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Biomedical subjects

Richard Trèves

Publications and source records attributed to Richard Trèves.

10 recordsLinked to original sources

Effects of the active metabolite of leflunomide, A77 1726, on cytokine release and the MAPK signalling pathway in human rheumatoid arthritis synoviocytes.

Inflammatory cytokines or soluble factors are essential in the pathogenesis of rheumatoid arthritis (RA). Leflunomide is an effective disease modifying antirheumatic drug (DMARD) in RA. The objective of the present study was to evaluate for the first time the effects of A77 1726 on cytokine (interleukin (IL)-8, IL-10, IL-11 secretion and tumor necrosis factor-alpha soluble receptor I (sTNFRI)) shedding in human RA fibroblast-like synoviocytes (FLS). At 100 microM, we observed an increase in IL-10 secretion, a decrease in IL-11 release and no effect on sTNFRI shedding and IL-8 secretion in IL-1beta-stimulated human RA FLS. Furthermore, at this dose, our results also confirmed that A77 1726 decreased IL-6 and prostaglandin E2 (PGE2) synthesis while it increased IL-1 receptor antagonist secretion (IL-1Ra). The mitogen-activated protein kinases (MAPKs) represent an attractive target for RA because they can regulate cytokine expression. At 100 microM, the effect of A77 1726 on IL-10 and IL-11 secretion seemed to be associated with the status of p38 MAPK activation. Our results confirmed the immunoregulatory action of leflunomide in the cytokine network involved in RA pathogenesis. It could shift the balance from cytokine mediated inflammation to cytokine directed inhibition of the inflammatory process.

Active Transport, Cell Nucleus↗

Is restless legs syndrome underrecognized? Current management.

Restless legs syndrome (RLS) is a poorly understood sensory-motor neurological disorder whose prevalence in Caucasian populations ranges from 10% to 15%. The patient reports unpleasant sensations in the lower limbs with dysesthesia resulting in an urge to move the legs. The symptoms occur during periods of inactivity, increasing in the evening and at night. Moving the legs provides relief. In 80% of cases, polysomnography shows periodic leg movements during sleep. Patients with idiopathic RLS often report similar symptoms in family members. Secondary RLS may be due to medications, diabetes mellitus, renal failure, iron deficiency, neurological disorders, or rheumatoid arthritis. In secondary RLS, the management rests on treatment of the cause. Symptomatic treatment is warranted in patients with moderate-to-severe symptoms that adversely affect the quality of life. Dopaminergic agents are tried first. When they fail or induce adverse effects, weak opioids, benzodiazepines, anticonvulsants or, if needed, strong opioids, may be used.

Diagnosis, Differential↗

Guidelines for the use of antidepressants in painful rheumatic conditions.

OBJECTIVES: Antidepressants are widely used to treat painful chronic rheumatic conditions but, contrary to neuropathic conditions, little is known about their true analgesic properties and value in these situations. Our group, which focuses on pain in rheumatology, aimed to develop recommendations for the use of antidepressants in rheumatology, based on evidence-based review of published data and expert opinion. METHOD: We identified relevant drugs and conditions and searched Medline, Embase and Pascal (1966-2003) for relevant publications in a number of European languages. We scored each study for quality, and used an expert consensus approach to formulate recommendations. RESULTS: We identified 77 studies and 12 meta-analyses and literature review on the use of antidepressant to treat painful rheumatological conditions. Forty-nine of these clinical studies were considered valid and were used to develop the recommendations. When evidence was lacking we based recommendations on our clinical experience. CONCLUSIONS: These recommendations for the treatment of painful rheumatological conditions with antidepressants were developed using evidence-based and expert consensus approaches and are the first of their kind in this field. Our review of the literature highlights the need for further, well-designed clinical studies of the use of antidepressants to treat painful rheumatological conditions.

Antidepressive Agents↗

Outcome of patients with undifferentiated chronic monoarthritis: retrospective study of 46 cases.

OBJECTIVE: To determine the natural history of undifferentiated monoarthritis of more than 3 months' duration and to evaluate the usefulness of classic diagnostic tools for identifying factors associated with outcomes. METHOD: Retrospective study of 46 patients with undifferentiated monoarthritis of more than 3 months' duration. RESULTS: Full resolution was the outcome in 50% of cases. Rheumatoid arthritis and spondyloarthropathy were the most common diagnoses in the remaining patients. HLA-B27 status was the only significant predictor of outcome: progression to spondyloarthropathy was significantly more common (P = 0.05) among HLA-B27-positive patients. Mean time to full recovery was significantly shorter than mean time to disease progression (12 vs. 45 months, P = 0.0015). Intraarticular glucocorticoid injections were effective in over 50% of patients. Arthritis relief during the month following the injection was associated with self-limited disease. The role for magnetic resonance imaging in managing patients with undifferentiated monoarthritis remains unclear. CONCLUSION: In patients with undifferentiated monoarthritis, the likelihood of a full recovery is 50%. The only significant predictor of outcome was positive HLA-B27 status, which was associated with progression to spondyloarthropathy.

Arthritis↗

Aggressive systemic mastocytosis.

Systemic mastocytosis is a rare and occasionally aggressive condition that raises major diagnostic challenges. We report a case in a 72-year-old patient in whom the diagnosis of malignant mastocytosis required two bone marrow smears and three bone marrow biopsies examined using specific staining techniques. Despite interferon therapy, a mast-cell sarcoma of the sternum developed 1 year after symptom onset, followed 1 year later by acute myeloblastic leukemia, which was rapidly fatal.

Aged↗

Adverse events associated with rofecoxib therapy: results of a large study in community-derived osteoarthritic patients.

OBJECTIVE: To evaluate the safety profile of rofecoxib, a selective cyclo-oxygenase-2 inhibitor, in patients with osteoarthritis who are receiving care in non-hospital practice settings. DESIGN: All patients participating in a large 24-week, open-label, nonpharmacological intervention trial were given rofecoxib for painful osteoarthritis of the knee or hip. They started at a dose of 12.5mg once daily for the first month, with the option of increasing to 25mg daily thereafter, if needed for efficacy. Adverse events were closely monitored. We considered all adverse events that occurred during treatment and within 14 days of discontinuation of rofecoxib. PATIENT GROUP STUDIED: 2896 patients (861 males and 2035 females) were involved in the safety analysis. Their mean (SD) age was 66.8 (9.9) years, and 631 patients (21.8%) were aged >/=75 years. There were 913 patients (31.5%) with hypertension and 151 (5.2%) with diabetes mellitus at the start of the study; 78 patients (2.7%) had a prior medical history of angina and/or myocardial infarction. The mean (SD) duration of rofecoxib treatment was 139 (62) days. RESULTS: A total of 519 patients (17.9%) discontinued rofecoxib. The main reasons for discontinuation were dyspepsia (4.4%), nausea (2.4%) and dizziness (2.1%). The annualised incidence rates (95% CI) of complicated and uncomplicated upper gastrointestinal ulcers, myocardial infarction, and stroke were 1.36 (0.76-2.23), 0.09 (0-0.50) and 0.45 (0.16-1.05), respectively. CONCLUSION: This study conducted in conditions close to daily practice confirms that the use of rofecoxib is associated with a low rate of serious adverse events in patients with osteoarthritis.

Administration, Oral↗

Is the relationship between spondyloarthropathy and Sjögren's syndrome in women coincidental? A study of 13 cases.

OBJECTIVE: To determine the prevalence of Sjogren's syndrome (SS) in women with spondyloarthropathy (SpA). METHODS: Forty-one women with SpA manifesting as inflammatory back pain and/or peripheral arthritis were diagnosed as having ankylosing spondylitis, undifferentiated spondyloarthropathy, psoriatic arthritis, or enteropathic arthropathy based on accepted criteria. A validated questionnaire was used to look for sicca symptoms in the SpA group and in 102 controls with degenerative rheumatic diseases. Women with SpA and sicca symptoms and/or positive antinuclear antibodies (ANA) were investigated for SS by minor salivary gland biopsy. In the SpA group, the following tests were done: HLA B27; HLA DR, DQ; ENA; and serology for CMV, EBV, HIV, hepatitis B, and hepatitis C. RESULTS: Thirteen women (31.7%) met European criteria for SS, compared to three (2.9%) of the controls. Of the 41 women with SpA, 16 (39%) were ANA-positive. ANA were detected in eight of the 16 (50%) patients with SS. HLA B27 was present in 11 of the 13 (84.6%) SS patients. HLA DR 04.04 and DQ 03.03 seemed more common in SS patients, but the difference was not statistically significant. CONCLUSION: SS was far more common in the women with SpA (31.7%) than in the controls (2.9%), suggesting that the SpA-SS association may not be coincidental.

Adolescent↗

Computed tomography in low back pain and sciatica. A retrospective study of 132 patients in the Haute-Vienne district of France.

AIMS: To evaluate physician compliance with the guidelines of the National Agency for Accreditation and Health Evaluation (ANAES) and the Consensus Conference on the use of medical imagery in low back pain and sciatica. METHODS: We performed a retrospective study of 132 computed tomography scans (CTs) of the lumbar spine performed in one public and one private healthcare facility in the Haute-Vienne district, France. For each patent, the clinical findings, results of other investigations, prescriptions, and procedures reimbursed by the universal health insurance system were recorded. RESULTS: Guidelines on imagery were followed in 2% of patients with chronic nonspecific low back pain. In 72% of patients, CT results had no influence on the subsequent clinical management. The guidelines were followed more often in patients with sciatica: 85% underwent CT more than 4 weeks after the initial painful episode. However, before CT was ordered, only 54% received appropriate initial treatment with analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or muscle relaxants. Among these patients, 25% also received second-line medical therapy consisting of facet joint injection, conventional traction and, after the initial acute phase, physical therapy. In 39% of the sciatica patients, the imaging results had no effect on subsequent management. Among these patients, 12% underwent surgery for disk herniation. CONCLUSIONS: Ten years after the consensus conference and despite the publication of the ANAES guidelines, there is still a wide gap between observed practice and recommendations for optimal management. The consequences of this extend beyond unnecessary expenses for the universal health insurance system to include important deleterious effects on the patients. In particular, prompt appropriate management may help to avoid progression to chronic low back pain and unnecessary imaging studies and surgical procedures, which often have devastating social and occupational consequences.

France↗