Objective: to study the incidence rates of angina, myocardial infarction (MI), stroke, and the frequency of endovascular interventions in patients with systemic vasculitides, and the incidence rate of atherosclerosis according to autopsy data. Subjects and methods. Three hundred and twenty-one patients with systemic vasculitides: Wegener's granulomatosis (n = 138), Takayasu's arteritis (n = 79), polyarteritis nodosum (n = 55), and Churg-Strauss syndrome (n = 49) were examined; 55 autopsies were analyzed in patients with the above diseases. Results. Fifty-one (15.6%) of the 321 patients were diagnosed as having cardiovascular diseases (CVD): angina pectoris (7.1%) and MI (3.1%) and endovascular interventions (0.9%). The risk of cardiovascular events was found to be associated with traditional risk factors, such as male gender and age. Arterial hypertension, hypercholesterolaemia, and increased serum creatinine were more frequently detected in the CVD group that showed no significant differences from the non-CVD group. According to autopsy results, atherosclerosis was identified in the patients with Wegener's granulomatosis (52%), Takayasu's arteritis (50%), polyarteritis nodosum (52.6%), and Churg-Strauss syndrome (57.1%). Conclusion. CVD and atherosclerosis are common in systemic vasculitides, which requires the traditional risk factors of atherosclerosis to be actively corrected.

Objective: to study vascular responsiveness parameters in rheumatoid arthritis (RA) patients with and without left ventricular diastolic dysfunction (DD) and to identify the predictors of DD among the characteristics of vascular responsiveness in RA patients having no cardiovascular diseases. Subjects and methods. The investigation enrolled 61 RA patients (mean age 47.1 years; 87% of females) without cardiovascular comorbidity. All the patients underwent standard echocardiographic study with diastolic function assessment in accordance with the 2005 European Society of Cardiology guidelines. Vascular responsiveness was studied using brachial artery Doppler ultrasonography in a 5-minute compression test. Associations between vascular responsiveness parameters and DD were studied using logistic regression models and adjusting for patient gender and age. Results and discussion. DD was found in 35 (57%) patients. The parameters of vascular responsiveness in RA patients with DD differed from those in RA patients without DD. The decrement in blood flow volumetric velocity in the brachial artery 10 sec (odds ratio [OR] 0.8; 95% confidence interval [CI] 0.7-0.97), and 1 min (OR 0.7; 95% CI 0.5-0.96) after decompression and the relative increment in blood flow volumetric velocity within the first minute after decompression (OR = 0.9; 95% CI 0.9-0.99) were associated with the presence of DD. There were no statistically significant associations of the changes in brachial artery diameter with DD. Conclusion. The decrement in blood flow volumetric velocity in the brachial artery, as evidenced by the compression test, is associated with DD in RA patients without cardiovascular diseases. The association of impairments in vasomotor and diastolic functions in RA shows the commonness of pathogenic mechanisms for the development of these changes and opens considerable scope for the earlier diagnosis of DD according to the results of the study of vascular responsiveness.

Objective: to study coagulative and vascular-thrombocytic hemostases in patients with rheumatoid arthritis (RA) and coronary heart disease (CHD) depending on therapy with different nonsteroidal anti-inflammatory drugs (NSAIDs) alone and in combination with low-dose aspirin. Subjects and methods. The trial enrolled 58 patients (43 women and 15 men) with a valid diagnosis of RA. The patients' mean age was 61.2 years; the disease duration averaged 10 years. All the patients received therapy with disease-modifying antirheumatic drugs (DMARDs) and NSAIDs. All had CHD; 52 of the 58 patients presented with arterial hypertension; 30 had noncoronary atherosclerosis. Cardiovascular diseases were first identified in 18 patients. All took heart medications. Coagulative and vascular-thrombocytic hemostases were studied in all the patients and the results were compared depending on to the taken NSAID (diclofenac, tenoxicam, nimesulide, meloxicam). Thirty-seven patients who had not previously received antiaggregant therapy were given aspirin in a dose of 100 mg when they were found to have platelet hyperaggregation and aggregation was restudied on aspirin therapy days 7-8. A control group consisted of 26 healthy men (mean age 55 years) who received no medications. Results. In patients with RA and CHD, activated coagulative hemostasis was identified in 65.5% of cases. The signs of hypercoagulation were observed in 35 of the 58 patients. When different NSAIDs were used, the coagulative hemostatic changes were unidirectional and no statistically significant differences were found between the groups. The patients taking diclofenac, nimesulide, or meloxicam were found to have activated vascular-thrombocytic hemostasis. Those receiving tenoxicam showed a tendency towards decreased adrenaline-induced platelet aggregation (the drug's aspirin-like effect); however, no statistical processing was made because of few cases. The use of aspirin in the patients taking diclofenac, nimesulide, or meloxicam resulted in lower platelet aggregation in the vast majority of cases despite NSAID intake. No adequate aspirin response was obtained in 32.4% of the patients. Conclusion. Aspirin is indicated in RA and CHD patients receiving NSAIDS. Antiaggregant therapy should be used under control of vascular-thrombotyc hemostasis as aspirin is insufficiently effective in one third of cases in this group.

Objective: to investigate the association of HLA Class I antigens with the predisposition to psoriatic arthritis (PsA) and the severity and types of articular syndrome in PsA. Subjects and methods. The investigation enrolled 99 patients (56 females and 43 males) aged 43.5+13 years with PA with a median duration of 2 (range 0.8-10) years. An oligoarthritic type was observed in 28 patients, polyarthritic, distal, and spondyloarthritic types were present in 28, 39, and 10 patients, respectively. Two patient groups were formed according to the age at onset of psoriasis: 1) 71 patients aged less than 40 years and 2) 23 patients aged over 40 years. Results. As compared with the control group, the patients with PsA were found to have a higher frequency of HLA-B13 (odds ratio [OR] 2.72; p < 0.004), HLA-В16 (OR 3.95; p < 0.0001), and HLA-B27 (OR 3.2; p < 0.003). There was an association of the types of joint injury with HLA antigens: the distal type with HLA-B13 (OR 3.38; p < 0.02) and HLA-В16 (OR 3.95; p < 0.01), the polyarthritic type with HLA-В16 (OR 5.90; p < 0.0001) and HLA-B27 (OR 3.26; p < 0.01), and the spondyloarthritic type with HLA-B27 (OR 6.32; p < 0.001). The young onset of psoriasis was associated with HLA-B13 (OR 3.29; p < 0.001). The detection rate of the B38 antigen (the subtype of HLA-B16) was higher in all X-ray stages of PsA and was 16.4% in Stages I-IIA, 25% in Stage IIB, and 40.9% in Stages III-IV versus 8.7% in the control group, the magnitude of the association being increased with the higher degree of joint destruction. Conclusion. The detailed analysis of the investigation revealed that HLA system antigens were differently involved in the development of PsA and clinical types of articular syndrome.

Objective: to estimate the significance of SAA1 gene polymorphism in the development of AA amyloidosis in patients with rheumatoid arthritis (RA) in the Moscow population. Subjects and methods. The investigation included 57 RA patients treated at the clinic of the Research Institute of Rheumatology, Russian Academy of Medical Sciences, for histologically verified AA amyloidosis. In 41 of them, polymorphism of exon 3 of the SAA1 gene (SNP rs1136747 c.224T→C and SNPrs1136743 c.209C→T) was studied by polymerase chain reaction and restriction fragment length polymorphism analysis. Results. The carriage of the а/а genotype increases the likelihood of AA amyloidosis by 3 times in patients with RA (odds ratio (OR) = 3.0; p = 0.007). At the same time, the presence of allele β in the α/β genotype epistatically suppresses the action of allele α, by showing a 3-fold reduction in the risk of secondary amyloidosis in RA patients who were carriers of this genotype. Conclusion. The а/а genotype at the SAA1 locus is a risk factor for AA amyloidosis in patients with RA in the Moscow population; at the same time its presence of allele β in the heterozygous or homozygous state is a factor for preventing the development of this complication.

Objective: to study the expression ratio of the non-tissue specific regulatory genes mTOR, р21, ATG1, caspase 3, tumor necrosis factor-а (TNF-а), and interleukin-6 (IL-6), as well as matrix metalloproteinase 13 (MMP-13) and X type collagen (COL10A1), cartilage resorption-associated MMP13 and COL10A1 in the blood and knee articular cartilage in patients with rheumatoid arthritis (RA). Subjects and methods. Twenty-five specimens of the distal femoral articular cartilage condyles were studied in 15 RA patients (mean age 52.4+9.1 years) after endoprosthetic knee joint replacement and in 10 healthy individuals (mean age 36.0+9.1 years) included into the control group. Twenty-eight blood samples taken from 28 RA patients (aged 52+7.6 years) prior to endoprosthetic knee joint replacement and 27 blood samples from healthy individuals (mean age 53.6+8.3 years; a control group) were also analyzed. Real-time quantitative polymerase chain reaction was applied to estimate the expression of the mTOR, p21, ATG1, caspase 3, TNF-а, IL- 6, COL0A1, and MMP-13 genes. The levels of a protein equivalent in the p70-S6K(activated by mTOR), p21, and caspase 3 genes concerned was measured in the isolated lymphocyte lysates, by applying the commercially available ELISA kits. Total protein in the cell extracts was determined using the Bradford assay procedure. Results. The cartilage samples from patients with end-stage RA exhibited a significantly higher mTOR, ATG1, p21, TNFа, MMP-13, and COL10A1 gene expressions than did those from the healthy individuals. At the same time, IL6 gene expression was much lower than that in the control group. The expressions of the mTOR, ATG1, p21, TNFа, and IL 6 genes in the blood of RA patients were much greater than those in the donors. Caspase 3 expression did not differ essentially in the bloods of the patients with RA and healthy individuals. The bloods failed to show MMP-13 and COL10A1 expressions. High mTOR and p21 gene expressions were accompanied by the elevated concentrations of the corresponding proteins in the cell lysates of the patients with RA compared to the controls. Conclusion. The findings suggest for the first time that regulatory mTOR, ATG1, p21, and TNFа gene expressions are enhanced in the blood and articular cartilage of RA patients. These changes are accompanied by the increased expression of MMP 13 gene that is responsible for articular cartilage resorption. Therefore, the higher expression of the examined regulatory genes in the blood of RA patients may be indicative of articular cartilage degradation.

Objective: to evaluate the clinical efficiency of tocilizumab (TCZ) versus rituximab (RTM) therapy using DAS 28, SDAI, and CDAI scores and to estimate remission rates using DAS 28 and the remission criteria proposed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) in 2011. Subjects and methods. Seventy-six patients with rheumatoid arthritis (RA) divided into 2 groups were examined. Group 1 included 42 patients receiving six TCZ infusions in an intravenous dose of 8 mg/kg at a 4-week interval during stable therapy with disease-modifying antirheumatic drugs (DMARDs) and glucocorticosteroids (GC); Group 2 comprised 34 persons who were given two RTM infusions in intravenous doses of 500 and 1000 mg at 2-week interval during therapy with DMARDS and GC in 12 (35%) and 22 (65%) patients, respectively. The EULAR criteria and SDAI and CDAI scores were used to evaluate therapeutic effectiveness. Remission was assessed using the EULAR criteria and the new 2011 EULAR/ACR remission ones. Results. In Group 1, the baseline DAS 28, SDAI, and CDAI scores were 6.44 [5.87; 7.04], 45.0 [36.2; 57.0], and 41.5 [32.0; 53.0]; in Group 2, these were 6.12 [5.52; 6.81], 34.3 [23.8; 45.9], and 31.3 [21.8; 38.5], respectively. At week 24 of therapy, Groups 1 and 2 patients achieved a DAS 28 remission in 71 and 23.5% of cases, a SDAI remission in 31 and 14.7%, and a CDAI remission in 33 and 17.6%, respectively. In the RTM-treated patients who had not previously received therapy with genetically engineered biological agents (GEBAs), DAS 28, SDAI, and CDAI remissions were observed more frequently (38, 23.8, and 28.6%, respectively) than in those receiving GEBAs (0%; p < 0.01) and their rate was comparable with that in Group 1 patients (according to SDAI and CDAI scores). In Groups 1 and 2, the remission rates according to the 2011 ACR/EULAR criteria were 24 and 11.8%, respectively. Conclusion. The results obtained during a 24-week trial are indicative of the high clinical efficiency of TCZ and RTM therapy. The number of TCZ-treated patients who had achieved a DAS 28 remission were much more while SDAI and CDAI remission rates among the patients who had not previously received GEBAs were virtually comparable with those when TCZ and RTM were administered.

Objective: to evaluate the impact of the active introduction of clinical guidelines for the diagnosis and treatment of osteoarthrosis (OA) by primary care physicians on the efficiency of performed therapy and patient adherence to treatment. Methods. This was an open pragmatic cluster randomized controlled trial covering 16 general practitioners who completed the trial and 92 patients clinically diagnosed as having knee and/or hip OA (63 in the intervention group and 29 in the control group). The intervention involved a one-day didactic educational seminar for the physicians, printed guideline materials, and patient brochures. The control group physicians received no additional information support. WOMAC pain and stiffness scores, body mass index (BMI), adherence to treatment (nonsteroidal anti-inflammatory drugs (NSAIDs), therapeutic exercises, alternative treatments) at 6 and 12 months after the intervention were taken into account when evaluating therapeutic effectiveness. Results. In the intervention group, the mean WOMAC pain scores were 6.9 and 13.3 points lower than in the controls at 6 (p = 0.16) and 12 (p = 0.017) months, respectively. The mean WOMAC stiffness scores in the intervention group were 6.7 and 14.7 points lower than in the controls at 6 (p = 0.29) and 12 (p = 0.039) months, respectively. The proportion of the patients using an alternative treatment dramatically decreased in the intervention group by 23 and 33% at 6 (p = 0.044) and 12 (p = 0.024) months, respectively. In the intervention group, the change in other parameters was less conclusive: by the end of the year, BMI slightly decreased (-1 kg/m 2; p = 0.95); the regular usage of NSAID reduced by 3% at 6 month (p = 0.7) and then increased by 10% at 12 month (p = 0.21). Adherence to regular physical exercises in the intervention group was 13 and 9% higher than in the controls at 6 (p = 0.23) and 12 (p = 0.42) months, respectively. Conclusion. The introduction of the clinical guidelines for the diagnosis and treatment of osteoporosis by means of a didactic educational seminar in combination with the printed methodical materials and patient brochures being given to physicians may optimize treatment and improve patient outcomes, but trials involving a larger sample are needed to confirm this effect.

The efficiency of incorporating genetically engineered biological agents (GEBAs) into a combination treatment regimen for rheumatic diseases (RD) (juvenile idiopathic arthritis, Behcet's disease) in relation to associated uveitis of varying severity was studied in 92 children aged 2 to 17 years. The follow-up lasted 1.5 to 49 months. Twenty-three patients took consecutively 2 to 5 GEBAs. When infliximab was used, remission of uveitis occurred in 21% of 38 children and the disease activity and/or recurrence rates reduced in an additional 21%. These were in 45 and 38.6% of 44 patients on adalimumab (ADA) and in 27.8 and 27.8% of 18 patients on abatacept, respectively. There was an association of the efficiency of therapy with the severity of uveitis at the start of treatment. The use of ADA induced a steady remission of panuveitis resistant to therapy with glucocorticoids and cyclosporine in both patients with Behcet's disease. One of 4 rituximab-treated patients achieved a steady remission. Tocilizumab therapy caused an exacerbation of uveitis in 1 patient. The postoperative period showed no inflammatory complications in most cases (37 operations, 26 eyes, 20 patients). No local adverse reactions were seen; systemic reactions occurred in 14% of the patients, this caused GEBAs to be discontinued in 7%. There is evidence for a need for further investigations into the efficacy of GEBAs in RD-associated uveitis in children in order to define success criteria, differentiated indications, and therapy regimens.