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ID PMID Title PublicationDate abstract
11571883 [Why are patients referred to outpatient clinic of rheumatology?]. 2001 Aug 20 BACKGROUND: Increasing numbers of patients are referred from general practitioners to out-patient clinics of rheumatology. Better selection of patients referred may shorten the long waiting lists. The study aimed at analysing causes of referrals with particular emphasis on determining which diagnostic problems that most often occur among such referrals. MATERIALS AND METHODS: All referrals from general practitioners to an out-patient clinic of rheumatology during one year were analysed. RESULTS: Diagnosis was the main cause of referral in 78% of the cases. The diagnosis of the specialist was identical to that of the general practitioner in 44% of the cases. The lowest degree of correlation was found for patients referred with rheumatoid arthritis and primary Sjögren's syndrome. INTERPRETATION: The diagnoses of rheumatoid arthritis and Sjögren's syndrome appear to be difficult in general practice.
10420385 Immunohistochemical detection of cytokines and cell adhesion molecules in the synovial mem 1999 Jun This paper describes the immunohistochemical techniques which can be used to detect cytokines and cell adhesion molecules in synovial membrane tissue, including a list of reagents and possible problems in each technique. It also describes three methods of quantitation of the resultant immunohistochemical detection, including the recent innovation computer-assisted digital video image analysis, and lists the advantages and disadvantages of each quantitation technique. This information will be a useful summary for any scientist interested in applying such techniques to the detection of cytokines and cell adhesion molecules in human tissue sections.
10792390 Immunosuppressant effect of gold on IgG subclasses and IgE; evidence for sparing of Th2 re 2000 May We set out to examine the effect of gold treatment on the Th2-dependent antibodies IgG4 and IgE in relation to other IgG subclasses in patients with rheumatoid arthritis (RA). Eighty-five gold-treated RA patients and 82 RA controls were studied. Serum IgG subclass concentrations were measured by ELISA, IgE was measured by automated enzyme immunoassay. Samples were studied serially in 13 gold-treated patients and in 11 patients with gold-induced adverse events. There was a significant reduction in the concentration of IgG1, IgG2 and IgG3 in gold-treated RA patients compared with RA controls (P 0.004-0.019), whereas IgG4 was less significantly reduced in gold-treated patients (P = 0.044) and there was no difference in IgE. In serial samples there was a significant fall in the concentration of IgG1 (P = 0.001), IgG2 (P = 0.001) and IgG3 (P = 0.026) with time but no change in IgG4 and IgE. The development of gold-induced adverse events was not associated with any change in the concentration of each IgG subclass or IgE. Deficiencies of IgG subclasses were found in 30% of gold-treated RA patients and 8.5% of RA controls, and were associated in gold-treated patients with a longer disease duration (P = 0.003) and with erosive disease (P = 0. 03). IgG2 was affected most frequently and in the majority of these cases subnormal specific IgG2 binding to widespread polysaccharide antigens (Pneumovax II) was found. Gold induces an overall immunosuppressant effect on IgG subclasses, with a deficiency in 21. 5%, adjusted for controls. The effect on the Th2-dependent antibodies IgG4 and IgE is less marked, suggesting a sparing of Th2 responses.
10805355 The costs of rheumatoid arthritis: an international long-term view. 2000 Apr OBJECTIVES: To review the literature on the measurable direct and indirect costs of rheumatoid arthritis (RA) in industrialized countries from a societal perspective and to develop a template for international use. METHODS: A literature search using MEDLINE and other sources identified 153 relevant published articles, press releases, and so forth on the costs of RA and rheumatism from the major Organization for Economic Cooperation and Development (OECD) countries in English and other languages. Sixty-eight publications provide some economic data for analysis and are included in the bibliography. Twelve publications provide sufficiently detailed and robust information for inclusion in country overview tables. The concept of varied costs at different disease stages measured by years since diagnosis and Health Assessment Questionnaire (HAQ) scores is used to guide rational decisions in the allocation of scarce health care resources. RESULTS: Direct costs increase overproportionately during the course of the disease. The most important driver of direct costs is hospitalization, especially in moderate and severe RA. Costs of medication represent a comparatively small proportion of direct costs. Indirect costs caused by work disability can be substantially higher than direct costs, particularly in working-age patients. The total costs of RA to society, and the different cost components such as direct and indirect costs, are broadly comparable in industrialized countries by their order of magnitude. Major confounding factors for international comparison are different study methodologies and patient samples. CONCLUSIONS: The cost template developed in this article can be used to estimate the likely costs of RA to society for industrialized countries. It probably will underestimate indirect costs because of their incomplete coverage in the studies examined. A long-term perspective is needed for chronic diseases such as RA to assess the future effects of early interventions. Treatment in the early stages of RA that effectively reduces long-term disability has the potential to save substantial costs to society.
11759234 [Outcome measurement in musculoskeletal diseases: recommendation for a core set of scales 2001 Oct By application of a standardized core set of outcome measurement instruments, comparison between studies as well as meta-analyses in rehabilitation research can be facilitated. The German Society for Rheumatology has commissioned its working group on rehabilitation with the development of a proposal for such a core set of outcome measurement instruments. In a first step, dimensions for outcome measurement in rehabilitation were defined by a group of experts which represented rehabilitation hospitals, acute care hospitals, and research groups specialized in outcome measurement. The Delphi method was used in a multiple step consensus process. In a second step, instruments and procedures to operationalize the relevant dimensions were chosen. Reliability, validity, sensitivity to change, and practicability were used as criteria for selecting measurement instruments. The main intention of the proposed core set of outcome measurement instruments is to facilitate the processes of planning and carrying out rehabilitation research studies. Furthermore, the proposed instruments can be used for clinical documentation systems as well as for internal or external quality assurance programs.
11600740 The validity of the Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire. 2001 Oct OBJECTIVE: To examine further the usefulness of a 30-item disease-specific quality of life (QoL) questionnaire in patients with rheumatoid arthritis (RA). METHODS: The Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire was applied to two groups consisting of 210 and 300 patients with RA, one group with increasing difficulty in performing activities of daily living and one group with stable disease. The associations between the RAQoL and measures of utility, QoL, functional status and disease activity were evaluated. Factor analysis was carried out to investigate if one or more QoL dimensions could be distinguished within this questionnaire. RESULTS: Similar results regarding the association between the RAQoL and different sets of outcome measures were found in the two groups of patients. Regression analysis showed that about 75% of the variance of the RAQoL could be explained with variables of QoL, functional status and disease activity. Physical contact could be distinguished as a separate dimension within the RAQoL, in addition to the dimensions mobility/energy, self-care and mood/emotion. CONCLUSION: The RAQoL is a valid instrument for measuring QoL in different populations of patients with RA. Physical contact, a dimension that is not covered by other common instruments in RA, could be distinguished as a separate dimension within the questionnaire.
9665348 Effects of the menstrual cycle on medical disorders. 1998 Jul 13 Exacerbation of certain medical conditions at specific phases of the menstrual cycle is a well-recognized phenomenon. We review the effects of the menstrual cycle on medical conditions, including menstrual migraine, epilepsy, asthma, rheumatoid arthritis, irritable bowel syndrome, and diabetes. We discuss the role of medical suppression of ovulation using gonadotropin-releasing hormone agonists in the evaluation and treatment of these disorders. Peer-reviewed publications from English-language literature were located via MEDLINE or from bibliographies of relevant articles. We reviewed all review articles, case reports and series, and therapeutic trials. Emphasis was placed on diagnosis and therapy of menstrual cycle-related exacerbations of disease processes. Abrupt changes in the concentrations of circulating ovarian steroids at ovulation and premenstrually may account for menstrual cycle-related changes in these chronic conditions. Accurate documentation of symptoms on a menstrual calendar allows identification of women with cyclic alterations in disease activity. Medical suppression of ovulation using gonadotropin-releasing hormone agonists can be useful for both diagnosis and treatment of any severe, recurrent menstrual cycle-related disease exacerbations.
10657671 Displacement of linker for activation of T cells from the plasma membrane due to redox bal 2000 Feb 15 The T lymphocytes that reside in the synovium of the inflamed joints in patients with rheumatoid arthritis display severe hyporesponsiveness upon antigenic stimulation, which is probably due to their constant subjection to high levels of oxidative stress. Here we report that the synovial fluid T lymphocytes exert severely impaired phosphorylation of the adaptor protein linker for activation of T cells (LAT), a crucial component of the TCR-mediated signaling pathways. In healthy T lymphocytes, LAT is a membrane-bound protein and becomes phosphorylated by zeta-associated protein of 70 kDa (ZAP-70) upon TCR engagement. The molecular basis underlying the deficient phosphorylation of LAT and consequently the hyporesponsiveness of the synovial fluid T lymphocytes lies in the membrane displacement of LAT. We demonstrate that the subcellular localization of LAT is sensitive to changes in the intracellular levels of the antioxidant glutathione. The membrane anchorage of LAT, and consequently the phosphorylation of LAT and the cellular activation of the synovial fluid T lymphocytes upon TCR engagement, is restored in synovial fluid T lymphocytes after supplementation of the intracellular glutathione levels with N-acetyl-l -cysteine. These data suggest a role for the membrane displacement of LAT in the hyporesponsiveness of the synovial fluid T lymphocytes as a consequence of oxidative stress.
10340546 Feasibility of adenovirus-mediated nonsurgical synovectomy in collagen-induced arthritis-a 1999 May 1 Gene transfer to synovial tissue by adenoviral vectors (Ad) was studied in vitro in cultured human synoviocytes and in vivo in seven primates with arthritis. Hyperplastic synovium was efficiently transduced with Ad.lacZ in vitro and in vivo in rhesus monkeys with collagen-induced arthritis, whereas chondrocytes were not transduced. Intraarticular injection of recombinant Ad harboring the luciferase gene showed the presence of reporter gene products only in Ad-injected joints. In addition, the feasibility of synovectomy by Ad harboring the herpes simplex virus thymidine kinase gene (tk) was studied. In vitro infection of synovium from rheumatoid arthritis patients with Ad.TK, followed by administration of ganciclovir, resulted in death of >90% of the synoviocytes. By mixing Ad.TK-infected with noninfected cells, it appeared that the presence of 10% infected synoviocytes resulted in the killing of more than 85% of the synoviocytes, demonstrating a substantial bystander effect. Intraarticular injection of Ad.TK in the knees of rhesus monkeys with arthritis, followed by treatment with ganciclovir for 14 days, resulted in increased apoptotic cell death in the synovium of Ad.TK-injected as compared with noninjected joints and ablation of the synovial lining layer. The procedure revealed no toxic side effects. These data suggest that nonsurgical synovectomy by tK gene therapy is feasible.
9307853 Analysis of the T cell receptor repertoire in rheumatoid arthritis. 1997 Sep OBJECTIVE: To evaluate whether there is a restricted T cell receptor repertoire in rheumatoid synovium and to analyse the CDR3 region of the V beta families found to be more expressed in the synovial membrane than in the peripheral blood, in order to ascertain the presence of clonotypic expansion of T lymphocytes. METHODS: The level of expression of individual V beta and V alpha families of the TCR was evaluated in paired synovial membrane and peripheral blood T cells from 8 female patients affected by rheumatoid arthritis, using the RT-PCR method. Nucleotide sequences of the CDR3 region of some V beta families were analysed in order to identify the presence of conserved sequences. Sequencing was carried out with the dideoxy chain termination method using modified T7 DNA polymerase. RESULTS: All of the V alpha and V beta families were amplified in both compartments of the 8 patients. Four patients did not show any preferential expression of the TCR alpha or beta chains in synovium compared with peripheral blood. The other 4 patients showed increased expression of one or more V alpha and/or V beta families in the synovium. We did not find any correlation between the duration of disease, rheumatoid factor status, HLA-DR type and the V gene families which were elevated in the synovium. Analysis of the CDR3 region showed the presence of conserved amino acid sequences in the synovium, but not in the peripheral blood. CONCLUSION: The V families found to be increased in 4 of the 8 patients studied were different, except for V beta 1 which was more highly expressed in 2 patients. The presence of conserved amino acid sequences in the CDR3 region is consistent with an antigen-driven T cell expansion at the site of autoimmune inflammation. These findings do not support our original hypothesis of the possible usefulness of therapy based on the inactivation or elimination of presumed pathogenic T cells using TCR-derived peptides or monoclonal antibodies against particular TCRs.
9542782 Antibiotic sensitivity and proticine typing of Proteus mirabilis strains associated with r 1998 Urinary isolates of Proteus mirabilis, obtained from 49 RA patients and 44 healthy controls, were tested for susceptibility to antibiotics by the disc diffusion method. In addition, P. mirabilis isolates were also tested for proticine production and sensitivity (p/s) typing by the inhibition of growth of each test isolate against 13 reference strains of P. mirabilis. The P. mirabilis isolates from both RA patients and healthy controls were highly susceptible to norfloxacin, ciprofloxacin and trimethoprim, but less to minocycline. The urine of RA patients contained fewer different types of P. mirabilis strains than those isolated from healthy controls. All of the strains found in the RA patients were proticine producers (P < 0.001), mostly of proticine 3 (P < 0.005). The presence of such strains provides evidence of a sub-clinical upper urinary tract infection with P. mirabilis in some RA patients. Therapeutic intervention in RA with relevant antibiotics requires evaluation.
11094422 B cells in rheumatoid arthritis. 2000 Normally the immune response is restricted to the peripheral secondary lymphoid organs. However, additional ectopic lymphoid tissue may develop at chronic sites of inflammation. In the synovium of rheumatoid arthritis patients the local production of proinflammatory cytokines seems to support the formation of a precisely structured microenvironment, which allows an antigen dependent immune response to take place. The analysis of the V-gene repertoire expressed in synovial B cells demonstrated that in the inflamed synovium a germinal centre reaction takes place. Antigen presented by a network of follicular dendritic cells may activate synovial B cells and support their differentiation into plasma cells secreting high affinity antibodies. The specificity of these antibodies remains to be determined.
11034720 Azathioprine for treating rheumatoid arthritis. 2000 OBJECTIVES: To assess the short-term effects of azathioprine for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register (issue 3, 2000), Medline up to and including August 2000 and Embase from 1988 to August 2000. We also conducted a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials and controlled clinical trials comparing azathioprine against placebo in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: Data was extracted independently by two reviewers (CS, EB); disagreements were resolved by discussion or third party adjudication (MS). The same reviewers (CS, EB) assessed the methodological quality of the trials using a validated quality assessment tool. Rheumatoid arthritis outcome measures were extracted from the publications for the six-month endpoint. The pooled analysis was performed using standardized mean differences for joint counts, pain and functional status assessments. Weighted mean differences were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals and for adverse reactions. The 95% confidence intervals (95% CI) are presented. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout, since no statistical heterogeneity was found. MAIN RESULTS: Three trials with a total of 81 patients were included in the analysis. Forty patients were randomized to azathioprine and forty-one to placebo. A pooled estimate was calculated for two outcomes. A statistically significant benefit was observed for azathioprine when compared to placebo for tender joint scores. The standardized weighted mean difference between treatment and placebo was -0.98 (95% CI -1.45, -0.50). Withdrawals from adverse reactions were significantly higher in the azathioprine group OR=4.56 (95% CI 1.16, 17.85). REVIEWER'S CONCLUSIONS: Azathioprine appears to have a statistically significant benefit on the disease activity in joints of patients with RA. This evidence however is based on a small number of patients, included in older trials. Its effects on long-term functional status and radiological progression were not assessed due to lack of data. Toxicity is shown to be higher and more serious than that observed with other disease-modifying anti-rheumatic drugs (DMARDs). Given this high risk to benefit ratio, there is no evidence to recommend the use of azathioprine over other DMARDs.
9231507 [Pharmacokinetics of methotrexate in rheumatoid arthritis: therapeutic implications]. 1997 Mar The fraction of oral methotrexate (MTX) absorbed averages 70 per cent at low doses (< or = 10 mg/m2), both fasting and after food. The mean binding of MTX to serum albumin is 42-57 per cent. Less than 10 per cent of MTX is oxidised to 7-OH-MTX. Furthermore, MTX is partly converted to polyglutamate derivatives which accumulate in some cells resulting in sustained efficacy of the drug in spite of its relatively short plasma elimination half-life. MTX is mainly excreted by the kidney as intact drug. Accordingly careful monitoring of renal function is justified. MTX undergoes bidirectional transport within the renal tubules leading to drug interactions. Oral, intramuscular and subcutaneous routes of administration were reported to result in comparable bioavailability. There is a marked interindividual variability in MTX disposition. Conversely, the intraindividual variability is moderate even over a long time period. Finally, no clear relationship between pharmacokinetic parameters and clinical response or toxicity has been found in patients with rheumatoid arthritis.
10914842 Estrogen and progesterone regulation of human fibroblast-like synoviocyte function in vitr 2000 Jul OBJECTIVE: Despite increasing evidence regarding the significance of sex hormones in rheumatoid arthritis (RA), their etiopathological role and potential longterm effect on joint destruction remain unclear. We hypothesized that estrogen receptors (ER-alpha) are present in fibroblast-like synoviocytes, and 17beta-estradiol can modulate the production and activity of matrix degrading enzymes produced by these cells. Thus, depending on the endocrine balance, fibroblast-like synoviocyte activity can be suppressed or enhanced, leading to amelioration or exacerbation of the disease process, respectively. METHODS: By utilizing an in vitro cartilage invasion model, in combination with the molecular analyses of hormone receptors, matrix metalloproteinases (MMP) and their respective inhibitors, we investigated the effect of hormones (i.e., estrogen and progesterone) on fibroblast-like synoviocyte phenotypic changes, with particular emphasis on their functional interactions with cartilage. RESULTS: Our studies reveal the presence of functional ER-alpha in fibroblast-like synoviocytes. The findings indicate that estrogen exerts a stimulatory effect, while progesterone has an inhibitory effect on the expression of MMP, their tissue inhibitors (TIMP), and enzymatic activity of MMP produced by these cells. Furthermore, transfection of fibroblast-like synoviocytes with the ER-alpha gene resulted in the increased degradation and invasion of cartilage. CONCLUSION: We identified the presence of functional ER-alpha in fibroblast-like synoviocytes. This renders fibroblast-like synoviocytes as target cells for hormonal regulation. The regulatory effect of estrogen is partly targeted to the MMP and their respective inhibitors associated with fibroblast-like synoviocytes. Such studies provide a link between hormonal status and disease activity in RA and open new venues for future therapeutic intervention to combat this debilitating disease.
10234545 Accessible xenografts of human synovium in the subcutaneous tissues of the ears of SCID mi 1999 Apr This work was undertaken to examine whether human synovium could be engrafted into subcutaneous pouches in the ears of severe combined immunodeficient (SCID) mice. Synovium was transplanted into surgically constructed ear pouches. The grafts were examined by histological and immunohistochemical methods after varying periods after engraftment, or after percutaneous injection of TNF-alpha. Normal, osteo-arthritic and rheumatoid synovium was engrafted successfully in subcutaneous ear pouches. The general morphology and cellular compositions of xenografts were retained including human endothelial cells. In rheumatoid xenografts, macrophages, fibroblasts and lymphocytes persisted for at least 4 weeks. Vascular expression of intercellular adhesion molecule-1 (ICAM-1) was maintained but expression of vascular adhesion molecule-1 (VCAM-1), E-selectin and MHC class II diminished with time. Percutaneous injection of TNF-alpha induced up-regulation of VCAM-1. Human synovium can be engrafted into subcutaneous ear pouches in SCID mice. The xenografts are accessible and respond to injection of a pro-inflammatory cytokine.
10913051 Yttrium radiosynoviorthesis in the treatment of knee arthritis in rheumatoid arthritis: a 2000 Aug OBJECTIVE: To consider the question: How strong is the evidence in favour of yttrium synovectomy in chronic knee arthritis in patients with rheumatoid arthritis in comparison with placebo and intra-articular steroid treatment? METHODS: A systematic review of the literature was performed using Medline and the Embase database. RESULTS: Initially, seven papers were identified, but only two met the inclusion criteria. Neither study showed evidence in favour of yttrium synovectomy. CONCLUSION: From the point of view of evidence based medicine it should be seriously questioned whether yttrium synovectomy deserves a place in clinical practice.
10404159 Therapeutic antibodies elicited by immunization against TNF-alpha. 1999 Jul Tumor necrosis factor-alpha (TNF-alpha) is critically involved in the pathogenesis of several chronic inflammatory diseases. Monoclonal antibodies against TNF-alpha are currently used for the treatment of rheumatoid arthritis and Crohn's disease. This report describes a simple and effective method for active immunization against self TNF-alpha. This vaccination approach leads to a T-cell-dependent polyclonal and sustainable anti-TNF-alpha autoantibody response that declines upon discontinuation of booster injections. The autoantibodies are elicited by injecting modified recombinant TNF-alpha molecules containing foreign immunodominant T-helper epitopes. In mice immunized with such molecules, the symptoms of experimental cachexia and type II collagen-induced arthritis are ameliorated. These results suggest that vaccination against TNF-alpha may be a useful approach for the treatment of rheumatoid arthritis and other chronic inflammatory diseases.
9741310 Mutual antagonism of rheumatoid arthritis and hay fever; a role for type 1/type 2 T cell b 1998 May OBJECTIVES: The balance between interferon gamma (IFN gamma) and interleukin 4 (IL4) producing T cells (T1 and T2 cells) seems to be of importance in many (auto)immune disorders. In general, T1 cell activity is important in cellular immunity whereas T2 cell activity plays a part in humoral responses. T1 cell activity predominates in joints of patients with rheumatoid arthritis (RA) whereas T2 cell activity is characteristic of atopic syndromes. This study investigated whether the prevalence of hay fever in RA is low and if severity of RA (T1 cell activity) can be influenced by the concomitant occurrence of a T2 cell mediated disease (hay fever). METHODS: The prevalence of hay fever was assessed in 643 consecutive (RA and non-RA) patients seen in our outpatient clinic and confirmed by skin test and specific IgE. Of this group the 12 RA patients with hay fever were compared with RA patients without hay fever (matched for age, sex, and disease duration). RESULTS: The prevalence of hay fever in RA patients is lower than in non-RA patients (4% versus 8%), and yields a relative risk for RA patients to develop hay fever of 0.48. RA patients with hay fever showed a lower disease activity (erythrocyte sedimentation rate, C reactive protein, Thompson joint score, and radiographic joint damage (Sharp) score) than RA patients without hay fever. The clinical data were related to peripheral blood T1/T2 cell balance: a lower IFN gamma/IL4 ratio was observed for RA patients with hay fever, indicating a comparatively increased T2 cell activity in RA patients with hay fever. CONCLUSION: These results argue in favour of the exploration of treatments aimed at regulation of a possible imbalance in T1/T2 cell activity in RA.
9589469 Low-grade B cell lymphoma of mucosa-associated lymphoid tissue in the thymus of a patient 1998 Jan The majority of thymic lymphomas are either lymphoblastic lymphoma, large B cell lymphoma or Hodgkin's disease, and other types of non-Hodgkin lymphoma are rare. A case of low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT) in the thymus is reported. A 55-year-old Japanese female with a history of rheumatoid arthritis (RA) complained of back pain. A mediastinal tumor was identified by computerized tomography and magnetic resonance imaging, and the thymus was resected through median sternotomy. The solid and nodular tumor had several small satellite extensions and was completely confined to within the thymus. Histologically, monotonous medium-sized centrocyte-like cells occupied the medulla of the thymus and infiltrated Hassall's corpuscles (lymphoepithelial lesions). Immunohistochemically, tumor cells were positive for CD20 and CD79a. IgA and kappa light chain restriction were also found in plasmacytoid cells in the tumor. Clonal rearrangement of the immunoglobulin heavy chain gene was demonstrated by polymerase chain reaction. This case was diagnosed as MALT-type low-grade B cell lymphoma in the thymus. This is the first report of low-grade B cell lymphoma in the thymus associated with RA. As autoimmune diseases are known to be associated with lymphoid neoplasms, it is suggested that the RA played an important role in the development of malignant lymphoma in this case.