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ID PMID Title PublicationDate abstract
14740455 Cooperative induction of 15-lipoxygenase in rheumatoid synovial cells by IL-4 and proinfla 2003 Nov OBJECTIVE: To clarify the role of interleukin-4 (IL-4) in the expression of 15-lipoxygenase (15-LOX), whose metabolities are known to suppress the inflammatory reaction, in freshly prepared rheumatoid synovial cells. METHODS: Adherent synovial cells were prepared by enzymatic digestion of synovia obtained from patients with rheumatoid arthritis (RA). Protein expression of 15-LOX was determined by Western blot analysis. The messenger RNAs of 15-LOX were determined by reverse transcription and the polymerase chain reaction (RT-PCR). RESULTS: Freshly prepared rheumatoid synovial cells did not express 15-LOX at either the mRNA or protein levels. IL-4 induced the protein expression of 15-LOX after 24 hours of culture. Although interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha), major inflammatory cytokines in rheumatoid synovia, did not induce the expression of 15-LOX, IL-4 and these inflammatory cytokines synergistically enhanced the protein expression of 15-LOX. The synergistic effect was also observed at the level of mRNA. CONCLUSIONS: We demonstrate that IL-4 cooperated with the inflammatory cytokines IL-1 alpha and TNF alpha to enhance the expression of 15-LOX in rheumatoid synovial cells. Since 15-LOX metabolites have potent anti-inflammatory actions, our data suggest that IL-4 might downregulate rheumatoid inflammation via the induction of 15-LOX and its metabolites.
12583633 Amyloid arthropathy resembling seronegative rheumatoid arthritis in a patient with IgD-kap 2003 Jan A 67-year-old woman suffered from symmetrical polyarthralgia and multiple joint swelling simulating rheumatoid arthritis (RA). Laboratory examination showed negative results for rheumatoid factor, decreased levels of IgG, IgA, and IgM, and an increased level of IgD. Immunoelectrophoresis in her serum and urine revealed an IgD-kappa monoclonal component and Bence Jones protein (kappa), respectively. A bone marrow biopsy showed an excess of atypical plasma cells. A synovial biopsy revealed amyloid deposition composed of IgD-kappa. She was diagnosed with amyloid arthropathy (AmyA) secondary to IgD-kappa multiple myeloma. It is important to pay attention to AmyA due to multiple myeloma in patients with seronegative RA.
15448685 4-1BB-mediated immunotherapy of rheumatoid arthritis. 2004 Oct Collagen type II-induced arthritis is a CD4(+) T-cell-dependent chronic inflammation in susceptible DBA/1 mice and represents an animal model of human rheumatoid arthritis. We found that development of this condition, and even established disease, are inhibited by an agonistic anti-4-1BB monoclonal antibody. Anti-4-1BB suppressed serum antibodies to collagen type II and CD4(+) T-cell recall responses to collagen type II. Crosslinking of 4-1BB evoked an antigen-specific, active suppression mechanism that differed from the results of blocking the interaction between 4-1BB and its ligand, 4-1BBL. Anti-4-1BB monoclonal antibodies induced massive, antigen-dependent clonal expansion of CD11c(+)CD8(+) T cells and accumulation of indoleamine 2,3-dioxygenase in CD11b(+) monocytes and CD11c(+) dendritic cells. Both anti-interferon-gamma and 1-methyltryptophan, a pharmacological inhibitor of indoleamine 2,3-dioxygenase, reversed the anti-4-1BB effect. We conclude that the suppression of collagen-induced arthritis was caused by an expansion of new CD11c(+)CD8(+) T cells, and that interferon-gamma produced by these cells suppresses antigen-specific CD4(+) T cells through an indoleamine 2,3-dioxygenase-dependent mechanism.
12017869 [Ultrasound of the knee joint in gonarthritis]. 2002 Mar Ultrasound examination of the knee joint to detect early signs of inflammation is a useful diagnostic tool. The more specific the signs seen in connection with clinical and laboratory findings are, the more certain the diagnosis becomes. Static and dynamic examinations are necessary.
15139795 Pharmacokinetics of lumiracoxib in plasma and synovial fluid. 2004 BACKGROUND: Lumiracoxib is a new cyclo-oxygenase-2 (COX-2) selective inhibitor in development for the treatment of rheumatoid arthritis, osteoarthritis and acute pain. OBJECTIVE: To investigate the pharmacokinetics of lumiracoxib in plasma and knee joint synovial fluid from patients with rheumatoid arthritis. DESIGN: Open-label multiple-dose study evaluating the steady-state pharmacokinetics of lumiracoxib in plasma and synovial fluid after 7 days of treatment with lumiracoxib 400 mg once daily. PATIENT POPULATION: Males and females aged 18-75 years with rheumatoid arthritis, having moderate to significant synovial fluid effusion of the knee. OUTCOME MEASURES: Following a 7-day washout period for previous nonsteroidal anti-inflammatory drugs, 22 patients (17 female, 5 male) received lumiracoxib 400 mg once daily for seven consecutive days. On day 7, following an overnight fast, a final dose of lumiracoxib was administered and serial blood and synovial fluid samples were collected for up to 28 hours. Lumiracoxib and its metabolites (4'-hydroxy-lumiracoxib and 5-carboxy-4'-hydroxy-lumiracoxib) were measured by validated high performance liquid chromatography-mass spectrometry methods. The steady-state pharmacokinetics of lumiracoxib were evaluated in plasma and synovial fluid by both a population pharmacokinetic model and noncompartmental analysis. RESULTS: Lumiracoxib was rapidly absorbed (peak plasma concentration at 2 hours) and the terminal elimination half-life in plasma was short (6 hours). Lumiracoxib concentrations were initially higher in plasma than in synovial fluid; however, from 5 hours after administration until the end of the 28-hour assessment period, concentrations of lumiracoxib were higher in synovial fluid than in plasma. Peak drug concentration in synovial fluid occurred 3-4 hours later than the peak plasma concentration. The mean steady-state trough concentration of lumiracoxib in synovial fluid (454 microg/L) was approximately three times higher than the mean value in plasma (155 microg/L), and the area under the concentration-time curve from 12 to 24 hours after administration was 2.6-fold higher for synovial fluid than for plasma. Median lumiracoxib protein binding was similar in plasma and synovial fluid (range 97.9-98.3%). Concentrations of 4'-hydroxy-lumiracoxib, the active COX-2 selective metabolite, remained low in comparison with parent drug in both plasma and synovial fluid. The concentration of lumiracoxib in synovial fluid at 24 hours after administration would be expected to result in substantial inhibition of prostaglandin E(2) formation. CONCLUSION: The kinetics of distribution of lumiracoxib in synovial fluid are likely to extend the therapeutic action of the drug beyond that expected from plasma pharmacokinetics. These data support the use of lumiracoxib in a once-daily regimen for the treatment of rheumatoid arthritis.
15562720 [Effect of tongbiling on the expression of MCP-1 mRNA of synovial cells in rats with adjuv 2002 Oct OBJECTIVE: To study the effect of tongbiling, a complex preparation of Chinese traditional medicine, on the expression of MCP-1 mRNA of synovial cells in rats with adjuvant arthritis. METHOD: The expression level of MCP-1 mRNA in synoviocytes from rats with adjuvant arthritis was assayed by the method of RT-PCR. RESULT: The amounts of MCP-1 mRNA expression in synoviocytes from rats with adjuvant arthritis were distinctly decreased by tongbiling. It suggested that tongbiling had inhibition effect on rheumatoid arthritis by a down regulation for the expression of MCP-1 mRNA in the inflamed synoviocytes.
15242044 [A case report of severe laryngeal edema which occured before removal of a laryngeal mask 2004 Jun A 41-year-old woman was scheduled for a partial hip arthroplasty. She was suffering from malignant rheumatoid arthritis for a long time and we recognized her difficult airway. After epidural catheterization, anesthesia was induced with fentanyl, thiopental, and 5% sevoflurane with oxygen. A laryngeal mask airway (LMA ; size 3) was inserted smoothly on third trial after suxamethonium chloride administration. Anesthesia was maintained with fentanyl, vecuronium bromide, sevoflurane with oxygen and epidural anesthesia. No complications were observed during the operation. After reversal of muscle relaxant, spontaneous respiration returned. But inspiratory stridor and chest wall retraction occurred soon, and we found severe epiglottic edema by bronchoscopy. A tracheal tube (ID 5.5 mm) was intubated immediately through the LMA. Twenty hours later the pharyngeal edema was still very severe, and tracheotomy was performed. The edema disappeared three days later. We thought the edema had occurred as a result of blood flow disturbance caused by LMA in narrow pharyngeal space expanding to the epiglottis. It should be kept in mind that severe edema could develop after LMA in malignant rheumatoid arthritis.
12534797 The spectrum of cutaneous lesions in rheumatoid arthritis: a clinical and pathological stu 2003 Jan INTRODUCTION: Rheumatoid arthritis (RA) is an idiopathic arthropathy syndrome that has a propensity to affect the small joints of the hands and feet with extra-articular manifestations comprising skin lesions, neuropathy, pericarditis, pleuritis, interstitial pulmonary fibrosis and a systemic polyarteritis nodosa (PAN)-like vasculitic syndrome. The most widely recognized skin lesion is the rheumatoid nodule. Other skin manifestations are poorly defined. MATERIALS AND METHODS: Using a natural language search of the authors' outpatient dermatopathology databases, skin biopsies from 43 patients with RA were selected for retrospective analysis in an attempt to define the dermatopathological spectrum of RA and its clinical correlates. RESULTS: The biopsies were categorized by the dominant histologic pattern, recognizing that in most cases there were additional minor reaction patterns. Palisading and/or diffuse interstitial granulomatous inflammation was the dominant pattern seen in 21 patients; the lesions included nodules, plaques and papules with a predilection to involve skin over joints. Besides interstitial histiocytic infiltrates and variable collagen necrobiosis, these cases also showed interstitial neutrophilia, vasculitis and pauci-inflammatory vascular thrombosis. The dominant morphology in 11 other patients was vasculopathic in nature: pauci-inflammatory vascular thrombosis, glomeruloid neovascularization, a neutrophilic vasculitis of pustular, folliculocentric, leukocytoclastic or benign cutaneous PAN types, granulomatous vasculitis, and lymphocytic vasculitis and finally occlusive intravascular histiocytic foci for which the designation of "RA-associated intravascular histiocytopathy" is proposed. Rheumatoid factor (RF) positivity and active arthritis were common in this group, with anti-Ro and anticardiolipin antibodies being co-factors contributing to vascular injury in some cases. Immunofluorescent testing in three patients revealed dominant vascular IgA deposition. In nine patients, the main pattern was one of neutrophilic dermal and/or subcuticular infiltrates manifested clinically as urticarial plaques, pyoderma gangrenosum and panniculitis. CONCLUSIONS: The cutaneous manifestations of RA are varied and encompass a number of entities, some of which define the dominant clinical features, such as the rheumatoid papule or subcutaneous cords, while others allude to the histopathology, i.e. rheumatoid neutrophilic dermatosis. We propose a more simplified classification scheme using the adjectival modifiers of "rheumatoid-associated" and then further categorizing the lesion according to the dominant reaction pattern. Three principal reaction patterns are recognized, namely extravascular palisading granulomatous inflammation, interstitial and/or subcuticular neutrophilia and active vasculopathy encompassing lymphocyte-dominant, neutrophil-rich and granulomatous vasculitis. In most cases, an overlap of the three reaction patterns is seen. Co-factors for the vascular injury that we believe are integral to the skin lesions of RA include RF, anti-endothelial antibodies of IgA class, anti-Ro and anticardiolipin antibodies.
12823853 Gene expression induced by interleukin-17 in fibroblast-like synoviocytes of patients with 2003 Interleukin-17 (IL-17) has been characterized as a proinflammatory cytokine produced by CD4+ CD45RO+ memory T cells. Overproduction of IL-17 was detected in the synovium of patients with rheumatoid arthritis (RA) compared with patients with osteoarthritis. This study examines differentially expressed genes after the stimulation of fibroblast-like synoviocytes of RA patients by IL-17. Among these genes we identified the following: tumor necrosis factor-stimulated gene-6 (TSG-6), IL-6, IL-8, GRO-beta, and bone morphogenetic protein-6 with an expression 3.6-10.6-fold that in the unstimulated control. IL-17 augmented the expression of TSG-6, a hyaluronan-binding protein, in a time- and dose-dependent manner. IL-17 showed additive effects with IL-1beta and tumour necrosis factor-alpha on the expression of TSG-6, IL-6 and IL-8. The mitogen-activated protein kinase p38 seems to be necessary for the regulation of TSG-6 expression by IL-17, as shown by inhibition with SB203580. Our results support the hypothesis that IL-17 is important in the pathogenesis of RA, contributing to an unbalanced production of cytokines as well as participating in connective tissue remodeling.
14991279 [Contribution of leflunomide to the cost effectiveness of sequential DMARD therapy of rheu 2004 Feb Since November 1999, leflunomide (LEF), an innovative disease-modifying antirheumatic drug (DMARD), is available in Germany for treatment of rheumatoid arthritis (RA). LEF slows radiographic disease progression and improves functional capacity as well as healthrelated quality of life of RA patients. Resources for health care of the patients are limited in Germany as in all other countries. The purpose of the analysis therefore was to compare the cost effectiveness of the following alternatives: LEF in sequential monotherapy with other DMARDs versus sequential monotherapy of other DMARDs. The target variables of this cost-effectiveness comparison were additional direct costs per ACR20-response year (ACR20RY) gained and per quality-adjusted life year (QALY) gained, respectively, each after three years of treatment. The cost-effectiveness comparison was carried out using a modeling study after secondary analysis of relevant data. Oral methotrexate (MTX), sulphasalazine (SSZ), antimalarials (CQ/HCQ), intramuscular gold (IMG), and azathioprine (AZA) were selected as "other" DMARDs representing the current status of sequential monotherapy. Based on health care regulation in Germany-Guidelines on the Prescription of Drugs amended by the Federal Commission of Medical Practitioners and Health Insurance Funds on 10 December 1999-LEF was exclusively considered second within a DMARD sequence. Direct costs were given by outpatient and inpatient treatment, long-term care, and rehabilitation treatment. Prices relate to the period of 1998 to 2001 and were converted to Euro (euro), according to the official exchange rate of 1 euro = 1.95583 DM (1 euro approximately 0.90 US dollars; 2001 values). The comparative cost-effectiveness analysis covered a treatment period of more than one year. To estimate the net present value of future costs and effectiveness, a discount rate of 5% per year was applied. In the case of DMARD-naïve patients with RA, the sequence MTX, LEF, SSZ, IMG, AZA, CQ/HCQ was the most cost effective with direct costs of 7297 euro per ACR20RY and 6499 euro per QALY. In order to estimate the consequences of introducing LEF into the prescribing practice in Germany, the distribution of RA patients by individual DMARD in rheumatological care in 1998 was considered. This distribution was taken from the National Database of the German Collaborative Arthritis Centres. Though the sequences comprising LEF incurred 3% higher direct costs, they led to a higher effectiveness of 6% and 3% in the case of ACR20RYs and QALYs, respectively. Choosing sequences comprising LEF, there were additional direct costs of 5004 euro per ACR20RY gained and 8301 euro per QALY gained, as compared to the corresponding sequences without LEF. In comprehensive sensitivity analyses, the robustness of the model and its results was shown. The contribution of LEF to the cost effectiveness of sequential DMARD therapy is obvious. The modeling study revealed advantages for the patients and the cost carriers. Though there were initially higher medication costs of the sequences comprising LEF, these costs were nearly compensated to remaining excess costs of just 3% after three years. This was caused by cost savings in other sectors of the health care system due to the higher effectiveness of the sequences comprising LEF.
12898296 Quantitative assessment of hand radiographs of rheumatoid arthritis: interobserver variati 2003 We investigated interobserver variations in the Larsen radiographic scoring method on hand radiographs of rheumatoid arthritis (RA) patients in a multicenter trial and developed a new radiographic scoring method. Thirteen experienced rheumatologists scored 10 representative RA hand radiograms with the Larsen scoring method and clarified the precipitating factors of interobserver variation. Based on this study, it was proved that the ankylotic joint, overlapping joint, and more precise erosive joint are needed for optimal radiographic evaluation. Therefore, we modified the Larsen scoring method on the basis of these precipitating factors and developed a novel radiographic scoring method. Finally, to determine which scoring system was most reliable, the interobserver variation using three methods (original Larsen method, revised Larsen method, our scoring method) were compared by 13 experienced rheumatologists and 13 residents. Our scoring method proved to have simplicity, reliability, and ease of learning. These results suggest that our novel radiological quantitative assessment method has useful applications for clinical studies in patients with RA.
12634224 Cyclosporin A monotherapy versus cyclosporin A and methotrexate combination therapy in pat 2003 Apr OBJECTIVE: To compare the efficacy and toxicity of cyclosporin A (CsA) monotherapy with CsA plus methotrexate (MTX) combination therapy in patients with early rheumatoid arthritis (RA). PATIENTS AND METHODS: 120 patients with active RA, rheumatoid factor positive and/or erosive, were randomly allocated to receive CsA with MTX (n=60) or CsA with placebo (n=60). Treatment with CsA was started in all patients at 2.5 mg/kg/day and increased to a maximum of 5 mg/kg/day in 16 weeks. MTX was started at 7.5 mg/week and increased to a maximal dose of 15 mg/week at week 16. Primary outcomes were clinical remission (Pinals criteria) and radiological damage (Larsen score), at week 48. RESULTS: Treatment was discontinued prematurely in 27 patients in the monotherapy group (21 because of inefficacy, and six because of toxicity) and in 26 patients in the combination therapy group (14 and 12, respectively). At week 48, clinical remission was achieved in four patients in the monotherapy group and in six patients in the combination therapy group (p=0.5). The median Larsen score increased to 10 (25th, 75th centiles: 3.5; 13.3) points in the monotherapy group and to 4 (1.0; 10.5) points in the combination therapy group (p=0.004). 28/60 (47%) of patients in the monotherapy group v 34/60 (57%) of patients in the combination therapy group had reached an American college of Rheumatology 20% (ACR20) response (p=0.36) at week 48; 15/60 (25%) v 29/60 (48%) of patients had reached an ACR50 response (p=0.013); and 7 (12%) v 12 (20%) of patients had reached an ACR70 response (p=0.11). Their was a tendency towards more toxicity in the combination therapy group. CONCLUSIONS: In patients with early RA, neither CsA plus MTX combination therapy nor CsA monotherapy is very effective in inducing clinical remission. Combination therapy is probably better at improving clinical disease activity, and definitely better at slowing radiological progression. Combination therapy should still be compared with methotrexate monotherapy.
14996878 The rates of osteolysis and loosening associated with a modular posterior stabilized knee 2004 Mar BACKGROUND: Osteolysis and increased polyethylene wear have been reported in association with several designs of modular total knee prostheses. The purpose of the present study was to evaluate a modular posterior stabilized prosthesis to determine its clinical performance as well as the rates of component loosening and osteolysis. METHODS: We performed a prospective, consecutive study of 193 knees in 131 patients who were managed with the modular Insall-Burstein II posterior stabilized total knee prosthesis by one surgeon. The mean age of the patients at the time of surgery was sixty-eight years, and the mean duration of follow-up was seven years (range, five to fourteen years). Clinical evaluation was performed with use of standard knee-scoring systems. Radiographs were evaluated for the presence of radiolucent lines, osteolysis, and loosening. RESULTS: The overall result (as determined with the Hospital for Special Surgery scoring system) was rated as excellent for 112 knees, good for sixty, fair for fifteen, and poor for six. The mean postoperative flexion was 112 degrees. No clinical or radiographic loosening of the tibial component was noted. Eight knees had osteolytic lesions of the tibia. Thin, incomplete, nonprogressive radiolucent lines were noted around thirty tibial components (16%). There were three reoperations. CONCLUSIONS: Despite previous reports of osteolysis, polyethylene wear, and loosening in association with some modular total knee implant designs, there was no loosening in this series of posterior stabilized total knee replacements and only eight knees had tibial osteolysis after a mean duration of follow-up of seven years. We believe that total knee arthroplasties that are performed with use of cemented modular posterior stabilized components can have a high rate of intermediate-term success. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence.
11893456 Spontaneous external auditory canal cholesteatoma complicated by rheumatoid arthritis--cas 2002 Apr A 63-year-old woman with rheumatoid arthritis sought medical assistance for dull and chronic pain in her left ear two and half years after her initial diagnostic examination. Otoscopic examination revealed that the posteroinferior wall of the bony external ear canal was eroded and that the small cavity was filled with squamous debris. The condition was diagnosed as external auditory canal cholesteatoma (EACC). The existence of EACC might suggest complications of bone disease, aging cerumen gland, or a low migratory rate of the epithelium.
12729111 A femoral component with proximal HA coating. An analysis of survival and fixation at up t 2003 Apr We describe the survival at ten years of 100 femoral components of the Freeman hip prosthesis. It is proximally hydroxyapatite (HA)-coated and was fixed without cement. Radiological assessment identified radiolucent lines (RLLs) and lytic lesions and was used to measure migration. The criterion of failure was revision or impending revision for aseptic femoral loosening. No femoral components were revised or are awaiting revision for aseptic loosening, giving 100% survival at ten years (95% confidence interval, 95.7 to 100), although 59 were at risk at ten years. Two components were revised for fracture of a ceramic head with damage to the trunnion. Although well fixed in each, for survival analysis we evaluated the hip as if the patient had died. Twelve acetabular components were revised and at each operation the femoral component was found to be well fixed, was not disturbed and remained in the survival analysis. Three patients were lost to follow-up, and 12 died with well-functioning prostheses. Radiologically, all except one of the components appeared to be well fixed with no RLLs and no lytic lesions at the latest follow-up. The mean vertical migration was 0.4 mm at one year, 0.8 mm at two years and 1.4 mm at ten years. One component had migrated 7.6 mm at ten years (2.1 mm in year 1) and developed RLLs in Gruen zones I and II. The symptoms, however, were only minor and revision was not indicated. Our study has shown that proximal HA coating gives effective fixation for a femoral component.
12722610 [What has become of inflammatory amyloidosis?]. 2003 Mar 1 Inflammation associated amyloidosis (AA amyloid) remains a severe complication of chronic inflammatory diseases, namely of rheumatoid arthritis and of juvenile arthritis. Infectious causes of AA amyloid have become uncommon. In the course of chronic inflammatory diseases, amyloid should be regularly screened by proteinuria. The proof of amyloidosis requires tissue analysis examplifying specific apple-green birefringence after staining with Congo red. When amyloidosis is progressive in the course of one chronic disease, powerful anti-inflammatory and immunosuppressive drugs can be used.
15290725 Osteoprotegerin and receptor activator of nuclear factor-kappaB ligand mRNA expression in 2004 Aug OBJECTIVE: To further understand the role of osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANK-L) in rheumatoid arthritis (RA), we studied the levels of RANK-L and OPG mRNA in peripheral blood mononuclear cells (PBMC) and synovial tissue of patients with RA and controls. METHODS: RANK-L and OPG mRNA levels were measured in PBMC and CD4+/CD8+ T cell subsets of patients with chronic RA, osteoarthritis (OA), and healthy controls, using quantitative real-time polymerase chain reaction. OPG and RANK-L mRNA levels were measured in paired blood and synovial tissue samples of patients with early, untreated RA at 2 timepoints with an interval of 16 weeks. RESULTS: RANK-L mRNA levels were significantly higher in PBMC of patients with early and chronic RA compared to healthy controls. Contrary to healthy controls, RANK-L mRNA levels in patients with chronic RA were mainly of CD4+ T cell origin. OPG mRNA was observed in the blood of all (17/17) early RA patients, but could not be detected in chronic RA patients (0/14) or in patients with OA (0/8). Three out of 17 healthy controls showed measurable levels of OPG mRNA. The OPG/RANK-L ratio tended to be higher in the synovium than in the PBMC of early RA patients. RANK-L mRNA in synovial tissue was mainly of non-T cell origin. CONCLUSION: Since RANK-L and OPG mRNA levels are elevated in PBMC of RA patients, and CD4+ T cells are the major contributors to RANK-L mRNA expression, mononuclear cells in patients with RA may be involved in the pathways that regulate bone metabolism.
12491114 [What can experimental research offer to rheumatology today--the viewpoint of molecular bi 2002 Molecular biology plays an increasing role for the development of innovative approaches to analyze the pathogenesis of rheumatic diseases and to improve diagnosis and therapy of these disorders. Some of these approaches/techniques have recently yielded important results, e.g. the analysis of 1) chromosomal aberrations (numerical and, in part, structural aberrations in synovial fibroblasts/macrophages from chronic joint inflammation); 2) cell clonality (oligoclonal expansion of synovial T-cells, B-cells, but also fibroblasts); 3) the importance of genetic factors (genome-wide screening for arthritis susceptibility genes); 4) mutations in key genes of cell cycle and/or function (mutations in p53 and proto-oncogenes in the inflamed synovial membrane); and 5) gene expression patterns (e.g. by high-density microarrays, custom arrays, in situ hybridization, and real-time PCR). It can be expected that these analyses will result in central new findings concerning the understanding of the pathogenetic basis of chronic inflammatory rheumatic diseases, with the potential to develop differential diagnostic criteria for these hitherto extremely heterogeneous diseases, and to create the basis for individual-oriented therapy.
11920401 Inadequately low serum levels of steroid hormones in relation to interleukin-6 and tumor n 2002 Mar OBJECTIVE: To compare levels of steroid hormones in relation to cytokines and to study levels of cortisol or dehydroepiandrosterone (DHEA) in relation to other adrenal hormones in untreated patients with early rheumatoid arthritis (RA) and reactive arthritis (ReA) compared with healthy controls. METHODS: In a retrospective study with 34 RA patients, 46 ReA patients, and 112 healthy subjects, we measured serum levels of interleukin-6 (IL-6), tumor necrosis factor (TNF), adrenocorticotropic hormone (ACTH), cortisol, 17-hydroxyprogesterone (17-OH-progesterone), androstenedione (ASD), DHEA, and DHEA sulfate (DHEAS). RESULTS: RA patients had higher serum levels of IL-6, TNF, cortisol, and DHEA compared with ReA patients and healthy subjects, but no difference was noticed with respect to ACTH and DHEAS. However, in RA and ReA patients compared with healthy subjects, levels of ACTH, cortisol, ASD, DHEAS, and 17-OH-progesterone were markedly lower in relation to levels of IL-6 and TNF. Furthermore, the number of swollen joints correlated inversely with the ratio of serum cortisol to serum IL-6 in RA (R(Rank) = -0.582, P = 0.001) and, to a lesser extent, in ReA (R(Rank) = -0.417, P = 0.011). In RA patients, the mean grip strength of both hands was positively correlated with the ratio of serum cortisol to serum IL-6 (R(Rank) = 0.472, P = 0.010). Furthermore, in these untreated patients with RA and ReA, there was a relative decrease in the secretion of 17-OH-progesterone, ASD, and DHEAS in relation to DHEA and cortisol. This indicates a relative predominance of the nonsulfated DHEA and cortisol in relation to all other measured adrenal steroid hormones in the early stages of these inflammatory diseases. CONCLUSION: This study indicates that levels of ACTH and cortisol are relatively low in relation to levels of IL-6 and TNF in untreated patients with early RA and ReA compared with healthy subjects. The study further demonstrates that there is a relative increase of DHEA and cortisol in relation to other adrenal hormones, such as DHEAS. This study emphasizes that adrenal steroid secretion is inadequately low in relation to inflammation. Although changes in hormone levels are similar in RA and ReA, alteration of steroidogenesis is more pronounced in RA patients than in ReA patients.
15452767 Comparison of estimated medical costs among patients who are defined as having rheumatoid 2004 Feb Accurate estimation of medical care costs raises a host of challenging issues. We examined whether pure administrative claims data without clinical validation of diagnosis allow reasonable estimation of disease-related costs in rheumatoid arthritis (RA). Three patient groups were examined: patients with clinically confirmed RA (group A, n=338), patients with likely RA (administrative claims data reported the diagnosis of RA and patients were treated with disease modifying antirheumatic drugs, DMARDs; group B, n=303), and patients with possible RA (same as group B but patients had no DMARD treatment; group C, n=685). The payer's perspective was taken for this analysis. Only direct costs were included in the analysis. Cost data and data for several covariates were obtained from a major German statutory health insurance plan, the AOK Niedersachsen. A patient-per-patient microcosting approach was performed. A repeated measures, fixed effects model was applied to examine differences between the three study groups. Mean+/-SEM annual RA-related direct costs were euro 2,017+/-183 per patient-year in group A, euro 1,763+/-192 in group B, and euro 805+/-58 in group C. Outpatient (inpatient) costs were euro 1,636 (328) in group A, euro 1344 (340) in group B, and euro 546 (136) in group C. DMARD costs were by far the single most important cost driver in groups A and B. The difference in total RA-related direct cost between groups A and B was not significant whereas the differences between groups A and C (group B and C respectively), were significant. Pure administrative claims data allowed for an accurate estimate of disease-related costs in RA patients that received DMARD therapy. However, the high number of patients for whom administrative claims data listed the diagnosis RA, but no DMARD treatment was given poses a challenge for further research.