Vol 80, No 5 (2008)


Perspectives of rheumatology in the XXI century

Nasonova V.A.
Terapevticheskii arkhiv. 2008;80(5):5-8
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Early diagnosis of rheumatoid arthritis in modern clinical practice (results of a follow-up of a Moscow cohort of early arthritis patients participating in the program RADICAL)

Karateev D.E., Luchikhina E.L., Tiurina L.N., Chemeris N.A., Pogozheva E.I., Lukina G.V., Potanin A.I., Shostak N.A., Kogan K.M., Demidova N.V., Kasumova K.A., Pozdniakova E.S., Fedorenko E.V., Aleksandrova E.N., Novikov A.A., Smirnov A.V., Nasonov E.L.


Aim. To estimate potentialities of early diagnosis of rheumatoid arthritis (RA) diagnosis in clinical practice in the course of the RADICAL program. Material and methods. Of 366 patients participating in the trial 61 (16.7%) were males and 305 (83.3%) were females at the age of 47.76 ± 14.1 years. The longest duration of the symptoms before consulting a doctor was 51 weeks, mean duration - 5.7 weeks, 55% patients had the symptoms for 3 weeks. All the patients have undergone laboratory examination including leukocyte count, platelet count, estimation of ESR, concentration of C-reactive protein (CRP), rheumatoid factor (RF) and antibodies to a cyclic citrullated peptide (ACCP); roentgenography of the wrists and feet. On demand, antinuclear factor (ANF) and HLA-B27 were investigated. RA was diagnosed on the basis of ACR classification criteria. If the criteria were not complete at the moment of the study, the patient was referred to the group of "undifferentiated arthritis" (UA). The patients were examined before the treatment, 6 and 12 months later. The treatment was made according to Russian clinical recommendations. Results. Prior to admission to hospital, 58% patients were suspected for RA, 18.3% - osteoarthrosis (OA), 14% - reactive arthritis. 18.9% were not diagnosed, other diagnoses were considered in 12.6% patients. At primary examination RA was diagnosed in 212 (57.9%) patients, UA was in 133 (36.3%) patients, 21 (5.7%) patients had other diagnoses. Twelve months later RA, UA and other diseases were diagnosed in 256 (69.9%), 70 (19.1%) and 40 (10.9%) patients, respectively. Conclusion. A 3-stage algorithm of early RA diagnosis is proposed. At the stage of the first contact with the patient in an outpatient clinic a valid RA suspition with consideration of modified EULAR criteria must be formulated. At the second stage a district rheumatologist must examine the patient outpatiently with determination of ACR classification criteria. In diagnosis verification the treatment must be started according to APP and EULAR clinical recommendations. If RA diagnosis can not be verified or rejected, the patient must be refered to hospital (stage 3). If verification of RA diagnosis is impossible, the diagnosis should be formulated as UA.
Terapevticheskii arkhiv. 2008;80(5):8-13
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Diagnosis of wrist joint lesions by arthrosonography in early rheumatoid arthritis

Epifanova O.E., Shilkina N.P.


Aim. To assess joint and extraarticular wrist lesions in RA patients with arthrosonography in the disease duration up to 6 months. Material and methods. 38 RA patients aged 40 ± 10.5 years (25 females and 13 males) entered the study. These patients and 20 controls without musculoskeletal pathology matched by age and sex have undergone sonographic examination of the wrists and extrajoint structures. Results. The following ultrasonographic signs of intra- and extra-articular inflammation were determined: joint cavity expansion, the presence of anechoic/hypoechoic synovial fluid, effusions, synovial thickening, digital flexor and extensor tenosynovitis, incongruous articular surfaces, bone erosions. Conclusion. Wrist arthrosonography is an informative diagnostic method in early RA as it detects bone erosions, alterations in the cartilages, muscles, tendons and ligaments.
Terapevticheskii arkhiv. 2008;80(5):13-16
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Painless myocardial ischemia in patients with rheumatoid arthritis

Striuk R.I., Leonova E.A., Tedikova N.S., Gosteva O.V.


Aim. To ascertain prevalence and prognostic implication of painless myocardial ischemia (PMI) in patients with rheumatoid arthritis (RA) in respect to stage, severity of inflammation and characteristics of the lipid profile. Material and methods. A 24-h Hotter ECG monitoring, tests for total cholesterol, triglycerides and lipid spectrum were made in 94 patients with a documented rheumatoid arthritis (RA) aged 36-68 years (mean age 54.8 ± 8.0years, 13 males and 81 females) admitted to Toliatti municipal hospital N 4. The control group consisted of 20 patients with a history of myocardial infarction. Forty RA patients were followed up for mean 1.1 year after basic therapy. Results. Hotter ECG monitoring detected ischemic depression of ST segment in 46 (48.9%) RA patients and 9 (45%) patients with coronary heart disease. RA patients with PMI had changes in the lipid profile in the direction of elevation of atherogenic components and C-reactive protein characterizing severity of inflammation. Basic treatment of RA eliminated PMI symptoms in some patients. This correlated with attenuation of inflammation. Some RA patients had first symptoms of PMI, on the average, on follow-up year 1.1 and higher plasmic atherogenicity. Conclusion. About 50% RA patients free of clinical symptoms of coronary heart disease had PMI caused by both coronarogenic (atherosclerotic) factors and non-coronarogenic (immunocomplex inflammation) mechanisms.
Terapevticheskii arkhiv. 2008;80(5):16-20
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Characteristics of a cytokine profile of t-lymphocytes of peripheral blood and synovial fluid in rheumatoid arthritis

Kolotova G.B., Lagereva I.G., Beĭkin I.B.


Aim. To assess cytokine-producing activity of T-lymphocytes of peripheral blood and synovial fluid in rheumatoid arthritis (RA). Material and methods. The study group consisted of 58 RA female patients aged 28-53 years (mean age 42.1 ± 2.9 years) with at least 5-year history of RA (mean 10.7 ± 4.9 years). The control group consisted of 37 healthy women matched by age. Spontaneous production of IL-2, IL-4, IFNgamma (IFNγ) and TNFalpha (TNFα) by CD3+ and CD3- lymphocytes was estimated after 4 hours of incubation in 37°C with phorbol-12-myristate-13-acetate (PMA, 50 ng/ml, Sigma, France), ionomycin (1 mcg/ml, Sigma, France) and brefeldin A (10 mcg/ml, Sigma, France). Results. In RA there is a decrease in a relative and absolute count of peripheral blood T-lymphocytes which occurs spontaneously and due to nonspecific stimulation of synthesizing IL-4, TNFα and IFNγ. IFNγ-producing lymphocytes (CD3+IFNg+/CD3+IL-4+=4.45 ± 1.56) prevail in the synovial fluid in RA, but count of lymphocyte IFNγ, IL-2 and TNFα+ in the synovial fluid is lower than in peripheral blood. Conclusion. One of the causes of low count of TNFα, IFNγ and IL-4 producing T-lymphocytes in peripheral blood is migration of relevant TC-subpopulations to the affected joints. Migration of TC1-lymphocytes into the synovial fluid does not result in their prevailing count in the synovial fluid vs peripheral blood.
Terapevticheskii arkhiv. 2008;80(5):21-25
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Comparison of efficacy and tolerability of triple combination therapy (methotrexate + sulfasalazine + hydroxychloroquine) with methotrexate monotherapy in patients with rheumatoid arthritis

Gubar' E.E., Bochkova A.G., Bunchuk N.V.


Aim. To compare efficacy and tolerability of combined therapy with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ) with MTX-monotherapy in patients with rheumatoid arthritis (RA). Material and methods. RA patients (n=60) who had not been treated with the above drugs were randomized (1:1) to receive either the triple drug combination or MTX alone in a 2-year open study. SSZ was given in a dose of 2.0 g/day, HCQ - 200 mg/day. A MTX dose was gradually increased from 7.5 mg/week to 17.5 mg/week in an attempt to achieve remission in all the patients. Basic criterion of the treatment efficacy was achievement of a significant clinical effect (>50% response according to the American College of Rheumatology - ACR criteria) in stability of the positive effect beginning from the ninth month of the study up to its end with no evidence of serious drug toxicity. Results. 13 of 18 patients treated with the triple therapy (72.2%) and 6 of 20 patients treated with MTX alone (30.0%; p = 0.013) achieved an ACR >50% response by the end of 18 months of therapy. 11 of 18patients (61.1%) from the combined therapy group and 5 of 20patients (25%; p=0.024) from MTX monotherapy group maintained ACR>50% response from month 9 to 18 of the study without any evidence of major drug toxicity. Two patients (11.1%) in the combined therapy group and 4 patients (20%) in the MTX group discontinued the treatment because of drug toxicity. Conclusion. In patients with RA the triple combination therapy with MTX, SSZ and HCQ given during 1.5 year is more effective than MTX alone. The triple combination of MTX, SSZ and HCQ is well tolerated.
Terapevticheskii arkhiv. 2008;80(5):25-30
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Neutralisation of interferon gamma - a new trend in therapy of rheumatoid arthritis

Nasonova V.A., Lukina G.V., Sigidin I.A.


Aim. To evaluate objectively therapeutic potentialities of a novel method of biological therapy - blocking interferon gamma (IF-γ) - by means of a comparative analysis of using antibodies to IF-g (anti-IF-γ) and tumor necrosis factor alpha (anti-TNF-α) in resistant rheumatoid arthritis (RA). Material and methods. A double blind trial included 55 patients with resistant RA. They received 5 intramuscular injections of anti-IF-y (n = 20), anti-TNF-a (n = 20) and placebo (15 patients). The results were assessed on the treatment day 7 and 28. Results. 16 patients withdrew because of the treatment uneffectiveness (2 from the group on anti-IF-g, 3 - on anti-TNF-α, 11 - on placebo). To the treatment day 28 the patients given anticytokines achieved significant improvement of all clinical indices while placebo group had no improvement. The highest response was observed in the group on anti-IF-γ (ACR 70). As shown by ultrasound investigation, a significant reduction of the synovial membrane thickness took place also in administration of anti-IF-γ Most frequent side effect of the anticytokine therapy was mild dermatitis at injection site on treatment day 8-11. Conclusion. Therapeutic efficacy of anti-IF-γ was comparable with efficacy of anti-TNF-α and even was superior in some aspects. The block of IF-γ holds much promise in the treatment of RA.
Terapevticheskii arkhiv. 2008;80(5):30-37
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Soluble CD40 Ligand in systemic lupus erythematosus: link with atherosclerotic vascular affection

Popkova T.V., Panafidina T.A., Aleksandrova E.N., Novikova D.S., Novikov A.A., Alekberova Z.S., Mach É.S., Nasonov E.L.


Aim. To evaluate clinical implications of pCD40L as a marker of atherosclerotic vascular affection in systemic lupus erythematosus (SLE). Material and methods. The examination of 132 females (mean age 35 years, SLE duration 96 months) assessed classic factors of atherosclerosis risk (AR), total coronary risk (TCR), detected subclinical atherosclerosis with ultrasonic scanning of the carotid arteries. Serum level of pCD40L was measured with enzyme immunoassay (EIA). Results. Concentration of pCD40L in SLE patients was higher than in the control group (7.1 ± .9 and 5.8 ± 3.1 ng/ml, respectively) but the difference was insignificant (p>0.05). Upper limit of normal value (M + 2SD) for pCD40L was 12 ng/ml. Elevation of pCD40L level was seen in 21% of SLE patients. Clinical manifestations of atherosclerosis risk were seen in 13% SLE patients, subclinical in 19 and 17% (increased intima-media thickness and atherosclerotic plaques, respectively). No correlations were found between pCD40L level and atherosclerotic symptoms. The pCD40L level was higher in SLE patients with the plaques than in those without them (p = 0.005). A positive correlation exists between a pCD40L concentration and maximal intima-media thickness (r = 0.2; p = 0.02), total cholersterol (r = 0.3; p = 0.002), LDLP cholesterol (r = 0.3; p=0.004), LDLP cholesterol (r = 0.2; p = 0.04) and age of the patients (r = 0.2; p = 0.03). In patients with TCR > 20% a pCD40L was significantly higher than in patients with TCR < 20% (p = 0.01). Conclusion. Elevated pCD40L level is a marker of atherosclerotic affection of the vessels, has an important clinical role for predicting risk of cardiovascular diseases in SLE and elicidation of the role of activation of cell immunity in development of atherosclerosis in this disease.
Terapevticheskii arkhiv. 2008;80(5):37-41
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Interleukin-18 in systemic lupus erythematosus: link with clinical symptoms and vascular atherosclerosis

Panafidina T.A., Popkova G.V., Alekberova Z.S., Mach É.S., Aleksandrova E.N., Nasonov E.L.


Aim. To examine correlation between IL-18 concentration, SLE manifestations and atherosclerotic vascular affection. Material and methods. We examined 162 SLE female patients (age 26-43 years, mean age 35 years, duration of SLE 28-204 months, mean duration 96.0 months) and 64 healthy controls (women aged 30.0-45.0 years, mean age 35.5 years). We analysed correlation between IL-18 concentration, SLE symptoms, classic risk factors for cardiovascular diseases, subclinical and clinical signs of atherosclerosis. Results. IL-18 in blood serum of SLE patients was much higher than in the control group (p < 0.00001). A positive correlation exists between IL-concentration and the disease activity by scale SLEDAI-2K, the level of antibodies to IgG cardiolipin, ESR, SLE, titers of antibodies to double-chain DNA, concentration of creatinin, urine, glucocorticoids dose taken by the patients at examination. In SLE patients with stomatitis, hematological, immunological disorders, a positive test for antinuclear factor, IL-18 was much higher than in patients without the above signs. No significant correlation was seen between IL-18 concentration, subclinical and clinical signs of atherosclerosis, of risk factors, there was a negative correlation between total cholesterol concentration, LDLP and HDLP cholesterol. Conclusion. In SLE patients a high IL-18 level reflects activity of the basic disease and is not related with vascular atherosclerosis.
Terapevticheskii arkhiv. 2008;80(5):41-46
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Efficacy and safety of bivalos therapy for postmenopausal osteoporosis. results of russian multicenter trial

Rozhinskaia L.I., Arapova S.D., Dzeranova L.K., Molitvoslovova N.N., Marova E.I., Il'in A.V., Benevolenskaia L.I., Nikitinskaia O.A., Korotkova T.A., Toroptsova N.V., Smirnov A.V., Demin N.V., Rodionova S.S., Buklemeshev I.V., Shumskiĭ A.A.


Aim. To study effects of one-year therapy with bivalos on mineral bone density (MBD) of the spine in patients with postmenopausal osteoporosis (PMO), effects of bivalos (strontium ranelate) on MBD of the neck of the femur and femur, the levels of bone metabolism markers, quality of life, tolerance of long-term therapy. Material and methods. The study was made of 60 females aged 54-75 years with PMO. MBD was measured with x-ray absorptiometry in the vertebra and proximal femur. Bone markers in blood serum were detected by enzyme immunoassay . Results. After a year of taking bivalos MBD in lumbar vertebra increased by 4.68 ± 4.94%, in the neck of the femur - by 2.0 ± 4.29%, in the proximal femur - by 3.10 ± 3.34%. A significant 19.5% rise in bone alkaline phosphatase and a 16.5% fall in the level of CT were noted showing a stimulating effect of bivalos on bone formation and an inhibiting effect - on bone tissue resorption. Bivalos treatment raised quality of life of the patients: better motility, regress of depression, improved self-appraisal, decreased number of patients with pain in the spine, attenuated pain. The drug was well tolerated, unwanted effects arose in 15% patients, discontinuation of the drug because of toxicity occurred in 5%. Serious side effects were not observed. Conclusion. Strontium ranelate is effective in PMO and is well tolerated.
Terapevticheskii arkhiv. 2008;80(5):47-52
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Frequency of diagnosis of postmenopausal osteoporosis of the spine, distant radius and extravertebral fractures in women with normal body mass, overweight and obesity

Popov A.A., Izmozherova N.V., Fominykh M.I., Tagil'tseva N.V., Kozulina E.V., Gavrilova E.I.


Aim. To assess features and peculiarities of postmenopausal osteoporosis (OP) in women with normal body mass, overweight and obesity. Material and methods. Dual energy X-ray absorptiometry of the lumbal spine (Lunar DPX) and distal radius X-ray absorptiometry (DTX 200) were performed during cross-section study of 730 symptomatic postmenopausal women. Results. OP was diagnosed in 253 (34.7%) women, 30.5% of them had normal body mass, 43.2% had overweight and 26.3% were obese. Among them 227 had atraumatic fractures at the age over 50 years. Obese OP patients had significantly higher frequency of arterial hypertension, chronic heart failure, osteoarthritis and glucose metabolism disorders than osteoporotic patients with normal body mass. Fracture frequency did not differ between groups with normal body mass, overweight and obesity. Conclusion. Excessive body mass did not decrease fracture risk in women with postmenopausal OP.
Terapevticheskii arkhiv. 2008;80(5):52-56
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Behcet's disease and joint affection

Alekberova Z.S., Elonakov A.V., Goloeva R.G., Smirnov A.V., Guseva I.A., Nasonov E.L.


Aim. To study joint pathology in patients with Behcet's disease (BD). Material and methods. The trial enrolled 183 BD patients (128 males, 54 females, mean age 32,0 ± 9.8 years, age at BD onset 22.3 ± 9.9 years, mean duration of the disease 9.5 ± 8.9 years. Results. Joint pathology occurred in 74.8% patients, in 10.9% patients the disease onset was associated with arthritis and arthralgia. 3 patients had aceptic necrosis of the head of the femur and knee joint, 3 patients - bone marrow infarction. Knee joints were affected more frequently than others (up to 40%) followed by ankle, elbow and radiocarpal and other joints. In BD duration about 10 years, none of the examinees had stage III of sacroiliitis, stage II was diagnosed only in 4 patients, stage I (suspicion) - in 9. Significant sacroillitis was not registered, bilateral sacroillitis occurred only in 9 patients. HLA B5 was detected in 61% patients while HLA B27 - only in 9.7%. Conclusion. The articular syndrome was seen in 3/4 of BD patients. Arthritis runs a recurrent course. Erosive arthritis, sacroillitis and combination of the latter with HLA B27 are rare.
Terapevticheskii arkhiv. 2008;80(5):56-58
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Low back pain in general medical practice

Érdes S.F., Dubinina T.V., Galushko E.A.


Aim. To characterize prevalence and features of low back pain (LBP) in Moscow outpatients. Material and methods. The questionnaire designed in the Rheumatology Institute of Russian Medical Academy was used in the trial performed for a month with participation of 1300 Moscow outpatients aged 18 to 50 years. Results. LBP is a frequent cause of consulting a physician in an outpatient practice. Most of the outpatients complained of acute and subacute moderate or severe LBP. This pain often caused disability. Of diagnostic tools most frequent was x-ray investigation of the spine. Conclusion. Spinal osteochondrosis is the most frequent diagnosis made in LBP outpatients. Detectability of threat marks in LBP patients is not more than 10%.
Terapevticheskii arkhiv. 2008;80(5):59-61
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Development and relapse of gastroduodenal ulcer in patients taking nonsteroid anti-inflammatory drugs: effects of standard risk factors

Karateev A.E., Nasonova V.A.


Aim. To investigate incidence and recurrence rate of endoscopic ulcers in patients with rheumatic diseases (RD) taking NSAID in respect to factors of NSAID gastropathy risk. Material and methods. Endoscopic findings in the gastrointestinal tract were analysed for 6103 patients (age 50.1 ± 14.6 years, 83.1% females) with RD taking NSAID regularly, 1642 of them took also glucocorticoids (GC). Control RD patients (n = 504) matched by age and sex took no NSAID, GC and low dose aspirin a month and more before the trial. Results. Gastric or duodenal ulcers were detected in 763 (12.5%) RD patients treated with NSAID, in 20 (4.0%) in the control group, p < 0.0001. Ulcers were more frequent in older patients (65 years of age and older) with ulcer history treated with nonselective NSAID in combination with low aspirin doses (15.1 and 12.0, p < 0.05; 27.3 and 9.7%, p < 0.001; 13.1 and 9.8%, p<0.001; 19.1 and 12.2%, p < 0.001; respectively). No significant difference in ulcer occurrence was observed in patients given NSAID+GC and NSAID only (11.3 and 12.9%, respectively; p = 0.041). The recurrence rate was assessed in 407 patients with NSAID-induced ulcer 12 months later. Control consisted of 1640 patients having no ulcer, multiple erosions after 12 months of regular intake of NSAID. Ulcer recurrence rose in 163 of 407patients (40%) while only in 107 of 1640 controls (6.5%, p < 0.0001). Old age and GC administration had no impact on the recurrence rate. Recurrences were less frequent in patients taking nonselective NSAID than those taking nonselective ones (23.4 and 46.5%, respectively; p < 0.001) and in patients treated with NSAID in combination with proton pump inhibitors (24.6 and 42.6%, respectively; p < 0.001). Prophylactic intake of H-2 blockers did not reduce recurrence rate. Conclusion. Old age, ulcer history and intake of nonselective NSAID increased the risk of endoscopic GI ulcer. Combined use of NSAID and GC did not increase the risk of ulcer development or recurrence. In a year or later of NSAID continuation recurrences arose in 40% patients with NSAID-induced ulcers. Recurrence risk was reduced by selective NSAID and proton pump inhibitors.
Terapevticheskii arkhiv. 2008;80(5):62-66
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Changes in st segment on ecg of hypertensive patients

Riabykina G.V., Liutikova L.N., Saidova M.A., Botvina I.V., Kozhemiakina E.I., Shchedrina E.V., Sobolev A.V.


Aim. To evaluate ST depression in hypertensive patients with electrocardiographic signs of left ventricular hypertrophy (LVH), correlation of ST segment changes with heart rate (HR) and blood pressure (BP) during Holier monitoring (HM) and bi-functional ECG and BP monitoring (BFM), and to compare ST depression and local left ventricular contractility during stress-echocardiography in hypertensive patients with unaffected coronary arteries according to the data of coronary angiography. Material and methods. We examined 344 hypertensive patients without clinical signs of ischemic heart disease. Correlation between ST segment depression and ECG signs of LVH was evaluated in 192 patients. 180 patients underwent HM, 122 - BFM and 30 hypertensive patients with normal coronary arteries according to the data of coronary angiography underwent stress-echocardiography. Results. According to the data of 12 lead ECG 40 cases of ST depression were found, with LVH signs in 26 (65%) of these patients. During HM in 34 of 180 patients 2 types of ST depression were found: type 1 - short periods of transient ST depression without persistent ST depression was fond in 8 patients; type 2 - persistent ST depression more than 1 mm during the whole time of recording - in 26 patients. In 7 of 8 cases of type 1 and in 5 of 26 cases of type 2 ST depression had rhythm-dependent character. During BFM in 9 cases ST depression during HR or BP increase was found. In 2 cases ST depression during BP increase was unrelated to HR increase which may be consequence of systolic myocardial strain syndrome. In 7 of 30 hypertensive patients with normal coronary arteries and without local myocardial contractility disturbances according to the data of stress-echocardiography positive criteria of ischemia were found. Conclusion. The cause of ST segment depression in hypertensive patients more often are secondary disturbances of repolarizaion processes related with LVH development. In some cases such patients during HM show rhythm-dependent valuable ST depressions. In BFM cases of left ventricular myocardial strain syndrome are found, similar cases are also seen in stress-echocardiography. However, in some cases one fails to define the reason of ST changes even approximately. One of the factors leading to disturbances of repolarization processes in hypertensive patients may be disturbances of microcirculation at the level of prearteriols and capillaries.
Terapevticheskii arkhiv. 2008;80(5):67-73
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Unusual variant of pulmonary lesion (lymphocytic interstitial pneumonitis) in systemic lupus erythematosus

Blagova O.V., Sarkisova N.D., Nedostup A.V., Petukhova N.V., Rodionov A.V.
Terapevticheskii arkhiv. 2008;80(5):79-82
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Variants of antiphospholipid syndrome: some new conceptions?

Asherson R.A.
Terapevticheskii arkhiv. 2008;80(5):83-85
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Arterial hypertension and systemic inflammatory process: current status

Shilkina N.P., Iunonin I.E., Stoliarova S.A., Mikhaĭlova É.V.
Terapevticheskii arkhiv. 2008;80(5):91-96
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