Vol 88, No 12 (2016)


Prospects for rheumatoid arthritis pharmacotherapy: New opportunities and recommendations

Nasonov E.L.


The paper considers a current strategy, international and Russian recommendations for the pharmacotherapy of rheumatoid arthritis (RA), one of the most common and severe human immune-mediated inflammatory diseases. It emphasizes the need for early diagnosis and therapy with disease-modifying antirheumatic drugs, primarily methotrexate (MT), starting at the onset of the disease, and careful monitoring of therapeutic effectiveness, allowing RA remission to be achieved with a treatment-to-target strategy. The author discusses recent RA pharmacotherapy advances that are related to the rational use of MT, biological agents, and the new targeted JAK inhibitor tofacitinib.
Terapevticheskii arkhiv. 2016;88(12):4-10
pages 4-10 views

The values of cardio-ankle vascular and ankle-brachial indices in patients with carbohydrate metabolic disorders: The ESSE-RF study in the Kemerovo Region

Sumin A.N., Bezdenezhnykh N.A., Fedorova N.V., Shcheglova A.V., Indukaeva E.V., Artamonova G.V.


Aim. To investigate factors associated with pathological cardio-ankle vascular and ankle-brachial indices (CAVI and ABI) in patients with carbohydrate metabolic disorders (CMD). Subjects and methods. A cross-sectional study was conducted in the framework of the multicenter epidemiological study “Epidemiology of Cardiovascular Diseases and Their Risk Factors in the Russian Federation” (ESSE-RF) in March to October 2013. The standard ESSE-RF protocol was extended by an additional study of peripheral arterial stiffness, by estimating CAVI and ABI automatically. A sample of 1619 people was formed in several stages, in which 311 patients with type 2 diabetes mellitus and prediabetes were identified and divided into 3 groups: 1) 41 patients with pathological CAVI values (≥9.0); 2) 241 with normal CAVI (<9.0); 3) 29 with pathological ABI (<0.9). Results. In the population-based sample of patients with CMD, the pathological CAVI values (≥9.0) were detected in 14.5%, and the pathological ABI was in 9.3% of the examinees. Regression analysis showed that the pathological vascular indices (both CAVI and ABI) were significantly associated with increases in blood pressure (BP) and heart rate (HR), and a decrease in glomerular filtration rate. At the same time, only the pathological CAVI was associated with advancing age (odds ratio (OR), 1.111; 95% confidence interval (CI), 1.050-1.176; p < 0.001), visceral obesity (OR, 3.088; 95% CI, 1.001-10.495; p=0.038), smoking duration (OR, 1.093; 95% CI, 1.008-1.185; p=0.009), prior stroke (OR, 4.695; 95% CI, 1.408-15.658; p=0.018), and a need for insulin therapy (OR, 18.947; 95% CI, 1.902- 87.783; p=0.006). The pathological ABI was associated with male sex (OR, 2.227; 95% CI, 1.040-4.765; p=0.039), prior myocardial infarction (OR, 8.646; 95% CI, 2.174-34.378; p=0.005), obesity (OR, 2.439; 95% CI, 1.010-5.889; p=0.034); hyperglycemia (OR, 2.439; 95% CI, 1.010-5.889; p=0.034), hyperuricemia (OR, 4.009; 95% CI, 1.850-8.684; p=0.033), and increases in triglyceride levels (OR, 2.984; 95% CI, 1.376-6.470; p=0.004) and CAVI (OR, 1.193; 95% CI, 1.034-1.377; p=0.005). Conclusion. The pathological vascular indices CAVI and ABI are associated with different risk factors for cardiovascular events in a cohort of patients with CMD. The common factors associated with both CAVI and ABI are increases in blood pressure and HR and a reduction in glomerular filtration rate. The common factors associated with both CAVI and ABI are increases in blood pressure and HR and a reduction in glomerular filtration rate.
Terapevticheskii arkhiv. 2016;88(12):11-20
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Evaluation of the hemostatic potential at coronary artery bypass surgery during long-term aspirin therapy

Gruzdeva O.V., Fanaskova E.V., Akbasheva O.E., Uchasova E.G., Penskaya T.Y., Plotnikov G.P., Dyleva Y.A., Krivoshapova K.E., Barbarash O.L.


Aim. To estimate thrombin generation test parameters in patients with coronary heart disease during coronary artery bypass surgery under extracorporeal circulation after transfusion of donor platelet concentrates during long-term therapy with acetylsalicylic acid (ASA). Subjects and methods. A total of 148 patients with coronary heart disease who had undergone elective primary coronary artery bypass surgery under extracorporeal circulation during preserved therapy with ASA (75-100 mg/day) were examined. According to donor platelet concentrate transfusion, all the patients were divided into 2 groups: 1) 76 patients undergoing donor platelet transfusion and 2) 72 without this procedure. A control group consisted of 20 apparently healthy individuals. At the pre-, intra-, and early postoperative stages, the investigators evaluated the following thrombin generation test parameters: lag time (min); peak thrombin concentration (nM/l); time to peak (min); the area under the thrombin generation curve (nM), and thrombin generation rate (nM/min). Results. During long-term ASA therapy, the patients were found to have an activated endogenous thrombin potential in the pre- and intraoperative periods, as evidenced by the high peak concentration of thrombin and the increased rate of its generation. At the same time, the time of prothrombinase complex activation and that of thrombin generation were longer than those in the control group. In the early postoperative period, the patients who had not been transfused with platelet concentrates with a further increase in the temporal parameters, showed a decreased hemostatic potential, reaching the control level, whereas donor platelet transfusion stimulated endogenous thrombin generation: the time to initiate clotting and that to reach the peak were shorter; in this case, the thrombin generation rate and concentrations increased, but the preoperative level was not reached. No perioperative (hemorrhagic or thrombotic ischemic) events were noted in the examined groups. Conclusion. The hemostatic potential was preserved in patients receiving long-term therapy for ASA. Taking into account laboratory and clinical findings, platelet concentrate transfusions are unnecessary for preventive purposes. The appropriateness of donor platelet transfusion should be strictly individually approached with regard to the laboratory parameters of the thrombin generation test, by minimizing the risk of perioperative ischemic and hemorrhagic events in each specific patient.
Terapevticheskii arkhiv. 2016;88(12):21-27
pages 21-27 views

Estimation of poor prognostic factors in patients with pulmonary artery thromboembolism

Vasiltseva O.Y., Vorozhtsova I.N., Lavrov A.G., Karpov R.S.


Aim. To identify predictors of fatal outcome in hospitalized patients with risk factors (RF) for pulmonary artery thromboembolism (PATE) during its occurrence. Subjects and methods. To determine predictors of fatal outcome in patients with PATE, the data of a 10-year city hospital pulmonary embolism registry were used to analyze RF for PATE (according to European and Russian guidelines), complaints, medical histories, and laboratory and instrumental data, which can be identified at general surgery or general therapy hospital, as well as a nosological entity existing in the patients. Results. According to the existing idea on thrombogenesis, RF for PATE and its fatal outcome, information about used treatment, and autopsy data, 137 parameters were selected in patients with PATE. For estimating the risk of death in patients with PATE, a logistic regression analysis was employed to make a mathematical model encompassing 10 indicators: bed rest; the presence/absence of lung diseases; chronic venous insufficiency; obesity; the symptom complex of cor pulmonale; postinfarction cardiosclerosis of the left ventricle, pericardial effusion; right atrial dilatation; right ventricular dilation; right ventricular systolic pressure >36 mm Hg as evidenced by echocardiography. Conclusion. The mathematical model built during the study allows the calculation of a risk for fatal outcome in the development of PATE for a specific patient in terms of its individual characteristics.
Terapevticheskii arkhiv. 2016;88(12):28-32
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Triple antianginal combinations in the treatment of elderly and senile patients with stable angina

Kanorskii S.G., Smolenskaya N.V.


Aim. To compare the efficiency and safety of antianginal therapy (AAT) using a combination of bisoprolol, ivabradine, and trimetazidine or ranolazine in elderly and senile patients with stable angina. Subjects and methods. The study enrolled 107 patients aged 60 to 79 years with coronary heart disease and Functional Class II and III angina. When the patients taking bisoprolol 1.25—2.5 mg once daily and ivabradine 2.5—7.5 mg twice daily continued to have angina and/or silent myocardial ischemia, after randomization 54 patients received an additional 35 mg of trimetazidine twice a day and 53 patients had ranolazine 500 mg twice daily. A comprehensive clinical and instrumental study was conducted prior to randomization and after 6 months of triple AAT. Results. The patients tolerated well both treatments that substantially improved the results of a treadmill exercise test. Trimetazidine reduced to a greater extent the duration of silent ST-segment depression, as evidenced by Holter monitoring. Trimetazidine and ranolazine comparably improved left ventricular systolic and diastolic function, large arterial structure and function, and quality of life in the patients. Conclusion. The combinations of the low-dose β-blocker with ivabradine and trimetazidine or ranolazine may be used to treat refractory stable angina in elderly and senile patients. Trimetazidine is preferred due to its higher efficacy in treating silent myocardial ischemia and to its lower cost.
Terapevticheskii arkhiv. 2016;88(12):33-40
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Anti-Müllerian hormone as an indicator of reproductive health in women with obesity and concomitant polycystic ovary syndrome

Durmanova A.K., Otarbaev N.K.


Aim. To investigate the ovarian reserve and a relationship between the level of anti-Müllerian hormone (AMH) with that of hormones in reproductive-aged women with abdominal obesity concurrent with and without polycystic ovary syndrome (PCOS). Subjects and methods. A total of 157 women aged 18 to 45 years with a body mass index (BMI) of more than 30 kg/m2 were examined. The 157 women with abdominal obesity were conventionally divided into 2 groups: 1) 20 with PCOS and 2) 137 without this condition. Morphometric parameters, the indicators of carbohydrate and lipid metabolism, and the levels of hormones, including AMH, were studied. Results. The patients with PCOS had statistically significantly elevated AMH levels (11.26±2.63 ng/ml; p<0.0001). The group of obese patients without PCOS showed a negative correlation of the levels of AMH with those of follicle-stimulating hormone (FSH) (p=0.0004), luteinizing hormone (LH) (p=0.0171), and HOMA-IR (p=0.0572). Conclusion. In reproductive-aged women with abdominal obesity without concomitant PCOS in the presence of insulin resistance, the ovarian reserve decreases and the levels of FSH and LH increase, which leads to accelerated aging processes in the reproductive system. In this case, the patients with PCOS display a significant increase in the AMH levels; therefore, their determination can be used in the algorithm for diagnosing PCOS.
Terapevticheskii arkhiv. 2016;88(12):41-44
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Impact of smoking on kidney transplantation outcomes

Stolyar A.G., Tomilina N.A.


Aim. To investigate the impact of smoking on kidney transplantation outcomes. Subjects and methods. The materials of 350 patients (including 229 (65.4%) men aged 37.1±0.6 years) who had undergone kidney allotransplantation (KAT) for end-stage renal disease were analyzed. The main outcomes of KAT (patient status (alive or dead); renal allograft (RAG) function or dysfunction; development of chronic transplant nephropathy (CTN)), were studied. Results. There were 52 (14.8%) smoking patients (50 (96.2%) men and 2 (3.8%) women). The survival rate of smokers after KAT was significantly lower (p=0.043), as was the duration of graft function in the smoking patients (p=0.038). There were statistically significant associations of smoking with age, sex, time to normalize post-KAT serum creatinine concentrations, the development of CTN and graft rejection crises, postoperative hypertension, post-KAT serum creatinine, hemoglobin, and albumin levels, pretransplantation alanine aminotransferase concentrations, pre-KAT left ventricular hypertrophy, patient compliance with the prescribed treatment regimen, the presence or absence of a job in the patient after KAT (p<0.05). The investigators built models for predicting the outcome of KAT for a patient’s life and the development of CTN from preoperative patient risk factors, as well as a model of a RAG outcome from the factors of the pre-transplantation period and those seen one year after KAT. The impact of smoking on outcomes of KAT was revealed in all models along with other predictors. Conclusion. Smoking is an important predictor of kidney transplantation outcome for both patients’ lives and RAG function.
Terapevticheskii arkhiv. 2016;88(12):45-50
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Role of fibroblast growth factor 23 in the development of cardiovascular diseases in patients with end-stage renal failure on programmed hemodialysis

Dzgoeva F.U., Sopoev M.Y., Bestaeva T.L., Khamitsaeva O.V., Ktsoeva F.A., Sageeva R.O.


Aim. To determine the nature of changes in fibroblast growth factor 23 (FGF-23) and other bone mineral metabolism parameters detectable in the blood of patients with end-stage chronic renal failure (CRF) and to analyze their links to the development of cardiovascular events in uremic intoxication. Subjects and methods. A total of 75 patients (45 men and 30 women) aged 23 to 66 years (mean age, 53±2.1 years) with Stage VD CKF were examined. The levels of parathyroid hormone (PTH), calcium, phosphorus, the morphogenetic protein FGF-23, and the cardiospecific protein troponin I were investigated. Doppler echocardiography was performed on an Aloka 4000 machine. Left ventricular (LV) mass index (LVMI), LV systolic and diastolic function, and peak systolic blood flow velocity in the aortic arch (Vps) were estimated. Results. As LVMI became higher, there were increases in the level of PTH and that of FGF-23 that plays a significant role in the processes of bone remodeling and vascular calcification. Analysis of correlations between a change in FGF-23 concentrations depending on the morphological and functional parameters of the cardiovascular system (CVS) revealed a strong direct correlation between FGF-23 levels and LVMI (r=0.746; p<0.01), a significant inverse correlation between FGF-23 and ejection fraction (r=-0.901; p<0.05), and a direct correlation of FGF-23 and troponin I (r=0.544; p<0.05). Conclusion. FGF-2 increasing from moderate to very high levels indicates that there is a high risk for remodeling processes in the CVS even in the absence of baseline echocardiographic signs of myocardial hypertrophy, normal aortic pulse wave velocity, and compensation of other risk factors, such as hypertension, uremia, hyperparathyroidism, even without increasing the markers of cardiovascular events, such as hyperphosphatemia. The elevated level of FGF-23 suggests that there is a need for cardioprotective therapy, the goal of which is to correct of the level of this factor.
Terapevticheskii arkhiv. 2016;88(12):51-56
pages 51-56 views

The role of renal anemia and cardiovascular disease in the progression of chronic glomerulonephritis

Murkamilov I.T., Gordeev I.G., Kaliev R.R.


Aim. To study the rate of chronic glomerulonephritis progression when added by anemia and cardiovascular disease (CVD). Subjects and methods. 231 patients (133 men and 98 women) with predialysis chronic glomerulonephritis (CGN) were examined. The patients’ mean age of was 35.8±11.8 years; the disease duration was 1 to 17 years. The disease onset was the date when urinalysis showed evidence of persistent proteinuria and (or) hematuria. Besides, the time when anemia developed and the clinical and instrumental signs of CVD appeared was taken as the initial reference point; the time when end-stage renal failure was diagnosed was taken to be the endpoint. Red blood cell counts with the inclusion of its indices, hemoglobin concentration, hematocrit values, daily proteinuria values, and glomerular filtration rate were analyzed. The biochemical parameters included the concentrations of electrolytes, creatinine, fibrinogen, iron, cholesterol, total protein and C-reactive protein (CRP). Electrocardiography and echocardiography, bicycle ergometry and 24-hour ECG monitoring were used to detect CVD. Results. The presence of anemia and CVD in patients with predialysis CGN versus those without anemia and CVD was associated with an increase in the concentrations of CRP [36.2 and 12.6%; respectively; (p<0.05)], creatinine [123.0 (83.2—217.0) and 86.5 (72.0—128.5) µmol/L; (p<0.05)] and a decrease in GFR [65.4 (30.8—95.5) and 92.7 (64.5—122.3) ml/min; (p<0.05)]. The 8-year survival of patients with CGN concurrent with CVD was noted to be 58% whereas the renal survival in patients with CGN + CVD + anemia was shorter and the 6-year survival in this case was as high as 52%. Conclusion. Anemia and CVD in patients with CGN serve as additional independent factors for the progression of the underlying disease. The concurrence of CGN, anemia, and CVD substantially reduces the predialysis period.
Terapevticheskii arkhiv. 2016;88(12):57-61
pages 57-61 views

The informative value of non-invasive liver fibrosis markers in patients with nonalcoholic fatty liver disease

Livzan M.A., Akhmedov V.A., Krolevets T.S., Gaus O.V., Cherkaschenko N.A.


Aim. To estimate the diagnostic and informative value of clinical and laboratory parameters in the development and progression of liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) to enhance efficiency of their treatment. Subjects and methods. An open-label case-control study included 77 patients with NAFLD. Clinical and laboratory examinations were done. To search for additional noninvasive fibrosis markers, the investigators studied the serum concentrations of insulin, leptin, adiponectin, matrix metalloproteinase-9 (MMP-9) and its inhibitors, such as tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) and TIMP-2. All the patients underwent elastometry to assess the degree of liver fibrosis with the Metavir scale with the use of a Fibroscan machine. Results. The serum levels of low-density lipoproteins, glucose, MMP-9, and leptin proved to be most informative in assessing the progression of the initial stages (1-2) of fibrosis, as were the increased liver size detected by physical examination, systolic blood pressure, carbohydrate metabolic disorders, alanine/aspartate aminotransferase levels, waist-to-hip ratio, TIMP-1, and TIMP-2 in evaluating the progression of Stage II fibrosis 2 to Stage 3. Conclusion. The clinical and laboratory parameters can serve as reliable noninvasive markers that reflect the progression of fibrotic changes in liver tissue.
Terapevticheskii arkhiv. 2016;88(12):62-68
pages 62-68 views

Efficiency of interferon therapy in patients with essential thrombocythemia or polycythemia vera

Sokolova M.A., Turkina A.G., Melikian A.L., Sudarikov A.B., Treglazova S.A., Shukhov O.A., Gemdzhian E.G., Abdullaev A.О., Kovrigina A.M., Misyurin A.V., Pliskunova Y.V., Ivanova V.L., Moiseeva T.N.


Aim. To evaluate the efficiency of interferon (IFN) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Subjects and methods. A total of 61 patients (41 with ET and 20 with PV) were examined. Prior to study enrolment, 44 (72%) patients with ET or PV received one or other therapy (aspirin was not taken into account). The mean Jak2V617F mutant allele at baseline was 23% (6—54%) in the patients with ET and 40% (11—88%) in those with PV. The median time from diagnosis to enrollment was 49 months. Results. The paper presents the clinical and molecular findings of long-term INF-α therapy in patients with ET or PV. The median follow-up was 52 months. Recombinant IFN-α2 showed its ability to induce complete hematologic remission (ET (76%), PV (70%)) and a complete molecular response. 22 (69%) out of 32 patients were noted to have a smaller number of cells with the Jak2V617F mutation. In the patients with PV and in those with ET, the relative reduction in the proportion of cells with the Jak2V617F mutant gene averaged 85% and 56% of the baseline values, respectively. There was a reduction in the proportion of cells expressing the Jak2V617F mutation in both the ET (from 12 to 2.2%; p=0.001) and PV (from 32.7% to 3.2%) groups (р=0.001). Ten (31%) patients achieved a deep molecular remission (≤2% Jak2V617F allele); among them, 5 patients were not found to have Jak2V617F mutation. The obtained molecular response remained in 7 of the 10 patients untreated for 11 to 86 months. The long-term treatment with IFN-α led to normalization of the morphological pattern of bone marrow in 5 of the 7 PV or ET patients. Conclusion. Significant molecular remissions achieved by therapy with recombinant interferon-α2 confirm the appropriateness of this treatment option in in the majority of patients with ET or PV.
Terapevticheskii arkhiv. 2016;88(12):69-77
pages 69-77 views

The efficacy and safety of etoricoxib versus meloxicam in the treatment of patients with gonarthrosis

Zavodovsky B.V., Sivordova L.E., Polyakova Y.V., Akhverdyan Y.R., Kuznetsova M.I., Zborovskaya I.A.


Aim. To evaluate the clinical efficacy and tolerability of etoricoxib and meloxicam in patients with gonarthrosis. Subjects and methods. A postregistration, open-labeled, prospective, comparative randomized study was conducted. 40 patients aged 37 to 75 years with primary knee osteoarthritis were examined. Therapeutic effectiveness was evaluated determining the functional index WOMAC with the use of a visual analogue scale (VAS). The tolerability of the drugs was assessed according to the opinions of a patient and a physician. Results. Both drugs caused a reduction in WOMAC and VAS scores for pain and the severity of the disease. Etoricoxib demonstrated a significantly high rate of occurrence and completeness of its analgesic effect. Meloxicam showed a less pronounced decrease in joint stiffness and an insufficient analgesic effect. The incidence of side effects was similar in both groups. Conclusion. Both drugs demonstrated a good tolerability and a low incidence of side effects. The efficacy of etoricoxib was significantly higher than that of meloxicam.
Terapevticheskii arkhiv. 2016;88(12):78-81
pages 78-81 views

Oligosecretory monoclonal gammopathy with renal involvement

Kozlovskaya L.V., Rameev V.V., Androsova T.V., Kogarko I.N., Kogarko B.S., Mrykhin N.N., Rekhtina I.G.


The article deals with the so-called monoclonal gammopathy of undetermined significance (MGUS), which is being actively explored in the world and has been recently investigated in Russia. It indicates the principles of identifying the phenotypes of MGUS and criteria for assessing the risk of its progression to cancer. There is an update on the possible involvement of monoclonal proteins in the pathogenesis of certain non-neoplastic kidney diseases, renal injuries in particular. The paper gives their classification and enumerates differential diagnostic techniques, including the Freelite method, a highly sensitive one to determine free light chains (FLC), prognostic criteria, and approaches to treating each separate form in relation to the phenotype of a monoclonal protein. The authors present their own data on detection rates for MGUS at a multidisciplinary hospital and a clinical case of MGUS-associated membranoproliferative glomerulonephritis, by justifying a treatment regimen containing bortezomib (velcade).
Terapevticheskii arkhiv. 2016;88(12):82-87
pages 82-87 views

A clinical case of long-term macitentan therapy in a female patient with idiopathic pulmonary hypertension

Arkhipova O.A., Martynyuk T.V., Chazova I.E.


In late 2015, the Russian Federation registered the new non-selective endothelin receptor antagonist macitentan for the pathogenetic therapy of pulmonary arterial hypertension. The given clinical case demonstrates the possibility of using macitentan in a female patient with idiopathic pulmonary hypertension and its ability to affect the clinical, hemodynamic, and functional status of patients and to slow down the progression of the disease.
Terapevticheskii arkhiv. 2016;88(12):88-93
pages 88-93 views

Polypragmasy: A clinical pharmacologist’s view

Sychev D.A., Otdelеnov V.A., Krasnova N.M., Ilyina E.S.


In the modern world, there is a rapid advance in the design and clinical introduction of a huge number of drugs that are able to cure a patient or to improve his/her health status on the one hand and to cause significant harm to his/her health on the other. Polypragmasy is the desire to enhance the efficiency of treatment and to help the patient recover from all developed diseases inevitably leads to the use of a large number of medications. At the present time, polypragmasy as a result of iatrogenia is a serious public health problem, as it is clinically manifested by a reduction in the effectiveness of pharmacotherapy, by the development of severe adverse drug reactions, and by a considerable increase in healthcare expenditures. The reason for the simultaneous prescription of multiple drugs may be comorbidity (multimorbidity), the availability of drugs, as well as clinical guidelines, manuals of professional medical associations, treatment standards that contain recommendations for using combination therapy with more than 5 drugs for only one disease in some cases, the efficiency of which corresponds to a high level of evidence. Currently, the fight against polypragmasy is one of the important tasks in rendering medical care to elderly and senile patients since it is a major risk factor of adverse drug reactions in this category of people. To minimize polypragmasy in elderly patients, it is necessary to use current methods for analyzing each prescription of a drug (the index of rational drug prescribing; an anticholinergic burden scale) and those for optimizing pharmacotherapy with the use of restrictive lists (Beers criteria, STOPP/START criteria) that will be able to reduce the number of errors in the administration of drugs and to maximize the efficiency and safety of pharmacotherapy.
Terapevticheskii arkhiv. 2016;88(12):94-102
pages 94-102 views

Idiopathic pulmonary fibrosis: The current state of the problem

Shmelev E.I.


Idiopathic pulmonary fibrosis (IPF) is a severe lung disease, with death occurring within 2-5 years after its onset. IPF affects people in the second half of life. Its causes are unknown. Before 1999, IPF was out from the group of idiopathic interstitial lung diseases as a separate nosological entity. Practitioners very often (80%) make diagnostic errors in IPF and prescribe antibiotics, anti-inflammatory drugs, which worsen the course of this disease. The distinctive feature of the pathogenesis of IPF is the absence of inflammation, which is clinically manifested by the inefficacy of glucocorticosteroids and other anti-inflammatory drugs. Pharmacological agents for the treatment of IPF have been designed since 2000. One of them has been registered and permitted for use in the Russian Federation. This paper is a review of an update on the problem of IPF, which should facilitate the appropriate orientation of physicians in diagnosing and treating this severe disease.
Terapevticheskii arkhiv. 2016;88(12):103-108
pages 103-108 views

Enoxaparin is a low-molecular-weight heparin with a complex chemical structure and various non-anticoagulant properties

Zyryanov S.K., Ushkalova E.A.


The paper discusses the non-anticoagulant properties of unfractionated heparin and enoxaparin and their relation to their chemical structures. It is emphasized that enoxaparin has multiple, often interrelated, non-anticoagulant effects that can complement its antithrombotic activity and enhance the efficiency of therapy in patients receiving the drug for various indications. The realization of these effects requires the complex structure with the standard distribution of molecular weight (Mw) (average Mw, about 4500 Da, as well as Mw of less than 2000 Da (<20%), 2000 to 8000 Da (>68%), and more than 8000 Da (<18%), and with the standard content of 1.6-anhidro rings (15—25%), which is determined by the source of raw materials and by the production technology of the original drug and cannot be fully reproduced when designing its bioanalogues.
Terapevticheskii arkhiv. 2016;88(12):109-115
pages 109-115 views

Depression, anxiety, stress, and mortality

Belialov F.I.


The analytical paper summarizes the main results of recent investigations of the relationships of depression, anxiety, and stress with overall and cardiovascular mortality. It shows that depression and stress are associated with an increased risk of death mainly from cardiovascular diseases, and depression treatment and stress control can increase life expectancy.
Terapevticheskii arkhiv. 2016;88(12):116-119
pages 116-119 views

Hereditary afibrinogenemia: A literature review and clinical observations

Yakovleva E.V., Surin V.L., Selivanova D.S., Sergeeva A.M., Gonсharova M.V., Demidova E.Y., Soboleva N.P., Makhinya S.A., Dezhenkova A.V., Likhacheva E.A., Zozulya N.I.


Afibrinogenemia is a rare congenital coagulopathy that leads to life-threatening bleeding. In afibrinogenemia, plasma fibrinogen levels are less than 0.1 g/L. The clinical manifestations of the disease can be both bleeding and thromboses of different localizations, which is determined by the multifunctional role of fibrinogen in hemostasis. The described cases demonstrate different clinical phenotypes of the disease. In both cases the diagnosis was confirmed by genetic examinations that revealed homozygous mutations in the fibrinogen A genes. The nature of the mutations assumes consanguineous marriages, as confirmed by the results of a genealogical analysis. Fibrinogen preparations are promising in treating afibrinogenemia in Russia.
Terapevticheskii arkhiv. 2016;88(12):120-125
pages 120-125 views

Adiponectin in health and disease

Tereshchenko I.V., Kamenskikh Y.A., Suslina A.A.


Over the past 20 years after the discovery of adiponectin, much knowledge about its effect in health and disease has been gained. Adiponectin has antidiabetic, antiatherogenic, anti-inflammatory, immunomodulatory, metabolic, vasoprotective, and antiapoptotic properties. However, an understanding stems from the given literature review that much remains to be explored. Adiponectin has not yet commonly used in clinical practice, but cardiologists, endocrinologists, pediatricians, oncologists, and physicians of many specialties are interested in its preventive and therapeutic applications.
Terapevticheskii arkhiv. 2016;88(12):126-132
pages 126-132 views

Small bowel injuries due to nonsteroidal anti-inflammatory drugs and antiplatelet therapy. Approaches to prevention and treatment

Drapkina O.M., Korneeva O.N.


Nonsteroidal anti-inflammatory drug (NSAID)-induced small bowel injuries (NSAID enteropathies) become clinically important. Videocapsule endoscopy shows that the small bowel is involved in NSAID-related gastrointestinal tract (GIT) injury in almost two-thirds of all cases. Due to a large number of patients who receive NSAIDs, combined antiplatelet therapy, or long use anticoagulants, GIT injury prevention becomes an actual problem. Treatment for NSAID enteropathy is different from that for NSAID gastropathy. In NSAID enteropathy, it is advisable to use drugs that are able to increase the production of prostaglandins and mucus, to restore intestinal epithelial permeability, and to exert anti-inflammatory and antioxidant effects. Rebamipide that produces many pleiotropic effects and also has cytoprotective properties may become the drug of choice for treating patients with NSAID enteropathy. In addition, rebamipide has no effects on various cytochrome P-450 enzyme systems, by reducing the risk of drug interactions.
Terapevticheskii arkhiv. 2016;88(12):133-139
pages 133-139 views

Use of probiotics and probiotic-based immunomodulators as adjuvant therapy for Helicobacter pylori eradication

Konorev M.R., Andronova T.M., Matveenko M.E.


At present, Helicobacter pylori (Нр) infection is the most common chronic bacterial infection in humans, the pathogen of which colonizes approximately 50% of the world’s population. Hp eradication is required to control complications of Hp-related diseases (gastric and duodenal ulcers). Nevertheless, a number of investigations have demonstrated widespread antibacterial therapy inefficiency due to Hp antibiotic resistance and patient non-compliance with treatment regimens. Due to the growing need to elaborate alternative eradication regimens, some researchers have drawn their attention to probiotics and immunomodulators derived from Lactobacillus in particular for eradication therapy in Нp-positive patients to enhance the effect of antibacterial drugs. The review analyzes the results of 10 meta-analyses of randomized clinical trials with a similar design, which were published in 2007 to 2015, and other clinical trials assessing the role of probiotics and probiotic-based immunomodulators as an adjuvant therapy for Hp eradication. The results of the analysis have established that Lactobacillus strain-containing probiotics, both monocomponent probiotics and those as part of multicomponent ones, when used as an adjunct to anti-Hp therapy, significantly increase the level of Нp eradication by 8.1—20.0% (p<0.05; Level of Evidence, 1A; Recommendation Grade A). The use of N-acetylglucosaminyl-N-acetylmuramyl dipeptide (Licopid, a Lactobacillus bulgaricus-based immunomodulator) 0.001 and 0.01 g/day as an adjuvant to first-line triple anti-Hp therapy was shown to increase the level of Hp eradication by 7.1—8.9%. The intake of licopid 0.001 and 0.01 g/day during 7-day triple anti-Hp therapy results in the absence of recurrent Hp infection, as compared with 7- and 14-day treatment protocols without licopid, and leads to a significantly low incidence of Hp reinfection within 2—5 years after successful bacterial eradication, as compared with the 7-day protocol without adjuvant therapy with glucosaminylmuramyl dipeptide (p<0.05).
Terapevticheskii arkhiv. 2016;88(12):140-148
pages 140-148 views

Meloxicam in Russia: 20 years together

Karateev A.E., Nasonov E.N.


Meloxicam is one of the most commonly used representatives of the group of nonsteroidal anti-inflammatory drugs prescribed in our country. It has been used in Russian clinical practice for 20 years and established itself as an effective and rather safe analgesic and anti-inflammatory medications. During this period almost 48 million packages of brand-name meloxicam have been sold; millions of people in our country have been successfully treated with this drug. During this period, there have been at least 29 Russian clinical trials of brand-name meloxicam, which covered 3,736 patients. In all the trials, meloxicam has demonstrated a good therapeutic potential (a substantial improvement in more than 75% of patients) and a low incidence of side effects, which averaged 6.4% (30.5% in the control groups). The good tolerability of brand-name meloxicam (Movalis) is confirmed by a total of 120 spontaneous reports of the adverse events due to this drug, which were sent to the Federal Service for Health Supervision in December 2008 to July 2015 (over the last 7 years). This number seems negligible (nearly 30 million packages) if the amount of meloxicam sold over the period is taken into account. Extensive experience in clinical practice with this drug and a wide series of national clinical trials support the good reputation of brand-name meloxicam among Russian physicians and patients. This review briefly gives the data of Russian and main foreign clinical trials of the therapeutic effect and safety of meloxicam.
Terapevticheskii arkhiv. 2016;88(12):149-158
pages 149-158 views

Central regulation of pain in patients with joint disease and approaches to therapy

Filatova E.S., Erdes S.F., Filatova E.G.


The paper reviews investigations studies that have demonstrated that chronic pain syndrome is mixed in rheumatic diseases. The nervous system is involved in its pathogenesis with different frequency and different mechanisms. Under the influence of afferent pain impulses from damaged joints, there are changes in the excitability of spinal cord neurons, which is called central sensitization (CS). A number of patients have enhanced CS and clinical manifestations as neuropathic sensitive phenomena. The mixed model of the development of chronic pain in joint diseases and its presence along with nociceptive (inflammatory) and neuropathic pain components may explain the discrepancy between joint inflammatory and structural changes and pain intensity, the presence of distant pain and sensitive disorders in the areas outside the joint, and sometimes the efficiency of anti-inflammatory therapy. The presence of the neuropathic pain component serves as a rationale for combined therapy by adding centrally acting drugs, such as anticonvulsants.
Terapevticheskii arkhiv. 2016;88(12):159-164
pages 159-164 views

Nosocomial obstetric infections: Yesterday, today, tomorrow

Kuzmin V.N., Arslanyan K.N., Kharchenko E.I., Adamyan L.V.


Antibiotic resistance of microorganisms is one of the most acute problems of modern obstetrics. The paper analyzes current antibiotic resistance. It considers the mechanisms of its formation and ways to overcome the resistance.
Terapevticheskii arkhiv. 2016;88(12):165-168
pages 165-168 views

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