Vol 50, No 1 (2012)
Articles
Elena Nikolayevna Aleksandrova,
A S Avdeyeva,
G V Lukina,
A A Novikov,
M V Cherkasova,
T V Popkova,
O G Lineva,
G Kh Kuzikyants,
E L Nasonov
14-21 1842
Abstract
Objective: to study the time course of changes in acute-phase parameters and in the levels of autoantibodies, B lymphocytes, immunoglobulin (Ig) classes G, M, and A in patients with rheumatoid arthritis (RA) 2, 8, 16, and 24 weeks after initiation of therapy with rituximab (RTM).
22-26 963
Abstract
Objective: to study the qualitative and quantitative composition of serum extracellular DNA (exDNA); apoptotic (nucleosomes) and necrotic fragmentation; complexification of monometinic proteins with exDNA; and the levels of exDNA methylation as compared to those of autoimmune and inflammatory markers in patients with rheumatic diseases (RD). Subjects and methods. One hundred and one patients, including 28 with rheumatoid arthritis (RA), 20 with systemic lupus erythematosus (SLE), 14 with ankylosing spondylitis (AS), 31 with scleroderma systematica (SDS), and 8 with other RDs, were examined. All the patients met the classification criteria accepted at the Research Institute of Rheumatology. A control group included 15 healthy individuals. The investigators studied the serum concentration of exDNA, the content of DNA fragments of different lengths and the monometinic protein complexified with DNA, the degree of DNA methylation, the levels of serum C-reactive protein (CRP) detectable by a high-sensitivity method, rheumatoid factor (RF), anti-DNA antibodies, and antinuclear antibodies (ANA).
Results. 50-70% of the patients with RA, SLE, AS, and SDS were found to have elevated serum levels of exDNA, apoptotic and necrotic DNA; the degree of exDNA methylation (hypo- and hypermethylation) was altered. In SLE and SDS, exDNA hypomethylation was attended by autoimmune disorders: the presence of proper DNA autoantibodies and ANA. In RA, the high levels of exDNA methylation were associated with autoimmunity and inflammation (increased RF and CRP levels). In AS, the hypermethylation of apoptotic and necrotic DNA and monometinic proteins correlated with inflammatory activity and autoantigenicity (the appearance of ANA and anti-neutrophil antibodies).
Conclusion. RDs are characterized by the higher concentration of apoptotic and necrotic DNA, impaired exDNA methylation, varying complexification of exDNA with monometinic proteins, which is associated with the hyperproduction of autoantibodies (including anti-exDNA antibodies) and inflammatory markers.
Results. 50-70% of the patients with RA, SLE, AS, and SDS were found to have elevated serum levels of exDNA, apoptotic and necrotic DNA; the degree of exDNA methylation (hypo- and hypermethylation) was altered. In SLE and SDS, exDNA hypomethylation was attended by autoimmune disorders: the presence of proper DNA autoantibodies and ANA. In RA, the high levels of exDNA methylation were associated with autoimmunity and inflammation (increased RF and CRP levels). In AS, the hypermethylation of apoptotic and necrotic DNA and monometinic proteins correlated with inflammatory activity and autoantigenicity (the appearance of ANA and anti-neutrophil antibodies).
Conclusion. RDs are characterized by the higher concentration of apoptotic and necrotic DNA, impaired exDNA methylation, varying complexification of exDNA with monometinic proteins, which is associated with the hyperproduction of autoantibodies (including anti-exDNA antibodies) and inflammatory markers.
PREDICTION OF THE COURSE OF OSTEOARTHROSIS FROM mTOR (MAMMALIAN TARGET OF RAPAMYCIN) GENE EXPRESSION
E V Chetina,
E A Bratygina,
E M Zaitseva,
E P Sharapova,
L A Semenova,
N A Demin,
L I Alekseyeva,
S I Glukhova,
V V Kolomatsky,
M A Makarov,
A L Logunov,
A A Roskidailo,
S A Makarov
27-32 1052
Abstract
Objective: To study whether the course of the disease can be predicted in patients with osteoarthrosis (OA), by monitoring mTOR (Mammalian Target Of Rapamycin) gene expression in their blood.
Material and methods. The investigation was conducted on the peripheral blood samples from 33 outpatients (58.4±7.4 years) with OA; 10 patients (56.5±8.9 years) before endoprosthetic knee joint replacement, и 27 healthy individuals (55.6+8.3 years) who formed a control group. Total RNA was isolated from the blood and used to estimate the gene expression of mTOR, autophagy-related protein 1 (ATG1), the cyclin-dependent kinase inhibitor p21, caspase
3, and tumor necrosis factor-а (TNF-а) by real-time polymerase chain reaction.
Results. Analysis of gene expression in the outpatients with OA identified two subgroups: in one subgroup (n = 13) mTOR expression was considerably much less than that in the control group; the expression of ATG1 and p21 did not differ greatly from the control and that of caspase 3 and TNF-α was significantly higher. The other outpatients (n = 20) and all the examined patients needing endoprosthetic replacement were ascertained to have a higher gene expression of mTOR, ATG1, p21, caspase 3, and TNF-α than in the control group. Before endoprosthetic replacement, severe joint destruction in patients with OA was associated with enhanced gene expression of mTOR, ATG1, p21, and caspase 3. Conclusion. In early-stage disease, increased mTOR gene expression may serve as a prognostic marker of the severity of the disease and articular cartilage destruction.
Material and methods. The investigation was conducted on the peripheral blood samples from 33 outpatients (58.4±7.4 years) with OA; 10 patients (56.5±8.9 years) before endoprosthetic knee joint replacement, и 27 healthy individuals (55.6+8.3 years) who formed a control group. Total RNA was isolated from the blood and used to estimate the gene expression of mTOR, autophagy-related protein 1 (ATG1), the cyclin-dependent kinase inhibitor p21, caspase
3, and tumor necrosis factor-а (TNF-а) by real-time polymerase chain reaction.
Results. Analysis of gene expression in the outpatients with OA identified two subgroups: in one subgroup (n = 13) mTOR expression was considerably much less than that in the control group; the expression of ATG1 and p21 did not differ greatly from the control and that of caspase 3 and TNF-α was significantly higher. The other outpatients (n = 20) and all the examined patients needing endoprosthetic replacement were ascertained to have a higher gene expression of mTOR, ATG1, p21, caspase 3, and TNF-α than in the control group. Before endoprosthetic replacement, severe joint destruction in patients with OA was associated with enhanced gene expression of mTOR, ATG1, p21, and caspase 3. Conclusion. In early-stage disease, increased mTOR gene expression may serve as a prognostic marker of the severity of the disease and articular cartilage destruction.
S M Noskov,
A A Zavodchikov,
A V Evgenyeva,
A A Lavrukhina,
A N Chamorovsky,
O N Prokopenko,
V S Poletayeva
33-37 1029
Abstract
Objective: to study the prevalence of a number of surrogate measures of atherosclerosis among patients with knee osteoarthrosis (KOA) and chronic coronary heart disease (CCHD) and to determine the nature of their relationship to their functional state and the amount of muscle mass.
Subjects and methods. Twenty patients with KOA and CCHD were examined. The rigidity of the vascular wall was judged from pulse wave velocity (PWV) in the elastic vessels, by calculating a carotid-femoral index (CFI). Endothelial function was evaluated from endothelium-dependent vasodilation (EDVD) in a reactive hyperemia test. Common carotid artery scanning was used to estimate the thickness of the intima-media complex (IMC) in the carotid arteries. A bicycle ergometry exercise was performed in all the patients; exercise tolerance (ET) was determined by the amount of oxygen consumed while calculating a metabolic equivalent (MET). A bioimpedance analyzer was applied to measure the amount of muscle mass, by determining the percentages of active cell mass (ACM%) and lean mass (LM%) of total body weight. The levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were determined. A control group consisted of 20 matched individuals without CCHD.
Results and discussion. There was a prognostically favorable CFI increase (> 12 m/sec) in 20% of the patients with CCHD and in 10% of the controls (z = 0.15; p = 0.78), endothelial vasomotor dysfunction (EDVD < 10%) in 55% of the patients with CCHD and in 50% of the controls (z = 0.76; p = 0.55); a more than 0.9-mm IMC increase in 60% of the patients with CCHD. The bulk of the patients with pathological vascular rigidity and endothelial vasomotor dysfunction had a low ET. The CCHD patients with a low ET showed significant correlations of CFI and ACM% and LM% (r = -0.36; p < 0.05 and r = -0.39; p < 0.05, respectively), EDVD with ACM% and LM% (r = 0.51; p < 0.05 and r = 0.45; p <0.05, respectively), CFI and EDVD (r = -0.39; p < 0.05). In the control patients with a low ET, EDVD also correlated with ACM% and LM mass% (r = 0.78; p < 0.05 and r = 0.66; p < 0.05, respectively). There was a correlation of ACM% and LM % with MET in both groups (r = 0.52; p < 0.05 and r = 0.61; p < 0.05; respectively, and also r = 0.44; p < 0.05 and r = 0.35; p < 0.05, respectively). Thus, EDVD and PWV reflect to a greater extent the decreases in the physical activity and functional status of patients rather than surrogate atherosclerosis.
Subjects and methods. Twenty patients with KOA and CCHD were examined. The rigidity of the vascular wall was judged from pulse wave velocity (PWV) in the elastic vessels, by calculating a carotid-femoral index (CFI). Endothelial function was evaluated from endothelium-dependent vasodilation (EDVD) in a reactive hyperemia test. Common carotid artery scanning was used to estimate the thickness of the intima-media complex (IMC) in the carotid arteries. A bicycle ergometry exercise was performed in all the patients; exercise tolerance (ET) was determined by the amount of oxygen consumed while calculating a metabolic equivalent (MET). A bioimpedance analyzer was applied to measure the amount of muscle mass, by determining the percentages of active cell mass (ACM%) and lean mass (LM%) of total body weight. The levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were determined. A control group consisted of 20 matched individuals without CCHD.
Results and discussion. There was a prognostically favorable CFI increase (> 12 m/sec) in 20% of the patients with CCHD and in 10% of the controls (z = 0.15; p = 0.78), endothelial vasomotor dysfunction (EDVD < 10%) in 55% of the patients with CCHD and in 50% of the controls (z = 0.76; p = 0.55); a more than 0.9-mm IMC increase in 60% of the patients with CCHD. The bulk of the patients with pathological vascular rigidity and endothelial vasomotor dysfunction had a low ET. The CCHD patients with a low ET showed significant correlations of CFI and ACM% and LM% (r = -0.36; p < 0.05 and r = -0.39; p < 0.05, respectively), EDVD with ACM% and LM% (r = 0.51; p < 0.05 and r = 0.45; p <0.05, respectively), CFI and EDVD (r = -0.39; p < 0.05). In the control patients with a low ET, EDVD also correlated with ACM% and LM mass% (r = 0.78; p < 0.05 and r = 0.66; p < 0.05, respectively). There was a correlation of ACM% and LM % with MET in both groups (r = 0.52; p < 0.05 and r = 0.61; p < 0.05; respectively, and also r = 0.44; p < 0.05 and r = 0.35; p < 0.05, respectively). Thus, EDVD and PWV reflect to a greater extent the decreases in the physical activity and functional status of patients rather than surrogate atherosclerosis.
38-41 991
Abstract
Objective: to evaluate the specific features of the diagnosis and clinical manifestations of ankylosing spondylitis (AS) in patients followed up in the Kazan City Rheumatology Center (City Clinical Hospital Seven).
Subjects and methods. Fifty-two patients who had been treated at hospital or who visited a polyclinic rheumatologist in the period February to April 2010 for a verified diagnosis of AS according to the modified New York classification criteria were examined. More than half of the patients had high clinical (BASDAI ≥4 in 71.2%) and laboratory (C-reactive protein >6 mg/l in 67.3%) activities, an active inflammatory process according to the results of magnetic resonance imaging, and a significantly limited functional state (BASFI ≥4 in 61.5%). Women were 26.9% of all the examinees, their clinical picture of peripheral arthritis prevailed, and they were referred for a rheumatologist for their being diagnosed as having reactive arthritis. Results. AS was verified an average of 4.2±1.2 years after the appearance of its first clinical symptoms, which is rather promptly as compared to the data available in the literature (on the average 7-8 years). In the peripheral form of the disease, the diagnosis was established earlier (3.7±1.4 years) than in its central form (5.1±1.8 years). These results were achieved due, among other things, to the execution of educational programs for primary physicians.
Subjects and methods. Fifty-two patients who had been treated at hospital or who visited a polyclinic rheumatologist in the period February to April 2010 for a verified diagnosis of AS according to the modified New York classification criteria were examined. More than half of the patients had high clinical (BASDAI ≥4 in 71.2%) and laboratory (C-reactive protein >6 mg/l in 67.3%) activities, an active inflammatory process according to the results of magnetic resonance imaging, and a significantly limited functional state (BASFI ≥4 in 61.5%). Women were 26.9% of all the examinees, their clinical picture of peripheral arthritis prevailed, and they were referred for a rheumatologist for their being diagnosed as having reactive arthritis. Results. AS was verified an average of 4.2±1.2 years after the appearance of its first clinical symptoms, which is rather promptly as compared to the data available in the literature (on the average 7-8 years). In the peripheral form of the disease, the diagnosis was established earlier (3.7±1.4 years) than in its central form (5.1±1.8 years). These results were achieved due, among other things, to the execution of educational programs for primary physicians.
42-44 811
Abstract
Objective: to study the specific features of the «native course» of rheumatoid arthritis (RA) in real clinical practice (according to the data of an inpatient registry).
Subjects and methods. The inpatient registry (642 patients with RA verified according to the 1987 ACR criteria) was used to identify a group of 80 (12.5%) subjects who had been first admitted to the Rheumatology Unit, Voronezh Regional Clinical Hospital One, to undergo examinations and who had received no disease-modifying anti-rheumatic drugs (DMARDs) throughout the disease before being included into the registry. The patients were conventionally called a group of the native course of RA and examined by 70 items involving sociodemographic, clinical, laboratory, and functional variables.
Results. In the native-course group, the activity of an inflammatory process, the progression of X-ray changes, and functional class were significantly higher than those in the group of PA patients receiving DMARDs.
Conclusion. The findings indicate that the early use of DMARDs, continuity and effective monitoring of the course of RA at all stages of medical care are important goals of clinical rheumatology.
Subjects and methods. The inpatient registry (642 patients with RA verified according to the 1987 ACR criteria) was used to identify a group of 80 (12.5%) subjects who had been first admitted to the Rheumatology Unit, Voronezh Regional Clinical Hospital One, to undergo examinations and who had received no disease-modifying anti-rheumatic drugs (DMARDs) throughout the disease before being included into the registry. The patients were conventionally called a group of the native course of RA and examined by 70 items involving sociodemographic, clinical, laboratory, and functional variables.
Results. In the native-course group, the activity of an inflammatory process, the progression of X-ray changes, and functional class were significantly higher than those in the group of PA patients receiving DMARDs.
Conclusion. The findings indicate that the early use of DMARDs, continuity and effective monitoring of the course of RA at all stages of medical care are important goals of clinical rheumatology.
45-53 1623
Abstract
Objective. To evaluate the efficacy of an individual rehabilitation program (IRP) for patients with rheumatoid arthritis (RA), by using hardware methods (COBS platform, En-Tree M motion analysis) and the quality-of-life index RAPID3. Subjects and methods. The study enrolled 46 patients with RA. Of them, 35 patients underwent drug therapy and IRP (40-min exercise therapy for large joints under the supervision of a trainer, 40-min occupational therapy, local air cryotherapy (-60°C) for hand, knee, or ankle joints for 15 min, 10 sessions), 11 patients received only drug therapy (a control group). The COBS platform was used to measure a symmetry index (SI) and load distribution in different modes. The authors determined the average power of knee extension and ankle flexion by the En-Tree M system, hand grip strength, and DAS28 and RAPID3 scores.
Results. Thirty-two patients finished IRP. After IRP, the grip strength of a more affected hand was enhanced by 29% (p < 0.05). RAPID3 scores decreased by 3.25±0.43 (27%) (p < 0.05). The reduction in DAS28 scores was not statistically significant. In the patients with knee arthritis, the pressure from habitual standing on the COBS platform of an extremity with a more affected joint increased by 11% (p < 0.05) and SI rose by 13% (p < 0.05). The rising-from-sitting load on the limb with a more affected joint was elevated by 13% (p < 0.05), SI increased by 25% (p < 0.05). The average extension power for a weaker knee was increased by 88% (p < 0.01). In the patients with ankle arthritis, the habitual-standing pressure on the COBS platform of an extremity with a more affected joint was enhanced by 14% (p < 0.05), SI increased by 18% (p < 0.05). The toes-rising load on the limb with a more affected joint increased by 12% (p < 0.05), SI rose by 20% (p < 0.05). The flexion power of a weaker ankle joint was increased by 68% (p < 0.01). There were no statistically significant changes in most parameters in the control group.
Conclusion. The COBS platform and En-Tree M motion analysis allow one to estimate the functional status of each joint group of the lower limbs. IRP improves functional ability and motion activity (hand grip strength, power, symmetry of movements, load distribution) and quality of life in RA patients immediately after its completion.
Results. Thirty-two patients finished IRP. After IRP, the grip strength of a more affected hand was enhanced by 29% (p < 0.05). RAPID3 scores decreased by 3.25±0.43 (27%) (p < 0.05). The reduction in DAS28 scores was not statistically significant. In the patients with knee arthritis, the pressure from habitual standing on the COBS platform of an extremity with a more affected joint increased by 11% (p < 0.05) and SI rose by 13% (p < 0.05). The rising-from-sitting load on the limb with a more affected joint was elevated by 13% (p < 0.05), SI increased by 25% (p < 0.05). The average extension power for a weaker knee was increased by 88% (p < 0.01). In the patients with ankle arthritis, the habitual-standing pressure on the COBS platform of an extremity with a more affected joint was enhanced by 14% (p < 0.05), SI increased by 18% (p < 0.05). The toes-rising load on the limb with a more affected joint increased by 12% (p < 0.05), SI rose by 20% (p < 0.05). The flexion power of a weaker ankle joint was increased by 68% (p < 0.01). There were no statistically significant changes in most parameters in the control group.
Conclusion. The COBS platform and En-Tree M motion analysis allow one to estimate the functional status of each joint group of the lower limbs. IRP improves functional ability and motion activity (hand grip strength, power, symmetry of movements, load distribution) and quality of life in RA patients immediately after its completion.
54-59 6821
Abstract
Esophageal lesion is a characteristic visceral manifestation of scleroderma systematica (SDS). Sclerodermic esophagitis complications, such as ulcers and Barretts esophagus (BE), bring a threat to life and require active and long-term therapy. Objective: to evaluate the incidence, clinical symptoms, and endoscopic picture of esophageal pathology in patients with SDS, as well as the efficiency of therapy with proton pump inhibitors (PPIs).
Subjects and methods. Three hundred and fifty-six patients (women, 92.6%; men, 7.4%) aged 47.8±19.7 years with SDS and 1018 patients (women, 89.0%; men, 11.0%) aged 44.1±16.3 years with rheumatoid arthritis (RA) were examined. Out of them, 66.7 and 52.6% took glucocorticoids (GC), 21.6 and 82.9% received nonsteroidal antiinflammatory drugs (NSAIDs), 13.2 and 0% had D-penicillamine, 15.7 and 56.5% had cytotoxic drugs, and 23.7 and 8.7% had PPIs, respectively. All the patients underwent endoscopic study of the upper gastrointestinal tract.
Results. The subjective symptoms of esophageal pathology were in 64.0 and 33.9% of the patients with SDS or RA, respectively (p < 0.001). Dysphagia and retrosternal pain were observed in 10.1 and 7.0% of the patients with SDS, respectively, and in only 1.7% of the patients with RA. Endoscopy revealed mucosal hyperemia in 27.4 and 1.5% of the patients, erosive esophagitis in 21.9 and 2.2%, and esophageal ulcers in 4 (1.1%) and 0%, respectively (p = 0.000). Esophageal mucosal biopsy was performed in 92 of the 356 patients with SDS, which could identify BE (intestinal metaplasia) in 19 (20.1%) cases. There was a significant correlation between the clinical symptoms of the esophagus and the endoscopic signs of erosive esophagitis (p = 0.001). There was no relationship between esophageal pathology, age, and the use of drugs (NSAIDs, GC, cytotoxic drugs). Erosive esophagitis and BE were detected in 35.0 and 36.8% of the SDS patients (n = 90) during their regular use of PPIs. All 4 patients with esophageal ulcers regularly took PPIs.
Conclusion. Esophageal pathology is noted in the majority of patients with SDS and in only individual patients with RA. BE is a common complication of SDS, which requires a regular endoscopic examinations in all patients with this disease. PPIs are not always rather effective, which determines it necessary to use large doses of these drugs or combination therapy.
Subjects and methods. Three hundred and fifty-six patients (women, 92.6%; men, 7.4%) aged 47.8±19.7 years with SDS and 1018 patients (women, 89.0%; men, 11.0%) aged 44.1±16.3 years with rheumatoid arthritis (RA) were examined. Out of them, 66.7 and 52.6% took glucocorticoids (GC), 21.6 and 82.9% received nonsteroidal antiinflammatory drugs (NSAIDs), 13.2 and 0% had D-penicillamine, 15.7 and 56.5% had cytotoxic drugs, and 23.7 and 8.7% had PPIs, respectively. All the patients underwent endoscopic study of the upper gastrointestinal tract.
Results. The subjective symptoms of esophageal pathology were in 64.0 and 33.9% of the patients with SDS or RA, respectively (p < 0.001). Dysphagia and retrosternal pain were observed in 10.1 and 7.0% of the patients with SDS, respectively, and in only 1.7% of the patients with RA. Endoscopy revealed mucosal hyperemia in 27.4 and 1.5% of the patients, erosive esophagitis in 21.9 and 2.2%, and esophageal ulcers in 4 (1.1%) and 0%, respectively (p = 0.000). Esophageal mucosal biopsy was performed in 92 of the 356 patients with SDS, which could identify BE (intestinal metaplasia) in 19 (20.1%) cases. There was a significant correlation between the clinical symptoms of the esophagus and the endoscopic signs of erosive esophagitis (p = 0.001). There was no relationship between esophageal pathology, age, and the use of drugs (NSAIDs, GC, cytotoxic drugs). Erosive esophagitis and BE were detected in 35.0 and 36.8% of the SDS patients (n = 90) during their regular use of PPIs. All 4 patients with esophageal ulcers regularly took PPIs.
Conclusion. Esophageal pathology is noted in the majority of patients with SDS and in only individual patients with RA. BE is a common complication of SDS, which requires a regular endoscopic examinations in all patients with this disease. PPIs are not always rather effective, which determines it necessary to use large doses of these drugs or combination therapy.
ISSN 1995-4484 (Print)
ISSN 1995-4492 (Online)
ISSN 1995-4492 (Online)