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F Lioté

Publications and source records attributed to F Lioté.

At least 37 records · Page 2Linked to original sources

New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study.

Rheumatoid arthritis (RA), the most common autoimmune disease, is associated in families with other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM). Its genetic component has been suggested by familial aggregation (lambdas = 5), twin studies, and segregation analysis. HLA, which is the only susceptibility locus known, has been estimated to account for one-third of this component. The aim of this paper was to identify new RA loci. A genome scan was performed with 114 European Caucasian RA sib pairs from 97 nuclear families. Linkage was significant only for HLA (P < 2.5.10(-5)) and nominal for 19 markers in 14 other regions (P < 0.05). Four of the loci implicated in IDDM potentially overlap with these regions: the putative IDDM6, IDDM9, IDDM13, and DXS998 loci. The first two of these candidate regions, defined in the RA genome scan by the markers D18S68-D18S61-D18S469 (18q22-23) and D3S1267 (3q13), respectively, were studied in 194 additional RA sib pairs from 164 nuclear families. Support for linkage to chromosome 3 only was extended significantly (P = 0.002). The analysis of all 261 families provided a linkage evidence of P = 0. 001 and suggested an interaction between this putative RA locus and HLA. This locus could account for 16% of the genetic component of RA. Candidate genes include those coding for CD80 and CD86, molecules involved in antigen-specific T cell recognition. In conclusion, this first genome scan in RA Caucasian families revealed 14 candidate regions, one of which was supported further by the study of a second set of families.

Arthritis, Rheumatoid↗

Lymphoproliferative disorders in rheumatoid arthritis patients on low-dose methotrexate.

Methotrexate is the most widely used second-line treatment in rheumatoid arthritis because of its excellent efficacy and safety profile. However, since 1991, about 100 cases of lymphoproliferative disorders have been reported in rheumatoid arthritis patients under methotrexate therapy. Four characteristics similar to those in lymphomas associated with immunodeficiency were identified during a review of the 48 cases for which detailed information is available. (1) Most cases were non-Hodgkin's B-cell lymphomas of the large cell or diffuse mixed type. (2) Extranodal involvement (55% of cases) was unusually common. (3) Evidence of Epstein-Barr infection was found in 46% of tested patients. (4) Of the 14 patients treated by methotrexate withdrawal alone, eight achieved a full remission, with follow-ups ranging from one to five years. These characteristics suggest a role for two factors: (1) the abnormalities in cell-mediated immunity seen in rheumatoid arthritis may promote latent Epstein-Barr virus infection, which may in turn lead to proliferation of malignant lymphoid cells; (2) the immunomodulatory effects of methotrexate may promote the development not only of opportunistic infections but also of Epstein-Barr virus-related lymphoproliferative disorders. There is no firm evidence to date that methotrexate has a direct oncogenic effect and no excess in malignant diseases has been reported with this drug. In conclusion, the rate of occurrence of lymphoproliferative disorders induced by low-dose methotrexate therapy remains controversial, although the characteristics of the malignancies and the possibility of a complete remission after methotrexate withdrawal militate against a chance association. Epidemiologic and other studies are needed to clarify this issue.

Adolescent↗

A randomized, double blind, placebo controlled multicenter trial of murine anti-CD4 monoclonal antibody therapy in rheumatoid arthritis.

OBJECTIVE: To assess safety and efficacy of a murine anti-CD4 monoclonal antibody (Mab) in a population of patients with rheumatoid arthritis (RA) compared to treatment with placebo. METHODS: Fifty-eight patients with defined RA were included in this placebo controlled, randomized, double blind, multicenter study. Of the 48 women and 10 men (mean age 54.5 years), 25 were functional class II and 31 were class III, with 9 years' disease duration; the mean of previous disease modifying antirheumatic drugs was 4; 49 were taking steroids (mean dosage 11 mg/day of prednisone). Eighty percent were rheumatoid factor positive. All were in an active state of the disease with: pain > 4 (mean at inclusion 6.6), tender joints > 4 (mean 12), swollen joint count > 3 (mean 9), morning stiffness > 45 min (mean 185), erythrocyte sedimentation rate > 30 mm (mean 59) or C-reactive protein (CRP) > 30 mg/l (mean 63). Treatment was randomized between murine anti-CD4 Mab (B-F5, Diaclone, 20 mg/day) or placebo intravenously for 10 consecutive days. Efficacy was assessed with a composite index (Paulus), with evaluation of number of patients with 20 or 50% improvement in each group. Changes in measures of single clinical or biological variables were also evaluated. RESULTS: The 2 groups were comparable at inclusion. Treatment was well tolerated. Mild side effects (chills, fever, rash) were seen in both groups. Percentage of patients with global 20 or 50% response did not differ between placebo and Mab groups at Day 10 or at Day 30. Evaluation of single variables showed reduced CRP, swollen joint count, and Ritchie index in some B-F5 patients at Day 10, although in the B-F5 group as a whole only CRP was significant. CONCLUSION: No significant improvement in RA after murine anti-CD4 Mab was observed.

Adult↗

Magnetic resonance appearance of monoclonal gammopathies of unknown significance and multiple myeloma. The GRI Study Group.

STUDY DESIGN: A prospective multicenter study. OBJECTIVES: To evaluate the use of magnetic resonance imaging, in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. SUMMARY OF BACKGROUND DATA: Although multiple myeloma has been studied extensively with magnetic resonance imaging, to the authors' knowledge, no study has evaluated the clinical interest of magnetic resonance imaging in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. METHODS: The magnetic resonance examinations of the thoracolumbar spine in 24 patients with newly diagnosed monoclonal gammopathies of unknown significance were compared with those performed in 44 patients with newly diagnosed nontreated multiple myeloma. RESULTS: All findings on magnetic resonance examination performed in patients with monoclonal gammopathies of unknown significance were normal, whereas findings on 38 (86%) of the 44 magnetic resonance examinations performed in patients with multiple myeloma were abnormal. CONCLUSION: Magnetic resonance imaging can be considered as an additional diagnostic tool in differentiating between monoclonal gammopathies of unknown significance and multiple myeloma, which may be helpful when routine criteria are not sufficient. An abnormal finding on magnetic resonance examination in a patient with monoclonal gammopathies of unknown significance should suggest the diagnosis of multiple myeloma after other causes of marrow signal abnormalities are excluded. Magnetic resonance imaging also may be proposed in the long-term follow-up of monoclonal gammopathies of unknown significance when a new biologic or clinical event suggests the diagnosis of malignant monoclonal gammopathy.

Bone Marrow↗

[Epidemiological aspects of osteoarticular tuberculosis in adults. Retrospective study of 206 cases diagnosed in the Paris area from 1980 to 1994].

OBJECTIVES: The aim of this study was to determine the epidemiologic features of bone and joint tuberculosis in the Paris area from 1980 to 1994. METHODS: This retrospective study included 206 cases of confirmed bone and joint tuberculosis (in situ specimen) diagnosed from 1980 to 1994 in 7 hospital units (mainly rheumatology clinics) in Paris and suburban areas. RESULTS: The number of cases increased by a mean 12 per year from 1980 to 1989 then by 17 cases per year from 1990 to 1994. In both 1993 and 1994 there were 21 cases per year. The percentage of immigrant patients was 53% from 1980 to 1989 then reached 74% for 1990-1994, predominantly in subjects from black Africa. Only one patient in the series had human immunodeficiency virus (HIV) infection. A favoring factor was found in 23% of the immigrant and in 45% of the native French patients. Mean age was 37 years in immigrants and 58 years in French patients. Compared with French patients, immigrants had a higher rate of multifocal bone and joint tuberculosis, peripheral osteitis and spondylitus. CONCLUSION: Our findings suggest that the incidence of bone and joint tuberculosis has increased in Paris in 1993 and 1994. Two populations are especially susceptible: the elderly and/or immunodepressed French population and immigrants coming from endemic zones. The role or HIV infection was minimal in this predominantly rheumatology series.

Adult↗

Association of rheumatoid arthritis with an amino acid allelic variation of the T cell receptor.

OBJECTIVE: To investigate allelic variations of T cell receptor residues for a contribution to rheumatoid arthritis (RA) susceptibility. METHODS: We conducted an RA case-control study involving 1,579 northwest Europeans: 766 patients with erosive and rheumatoid factor-positive disease and 813 control subjects. Productive changes of segments TCRAV6S1, TCRAV7S1, TCRAV8S1, TCRAV10S2, and TCRBV6S1, TCRBV6S7 were investigated by single-strand conformation polymorphisms. The TCRAV8S1 association was confirmed by restriction fragment length polymorphism. RESULTS: In the systematic study (77 patients and 119 controls), an increase in 1 TCRAV8S1 genotype was found in the RA patients (P = 0.0004). This finding was replicated in 2 further populations, one from France (212 patients and 254 controls) and the other from Britain (477 patients and 440 controls), with a similar odds ratio (OR), which allowed pooling of the data and confirmation of the association (OR 1.3 [95% confidence interval 1.1-1.7], P = 0.008). CONCLUSION: These findings show evidence that TCRA is an RA susceptibility locus.

Alleles↗

Mesalazine-induced lupus.

We report a case of lupus induced by mesalazine therapy taken for over a year for Crohn's disease. The patient had polyarthritis, alopecia, lymphoneutropenia, antinuclear factors, anti-histone antibodies, anti-Sm and anti-RNP. Discontinuation of mesalazine was followed by rapid resolution of the joint manifestations, alopecia and lymphoneutropenia; the anti-histone antibodies fell to undetectable levels and the titers of the other auto-antibodies decreased gradually.

Anti-Inflammatory Agents, Non-Steroidal↗

[The hand and rheumatism].

The hand is a major site of musculoskeletal disorders. Clinical features to be studied include the patient's age and sex, pain, stiffness, range of motion of the various joints of the wrists and hands, soft tissue swelling (particularly tendons sheaths), bone excrescences, skin changes. Radiological abnormalities in the hands, if any, may confirm the clinical diagnosis. The main features of rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, erosive degenerative changes, Südeck syndrome, calcium pyrophosphate dihydrate deposition disease, etc., are reviewed.

Age Factors↗

Inhibition and prevention of monosodium urate monohydrate crystal-induced acute inflammation in vivo by transforming growth factor beta1.

OBJECTIVE: We investigated the effects of transforming growth factor beta 1 (TGF beta 1) on monosodium urate monohydrate (MSU) crystal-induced acute inflammation in vivo. METHODS: One hour after MSU crystal-induced acute inflammation was produced in the rat subcutaneous air pouch model, the effects of recombinant human TGF beta 1 (rHuTGF beta 1; 10-100 pg/animal) and ultrapure TGF beta 1 (UPTGF beta 1; 100 and 500 pg/animal) were assessed, based on absolute and differential white blood cell counts in the exudate. The effects of 10 pg of rHuTGF beta 1 preincubated with a specific anti-TGF beta antibody, and the effects of coinjection of crystals and rHuTGF beta 1, were also studied. RESULTS: UPTGF beta 1 and rHuTGF beta 1 markedly reduced MSU crystal-induced inflammation. Recombinant human TGF beta 1 also reduced inflammation when administered concomitantly with MSU crystals. Moreover, rHuTGF beta 1 and UPTGF beta 1, injected 1 hour after MSU crystal injection, reduced the inflammatory response in a dose-dependent manner. Injection of rHuTGF beta 1 (100 pg/animal) resulted in a > 90% reduction in the maximal white blood cell count, achieved 6 hours after crystal injection. Preincubation of rHuTGF beta 1 with a specific anti-TGF beta 1 antibody significantly (P < 0.01) reversed the inhibitory effect of rHuTGF beta 1 on the inflammatory response. Consistent with the regulation of inflammatory cell recruitment into the joint, the percentage of monocytes markedly decreased (P < 0.01) following local injection with rHuTGF beta 1 6 hours after MSU crystal injection. CONCLUSION: Exogenous TGF beta 1 prevents and inhibits MSU crystal-induced acute inflammation in vivo. Its role in the self-limitation of gouty attacks deserves consideration, among the various other factors involved.

Acute Disease↗

Variation in the inflammatory properties of basic calcium phosphate crystals according to crystal type.

OBJECTIVE: To determine the inflammatory potential of basic calcium phosphate (BCP) crystals, which have been identified in human joints. METHODS: Hydroxyapatite, carbonate apatite, whitlockite, and octacalcium phosphate crystals were injected in rat air pouches. Volume and cellularity of the exudate were measured. Physicochemical properties of the injected BCP crystals were determined, and correlations with the magnitude of induced inflammatory responses were sought. RESULTS: Significant differences were observed among the volumes and white blood cell (WBC) counts of the pouch exudates, based on the various crystal types used to induce inflammation. A strong correlation was demonstrated between the specific surface (SS) area of the injected crystals and the area under the curve for induced WBC count versus time (R2 = 0.88, P = 0.05). This correlation was observed for SS area values below 50 m2/gm, but when SS area increased further, this parameter plateaued. Another parameter of inflammatory response was obtained by dividing the area under the curve figuring WBC counts versus time by the corresponding SS area for each crystal type. This parameter increased linearly with the Ca:P ratio (R2 = 0.97, P = 0.0003). CONCLUSION: The inflammatory potential of BCP crystals appeared to vary according to crystal features. SS area and the Ca:P ratio (which correlates with crystal solubility) influenced inflammatory properties. These results could explain the variable clinical consequences of BCP deposits, and must be taken into account in the choice of apatite ceramics for use as biomaterials.

Animals↗

Blood monocyte activation in rheumatoid arthritis: increased monocyte adhesiveness, integrin expression, and cytokine release.

Infiltration of the synovium by mononuclear cells, namely lymphocytes and monocytes, is one of the main features of rheumatoid arthritis (RA) and is considered to be responsible for the development of the disease. In this study in 31 consecutive patients with RA, we investigated whether peripheral blood monocytes exhibited markers of cellular activation related to cell migration. Using flow cytometry with the respective specific antibodies, we studied the expression of integrins CD11a, CD11b, CD11c, CD49d (VLA-4), and CD49e (VLA-5) on monocytes from patients with RA and from normal (N) subjects. IL-1 beta, IL-6, and tumour necrosis factor-alpha (TNF-alpha) production by cultured monocytes was measured by immunoassay. Adhesiveness of monocytes was studied on various surfaces (plastic, human fibronectin, gelatin-coated plasma, subendothelial matrix) and on cultured endothelial cells under basal conditions or after stimulation by IL-1 beta. An increased number of CD14+ monocytes (Mo) from RA patients expressed the CD11b molecule (RA Mo = 90.3%, N Mo = 83.4%, P < 0.005). The expression of CD11b on CD14+ monocytes was significantly increased in RA patients (median fluorescence intensity (FI): RA Mo = 145 (range 80-466) units; normal Mo = 95 (range 24-164) units; P < 0.003). Production of extracellular IL-1 beta and IL-6 by RA monocytes was significantly enhanced compared with monocytes from normal subjects (IL-1 beta: RA = 2.65 +/- 0.91 ng/ml versus N = 1.35 +/- 0.85 pg/ml, P < 0.05; IL-6: RA = 4.83 +/- 0.90 ng/ml versus N = 2.40 +/- 0.95 ng/ml, P < 0.05). Compared with normal monocytes, RA monocytes exhibited increased adhesion to the various surfaces studied (plastic, P < 0.01; fibronectin, P < 0.01; and gelatin-coated normal or RA plasma, P < 0.01) as well as to unstimulated (P < 0.01) and IL-1 beta-stimulated endothelial cells (IL-1 beta for 4 h, P < 0.05; IL-1 beta for 24h, P < 0.05). In our study, blood monocytes from RA patients exhibited features of activation related to cell adhesion.

Arthritis, Rheumatoid↗

Sulphasalazine in psoriatic arthritis: a randomized, multicentre, placebo-controlled study.

A prospective double-blind, placebo-controlled, randomized study of 24 weeks duration was carried out comparing the efficacy and tolerability of sulphasalazine (SSZ) versus placebo in patients with psoriatic arthritis. A total of 120 patients were included in nine centres. All patients had active disease and fulfilled the criteria of definite psoriatic arthritis of at least 3 months duration. They received either SSZ (2.0 g/day) or placebo. Efficacy variables included pain, patient's overall assessment of joint and skin improvement, morning stiffness, Ritchie articular index, ESR and CRP. An intention-to-treat (ITT) analysis was performed for the 117 patients who qualified (three patients did not qualify due to missing data after baseline). A per-protocol analysis was performed for the 81 patients who completed the 6 months study period (SSZ = 38, placebo = 43). Major reasons for withdrawal were inadequate response (SSZ = 4, placebo = 7) and adverse events (SSZ = 8, placebo = 12). Pain was the only statistically significantly different primary outcome variable at end point in favour of SSZ in the ITT analysis. No significant differences were present in other clinical or biological variables, although there was a trend in favour of SSZ for some variables. SSZ, at a dose of 2.0 g/day, appeared to be a safe treatment in patients with psoriatic arthritis. At this dosage, its efficacy was only demonstrated for the pain variable.

Adult↗

Hypersensitivity to glucocorticoids: does it exist?

Hypersensitivity to corticosteroids is a classical but rarely reported event. We report a 30-year-old patient who developed generalized urticaria after her first methylprednisolone bolus. We reviewed the relevant literature to look for factors associated with hypersensitivity to corticosteroids. Causality should be evaluated on a case-by-case basis using diagnostic criteria for drug hypersensitivity reaction. Etiopathogenesis may involve either an IgE-mediated immunoallergic reaction or semi-delayed hypersensitivity. The main problems are identification of the offending agent and evaluation of the safety of further corticosteroid therapy. Although a few fatal reactions have been reported, some were probably due to underlying cardiovascular disease or serum electrolyte abnormalities.

Adult↗

Acetabular fractures due to bone insufficiency. Two case-reports.

Acetabular fractures due to bone insufficiency are rare and difficult to diagnose based on clinical findings alone. Plain films are often normal for a long period of time. We report two cases of acetabular fractures in women aged 78 and 90 years, respectively. An acetabular fracture should be considered in elderly females with sudden onset of pain in the groin occurring immediately upon weight-bearing, a clinostatic syndrome, and increased radionuclide uptake by the acetabulum. Computed tomography and magnetic resonance imaging are useful when the diagnosis remains in doubt.

Acetabulum↗

Magnetic resonance imaging of the spine in plasma cell dyscrasias. A review.

This review of recent data on the techniques and results of spinal magnetic resonance imaging in plasma cell dyscrasias provides a basis for selecting those patients who are most likely to benefit from this investigation. Sagittal images should be obtained using T1-weighted spin-echo and T2-weighted gradient-echo sequences. Epiduritis is best detected on sagittal or axial images acquired after gadolinium injection using T1-weighted spin-echo or phase-opposed gradient-echo sequences. Among patients with symptomatic multiple myeloma, 80% have abnormal magnetic resonance images of the lower spine due to plasma cell infiltration and this proportion increases with the stage in the Durie and Salmon staging system. Bone marrow signal abnormalities can be focal, diffuse and homogeneous, or diffuse and variegated. Vertebral fractures due to spinal infiltration or osteoporosis are seen in 48% of cases and spinal canal narrowing with impingement of bone tumors or epiduritis on nervous structures in 20%. The response to chemotherapy as evaluated based on conventional criteria is fairly well correlated with changes in magnetic resonance imaging findings. Among asymptomatic multiple myeloma patients with normal roentgenograms, 50% have tumor-related abnormalities on magnetic resonance images of the lower spine, which are associated with an increased likelihood of rapid progression to symptomatic disease. Similarly, one third of patients with an apparently solitary plasmacytoma of bone have evidence of other plasma cell tumors on magnetic resonance images of the lower spine, and this finding is associated with persistence of monoclonal component production after irradiation therapy, which may be of adverse prognostic significance. Patients with monoclonal gammopathies of uncertain significance have no evidence of tumorous lesions on magnetic resonance images of the lower spine.

Bone Marrow↗

Asplenism and systemic lupus erythematosus.

Although functional hyposplenism, secondary to Fc-receptor blockage by circulating immune complexes saturation, has been described in systemic lupus erythematosus (SLE), only few cases of complete asplenism have been reported. We observed a 60-year-old woman with congenital asplenism who presented with active SLE. The course and the clinical characteristics of such patients are reviewed and the relationship between the asplenic state and initiation and severity of SLE are discussed. These patients are at high risk for fatal pneumococcemia and pneumococcal vaccine is recommended even if long term results are still conflicting.

Adolescent↗