The protein binding of piroxicam in synovial fluid and plasma from patients with rheumatoid arthritis was studied in vitro by equilibrium dialysis. The binding parameters were calculated from the experimental data with the Scatchard model, assuming binding to two classes of sites. Each plasma sample was diluted to an albumin concentration equal to that of synovial fluid from the same patient. The association constants for primary and secondary binding sites in the concentration range of piroxicam 4.5-90 X 10(-5) mol/l were similar in synovial fluid and in plasma. For synovial fluid K1 = 2.38 X 10(5) l/mol and K2 = 2.29 X 10(3) l/mol; for plasma K1 = 1.93 X 10(5) l/mol and K2 = 2.08 X 10(3) l/mol. The number of binding sites was also the same in the two fluids. Although the concentration of piroxicam in synovial fluid was about half that in plasma, the binding of piroxicam to protein in synovial fluid was the same as in plasma.
We used Alcian Blue (AB) and dimethylmethylene blue (DMB) methods to measure glycosaminoglycan (GAG) excretion in the first morning urine specimens of patients with osteoarthritis (OA), ankylosing spondylitis (AS), and rheumatoid arthritis (RA) in different stages of disease. By the AB method, urinary GAG excretion in patients with RA was not different from healthy control subjects. However, the DMB method showed significant differences (in milligrams of GAG per gram of creatinine) for OA (median 25.4, range 14.3-44.0, P less than 0.01, n = 23) and RA patients (median 33.0; range 10.0-147.6; P less than 0.001, n = 63) in comparison with unaffected individuals (median 20.2; range 8.9-41.4, n = 38). We noted a significant difference in urinary GAG excretion between RA and OA patients (P less than 0.01) and between RA and AS (P less than 0.01) patients. The DMB method was further investigated by clinical decision analysis. The DMB method is simple and rapid and may be useful in diagnosing RA by distinguishing between RA and OA or AS.
Background TNF-alfa blockers are highly effective for signs and symptoms in patients with ankylosing spondylitis (AS). Many clinical studies and data from various national registries assign concerns about serious infections, especially tuberculosis (TB). Objectives Our aim was to look on the incidence rate (IR) of TB infection in AS patients during anti-TNF therapy in Slovakia. Methods AS patients on anti-TNF treatment were retrospectively analyzed in Slovak national database of patients with biological therapy. This analysis covered AS patients on infliximab, etanercept, adalimumab and golimumab since March 3rd 2003, when the first patient was initiated on TNF-alfa blocker until December 31st 2012. Duration of anti-TNF treatment was calculated on patient-years (PY). IR for development of TB on 100 PY was calculated. The occurence of TB reactivation was subsequently analysed after initiation of national guidelines for screening of latent TB. Results 314 patients with AS on anti-TNF therapy, 278 men (89%) and 36 women (11%), were analysed. The mean age of patients at the time of initiation of TNF-alfa blockers was 39.27 (19-72) years. The time on biological treatment since the first patient was initiated until December 31st 2012 was calculated on 915 PY. 75 patients (72 men, 3 women) on infliximab were together treated 248 PY, 87 patients (71 men, 16 women) on etanercept 339 PY, 122 patients (112 men, 10 women) on adalimumab 286 PY, and 30 patients (23 men, 7 women) were under the treatment with golimumab 41 PY. The occurrence of pulmonary TB in AS patients treated by TNF-alfa inhibitors was found only in one patient on infliximab, and it was before the initiation of screening of latent TB. There was no case of active TB during etanercept, adalimumab or golimumab therapy. One patient on infliximab developed atypical mycobacterial infection of skin with histological finding of aquarium granuloma. One patient on etanercept had to stop treatment due to his contact with person with active TB, but after prophylactic treatment with isoniaside (INH) he could continue on biologic agent without development of active TB. Calculated incidence of TB infection (typical and atypical) in Slovak AS patients on anti-TNF therapy was 0.21/100 PY. The IR for reactivation of latent TB was calculated on 0.1/100 PY. After applying the national guidelines for screening of latent TB before starting TNF-inhibitors there was no case of TB reactivation in Slovak AS patients. There were 7 patients with positive IGRA test before starting infliximab, 5 patients before etanercept, 11 patients before adalimumab and 3 patients before starting golimumab. All patients with positive IGRA test underwent prophylactic treatment with INH and no reactivation of latent TB was observed. Conclusions The risk of TB infection in AS patients on anti-TNF therapy in Slovakia is 0.21/100 patient-years, with the IR for reactivation of latent TB during the treatment 0.1/100 patient-years. After applying national guidelines for screening latent TB before starting...
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