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J Sany

Publications and source records attributed to J Sany.

At least 91 records · Page 5Linked to original sources
PubMed1994

Efficacy and tolerability of a new formulation of oral tiludronate (tablet) in the treatment of Paget's disease of bone.

We sought to assess efficacy and safety of a new oral formulation (tablet) of tiludronate in Paget's disease of bone. We studied 128 patients with Paget's disease in an open-label uncontrolled trial. Patients received a daily dose of 400 mg oral tiludronate (two tablets). Treatment was for 6 months. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatine (OH/Cr) were measured every 3 months, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self-evaluated from a visual analog scale (VAS). Statistical analysis revealed a significant reduction from baseline in SAP and OH/Cr levels, as well as VAS scores. In the whole population with evaluation under treatment, there was a reduction in initial SAP activity after 3 months (47.2 +/- 2.2%, mean +/- SEM) and 6 months (58.3 +/- 2.3%). In the population with SAP levels above twice the upper limit at inclusion and with evaluation at month 3 and month 6 (n = 96), the reduction in SAP levels was 49.3 +/- 2.4% after 3 months and of 59.5 +/- 2.6% after 6 months (ANOVA time effect, p = 0.0001). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance was good. Exhaustive biochemical investigation failed to reveal significant toxicity of tiludronate tablets at the dose of 400 mg/day. The dose of 400 mg daily of this new formulation appears to be a satisfactory tiludronate regimen for the treatment of Paget's disease of bone.

Aged↗
PubMed1994

Intravenous immunoglobulin therapy for rheumatic diseases.

Although clearly demonstrated in idiopathic thrombocytopenic purpura and Kawasaki disease, the efficacy of intravenous immunoglobulins in the treatment of rheumatic and connective tissue diseases remains to be confirmed in double-blind placebo-controlled studies. This article is a review of some rheumatic and connective tissue diseases (ie, rheumatoid arthritis, juvenile rheumatoid arthritis, Still's disease, systemic lupus erythematosus, dermatomyositis-polymyositis, and vasculitis) in which anecdotal open studies occasionally have shown impressive clinical and biologic results with good tolerance. Intravenous immunoglobulins contain idiotypic antibodies directed against pathologic autoantibodies and appear to be an interesting source of immunomodulating antibodies, which could be useful in the treatment of autoimmune diseases.

Arthritis, Rheumatoid↗
PubMed1994

Human mucosyl lymphocyte marker expression in synovial fluid lymphocytes of patient with rheumatoid arthritis.

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.

Adult↗
PubMed1994

Effect of etodolac on methotrexate pharmacokinetics in patients with rheumatoid arthritis.

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.

Adult↗
PubMed1993

Increased percentage of CD3+, CD57+ lymphocytes in patients with rheumatoid arthritis. Correlation with duration of disease.

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.

Adult↗
PubMed1993

Variation in the serum IgA concentration and the production of IgA in vitro in rheumatoid arthritis treated by sulfasalazine.

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.

Arthritis, Rheumatoid↗
PubMed1993

Investigation of the HLA component involved in rheumatoid arthritis (RA) by using the marker association-segregation chi-square (MASC) method: rejection of the unifying-shared-epitope hypothesis.

In order to investigate the HLA component involved in rheumatoid arthritis (RA), we tested genetic models by the marker association-segregation chi 2 (MASC) method, using the HLA genotypic distribution observed in a sample of 97 RA patients. First we tested models assuming the involvement of a susceptibility gene linked to the DR locus. We showed that the present data are compatible with a simple model assuming the effect of a recessive allele of a biallelic locus linked to the DR locus and without any assumption of synergistic effect. Then we considered models assuming the direct involvement of the DR allele products, and we tested the unifying-shared-epitope hypothesis, which has been proposed. Under this hypothesis the DR alleles are assumed to be directly involved in the susceptibility to the disease because of the presence of similar or identical amino acid sequences in position 70-74 of the third hypervariable region of the DRBI molecules, shared by the RA-associated DR alleles DR4Dw4, DR4Dw14, and DR1. This hypothesis was strongly rejected with the present data. In the case of the direct involvement of the DR alleles, hypotheses more complex than the unifying-shared-epitope hypothesis would have to be considered.

Adult↗
PubMed1993

[A comparative controlled trial of 2 administration modalities of tiopronin in rheumatoid arthritis].

Thiopronin is a second line drug for rheumatoid arthritis with proven efficacy in controlled trials versus a placebo, D-penicillamine, or gold salts. This 4-month study was aimed mainly at comparing the efficacy and safety of two thiopronin regimens, i.e., 1 g/d for 2 weeks followed by 1.5 g/d (regimen A) versus 0.5 g/d for 1 month, 0.750 g/d during the second month, then 1 g/d (regimen B). Because earlier investigations have suggested a role for copper in the activity of D-penicillamine, a secondary goal of this study was to evaluate whether the clinical effects of thiopronin were related to changes in serum copper and ceruloplasmin levels. Among the 61 included patients, 32 received regimen A and 29 regimen B. The primary efficacy criterion was the physician's overall efficacy assessment. Efficacy was rated good or excellent in 65.5% of regimen A patients and 55.6% of regimen B patients. Eighteen of the 32 regimen A patients and 23 of the 29 regimen B patients experienced at least one adverse event (p = 0.055). Failure to tolerate the drug required withdrawal in 12 of the 32 regimen A patients (37.5%) versus 11 of the 29 regimen B patients (37.9%). Declines in serum copper and ceruloplasmin levels were not correlated with treatment efficacy or tolerance. These findings, together with previously reported data, suggest that treatment should be initiated in a dosage of 1 g/day and that thiopronin-related adverse events are not dose-dependent.

Adult↗
PubMed1993

Accelerated nodulosis and systemic manifestations during methotrexate therapy for rheumatoid arthritis.

OBJECTIVES: Methotrexate is successfully used in the treatment of arthritis but little is known about its effects on extra-articular manifestations of rheumatoid arthritis. We focused this work on the incidence and clinical course of extra-articular manifestations during long-term treatment with methotrexate. METHODS: The effect of methotrexate on extra-articular manifestations was investigated in 176 patients with rheumatoid arthritis who had obtained, in a prospective study, a good clinical response to methotrexate (10 mg/week) taken for 33 months (range 4-68). RESULTS: Before taking methotrexate, 44 patients (25.1%) had extra-articular manifestations: nodules (n = 40) and vasculitis (n = 9). With methotrexate, nodulosis and vasculitis were stable in 31 cases, improved in 3 and worsened in 10 (23%). Among the 132 patients without extra-articular manifestations before methotrexate therapy, 15 (11%) developed accelerated nodulosis preferentially located on the fingers, 7 had a vasculitis and 3 a pericarditis during methotrexate therapy. Extra-articular manifestations occurred between 1 and 24 months of initiating methotrexate therapy. Rheumatoid factor was positive in 88% of the patients with extra-articular manifestations. No relationship was noted between extra-articular manifestations and HLA type or antinuclear antibodies. In 3 out of 4 patients who developed accelerated nodulosis while taking methotrexate, the addition of hydroxychloroquine (400 mg/day) resulted in a significant reduction in the number and size of the nodules within 3 to 10 months after starting combined therapy. CONCLUSION: These data suggest that methotrexate is not effective in the treatment of extra-articular manifestations in rheumatoid arthritis and that nodulosis may occur in about 11% of patients taking methotrexate therapy for rheumatoid arthritis. The combination of hydroxychloroquine and methotrexate may have a beneficial effect on nodulosis that needs to be evaluated.

Adolescent↗
PubMed1993

[New immunologic treatment of rheumatoid arthritis].

Rheumatoid arthritis is a heterogeneous disease for which no satisfactory therapy is available. Conventional treatments have nonselective immunological effects. Cyclosporin A ensures partially selective immunotherapy. Recently developed selective immunotherapy methods target CD4+ T-cells and their receptors, antigen-presenting cells including macrophages with surface expression of class II HLA antigens, antigen peptide(s) presented by macrophages, class II HLA antigens or T-cell receptors. T-cell suppression can be achieved using monoclonal antibodies or the still experimental T-cell vaccination. Monoclonal antibodies against activation antigens, including CD4, CD5, CD25 (interleukin 2 receptor), CD52, and adhesion molecules, have been investigated in animal studies and open trials in humans. Monoclonal antibodies directed against class II HLA antigens or antigen-presenting cells have been studied in animals. Peptide immunotherapy has yielded promising results in a variety of animal models. Other immunotherapy methods target cytokines, especially those which promote inflammation. Encouraging preliminary results have been obtained in rheumatoid arthritis patients with interleukin-1 receptor antagonists and monoclonal antibodies against tumor necrosis factor alpha. Problems raised by selective immunotherapy for rheumatoid arthritis and potential indications are discussed.

Animals↗
PubMed1993

Influence of methotrexate on the frequency of postoperative infectious complications in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the influence of methotrexate (MTX) on the frequency of postoperative complications in patients with rheumatoid arthritis (RA). METHODS: We conducted a randomized unblinded prospective study in 64 patients with RA treated with MTX and who underwent orthopedic surgery. Two groups of patients were constituted: in Group A (32 patients), MTX was interrupted 7 days before the surgery; in Group B (32 patients), MTX was not discontinued. RESULTS: Fifty surgical procedures were performed in Group A and 39 procedures in Group B. No postoperative infection was observed in any group. A prolonged wound healing was noticed in 6 cases in Group A and in 4 cases in Group B (not significant). CONCLUSION: We suggest that the interruption of MTX is not required in patients with RA when an orthopedic surgical treatment is planned. However a large prospective study is needed to make a definitive conclusion.

Adult↗
PubMed1992

The B cell repertoire in rheumatoid arthritis. III. Preferential homing of rheumatoid factor-producing B cell precursors in the synovial fluid.

OBJECTIVE: We sought to compare the frequencies of precursors producing IgM rheumatoid factors (IgM-RFs) in synovial fluid and peripheral blood B cells from patients with rheumatoid arthritis (RA). METHODS: We used limiting-dilution analysis of Epstein-Barr virus-activated B cells from seropositive and seronegative patients. B cell precursors producing IgM against insulin, an irrelevant autoantigen, were also assessed for comparison. RESULTS: On average, IgM-RF-producing precursors were 15-fold higher in the synovial fluid than in the peripheral blood of seropositive RA patients, but not in seronegative RA patients. The frequency of B cell precursors producing IgM against insulin was lower in the synovial fluid than in the peripheral blood of both the seropositive and the seronegative patient groups; moreover, the concentrations were similar in both groups. CONCLUSION: The findings provide evidence against a nonspecific accumulation of IgM-producing cells in the synovial fluid, and suggest that there is an active attraction of the RF-producing B cell precursors toward sites of inflammation in RA.

Adult↗