Objective. To estimate the extent and pattern of myocardial damage in different types of rheumatoid arthritis (RA) during disease-modifying antirheumatic drug (DMARD) or biological therapy.
Subjects and methods. Seventy-one patients with RA were examined; some of them received biological therapy with infliximab, while the others took DMARDs. A group of patients with incipient RA was also identified. B-type brain natriuretic peptide levels were estimated and electrocardiography, echocardiography (EchoCG), and cardiac magnetic resonance imaging (MRT) using the contrast medium Dotarem were conducted in all the patients. The follow-up totaled 6 months. A control examination was made at the moment of randomization and 6 months posttreatment.
Results. Tn the bulk of patients, the level of B-type brain natriuretic peptide did not differ from the reference values, however, its lower level was observed in the incipient RA group, which was associated with the absence of cardiovascular diseases and with a younger age group. There were no negative EchoCG changes in myocardial viability values. Cardiac MRT demonstrated that the majority of patients had the similar changes that failed to affect myocardial kinetics and ejection fraction. These changes were not found in incipient RA patients without cardiovascular diseases. No improvement in myocardial viability was recorded in the patients receiving the biological therapy.
Conclusion. Thus, cardiac MRT showed the similar changes that failed to affect myocardial kinetics and ejection fraction in patients with RA during both methotrexate and infliximab therapy.

The duration of continuous use of infliximab is more than 8 years in patients with ankylosing spondylitis (AS). The efficiency of the drug persists in most patients during its long-term regular therapy.
Objective. To evaluate the effectiveness and safety of long-term infliximab therapy in patients with AS, particularly in those with a treatment interruption of ≥16 weeks, and to analyze the effect of the drug on various clinical manifestations of AS.
Subjects and methods. The follow-up included 62 patients with a valid diagnosis of AS (New York criteria 1984) who received long-term (≥1 year) regular infliximab therapy in the Anticytokine Therapy Room, Research Institute of Rheumatology, Russian Academy of Medical Sciences. The dose of infliximab was 5 mg/kg. The following parameters: BASDAI and BASFI indices, global AS activity, the number of inflamed joints, enthesitis, and erythrocyte sedimentation rate were estimated in all the patients before therapy and each infusion. Improvement was determined by the ASAS criteria. Effectiveness was ascertained based on the maximum ASAS improvement that was observed per at least 75% of visits. Account was taken of the following clinical manifestations of AS: spondylitis, peripheral arthritis, coxitis, dactylitis, heel enthesitis, psoriasis, and inflammatory bowel diseases. A subgroup of 17 patients who had a forced increase in infliximab infusion intervals from 16 weeks to 3 years was separately identified in the study group.
Results. The mean age of all the patients was 32.7 years; the mean duration of AS was 13.4 years; the mean therapy duration was 2.5 years. The therapy was performed for more than 3 and more than 5 years in 13 and 22 patients, respectively. According to therapy response, all the patients were divided into 3 groups: 1) those with ASAS improvement; 2) those with partial remission; 3) those with secondary inefficiency. Partial remission was observed in 35 (57%) patients; ASAS 40 improvement was seen in 15 (24%); secondary inefficiency developed in 12 (19%) patients. Peripheral arthritis was significantly less common in the group of patients who had achieved partial remission versus those who had achieved 40% improvement and those who had developed secondary inefficiency (p < 0.05, Fisher's exact test). The reasons for a time break in therapy with infliximab were the absence of the drug (n = 11), Mantoux test conversion (n = 2), pregnancy (n = 2), adverse events (n = 2). The mean therapy break was 20.7 (range 16-144) weeks. After therapy resumption, persistent efficacy of infliximab remained in all the patients. During the first infusion after interruption, all the patients were given premedication with the H1- histamine receptor blocker cetirizine in a dose of 10 mg/day and 10 patients received additionally glucocorticoid (GC) premedication. Infusion reactions were observed in 4 (24%) patients during the second (after interruption) infusion without GC premedication. Infliximab was discontinued because of infusion reactions in 2 (12%) of these patients.
Conclusion. The majority of patients with AS could achieve persistent partial remission during long-term infliximab therapy. Secondary infliximab inefficacy occurred more commonly in patients with peripheral arthritis. When the treatment was forcedly interrupted, the efficacy of infliximab after therapy resumption was not decreased and its tolerability became slightly worse - infusion reactions were seen in 24% of the patients; 12% required infliximab to be discontinued because of infusion reactions. When therapy is resumed after its > 16- week interruption, it is expedient to use cetirizine for 5 days and/or premedication with GC (prednisolone in a dose of 50 mg or dexaven in a dose of 8 mg).

Objective. To evaluate the functional state of rheumatoid arthritis (RA) patients receiving Infliximab therapy (IF) in real clinical practice and its efficiency.
Subjects and methods. The analysis covered 225 patients receiving IF therapy, the follow-up duration in whom was 54 weeks. Disease activity was estimated by the DAS 28 index; functional status was assessed according to the Health Assessment Questionnaire (HAQ).
The authors made an analysis of a Per-Protocol (PP) population (n = 154) at 54 weeks of treatment and an analysis that could consider the results of treatment (by the ACR and EULAR criteria) in patients who had been withdrawn before the control time - a LOCF (Last Observation Carried Forward analysis) population.
Results. The mean age of the patients was 47.6±11.4 years; the duration of the disease was 7.8±6.4 years; DAS 28 activity scores were 6.6±1.1; the majority of patients had significant functional impairments (HAQ scores of 2.0±0.7), 86.7% of the patients had extraarticular manifestations; 79.6% were found to have rheumatoid factor (RF); the patients received an average of > 2 disease-modifying antirheumatic drugs (DMARDs).
After 2 week-therapy, there was a reduction in RA activity by DAS 28 index in both the PP (from 6.7±1.1 to 4.0±1.4) and LOCF (6.6±1.1 and 4.2±1.4; p < 106) populations.
Drug-induced remission (DAS 28 < 2.6) at 54 weeks was observed in 16.9 and 15.1% of the patients, respectively. Functional improvement was noted in the PP population: HAQ decreased from 2.0±0.7 to 1.7±0.7 scores by week 2; its reduction continued until week 14 (p < 0.05), by remaining stable later on. HAQ dropped from 2.0±0.7 to 1.2±0.7 scores in the LOCF population. At 54 weeks, normal population values of functional activity were achieved in 16.4%.
Log regression analysis in the LOCF population indicated that the previous use of DMARDs and a short history of the disease were predictors of an ACR70 response to IF therapy [OR=1.61 (1.13-2.30), p = 0.008 and OR = 0.91 (0.84-0.98), p = 0.018, respectively]. RF seronegativity was a predictor for achievement of low RA activity [OR = 0.44 (0.23-0.84)]. The previous use of glucocorticoids failed to increase the probability of a good response to IF therapy and achievement of clinical remission [OR = 0.26 (0.11-0.60), p = 0.001].
Conclusion. Therapy with IF in combination with methotrexate or other DMARDs reduces RA activity and improves the functional capacities of patients with RA in real clinical practice.

Endothelial dysfunction plays a key role in the pathogenesis of atherosclerosis. An increased cardiovascular risk in patients with rheumatoid arthritis (RA) suggests that inflammation is of importance for the occurrence and progression of atherosclerosis. Rituximab (RTM, monoclonal antibodies to CD20-positive B lymphocytes) is used to treat patients with active RA. Objective. To evaluate the effect of RTM on endothelial function in patients with active RA.
Subjects and methods. The study enrolled 20patients with active RA (DAS 28 >5.0); their mean age was 50 (range 41.5 to 63) years; mean disease duration was 95.7 (range 24 to 144) months. Intravenous RTM was used (as a course of 2 infusions in a dose of 1000 mg at a 2-week interval) in all the patients. Brachial artery flow-dependent vasodilation (FDVD) that was carried out in all the patients at screening (before the first infusion) and also at 2, 8, 16, and 24 weeks after the second infusion was employed to evaluate endothelial function.
Results. Before RTM therapy, the study group of patients showed no statistically significant deviations of FDVD values from those in the gender- and age-matched control group. FDVD correlated with age (r=-0.44; p=0.049), disease duration (r = 0.6; p=0.017), cholesterol level (r=0.48; p=0.045), common carotid artery intima-media thickness (r=0.52; p=0.023), and cardiovascular risk factors (r=0.51; p=0.027). No statistically significant differences were found in the baseline value of FDVD and those observed after a course of RTM therapy and at weeks 8, 16, 24 (12.8±5.7, 11.3±5.2, 14.3±7.1, and 12.5±5.2%, respectively). All the patients were
divided into 2 groups according to their response (an increase or a reduction in FDVD over time). Group 1 patients (n=10) demonstrated a significant increase in this index from 10.74±5.75 (at screening) to 14.17±5.13% (at week 24) (p<0.05). In Group 2 patients (n = 10), the reduction in FDVD was also statistically significant (from 14.87±5.15 to 10.88±4.89%). Four patients from Group 2 had endothelial dysfunction by week 24. Patients with improved endothelial function were found to have a longer RA duration (144±111 versus 47±38 months), a lower baseline C-reactive protein level (26.5 versus 35.6 mg/l), and a lower screening FDVD index ((10.1±5.8 versus 14.9±5.2%). No group differences found in age, disease activity (DAS 28), and cardiovascular risk factors and/or carotid artery atherosclerosis.
Conclusion. Our study has shown that the use of RTM generally fails to affect endothelial function in patients with active RA. The found heterodirectional postocclusive reactive hyperemia makes it necessary to widely introduce methods for evaluating the cardiovascular system in patients with RA.

Objective. To identify intrarenal hemodynamic disorders in patients with systemic lupus erythematosus (SLE), to assess their prognostic role, and to reveal an association between tubular dysfunction and intraglomerular hemodynamics.
Subjects and methods. Twenty-nine SLE patients, 86.2% of them were diagnosed as having a renal lesion, were examined. The levels of ethanolamine, uric acid, calcium, and phosphorus were determined in their daily urine and serum; the renal functional reserve (RFR) was estimated to detect intrarenal hemodynamic disorders.
Results. In the patients with SLE, RFR was considerably smaller: by an average of 6.0% (-25.9; 49.5%) than that in the control group: by an average of 30.9% (16.6; 46.8%); p <0.01. There was a direct correlation between the blood levels of ethanolamine and phosphorus, daily phosphorus excretion, and phosphate clearance and a correlation between the blood content of calcium and its clearance in relation to the RFR (p < 0.05).
Conclusion. The smaller and no RFR in patients without signs of nephropathy may suggest occult intrarenal hemodynamic disorders detected during the dopamine stress test. Tubular impairments in SLE were largely characteristic of patients with intrarenal hemodynamic disorders.

Objective. To estimate arterial rigidity parameters from noninvasive arteriographic readings in patients with gout and essential hypertension (EH). Subjects and methods. One hundred and twenty-eight patients with gout and EH were examined by noninvasive arteriography (Tensio Clinic TL1 arteriograph, Tensio Med, Hungary).
Results. In patients with gout, central artery stiffness is higher than that in healthy individuals and patients with EH and characterized by the increases in pulse wave velocity and augmentation index. Impaired arterial rigidity suggests that these changes play a prominent role in the pathogenesis of cardiovascular disorders in these patients.
Conclusion. By taking into account the findings and an increasing interest in the study of arterial stiffness as a reliable predictor of cardiovascular risk, there is a need for further investigations in this area to specify the mechanisms of cardiovascular disorders in gout.

Objective. To study the prevalence and origin of dyspnea in patients with rheumatoid arthritis (RA) and to specify its impact on exercise endurance (EE) and quality-of-life (QL) indices.
Subjects and methods. One hundred and four patients with RA and 100 patients without RA and chronic respiratory diseases were examined. General clinical examination was performed; QL was estimated using the Saint George's Respiratory Questionnaire and the EQ-5D; spirometry, body plethysmography, estimation of pulmonary diffusion capacity, pulmonary multislice spiral computed tomography (MSCT),
and echocardiography were made. Five patients with RA underwent cardiopulmonary testing on a graded exercise treadmill with gas analysis (ergospirometry).
Results. Dyspnea during exercise was reported by 54 (52%) patients with RA and 9 (9%) control patients (p < 0.001). Dyspnea was more frequently detected and more significant in RA patients with other symptoms of respiratory organ lesions (cough, sputum discharge, chest pain on breathing and coughing), anemia, and emotional disorders of the anxious-depressive type. The degree of dyspnea correlated with DAS 28 scores (r = 0.33; p < 0.01). No correlation was found between lung function parameters and blood gas composition. Pulmonary MSCT in RA patients with dyspnea more frequently revealed signs of bronchiolitis and lesion of the lung as its interstitial fibrotic type. Conclusion. Dyspnea is a common symptom and an important factor in reducing EE and QL in patients with RA. Dyspnea in these patients has a multifactorial origin. Of importance in its occurrence are the involvement of the lung and bronchi in the pathological process irrespective of the lung function, as well as RA-associated factors (including anemia), and nosogenic emotional disorders (anxiety and/or depression).

Objective. To evaluate the elastic properties of the vascular wall in patients with rheumatoid arthritis (RA) as applied to the course of the underlying disease and the changes in blood pressure (BP) from one-year follow-up results.
Subjects and methods. Therapeutic effectiveness was evaluated in 52 patients with RA according to the EULAR and ACR criteria; pulse wave propagation velocity (PWPV) along the vessels of elastic and muscular types was measured on an apparatus (OOO Neurosoft) at baseline and after one-year follow-up.
Results. PWPV values were found to correlate with age, functional class of RA, risk level by the Framingham model, ventricular septal thickness, left ventricular relative wall thickness, erythrocyte sedimentation rate, and the presence of C-reactive protein. After one-year follow-up, the diminished elasticity of vessels correlated with the baseline duration of morning stiffness, the number of swollen joints, and ineffective therapy for RA. The RA patients in whom BP increased to the upper normal range or who developed essential hypertension (EH) had significantly higher values of vascular wall rigidity at the beginning of the follow-up. BP elevation was also associated with age, baseline clinical activity, the systemic manifestations of RA, the cardiovascular risk by the Framingham model. There was an association of vascular elastic properties in RA patients with the magnitude and uncontrolled activity of inflammation and with elevated BP. Conclusion. The findings show it important to reduce the elastic properties of vessels in the emergence of EH in RA.

Objective: To study the effect of type II collagen peptide (CP) on the decomposition of type II collagen and the differentiation of embryonic chondrocytes of various morphotypes, isolated from the bovine growth plate.
Material and methods. Bovine growth plate chondrocytes were separated into morphotypes on a Percoll gradient in accordance with different differentiation stages and then cultured in the presence or absence of 10 ßM of CP. Cartilage explants from patients with osteoarthrosis (OA) were also cultured in the presence of 10 μM of CP. Type II collagen decomposition activity was evaluated by ELISA. Gene expressions were determined by reverse transcription polymerase chain reaction (RT-PCR).
Results. The cells having the highest buoyant density on a Percoll gradient (subpopulation A) were represented as early proliferative zone chondrocytes in the growth plate. In their presence of CP, there was increased expression of the genes of transforming growth factor (TGF) β2, parathyroid hormone-related peptide (PTHrP), fibroblast growth factor (FGF) 2, and cyclin B2, which were expressed in the proliferative zone of the growth plate, as well as metalloproteinase matrix (MMP) 13 and collagen decomposition activity. The large cells with the lowest buoyant density on a Percoll gradient (subpopulation B) were represented as hypertrophic chondrocytes. Cultivation of these cells in the presence of CP increased the expression of the genes associated with the terminal chondrocyte differentiation of type X collagen (COL10A1), Indian hedgehog (Ihh), core-binding factor (CBFA) 1 and TGF β1; and the expression of MMP 13 was suppressed. At the same time, collagen decomposition activity in cultured chondrocytes remained unchanged in the presence of CP. Although type II collagen was able to induce the collagen decomposition in the healthy articular cartilage explants, which was attended by the increased expression of the genes associated with the hypertrophic zone of an embryonic growth plate, it did not affect collagen decomposition rate in the cartilage of patients with OA.
Conclusion. The effect of CP on gene expression and collagen decomposition activity depends on the morphotype of embryonic chondrocytes. Lack of effect of CP on collagen decomposition activity in both the embryonic hypertrophic chondrocytes and the cartilage

explants from OA patients supports the hypothesis that the hypertrophic morphotype is a dominant morphotype of articular chondrocytes in OA. Moreover, collagen decomposition products can be involved in the resorption of matrix in OA and in the maintenance of chronic nature of the pathology.

Clinicoeconomic studies require that the health utility index be used to calculate quality-adjusted life years (QALY). Choice of an adequate method for determining health utility for patients with rheumatoid arthritis (RA) makes it necessary to compare various approaches to this assessment.
Objective. To compare health utility values obtained with a time to trade-off (TTO) method and those with the EQ-5D questionnaire. Subjects and methods. A single interview was made in 45 patients with RA (mean RA duration 11.7±6.6 years) with a mean HAQ of 1.22±0.52. Utility was assessed using the direct TTO method, EQ-5D index, and visual analogue scale of general health (VAS-GH); functional disease activity index was assessed according to the Health Assessment Questionnaire (HAQ).
Results. Five (11.2%) patients with RA could not answer a question to calculate TTO. The mean TTO, EQ-5D, and VAS-GH "thermometer" indices were 0.55±0.36, 0.30±0.32, and 0.47±0.23, respectively. Conversion from EQ-5D to utility index yielded the values similar to those with a mean TTO of 0.54±0.29.
The values of the utility index calculated by TTO failed to correlate with those of HAQ and EQ-5D. The disease duration was unrelated to the values of the utility index calculated by any of the methods used. The association of TTO index was found only for VAS-GH "thermometer". Conclusion. EQ-5D index and VAS-GH are the methods of choice in determining health utility for a clinicoeconomic analysis in patients with RA.