Rheumatoid Arthritis: Pavelka K

Senolt L, Braun M, Olejárová M, Forejtová S, Gatterová J, Pavelka K. · Institute of Rheumatology, Na Slupi 4, 12850 Prague 2, Czech Republic. · Ann Rheum Dis. · Pubmed #15897309 links to  free full text

Abstract: BACKGROUND: Pentosidine, an advanced glycation end product, increasingly accumulates in articular cartilage with age, and contributes to the pathogenesis of osteoarthritis (OA). Increased pentosidine concentrations are associated with inflammatory disorders-for example, rheumatoid arthritis. OBJECTIVE: To compare pentosidine serum concentrations in patients with knee OA and in healthy volunteers and to determine a relationship between pentosidine and cartilage oligomeric matrix protein (COMP)-a marker of articular cartilage destruction. METHODS: Paired serum and synovial fluid samples were obtained by arthrocentesis from 38 patients with knee OA and from 38 healthy volunteers. Pentosidine concentration was measured by reverse phase high performance liquid chromatography with fluorescent detection and COMP was determined by sandwich ELISA. RESULTS: Significantly increased serum pentosidine (p<0.01) and COMP (p<0.05) levels were detected in the patients with OA compared with the control group. Serum pentosidine correlated significantly with synovial fluid pentosidine (p<0.001). Pentosidine in synovial fluid (p<0.05) and in serum (p<0.05) correlated significantly with synovial fluid COMP. Pentosidine and COMP concentrations did not correlate significantly with the radiological stage of the disease. CONCLUSION: Increased pentosidine serum concentration in patients with OA and its correlation with the cartilage destruction marker COMP in synovial fluid suggests that pentosidine may be important in OA pathology and is a new potential OA marker.

Klézl Z, Olejárová M, Veselá M, Sedová L, Pavelka K. · Ortopedicko-traumatologické oddelení VN, Praha. · Acta Chir Orthop Traumatol Cech. · Pubmed #15456097 No free full text.

Abstract: PURPOSE OF THE STUDY: Patients with rheumatoid arthritis (RA) often suffer from instability of the upper cervical spine. The most common instability is anterior atlanto-axial subluxation (AAS). Instability may lead to neurologic deficits from spinal cord compression and intractable pain, decreasing quality of life and its length. MATERIAL AND METHODS: This prospective study analyzed different fixation methods and the influence of atlanto-axial and occipito-cervical fusion on clinical and radiological outcome. 41 patients with RA with instability of the upper cervical spine were treated surgically for progressive instability, pain and neurological deficit. Average age of our patients was 52.4 years (21-76 years). At the time of surgery, duration of the disease was in average 18.6 years (2-47 years). Patients had advanced stage of the disease according to Steinbroker, on hands stage 3.7 and feet stage 2.9. Atlanto-axial fixation was done for AAS in 27 (24 Magerl transarticular fixations and Brooks-Jenkins technique in 3 patients). Occipito-cervical fusion was done in 13 patients (3 with Ransford loop and sublaminar wires and 9 with CerviFix). One patient was managed in halo-cast fixation. Spinal fusion was performed in all patients using autologenous bone graft. Patients were evaluated by using Functional Rating Index (FRI), Health Assessment Questionnaire (HAQ) and visual pain analogue scale (VAS) before and after surgery in set intervals, when radiological examination was also performed including dynamic films. RESULTS: Three patients died in the postoperative period (3 weeks, 11 and 18 months). 38 patients remained for follow up, which was in average 28.4 months. Fusion was considered when hardware was intact and patient was satisfied, no motion was detected on dynamic X rays or bony fusion was clearly visible. Fusion was assessed in 40 patients, 32 fused, 8 had fibrous non-union. 3 of these patients had hardware failure. 9 patients had preoperatively verified panus formation peridentally, which resorbed after the surgery. FRI evaluation was done in 40 patients, 30 improved (14 patients by more than 10 points), 6 patients did not change and 4 worsened. The improvement after 3 and 12 months was statistically significant (p < 0.001). Average HAQ score decreased after surgery, but the change was not statistically significant (p > 0.05). Average VAS score decreased significantly after surgery (p < 0.05). There were 5 hardware related complications including one vertebral artery injury. None of these complications required subsequent surgery nor had any influence on good clinical outcome. DISCUSSION: Results of FRI and VAS show the benefit from early indication of surgical stabilization of upper cervical spine in patients with RA. Based on our experience, as well as other authors, fixation of AAS by transarticular screw fixation according to Magerl is the preferred method in the younger patient group. Once destruction of the atlanto-axial joints, lateral subluxation or cranial migration of the dens is present, occipito-cervical fusion using titanium malleable implant (CerviFix) is necessary. CONCLUSION: Positive clinical outcomes advocate early surgical intervention as described in recent literature. Surgery prevents subsequent neurological damage life quality deterioration and shortening of life expectancy.

Vilím V, Vobůrka Z, Vytásek R, Senolt L, Tchetverikov I, Kraus VB, Pavelka K. · Institute of Rheumatology, Na Slupi 4, 128 50 Prague 2, Czech Republic. · Clin Chim Acta. · Pubmed #12559599 No free full text.

Abstract: BACKGROUND: Cartilage oligomeric matrix protein/thrombospondin 5 (COMP/TSP 5) is one of the most promising serologic markers with regard to an ability to prognose development of osteoarthritis (OA). Our aim was to map the epitopes of three monoclonal antibodies (mAb) to COMP and to develop and characterize a sandwich enzyme-linked immunosorbent assay (ELISA) for measuring COMP levels in human body fluids. METHODS: COMP was digested with trypsin and the NH(2)-terminal sequence of the fragments recognized by each of the mAbs was determined. Steric competition among the mAbs was tested with an antibody capture assay. A sandwich ELISA was developed using unlabeled mAb 16-F12 as a capture antibody, and mAb 17-C10 labeled with biotin as the second antibody. RESULTS: Epitopes of the three mAbs were mapped to three different domains within the COMP subunit (16-F12, NH(2)-terminal domain; 17-C10, EGF-like domain; 12-C4, COOH-terminal domain). These epitopes did not overlap. mAbs 17-C10 and 12-C4 yielded similar serum COMP results when used as the secondary antibodies. Serum COMP levels measured with the new sandwich ELISA using mAbs 16-F12 and 17-C10 correlated strongly with results based on an inhibition ELISA with mAb 17-C10 alone (r(2) = 0.836; P < 0.0001). We characterized the new sandwich ELISA with regards to inter- and intra-assay variability, the range of COMP levels that can be expected in human synovial fluids (SF) and sera (controls and OA and rheumatoid arthritis (RA) patients), and the day-to-day and diurnal variability of COMP levels in sera. CONCLUSIONS: We have developed and characterized a sandwich ELISA for COMP that is sensitive and yields highly reproducible COMP results upon analysis of human sera and synovial fluids.

Pavelka K, Forejtová S, Pavelková A, Zvárová J, Rovenský J, Tuchynová A. · Institute of Rheumatology, HA Slupi 4, 12850 Prague, Czech Republic. · Clin Rheumatol. · Pubmed #12111628 No free full text.

Abstract: The aim of the study was to evaluate the efficacy and safety of disease-modifying drugs (DMARDs) in everyday clinical practice in Central European States (the Czech and Slovak republics). This was a retrospective, multicentre study. With the help of a special questionnaire, the medical files of 760 patients in 15 centres were analysed looking for reasons for DMARD discontinuation (e.g. insufficient efficacy, toxicity). The secondary endpoints were duration of therapy with individual DMARDs and the influence of other factors (demographic, disease specific, concomitant therapy) on duration of therapy. In 47.1 % of patients therapy was interrupted because of lack of efficacy, in 43.2 % because of adverse events, and in 9 % for undefined reasons. Toxic reactions leading to withdrawal were most common with gold (62.6 %) and methotrexate (62.5 %). Because of insufficient effect, treatment was most frequently interrupted with antimalarials (62.3 %) and penicillamine (53.2 %), but in only 22% treated with methotrexate. The mean duration of one treatment episode with DMARDs was 28.1 +/- 48.9 months. Surprisingly, it was longest for cyclophosphamide (53.5 + 55.1 months) and shortest for cyclosporin (7.0 +/- 6.7 months). The mean duration of treatment with methotrexate was only 14.9; +/- 16.2 months. The mean duration of treatment with one DMARD was statistically longer in patients with positive rheumatoid factor, extra-articular disease and age lower than 50 years. There was no impact of sex, concomitant steroid treatment and high or low sedimentation rate on treatment duration. Considerable differences in everyday clinical practice with DMARDs between Central European states and published data from the US and western Europe have been found. More education about modern strategies in the treatment of RA is probably necessary for practising rheumatologists.

Desser L, Holomanova D, Zavadova E, Pavelka K, Mohr T, Herbacek I. · Institute of Cancer Research, University of Vienna, Austria. · Cancer Chemother Pharmacol. · Pubmed #11561866 No free full text.

Abstract: Therapy with oral proteolytic enzymes (OET) with combination drug products containing papain, bromelain, trypsin, and chymotrypsin has been shown to be beneficial in clinical settings such as radiotherapy-induced fibrosis, bleomycin pneumotoxicity and immunosuppression in cancer, all of which are nowadays known to be accompanied by excessive transforming growth factor-beta (TGF-beta) production. It has been demonstrated that proteolytic enzymes reduce TGF-beta levels in serum by converting the protease inhibitor alpha2 macroglobulin (alpha2M) from the "slow" form into the "fast" form, whereby the "fast" form binds and inactivates TGF-beta irreversibly. In this study we have investigated the effect of OET on the concentration of TGF-beta1 in serum of patients with rheumatoid arthritis (RA) (n = 38), osteomyelofibrosis (OMF) (n = 7) and herpes zoster (HZ) (n = 7). Seventy-eight healthy volunteers served as controls. TGF-beta1 levels in serum were assessed by enzyme-linked immunosorbent assay (ELISA). We have demonstrated that in healthy volunteers and in patients there exists a correlation between active and latent TGF-beta1 in serum (r=0.8021; P<0.0001). Treatment with OET had no significant effect on TGF-beta1 concentration in healthy volunteers or patients with a normal level of TGF-beta1. In patients with elevated TGF-beta1 concentration (> 50 ng/ml serum), OET reduced TGF-beta1 in RA (P < 0.005), in OMF (P < 0.05) and in HZ (P < 0.05). Conclusion: These results support the concept that OET is beneficial in diseases characterized in part by TGF-beta1 overproduction.