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ID PMID Title PublicationDate abstract
11598150 Interleukin-18 induces rheumatoid arthritis synovial fibroblast CXC chemokine production t 2001 Oct Interleukin-18 (IL-18) is a novel proinflammatory cytokine that was recently found in synovial fluids and in synovial tissues from patients with rheumatoid arthritis (RA). To determine the participation of IL-18 in the inflammation observed in RA, we investigated the effect of IL-18 on RA synovial fibroblast chemokine production. Using FACS analysis, we showed that IL-18 induced a doubling in the production of intracellular IL-8 by RA synovial fibroblasts, and this result was confirmed by Western blot. At the extracellular level, IL-18 up-regulated the secretion of IL-8 in a dose- and time-dependent manner. IL-18 also up-regulated the other CXC chemokines, epithelial-neutrophil activating protein (ENA-78) and growth-regulated oncogene (groalpha), in a dose dependent manner, but failed to induce the production of the CC chemokine, macrophage inflammatory protein (MIP)-1alpha. By immunofluorescence and Western blot, we demonstrated that IL-18 activates the translocation of the transcription factor nuclear factor kappa B (NFkappaB) into the nucleus of RA synovial fibroblasts. IL-18 induces IL-8 secretion through NFkappaB because RA synovial fibroblasts pretreated with antisense to NFkappaB p65 oligonucleotide produce a mean of 44% less IL-8 compared with cells pretreated with the control sense oligonucleotide. These results indicate a novel role for IL-18 in inducing RA synovial fibroblast expression of CXC chemokines through NFkappaB and place this cytokine in a strategic role in the local inflammation observed in RA.
11176997 Elevated vitreous concentration of monoclonal immunoglobulin manifesting as schlieren in j 2001 Feb We report the clinical findings and analysis of the immunoglobulin (Ig) composition of the vitreous of a 10-year-old girl with juvenile rheumatoid arthritis-associated uveitis. The vitreous had a schlieren appearance at the time of pars plana lensectomy and vitrectomy. Analysis of the vitreous fluid revealed marked elevation of IgG, IgM, IgA, and albumin levels relative to vitreous fluids from control patients without uveitis. The immunoglobulin coefficients were also elevated for the IgG and IgM classes of immunoglobulins. Immunofixation electrophoresis of the vitreous fluid revealed 2 distinct bands of restricted electrophoretic mobility. These studies suggest that there may be local (intraocular) production of immunoglobulins as an immunologic response in ocular inflammatory diseases such as juvenile rheumatoid arthritis-associated uveitis and that this immunologic response may be monoclonal (possibly biclonal or oligoclonal) in nature.
9020467 A new radiographic method of measuring carpal collapse. 1997 Jan We assessed carpal collapse by measuring the capitate-radius (CR) distance on standard plain radiographs. This new method required validation of diagnostic accuracy, so we compared it with the method of Nattrass et al known as revised carpal height (RCH). We studied wrist radiographs from 16 normal subjects and 11 patients with unilateral Kienböck's disease. We found that there was a significant difference in the left/right CR index between the normal wrists and those with Kienbock's disease (p < 0.001). The use of left/right RCH index showed no significant difference (p = 0.30). Diagnostic accuracy was shown to be higher for the CR index using ROC curves. We then assessed 40 normal wrists and found the mean CR index to be 0.999 +/- 0.034, and suggest that values less than 0.92 are abnormal. The CR index can be used for diagnosis in unilateral carpal collapse, and for monitoring progress where the condition is bilateral.
11359453 HLA-DRB1 gene transcripts in rheumatoid arthritis. 2001 Apr Susceptibility to rheumatoid arthritis (RA) is associated with defined HLA-DRB1 alleles. However the molecular basis of this association is not known. Peculiarities in the expression of disease-linked DRB1 alleles could be involved since in healthy controls HLA-DRB1 gene expression varies according to the alleles in B cells. Peripheral blood B cells of healthy controls and RA patients were examined for their level of allelic DRB1 transcripts using a competitive PCR approach. Levels of DRB1 transcripts were greatly modified in RA and influenced by HLA-DRB1 genotype: patients with double dose of RA-associated alleles displayed up-regulated amounts of DRB1 gene transcripts whereas patients carrying either a single or no at risk allele had low levels of DRB1 transcripts, compared to control individuals. These differential levels of DRB1 gene expression were not influenced in any way by clinical, biological or therapeutic features of the patients. Various amounts of DRB1 mRNA may be related to variations of the density of DR molecules on B cells and consequently could influence the response of CD4 T cells. This particular regulation of DRB1 gene expression in RA patients could therefore represent one of the molecular mechanisms involved in the association of HLA DRB1 genes to RA.
11196534 Stromelysin-1 (MMP-3) in synovial fluid of patients with rheumatoid arthritis has potentia 2001 Jan OBJECTIVE: To investigate the relationship between matrix metalloproteinases (MMP) and the soluble form of Fas ligand (sFasL) in the synovial fluid (SF) of patients with rheumatoid arthritis (RA), and to determine which MMP have a major role in cleaving FasL. METHODS: The concentrations of sFas and sFasL in SF from 48 patients with RA and 43 patients with osteoarthritis (OA) were measured using specific ELISA. The levels of different MMP (MMP-1, 2, 3, 7, 9) in SF were also measured by ELISA. The active forms of gelatinases were detected by gelatin zymogram. Human FasL-expressing transfected cells (hFasL/L5178Y) were used to investigate whether FasL is cleaved from membrane bound FasL. RESULTS: Significantly higher levels of MMP-1, 3, and 9 were found in SF from RA patients compared to OA patients, but MMP-7 was not detectable in either group. The concentrations of sFas and sFasL in SF were also higher in RA than in OA patients. However, there was no relationship between the concentration of sFas and sFasL. Among MMP, MMP-3 concentrations in SF were closely correlated with the level of sFasL and with disease activity of RA. Enzymatic cleavage assay indicated that MMP-3 has potential to cleave the FasL expressed on hFasL/L5178Y cells and to produce sFasL. CONCLUSION: There was significant correlation between the concentration of sFasL and MMP-3 in SF of patients with RA. In addition, our data indicate that the shedding of FasL may be regulated by MMP-3 in the joint of patients with RA.
10433095 Rheumatoid arthritis sera react with a phage-displayed peptide selected by a monoclonal an 1999 Antibodies to type II collagen, and to Epstein Barr virus nuclear antigen-1 (EBNA-1) have been associated with rheumatoid arthritis (RA). In studies involving probing of phage-displayed random peptide libraries with an antibody to type II collagen, CII-C1, we observed that among 17 phagotopes selected 5 expressed peptides with homology with the sequence of EBNA-1. The residues in common were RLPFG. Hence we tested sera from 50 patients with RA, of whom 26 had antibodies to native type II collagen, and 43 healthy controls, for reactivity by ELISA with a phagotope selected 4 times, which expressed the peptide RRLPFGSQM. Eight RA sera (16%) but no normal sera reacted with the phagotope (p = 0.025). This reactivity could not be correlated with reactivity of RA sera with EBNA-1 by semi-quantitative western blot, with which reactivity occurred in 78% of RA patients and 81% of controls. Evidence for molecular mimicry was not found insofar as the phagotope did not inhibit reactivity of RA sera with EBNA-1 and CII-C1 was not reactive with EBNA-1. We conclude that the reactivity of the RA sera with the phagotope is most likely due to the phagotope being a mimic of an epitope of type II collagen for a proportion of RA sera.
10796440 Penicillamine for rheumatoid arthritis. 2000 OBJECTIVES: To estimate the short-term effects of D-penicillamine for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline up to and including December 1998 and Embase from 1988-1998. We also carried out 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 D-penicillamine against placebo in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed independently by two reviewers (CS, EB) and checked by a third (MS) using a validated quality assessment tool. Rheumatoid arthritis outcome measures were extracted from the publications for the six-month endpoint and stratified according to D-penicillamine dosages: low (<500mg/day), moderate (500 to <1000mg/day) and high (1000 mg/day or greater). Data was abstracted by one reviewer and checked by a second (CS, MS). The pooled analysis was performed using the standardized mean difference for joint counts, pain and global assessments. The weighted mean difference was used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals and adverse reactions. 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: Six trials were identified, with 425 patients randomized to D-penacillamine and 258 to placebo. A statistically significant benefit was observed for D-penicillamine when compared to placebo for all three-dose ranges and for most outcome measures including: tender joint counts, pain, physician's global assessments and ESR. The standardized weighted mean differences between treatment and placebo in moderate doses were -0. 51 [95% CI -0.88, -0.14] for tender joint counts, -0.56 (95% CI -0. 87, -0.26) for pain and -0.97 (95% CI -1.25, -0.70) for global assessment. The difference for ESR was -10.6 mm/hr. Similar results were observed for the higher dose group. Total withdrawals were significantly higher in the moderate and high dosage D-penicillamine groups (OR=1.63 and 2.13 respectively), mostly due to increased adverse reactions (OR = 2.60 and 4.95 respectively), including renal and hematological abnormalities. REVIEWER'S CONCLUSIONS: D-penicillamine appears to have a clinically and statistically significant benefit on the disease activity of patients with rheumatoid arthritis. Its efficacy appears to be similar to that of other disease modifying anti-rheumatic drugs (DMARDs), but with a significantly higher toxicity. Its effects on long-term functional status and radiological progression are not clear from this review.
11681539 Serum levels of parathyroid hormone and markers of bone metabolism in patients with rheuma 2001 OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before and after treatment with GC. METHODS: A range of biochemical markers of bone metabolism and calcium homeostasis were measured in 95 patients with definite RA stratified into groups according to disease activity and GC treatment. In a subgroup of 12 patients with active disease, initiating slow-acting-anti-rheumatic-drugs (SAARDs) +/- GC, the PTH secretion and calcium set point were evaluated by use of the Cica clamp technique before and after 1 month of treatment. RESULTS: S-osteocalcin, s-total alkaline phosphatase (s-TAP) and s-carboxyterminal cross-linked telopeptide of type I collagen (s-ICTP) were elevated in all groups. The levels of urine pyridinoline (Pyr) and s-albumin-corrected calcium (s-AlbCorrCa2+) were elevated in patients with active disease and patients treated with GC. S-PTH and s-phosphate were within normal ranges. S-TAP, s-ICTP, Pyr and s-AlbCorrCa2+ correlated positively with indices of disease activity. In the subgroups undergoing the Cica clamp technique, no difference in PTH responsiveness of B-Ca2+ was unveiled. CONCLUSION: Neither active disease nor GC therapy appears to induce secondary hyperparathyroidism, nor is there an alteration in PTH responsiveness of B-Ca2+ in patients with RA. The increased levels of markers of type I collagen metabolism (s-ICTP, Pyr) and s-AlbCorrCa2+ in patients with active disease and patients treated with GC may be a result of increased degradation in synovium, cartilage and bone due to the inflammatory process.
10206202 Immunocytochemical demonstration of lymphocyte subsets and MHC class II antigen expression 1999 Mar 1 The study describes the distribution of canine leucocyte antigens in synovial membrane biopsies from six dogs with canine rheumatoid arthritis (CRA) and from eight dogs with osteoarthritis (OA) secondary to spontaneous rupture of the cranial cruciate ligament (CCL) (n = 5) or patellar luxation (n = 3). Synovial membranes from five dogs without evidence of joint lesions were used as control tissues. In the subsynovium of dogs with normal joints CD5+, CD4+, CD8+ and alpha beta TCR+ lymphocytes were present only in low numbers. With monoclonal antibody (mAb) to MHC class II antigen, either none or up to 20-30% of synovial lining cells were immunoreactive. Furthermore, scattered MHCII+ stromal cells were seen in the deeper subsynovial layer. In synovial membrane biopsies from dogs with CRA numerous diffusely and perivascularly distributed CD5+ lymphocytes were found in the subsynovium. CD4+ cells outnumbered CD8+ cells and were more numerous in the perivascular areas. In all the CRA cases examined, there were markedly higher numbers of alpha beta TCR+ cells compared with gamma delta TCR+ cells. With mAb to CD21, low numbers of immunoreactive lymphocytes were demonstrated. In all the CRA cases, a marked increase of MHC class II antigen expression was noted. In the majority of samples, 50% or more than 90% of the synovial lining cells were strongly MHC class II+. Throughout the subsynovial layer there were numerous MHC class II+ cells and included those with dendritic morphology and inflammatory mononuclear cells. Furthermore, marked perivascular immunoreactivity for MHC class II antigen was found. In biopsies from dogs with OA, there were markedly lower numbers of subsynovial CD5+, CD4+ and CD8+ lymphocytes. T-cells were mainly diffusely distributed. In three of the eight OA dogs examined, there was an increased percentage of synovial lining cells expressing MHC class II. The majority of OA cases had subsynovial major histocompatibility complex (MHC) class II+ cells with a dendritic morphology.
9751472 Early referral and outcome in rheumatoid arthritis. 1998 In a cross-sectional study of 200 outpatients with rheumatoid arthritis (RA) we tested the hypothesis that early specialist referral within one year of disease onset reduces subsequent functional disability. Early referral was defined as being seen in a specialist unit within one year of the onset of symptoms. Functional outcome was measured using the physical functional section of the full test (NHP) and (HAQ). Additional information was collected on other factors likely to influence disability including age, sex, pain scores, and rheumatoid factor positivity. The difference in average HAQ and NHP physical function scores between late and early referrals was 0.34 and 11.0 respectively (p< 0.01 in both cases) using unequal-variance t-test. After adjusting for the other risk factors, multiple regression analysis showed late referral patients had greater NHP physical function scores than early-referred patients by approximately 8 points and there was a similar trend with HAQ. We conclude that early referral for specialist advice is associated with improved health status, with reduced physical function scores on the NHP.
11199350 Recombinant human erythropoietin therapy for autologous blood donation in rheumatoid arthr 2001 Jan The effect of recombinant human erythropoietin on autologous blood donation was investigated in 73 rheumatoid arthritis patients who underwent hip or knee arthroplasty. Autologous blood donation of 400 mL was successful with recombinant human erythropoietin (12,000 U per week), and no homologous blood was required. The mean period of blood collection was 33.8 days. Mean hemoglobin levels were 9.7 g/dL before treatment, 10.7 g/dL before surgery, and 10.2 g/dL after surgery. This study confirmed recombinant human erythropoietin is effective for enabling preoperative blood donation in rheumatoid arthritis patients.
11302881 HLA-DRB1 genes and patients with late onset rheumatoid arthritis. 2001 May OBJECTIVE: To determine the influence of HLA-DRB*1 genes on susceptibility to and severity of rheumatoid arthritis (RA) in patients with late onset compared with younger onset disease. METHODS: The clinical, biological, and HLA-DRB1 typing characteristics of two groups of patients were studied retrospectively. Group 1 consisted of 262 patients whose disease onset was before or at the age of 60 (young onset RA (YORA)). Group 2 included 60 patients whose illness began after the age of 60 (elderly onset RA (EORA)). RESULTS: The shared epitope level was similarly increased in both groups of patients compared with normal controls (195/262 (74%) in group 1 and 43/60 (72%) in group 2 v 645/1609 (40.1%) in controls). No differences were noted between the two groups of patients for each separate disease related allele. In contrast, when studying all HLA-DRB1*04 RA related alleles as a group, these alleles were underrepresented in EORA compared with YORA (22/60 (37%) v 135/262 (52%); odds ratio 2.0; 95% confidence interval 1.0 to 3.3). An inverse trend was seen for HLA-DRB1*01 alleles. There were no differences in biological characteristics or extra-articular manifestations between the patient groups. The differences noted in radiological evaluation or the number of prescribed disease modifying antirheumatic drugs seemed to be linked with differences in disease duration. CONCLUSION: HLA-DRB1 RA related alleles influence both EORA and YORA. However, HLA-DRB1*04 RA linked alleles are not as closely associated with RA in the elderly as they are in younger patients. This suggests that the importance of these genes in the susceptibility to RA may be lower in elderly patients.
10674972 Lack of a strong association of CTLA-4 exon 1 polymorphism with the susceptibility to rheu 1999 Dec CTLA-4 is considered to be one of the attractive candidates for the susceptibility genes to rheumatic diseases. In the present study, the association of CTLA-4 polymorphism with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) was examined in the Japanese population using the case-control association analysis. Polymerase chain reaction-preferential homoduplex formation assay (PCR-PHFA) was applied for the screening of genetic variations and for the genotyping of a large number of samples. A greater proportion of Japanese patients with RA (44%) and SLE (44%) compared with healthy individuals (37%) had exon 1 49 G/G genotype, but the difference did not reach statistical significance. However, when the patients with RA and healthy individuals were stratified according to HLA-DRB1 alleles, a weakly significant increase of the positivity of CTLA-4 49G allele was observed in HLA-DRB1*0405-positive patients (87%) compared with DRB1*0405-positive healthy individuals (71%) (P = 0.014, odds ratio = 2.77). These results indicate that CTLA-4 exon 1 polymorphism does not contribute greatly to the susceptibility to RA and SLE, at least in Japanese, although the presence of CTLA4 49G allele could be a minor predisposing factor for RA in HLA-DRB1*0405-positive individuals. In addition, PCR-PHFA was shown to be useful for a mass screening of gene variations.
10660945 Cyclosporine A pharmacokinetics in rheumatoid arthritis patients after 6 months of methotr 1999 Dec To evaluate the effects of a 6-month methotrexate (MTX) treatment period on cyclosporine A (CsA) pharmacokinetics were subsequently added in patients with rheumatoid arthritis (RA) in comparison with patients treated with CsA only, CsA was administered to 30 subjects with RA (group A) treated with MTX (10 mg week-1 i.m.) for 6 months and to 30 patients (group B) who received no MTX treatment. The mean doses +/- SD of CsA used in groups A and B were 3.2 +/- 0.5 and 3.3 +/- 0.4 mg kg-1, respectively. CsA levels were determined in whole blood by means of a fluorescence polarization immunoassay (FPIA) method with a specific monoclonal antibody. The following pharmacokinetics parameters were calculated: area under the curve from 0 to 24 h (AUC0-24), half-life of the elimination phase (T1/2 beta), total body clearance CL.F-1; V.F-1 and apparent volume of distribution (Vd beta). The mean blood concentrations and the pharmacokinetic parameters calculated in group A did not present significant statistical differences in comparison to group B. In conclusion, a 6-month MTX therapy does not produce liver function modifications to such an extent as to modify the pharmacokinetics of CsA subsequently added. Therefore, from a clinical pharmacological point of view, an MTX-CsA cotreatment appears feasible.
10591976 [Influence of osteoarthrosis, osteoporosis, and rheumatoid arthritis at precision of osteo 1999 Oct Precision of osteodensitometric measurements using dual energy X-ray absorptiometry (DEXA) depends on various known factors, such as positioning, aortic calcification or vertebral fractures. The purpose of this study was to investigate the influence of various diseases or bone density on the reproducibility of measurements in the lumbar spine and the proximal femur. Measurements in the LWS p.a. , LWS lat. and at Ward's triangle were made in a total of 100 patients. The subjects were repositioned between measurements. In order to be able to determine the influence of various diseases, four groups of 25 patients each were formed: three with the diagnosis osteoarthrosis, osteoporosis and rheumatoid arthritis and one control group. The mean percentual difference and coefficient of variation were calculated as the measure for reproducibility. Mean percentual differences of 0.18 to 2.6% were found in the four groups at the three measurements sites. After calculation of coefficient of variation, a value between 1.2 and 2.7% was found for LWS p.a., between 7.1 and 15.7% for LWS lat. and between 4.1 and 9.9% at Ward's triangle. It was also conspicuous that the difference in coefficient of variation in osteoporosis patients was nearly double that in the control group in all measured areas. CONCLUSION: Lateral lumbar spinal measurements using DEXA cannot presently be recommended. LWS p.a. measurements and, with limitations, measurements at Ward's triangle have good precision and could be used for course documentation of bone density.
9554551 Relative predispositional effects and mode of inheritance of HLA-DRB1 alleles among commun 1998 Multiple HLA-DRB1 alleles encoding a shared epitope (SE) at amino acid positions 70-74 are associated with susceptibility to rheumatoid arthritis (RA). However, the nature of the association and the mode of inheritance differ depending upon the source of RA patients and laboratory methodology. We studied the relative predispositional effects (RPE) and mode of inheritance of DRB1 alleles among a community-based sample of 180 RA patients and 116 healthy controls, all Caucasian females. Polymerase chain reaction (PCR)-based assays were used for DRB1 genotyping, and the genotypic distributions were analyzed by both the RPE and antigen genotype frequency among patients (AGFAP) methods. We examined the evidence of synergy among DRB1 alleles for RA risk by comparing the observed DRB1 genotype distribution to that predicted under Hardy-Weinberg equilibrium. Fifty-six percent of RA cases were attributable to DRB1 alleles encoding the SE. The RPEs of DRB1 alleles were *0401 > *0404 > *1001 > *0408 > *0101. The strength of the RA association was not significantly different for these alleles. The AGFAP analysis was consistent with a recessive mode of inheritance for DRB alleles, while an additive (dominant) model was rejected. We found no evidence of synergy for RA risk among individual DRB1 alleles based on comparison of the observed vs. predicted genotype distributions. These results suggest that among community-based Caucasian females with RA, the DRB1 RA susceptibility gene influences disease risk in a recessive fashion without synergy among individual DRB1 alleles.
9489809 Telomerase activity in rheumatoid synovium correlates with the mononuclear cell infiltrati 1998 Feb OBJECTIVE: To determine whether the presence of telomerase activity in synovial tissues could provide insights into the pathogenesis of rheumatoid arthritis (RA). METHODS: Synovial tissue samples obtained from patients with RA or osteoarthritis (OA) were examined for telomerase activity using the telomeric repeat amplification protocol (TRAP). RESULTS: Telomerase activity was detected in over half the RA synovial tissues (14/25, 56%) but in no OA synovial tissue samples (0/15). Telomerase activity was detected in the mononuclear cells isolated from telomerase-positive RA synovial tissue, but not in cultured adherent cells. In RA synovial tissue with positive telomerase activity mononuclear cell infiltration levels were increased (p < 0.001). In addition, patients with RA with positive telomerase activity had undergone joint operations at an earlier age (p = 0.030) and more often (p = 0.023) compared to those without telomerase activity. CONCLUSION: Telomerase activity in RA synovial tissue is likely derived from infiltrating mononuclear cells and may be involved in the pathogenesis of RA. Clinically, the presence of telomerase activity in RA may be an indicator of a more aggressive phenotype.
11333350 One-year inhibition of tumor necrosis factor-alpha: a major success or a larger puzzle? 2001 May The concept suggesting the involvement of the proinflammatory cytokine tumor necrosis factor (TNF)-alpha in the pathogenesis of rheumatoid arthritis (RA) has been demonstrated by several clinical trials targeting TNF-alpha. In addition to reduction of pain and swelling, a dramatic effect of TNF blocking therapies on the progression of joint destruction was shown. Nevertheless, complete remissions of the disease are rare even with these powerful therapeutic agents, and the optimal doses and dosage intervals of TNF blockers remain to be determined. Some insights into the pathogenesis of RA are provided by studying the effects of therapeutic TNF blockade on the biology of the disease. The fact that inflammation is not completely halted and destruction is ongoing in some patients suggests that other mechanisms may also be involved, including other cytokines such as interleukin-1 and interleukin-6. In addition to the necessity of understanding the pathogenic events proximal to TNF-alpha induction, pharmacologic intervention with small molecules in the TNF signaling pathways may constitute a promising strategy.
11595971 Magnetic resonance imaging of the wrist in rheumatoid arthritis. 2001 Sep Despite the extraordinary advances made in medical imaging over the past two decades and the central role that magnetic resonance imaging (MRI) and other sophisticated technologies now play in routine clinical practice, rheumatology has benefited relatively little from these advances thus far. Over the past few years, however, evidence has accumulated to show that MRI can identify joint damage in patients with rheumatoid arthritis earlier and more sensitively than other techniques can, and that MRI can directly visualize and monitor changes in synovium and bone that precede actual bone erosion. Much of this development is being driven by the pharmaceutical and biotechnology industries as they search for novel therapies to combat this disease. Accordingly, the imaging tools that ultimately will be used to direct patients to specific therapies and then to monitor treatment effectiveness and safety are currently being refined and validated in rigorous multicenter and multinational clinical trials aimed at gaining regulatory approval of these new therapies. As these therapies become available for clinical use, radiologists can anticipate increased demand for expertise and experience in evaluating disease progression and treatment response with these techniques and the emergence of MRI systems specifically adapted for this application. The following discussion reviews the current status of this development, and points to areas where further advances are anticipated in the near future.
9448591 Decrease of interleukin 6 during the first 12 months is a prognostic marker for clinical o 1997 Dec The aim of this study was to determine prognostic markers for the outcome after 36 months of therapy with disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) and to study serial cytokine serum levels. During 36 months, 20 patients receiving DMARDs (nine patients gold sodium thiomalate and 11 patients methotrexate, no comparison undertaken) were followed for clinical and laboratory data. Investigation at baseline, 12, 24 and 36 months, included clinical, radiological and laboratory parameters such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and interleukin (IL)-1 beta, IL-6, tumor necrosis factor alpha (TNF-alpha), IL-1 receptor antagonist (IL-1RA) and IL-2. During the 3 yr of therapy, the patients showed significant clinical improvement and decline of ESR, CRP, and serum levels of IL-6 and IL-2. The decrease in IL-6 serum levels during the first year of therapy correlated significantly with the decrease, after 36 months, in the number of inflamed joints (r = 0.7608, P < 0.005), Lansbury index (r = 0.6642, P < 0.005) and morning stiffness (r = -0.6561, P < 0.005). In contrast to IL-6 or IL-2, TNF-alpha and IL-1RA did not vary significantly during the 3 yr of therapy. During 36 months of therapy, patients treated with DMARD showed significant improvement of clinical parameters and a trend for delayed progression of radiographic damage. The decrease in IL-6 concentration in serum during the first 12 months was the best prognostic marker for the clinical outcome after 36 months of DMARD therapy.