The active metabolite of leflunomide, A77 1726, increases proliferation of human synovial fibroblasts in presence of IL-1β and TNF-α

Abstract.: Objective and design: Excessive synovial fibroblast (SF) proliferation is detrimental in rheumatoid arthritis. We therefore sought to determine the effects of A77 1726, the active metabolite of leflunomide, on SF proliferation. Methods: Human SFs were used. Cell proliferation was investigated using MTS assay, by 3H-thymidine incorporation and cell counts. Results: Whereas A77 1726 alone had no effects, it significantly increased the mitogenic effects of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Cyclooxygenase inhibition might be at least partly involved, since indomethacin displayed similar effects, and since prostaglandin E2 inhibited SF proliferation. In contrast, the effect of A77 1726 did not appear to be mediated through depletion of the pyrimidine pool or inhibition of tyrosine kinases. Conclusion: A77 1726 displays proliferative effects in presence of IL-1β and TNF-α. Further elucidation of involved mechanisms may prove useful for the utilization of leflunomide, the development of related compounds or elaboration of new therapeutic strategie

Improving In Vitro Generated Cartilage-Carrier-Constructs by Optimizing Growth Factor Combination

The presented study is focused on the generation of osteochondral implants for cartilage repair, which consist of bone substitutes covered with in vitro engineered cartilage. Re-differentiation of expanded porcine cells was performed in alginate gel followed by cartilage formation in high-density cell cultures. In this work, different combinations of growth factors for the stimulation of re-differentiation and cartilage formation have been tested to improve the quality of osteochondral implants. It has been demonstrated that supplementation of the medium with growth factors has significant effects on the properties of the matrix. The addition of the growth factors IGF-I (100 ng/mL) and TGF-β1 (10 ng/mL) during the alginate culture and the absence of any growth factors during the high-density cell culture led to significantly higher GAG to DNA ratios and Young’s Moduli of the constructs compared to other combinations. The histological sections showed homogenous tissue and intensive staining for collagen type II

Effect of dynamic compressive loading and its combination with a growth factor on the chondrocytic phenotype of 3-dimensional scaffold-embedded chondrocytes

Background and purpose Three-dimensionally (3D-) embedded chondrocytes have been suggested to maintain the chondrocytic phenotype. Furthermore, mechanical stress and growth factors have been found to be capable of enhancing cell proliferation and ECM synthesis. We investigated the effect of mechanical loading and growth factors on reactivation of the 3D-embedded chondrocytes

Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial

Background. Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design. A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion. This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy. Trial registration. Netherlands Trial Register (NTR1636)

[Arthropathy - Frequently the Inaugural Symptom of Hemochromatosis]

Idiopathic hemochromatosis is a recessive autosomal disorder of iron metabolism manifested by a tissue overload affecting many organs, including the liver, the heart, the endocrine glands and the joints. Of 53 patients we studied, 66% had articular symptoms (mainly arthralgias of the metacarpophalangeal joints) and 49% had radiological lesions such as chondrocalcinosis and structural joint damage. The radiological signs were slightly more frequent in women (56.3%) than men (45.9%). Mean age at diagnosis was moderately higher in the group with arthropathy (52 years) than in the group without (44 years). Analysis of clinical, radiological and biological data, including parathormone values, did not reveal other parameters differentiating the two groups. A family study does not support the hypothesis of double heredity for hemochromatosis and arthropathy. In 20% of the patients the arthropathy was the inaugural feature of the hemochromatosis. The interval between first symptoms and diagnosis for these patients (5.3 years on average) is unfortunately long. Determination of transferrin saturation allows early diagnosis

Epaule douloureuse atraumatique: diagnostic radiologique

Shoulder pain is a common cause of consultation in primary care medicine. A detailed history and a carefully carried out physical exam allow to orientate the diagnosis towards an intrinsic or extrinsic cause and to the differential diagnosis. Rotator cuff injury is the most frequent affection. Plain radiography will often be done in first intention since it identifies direct or indirect signs associated with certain pathologies. Ultrasonography is an excellent way of evaluating soft tissue injury and allows a diagnosis in most cases (rotator cuff injury, tendinopathy of the long head of the biceps, bursitis, effusion, calcifications). Other imaging studies may be carried out depending on the pathology suspected

chroniques de l'enfant: approche pratique et donnees epidemiologiques. [Chronic arthroses in children: practical approach and epidemiological data]

Osteo-articular symptoms are frequent in pediatrics, but chronic arthritis is rare in childhood. Arthritis may be difficult to recognize in children and there is a large differential diagnosis including infectious and neoplastic diseases. Even if juvenile arthritis has often a favourable course, significant functional damage may occur. The diagnosis and the follow-up of chronic arthritis should be performed in collaboration with a specialized consultation in pediatric rheumatology, in order to allow access to multidisciplinary medical care and help to increase the clinical and epidemiological knowledge in these rare diseases. A study is starting this fall aimed at collecting epidemiological datas on childhood arthritis in the french part of Switzerland

Low pre-treatment B-cell counts are not a risk factor of infection in patients treated with rituximab for autoimmune diseases: An observational study

Rituximab (RTX) is increasingly used in patients with refractory rheumatoid arthritis (RA) and other severe autoimmune diseases (AID). In practice, many clinicians are reluctant to prescribe RTX in patients with low B-cell counts because of the presumed risk of infection. The aim of this study was therefore to investigate whether B-cell counts before treatment or retreatment with RTX predict the occurrence of infections