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Ferdinand C Breedveld

Publications and source records attributed to Ferdinand C Breedveld.

45 records · Page 3Linked to original sources
PubMed2002

Comparative assessment of leflunomide and methotrexate for the treatment of rheumatoid arthritis, by dynamic enhanced magnetic resonance imaging.

OBJECTIVE: Ethical constraints on the conduct of placebo-controlled trials evaluating new therapies for serious chronic diseases, such as rheumatoid arthritis (RA), indicate the need for discerning methods to assess treatment effect in active-controlled clinical trials. Dynamic gadolinium-enhanced magnetic resonance imaging (DEMRI) is a sensitive technique for the detection of synovial inflammation in RA. Therefore, this investigation was undertaken to evaluate DEMRI as an efficacy assessment tool for differentiating treatment effect in a randomized, active-controlled trial comparing leflunomide and methotrexate. METHODS: Patients with active RA (n = 39) were randomized in a 2-center, prospective, double-blind clinical trial to receive either leflunomide (n = 18) or methotrexate (n = 21) therapy for 4 months. DEMRI scans were obtained at baseline and at 4 months, and the initial rate of enhancement (IRE) and the maximal signal intensity (SI) enhancement (ME) were calculated from the SI curves. Clinical improvement was assessed by conventional outcome measures. RESULTS: Thirty-four patients (17 treated with leflunomide and 17 with methotrexate) had usable baseline and end point DEMRI scans. Leflunomide treatment was associated with a significantly greater improvement in IRE compared with methotrexate treatment (P < 0.05). Average values of ME indicated reduction of inflammation with both leflunomide and methotrexate. The improvement in clinical signs and symptoms, as measured by traditional assessments, was comparable for both active treatments. CONCLUSION: Results of this study validate the sensitivity of DEMRI in detecting inflammatory changes in active RA in response to treatment. Improvement in synovial inflammation as measured by IRE was significantly better with leflunomide than with methotrexate over 4 months of therapy.

Adult↗
PubMed2002

How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis.

OBJECTIVE: To develop a clinical model for the prediction, at the first visit, of 3 forms of arthritis outcome: self-limiting, persistent nonerosive, and persistent erosive arthritis. METHODS: A standardized diagnostic evaluation was performed on 524 consecutive, newly referred patients with early arthritis. Potentially diagnostic determinants obtained at the first visit from the patient's history, physical examination, and blood and imaging testing were entered in a logistic regression analysis. Arthritis outcome was recorded at 2 years' followup. The discriminative ability of the model was expressed as a receiver operating characteristic (ROC) area under the curve (AUC). RESULTS: The developed prediction model consisted of 7 variables: symptom duration at first visit, morning stiffness for > or =1 hour, arthritis in > or =3 joints, bilateral compression pain in the metatarsophalangeal joints, rheumatoid factor positivity, anti-cyclic citrullinated peptide antibody positivity, and the presence of erosions (hands/feet). Application of the model to an individual patient resulted in 3 clinically relevant predictive values: one for self-limiting arthritis, one for persistent nonerosive arthritis, and one for persistent erosive arthritis. The ROC AUC of the model was 0.84 (SE 0.02) for discrimination between self-limiting and persistent arthritis, and 0.91 (SE 0.02) for discrimination between persistent nonerosive and persistent erosive arthritis, whereas the discriminative ability of the American College of Rheumatology 1987 classification criteria for rheumatoid arthritis was significantly lower, with ROC AUC values of 0.78 (SE 0.02) and 0.79 (SE 0.03), respectively. CONCLUSION: A clinical prediction model was developed with an excellent ability to discriminate, at the first visit, between 3 forms of arthritis outcome. Validation in other early arthritis clinics is necessary.

Adolescent↗
PubMed2002

Cell-derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII-dependent mechanism.

OBJECTIVE: To determine the cellular origin of synovial microparticles, their procoagulant properties, and their relationship to local hypercoagulation. METHODS: Microparticles in synovial fluid and plasma from patients with rheumatoid arthritis (RA; n = 10) and patients with other forms of arthritis (non-RA; n = 10) and in plasma from healthy subjects (n = 20) were isolated by centrifugation. Microparticles were identified by flow cytometry. The ability of microparticles to support coagulation was determined in normal plasma. Concentrations of prothrombin fragment F(1+2) (by enzyme-linked immunosorbent assay [ELISA]) and thrombin-antithrombin (TAT) complexes (by ELISA) were determined as estimates of the coagulation activation status in vivo. RESULTS: Plasma from patients and healthy controls contained comparable numbers of microparticles, which originated from platelets and erythrocytes. Synovial microparticles from RA patients and non-RA patients originated mainly from monocytes and granulocytes; few originated from platelets and erythrocytes. Synovial microparticles bound less annexin V (which binds to negatively charged phospholipids) than did plasma microparticles, exposed tissue factor, and supported thrombin generation via factor VII. F(1+2) (median 66 nM) and TAT complex (median 710 microg/liter) concentrations were elevated in synovial fluid compared with plasma from the patients (1.6 nM and 7.0 microg/liter, respectively) as well as the controls (1.0 nM and 2.9 microg/liter, respectively). CONCLUSION: Synovial fluid contains high numbers of microparticles derived from leukocytes that are strongly coagulant via the factor VII-dependent pathway. We propose that these microparticles contribute to the local hypercoagulation and fibrin deposition in inflamed joints of patients with RA and other arthritic disorders.

Adult↗
PubMed2002

High dose chemotherapy and autologous hematopoietic stem cell transplantation for rheumatoid arthritis: a review.

A new treatment approach, involving intense immunosuppression and autologous hematopoietic stem cell transplantation (SCT), has emerged in recent years for the treatment of severe, refractory rheumatic autoimmune diseases including rheumatoid arthritis (RA). The rationale of this strategy is based on the concept of immunoablation by intense immunosuppression with subsequent regeneration of naïve T lymphocytes derived from reinfused hematopoietic progenitor cells. Patients with a therapy-refractory, progressively erosive disease who are at risk of functional disability and early mortality are considered eligible for treatment with autologous SCT. The goal is long-term improvement of disease activity and quality of life. However, when offering SCT to RA patients these benefits should be balanced against toxicities and treatment-related mortality. In several patients with intractable RA, long-term remissions were observed with this strategy, but failures have been reported as well. Only small numbers of RA patients have been treated thus far. Although different treatment protocols have been used, high dose chemotherapy as a means to achieve immunoablation has been invariably used in all studies. In this review we discuss background, clinical results, protocols, and future prospects of high dose chemotherapy and autologous SCT for RA.

Adoptive Transfer↗
PubMed2002

Effect of redox balance alterations on cellular localization of LAT and downstream T-cell receptor signaling pathways.

The integral membrane protein linker for activation of T cells (LAT) is a central adapter protein in the T-cell receptor (TCR)-mediated signaling pathways. The cellular localization of LAT is extremely sensitive to intracellular redox balance alterations. Reduced intracellular levels of the antioxidant glutathione (GSH), a hallmark of chronic oxidative stress, resulted in the membrane displacement of LAT, abrogated TCR-mediated signaling and consequently hyporesponsiveness of T lymphocytes. The membrane displacement of LAT is accompanied by a considerable difference in the mobility of LAT upon native and nonreducing denaturing polyacrylamide gel electrophoresis analysis, a finding indicative of a conformational change. Targeted mutation of redox-sensitive cysteine residues within LAT created LAT mutants which remain membrane anchored under conditions of chronic oxidative stress. The expression of redox-insensitive LAT mutants allows for restoration of TCR-mediated signal transduction, whereas CD28-mediated signaling pathways remained impaired. These results are indicative that the membrane displacement of LAT as a result of redox balance alterations is a consequence of a conformational change interfering with the insertion of LAT into the plasma membrane. Conclusively, the data suggest a role for LAT as a crucial intermediate in the sensitivity of TCR signaling and hence T lymphocytes toward chronic oxidative stress.

Adaptor Proteins, Signal Transducing↗