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Biomedical subjects

Frédéric Lioté

Publications and source records attributed to Frédéric Lioté.

At least 19 recordsLinked to original sources
PubMed2006

Role for positron emission tomography in skeletal diseases.

Imaging plays a prominent role in the diagnosis and management of rheumatic diseases. Conventional imaging methods provide high-resolution structural information but usually fail to distinguish between active lesions and residual changes. Positron emission tomography (PET) with the tracer 18F-fluorodeoxyglucose (18F-FDG) was recently introduced into clinical practice as a means of obtaining information on both structure and metabolic activity. 18F-FDG-PET is widely used in oncology and may be valuable in patients with infections or inflammatory diseases, most notably vasculitis. Although encouraging results have been published, the number of studies remains small, as 18F-FDG-PET is an expensive investigation that is not available everywhere. Further work is needed to determine the cost-effectiveness ratio of 18F-FDG-PET in patients with infections or inflammatory diseases. Imaging plays a prominent role in the diagnosis and management of many musculoskeletal diseases. Although considerable progress has been made recently, the structural information supplied by conventional imaging methods is inadequate in some patients. Positron emission tomography (PET) after injection of 18fluorodeoxyglucose (18F-FDG) provides information on tissue metabolism. The usefulness of 18F-FDG-PET in oncology is now widely recognized. Other uses are emerging, in part thanks to the development of new cameras that combine dedicated detectors and an X-scanner in order to ensure accurate three-dimensional localization of metabolically active lesions. However, the exact role for 18F-FDG-PET needs to be studied in larger populations of patients.

Arthritis↗
PubMed2006

Clinical practice format for choosing a second-line disease modifying anti-rheumatic drug in early rheumatoid arthritis after failure of 6 months' first-line DMARD therapy.

BACKGROUND: The objective was to develop a clinical practice format for choosing a second-line disease-modifying anti-rheumatic drug (DMARD) after a 6-month course of a first-line DMARD in patients with early RA. METHODS: A panel of 34 experts selected treatment option from various scenarios using the Thurstone pairwise method. The experts had to choose between two proposed DMARDs without proposing other options. The scenarios were obtained using the three items: DAS28, rheumatoid factor status and radiographic structural damage. A sample of 240 among 480 scenarios for each expert was taken at random. Responses given by at least 20% of the experts were considered pertinent. RESULTS: Recommendations for choosing a second DMARD for early RA after failure of a 6-month course of a first-line DMARD were established according to 4 parameters: type of first-line DMARD, activity, RF status and radiographic joint damage. The results of this study suggest that in patients with early RA who fail a 6-month course of first-line DMARD therapy, the best options may be addition of corticosteroid when disease activity is moderate to high and switching to a biologic agent when further radiographic joint damage occurs, particularly in patients with positive tests for RF. CONCLUSION: Although our scenarios did not include step-up (add instead of substitute) strategies, except for corticosteroids, we feel that the format presented here can optimise the management of patients with early RA seen in clinical practice.

Antirheumatic Agents↗
PubMed2006

A critical role for adrenomedullin-calcitonin receptor-like receptor in regulating rheumatoid fibroblast-like synoviocyte apoptosis.

Rheumatoid arthritis (RA) is characterized by fibroblast-like synoviocyte (FLS) hyperplasia, which is partly ascribable to decreased apoptosis. In this study, we show that adrenomedullin (ADM), an antiapoptotic peptide, is constitutively secreted in larger amounts by FLS from joints with RA (RA-FLS) than with osteoarthritis (OA-FLS). ADM secretion was regulated by TNF-alpha. Peptidylglycine alpha-amidating monooxygenase, the ADM-processing enzyme, was expressed at the mRNA level by both RA-FLS and OA-FLS. Constituents of the ADM heterodimeric receptor calcitonin receptor-like receptor (CRLR)/receptor activity-modifying protein (RAMP)-2 were up-regulated at the mRNA and protein levels in cultured RA-FLS compared with OA-FLS. ADM induced rapid intracellular cAMP production in FLS and reduced caspase-3 activity, DNA fragmentation, and chromatin condensation in RA-FLS exposed to apoptotic conditions, indicating that CRLR/RAMP-2 was fully functional. ADM-induced cAMP production was less marked in OA-FLS than in RA-FLS, suggesting differences in receptor regulation and expression. ADM dose-dependently inhibited RA-FLS apoptosis, and this effect was reversed by the 22-52 ADM antagonist peptide. ADM inhibited RA-FLS apoptosis triggered by extrinsic and intrinsic pathways. Our data suggest that ADM may prevent or reduce RA-FLS apoptosis, via up-regulation of its functional receptor CRLR/RAMP-2. Regulation of ADM secretion and/or CRLR/RAMP-2 activation may constitute new treatment strategies for RA.

Adenylyl Cyclases↗
PubMed2006

Gout: update on some pathogenic and clinical aspects.

Pathogenesis of gout inflammation remains unknown, but recent advances have been made with respect to initiation, amplification, and self-limitation. Direct crystal-cell membrane contact leads to cell activation, involving membrane-associated molecules. Resolution of acute gout inflammation is a mechanism that is controlled by monocyte-macrophage switch, which results in the loss of cytokine production capability and, conversely, the ability to produce anti-inflammatory molecules. MRI and ultrasound findings provide preliminary data that are not yet used in clinical trials. Diagnosis and management recommendations are missing, but this gap will be filled soon with the upcoming European League Against Rheumatism Task Force's recommendations on gout.

Crystallization↗
PubMed2006

Muscle involvement in sarcoidosis: a retrospective and followup studies.

OBJECTIVE: Muscle involvement is a frequent histopathologic feature of sarcoidosis, but its clinical presentation has been rarely reported and its longterm outcome is unclear. We describe the features and outcome of 5 patients with muscle sarcoidosis. METHODS: A retrospective study from hospital charts over the period 1985-2001 in 2 academic rheumatology centers. RESULTS: Muscle involvement was identified in 5 patients (3 women, 2 men) aged 37 to 61 years, out of a cohort of 45 patients with sarcoidosis. No symptomatic muscle involvement was observed in the 20 patients with Lofgren syndrome of our series. Muscle involvement was the initial feature of the disease in 2 patients. Three patients had nodular type and the 2 others the myositic type. Chronic myopathy was not observed. Followup of patients with muscle disease ranged from 30 to 144 months (mean 72.6). Prednisone was used at a starting dose from about 0.33 to 1 mg/kg/day in all patients, then progressively tapered, and was associated with use of hydroxychloroquine (HCQ) in 2 cases. One poorly compliant patient was persistently prescribed 40 mg/day prednisone and HCQ by his general practitioner and was still complaining of diffuse myalgia at the last 30-month followup visit. One patient also receiving HCQ experienced cardiac and renal relapse, leading to transient increase in steroid dosage, but remained symptom-free 3 years after steroid discontinuation. Muscle relapses occurred in the 3 other patients. Muscle symptoms disappeared after readministration of corticosteroids or increase of prednisone dosage. The first patient was symptom-free without any treatment at the last followup visit. The second was still taking 10 mg/day 144 months after disease onset because of steroid-dependent myalgia. The last patient was asymptomatic with 10 mg/day prednisone at the last evaluation. CONCLUSION: Symptomatic muscle involvement may be an initial feature of chronic, and usually the systemic form of, sarcoidosis. It responds to corticosteroid therapy, but relapse seems to be frequent.

Adult↗
PubMed2005

[Armentarium and strategies for the treatment of rheumatoid arthritis].

Rheumatoid arthritis is characterized by chronic synovitis resulting in bone and joint destruction in various delays, and ultimately leading to handicap. Remission can be induced at the beginning of the disease. It is well established that slow-acting remitting drugs can efficiently halt radiological progression and improve functional outcome. Besides symptomatic agents (NSAID, steroids, joint injections and synoviorthesis), several long-acting treatment strategies have been proposed based upon methotrexate, alone or in combination with sulfasalazine, hydroxychloroquine, and also anti-TNF agents. Several strategies have been compared according to the disease profile, and suggested that both combination and mainly tight control of the disease clearly improve the clinical, radiological and functional outcomes. The indication of anti-TNF agents is still discussed case by case with respect to treatment failure and risk-benefit ratio at mid and long term. General practitioners should contribute to an early management and regular follow-up by rheumatologists and to general managements of comorbidities.

Administration, Oral↗
PubMed2005

Systemic sarcoidosis: the "leopard-man" sign.

Systemic sarcoidosis is often diagnosed late. A 37 year-old man from the Antilles was admitted for evaluation of arthralgia, subcutaneous and cutaneous nodules, multiple enlarged lymph nodes, and an epididymal lump. He had been given a diagnosis of epididymal and nodal tuberculosis but had not responded to antitubercular agents. Gallium-67 scintigraphy showed multiple hot spots in the soft tissues, skin, muscles, mediastinum, and lachrymal glands, producing a diffuse dappled pattern. Magnetic resonance imaging of the thighs confirmed the muscular and subcutaneous involvement. Systemic sarcoidosis was diagnosed. Prednisone therapy was promptly effective. We suggest the term "dappled-body sign" or "leopard-man sign" to designate the heretofore undescribed scintigraphic pattern in our patient.

Adult↗
PubMed2005

Octacalcium phosphate crystals directly stimulate expression of inducible nitric oxide synthase through p38 and JNK mitogen-activated protein kinases in articular chondrocytes.

Basic calcium phosphate (BCP) crystals, including hydroxyapatite, octacalcium phosphate (OCP) and carbonate-apatite, have been associated with severe osteoarthritis and several degenerative arthropathies. Most studies have considered the chondrocyte to be a bystander in the pathogenesis of calcium crystal deposition disease, assuming that synovial cell cytokines were the only triggers of chondrocyte activation. In the present study we identified direct activation of articular chondrocytes by OCP crystals, which are the BCP crystals with the greatest potential for inducing inflammation. OCP crystals induced nitric oxide (NO) production and inducible nitric oxide synthase (NOS) mRNA expression by isolated articular chondrocytes and cartilage fragments, in a dose-dependent manner and with variations over time. OCP crystals also induced IL-1beta mRNA expression. Using pharmacological and cytokine inhibitors, we observed that OCP crystals induced NO production and inducible NOS mRNA activation were regulated at both the transcriptional and the translational levels; were independent from IL-1beta gene activation; and involved p38 and c-Jun amino-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, as further confirmed by OCP crystal-induced p38 and JNK MAPK phosphorylation. Taken together, our data suggest that the transcriptional inducible NOS response to OCP crystals involved both the p38 and the JNK MAPK pathways, probably under the control of activator protein-1. NO, a major mediator of cartilage degradation, can be directly produced by BCP crystals in chondrocytes. Together with synovial activation, this direct mechanism may be important in the pathogenesis of destructive arthropathies triggered by microcrystals.

Animals↗
PubMed2005

Cervical spine and crystal-associated diseases: imaging findings.

The cervical spine may be specifically involved in crystal-associated arthropathies. In this article, we focus on the three common crystals and diseases: hydroxyapatite crystal deposition disease, calcium pyrophosphate dihydrate (CPPD) deposition disease, and monosodium urate crystals (gout). The cervical involvement in crystal-associated diseases may provoke a misleading clinical presentation with acute neck pain, fever, or neurological symptoms. Imaging allows an accurate diagnosis in typical cases with calcific deposits and destructive lesions of the discs and joints. Most of the cases are related to CPPD or hydroxyapatite crystal deposition; gout is much less common.

Adult↗
PubMed2005

Monosodium urate and calcium pyrophosphate dihydrate (CPPD) crystals, inflammation, and cellular signaling.

Monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals are responsible for acute synovial inflammation but also contribute to cartilage degradation and bone lesions within the joint. They activate multiple signal transduction pathways leading to cell activation and recruitment. Some signalling pathways are activated by both types of crystals, and other pathways may only be activated by one type depending on cell type, namely neutrophils, monocytes, macrophages, synovial fibroblasts, endothelial cells and chondrocytes. Cascades of activated proteins involve cytoplasmic membrane related proteins (FAK complex, Src family tyrosine kinases), but also MAPK and NF-kB pathways, leading to NO, prostanoid and cytokine production, and protease activation. This review will also focus on potential therapeutic targets related to cellular signalling in MSU and CPPD crystal-induced inflammation.

Animals↗
PubMed2004

Proline-rich tyrosine kinase 2 and Src kinase signaling transduce monosodium urate crystal-induced nitric oxide production and matrix metalloproteinase 3 expression in chondrocytes.

OBJECTIVE: Articular deposition of monosodium urate monohydrate (MSU) crystals may promote cartilage and bone erosion. Therefore, the aim of this study was to determine how MSU crystals stimulate chondrocytes. METHODS: Nitric oxide (NO) release, and expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase 3 (MMP-3) were assessed in cultured chondrocytes treated with MSU. MSU-induced functional signaling by specific protein kinases (p38, Src, and the focal adhesion kinase [FAK] family members proline-rich tyrosine kinase 2 [Pyk-2] and FAK) was also examined using selective pharmacologic inhibitors and transfection of kinase mutants. RESULTS: MSU induced MMP-3 and iNOS expression and NO release in chondrocytes in a p38-dependent manner that did not require interleukin-1 (IL-1), as demonstrated by using IL-1 receptor antagonist. MSU induced rapid tyrosine phosphorylation of Pyk-2 and FAK, their adaptor protein paxillin, and interacting kinase c-Src. Pyk-2 and c-Src signaling both mediated p38 MAPK activation in response to MSU. Pyk-2 and c-Src signaling played a major role in transducing MSU-induced NO production and MMP-3 expression. But, despite the observed FAK phosphorylation, a selective pharmacologic FAK inhibitor and a FAK dominant-negative mutant both failed to block MSU-induced NO release or MMP-3 expression in parallel experiments. CONCLUSION: In chondrocytes, MSU crystals activate a signaling kinase cascade typically employed by adhesion receptors that involves upstream Src and FAK family activation and downstream p38 activation. In this cascade, Pyk-2, Src, and p38 kinases transduce MSU-induced NO production and MMP-3 expression. Our results identify Pyk-2 and c-Src as novel sites for potential therapeutic intervention in cartilage degradation in chronic gout.

Animals↗
PubMed2004

Calcium pyrophosphate dihydrate and basic calcium phosphate crystal-induced arthropathies: update on pathogenesis, clinical features, and therapy.

Calcium-containing crystals are the most common class for the osteoarthritic joint. They are responsible for acute periarthritis and destructive arthropathies, and for tissue deposits mimicking tumor-like masses. These crystals encompassed mainly calcium pyrophosphate dihydrate and basic calcium phosphate crystals, with the latter being related to hydroxyapatite, carbonate-substituted apatite, and octacalcium phosphate. Calcification deposit mechanisms will be reviewed with respect to extracellular inorganic pyrophosphate dysregulation mainly caused by modulation of specific membrane channel disorders. Genetic defects have been extensively studied and identified mutation of specific genes such as ANKH and COL. Pathogenesis of crystal-induced inflammation is related to synovial tissue and direct cartilage activation. Besides classical knee or wrist pseudogout attacks or Milwaukee shoulder arthropathies, clinicians should be aware of other specific common presentations, such as erosive calcifications, spinal cord compression by intraspinal masses, ligamentum flavum calcification, or atypical calcified tophus. Promising clinical results for preventing calcium crystal deposits and cartilage degradation are lacking. Practical imaging tools are needed to monitor reduction of calcification of fibrocartilage and articular cartilage as markers of drug efficacy.

Arthritis↗
PubMed2004

Somatostatin and somatostatin analog scintigraphy: any benefits for rheumatology patients?

Somatostatin is a hormone that regulates several physiological cell processes via specific receptors expressed throughout the body, in particular by nerve cells, many neuroendocrine cells, and cells mediating inflammation and immune responses. Somatostatin receptor scintigraphy achieved by administration of somatostatin labeled with a gamma-emitting isotope has become an integral part of the work-up and treatment-monitoring program in patients with neuroendocrine tumors, most of which overexpress somatostatin receptors. Several studies have convincingly established that somatostatin receptor scintigraphy benefits patients with a number of chronic inflammatory diseases, including sarcoidosis and other granulomatous diseases. In the evaluation of hematological diseases and detection of mesenchymatous tumors manifesting as oncogenic osteomalacia, the preliminary results are sufficiently promising to warrant larger studies aimed at defining the role for this noninvasive whole-body imaging technique. In the treatment area, the development of somatostatin analogs with antisecretory and antiproliferative effects has radically changed the management of gastroenteropancreatic neuroendocrine and pituitary tumors. The antiinflammatory and analgesic effects of these drugs remain incompletely understood, but may prove useful in a number of autoimmune diseases.

Humans↗
PubMed2004

Osteoporotic fracture of the dens revealed by cervical manipulation.

Osteoporotic vertebral fractures selectively affect the thoracolumbar junction, usually sparing the cervical spine. A 65-year-old woman with documented osteoporotic fractures and chronic alcohol abuse presented with neck pain and occipital neuralgia that started after she suddenly flexed then extended her neck. Following several sessions of cervical manipulation, her pain became more severe, and she was admitted. Imaging studies showed multiple fractures in the dens, C6 and C7. These apparently spontaneous fractures suggested a bone tumor, for which investigations were negative. Osteoporosis was the only identifiable cause. The spinal manipulations probably worsened the lesions which were performed by a chiropractor who is not a physician and did not obtain cervical spine radiographs before treating the patient. Osteoporosis contraindicates spinal manipulation at any level, including the cervical spine.

Aged↗
PubMed2003

Hyperuricemia and gout.

Gout is not a new disease for clinicians; nevertheless, there are still many secrets awaiting discovery for improving knowledge with respect to uric acid metabolism and monosodium urate crystal-induced inflammation. This review of the literature will focus on new insights on the pathogenesis of idiopathic hyperuricemia, and on secondary hyperuricemia and gout. There are also important advances on the pathophysiology of acute gout, especially as a self-limited process (switch from monocyte to macrophage, peroxisome proliferator activated receptor-gamma, and nitric oxide), but also of chronic gouty arthropathy. Armaments for treating hyperuricemia and gout may be already improved by losartan or fenofibrate and, in the future, by urate oxydase-polyethylene glycol 20 and renal handling regulatory molecules. Finally, control of hyperuricemia may also be considered in the prevention and treatment of cardiovascular disease.

Gout↗