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Biomedical subjects

E Vignon

Publications and source records attributed to E Vignon.

At least 19 recordsLinked to original sources
PubMed2000

Matrix metalloproteinase-13 expression in rabbit knee joint connective tissues: influence of maturation and response to injury.

The hypothesis of the present work was that expression of matrix metalloproteinase-13 (MMP-13, collagenase-3) would be induced during conditions involving important matrix remodeling such as ligament maturation, scar healing and joint instability. Therefore, MMP-13 expression in the medial collateral ligament (MCL) during the variable situations of tissue maturation and healing was assessed. MMP-13 expression in three intra-articular connective tissues of the knee (i.e. articular cartilage, menisci and synovium) following the transection of the anterior cruciate ligament of the knee was evaluated at 3 and 8 weeks post-injury. MMP-13 mRNA (semi-quantitative RT-PCR) and protein (immunohistochemistry and Western blotting) were detected in all of the tissues studied. Significantly higher MCL mRNA levels for MMP-13 were detected during the early phases of tissue maturation (i.e. 29 days in utero and 2-month-old rabbits) compared to later phases (5- and 12-month-old rabbits). This pattern of expression was recapitulated following MCL injury, with very high levels of expression in scar tissue at 3 weeks post-injury and then a decline to levels not significantly different from control values by 14 weeks. Elevated mRNA levels correlated with increased protein levels for MMP-13 in both menisci and synovium following the transection of the anterior cruciate ligament and during medial collateral ligament healing. These results indicate that MMP-13 expression is regulated by a number of variables and that high levels of expression occur in situations when connective tissue remodeling is very active.

Animals↗
PubMed2000

Glucosamine sulfate modulates dysregulated activities of human osteoarthritic chondrocytes in vitro.

OBJECTIVE: The efficacy of glucosamine sulfate (GS) in the symptomatic treatment of patients with osteoarthritis (OA) is suggested to be mediated by still unknown effects on the altered OA cartilage. DESIGN: Using human OA chondrocytes in culture, the effects of GS on protein synthesis, caseinase, collagenase, phospholipase A2 (PLA2) and protein kinase C (PKC) activities as well as production of nitric oxide and cyclic AMP were studied in both cells and culture medium. RESULTS: GS significantly reduced PLA2 activity, and more modestly collagenase activity, in the OA chondrocytes in a dose-dependent manner. By contrast, PLA2 and collagenase activity of the culture medium was not modified. No effects on caseinase activity was seen. GS significantly and dose-dependently increased protein synthesis. GS did not modify nitric oxide and cAMP production but significantly increased PKC production. CONCLUSION: GS modified cultured OA chondrocyte metabolism by acting on PKC, cellular PLA2, protein synthesis and possibly collagenase activation. Extrapolation of the effect to the in-vivo situation remains hypothetical but they might represent some possible mechanisms of action of the drug in human.

Caseins↗
PubMed2000

Hepatic fibrosis in rheumatoid arthritis patients treated with methotrexate: application of a new semi-quantitative scoring system.

OBJECTIVE: Evaluation of hepatic lesions in patients treated with methotrexate (MTX) generally used the Roenigk histological score. However, the sensitivity of the method for hepatic fibrosis assessment has been discussed. The semi-quantitative histological scoring system (SSS) offers a sensitive and specific evaluation of liver fibrosis. Both scores have been evaluated in liver biopsies of patients with rheumatoid arthritis. METHODS: Seventy-four liver biopsies were obtained in 57 rheumatoid arthritis patients before initiation of MTX (group 1, 38 cases), in cases of a persistently high level of transaminases during 1 yr of treatment (group 2, 10 cases) and after a MTX total dose of 2 g (group 3, 26 cases). Eleven biopsies of groups 1 and 3 originated from the same patient in 11 cases. Specimens were examined blindly by two anatomopathologists. The three groups were compared with an ANOVA. Sequential biopsies performed in 11 patients were compared with the Wilcoxon paired test. RESULTS: The Roenigk score and the SSS were significantly correlated (P<0.0001). Only a mild fibrosis was found in 33.8% (25/74) of the biopsies with the Roenigk score. Liver fibrosis, graded as mild (48.6%), moderate (41.8%) or severe (4%), was demonstrated in 94.6% (70/74) of the biopsies with the SSS. The Roenigk score and the SSS of the three patient groups were not statistically significantly different. The scores did not progress in the 11 patients who had serial biopsies. CONCLUSION: SSS is much more sensitive than the Roenigk score for the evaluation of hepatic fibrosis. However, SSS did not show progression of hepatic fibrosis in patients with rheumatoid arthritis treated with MTX.

Adult↗
PubMed2000

Serum levels of YKL-40 and C reactive protein in patients with hip osteoarthritis and healthy subjects: a cross sectional study.

BACKGROUND: YKL-40 is a 40 kDa glycoprotein secreted by chondrocytes and synoviocytes. It has been suggested that it is a surrogate marker of synovial inflammation and joint destruction in rheumatoid arthritis (RA) and osteoarthritis (OA) and related to C reactive protein (CRP) serum levels in RA. OBJECTIVE: To study serum levels of YKL-40 in patients with hip OA and its relation with CRP. METHODS: YKL-40 and CRP were assayed in serum samples from 45 patients (24 women, 21 men, mean age 65) with symptomatic OA of the hip and 33 healthy controls. YKL-40 was assayed by immunoassay and CRP by ultrasensitive immunonephelometry. OA severity was assessed by the measurement of joint space width with a computer analysis system of digitised hip radiographs. Statistical analysis was performed to determine correlations between serum markers and radiological joint space width. RESULTS: The mean (standard error) YKL-40 level was 90.3 (8.2) ng/ml in patients with hip OA and 66.9 (8.2) ng/ml in controls (p=0.03). The mean CRP level was 2.93 (3.03) mg/l in OA and 1.40 (1.61) mg/l in controls (p=0.006). The serum levels of YKL-40 and CRP increased with age and were significantly correlated (Spearman test: r(s)=0.42, p=0.005) in patients but not in controls. Neither YKL-40 nor CRP correlated with radiographic joint space width. CONCLUSIONS: Serum YKL-40 was significantly increased in patients with hip OA. The correlation between YKL-40 and CRP suggests that YKL-40 may be a marker of joint inflammation in OA. Longitudinal studies are required to assess the usefulness of YKL-40 in the monitoring of patients with hip OA.

Adipokines↗
PubMed2000

Articular diffusion of meloxicam after a single oral dose: relationship to cyclo-oxygenase inhibition in synovial cells.

OBJECTIVE: To investigate the distribution of meloxicam in the human knee joint and to compare it with the inhibition of cyclo-oxygenase (COX) activity in synovial cells. DESIGN: Prospective pharmacokinetic study and in vitro laboratory investigation. PATIENTS AND PARTICIPANTS: 42 male and female patients aged 26 to 85 years hospitalised for rheumatic disease and requiring a diagnostic and/or therapeutic knee puncture. METHODS: After a single oral dose of meloxicam 15mg, synovial fluid and blood samples were collected once per patient at various intervals after administration. Meloxicam concentrations were determined by a validated high performance liquid chromatography assay, protein binding by equilibrium dialysis, and pharmacokinetic parameters were calculated by noncompartmental analysis from the mean drug concentration-time profiles. The inhibitory effect of meloxicam on COX activity was investigated separately in unstimulated or interleukin-1beta-stimulated human synovial cells from osteoarthritic patients. RESULTS: Meloxicam was found in synovial fluid at the earliest sampling time (1 hour). Peak concentrations were reached approximately 6 hours postdose in both plasma (842 microg/L) and synovial fluid (320 microg/L). A plateau was observed after the distribution phase (6 hours), corresponding to a constant ratio of drug concentration between synovial fluid and plasma of about 0.47. This ratio was higher in patients with acute inflammation (0.58) than in those with no inflammation (0.38). Meloxicam was extensively bound to protein, mainly to serum albumin. The area under the drug concentration-time curve (AUC) in plasma was more than 2.5 times that in synovial fluid. The AUC for free meloxicam was similar in plasma and synovial fluid. The 50% inhibitory concentrations (IC50) for basal and stimulated COX activity in human synovial cells were 33.7 nmol/L (11.8 microg/L) and 2.0 nmol/L (0.70 microg/L), respectively. The free concentration of meloxicam in synovial fluid was higher than the IC50 for stimulated COX activity from 6 to 36 hours postdose. CONCLUSION: On the basis of free synovial concentrations and the IC50 for stimulated COX activity, meloxicam is expected to have a long duration of action. Inhibition of COX activity is expected to be more marked in inflamed synovium compared with non-inflamed synovium.

Administration, Oral↗
PubMed1999

Evaluation of the 'Lequesne's false profile' of the hip in patients with hip osteoarthritis.

OBJECTIVES: To compare the value of Lequesne's false profile (LFP) radiograph of the hip and antero-posterior (AP) X-ray of the pelvis in the assessment of joint space narrowing (JSN) and osteophyte (Ost) in patients with hip osteoarthritis (OA). METHODS: AP and LFP radiographs of the hip were performed using a standardized method in 50 consecutive patients with hip OA. JSN and Ost were graded at different days by a single observer blinded for patients identity, using a six point scale (JSN:0-5) and a four point scale (Ost:0-3) from AP and LFP respectively. Scores obtained from AP and LFP were compared. RESULTS: Mean JSN grade was significantly higher for LFP (2. 7+/-1.0) than AP (2.4+/-1.2) (P=0.001). It was identical for AP and LFP in 28 patients (56%) while the highest grade was found on LFP in 16 (32%) and on AP in 6 (12%). No significant difference between LFP and AP was found for osteophyte grading. CONCLUSION: These data suggest that the combination AP+LFP provide more information than AP alone for the evaluation of joint space narrowing in about one third of patients. LFP may be helpful for the radiographic assessment of OA changes particularly in structure modifying drugs evaluation.

Aged↗
PubMed1999

Radiographic assessment of hip and knee osteoarthritis. Recommendations: recommended guidelines.

Pathological lesions of osteoarthritis, demonstrated by conventional radiography, can be assessed by scoring systems and/or measurement with a quite acceptable reproducibility. Scores are recommended for a rough staging of osteoarthritis and of bone changes. Measurement is recommended for assessment of joint space narrowing progression. A good assessment of progression implicates a perfect reproducibility of the radiographic image of the joint. Accuracy of standard radiograph is improved by some views such as the hip profile and the schuss view.

Humans↗
PubMed1999

Rheumatic disorders developed after hepatitis B vaccination.

OBJECTIVE: To obtain an overview of rheumatic disorders occurring after hepatitis B vaccination. METHODS: A questionnaire was sent to rheumatology departments in nine French hospitals. Criteria for entry were rheumatic complaints of 1 week's duration or more, occurrence during the 2 months following hepatitis B vaccination, no previously diagnosed rheumatic disease and no other explanation for the complaints. RESULTS: Twenty-two patients were included. The observed disorders were as follows: rheumatoid arthritis for six patients; exacerbation of a previously non-diagnosed systemic lupus erythematosus for two; post-vaccinal arthritis for five; polyarthralgia-myalgia for four; suspected or biopsy-proved vasculitis for three; miscellaneous for two. CONCLUSIONS: Hepatitis B vaccine might be followed by various rheumatic conditions and might trigger the onset of underlying inflammatory or autoimmune rheumatic diseases. However, a causal relationship between hepatitis B vaccination and the observed rheumatic manifestations cannot be easily established. Further epidemiological studies are needed to establish whether hepatitis B vaccination is associated or not with an incidence of rheumatic disorders higher than normal.

Adolescent↗
PubMed1999

Requirement for total hip arthroplasty: an outcome measure of hip osteoarthritis?

OBJECTIVE: To assess if total hip arthroplasty (THA) is a valid outcome measure of hip osteoarthritis (OA), in respect to clinical and radiological assessments. METHODS: A prospective 3 year study of patients who had painful hip OA with an initial radiographic joint space width > or =1 mm at the narrowest point. Dependent variable was THA. Patient data including body mass index, OA structural severity by radiograph, OA symptomatic severity (pain, function), and OA localization were recorded at entry. Pelvic radiographs were obtained before THA, when available, and once yearly during the study. RESULTS: During the study 106 of 506 patients underwent THA. Risk was estimated (Kaplan-Meier method) to be 8+/-1, 16+/-2, and 23+/-2% after 1, 2, and 3 years, respectively. Factors predisposing to requirement for surgery were: age > or =70 years, female sex, superolateral migration of the femoral head, joint space width <2 mm, Kellgren-Lawrence grade > or =3, pain (visual analog scale) > or =50 mm, and Lequesne index > or =10 with a relative risk of 1.65, 1.71, 1.96, 1.85, 1.89, 1.86, and 2.59, respectively. Mean change in joint space width was 0.22+/-0.50 vs 0.97+/-1.35 mm/year in patients without and with THA, respectively (p<0.0001). Changes in radiological joint space width during the first year were highly predictive of requirement for THA during the 2 following years (risk of 5, 13, 25, and 79% in patients with a radiological joint space width worsening during the first year of 0, < or =25, >25 and < or =50, and >50%, respectively). CONCLUSION: These data suggest that THA could be considered as a valid outcome measure in OA. However, further studies should be conducted in other countries with different health care systems to evaluate the inter-country reliability of this measurement.

Aged↗
PubMed1998

Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study.

The aim of this study was to assess the clinical, radiological and biological efficacy and tolerability of the SYSADOA, chondroitin 4- and 6-sulfate (CS, Condrosulf, IBSA, Lugano, Switzerland), in patients suffering from knee osteoarthritis. This was a 1-year, randomized, double-blind, controlled pilot study which included 42 patients of both sexes, aged 35-78 years with symptomatic knee OA. Patients were treated orally with 800 mg chondroitin sulfate (CS) per day or with a placebo (PBO) administered in identical sachets. The main outcome criteria were the degree of spontaneous joint pain and the overall mobility capacity. Secondary outcome criteria included the actual joint space measurement and the levels of biochemical markers of bone and joint metabolism. This limited study confirmed that chondroitin sulfate was well-tolerated and both significantly reduced pain and increased overall mobility capacity. Treatment with CS was also associated in a limited group of patients with a stabilization of the medial femoro-tibial joint width, measured with a digitized automatic image analyzer, whereas joint space narrowing did occur in placebo-treated patients. In addition, the metabolism of bone and joint assessed by various biochemical markers also stabilized in the CS patients whereas it was still abnormal in the PBO patients. These results confirm that oral chondroitin 4- and 6-sulfate is an effective and safe symptomatic slow-acting drug for the treatment of knee OA. In addition, CS might be able to stabilize the joint space width and to modulate bone and joint metabolism. This is the first preliminary demonstration that a SYSADOA might influence the natural course of OA in humans.

Administration, Oral↗
PubMed1998

Quantitative evaluation of joint space width in femorotibial osteoarthritis: comparison of three radiographic views.

OBJECTIVE: Quantitative evaluation of radiographic methods proposed to improve the detection of joint space narrowing (JSN) in femorotibial osteoarthritis (OA). METHODS: Thirty-two consecutive patients with knee OA and five normal controls had three different weight-bearing radiographs of the knee: (1) anteroposterior film of both knees in full extension (extended knees), (2) anteroposterior film of one knee in extension while the patient was standing on the homolateral foot (standing on homolateral foot), (3) posteroanterior film of both knees flexed at 30 degrees (schuss view). Joint space was analyzed blind using both an evaluation of JSN with a six-grade scale (JSN score) and an image analyser computer measurement of the mean joint space width (mean JSW). The medial compartment of medial femorotibial OA knees, the lateral compartment of lateral femorotibial OA knees, as well as both compartments of control knees, were measured. Extended knee and schuss views were made 1 year later in 10 patients for the evaluation of sensitivity to change. RESULTS: The JSN scores +/- S.D. in schuss, standing on the homolateral foot and extended knee views were 2.75 +/- 1.31, 1.95 +/- 1.3 and 1.66 +/- 1.27, respectively. The mean JSW +/- S.D. in schuss, standing on the homolateral foot, and extended knee views were 2.9 +/- 1.9 mm, 3.5 +/- 1.6 mm and 3.8 +/- 1.5 mm, respectively. Changes in JSN scores and mean JSW with schuss view increased with OA severity. In controls, JSW of the medial compartment did not vary in the three views. JSW of the lateral compartment of controls was significantly larger in the schuss view. The change in JSW after 1 year was -0.41 mm (P = 0.02) in the schuss view and -0.17 mm (P > 0.05) in the extended knee view. CONCLUSION: The schuss view is suggested as the most accurate method for the evaluation of JSW in femorotibial OA.

Adult↗