosorbent assay. Chemotaxis was performed using the modified Boyden chamber method. RESULTS: Serum RANTES levels were significantly increased in all onset types of JRA, with the highest levels present in systemic-onset JRA. Serum MCP-1 levels were significantly elevated in patients with systemic-onset JRA and were associated with current systemic features. Although serum levels of RANTES and MCP-1 decreased significantly after treatment, RANTES and MCP-1 levels during disease remission were still significantly higher in JRA patients than in controls. A relationship was found between serum RANTES levels during remission and the duration of clinical remission, with low levels being associated with prolonged clinical remission and high levels with shorter clinical remission. Serum RANTES levels correlated with C-reactive protein concentrations, hemoglobin values, white blood cell (WBC) counts, and platelet counts, whereas serum MCP-1 levels correlated with WBC counts and serum ferritin levels. Levels of RANTES and MCP-1 in SF were elevated as compared with levels in serum. SF chemotactic activity for mononuclear leukocytes was significantly inhibited by either anti-RANTES or anti-MCP-1 antibody. CONCLUSION: RANTES is a key molecule in the pathogenesis of all onset groups of JRA, whereas MCP-1 is particularly important in systemic-onset JRA. Serum levels of these CC chemokines represent more highly sensitive markers of disease activity than conventional markers of inflammation.
15965548 Lyme arthritis in 20 children residing in a non-endemic area. 2005 Jun In non-endemic areas of the country, Lyme disease may not be considered in children who present with arthritis. This report details the clinical features of Lyme arthritis in 20 children residing in central Virginia. All patients presented with transient, often recurrent oligoarthritis of large joints, particularly the knee. Most patients were referred with a presumptive diagnosis of juvenile rheumatoid arthritis (JRA). This report reiterates the clinical presentation of Lyme arthritis in children and reminds physicians to consider the diagnosis of Lyme arthritis in children who present with acute arthritis even if they reside in a non-endemic area of the country. In addition, it differentiates the clinical presentation of Lyme arthritis from JRA.
16739206 Differences in disease outcomes between medicaid and privately insured children: possible 2006 Jun 15 OBJECTIVE: To determine the relationship between health insurance status and disease outcome in children with juvenile rheumatoid arthritis (JRA). METHODS: JRA patients followed at a tertiary pediatric rheumatology center were assessed for the number of active joints and number of joints with limited range of motion. Disease activity, patient well-being, and pain were measured. Disability was assessed by the Childhood Health Assessment Questionnaire, health-related quality of life by the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale, and the PedsQL Rheumatology Module. Health care resource utilization was estimated based on the number of billing events for health services coded in administrative databases; these databases also provided information on patient health insurance status. Children insured by Medicaid or similar state programs for low-income families were considered to have Medicaid status. Disease outcomes of children with Medicaid status was compared with that of children with private health insurance. RESULTS: Forty (14%) of the 295 children with JRA had Medicaid status. Patients with Medicaid status were more often of nonwhite race (P < or = 0.04) and more frequently had a polyarticular or systemic disease course (P = 0.04) compared with other patients (n = 255). After correction for differences in disease duration, race, JRA onset, and JRA course between groups, children with Medicaid status continued to have significantly higher disability (P < 0.0003), and lower mean PedsQL Generic Core Scale scores (P < 0.05), while health resource utilization appeared similar between groups. CONCLUSION: Despite apparently similar health resource utilization and joint involvement, Medicaid status is associated with significantly lower health-related quality of life and higher disability in JRA.
16287594 Conventional disease-modifying antirheumatic drugs in early arthritis. 2005 Nov This article reviews the use of conventional disease-modifying antirheumatic drugs (DMARDs) in the treatment of early rheumatoid arthritis (RA). The Finnish early RA cohorts are used as examples of how early and active treatment strategies have improved over time with increasing variety of available DMARDs. Therapy goals of early RA include remission to prevent severe long-term outcomes of RA. Remission can be achieved in a third of patients with early RA using a combination of conventional DMARDs, including methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone. Of patients with early RA, 20% to 30% do not improve enough with conventional treatments and should be identified at early phases to consider institution of biologic agents.
18038609 [Pain versus activity and fatigue in adolescents hospitalized because of cancer and rheuma 2006 INTRODUCTION: Chronic disease in adolescence is followed by many negative effects of somatic and psychosocial nature. These effects can be observed especially in oncological and rheumatologic diseases. This is due not only to the character of the disease, its chronic course, but also aggressive treatment. The objective of this work was to evaluate relationship between pain experience and sleep, fatigue and physical, social and intellectual functioning of teenage patients. MATERIAL AND METHODS: 124 adolescents, 14 to 20 years old, hospitalized because of cancer and juvenile rheumatoid arthritis participated in the study. Level of experienced pain was measured with VAS--Visual Analog Scale and NRS--Numeric Rating Scale. Quality of sleep was assessed with Polish version of Melzacks Questionnaire. Fatigue and activity were assessed with a questionnaire of our own construction. RESULTS: Pain was a significant symptom accompanying rheumatologic and oncological disease, although the sources of pain experience were different. Significant percentage of participants suffered from sleep disruption and activity impairment. An important relationship between increase of pain intensity and sleep disruption in oncological patients was found. Significant relationships between pain intensity vs. fatigue and also pain intensity vs. functioning were identified. CONCLUSIONS: Pain, fatigue and sleep disruption account for important factors in rheumatologic and oncological diseases. They also cause decrease in physical, social and mental functioning of teenage patients. Results show that there is a significant relationship between outcomes of disease, its treatment and impact on functioning and developmental course of adolescents. Care delivered to those patients must be integrated and involve multidisciplinary factors.
16763455 Synovial biomarkers in the spondylarthropathies. 2006 Jul PURPOSE OF THE REVIEW: To explore the concept of a biomarker, or surrogate endpoint, to enhance early diagnosis or predict the response to therapeutic intervention in patients with spondylarthropathy. RECENT FINDINGS: Immunopathologic studies have suggested that the features of spondylarthropathy are distinctive, supporting a prominent role for innate immune cells, and can be consistently differentiated from rheumatoid arthritis. Successful treatment of spondylarthropathy synovitis resulted in rapid and sustained decrease in infiltration by macrophage populations and neutrophils, and decreased expression of many proinflammatory mediators. Consistent with studies in rheumatoid arthritis, significant correlations between the effects of both methotrexate and infliximab on disease activity and sublining macrophage populations were reported. These observations highlight the possibility that macrophage populations may be a synovial tissue biomarker of therapeutic intervention in spondylarthropathy. Preliminary studies have evaluated advanced genomic and proteomic methodologies in spondylarthropathy. SUMMARY: Defining the immunopathology of spondylarthropathy has been associated with identifying potential biomarkers of the clinical response to therapeutic intervention. A surrogate marker of arthritis activity in spondylarthropathy could profoundly enhance screening for efficacy and optimization of dose ranges in early-phase randomized clinical trials.
16777575 Psoriatic arthritis: one or more diseases? 2006 Jun Psoriatic arthritis (PsA) is a common, debilitating auto-immune disease with diverse clinical features. In this paper, published evidence is examined, which addresses the issues that (a) PsA exists; and (b) PsA can or cannot be viewed as a distinct rheumatic disease from other spondyloarthritides. Evidence derived from epidemiological, clinical, genetic and immunohistological studies is included. Summarizing the evidence, it is clear that PsA does indeed exist, with the prevalence of rheumatic disease in patients with psoriasis (Ps) higher than would be expected. Certain clinical features also occur more commonly in PsA, although none can differentiate consistently from other arthropathies. Both genetic and immunohistological studies suggest that PsA, both oligo- and polyarticular disease, can be clearly separated from rheumatoid arthritis and that it belongs to the family of spondyloarthritides. The presence of Ps may confer a more severe clinical phenotype with poor radiological outcome. It may be that, with time, a specific genetic marker or diagnostic feature will emerge; additional, more detailed pathogenic studies are required. In the meanwhile, particularly with new treatments being evaluated, it is important to continue to develop specific classification or diagnostic criteria and to define both clinical and laboratory-based outcome measures.
16378499 Inhibitors of TACE and Caspase-1 as anti-inflammatory drugs. 2005 TNF-alpha neutralising agents such as Infliximab (Remicade), Etanercept (Enbrel) and the IL-1 receptor antagonist Anakinra (Kineret), are currently used clinically for the treatment of many inflammatory diseases such as Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis and psoriasis. These protein preparations are expensive to manufacture and administer, need to be injected and can cause allergic reactions. An alternative approach to lowering the levels of TNF-alpha and IL-1beta in inflammatory disease, is to inhibit the enzymes that generate these cytokines using cheaper small molecules. This paper is a broad overview of the progress that has been achieved so far, with respect to small molecule inhibitor design and pharmacological studies (in animals and humans), for the metalloprotease Tumour Necrosis Factor-alpha Converting Enzyme (TACE) and the cysteine protease Caspase-1 (Interleukin-1beta Converting Enzyme, ICE). Inhibitors of these two enzymes are currently considered to be good therapeutic targets that have the potential to provide relatively inexpensive and orally bioavailable anti-inflammatory agents in the future.
17004912 Mulberry extract supplements ameliorate the inflammation-related hematological parameters 2006 Fall Mulberry fruit (Morus Lhou Koidz.), a rich source of the major anthocyanin, cyanidin 3-glucoside (C3G), has traditionally been used for the treatment of inflammatory conditions including rheumatic arthritis. In this study, we evaluated the efficacy of orally administrated methanolic mulberry fruit extract (ME) in carrageenan-induced arthritic rats, based on previously observed in vitro antioxidant and anti-inflammatory activities. A significant attenuation of hind paw inflammation characterized by fluid accumulation, uric acid production, and rheumatoid factors induced by carrageenan was observed following the intake of both ME (50 mg/kg of body weight) and C3G (10 mg/kg of body weight). Moreover, alterations in hematological parameters such as serum triglyceride, high-density lipoprotein-cholesterol, and atherogenic index following carrageenan administration were partially reversed by the administration of ME. It is concluded that dietary mulberry fruit extracts elicited protection against carrageenan-induced inflammation.
16283419 Acute respiratory failure revealing adult-onset Still's disease: diagnostic value of low g 2006 Sep The authors report three cases of adult-onset Still's disease with severe hypoxemic pulmonary involvement, mimicking severe pulmonary sepsis. Clinicians must be aware of this rare form of such disease. Low (<20%) glycosylated ferritin level in the presence of unexplained prolonged fever with leukocytosis can help in the diagnosis.
16507116 Intra-articular injection of recombinant TRAIL induces synovial apoptosis and reduces infl 2006 We demonstrated previously that local, intra-articular injection of an adenoviral vector expressing human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a rabbit knee model of inflammatory arthritis stimulated synovial apoptosis and reduced inflammation. To examine whether intra-articular injection of recombinant chimeric human TRAIL protein (rTRAIL) also induces apoptosis of proliferating rabbit synovium and reduces inflammation, we used an experimental rabbit arthritis model of rheumatoid arthritis, induced by intra-articular introduction of allogeneic fibroblasts genetically engineered to secrete human IL-1beta. Analysis of synovium isolated from the rabbits treated with intra-articular injection of rTRAIL, relative to saline control, showed areas of extensive acellular debris and large fibrous regions devoid of intact cells, similar to adenoviral mediated TRAIL gene transfer. Extensive apoptosis of the synovial lining was demonstrated using TUNEL analysis of the sections, corresponding to the microscopic findings in hematoxylin and eosin staining. In addition, leukocyte infiltration into the synovial fluid of the inflamed knee joints following rTRAIL treatment was reduced more than 50% compared with the saline control. Analysis of the glycosaminoglycan synthetic rate by cultured cartilage using radiolabeled sulfur and cartilage histology demonstrated that rTRAIL did not adversely affect cartilage metabolism and structure. Analysis of serum alanine aminotransferase showed that intra-articular injection of rTRAIL did not have adverse effects on hepatic function. These results demonstrate that intra-articular injection of rTRAIL could be therapeutic for treating pathologies associated with rheumatoid arthritis.
21655530 An unusual cause of meningitis. 2005 A 57 year old man patient presented with fever and frontal headache. He had a background history of sero-positive rheumatoid arthritis which was well controlled on immunomodulatory disease modifying anti-rheumatoid drugs (DMARDS) including methotrexate and lef lunomide. Six months earlier he had returned from Massachussetts in the USA after a one year period of residence there. On examination his vital signs were within normal limits and he was afebrile with a temperature of 36.1oC. His left elbow joint was warm, tender and swollen; examination was otherwise normal.