A randomised, double-blind, placebo-controlled trial of dolasetron, a 5-hydroxytryptamine 3 receptor antagonist, in patients with fibromyalgia.

OBJECTIVE: The purpose of the study was to evaluate the efficacy and safety of dolasetron for symptomatic relief of pain associated with fibromyalgia (FM). METHODS: This prospective, double-blind, placebo-controlled trial randomly assigned 60 patients with FM to receive placebo (n = 31) or dolasetron (n = 29) 12.5mg/d via the intravenous route on 4 days at baseline (M0), 1 month (M1), 2 months (M2) and 3 months (M3) with follow-up to month 12. The primary outcome variable was the reduction in pain intensity measured by visual analogue scale (VAS) between M0 and M3. The secondary outcome variables were patient global impression of change (PGIC), the FM impact questionnaire, assessment of quality of life (SF-36), the hospital anxiety and depression scale, the manual tender point count, and functional symptoms associated with FM. RESULTS: Reduction in pain intensity at M3 was significantly greater in dolasetron-treated patients (p = 0.04, -21.3 on a 0-100 scale) compared with placebo controls (-5.9). More patients in the dolasetron group had ≥ 30% and ≥ 50% improvement in pain (42.5% and 28% respectively in the dolasetron group versus 25% and 16% in the placebo group). The PGIC was significantly greater in the dolasetron group at M3 (p = 0.02). The other secondary outcomes failed to reach statistical significance. The most common adverse events were constipation, nausea, dizziness and headache, with no significant differences between the two groups. CONCLUSION: Intermittent IV dolasetron was safe and efficacious for the reduction of pain intensity associated with FM at 3 months.

Ultrasonography in chondrocalcinosis.

Ultrasonography can visualize calcific deposits within soft tissues. The appearance and location of the deposits distinguishes articular chondrocalcinosis from other crystal deposition diseases. The most common findings are hyperechoic dots or lines running parallel to the joint surface, hyperechoic images within fibrous cartilage (menisci and triangular fibrocartilage complex), and deposits within tendons (Achilles tendon). Studies found that ultrasonography was highly sensitive and specific for detecting calcifications, using calcium pyrophosphate dihydrate crystal detection in joint fluid as the reference standard. Good agreement has been demonstrated between radiographs and ultrasonography for the detection of calcifications. Thus, ultrasonography is valuable for diagnosing articular chondrocalcinosis via the detection of calcifications within the joint cartilage, fibrocartilage, and tendons. In addition, ultrasonography is a noninvasive, widely available, inexpensive investigation that requires no radiation exposure.

Clinically relevant VAS pain score change in patients with acute rheumatic conditions.

INTRODUCTION: Pain assessment is a crucial step in the management of patients with rheumatic diseases. Among validated pain scores, the visual analog scale (VAS) score is the most widely used, in both clinical practice and therapeutic trials. OBJECTIVE: To determine the VAS pain score decrease that constitutes meaningful pain relief, with the goal of evaluating treatment effects. METHODS: We included patients with acute pain caused by non-malignant rheumatic conditions. Pain duration of less than 1month and a baseline VAS score greater than 50/100mm were required. Twice daily, patients evaluated pain intensity using the VAS and pain relief using a five-category verbal rating scale (VRS) where 0 indicated no pain relief and 4 excellent relief. RESULTS: Fifty patients were included. VAS score changes correlated linearly with VRS score changes (r=0.7 and P<0.001). A one-category improvement on the VRS was associated with a 20-mm decrease in the VAS score (P<0.0001) and a two-category improvement with a 40-mm decrease (P<0.0003). CONCLUSION: The dearth of published data on clinically relevant VAS pain score changes in patients with acute rheumatic pain requires further studies, in order to improve patient care and the comparability of therapeutic trials.

[Contribution of sacroiliac magnetic resonance imaging (MRI) to the evaluation of infliximab efficacy in spondyloarthropathy (a prospective study of 34 patients)]. / Contribution de l'IRM des sacro-iliaques dans l'evaluation des spondylarthropathies sous infliximab (etude prospective sur 34 patients).

Thirty-four patients who met ESSG criteria for spondylarthropathy and were eligible for anti-TNFalpha treatment (infliximab) were enrolled in this open-label study lasting 14 weeks. The aims were to evaluate the progression of sacroiliitis by means of MRI, and to determine the positive predictive value of this exam for the treatment response. Patients underwent MRI of the sacroiliac region at baseline (W0), and also at 14 weeks if the baseline MRI showed sacroiliitis. Two blinded readers reviewed all imaging studies. The patients also had a physical examination and ESR and CRP assays at W0 and W14. Sacroiliitis was found in 22 patients (65%) at W0, but only 18 of these patients had a second MRI at W14, for technical reasons. After 14 weeks of therapy, MRI signs of sacroiliac inflammation diminished by 77.7% on average. Clinical and biological parameters also improved. However, MRI was not predictive of the treatment response. Sacroiliac MRI seems to be interesting for objective therapeutic evaluation and monitoring of patients with spondyloarthropathy.

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.

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.

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.

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.