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Biomedical subjects

E Vignon

Publications and source records attributed to E Vignon.

At least 37 records · Page 2Linked to original sources
PubMed2001

Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Evaluation of the Chondromodulating Effect of Diacerein in OA of the Hip.

OBJECTIVE: To evaluate the ability of diacerein, an interleukin-1beta inhibitor, to slow the progressive decrease in joint space width observed in patients with hip osteoarthritis (OA). METHODS: In this randomized, double-blind, placebo-controlled 3-year study, 507 patients with primary OA of the hip (by the American College of Rheumatology criteria) received diacerein (50 mg twice a day) or placebo. The minimal hip joint space width was measured by a central reader on yearly pelvic radiographs, using a 0.1-mm-graduated magnifying glass. RESULTS: Baseline characteristics were comparable in the 2 treatment groups (255 patients receiving diacerein, 252 receiving placebo); 238 patients (47%) discontinued the study, mainly because of adverse events in the diacerein group (25% versus 12% with placebo) and because of inefficacy in the placebo group (14% versus 7% with diacerein). The percentage of patients with radiographic progression, defined by a joint space loss of at least 0.5 mm, was significantly lower in patients receiving diacerein than in patients receiving placebo, both in the intent-to-treat analysis and in the completer analysis (50.7% versus 60.4% [P = 0.036] and 47.3% versus 62.3% [P = 0.007], respectively). In those patients who completed 3 years of treatment, the rate of joint space narrowing was significantly lower with diacerein (mean +/- SD 0.18 +/- 0.25 mm/year versus 0.23 +/- 0.23 mm/year with placebo; P = 0.042). Diacerein had no evident effect on the symptoms of OA in this study. However, a post hoc covariate analysis that took into account the use of analgesics and antiinflammatory drugs showed an effect of diacerein on the Lequesne functional index. Diacerein was well tolerated during the 3-year study. The most frequent adverse events were transient changes in bowel habits. CONCLUSION: This study confirms previous clinical findings indicating that the demonstration of a structure-modifying effect in hip OA is feasible, and shows, for the first time, that treatment with diacerein for 3 years has a significant structure-modifying effect as compared with placebo, coupled with a good safety profile. The clinical relevance of these findings requires further investigation.

Anthraquinones↗
PubMed2001

Early changes in lapine menisci during osteoarthritis development: Part I: cellular and matrix alterations.

OBJECTIVE: Osteoarthritis (OA) is the most common form of arthritis and patients with meniscal and ligament injuries of the knee are at high risk to develop the disease. The purpose of this study was to evaluate changes occurring in both medial and lateral menisci from the knees of anterior cruciate ligament (ACL) transected rabbits during the early stages of OA development. DESIGN: Meniscal tissues from control and experimental rabbits were processed for histology and immunohistochemistry for assessment of matrix organization and composition. RESULTS: At 3 and 8 weeks following ACL transection, histological examination demonstrated extensive extracellular matrix deterioration. Altered cell distribution, areas depleted of cells, and areas of cell clusters were found within the medial but not in the lateral meniscus. Immunohistochemistry of both medial and lateral menisci demonstrated significant changes in collagen distribution. Type I and III collagen staining was increased in both medial and lateral menisci. In contrast, type II collagen staining was overtly increased only in the medial meniscus. CONCLUSION: These results demonstrate that after ACL transection, extracellular matrix deposition as well as altered matrix organization and altered cell distribution occur early in the medial meniscus.

Animals↗
PubMed2001

Early changes in lapine menisci during osteoarthritis development: Part II: molecular alterations.

OBJECTIVE: Osteoarthritis (OA) is the most common form of arthritis and patients with meniscal and ligament injuries of the knee are at high risk to develop the disease. The purpose of this study was to evaluate changes occurring in both medial and lateral menisci from the knees of anterior cruciate ligament (ACL) transected rabbits at 3 and 8 weeks post-surgery. This study describes both molecular and cellular alterations in menisci during the early stages of OA development. DESIGN: Rabbit meniscal tissues were processed for molecular analysis: DNA and RNA concentrations were assessed, as well as semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for a subset of relevant molecules was performed. In situ DNA fragmentation was evaluated using the TUNEL assay. RESULTS: Total RNA yields from the medial meniscus were significantly elevated at both 3 and 8 weeks post-ACL transection, while in the lateral meniscus total RNA levels were unchanged following ACL transection. DNA concentrations were significantly decreased in the medial menisci only at 8 weeks post-ACL transection. Following ACL transection, analysis of in situ DNA fragmentation using the TUNEL assay demonstrated an increase in the number of apoptotic cells in the medial meniscus only, in particular at 3 weeks post-ACL transection, a finding which correlates with declines in DNA content. Analysis of specific mRNA levels by RT-PCR demonstrated complex changes in both menisci following ACL transection. At 3 and 8 weeks post-ACL transection, in both medial and lateral menisci, mRNA levels for type I collagen and TIMP-1 were significantly increased, while mRNA levels for decorin, TNF-alpha and IGF-2 were significantly depressed. In the medial meniscus, significant increases in mRNA levels for type II collagen, biglycan as well as iNOS and PAI-1 were detected at both time periods, while mRNA levels for aggrecan, type III collagen and COX-2 were significantly elevated at 3 weeks post-ACL transection and mRNA levels for MMP-1 were significantly elevated at 8 weeks post-ACL transection. In contrast, mRNA levels for COL2 and aggrecan were unchanged in the lateral meniscus following ACL transection. In the lateral meniscus, at 3 weeks post-ACL transection, type III collagen mRNA levels were dramatically increased while fibromodulin mRNA levels were significantly depressed. In the lateral meniscus, significant increases in mRNA levels for biglycan were detected at 8 weeks post-ACL transection. CONCLUSION: These results show that after ACL transection complex molecular changes, as well as apoptosis, occur early, particularly in the medial meniscus.

Animals↗
PubMed2001

Measurement of the radiological hip joint space width. An evaluation of various methods of measurement.

OBJECTIVE: To determine the most relevant method of measurement of the radiographic hip joint space width (JSW). DESIGN: Seventy hips were examined from 36 patients of the ECHODIAH study having had one to four X-rays of the pelvis during the 3-year course of the study. Minimum interbone distance (MIDc), mean width of both the whole joint space (MJSWL) and a region of interest of the joint space (MJSWroi) were measured using computerized analysis of digitized radiographs. MID was also measured using a graduated eyepiece (MIDge). Reproducibility of the measurement was assessed by the intraclass coefficient of correlation. Sensitivity to change was evaluated by the standardized response mean. RESULTS: The intraobserver intraclass coefficient of correlation of MIDc and MJSWroi was 0.98 and 0.94, respectively. The mean value degrees S.D. of MJSWL, MJSWroi, MIDc and MIDge was 3.3 degrees 0.9, 2.6 degrees 0.9, 2.4 degrees 0.9 and 2.6 degrees 1.2 mm, respectively. MIDge was significantly larger than MIDc (mean difference: 0.21 degrees 0.62 mm, P<0.001), in both normal and osteoarthritic hips. However, the difference between MIDge and MIDc varied largely when considering topography of femoral head migration. Whatever the method was, a significant (P<0.001) mean decrease of nearly 0.5 mm was found in osteoarthritic hips over the 3 year follow-up. The standardized response mean for MJSWL, MJSWroi, MIDge and MIDc was 0.73, 0.75, 0.79 and 0.85, respectively. Superiority of MIDc, in term of sensitivity to change, was mainly seen in osteoarthritic hips showing a superomedial or a concentric migration of the femoral head. CONCLUSION: Minimum interbone distance measured with a computer assisted method is suggested as the most suitable method for the evaluation of hip osteoarthritis (OA) progression.

Female↗
PubMed2001

Tissue inhibitor of metalloprotease-1 (TIMP-1) serum level may predict progression of hip osteoarthritis.

OBJECTIVE: To determine the predictive value of serum levels of TIMP-1 and hyaluronic acid in a 1 year prospective study in hip osteoarthritis (OA). METHODS: Twenty-nine patients with OA of the hip were enrolled in a 1-year prospective study (median follow-up, 13 months). Biochemical analysis was used to assess TIMP-1 and hyaluronic acid at entry and at the end of the study. Radiographic evaluation with an assisted computed program was performed to calculate progression of joint space narrowing. Statistical tests served to determine correlations between observed serum levels and radiograph joint space narrowing. RESULTS: Among the 29 patients, 10 showed joint space narrowing greater than 0.6 mm per year. The initial concentration of TIMP-1 as well as delta value of variation in serum levels of TIMP-1 (difference between TIMP-1 concentration at entry and at the end) correlated with the progression of joint space narrowing. A cut-off value of 600 ng/ml of TIMP-1 allowed the patients who progressed slowly from those who progressed more rapidly. Hyaluronic acid serum level was not predictive of evolution. CONCLUSION: TIMP-1 serum level may serve to predict the evolution of patients with hip OA.

Adult↗
PubMed2001

Cross sectional evaluation of biochemical markers of bone, cartilage, and synovial tissue metabolism in patients with knee osteoarthritis: relations with disease activity and joint damage.

OBJECTIVE: To analyse the relations between the urinary levels of type II collagen C-telopeptide (CTX-II) and glucosyl-galactosyl pyridinoline (Glc-Gal-PYD)-two newly developed biochemical markers of type II collagen and synovial tissue destruction respectively-disease activity and the severity of joint destruction in patients with knee osteoarthritis (OA). The clinical performance of these two new markers was compared with that of a panel of other established biochemical markers of connective tissue metabolism. METHODS: The following biochemical markers were measured in a group of 67 patients with knee OA (mean age 64 years, median disease duration eight years ) and in 67 healthy controls: for bone, serum osteocalcin, serum and urinary C-telopeptide of type I collagen (CTX-I); for cartilage, urinary CTX-II, serum cartilage oligomeric matrix protein (COMP), and serum human cartilage glycoprotein 39 (YKL-40); for synovium, urinary Glc-Gal-PYD, serum type III collagen N-propeptide (PIIINP), serum hyaluronic acid (HA); and for inflammation, serum C reactive protein. Biochemical markers were correlated with pain and physical function (WOMAC index) and with quantitative radiographic evaluation of the joint space using the posteroanterior view of the knees flexed at 30 degrees. RESULTS: All bone turnover markers were decreased in patients with knee OA compared with controls (-36%, -38%, and -52%, p<0.0001 for serum osteocalcin, serum CTX-I and urinary CTX-I, respectively). Serum COMP (+16%, p=0.0004), urinary CTX-II (+25%, p=0.0009), urinary Glc-Gal-PYD (+18%, p=0.028), serum PIIINP (+33%, p<0.0001), and serum HA (+ 233%, p<0.0001) were increased. By univariate analyses, increased urinary Glc-Gal-PYD (r=0.41, p=0.002) and decreased serum osteocalcin (r=-0.30, p=0.025) were associated with a higher total WOMAC index. Increased urinary CTX-II (r=-0.40, p=0.0002) and Glc-Gal-PYD (r=-0.30, p=0.0046) and serum PIIINP (r=-0.29, p=0.0034) were the only markers which correlated with joint surface area. By multivariate analyses, urinary Glc-Gal-PYD and CTX-II were the most important predictors of the WOMAC index and joint damage, respectively. CONCLUSION: Knee OA appears to be characterised by a systemic decrease of bone turnover and increased cartilage and synovial tissue turnover. CTX-II, Glc-Gal-PYD, and PIIINP may be useful markers of disease severity in patients with knee OA.

Aged↗
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

Hand osteoarthritis and generalized osteoarthritis: a need for clarification.

A proportion of patients with osteoarthritis (OA) have polyarticular involvement and are categorized as having generalized OA (GOA). However, a widely accepted definition of GOA does not exist. The topography of affected joints as well as the threshold number of affected joints used in defining GOA remain unidentified. According to number, site and clustering of affected joints, various subtypes of GOA, possibly related to different genetic factors, may exist. Such subtypes have still to be clearly identified. Among them, the association of hand and knee OA emerges as a probable subtype. Polyarticular involvement of hand joints is common, but may include various subtypes of differing significance. Further studies are needed to clarify the definition of GOA.

Diagnosis, Differential↗
PubMed2000

Session 2: clinical aspects. Clinical assessment of hand OA.

The aim of the session was to discuss the current definitions of and criteria for hand osteoarthritis (OA) and to review the tools proposed for the clinical assessment of hand OA in research and trials. The American College of Rheumatology criteria for the classification and reporting of hand OA were discussed and their limitations noted; specifically, they are designed for symptomatic OA and based on physical examination. The differences between erosive and non-erosive hand OA were discussed as was the relationship between hand OA and generalized OA, since hand OA represents a generalized OA of hand joints and can be considered as a marker for developing generalized OA (i.e. OA at other sites). Different clinical tools to assess patients were presented and discussed, such as pain assessment, Dreiser's functional index or Bellamy's AUSCAN for function assessment, assessment of the mobility, stiffness, inflammation and aesthetic damages. The agreements, disagreements and further studies to be performed to answer questions still debated are presented.

Hand Deformities, Acquired↗
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↗