[The place of riociguat in the treatment of patients with pulmonary arterial hypertension associated with systemic connective tissue diseases].

Pulmonary hypertension (PH) can develop in different systemic autoimmune rheumatic diseases (SARD), such as systemic scleroderma (SSD), systemic lupus erythematosus, rheumatoid arthritis, and mixed connective tissue disease In most cases, patients with SARD develop WHO group I PH (pulmonary arterial hypertension associated with systemic connective tissue diseases, PAH-SCTD). General prevalence of this pathology reaches 15 cases per million adults. Most cases of PAH-SCTD are induced by SSD. Survival of PAH-SCTD patients is generally lower than survival of patients with other forms of LAH. Treatment of any SARD, including in LAH, implies a complex approach using glucocorticoids, disease-modifying anti-rheumatic drugs (cyclophosphamide, methotrexate, azathioprine, and others), and genetically engineered biologics. Specific targeted therapy is indicated for most patients with PAH-SCTD. The representative of a new class (soluble guanylate cyclase (sGC) stimulators), riociguat, has been approved for the treatment of PAH. This drug has a unique double mechanism of action: (i) sGC sensibilization to endogenous nitric oxide (NO) by stabilizing the NO-sGC bond; and (ii) direct, NO-independent sGC stimulation. For patients with PAH-SCTD, riociguat is the major alternative to phosphodiesterase-5 inhibitors both as monotherapy and combination therapy.

[A clinical case of visceral toxocariasis as a cause of eosinophilic polyserositis].

The aim of the present report is to describe a clinical case of toxocariasis. 37-year - old man was admitted to Pirogov Municipal Clinical Hospital No.1 in Moscow. He was presented with intense generalized abdominal pain. Three months before the described hospitalization, the patient had acute bronchitis, then pneumonia. During the examination there were found hyperthermia, ascites, shortness of breath, sweating, hypereosinophilia. Patient lost 8 kilos over the last 6 months. There were arisen many hypotheses, however, after a more detailed survey about patient's life it turned out that he travelled a lot. So that the parasitosis became the main conjecture, which later was confirmed by serological tests.

Clinical observation pseudoobstruction syndrome of the stomach's output part and small intestine of a patient with systematic lupus erythematosis.

Stomach's output part and small intestine, combining with damaging of the urinary tract is a rare systemic lupus eritematosus (SLE) manifestation. The patient is 32 years old, suffering from SLE with damaged join, blood system, secondary antiphospholipid syndrome with pulmonary embolism in the history and formation of high postembolic pulmonary hypertension on therapy with hydroxychloroquine and low doses of corticosteroids, was hospitalized because of persistent nausea, vomiting, loss of more than 10 kg body weight 1.5 months. The research have shown the obstruction's formation of the stomach's output part, small bowel obstruction at several levels, as well as thickening of the bladder wall and the unilateral expansion of the ureter. Against the backdrop of strengthening of immunosuppressive therapy these lesions completely regressed.

[The clinical observation of NK/T-cell lymphoma of the nasal type]. / Klinicheskoe nabliudenie NK/T-kletochnoi limfomy nazal'nogo tipa.

The objective of the present work was to present the results of the clinical analysis of the patient presenting with natural killer (NK)/T-cell lymphoma of the nasal type. We undertook the analysis of the medical documentation concerning the case of interest. It was shown that the development of progressive perforation of the nasal septum and the pronounced destructive changes in the intranasal and adjacent structures following the endonasal surgical interventions made necessary differential diagnostics between the condition under consideration and certain latent disorders (such as Wegener's granulomatosis, leprosy, syphilis, leishmaniasis, dirofilariasis tuberculosis, etc.). The study has demonstrated that the negative results of the analysis imply the necessity of special attention to the possibility of development of oncological diseases including hematological disorders (e.g. NK/T-cell lymphoma) and the repeat careful follow-up examination of the patients by the experienced experts.

[The problem of cardiac safety of nonsteroidal anti-inflammatory drugs].

The paper considers an update on the mechanisms for the development of adverse reactions of nonsteroidal anti-inflammatory drugs on the cardiovascular system.

[The post-streptococcal diseases in the clinical practice].

The authors describe various clinical forms of streptococcal infections, the pathogenetic mechanisms underlying these conditions, and peculiarities of their clinical picture. Also considered are the modern methods employed for laboratory diagnostics of streptococcal infections. The probability of the risk of development of post-streptococcal diseases in the children is evaluated. Measures for the prevention of these conditions are proposed.

[Analysis of the state-of-the-art of consulting medical care to patients with glucocorticoid-induced osteoporosis or its risk according to the data of a questionnaire survey (GLUCOST study)].

AIM: To analyze the state-of-the-art of consulting medical care to Russian patients with glucocorticoid-induced osteoporosis (GCOP) or its risk. SUBJECTS AND METHODS: This GLUCOST study was organized and conducted by the Russian Association of Osteoporosis. A total of 1129 patients with chronic inflammatory diseases, who had been taking oral glucocorticosteroids (OGCSs) a long time (3 months or more), were examined. The patients filled out an anonymous questionnaire on their own. Whether the measures taken to diagnose, prevent, and treat GCOP complied with the main points of Russian clinical guidelines was assessed. RESULTS: 61.8% of the patients knew that the long-term treatment of GCOP might cause osteoporosis. 48.1% of the respondents confirmed the results of bone densitometry; 78.1% of the patients reported that they had been prescribed calcium and vitamin D supplements by their physician, but their regular intake was confirmed by only 43.4%; 25.4% of the patients had sustained one low-energy fracture or more. Treatment for GCOP was prescribed for 50.8% of the patients at high risk for fractures, but was actually received by 40.2%. Therapeutic and diagnostic measures were implemented in men less frequently than in women. When the patient was aware of GCOP, the probability that he/she would take calcium and vitamin D supplements rose 2.7-fold (95% Cl; 2.1 to 3.5; p = 0.001) and that he/she would follow treatment recommendations did 3.5-fold (95% Cl; 2.3 to 5.3; p = 0.001). Bone densitometry increased the prescription rate for antiosteoporotic medication and patient compliance. CONCLUSION: According to the data of Russia's large-scale GLUCOST survey, every four patients with chronic inflammatory disease who are on long-term OGCS therapy have one low-energy fracture or more. Due to inadequate counseling, the patients are little aware of their health and do not get the care required to prevent the disease. Less than 50% of patients who have GCOP and a high risk for fractures undergo examination and necessary treatment aimed at preventing fractures.

[Characteristics of immune response and inflammatory reaction in atherothrombotic stroke and myocardial infarction]. / Osobennosti immunnogo otveta i vospalitel'noi reaktsii pri aterotromboticheskom insul'te i infarkte miokarda.

AIM: To study characteristics of ischemic tissue damage basing on the assessment of the correlations between markers of immune response, inflammation and apoptosis in patients with myocardial infarction (MI) and atherothrombotic stroke (AS). MATERIAL AND METHODS: Concentrations of matrix metalloproteinase-9 (MMP-9), immune complexes with cryogenic properties, soluble Fas-ligand, tumor necrosis factor alpha, interleukin-10 measured with ELISA as well as the activity of spontaneous apoptosis of mononuclear cells and surface expression of Toll-like receptors-4 and intracellular heat shock proteins measured with flow cytofluorometry were determined in the blood of 93 patients with the first AS and 94 patients with MI without concomitant inflammation in the 1st and 7th day of the disease. RESULTS AND CONCLUSION: Increased levels of the markers of immune response, inflammation, apoptosis and destruction of the extracellular matrix were identified at the beginning of MI and AS. The results provide the evidence that similar mechanisms may be involved in ischemic tissue damage. Multivariate analysis conducterd by of principal component analysis correlation matrix revealed the specificity of the relationships between all of these markers. This is the completely new approach to assessin the role and importance of defined parameters in the acute period of the myocardial ischemia and brain.

[Clinical efficacy instant goat milk in the complex therapy and prevention of osteoporosis in patients with rheumatoid arthritis].

Osteoporosis (OP) in rheumatoid arthritis (RA) refers to a secondary immune-mediated metabolic osteopathy characterized by periarticular and systemic decreased bone mass, impaired bone strength and increased risk of fractures. According to some studies, adding milk in the diet helps to increase bone mineral density and to reduce the risk of osteoporosis and maintain normal levels of vitamin D. To study the state of mineral and bone metabolism in RA patients zeith osteopenic syndrome and to evaluate the effectiveness of treatment and prevention of OP by adding dry goat milk "Amalteya" in the diet. The study included 42 patients with a documented diagnosis of RA (ACR, 1987) - 23 men (mean age 59 years) and 19 postmenopausal women (mean age 62 years) with the presence of osteoporosis and osteopenia according to the dual-energy X-ray absorptiometry. 21 (50%) RA patients (main group) received standard antiosteoporotichesky (alendronate 70 mg/week + calcium 1000 mg/day + Vitamin D3 800 IU/day) therapy and milk powder Amalteya® (400 ml/day). The control group (21 patients with RA) received only standard antiosteoporotic therapy. Follow-up lasted for 6 months. The concentration of total calcium in the blood of RA patients was on average 2.33 mmol/l, ionized Ca - 1,18 mmol/l and inorganic P - 1,09 mmol/l, which corresponds to normal values. Vitamin D deficiency was found in 17,5% of patients, and failure - in 32,5% of patients with RA. After 6 months of the treatment it was found that b-CrossLaps levels tend to be reducing in both of the groups and with reduction of bone formation marker osteocalcin in the group not receiving goat milk. Also, due to the background of ongoing combinative therapy it was clear that concentrations of 1,25(OH)2D and 25(OH)D in the blood serum are increasing (by 18,5-28,2% at the main group and by 8,0-17,9% at the control group), however, inter-group differences was below the level of the reliable importance. It was strongly marked in the group who received goat's milk "Amalteya®". Reduced levels of vitamin D in the blood is typical for 50% of RA patients with osteopenic syndrome with normal values of calcium-phosphorus metabolism. Combination therapy and prevention of osteoporosis in patients with RA with an additional inclusion in the diet of the daily administration of 400 ml of goat's milk Amalthea® has a positive impact on bone metabolism.

[Peculiarities of clinical and laboratory characteristics of the activity of streptococcal infection in the patients presenting with tonsillar pathology].

The objective of the present study was to characterize peculiar clinical and laboratory features of trivial tonsillitis for the substantiation of the necessity of prescription of antibacterial therapy. A total of 386 patients presenting with various forms of trivial tonsillitis were available for the determination of anti-streptococcal antibody (ASLO, anti-DN-ase B, ASPH) levels. The results of the measurement were compared based on the Centor scale generally used to estimate the necessity of prescribing antibacterial therapy for the treatment of sore throat. It is concluded that laboratory studies of characteristics of S. Рyogenes activity are needed in all the patients presenting with tonsillitis in order to elucidate the etiological factors responsible for pharyngalgia and the necessity of prescription of antibacterial therapy for the prevention of pyogenic systemic complications of streptococcal infection.

[Pulmonary hypertension in rheumatic heart disease: current approaches to diagnosis and therapy].

Pulmonary hypertension is a complex multidisciplinary problem in modern medicine. This review discusses its clinical and pathophysiological type associated with rheumatic heart disease. Current approaches to the pathogenesis and diagnosis of the disease are reflected; basic approaches to its treatment are discussed in terms of current clinical guidelines and new scientific achievements.

[The efficiency and safety of adalimumab treatment in patients with active rheumatoid arthritis unresponsive to standard therapy: Russian national study results].

AIM: To confirm the efficacy and safety of adalimumab (ADA) added to the standard antirheumatic therapy performed in patients with rheumatoid arthritis (RA) of moderate and high activities. SUBJECTS AND METHODS: The open-labeled multicenter study enrolled 100 adult patients (11 men, 89 women; mean age 50.9 +/- 11.1 years) with active RA according to the ACR criteria (1987) despite their treatment with disease-modifying antirheumatic drugs, the average number of which in the history was 2.1 per man. At baseline, DAS28 CRP was as many as 6.2 +/- 0.84 scores; C-reactive protein (CRP) was 37.1 +/- 34.7 mg/l. In accordance with the indications officially registered in the European Union and the Russian Federation, ADA was given in a dose of 40 mg 2 weeks. Before administration of the drug, every patient underwent screening examination for tuberculosis, which used a tuberculin test and chest X-ray. The screening covered a period of the treatment up to 24 weeks and its subsequent period within 70 days after administration of the last dose of ADA in order to study its safety. RESULTS: DAS28-CRP scores decreased from 6.14 +/- 0.86 (at baseline) to 3.39 +/- 1.1 (by the end of the study). At 12 weeks, 22% of the patients achieved a low RA activity (DAS28-CRP < or = 3.2 scores); 14% achieved clinical remission (DAS28-CRP < or = 2.6 scores); at 24 weeks, these were 37 and 25% of the patients, respectively. There were differences in effectiveness in terms of the baseline disease activity. At 24 weeks, ACR20, ACR50, and ACR 70 responses were achieved in 88, 67, and 26% of the patients, respectively. The HAQ functional index reduced from 1.9 +/- 0.6 (at baseline) to 1.081 +/- 0.64 (at 12 weeks) and 1.04 +/- 0.68 (at 24 weeks) scores. Twenty-four patients were recorded as having 40 adverse reactions (AR), including only one severe AR (septic arthritis). There were no cases of tuberculosis. CONCLUSION: The Russian multicenter study demonstrated the high clinical efficacy of ADA in patients with the moderate and high activity of RA unresponsive to standard therapy, as well as its satisfactory safety.

Cryoglobulin composition in patients with myocardial infarction.

The formation of an ischemic focus in the myocardium is paralleled by autoimmune processes involving immunoglobulins with abnormal thermal solubility, cryoglobulins. Serum levels of cryoglobulins and their complexes were measured in 25 patients with Q-forming myocardial infarction on days 1, 2, 3, 7, and 14 of the disease. Cryoprotein levels were measured by spectrophotometry, concentrations of IgM, IgA, IgG, and fibronectin by ELISA. Cryocomplexes in patients with myocardial infarction consist of polyclonal immunoglobulins of the main classes IgG and IgM, less often IgA, while cryoglobulinemia in this patient population is referred to type III according to the commonly used classification by Brouet. Fibronectin was detected in the cryocomplexes throughout the entire period of observation, its dynamics being opposite to that of the cryocomplexes level.

[Low back pain in young subjects: a new approach to therapy].

AIM: To evaluate the efficiency and safety of arthrofoon versus sublingual nimesulide in patients with degenerative disc disease (DDD) in two parallel groups. SUBJECTS AND METHODS: Fifty patients (males and females) aged 18-35 years who had acute and chronic low back pain (LBP) (visual analog scale (VAS), > 40 mm) associated with DDD were enrolled in the study. Therapeutic efficiency was evaluated from the intensity of pain (VAS), spinal function (Schober's test and Tomayer's test), the severity of disease (VAS), assessed by a physician and a patient, and the frequency of recurrent pain episodes. RESULTS: The evaluation of the efficacy of arthrofoon showed a statistically significant positive change in pain (VAS), which corresponded to that in the indices of the pain syndrome during nimesulide administration. There was a statistically significant reduction in the frequency of recurrences in patients with chronic intermittent LBP treated with arthrofoon (p < 0.01). Arthrofoon used alone and in combination with paracetamol demonstrated a good safety profile. CONCLUSION: In DDD-associated LBP, the use of arthrofoon is effective and safe in young patients with both the acute (in combination with nonsteroidal anti-inflammatory drugs as a short course) and chronic (requiring long-term anti-inflammatory therapy) types of the disease.

[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)].

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.

[An effect of perindopril on the level of tumor necrosis factor-alpha and matrix metalloproteinase-9 in peripheral blood in the acute period of atherothrombotic ischemic stroke and myocardial infarction].

Twenty-nine patients with acute atherothrombotic ischemic stroke and 36 patients with acute Q-wave myocardial infarction have been studied. Each group has been stratified into 2 subgroups: patients of subgroups A received an ACE inhibitor perindopril in the complex therapy from the 1st day of disease. Patients of subgroups B were not assigned to this drug. Along with routine tests, the level of tumor necrosis factor-alpha and matrix metalloproteinase-9 (MMP-9) measured with ELISA using test-systems (BCM Diagnostics, USA) and reagents (R&D, England) have been determined. The administration of perindopril did not cause side-effects, including arterial hypotonia after the first dosage, in patients in the acute period of atherothrombotic ischemic stroke and myocardial infarction. Perindopril may decrease the activity of MMP-9 in these patients and produces an anticytokine effect. Some similar mechanisms of ischemic lesions of the heart and the brain and a commonness of biochemical "response" to the same medical intervention (the administration of an ACE inhibitor perindopril) in patients of both groups were found. The results support the pathogenetic validity of perindopril therapy in the secondary prevention of ischemic stroke and myocardial infarction.

[Calcified aortal stenosis and osteoporosis: bone metabolism of systemic calcium metabolism in the elderly].

AIM: To examine bone tissue, systemic calcium metabolism and bone remodeling in patients with calcified aortal stenosis of degenerative origin (DAS). MATERIAL AND METHODS: The examination of 310 patients (mean age 73.2 years) was made with application of questioning, echocardiography, double energetic x-ray absorptionmetry, measurements of C-telopeptides, osteocalcin, vitamin D, parathyroid hormone with solid phase enzyme immunoassay. RESULTS: Bone tissue mineral density (BTMD) was abnormal in 71% of examinees (osteopenia--40%, osteoporosis--31%). Vitamin D concentration under 50 nmol/l was in 76.3%, parathyroid hormone elevated above 100 pg/ml in 15.8% patients. CONCLUSION: The severity of lumbar spine affection depended on severity of calcinosis of aortic valve, was associated with lowering of osteosynthetic activity and was not associated with the presence of osteoporosis risk factors, constitutional parameters, calcium metabolism changes. This suggests the existance of a special form of BTMD disorder in elderly patients with aortal stenosis.

[Nosological diagnosis and outcomes of arthritis associated with streptococcal infection].

AIM: To specify the course and outcomes of arthritides associated with streptococcal infection (AASI). MATERIAL AND METHODS: The trial comprised 60 patients with arthritis (mean age 26.8 +/- 14.0). The patients met the following criteria: arthritis, elevated (< 500 U) titers of antistreptolisin-0 in the absence of heart disorders detected at Doppler-echocardiography (2D-echoCG), urogenital infection, Yersinia infection, psoriasis. In addition to routine clinical tests, the following investigations were made: tests for alloantigen of B-lymphocytes D8/17 and antigen HLA-B27, antibodies to polysaccharide of streptococcus of group A, bacteriological test of laryngeal smears for streptococcal infection, prospective follow-up (mean 31.2 +/- 19.6 mon) with 2D-echoCG. RESULTS: Rheumatic arthritis was rejected in 33.3% patients. Other diseases were diagnosed: early rheumatoid arthritis (10%), seronegative spondylarthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, Still's disease, Konig's disease, sarcoidosis, gout, arthritis on the background of streptococcal nodular erythema. Acute rheumatoid fever (ARF) was diagnosed in 56.7% patients, poststreptococcal arthritis (PSA) in 10%. PSA differed from ARF by onset at the age of 36.0 +/- 10.2 years, short latent period (11.2 +/- 1.3 days), a significantly longer course of arthritis (95.0 +/- 3.9 days), recurrences. Alloantigen of B-lymphocytes was detected in 52.8% AASI patients (the difference from the control is highly significant (p < 0.001). Arthritis development was not associated with carriage of HLA-B27 carriage. CONCLUSION: In examination of AASI patients for diagnosis of ARV and PSA it is necessary to reject other diseases among which early RA (10%) is most frequent. It is recommended to make diagnosis of ARF in AASI patients with definition of risk factors (age 7-15 years, family history of rheumatic fever, carriage of alloantigen d8/17), 2.5-year and longer follow-up with 2D-echoCG. Diagnosis of PSA is made in rejection of ARF and in the presence of the following characteristics: development of the disease at the age 30-40 years, a short latent period of the infection, long-term persistent course of arthritis, insufficient effect of nonsteroid anti-inflammatory drugs, frequent affection of sacroiliac joints, recurrence, entezopathy.

Heart rate variability is related to disease activity and smoking in rheumatoid arthritis patients.

We investigated the heart rate variability (HRV) parameters in patients with rheumatoid arthritis (RA) and assessed their relationship with disease characteristics. Twenty-three female patients with RA [age 48+/-7 (mean+/-SD) years] free of cardiovascular diseases and 23 age- and gender-matched healthy controls were evaluated. After careful clinical examination, the following parameters were obtained after 24-h Holter recordings: average of all normal-to normal (NN) intervals over the entire 24-h ECG recording (meanNN, ms); the standard deviation for the time between NN complexes (SDNN, ms); the standard deviation of the average NN intervals for each 5-min period (SDANN, ms) and the square root of the mean-squared differences of successive NN intervals (rMSSD, ms). We also assessed quantitative parameters of the Poincaré plot: the standard deviation of the points perpendicular to the line-of-identity (SD1, ms); the standard deviation along the line-of-identity (SD2, ms) and their ratio (SD12). HRV parameters excluding SD2 were significantly lower in patients with RA, than in control group (p<0.05). Significant correlations of SDNN and SDANN with swollen joints count, Ritchie articular index, disease activity score (DAS) and disease duration were found. SDNN also correlated with leucocyte count and smoking. SD1 significantly correlated only with disease duration. Relationships between SDNN and smoking, swollen joints count and DAS were confirmed using multivariate analysis. Our data indicate that in patients with RA reduced HRV is independently associated with high disease activity and smoking. HRV assessment may be useful as a part of cardiovascular risk stratification in RA patients.