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ID PMID Title PublicationDate abstract
16769782 Glucocorticoid resorption and influence on the hypothalamic-pituitary-adrenal axis after i 2006 Jul BACKGROUND: Studies have shown that intra-articular glucocorticoid injection treatment for knee synovitis has a better outcome in resting patients than in mobile patients. One reason for this observation might be that rest retards steroid resorption, causing an enhanced local treatment effect. OBJECTIVES: To study drug resorption and the impact on hormone production in the hypothalamic-pituitary-adrenal axis after intra-articular glucocorticoid administration, with and without postinjection rest. METHODS: Twenty patients with rheumatoid arthritis and knee synovitis were randomised to either 24 hour bed rest or normal activity after intra-articular glucocorticoid treatment with 20 mg triamcinolone hexacetonide (THA). Serum levels of THA, cortisol, and adrenocorticotropic hormone (ACTH) were followed during 2 weeks. RESULTS: Short term and reversible decreases in serum cortisol and ACTH levels (p<0.001) were seen, without any significant differences between resting and mobile patients. The THA levels increased similarly in both groups, with the median serum peak seen after 8 hours. CONCLUSION: Immobilisation does not appear to retard glucocorticoid resorption after intra-articular administration. Further studies are therefore needed to clarify the mechanism behind the beneficial effects of rest after intra-articular glucocorticoid treatment for knee synovitis.
17991203 Reverse epidemiology beyond dialysis patients: chronic heart failure, geriatrics, rheumato 2007 Nov "Reverse epidemiology" refers to paradoxical and counterintuitive epidemiologic associations between survival outcomes and traditional cardiovascular risk factors such as obesity, high blood pressure, and high cholesterol. Reverse epidemiology has been well described in end stage renal disease, but also has been observed in chronic disease states, including chronic heart failure, rheumatoid arthritis, chronic obstructive pulmonary disease, and Acquired Immune Deficiency Syndrome, and in elderly populations. This review will highlight the recent medical literature on reverse epidemiology in these populations. Common pathophysiologic underpinnings in these chronic disease states may help explain the reversal of risk factors observed in these diverse populations. Furthermore, guidelines for the general population for optimal goals of weight, cholesterol levels, and blood pressure may not apply to special populations, including patients with chronic diseases or elderly persons.
18585457 Immunotherapeutic mechanisms of anti-CD20 monoclonal antibodies. 2008 Aug The anti-CD20, B-cell-specific mAb rituximab (RTX) has been approved for treatment of non-Hodgkin's B cell lymphoma and rheumatoid arthritis. Under conditions of high B cell burden, exhaustion of the body's effector mechanisms, for example, NK-cell-mediated killing, may lead to substantial decreases in the immunotherapeutic efficacy of this mAb. Moreover, RTX treatment of patients with chronic lymphocytic leukemia and high levels of circulating B cells can lead to removal of CD20 from the cells, thus allowing them to persist and resist clearance. RTX therapy for several autoimmune diseases has proven to be effective, but in numerous instances there has been little correlation between reductions in disease activity and changes in titers of pathogenic autoantibodies. This paradox may be explained by a separate mechanism: Binding of RTX to B cells generates immune complexes that act as decoys to attract monoycte/macrophages and thus reduce their inflammatory activity in certain autoantibody-mediated diseases. Several second-generation anti-CD20 mAbs with enhanced cytotoxic action have been developed and are being tested in the clinic for treatment of cancer and autoimmune diseases. The application of these mAbs, potentially in combination with immune effector modifying drugs, may successfully address the shortcomings of current anti-CD20 immunotherapy.
17653550 Measurement of advanced glycation endproducts in skin of patients with rheumatoid arthriti 2007 Dec Advanced glycation endproducts (AGEs) are the products of non-enzymatic glycation and oxidation of proteins and lipids. Low-turnover tissues such as articular cartilage seem to be susceptible to the accumulation of AGEs, which might lead to cartilage degradation. Recently, a non-invasive method for measuring skin AGE accumulation was developed by using the Autofluorescence Reader (AFR). To examine the usefulness of measuring skin AGE in patients with bone and joint diseases, we examined autofluorescence (AF) levels in skin of patients with osteoarthritis (OA), rheumatoid arthritis (RA), and dialysis-related spondyloarthropathy (DRSA). Ninety-three patients with RA, 24 patients with OA, and 29 patients with DRSA were examined, and 43 healthy volunteers were used as controls. Skin AF was assessed on the lower arm with the AGE-Reader. Mean AF was significantly higher in the patients with RA (median 2.13 and range 1.25-2.94) or with DRSA (median 2.21 and range 1.29-3.88) than in the patients with OA (median 1.63 and range 1.07-2.31) or in the controls (median 1.74 and range 1.10-2.46). There was no significant difference between OA and the controls, or between RA and DRSA. These findings suggest that differences of AGE accumulation in the skin might reflect the different pathologies of these diseases.
17299837 Hand function and activity limitation according to health assessment questionnaire in pati 2007 Feb OBJECTIVE: This study identifies baseline predictors of future activity limitation in rheumatoid arthritis (RA). To reinforce the utility of instruments assessing functional ability/activity limitation, we used reference data from healthy referents. METHODS: This study includes 189 patients (69% women) with recent-onset RA (onset of joint swelling not more than 12 months at diagnosis) in a prospective cohort ("the Swedish TIRA project") during 27 months from 1996 through 1998. Regular followups were done for a period of 5 years, and 123 healthy persons (50% women) were recruited as referents. Hand function was assessed by the "grip ability test (GAT)" and "signals of functional impairment" (SOFI). Grip force was measured with the electronic device Grippit. Activity limitation was assessed with the Swedish version of the Health Assessment Questionnaire (HAQ). RESULTS: Throughout the study and for both sexes, GAT, grip force, SOFI-hand, and HAQ were significantly different for the patients compared to healthy referents. In the healthy referents, HAQ was mainly related to age and GAT, whereas in RA HAQ was most obviously linked to grip force. Five years after diagnosis only 8% of HAQ outcome was explained by the baseline measures: HAQ, grip force, SOFI-lower limb, sex, walking speed, and GAT. CONCLUSION: Our study provides valuable reference data for several functional ability and activity limitation measures. The HAQ score was explained by different variables in healthy referents compared to patients with RA. Five years after diagnosis only 8% of HAQ outcome was explained by the variables assessed at inclusion.
17205826 [Toxicity attenuation and efficacy potentiation effect of liquorice on treatment of rheuma 2006 Dec OBJECTIVE: To investigate the toxicity attenuation and efficacy potentiation effect of liquorice on treatment of rheumatoid arthritis (RA) with Tripterygium wilfordii (TW). METHODS: One hundred and twenty RA patients were randomly assigned to two groups: the treated group treated with compound decoctum of TW and liquorice and the control group with TW ployglycosidium tablets both based on routine treatment. The therapeutic effect and adverse reaction were observed after 2 months of treatment. RESULTS: The total efficacy rate was 89.8% in the treated group and 79.6% in the control group with insignificant difference between the two groups; the effect was better in the treated group than that of the control group in decreasing the swollen joint index and increasing the average grip strength of both hands (P < 0.05); the total incidence of adverse reaction was obviously lower in the treated group than that of the control (P < 0.01). CONCLUSION: Liquorice has toxicity attenuation and efficacy potentiation effect on treatment of RA with TW.
19022816 Protection against rheumatoid arthritis by HLA: nature and nurture. 2008 Dec Rheumatoid arthritis (RA) is a complex genetic disorder in which the HLA region contributes most to the genetic risk. HLA-DRB1 molecules containing the amino acid sequence QKRAA/QRRAA/RRRAA (ie, HLA-DRB1*0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001 and *1402) at position 70-74 in the third hypervariable region of the DRB1 chain are associated with susceptibility to RA. HLA-DRB1 molecules containing the amino acids "DERAA" (ie, HLA-DRB1*0103, *0402, *1102, *1103, *1301, *1302 and *1304) at the same position are associated with protection from RA. Interestingly, not only inherited but also non-inherited HLA-antigens from the mother can influence RA susceptibility. A protective effect of "DERAA"-containing HLA-DRB1 alleles as non-inherited maternal antigen (NIMA) has recently been described. The underlying mechanism of this protective effect is currently unknown, although a possible explanation is covered below. In this review, an overview of the current knowledge on protection against RA is given and the inherited and NIMA effect of "DERAA"-containing HLA-DRB1 alleles are compared.
18417876 Serum transferrin receptor-ferritin index shows concomitant iron deficiency anemia and ane 2008 Jan Anemia is a frequent cause of morbidity in patients with rheumatoid arthritis (RA). We studied the prevalence of anemia of chronic disorders (ACD) and ACD with coexistent iron deficiency anemia (IDA) in patients with RA using sTfR/log ferritin ratio (sTfR - F index). Complete blood counts, percent transferrin saturation, serum ferritin, sTfR, sTfR-F index measurements were carried out in 100 anemic RA patients. Twenty-five IDA subjects without any other illness and 25 age- and sex-matched normal controls were studied. Prevalence of anemia in RA patients was 50.5%. Patients with sTfR-F index value < 1.5 were classified as pure ACD and patients with sTfR-F index value> 1.5 were classified as ACD with coexistent IDA. Using these criteria, 20% patients were found to have pure ACD and 80% patients had coexistent ACD and IDA. In the normal control group, sTfR-F index was found to be 0.16-1.8. We found that sTfR-F index can clearly distinguish IDA control cases and normal subjects with no overlap in the range of sTfR-F index.
17640450 Psychological well-being across 1 year with rheumatoid arthritis: coping resources as buff 2007 Sep OBJECTIVES: Using the transactional model of stress and coping, the present study investigated whether specific coping resources act as buffers of the relationship between perceived stress and psychological well-being among rheumatoid arthritis (RA) patients. DESIGN: A longitudinal observational study was carried out with assessments at baseline, 6 months and 1 year. METHODS: Measures of perceived stress, coping resources (optimism/pessimism, social support and explicit active coping strategies) and psychological well-being (anxiety, depression and life satisfaction) were completed by 134 RA patients. Demographics, RA duration, pain, fatigue, functional disability, antidepressant use and physical comorbidities were recorded and statistically controlled for. RESULTS: Perceived stress had the strongest relationship with psychological well-being at baseline, and affected anxiety after 6 months. Optimism and pessimism predicted psychological well-being across 1 year. Active behavioural coping buffered an association of stress with depression at baseline, while baseline active cognitive coping buffered the effect of baseline stress on life satisfaction after 6 months. CONCLUSIONS: Patients with RA under greater perceived stress who do not use active coping strategies appear to be at risk of psychological comorbidity and may therefore benefit from interventions teaching specific active coping strategies. Larger observational studies and interventions are required to confirm and extend these findings.
18058104 Unusual presentation of non-Hodgkin lymphoma: polyarthritis and uveitis mimicking a rheuma 2008 Apr We report a case of 45-year-old male who presented with polyarthritis and posterior uveitis. He was given azathioprine (AZA) 150 mg day(-1) and methyl-prednisolone 48 mg day(-1) for his uveitis and polyarthritis. Eye and joint complaints improved with these medications within 1 month. Three months later, while he was on AZA, the patient presented with pain on his anterior chest wall associated with diffuse hyperemic and warm mass lesion. A wedge biopsy of the lesion was reported as diffuse large B-cell NHL. Here, we briefly discuss the relationship between arthritis, uveitis and lymphoproliferative disease.
16881365 [Catalytic autoantibodies as a new molecular instrument in rheumatological practice]. 2006 AIM: To compare clinicopathogenetic value of DNA-hydrolizing autoantibodies or DNA-abzymes in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). MATERIAL AND METHODS: We studied sera from 180 patients with SLE, 180 RA patients and 128 healthy donors matched by age and gender; assessed catalytic and cytotoxic activity of DNA-abzymes in patients with different variants of SLE and RA course. RESULTS: The highest catalytic and cytotoxic activities of DNA abzymes were observed in SLE patients. In SLE catalytic and cytotoxic activities of DNA abzymes ranged widely and their mean values depended on SLE activity in patients with systemic lesions. DNA-abzymes in RA patients showed lower catalytic and cytotoxic activities in relation to substrate DNA and target cells than in SLE. DNA-abzymes occurred most frequently in patients with high activity of RA, slow-progressive and lingering course of RA, especially in early development of visceral (extra-articular) pathology. Characteristic for DNA-abzymes in RA and SLE is the phenomenon of wide-range fluctuations due to factors determinating probability of induction of function of Ab-mediated catalysis and, therefore, incidence rates of DNA-abzymes, probably catalytic autoAb of the other specificity in a population of patients with systemic autoimmune diseases. CONCLUSION: The data indicate the validity of DNA abzymes use in clinical practice for realization of diagnostic and therapeutic programs in SLE and RA.
16626993 Methotrexate therapy for rheumatoid arthritis: clinical practice guidelines based on publi 2006 Jul OBJECTIVES: To develop clinical practice guidelines for the use of methotrexate in rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing recommendations. Evidence providing answers to the five questions was sought in the Cochrane databases, PubMed, and proceedings of meetings of the French Society for Rheumatology, European League Against Rheumatism, and American College of Rheumatology. Using this evidence, a group of rheumatologists developed and validated the recommendations. For each recommendation, the level of evidence and the extent of agreement among experts were specified. RESULTS: The recommendations were as follows: 1: The starting dosage for methotrexate in patients with RA should not be less than 10 mg/week and should be determined based on disease severity and patient-related factors; 2: When a patient with RA shows an inadequate response to methotrexate, the dosage should be increased at intervals of 6 weeks, up to 20 mg/week, according to tolerance and patient-related factors; 3: When starting methotrexate treatment in a patient with RA, preference should be given to the oral route. A switch to the intramuscular or subcutaneous route should be considered in patients with poor compliance, inadequate effectiveness, or gastrointestinal side effects; 4: At present, there is no evidence indicating that a change in methotrexate dosage is in order when a TNF antagonist is given concomitantly; 5: The investigations that are mandatory before starting methotrexate therapy in a patient with RA consist of a full blood cell count, serum transaminase levels, serum creatinine with computation of creatinine clearance, and a chest radiograph. In addition, serological tests for the hepatitis viruses B and C and a serum albumin assay are recommended. In patients with a history of respiratory disease or current respiratory symptoms, lung function tests with determination of the diffusing capacity for carbon monoxide are recommended; 6: Investigations that are mandatory for monitoring methotrexate therapy in patients with RA consist of full blood cell counts and serum transaminase and creatinine assays. These tests should be obtained at least once a month for the first 3 months then every 4-12 weeks; 7: Folate supplementation can be given routinely to patients treated with methotrexate for RA. In practice, a minimal dosage of 5 mg of folic acid once a week, at a distance from the methotrexate dose, is appropriate; 8: In the event of respiratory symptoms possibly related to methotrexate toxicity, the drug must be stopped and symptom severity evaluated. Should evidence of serious disease be found, the patient should be admitted immediately or advice from a pulmonologist should be obtained immediately. CONCLUSION: Recommendations about methotrexate therapy for RA were developed. These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.
17642245 [Effective combination therapy of TNF antagonists with DMARDs]. 2007 Jul Efficacy and safety of anti-tumor necrosis factor (TNF) antagonists (infliximab, etanercept, adalimumab) in combination with methotrexate for rheumatoid arthritis is well determined. But methotrexate is not tolerable nor effective in some cases. Leflunomide in combination with anti-TNF antagonists is the alternative combination therapy in the world. But unfortunately, leflunomide itself is not tolerable for some Japanese cases because of fatal interstitial pneumonitis. A prospective open-label study of sulfasalazine, hydroxychloroquine, intramusculer gold in combination with etanercept indicated the efficacy and tolerability. Azathiopurine and bucillamine may be used when methotrexate is not effective or intolerable, although they need more examination.
16819609 Prevalence and correlates of inflammatory arthritis in Germany: data from the First Nation 2006 Nov The aim of this paper is to generate data on the prevalence of inflammatory arthritis in different subgroups of the population and to identify correlates on the basis of population-based cross-sectional data: the "First National Health Survey of the Federal Republic of Germany". This Survey investigated the prevalence of inflammatory arthritis, comorbidity and health-relevant behaviors on the basis of interviews with physicians and medical evaluations conducted in the period from October 1997 to March 1999. The study was based on a net sample comprising 6,461 subjects aged 18-79. Our data demonstrate an overall prevalence of 3.4% for inflammatory arthritis. The prevalence of inflammatory arthritis is significantly higher in women, the over-50, lower-income groups, and habitual smokers. Patients with inflammatory arthritis have a higher rate of numerous comorbidities such as osteoporosis, thyroid disease, chronic bronchial disease, hypertension, and elevated blood lipids versus healthy reference groups.
18696403 [Is the guideline, "Management of early rheumatoid arthritis," being followed in a rheumat 2008 Aug BACKGROUND: There are indications that the influence of external guidelines on the quality of health care is limited and they are little or not at all used in clinical practice. It was the aim of this study to examine how and to what extent the external S3 guideline "Management of Early Rheumatoid Arthritis" was applied in a rheumatism center. MATERIALS AND METHODS: In accordance with the data of all rheumatoid arthritis patients, who were treated November 2007, an investigation was carried out on the degree of application and realization of the S3 guideline which had been changed into an internal guideline. The primary objective was the Disease Modifying Anti-Rheumatic Drug (DMARD) therapy; secondary objectives were the administration of methotrexate with folic acid, the administration of glucocorticoids with calcium and vitamin D; and NSAR monotherapy. RESULTS: 94.6 % of the patients were given a therapy of basis drugs (DMARDs). 82.5 % of the methotrexate patients additionally received folic acid. 65.9 % of the patients received, in addition to glucocorticoids, calcium and vitamin D. In 99.1 % of the cases NSAR monotherapy was instituted. CONCLUSION: The high degree of application does not correspond with the results of previous studies on guideline compliance with external guidelines. A possible explanation of this may be the change made of the external guideline to a guideline within the hospital.
18706093 Cia5d regulates a new fibroblast-like synoviocyte invasion-associated gene expression sign 2008 INTRODUCTION: The in vitro invasive properties of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) have been shown to correlate with disease severity and radiographic damage. We recently determined that FLSs obtained from pristane-induced arthritis (PIA)-susceptible DA rats are also highly invasive in the same in vitro assay through Matrigel. The transfer of alleles derived from the arthritis-resistant F344 strain at the arthritis severity locus Cia5d (RNO10), as in DA.F344(Cia5d) congenics, was enough to significantly and specifically reduce the invasive properties of FLSs. This genetically controlled difference in FLS invasion involves increased production of soluble membrane-type 1 matrix metalloproteinase (MMP) by DA, and is dependent on increased activation of MMP-2. In the present study we aimed to characterize the pattern of gene expression that correlates with differences in invasion in order to identify pathways regulated by the Cia5d locus. METHODS: Synovial tissues were collected from DA and DA.F344(Cia5d) rats 21 days after the induction of PIA. Tissues were digested and FLSs isolated. After a minimum of four passages, FLSs were plated on Matrigel-covered dishes at similar densities, followed by RNA extraction. Illumina RatRef-12 expression BeadChip arrays were used. Expression data were normalized, followed by t-test, logistic regression, and cluster analysis. Real-time PCR was used to validate the microarray data. RESULTS: Out of the 22,523 RefSeq gene probes present in the array, 7,665 genes were expressed by the FLSs. The expression of 66 genes was significantly different between the DA and DA.F344(Cia5d) FLSs (P < 0.01). Nineteen of the 66 differentially expressed genes (28.7%) are involved in the regulation of cell cycle progression or cancer-associated phenotypes, such as invasion and contact inhibition. These included Cxcl10, Vil2 and Nras, three genes that are upregulated in DA and known to regulate MMP-2 expression and activation. Nine of the 66 genes (13.6%) are involved in the regulation of estrogen receptor signaling or transcription. Five candidate genes located within the Cia5d interval were also differentially expressed. CONCLUSIONS: We have identified a novel FLS invasion associated gene expression signature that is regulated by Cia5d. Many of the genes found to be differentially expressed were previously implicated in cancer cell phenotypes, including invasion. This suggests a parallel in the behavior of arthritis FLSs and cancer cells, and identifies novel pathways and genes for therapeutic intervention and prognostication.
18455684 Multipotent mesenchymal stromal cells in articular diseases. 2008 Apr Although cartilage defects are common features of osteoarthritis and rheumatoid arthritis, current treatments can rarely restore the full function of native cartilage. Recent studies have provided new perspectives for cartilage engineering using multipotent mesenchymal stromal cells (MSC). Moreover, MSC have been used as immunosuppressant agents in autoimmune diseases and have tested successfully in animal models of arthritis. However, the sequential events occurring during chondrogenesis must be fully understood before we can reproduce the complex molecular events that lead to MSC differentiation and long-term maintenance of cartilage characteristics in the context of chronic joint inflammation. This chapter focuses on the potential of MSC to repair cartilage, with an emphasis on the factors that are known to be required in inducing chondrogenesis and on their immunosuppressive potential.
17710405 Tumor necrosis factor alpha -308 polymorphism is associated with rheumatoid arthritis in H 2007 Dec The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) in tumor necrosis factor alpha (TNFalpha) promoter with rheumatoid arthritis (RA) in Chinese Han population. Six SNPs at positions -238, -244, -308, -376, -857, -863 within TNFalpha promoter were genotyped in 367 unrelated RA patients and 271 healthy controls, using direct DNA sequencing method. Allelic, genotypic, and haplotypic associations of these SNPs with RA were examined. The frequencies of TNFalpha -308A allele and the haplotype GACC (in order of -238, -308, -857, -863) were significantly lower in RA patients when compared with healthy controls (P = 0.0046, P = 0.0045, respectively) but TNFalpha -308 polymorphism was not related to the clinical manifestations of RA patients. These results implied that TNFalpha gene itself or a gene in linkage disequilibrium with it might be associated with RA in Han population of Eastern China.
16856547 [Therapeutic agents for rheumatoid arthritis: infliximab (a chimeric human IgG 1 monoclona 2006 Jul Tumor necrosis factor (TNF) plays an important role in the pathogenesis of rheumatoid arthritis (RA). The agents, interfering specifically with the cytokine, have been produced to ameliorate disease activity of RA. There are only two reagents available in the Japanese market. Infliximab, a chimeric (mouse/human) IgG 1 monoclonal antibody to TNF-alpha, shows better efficacy in the combination with methotrexate (MTX) which reduces antichimeric molecule antibody responses in the RA therapy. Etanercept is a soluble form of human TNF type II receptor linked to an IgG 1-Fc moietry. Both TNF-alpha antagonists demonstrated excellent clinical efficacy and the addition of MTX at the early phase from the onset protected bone destruction. Infections are most frequent in their adverse effects.
16565896 Oxidative status in rheumatoid arthritis. 2007 Jan The insufficiency of antioxidant defense systems and the acceleration of the oxidative reactions can be results of the pro-oxidant/antioxidant imbalance in rheumatoid arthritis (RA). The aim of our study was to investigate the changes in oxidant status by measuring two different parameters; one was the level of malondialdehyde (MDA) as an index of lipid peroxidation and the other was total oxidative status; we could then compare our results with the antioxidant status, superoxide dismutase (SOD) enyzme activities. All were assessed in 22 patients with active RA and 18 age- and gender-matched control subjects. While serum MDA levels were significantly increased in patients with RA compared to the control group (p<0.03), the total oxidative status levels were decreased in patients with RA compared to the control group (p<0.008), and serum SOD activities did not show any statistical difference between the two groups. In conclusion, the increased MDA levels in our study may be important as a marker but are not sufficient to conclude that there was an increase in oxidative stress in RA patients because supporting results were not obtained from SOD and oxidative status measurements. These results give further support to the concept of oxygen free radicals playing a role in the pathogenesis of chronic inflammatory disorders, but we also consider that there is a more complex relationship than has been assumed. We think that further studies are needed to clarify these conflicting results.