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ID PMID Title PublicationDate abstract
17122964 The active metabolite of leflunomide, A77 1726, increases proliferation of human synovial 2006 Nov OBJECTIVE AND DESIGN: Excessive synovial fibroblast (SF) proliferation is detrimental in rheumatoid arthritis. We therefore sought to determine the effects of A77 1726, the active metabolite of leflunomide, on SF proliferation. METHODS: Human SFs were used. Cell proliferation was investigated using MTS assay, by (3)H-thymidine incorporation and cell counts. RESULTS: Whereas A77 1726 alone had no effects, it significantly increased the mitogenic effects of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). Cyclooxygenase inhibition might be at least partly involved, since indomethacin displayed similar effects, and since prostaglandin E2 inhibited SF proliferation. In contrast, the effect of A77 1726 did not appear to be mediated through depletion of the pyrimidine pool or inhibition of tyrosine kinases. CONCLUSION: A77 1726 displays proliferative effects in presence of IL-1beta and TNF-alpha. Further elucidation of involved mechanisms may prove useful for the utilization of leflunomide, the development of related compounds or elaboration of new therapeutic strategies.
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.
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.
16341746 The difficulty of opening medicine containers in old age: a population-based study. 2005 Oct OBJECTIVES: To investigate elderly people's ability to open medicine containers, and how this ability correlates to some common disorders that may cause functional or cognitive impairment. METHODS: Cross-sectional study of older people age 81 years and older, from the second follow-up (1994-1996) of the Kungsholmen project, a population-based study of very old people in an urban area of Stockholm, Sweden. Six hundred and four persons (mean age 86.7 years) were tested for their ability to open three types of medicine containers. The disorders studied were rheumatoid arthritis, stroke, Parkinson's disease, cognitive impairment (measured by mini-mental state examination, MMSE) and impaired vision. RESULTS: We found that 14% were unable to open a screw cap bottle, 32% a bottle with a snap lid, and 10% a blister pack. Female gender, higher age, living in an institution, Parkinson's disease, rheumatoid arthritis, cognitive impairment and impaired vision were all associated with a decreased ability to open the containers. Less than half of the elderly people who were unable to open one or more of the containers received help with their medication. Among those living in their own homes only 27% received help. CONCLUSION: Older peoples' ability to open medicine containers is impaired by several conditions affecting physical and cognitive functioning. Many elderly people who are unable to open medicine containers do not receive help with their medication, particularly those living in their own homes.
16127897 [Giant rheumatoid nodule causing simultaneous complete atrioventricular block and severe m 2005 Aug A 65-year-old female was first treated under a diagnosis of rheumatoid arthritis at the age of 62 years. Just after subcutaneous rheumatoid nodules appeared, she suddenly complained of shortness of breath and vomiting. The diagnosis was overt congestive heart failure with complete atrioventricular block and severe mitral regurgitation. She was treated with temporary pacing, and a permanent pacemaker was implanted 1 month later. She suffered recurrence of congestive heart failure and died 8 months later. Autopsy revealed a giant rheumatoid nodule located on the mitral valve and extending to the atrioventricular node. Presumedly this solitary giant nodule had induced complete atrioventricular block and severe mitral regurgitation.
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.
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.
16095115 A retrospective study of the fluctuation in serum levels of anti-cyclic citrullinated pept 2005 Jul OBJECTIVE: To investigate the fluctuation in serum levels of anti-cyclic citrullinated peptide antibody (anti-CCP) retrospectively in patients with rheumatoid arthritis (RA). METHODS: Serum levels of anti-CCP were measured retrospectively in 131 patients with RA and 90 patients with non-RA rheumatic diseases using a commercially available kit. All sera were collected from patients during the 22-year period, 1982-2004. To analyze the fluctuation in anti-CCP levels, 17 RA patients were selected on the basis of showing a significantly higher anti-CCP level in a serum sample taken at the first visit (> 80 U/ml), and availability of preserved serum samples that had been taken from each patient at 10 time points. RESULTS: The test gave a sensitivity of 88% (115/131) and a specificity of 81% (73/90). The longitudinal study of 17 RA patients showed that anti-CCP levels were elevated at the first visit in 12 (71%) patients and then decreased gradually, whereas those in the other five (29%) patients fluctuated substantially. In both cases, anti-CCP levels tended to fluctuate in parallel with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level, reflecting the spontaneous aggravation of arthritis and the efficacy of anti-rheumatic drugs. The courses of three representative RA patients are illustrated in detail along with their therapeutic regimens, and these further confirm the correlation of anti-CCP levels with laboratory parameters (ESR and CRP) as well as the activity of arthritis. CONCLUSION: Measurement of serum anti-CCP levels was found to be useful for not only the diagnosis but also the management of RA.
16207318 Expression of CD147 on monocytes/macrophages in rheumatoid arthritis: its potential role i 2005 Monocytes/macrophages play an important role in rheumatoid arthritis (RA) pathogenesis. They can activate fibroblasts through many molecules, including IL-1 and tumor necrosis factor-alpha, but there have been very few reports on the role of CD147 in RA. In our study, the results of flow cytometry reveal that the mean fluorescence intensity (MFI) of CD147 expression on CD14+ monocytes of peripheral blood from RA patients was higher than that in normal control and ankylosing spondylitis (AS) patients. The MFI of CD147 expression on the CD14+ monocytes in RA synovial fluid was higher than that in RA peripheral blood. Immunohistochemical staining shows that CD147 expression in RA synovium correlated with matrix metalloproteinase (MMP)-1 expression. A double immunofluorescent assay shows that CD147 was expressed on CD68+ cells in RA synovium. The potential role of CD147 in cyclophilin A (CyPA)-mediated cell migration was studied using a chemotaxis assay in vitro and it was found that the addition of anti-CD147 antibody or a CD147 antagonistic peptide significantly decreased the chemotactic index of the mononuclear cells. The role of CD147 in MMP production and cell invasion in vitro were studied through the co-culture of human CD14+ monocytes or monocytic line THP-1 cells and human fibroblasts, as well as by gel zymography and an invasion assay. Significantly elevated release and activation of MMP-9 and/or MMP-2 were seen in the co-culture of human monocytes/THP-1 cells and fibroblasts compared with cultures of the cells alone. An increased number of cells invading through the filters in the invasion assays was also observed in the co-cultured cells. The addition of CD147 antagonistic peptide had some inhibitory effect, not only on MMP production but also on cell invasion in the co-culture. Our study demonstrates that the increased expression of CD147 on monocytes/macrophages in RA may be responsible for elevated MMP secretion, cell invasion and CyPA-mediated cell migration into the joints, all of which may contribute to the cartilage and bone destruction of RA. These findings, together with a better understanding of CD147, CyPA and RA, will help in the development of innovative therapeutic interventions for RA.
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.
16604876 [Infectious risks of immunomodulating therapies in rheumatology]. 2006 Mar 15 Corticosteroids and cytotoxic drugs form the conventional immunomodulators in rheumatology. This therapeutic arsenal has recently been widened by TNF-alpha antagonists and other anti-cytokines. If rheumatoid arthritis is itself associated with infections, immunomodulating therapies further increase the risk of infection, especially when used in combination therapies. Among conventional therapies, corticosteroids are associated with the highest risk for both common bacterial and opportunistic infections. Infliximab is the TNF-alpha antagonist associated with the highest risk of infection. Its use has been particularly associated with cases of severe tuberculosis. All patients at risk for tuberculosis, treated with corticosteroids or TNF-alpha antagonists, should therefore receive an adequate prophylaxis.
15818718 Indirect cost assessment in patients with rheumatoid arthritis (RA): comparison of data fr 2005 Apr 15 OBJECTIVE: To render information on the accuracy of patient-reported indirect cost data compared with payer-derived data of the real indirect costs on a patient-by-patient basis concerning disease-related productivity losses in rheumatoid arthritis (RA). METHODS: The assessment of indirect cost data was part of a clinical, multicenter, randomized RA trial. A total of 234 patients of working age with a diagnosis of RA (according to 1987 American College of Rheumatology criteria) were recruited. Demographics of the cohort were mean age 53 years, mean disease duration 8 years, 76% were women, and all had membership in the regional statutory health insurance plan. Every 3 months corresponding indirect cost data were derived for the cohort from a health economic questionnaire for cost assessment in patients with RA and the payer's database over a period of 18 months. Comparative statistical analyses were performed between patient-reported and insurance claims data. RESULTS: The mean annual productivity losses due to sick leave amounted to 14 and 17 days per patient (questionnaire versus payer data), and productivity losses due to work disability amounted to 3 days (both); monetary valuation renders overall costs of 1,240 and 1,590, respectively. The difference of 17% in overall productivity losses is not significant. Comparison of productivity losses reveals a strong correlation of r = 0.83 in those due to sick leave and of kappa = 0.84 in those due to work disability between questionnaire and payer data. CONCLUSION: The comparison of questionnaire and payer data shows that RA patients report their productivity losses adequately. Indirect cost assessment should therefore be included in further RA trials and observational studies.
15851522 B cells as a therapeutic target in autoimmune diseases other than rheumatoid arthritis. 2005 May Selective B-cell depletion with anti-CD20 therapy is a promising novel treatment option for patients with refractory autoimmune disease. The anti-CD20 antibody, rituximab, is the first therapeutic monoclonal antibody to have been approved by the European Medical Agency (EMEA) and the US Food and Drug Administration (FDA) for the treatment of relapsed, low-grade, follicular non-Hodgkin's lymphoma. Rituximab is now being studied in a range of autoimmune diseases, most notably rheumatoid arthritis, but also chronic immune thrombocytopenic purpura and systemic lupus erythematosus. Current data obtained from studies of rituximab single-agent therapy for autoimmune disease show good tolerability and sustained improvement in disease symptoms, although the precise mechanisms of action in autoimmunity remain to be fully clarified. Future research is likely to be focused on the optimization of responses with rituximab-based therapy. However, early observations suggest that this approach is likely to yield significant clinical benefits in a wide range of organ-specific and systemic autoimmune diseases.
16151416 Association study of VDR gene with rheumatoid arthritis in the French population. 2005 Dec Vitamin D is a potent regulator of calcium homeostasis and may have immunomodulatory effects. The influence of vitamin D on human autoimmune disease is controversial. The aim of this study was to investigate the role of vitamin D receptor gene (VDR) in rheumatoid arthritis (RA). Three polymorphisms for VDR gene FokI T>C (rs 10735810), BsmI A>G (rs 1544410) and TaqI C>T (rs 731236) were genotyped in 100 RA French nuclear families (set 1) and 100 additional French nuclear families for replication (set 2). The association analysis was performed using comparison of alleles frequencies (AFBAC), transmission disequilibrium test and genotype relative risk. Our results revealed a significant difference of F allele of FokI polymorphism between transmitted and nontransmitted frequencies (P=0.01) in set 1. Furthermore, the F/F genotype was more frequent in RA patients compared to controls (P=0.01) in set 1. The replication in set 2 showed similar patterns of transmission with a nonsignificant association. Association with FokI was found to be significant when the two sets were combined (P=0.006). These data suggest that the F allele and F/F VDR genotype are associated with RA. The mechanisms by which distinct receptor variants might confer disease susceptibility remain to be elucidated.
15813424 Tonsillar tuberculosis in a rheumatoid arthritis patient receiving anti-TNFalpha (adalimum 2005 Mar This case report describes a 61-year-old rheumatoid arthritis patient with an atypical clinical presentation of a sore throat. Because of rheumatoid arthritis refractory to conventional disease-modifying antirheumatic drug therapy, anti-TNFalpha was felt to be indicated, and a screening for tuberculosis was carried out. As the screening for tuberculosis (PPD) was positive, isoniazid was prescribed prophylactically for six months. After eight months of anti-TNFalpha (adalimumab) treatment, he developed tonsillar enlargement and nodular pulmonary lesions. Histopathological and microbial investigations established the diagnosis of tonsillar tuberculosis.
15903022 Comparison of dual X-ray absorptiometry (DXA), digital X-ray radiogrammetry (DXR), and con 2005 OBJECTIVE: To compare the relationship between bone mineral density (BMD) in the metacarpal bones and forearm measured by dual X-ray absorptiometry (DXA) and digital X-ray radiogrammetry (DXR) and radiological alterations in patients with early and established rheumatoid arthritis (RA). PATIENTS AND METHODS: In each of the three disease duration groups, 11 female RA patients were included. The patients were further divided into two groups according to bone erosions. BMD in the metacarpals was evaluated by DXA and DXR. RESULTS: A significant relationship between DXA-BMD and DXR-BMD was observed. DXR-BMD and the individually combined cortical thickness (CT) of the metacarpo-phalangeal (MCP) joints were related to disease duration and erosions. Patients with erosive disease had lower values of age- and sex-adjusted BMD measured with DXA, but most significantly with DXR. CONCLUSION: DXR appears to be a more sensitive method than DXA in detecting early bone loss in patients with RA. The relationship of DXR-BMD to disease duration and bone damage indicates that the DXR method may be useful in the evaluation of disease activity and progression.
16443164 Homocysteine from endothelial cells promotes LDL nitration and scavenger receptor uptake. 2006 Feb 1 We recently reported that methionine-loaded human umbilical vein endothelial cells (HUVECs) exported homocysteine (Hcy) and were associated with hydroxyl radical generation and oxidation of lipids in LDL. Herein we have analysed the Hcy-induced posttranslational modifications (PTMs) of LDL protein. PTMs have been characterised using electrophoretic mobility shift, protein carbonyl ELISA, HPLC with electrochemical detection and Western blotting of 3-nitrotyrosine, and LDL uptake by scavenger receptors on monocyte/macrophages. We have also analysed PTMs in LDL isolated from rheumatoid (RA) and osteo-(OA) arthritis patients with cardiovascular disease (CVD). While reagent Hcy (< 50 microM) promoted copper-catalysed LDL protein oxidation, Hcy released from methionine-loaded HUVECs promoted LDL protein nitration. In addition, LDL nitration was associated with enhanced monocyte/macrophage uptake when compared with LDL oxidation. LDL protein nitration and uptake by monocytes, but not carbonyl formation, was elevated in both RA and OA patients with CVD compared with disease-matched patients that had no evidence of CVD. Moreover, a direct correlation between plasma total Hcy (tHcy) and LDL uptake was observed. The present studies suggest that elevated plasma tHcy may promote LDL nitration and increased scavenger receptor uptake, providing a molecular mechanism that may contribute to the clinical link between CVD and elevated plasma tHcy.
15742463 Why does tumor necrosis factor targeted therapy reactivate tuberculosis? 2005 Mar Treatment of chronic inflammatory conditions, such as rheumatoid arthritis and Crohn's disease, with tumor necrosis factor (TNF) targeted biologics is associated with an increased risk of infectious complications, especially tuberculosis (TB). Clinical studies have revealed that monoclonal anti-TNF antibodies (e.g., infliximab) more frequently reactivate TB than a TNF receptor p75 immunoglobulin fusion construct (etanercept). Experimental studies in mice have shown TNF to be an essential component of protective granuloma formation. Based on these studies and the known pharmacological properties of the 2 prototype TNF targeted biologic agents, this review discusses 3 hypotheses that might explain the unpredicted differential risk of infectious complications: differential induction of target cell death, differential TNF receptor signaling, and differential net inhibition of TNF bioavailability.