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Objective: To determine methotrexate (MTX) concentrations in the synovial membrane (SM) and cortical and trabecular bone of rheumatoid arthritis (RA) patients., Methods: Ten RA patients (9 women, 1 man; mean +/- SD age 49.2 +/- 10.6, mean disease duration 13.2 +/- 9.9 years) undergoing surgical procedures for rheumatoid articular lesions participated in this study. Mean +/- SD MTX treatment duration was 26.4 +/- 21.3 months. The day preceding surgery, 10 mg of MTX was administered intramuscularly. During surgery, a mean +/- SD of 19.7 +/- 2.6 hours after MTX administration, SM, bone fragments, and blood were collected simultaneously. MTX was assayed by fluorescence polarization immunoassay in plasma and tissues., Results: The mean +/- SD plasma concentration was 0.0252 +/- 0.01 nmoles/ml at the time of tissue sampling. The mean MTX concentration in SM was 0.285 +/- 0.159 nmoles/gm. The mean MTX concentrations in trabecular and cortical bone were 0.292 +/- 0.164 and 0.286 +/- 0.126 nmoles/gm, respectively., Conclusion: After intramuscular administration, high MTX concentrations are found in SM and cortical and trabecular bone of RA patients.

Objective: Human mucosyl lymphocyte marker (HML-1) antigen is an activation antigen and adhesion molecule of the beta 7 integrin family, which is generally restricted to T cells found in the intestinal epithelium. Expression of the membrane antigen as defined by the monoclonal antibody HML-1 was studied on peripheral blood (PB) lymphocytes and synovial fluid (SF) lymphocytes in 10 patients with rheumatoid arthritis (RA) and in a control group of patients with osteoarthritis (OA)., Methods: Double fluorescence activated flow cytometry was used to assess HML-1 expression with T cell subtype antigens (CD3, CD4, CD8) or activation markers interleukin 2 receptor (IL-2R) (CD25), HLA-DR, and lymphocyte function associated antigen (LFA-1) (CD11a) were assessed by flow cytometry., Results: HML-1 antigen expression in PB lymphocytes of patients with RA (7.3%) was found to be comparable to the control group (6.4%). In contrast, 25.4% (range 14-43%) of SF lymphocytes expressed HML-1 antigen, compared to 13.6% of SF lymphocytes in patients with OA (p < 0.001). In RA, 62% of HML-1 positive cells from SF lymphocytes were the CD8 subtype, compared to 10.6% of PB lymphocytes (p < 0.003), and 18% of control SF lymphocytes (p < 0.05). Furthermore, HML-1 antigen and HLA-DR antigen were coexpressed in 75% of RA SF lymphocytes compared to 29.6% of control SF lymphocytes (p < 0.01). In contrast, coexpression of LFA-1 and the Il-2R did not differ from that of control., Conclusion: We describe overexpression of the adhesion molecule HML-1 in SF lymphocytes of patients with RA, preferentially in the CD8 subset. These results suggest a similarity between the expression of activation antigens in SF lymphocytes of patients with RA and T lymphocytes present in the intestinal epithelium.

Objective: To determine if the pharmacokinetics of methotrexate (MTX) is modified by the coadministration of etodolac., Methods: MTX (10 mg) was administered intramuscularly in the absence and presence of steady state levels of etodolac in 19 patients with rheumatoid arthritis. MTX levels were assayed by fluorescence polarization immunoassay. Concentrations of 7-hydroxymethotrexate (7-OH-MTX) were assayed by a reverse phase high performance liquid chromatography method. The unbound fraction was determined by ultrafiltration., Results: When etodolac was coadministered with MTX, the highest observed concentration decreased and the mean residence time increased to become statistically significant. However, these differences are not of great clinical importance especially given that the area under the curve and clearances were unchanged. There were no significant differences in binding protein and 7-OH-MTX concentrations between MTX with and without etodolac administration., Conclusion: The pharmacokinetics of MTX is slightly modified by coadministration of etodolac. Moreover, no clinical toxicity was observed.

We report the first case of choriocarcinoma occurring during the course of systemic lupus erythematosus (SLE). This choriocarcinoma was revealed by pulmonary metastasis associated with pulmonary hypertension secondary to neoplastic thrombi and pulmonary embolism, in parallel to a flare up of the SLE. The role of hormones in SLE is discussed.

Twenty-three per cent of rheumatoid arthritis (RA) patients show an increase of serum IgA concentrations. To determine the role of mucous-associated lymphoid tissue (MALT) in the elevation of serum IgA in RA, we studied the serum secretory-IgA (s-IgA) in 63 RA patients and in 30 healthy controls. We also analysed the secretion of circulating B cells producing IgA, which is known to reflect mucous tissue activity, in a subgroup of 15 patients with increased serum IgA concentrations, and in control patients. The mean s-IgA in the RA patients was 0.046 mg/ml +/- 0.064, versus 0.002 +/- 0.004 mg/ml in controls (not significant). Active disease defined by clinical criteria was associated with an increase in serum s-IgA (p < 0.001). Furthermore, in a subgroup of RA patients with high serum IgA levels, we found an increase in in vitro IgA production by circulating blood lymphocytes (17.39 +/- 15.2 micrograms/ml), versus RA patients with normal serum IgA levels or controls (p < 0.001). These results were not modified by LPS or PWM. Our results further support the hypothesis of primary MALT activation following environmental antigenic stimulation in RA patients.

Objective: To determine whether a small CD3+ lymphocyte population expressing 110-kd CD57 antigens (HNK1) is expanded in patients with rheumatoid arthritis (RA), as it is in patients who have undergone bone marrow transplantation and patients with the acquired immunodeficiency syndrome, and to investigate whether it is involved in the pathogenesis of RA., Methods: The phenotype of CD3+, CD57+ lymphocytes was analyzed by flow cytometry, and correlations between the percentage of these cells in the blood and various clinical and biologic parameters were investigated., Results: The percentage of CD3+, CD57+ lymphocytes was increased in RA patients compared with controls. These lymphocytes expressed T cell receptor alpha/beta. Eighty percent expressed the CD8 accessory molecule, and 20% expressed the CD4 accessory molecule. The leukocyte common antigen CD45RA isoform was expressed by these CD3+, CD57+ lymphocytes in blood. The HLA-DR antigen was expressed in synovial fluid but not in blood. Finally, the percentage of these lymphocytes in the blood correlated with the duration of RA., Conclusion: The expansion of the CD3+, CD57+ lymphocyte population and their activation in the synovial fluid of RA patients suggest that these cells are involved in the inflammatory process.

Sulfasalazine is an efficient treatment for rheumatoid arthritis (RA), but its mode of action is not known. In RA, a correlation has been demonstrated between disease activity and the secretion of immunoglobulin A (IgA) by peripheral blood lymphocytes (PBL) in culture. Furthermore, the IgA-producing cells of the peripheral blood have been shown to originate from the mucous-associate lymphoid tissue (MALT). We studied the variations in the total IgA concentration in the serum of RA patients, and the secretion of IgA by PBL after 7 days culture in vitro, before and after treatment with sulfasalazine. A significant decrease in the serum IgA concentration was obtained, but there was no modification of the spontaneous increase in the in vitro IgA synthesis by circulating mononuclear cells. Our results suggested that the decrease in serum IgA concentration after treatment with sulfasalazine was not linked to a decrease in the IgA secretion by PBL. This does not favour a direct effect of sulfasalazine on the mucous-associated lymphoid tissue.

A meningoencephalitis Behçet's disease revealing is reported. Magnetic resonance imaging is more sensitive than computerized tomography in detecting encephalitic lesions. However, no specific pattern may be retained. This exploration is non invasive and can be used to monitor the evolution after treatment.

Constrictive pericarditis is a rare complication of rheumatoid arthritis, with 78 published cases. We report a new typical case where the pericardial disease was associated with a severe seronegative rheumatoid arthritis of 17 years duration. Constrictive pericarditis generally occurs in men (62.8% of all cases) aged 52.4 +/- 11.5 years. Its clinical features are identical with those of constrictive pericarditis due to other causes. Diagnosis rests on echocardiography and, chiefly, on right heart catheterization. The arthritis is seropositive in 85.7% of the cases, frequently nodular (75%) and advanced. There is no relation between its duration (mean: 9.6 +/- 7.4 years) and the occurrence of the pericardial pathology. The pericardial fluid has no specific abnormality. Histology shows fibrosis and a non-specific inflammatory cell infiltrate. Immunoglobulin and complement deposits in the walls of the pericardial vessels are detected by immunofluorescence. The only treatment is pericardiectomy; without it the disease is constantly lethal.

The occurrence of ossifying enthesopathy during treatment with synthetic retinoids (etretinate, isotretinoin and acitretin) is a side-effect more and more frequently recorded. The authors report here a new case in a patient with a severe psoriatic arthritis. This observation is characterized by the size of ossifications on hips and lumbar spine which appeared after two years of etretinate therapy. The interest of this observation lies in the fact that ossifications occurred while the patient was treated with long-term corticotherapy. The disease for which retinoids are prescribed does not seem to influence the occurrence of those lesions and it is likely that the responsibility of these molecules is entire. Lesions are enthesitis ossification. They are frequent during these treatments (average of 70%) after an average time of 24 to 36 months for etretinate and of 10 months for isotretinoin. Lesions are asymptomatic in about 50% of the cases. After discontinuation of treatment, lesions become quiescent and does not disappear. Growth hormone or abnormalities in vitamin A metabolism could play a role in the physiopathology of lesions.