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M Dougados

Publications and source records attributed to M Dougados.

At least 217 records · Page 12Linked to original sources

Neutrophil expression of tumour necrosis factor receptors (TNF-R) and of activation markers (CD11b, CD43, CD63) in rheumatoid arthritis.

In vitro analysis of polymorphonuclear neutrophils (PMN) has allowed various stages of cell activation to be distinguished, characterized by the expression level of specific membrane markers and of functional receptors. Among those, TNF-alpha receptors (TNF-R) are modulated by various PMN activators, a mechanism which may be important to control cell responses to TNF in inflammatory reactions such as rheumatoid arthritis (RA). PMN, isolated from the blood of 36 RA patients and from the synovial fluid of 23 of them, were analysed for membrane expression of the two TNF-R (p55 and p75). Soluble p55 and p75 (sTNF-R) and TNF concentrations were measured in the plasma and synovial fluid by specific ELISA assays. Our results show that PMN from the blood of RA patients bear a normal number of TNF-R, with a normal p55/p75 ratio, compared with PMN from normal controls. Soluble TNF-R levels were similar in patients and normal plasma. In spite of high endogenous TNF concentration, patients' circulating PMN were not activated, as shown by a CD11b/CD18 expression similar to that of control resting cells. In contrast with blood neutrophils, PMN from RA patients' synovial fluids had an activated phenotype, characterized by increased expression of CD11b, decreased expression of leukosialin, CD43, and the appearance on the plasma membrane of an azurophil granule protein, CD63. High levels of soluble TNF-R were measured in RA synovial fluids. Nevertheless, membrane TNF-R levels and p55 and p75 proportions were similar to those of PMN from normal blood. These results suggest the existence of regulatory mechanisms which maintain a stable neutrophil expression of TNF-R as well as a balance between both types of receptors in inflammatory situations where neutrophils are strongly activated.

Antigens, CD↗

Effect of cyclosporin A on interleukin-6 and soluble interleukin-2 receptor in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the effect of cyclosporin A (CyA) therapy on circulating concentrations of interleukin-6 (IL-6) and soluble interleukin-2 receptor (sIL-2R) in patients with rheumatoid arthritis (RA). METHODS: Twenty four RA patients with active disease were studied. Plasma was collected before and after 16 weeks of CyA treatment. IL-6 was measured by B9 bioassay and sIL-2R by enzyme linked immunosorbent assay (ELISA). RESULTS: The initial median IL-6 concentration of 165 IU/ml decreased significantly to 71 IU/ml after 16 weeks (p < 0.05). Similarly, the initial median plasma sIL-2R value of 665 U/ml decreased significantly to 570 U/ml (p < 0.05). This decrease was accompanied by an improvement in clinical parameters of disease activity. Some association between sIL-2R, IL-6, haemoglobin, and platelets was also observed. CONCLUSIONS: This study has demonstrated that, in vivo, CyA therapy in RA can significantly reduce circulating concentrations of IL-6 and sIL-2R. Modulation of both T and non-T cell derived cytokines may be one mechanism by which CyA improves rheumatoid disease. Whether this is a direct effect of CyA on the cells within the rheumatoid joint producing these cytokines or an indirect effect mediated by other cytokines which can influence IL-6 and Il-2R values remains to be determined.

Adult↗

Joint lavage.

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Animals↗

Management of refractory ankylosing spondylitis and related spondyloarthropathies.

Ankylosing spondylitis is the prototype of an interrelated group of disorders termed spondyloarthropathies, which include reactive arthritis, psoriatic arthritis, and rheumatic disorders associated with inflammatory bowel disease. It can be difficult to differentiate between these disorders because they may occur simultaneously or sequentially. In addition, some of the clinical characteristics of these diseases, such as enthesiopathy and eye involvement, are similar no matter what the diagnosis. The monitoring, diagnosis, and treatment of these diseases are related more to their clinical presentation than to the precise diagnosis.

Bone Marrow Transplantation↗

Are classification criteria for spondylarthropathy useful as diagnostic criteria?

The authors used data from a study conducted under the auspices of the Société Française de Rhumatologie to evaluate the sensitivity and specificity of the individual items of two sets of criteria for spondylarthropathy. The study included 124 patients with spondylarthropathy and 1,964 controls. They found that the spondylarthropathy criteria with the highest sensitivities and specificities were useful not only for classifying patients but also for assisting in the diagnosis of spondylarthropathy.

Humans↗

Sensitivity to change of various roentgenological severity scoring systems for osteoarthritis of the hip.

RATIONALE: joint space assessment on roentgenograms is considered reliable for evaluating the anatomic severity of hip osteoarthritis. Methods for measuring this parameter include the scoring system developed by Kellgren and Lawrence, joint space width measurement, and joint space surface area measurement after digitalization of roentgenograms. OBJECTIVE: to compare the sensitivity to change of the three above-listed methods. PATIENTS AND METHODS: the study included patients with hip osteoarthritis meeting ACR criteria for whom two roentgenograms showing evidence of hip osteoarthritis taken 10 to 15 months apart were available. Roentgenograms were read by a single investigator who was unaware of the chronological order of films. Sensitivity to change of the three measurement techniques was determined by calculating standardized response mean (mean change/standard deviation of change). RESULTS: the study evaluated 34 hips (68 roentgenograms) in 22 patients (12 females and ten males, mean age 63 +/- 10 years) with osteoarthritis of one (n = 10) or both (n = 12) hips. Standardized response mean were 0.37, 0.33, and 0.16 for joint space width, joint space surface area, and the Kellgren-Lawrence score, respectively. CONCLUSION: this study suggests that joint space width or surface area may be more sensitive than the Kellgren-Lawrence score for monitoring the course of hip osteoarthritis.

Aged↗

Predictors of the need for total hip replacement in patients with osteoarthritis of the hip.

RATIONALE: the natural history and risk factors for hip osteoarthritis are still unknown. OBJECTIVE: to identify factors predicting a need for total hip replacement at some time during the course of hip osteoarthritis. PATIENTS AND METHODS: outpatients evaluated between 1981 and 1986 for hip osteoarthritis were studied retrospectively. The date of diagnosis and the characteristics of the patients and hip disease at diagnosis were recorded. The risk of eventual total hip replacement was estimated using the Kaplan-Meier method. Uni- and multivariate Cox proportional hazard models were used to determine the value of each variable for predicting total hip replacement. RESULTS: we included 149 patients (50 males). The risk of total hip replacement was estimated at 36 +/- 4% five years after diagnosis. Factors with significant effects in the multivariate analysis were age older than 54 years at diagnosis (relative risk 3.15), body mass index greater than 27 (relative risk 2.97), and severe radiological joint space narrowing at diagnosis (relative risk 2.26). CONCLUSION: this study confirmed the often severe course of hip osteoarthritis and identified several factors possibly associated with rapid progression.

Aged↗

[Chondroscopy: a new method for measuring osteoarthritis?].

Arthroscopy allows direct visual examination of joint cavity components and is useful for the diagnosis, treatment and evaluation of lesions. We investigated the contribution of arthroscopy to the evaluation of joint cartilage. The severity of cartilage lesions can be assessed using a total 100-mm visual analog scale (0 = no chondropathy; 100 = the worst possible lesions) or a more objective system based on the site, depth, and surface area of the lesions. This latter system was developed by the French Society for Arthroscopy (Société Française d'Arthroscopie) and provides a score and a class (SFA score and SFA grade). We investigated whether this system has the characteristics required of an evaluation tool, i.e., simplicity, reproducibility, clinical relevance, sensitivity to change, and discriminant capacity. Arthroscopy is an invasive procedure. However, we introduced several simplifications, including use of local rather than general anesthesia, performance on an outpatient basis, elimination of the tourniquet (to avoid muscular dysfunction), and use of a small arthroscope. This simplified technique is called chondroscopy. Intra-observer reproducibility is far better than inter-observer reproducibility. We found a good correlation between the two arthroscopy scales (visual analog scale and SFA scale). Chondroscopy and roentgenographic evaluations of cartilage lesions were closely correlated. Changes in the severity of cartilage lesions were correlated with changes in functional impairment. Chondroscopy proved capable of demonstrating statistically significant changes in cartilage lesions due to knee osteoarthritis between two evaluations done only one year apart, even in a small sample of patients (less than 20). A preliminary study of repeated hyaluronic acid injections suggested that chondroscopy may be capable of identifying truly chondromodulating agents.

Arthroscopes↗

Diacerhein in the treatment of osteoarthritis of the hip.

OBJECTIVE: To determine the efficacy and safety of diacerhein, a potential new therapeutic agent with properties differing from those of existing nonsteroidal anti-inflammatory drugs (NSAIDs), and of a combination of diacerhein and an NSAID (tenoxicam) in the treatment of osteoarthritis (OA) of the hip. METHODS: Two hundred eighty-eight patients with painful OA of the hip were enrolled in an 8-week randomized, double-blind, placebo-controlled, 2 x 2 factorial design study. Four treatment groups were defined: 1) diacerhein placebo and tenoxicam placebo, 2) tenoxicam and diacerhein placebo, 3) diacerhein and tenoxicam placebo, and 4) diacerhein and tenoxicam. The daily dosages of diacerhein and tenoxicam were 100 mg and 20 mg, respectively. RESULTS: Analyses of efficacy showed no interaction between diacerhein and tenoxicam in terms of efficacy, a clinically significant rapid (< or = 2 weeks) and persisting effect of tenoxicam during the 8 weeks of the study, and a slow-acting (6 weeks) effect of diacerhein. Moderate, transient diarrhea was the most frequent side effect observed in the diacerhein group (37%) compared with the placebo group (4%). CONCLUSION: Both tenoxicam and diacerhein appear to be superior to placebo, and neither agent appears to significantly enhance or detract from the efficacy of the other when they are administered concomitantly. The onset of action of diacerhein appears to be delayed (> or = 4 weeks).

Aged↗

The SFA system for assessing articular cartilage lesions at arthroscopy of the knee.

We proposed to establish a system of assessing severity of chondropathy taking into account localization, size, and depth of cartilage lesions. The design of the study was prospective and multicenter. The subjects were 755 patients who had undergone arthroscopy of the knee. Criteria for assessment of severity of chondropathy were as follows: (a) Physician's overall assessment using a 100-mm-long Visual Analogue Scale, and (b) size, grade, and localization of cartilage lesions recorded on a diagram. We used multivariate parametric and nonparametric analyses. The analyses resulted in two systems of assessing severity of chondropathy: SFA scoring for the three compartments of the knee, which is a continuous variable, and SFA grading, which is a semiquantitative variable. These systems seem to be of clinical relevance. However, more studies are required to further validate them and their capacity to detect changes in severity of chondropathy.

Adult↗

Ximoprofen in ankylosing spondylitis. A double blind placebo controlled dose ranging study.

Ximoprofen is a new propionic NSAID which has previously demonstrated its efficacy at a daily dose of 30 mg. The aim of the study was to evaluate the efficacy of different daily dosages of Ximoprofen in patients with active ankylosing spondylitis. For 2 weeks 5 parallel groups were studied: placebo and Ximoprofen at 5, 10, 20 and 30 mg daily. Response to treatment was defined as an improvement in pain (VAS 100 mm) of at least 50% during the study. 285 out of the 332 screened patients were included. At the end of the study, the percentage of responders was higher in the Ximoprofen groups (54%, 41%, 53%, 56% in the 5, 10, 20 and 30 mg groups, respectively) than in the placebo group (21%). The clearest dose related effect of Ximoprofen observed occurred after one week of treatment. This study 1/confirms the efficacy of Ximoprofen at a 30 mg daily dosage, 2/shows the persistence of this efficacy at lower dosages, 3/suggests that ankylosing spondylitis is a sensitive and relevant human model to assess NSAIDs at an early stage of clinical evaluation.

Adult↗

Predictive factors for the longterm outcome of spondyloarthropathies.

OBJECTIVE: To determine the predictive factors of outcome in patients with spondyloarthropathy (European Spondyloarthropathy Study Group or Amor criteria) monitored by a single investigator. METHODS: Classification of longterm outcome on a 3-grade scale. Candidate predictive factors: presence or not of 12 clinical or biological variables during the first 2 years of the disease, collected by history at the time of the first visit. Univariate analysis to pick up the factors statistically correlated with severity and then odds ratio and 95% confidence interval (CI) for each variable were calculated. RESULTS: Of the 328 patients with spondyloarthropathy, 151 had a followup of > or = 10 years and minor disease (81), severe (28), or moderate disease (42). Seven variables at entry were correlated with disease severity (odds ratio; CI 95%); hip arthritis (22.85; 4.43-118); erythrocyte sedimentation rate > 30 mm/h (7; 4.84-9.50); poor efficacy of nonsteroidal antiinflammatory drugs (8.33; 2.56-27.10); limitation of lumbar spine (7; 2-25); sausage-like finger or toe (8.45; 1.48-9); oligoarthritis (4.25; 1.38-13.10); onset < or = 16 years (3.47; 1.06-12.75). If none of these factors is present at entry a mild outcome can be predicted (sensitivity: 92.5%; specificity: 78%). If a hip is involved or if 3 factors are present, a severe outcome is predictable (sensitivity: 50%) and a mild disease practically excluded (specificity: 97.5%). CONCLUSION: Predictive factors of poor or benign longterm outcome could be defined very early after onset of spondyloarthropathy in a set of patients monitored by one observer.

Adolescent↗

[The risk/benefit ratio of low-dose cyclosporin in the treatment of severe rheumatoid arthritis].

Although the efficacy of cyclosporine therapy in rheumatoid arthritis has been established, there have been no long term studies of the risk/benefit ratio of cyclosporine A in severe rheumatoid arthritis. A prospective, open-label one-year study included 106 patients (83 women and 23 men; mean age 53 years; mean disease duration, 11 years) with rheumatoid arthritis. Mean number of previous second-line treatments was four and 69% of patients had failed methotrexate therapy. The initial dosage of cyclosporine was 3 mg/kg/d and was increased if needed up to 5 mg/kg/d. The dosage was reduced in the event of serum creatinine elevation (by more than 30% versus baseline) or diastolic blood pressure elevation (above 95 mmHg). The statistical analysis was performed on an intention-to-treat basis. In the 45 patients who completed the one-year study period, the mean dosage was 3.6 +/- 1 mg after six months and 3.3 +/- 1 mg/kg/d after one year. Significant improvements were seen in all the clinical efficacy parameters. The mean reduction in corticosteroid dosage was 0.5 mg/d. The study drug was discontinued prematurely in 61 patients (36 because of adverse events and 21 because of inefficacy). Twelve of the 56 patients with serum creatinine level elevation on at least one occasion and seven of the 35 patients with diastolic blood pressure elevation were taken off the study drug.

Adult↗

[The carpus-metacarpus-index distance: a measurement for quantifying radiological lesions in rheumatoid polyarthritis. Comparison with Larsen's scores and Steinbrocker's index].

The carpus-to-digits distance measured on a posteroanterior roentgenogram of the hands and wrists takes into account 18 different joints. This study demonstrates that the carpus-to-digit distance is a simple, reproducible score which reliably reflects progression of roentgenological rheumatoid arthritis lesions and is correlated with Larsen's lesion score and with Steinbrocker's index, but not with Larsen's erosion score during the first two years after onset of the disease. Larsen's erosion score and similar parameters should be preferred for clinical studies of recent-onset rheumatoid arthritis. The carpus-to-digit distance, which requires neither a reference film not observer training, is appropriate for long-term clinical studies.

Arthritis, Rheumatoid↗

Chondroscopy: a new method for scoring chondropathy.

The purpose of this study was to evaluate the performance (simplicity, reproducibility, relevance) of chondroscopy as a method for evaluating cartilage damage. Chondroscopy consisted in endoscopic evaluation of the knee using a 2.7-mm Storz arthroscope under local anesthesia and recorded on videotape. Scoring of chondropathy was based on physician's overall assessment using a 100-mm-length visual analogue scale (VAS) and size and grade of cartilage lesions. Reproducibility was evaluated by variability (coefficient of variation [CV]) in the reading of chondroscopic evaluations of five patients five times by one physician and one time each by four different physicians. The correlations between scoring of chondropathy (VAS) and radiological articular joint space narrowing, demographic data (sex, age, weight), and disease characteristics (localization, etiology, activity) were studied in 84 outpatients fulfilling the American College of Rheumatology criteria for the diagnosis of osteoarthritis of the knee. The grade and size of the lesions were both correlated with the physician's overall assessment (r = 0.713 and r = 0.816, respectively). These two variables accounted for 72% of the variance of the VAS (multiple regression analysis). Intraobserver reproducibility was better than interobserver reproducibility (CV, 9% and 37%, respectively). There was a strong correlation between the scoring of chondropathy (VAS) and radiological joint space narrowing (r = .646, P < .0001). Moreover, in 17 of 33 patients without radiological joint space narrowing, VAS was > 20 mm. At variance, the body mass index was the single clinical variable found to correlate with the scoring of chondropathy (r = .282, P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Arthroscopy↗

High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial.

Hyaluronic acid is a natural component of cartilage and is considered not only as a lubricant in joints but also as playing a physiological role in the trophic status of cartilage. Hyalectin, a selected fraction of hyaluronic acid extracted from cocks' combs, has exhibited efficacy in animal models of osteoarthritis. To assess the efficacy and tolerability of intra-articular injections of hyalectin, we conducted a prospective, randomized, placebo-controlled trial of 1 years' duration in 110 patients with painful hydarthrodial osteoarthritis of the knee. At entry and once a week for 3 weeks, aspiration of the knee effusion and intra-articular injections of either hyalectin 20 mg (H) or its vehicle (C) were performed. The vehicle acted as the control treatment. Four weeks after the last injection, the improvement was greater in the H group compared with the C group (pain: -35.5 +/- 26.4 mm vs -25.8 +/- 21.4, P = 0.03, Lequesne's functional index: -3.8 +/- 4.3 vs -2.3 +/- 3.3, P = 0.03). During the 1 year follow-up, the need to perform supplementary local therapies (joint fluid aspiration because of painful hydarthrodial episodes and/or local corticosteroid injections) was more frequent in group C (44% vs 30%, P = 0.03). Moreover, at the final visit, the physician's overall assessment of efficacy was in favor of H (77% vs 54%, P = 0.01) and the improvement in the functional index was greater in group H (-4.4 +/- 5.1 vs -2.7 +/- 4.1, P = 0.05). This study suggests that intra-articular injections of hyalectin may (1) improve clinical condition and (2) have a long-term beneficial effect in patients with osteoarthritis of the knee.

Aged↗