Vol 99, No 6 (2018)

Theoretical and clinical medicine
Clinical and functional characteristics of patients with colorectal cancer complicated by acute intestinal obstruction
Akhmetzyanov F.S., Saetgaraev A.K., Pasheev A.V., Valiev N.A., Levin M.V., Shaymardanov I.V., Sadykov K.K.

Aim. To study the clinical and functional features of patients with colorectal cancer complicated by acute intestinal obstruction.

Methods. A retrospective analysis of the data of 147 patients with colorectal cancer operated on from 2014 to 2016 for urgent indications for acute intestinal obstruction was performed. The study of lethality during the period from 1993 to 2016 was carried out separately. The study was performed in the clinic of urgent oncologic surgery of the State Autonomous Healthcare Institution “Republican Clinical Oncologic Dispensary” MH RT.

Results. Among patients with acute intestinal obstruction in colorectal cancer, a constant increase of the ration of elderly and senile patients is observed, as well as high anesthesia risk. Statistically significant indices of decrease of nutritional status in the group of patients of elderly and senile age and subtle manifestations of hypovolemia were revealed. In the elderly and senile patient group, polypragmasia was registered in 50.5 %.

Conclusion. Patients with colorectal cancer complicated by acute intestinal obstruction, have their own characteristics, different from patients operated on in clinics of urgent abdominal surgery with other diagnoses, the main ratio of which is made up of acute inflammatory diseases. This category of patients should be operated on in institutions where it is possible to provide specific highly skilled surgical and anesthesia-resuscitation care for malignant neoplasms.

Kazan medical journal. 2018;99(6):869-875
Pulmonary hypertension and respiratory function in parenchyma sparing surgical treatment of lung cancer
Kirshin A.A., Napol'skikh V.M.

Aim. To assess the effect of pulmonary hypertension on respiratory function in lung cancer surgery.

Methods. 92 patients diagnosed with non-small cell lung cancer, among them 69 men (75 %) and 23 women (25 %), were operated on with different variants of angioplastic lobectomy (APL), the average age was 57.8 ± 6.7 years. 91 patients underwent pulmonectomy (PE), among them 87 men (95.6 %) and 4 women (4.4 %), the average age was 59 ± 8.8 years.

Results. One year after angioplastic lobectomy FEV1 decreased by 0.69 liters (27 %), vital capacity decreased by 1.17 liters (32.9 %), FVC (the difference between the volumes of lungs at the beginning and at the end of forced expiration) reduced by 0.64 liters (20.5 %). After removal of the lung, dynamics of the decrease of similar indicators was 1.02 (42 %); 1.53 (43.8 %); 1.24 (40.3 %) liter respectively. The presence of a negative relationship between PA/A (pulmonary artery/aorta) and FEV1 was revealed. Thus, in the group of angioplastic lobectomy without initial pulmonary hypertension (PA/A less than 1) it was found that r = -0.42 (p < 0.01), with pulmonary hypertension (PA/A 1 or more) r = -0.4 (p < 0.01). In the group of pulmonectomy without initial pulmonary hypertension, the correlation index was -0.38 (p < 0.01), with initial pulmonary hypertension r = -0.33 (p < 0.01).

Conclusion. The analysis of the functional parameters of pulmonary system after the surgery revealed statistically significant advantage of organ-saving treatment, as well as negative correlation between pulmonary hypertension and respiratory function.

Kazan medical journal. 2018;99(6):876-879
Comparative analysis of clinical effectiveness of α1-adrenoblockers doxazosin, tamsulosin and silodosin in males with chronic non-inflammatory prostatitis
Lobkarev A.O., Khafiz'yanova R.K., Lobkarev O.A.

Aim. Comparative study of clinical effectiveness of doxazosin, tamsulosin and silodosin as monotherapy for patients with chronic non-inflammatory prostatitis.

Methods. Outpatient medical records (OMR) of patients with the diagnosis of chronic non-inflammatory prostatitis who were treated in “The clinic of ambulatory urology” (Kazan) in 2012-2017, were analyzed: all 173 OMR of patients receiving doxazosin 1 mg QD for 30 days as monotherapy; all 150 OMR of patients receiving doxazosin 2 mg per day BID for 30 days as monotherapy; all 54 OMR of patients receiving doxazosin 4 mg per day BID for 30 days as monotherapy; all 77 OMR of patients receiving tamsulosin 0.4 mg QD for 30 days as monotherapy; all 36 OMR of patients receiving silodosin 8 mg QD for 30 days as monotherapy. Based on these OMR the “Clinical index of chronic prostatitis” (CI CP) was analyzed before the start of pharmacotherapy and 30 days after the beginning. According to the clinical index, the discrete sample was ordered containing the values of CI from 0 points (no complaints) to 50 points (maximal score - the most marked symptoms).

Results. Before the beginning of the treatment every sample of patients is homogeneous and after 30-day treatment they lose homogeneity and tend to divide into several homogeneous samples.

Conclusion. Clinical effectiveness of doxazosin, tamsulosin and silodosin in men with CNP varies in wide range, is poorly predictable, poorly explainable and needs further studies according to the principles of modern evidence-based medicine.

Kazan medical journal. 2018;99(6):880-886
Cognitive functions in patients with atrial fibrillation at baseline and at different stages after pacemaker implantation depending on the received anticoagulant therapy
Davidovich I.M., Skopetskaya S.A., Neapolitanskaya T.E., Zharskiy S.L.

Aim. Comparative assessment of cognitive functions (memory, attention, cognition and neurodynamics) in patients with atrial fibrillation before and at different stages after implantation of permanent pacemaker depending on the received anticoagulant therapy.

Methods. We examined 44 patients (average age 65.5 ± 2.5 years) with ischemic heart disease (IHD) complicated by persistent or paroxysmal atrial fibrillation, which required implantation of a permanent pacemaker (PM). The patients were divided into 2 groups: receiving warfarin (28 patients - 63.6 %, average age 65.5 ± 1.6 years) and those who received oral anticoagulants (OAC) (16 patients - 36.4 %, average age 66.3 ± 1.4 years, p = 0.614). To assess the cognitive functions, psycho-physiological complex «Status PF» was used.

Results. Before PM implantation, the patients of both groups had decreased indices of visual memory. On days 5-7 after PM implantation, each group showed its increase (p = 0.001 and p = 0.013, respectively). On days 30-40, patients receiving warfarin developed a dramatic decrease of visual memory compared to the previous data and they became reliably lower than in the control group (p = 0.001). In the group receiving OAC, visual memory stayed unchanged (p = 0.076). Similar changes in warfarin group occurred at the assessment of auditory memory and attention volume (p = 0.001). Cognition indices (difficult analogues) were worse at baseline in warfarin group than in the group of OAC (7.0 ± 0.5 и 9.6 ± 0.6, р1 = 0.003) and this interrelation persisted on two following examinations (9.5 ± 0.4 and 10.8 ± 0.4, р1 = 0.041; 8.5 ± 0.4 and 9.8 ± 0.4, р1 = 0.048). Before PM implantation, the patients of both groups required more time of average exposure for neurodynamics test than in the control group (р = 0.001 and р = 0.002 respectively). On days 5-7 after PM implantation, the average exposure time decreased in both groups and they had no differences between each other and with the control (р1 = 0.132, р = 0.934 and р = 0.058). At the second testing only warfarin group had increased the mentioned time, and it exceeded the same parameter in the OAC group (p = 0.007).

Conclusion. A comparative assessment of cognitive functions in patients with IHD and atrial fibrillation demonstrated that in the warfarin group and the group receiving OAC patients had cognitive deficit more profound in the patients receiving warfarin. Those differences persisted at different stages after permanent PM implantation.

Kazan medical journal. 2018;99(6):887-893
Arterial hypertension in combination with atrial fibrillation and extracardiac diseases
Khidirova L.D., Yakhontov D.A., Zenin S.A.

Aim. To evaluate the character of the course and to determine the features of biochemical manifestations in patients with atrial fibrillation and arterial hypertension combined with extracardiac diseases.

Methods. To study the features of the course of persisting form of atrial fibrillation (AF) in patients with arterial hypertension (AH) stage 3 combined with extracardiac diseases. 374 patients aged 45 to 65 years were examined. Among them chronic obstructive pulmonary disease (COPD; n = 37), diffuse toxic goiter (DTG; n = 33), hypothyroidism (HT; n = 69), diabetes mellitus (DM; n = 49) and abdominal obesity (AO; n = 64) of mild and moderate degree were detected. 5 groups were formed: group 1 - AH + AF + COPD, group 2 - AH + AF + HT, group 3 - AH + AF + DTG, group 4 - AH + AF + DM, group 5 - AH + AF + AO. The control group included 56 patients with AH and AF without concomitant diseases, and the comparison group included 36 patients with AF without AH and 30 patients with AH without AF. The study evaluated clinical, anthropometric and laboratory parameters, the results of instrumental diagnostic investigation. The level of galectin-3 was determined in the serum by ELISA. The concentration of brain natriuretic peptide (NT-proBNP) was measured with a panel “NT-proBNP - ELISA - Best”. Multiple comparisons of the groups were performed with Kruskal - Wallis test. To compare binary and categorical parameters, exact two-tail Fisher’s test was used. Optimal multivariate regression models were developed directly and reversely. Verification of statistical hypotheses was carried out with critical value of significance p = 0.05 i.e. the difference was considered statistically significant if p < 0.05. All statistical calculations were performed with the use of R-Studio soft.

Results. When assessing the lipid profile in the studied groups, significant differences were detected for HDL (high density lipoprotein) the values of which were the highest in the control group; TC (total cholesterol) was significantly lower in group 1 and 2; LDL (low density lipoprotein) and TG (triglycerides) - in group 3. The level of uric acid in the serum in all clinical groups was higher compared to those of the control group but significance was reached only in group 3. The concentration of K+ in the blood was significantly higher in all groups compared to the control group. The study of NT-proBNP and galectin-3 as markers reflecting the processes of remodeling and myocardial fibrosis in patients with atrial fibrillation combined with arterial hypertension, demonstrated that the average level of NT-proBNP in all groups was higher than in the control group but the difference was significant only in group 5. The level of galectin-3 in the serum of patients with arterial hypertension and atrial fibrillation combined with comorbid extracardiac pathology was significantly higher in the groups compared to the control group (except for group 3 where the number of patients was the lowest) and significantly lower in the comparison group of patients with atrial fibrillation without arterial hypertension.

Conclusion. The course of arterial hypertension and atrial fibrillation with concomitant extracardiac diseases is characterized by the changes of biochemistry, which manifest as the changes of lipid profile, electrolyte content and factors inducing fibrosis. The obtained data confirm the possible role of galectin-3 as a biological marker of fibrosis and myocardial remodeling in patients with AF and AH and comorbid extracardiac pathology.

Kazan medical journal. 2018;99(6):894-899
Interleukins 4 and 6 as factors of modulation of subpopulation composition of blood monocytes in patients with ischemic cardiomyopathy
Azarova D.A., Chumakova S.P., Urazova O.I., Vins M.V., Shipulin V.M., Pryakhin A.S., Novitskiy V.V.

Aim. To evaluate the ratio of the fractions of classical, intermediate, non-classical and transitional monocytes in correlation with the concentration of interleukins 4 and 6 in the blood of patients with ischemic cardiomyopathy.

Methods. 18 patients with ischemic cardiomyopathy (17 men and 1 woman) aged 47-66 years with circulatory insufficiency of functional class II-III according to the classification of heart failure of the New York Heart Association, were examined. The control group included 14 healthy donors matched by gender and age to patients with ischemic cardiomyopathy without any diseases of cardiovascular system and other systems in an exacerbation stage. In blood of the patients with ischemic cardiomyopathy, the relative content of classical (CD14++CD16-), intermediate (CD14++CD16+), non-classical (CD14+CD16+) and transitional (CD14+CD16-) monocytes was assessed by flow cytometry and the concentration of interleukins 4 and 6 by enzyme-linked immunosorbent assay (ELISA).

Results. It was shown that the number of non-classical monocytes in the blood of patients with ischemic cardiomyopathy was 2 times lower than normal (5.05 % [4.08; 6.58] and 10.07 % [9.34; 13.84], respectively, p < 0.01), as well as the concentration of interleukin-4 (0.02 pg/ml [0; 0.04] and 0.15 pg/ml [0.05; 0.65], respectively, p < 0.05). The number of classical monocytes in the blood of patients had a tendency to decrease, and the proportion of intermediate monocytes and the concentration of interleukin-6, on the contrary, were slightly higher than in healthy individuals, and were interdependent (r = 0.61; p < 0.05). The relative content of transitional monocytes in the blood was comparable with that of healthy donors.

Conclusions. The subpopulation composition of blood monocytes in patients with ischemic cardiomyopathy is characterized by a deficiency of the fraction of non-classical monocytes with protective properties against endothelium, and interleukin-4 in the blood with a certain increase in the content of interleukin-6 and the number of intermediate cells with ability to cooperate with T-lymphocytes, which predisposes to diffuse atheromatosis of small coronary arteries and diffuse hypoxic myocardial damage in ischemic cardiomyopathy.

Kazan medical journal. 2018;99(6):900-905
Functional state of the myocardium and criteria for poor prognosis in mitral valve prolapse
Gadzhieva L.R., Muracheva N.V., Tkachenko S.B.

Aim. Study of the fnctional state of left ventricular myocardium and determination of diagnostic criteria of poor prognosis of mitral valve prolapse.

Methods. 151 patients (116 males and 35 females) with mitral valve prolapse (MVP) were examined. The average age was 34.8 ± 0.79 years. Division by the groups was performed depending on the severity of structural changes of the valve and width of the cusps: group 1 included 54 patients with classic form of MVP (cusp width ≥5 mm), group 2 included 55 patients with cusp width ≥3 mm, group 3 included 42 patients with MV cusp width less than 3 mm. All patients underwent complex clinical functional examination of cardiovascular system. The state of systolic and diastolic cardiac function was assessed using stationary high-tech ultrasound scanner «Philips iE-33» (Philips, Holland) according to conventional technique with determination of standard heart parameters and calculation of intracardiac hemodynamic parameters. Echocardiography was performed on admission and 12 to 18 month later.

Results. The study revealed that the most prominent changes of cardiohemodynamics and unfavorable disease course were observed in 72.2 % of patients with classic form of MVP (group 1). Patients with non-classic form of MVP (group 2) also had poor prognosis in 27.8 % of cases. Diagnostic criteria of poor prognosis of MVP according to echocardiography were determined: severe mitral regurgitation (degree ≥III), mitral valve cusp thickness during diastole over 6 mm, left ventricle dilation (EDS ≥ 60 mm; ESS ≥ 36 mm), left atrial dilation (anterior posterior size of LA ≥ 40 mm, LA volume ≥ 80 ml), mitral annulus dilation (diameter of MA ≥ 35 mm).

Conclusion. Differences of functional state of the myocardium of left ventricle were revealed depending on the type of mitral valve prolapse caused by the severity of connective tissue dysplasia. In classic form of MVP more severe disorders of intracardiac hemodynamics were observed as well as more severe mitral insufficiency.

Kazan medical journal. 2018;99(6):906-910
Evaluation of clinical efficacy of prostanoid therapy for Raynaud’s phenomenon in rheumatic diseases
Bagautdinova Z.R., Gaisin I.R., Glavatskikh M.M., Bragina T.A.

Aim. On the basis of clinical manifestations of Raynaud’s phenomenon (RP) to determine the RP expression level and to evaluate the long-term efficacy of treatment of RP in patients with rheumatic diseases (RD) with iloprost and alprostadil.

Methods. Treatment for indications with prostanoids (intravenous iloprost, alprostadil or their combinations) was administered to 40 patients with secondary RP in RD. During 3-year follow up, clinical instrumental parameters (frequency of attacks of Raynaud's, digital ulcers (DU) formation, pain intensity on visual analogue scale (VAS) were evaluated. The control group included 30 patients with RP in RD who did not receive prostanoid therapy. The method of factor analysis was used to determine the index of generalized expression of RP, on the basis of which the expression levels of the RP were determined.

Results. The “expression of RP” scale revealed in the course of factor analysis as an indicator of generalized manifestation of RP, is the average value of two subscales, the first one of which consisted of four indices - “digital ulcer”, “digital pitting scars”, “phalange amputation” and “Raynaud's attack frequency”, and the second one included “intensity of pain”, “duration of illness”, “whitening of fingers”. Verification of the correlation revealed during the study of subscales, showed its reliability (r = 0.294, p = 0.053). The final expression of RP was 1.51 ± 0.86. The low level of RP expression had values up to 0.65, high - over 2.37. When included in the study, a high level of RP expression was defined in 16 (22.9 %) patients, medium - in 43 (61.4 %), low - in 11 (15.7 %). The use of iloprost in the treatment of RP was effective for healing of DU and a statistically significant decrease of the generalized expression of RP from 2.25 [1; 3] to 1.75 [1; 2] (p = 0.012) was observed. On alprostadil treatment, statistically significantly decreased frequency of attacks from multiple daily (more than once a day) to once a month and reduced numbness during RP attack were observed as well as a decrease of the level of generalized index of RP expression from 1.26 ± 0.71 to 0.97 ± 0.57 (р = 0.038). The combination of prostanoids had a contradictory clinical effect: the pain and frequency of RP attacks decreased, but the formation of DU and new cases of amputations of phalanges were registered, the treatment had no effect on the value of RP expression.

Conclusion. Based on the clinical manifestations of RP, a generalized index of RP severity was identified and the levels of RP severity were determined. Treatment with iloprost and alprostadil has a significant effect on reducing the clinical manifestations of RP with a corresponding decrease in its severity.

Kazan medical journal. 2018;99(6):911-918
Features of antioxidant system in patients with obstructive jaundice of benign and malignant origin in dynamics
Elmanova N.G.

Aim. Study of the features of changes of antioxidant protection in patients with mechanical jaundice of benign and malignant origin in dynamics.

Methods. The author studied the role of antioxidant system in the progression of mechanical jaundice of various origins in 104 patients. Groups of patients with a syndrome of mechanical jaundice of benign (62 patients) and malignant origin (42 patients) were isolated. The material of the study was blood from the ulnar vein, which was taken in the morning on an empty stomach before surgery. In the dynamics (on the 7th day after the operation), 53 patients were examined. To assess the state of antioxidant protection, a spectrophotometric method of investigation was used.

Results. A high level of malonic dialdehyde, the product of lipid peroxidation, was determined in all patients regardless of origin. There was also a depression of the enzymatic link of antioxidant protection (a decrease in the activity of superoxide dismutase and catalase). After surgical intervention in patients with mechanical jaundice of benign origin, correction of the level of reduced glutathione was observed. In patients with mechanical jaundice of malignant origin in dynamics, the activity of antioxidant enzymes did not differ significantly from the norm (p1-3 = 0,23; p1-3 = 311).

Conclusion. After surgical intervention, partial improvement of the condition of patients with mechanical jaundice of benign origin was observed, and dysfunction of antioxidant protection persisted in patients with mechanical jaundice of malignant origin.

Kazan medical journal. 2018;99(6):919-923
Clinical and epidemiological characteristic of chronic brucellosis
Fazylov V.K., Gilmullina F.S., Khamidullina Z.L., Galina G.V.

Aim. To study clinical epidemiological and laboratory features of chronic brucellosis in the Republic of Tatarstan in ten-year aspect.

Methods. 59 patients infected with various forms of brucellosis in 2007-2017 were examined. Clinical laboratory and instrumental diagnosis of brucellosis was confirmed by the immunoassay (EIA) with determination of IgM and IgG antibodies, passive hemagglutination test with a brucellar diagnosticum, Coombs test, Wright and Hedelson agglutination test.

Results. Clinically 91 % of patients had asthenic-vegetative syndrome, 55 % - mild intoxication symptoms, 89 % - articular syndrome, 49 % - fibrositis. EIA revealed in 91 % of patients IgG (38 %) and IgM (53 %) antibodies to causative agents of brucellosis, 25 % of patients had positive Wright agglutination test, and 30 % - positive Hedelson agglutination test. In 9 % of cases the diagnosis was confirmed by Coombs test and in 26 % by passive hemagglutination test with brucellar diagnosticum. The retrospective analysis with clinical cases of patients with chronic brucellosis indicates introduced cases in 19 % (from the republics of Central Asia and Transcaucasia), local cases in 81 % (from the Republic of Tatarstan), their occupational character (57 %), the mixed (contact and alimentary) route of infection (21 %), and 64 % with clinically primary involvement of the musculoskeletal system and peripheral nervous system, i.e. prevalence of the mixed form of chronic brucellosis.

Conclusion. Chronic brucellosis in the Republic of Tatarstan is characterized by high risk of introduced cases, occupational history, prevalence of the mixed route of infection in females and working-age patients; with the features of systemic disease involving the musculoskeletal and peripheral nervous system against the background of mild syndrome of intoxication and moderate asthenic-vegetative syndrome. Divergence of the results of serological diagnostics requires careful studying of duration of infection, features of the immune response in each case on follow-up.

Kazan medical journal. 2018;99(6):924-930
Efficiency of modern correction methods of ovarian hyperandrogenism in puberty
Alieva E.M., Akhundova N.E.

Aim. To evaluate the effectiveness of correction of the ovarian hyperandrogenism (OHA) in girls in puberty.

Methods. 38 girls with OHA syndrome were examined. The average age of the girls was 14.39 ± 0.27 years. Ferriman-Gallwey hirsutism score was 19.7 ± 0.47, the hormonal score 18.14 ± 2.43, the indifferent score 2.34 ± 0.13. The comparison group included 20 girls matched by age (14.74 ± 0.15 years) with physiological course of puberty. The study included the evaluation of hirsutism severity by Ferriman-Gallway score, determination of the hormones of hypothalamus-pituitary-adrenal-ovarian system in early follicular phase on day 5-7 of menstrual cycle.

Results. The causes of OHA syndrome in the pubertal period were found to be polycystic ovary syndrome in 68.42 % and tumor-like formations (follicular cysts) in 31.58 % of girls. Compared to healthy girls, the girls with OHA syndrome had statistically significantly higher values of luteinizing hormone (LH) - 9.19 ± 0.96 mME/ml, LH/FSH ratio - 1.8 ± 0.15, total testosteron (Ttotal) - 1.3 ± 0.11 ng/ml, estrone (E1) - 109.5 ± 4.88 ng/ml, androstenedione (An) - 4.01 ± 0.12 ng/ml as well as low values of estradiol (E2) - 49.1 ± 2.6 pg/ml and sex hormone-binding globulin (SHBG) - 45.7 ± 2.14 nmol/l. The study demonstrated that correction of ovarian hyperandrogenism, promotes an increase in the level of E2, SHBG and decrease of the level of LH, LH/FSH ratio, Ttotal, An.

Conclusion. Complex pathogenetic therapy of OHA syndrome in girls in puberty leads to significant improvement of hormonal status in this group of patients.

Kazan medical journal. 2018;99(6):931-935
Experimental medicine
Reaction of hemostasis system in hypercapnic hypoxia after the course of mexidol assessed by the method of thromboelastography
Moskalenko S.V., Shakhmatov I.I., Bondarchuk Y.A., Alekseeva O.V., Ulitina O.M.

Aim. To study the reaction of hemostasis system to a single effect of hypercapnic hypoxia of maximum intensity in rats and possibility of correcting hemostasis disorders by means of a preliminary course of an antihypoxant - mexidol.

Methods. The study involved sexually mature male rats (48 specimens) of the Wistar line with an average mass of 274.0 ± 32.0 g. The rats were kept on a standard diet, food and water were fed once a day between 10 and 11 hours. In the evening, animals underwent a single hypercapnic hypoxia in a special flow chamber. The state of hypercapnic hypoxia of maximum intensity was modeled at O2 content of 5.0 %, CO2 - 5.0 % during a single 20-minute exposure. As a training regimen, a 30-fold course of mexidol was used, the drug was administered intraperitoneally to rats at a dose of 50 mg/kg for 1.5 hours prior to exposure to hypercapnic hypoxia.

Results. After a single exposure to hypercapnic hypoxia of maximum intensity, shortening of the onset of clot formation, an increase of alpha angle, and maximum clot density were recorded. Also, the clot formation time shortened and the maximum clot lysis index increased. With a single exposure to hypercapnic hypoxia of maximum intensity after the course of mexidol, a decrease in the maximum clot density was recorded.

Conclusion. A single exposure to hypercapnic hypoxia of maximum intensity was characterized by a shift of hemostatic potential toward hypercoagulability along with fibrinolytic system activation. The course use of antihypoxant mexidol, preceding hypercapnic hypoxia of maximum intensity, significantly reduces the risk of clot formation.

Kazan medical journal. 2018;99(6):936-941
Prevention of microcirculatory disorders in rats on suprathreshold physical exertion using the products of velvet antler industry
Blazhko A.A., Shakhmatov I.I., Kiselev V.I., Kovalev I.V.

Aim. To assess the microcirculatory bloodstream after suprathreshold physical load in rats with preceding intake of products of velvet antler industry, as well as to determine which microcirculatory reactions cause the adaptive effect.

Methods. The study included 30 male Wistar rats. Two groups of experimental animals received the concentrate containing blood and histolysate of Siberian stag reproductive organs, 4.5 ml per day. The rats of the first experimental group were subjected to an 8-hour physical load on day 31, and rats of the second group were not subjected to the load. Indices of microcirculation obtained by laser Doppler flowmetry in experimental animals were compared to those of intact rats.

Results. In animals of the first experimental group, the amplitude of respiratory waves increased in comparison with intact animals, while the remaining indices of the microcirculation system did not differ from those of the intact group. In the rats of the second experimental group, there was an increase in the flax, which indicates an increase in the modulation of the blood flow; in rats an increase in the amplitude of endothelial and vasomotor waves was revealed in comparison with intact animals against the background of constant amplitudes of respiratory and pulse waves.

Conclusion. Preceding 30-day intake of a concentrate containing blood and histolysate of Siberian stag reproductive organs, in general, was found to prevent the development of disturbances of the microcirculatory bloodstream in rats after the suprathreshold physical load due to active mechanisms of blood flow regulation - increase of the amplitudes of endothelial and vasomotor waves.

Kazan medical journal. 2018;99(6):942-946
Toxic effect of titanium dioxide nanoparticles on morphological characteristics of thymus
Sharafutdinova L.A., Sinel’nikov K.N., Valiullin V.V.

Aim. Study of effects of titanium dioxide nanoparticles administered orally on the rodent thymus morphological and functional state.

Methods. The study used classical morphological approaches and specific markers of proliferation - Ki-67, apoptosis - p53 protein and macrophages - CD68, which allow adequately identifying not only the cells themselves, but also their functional state. The rodent thymus was analyzed after oral administration (10 mg/kg of body weight of the animal, 28 days) of the TiO2 nanoparticles (rutile form, 40-60 nm) obtained by diluting the TiO2 powder in distilled water. Aggregation of the nanoparticles was prevented by processing a suspension of nanodispersed TiO2 in an ultrasonic bath. The rats of the control group were orally injected with distilled water in the same volume. Serial paraffin sections of the thymus were stained with hematoxylin-eosin, picrofuxin according to Van Gieson, immunohistochemical staining was performed with antibodies to Ki-67, CD68, p53.

Results. Significant changes of the tissue of thymus gland under the influence of TiO2 nanoparticles were revealed. In the thymus of experimental animals, a decrease in the proportion of cortex was found to be 17.6 %, a significant decrease in the density of the cell population due to decrease in the number of thymocytes was demonstrated. Immunohistochemical typing revealed that under the influence of TiO2 nanoparticles, a decrease in the number of Ki-67-positive cells in the cortex of the lobule of the thymus gland was observed, which indicates the inhibition of proliferation in these conditions. Under the influence of TiO2 nanoparticles, an increase of the amount of cells entering apoptosis in the cortex of the thymus segment of the experimental group by 5.18 times was observed, as evidenced by the results of immunohistochemical study of the expression of apoptosis marker p53 protein. Perhaps, as a compensatory mechanism there is a pronounced increase in the number of macrophages, as indicated by an increase in the average number of CD68 immunopositive cells in the cortex of the thymus of the test group by 2.61, and in the brain substance by 1.35.

Conclusion. The revealed morphological and functional changes of the thymus with oral administration of TiO2 nanoparticles indicate their immunosuppressive effect.

Kazan medical journal. 2018;99(6):947-953
Cervical elasticity during pregnancy: current state of the problem
Tukhbatullin M.G., Yanakova K.V.

Uterine cervix undergoes various changes throughout the pregnancy, which are characterized by the general term “remodeling”. In particular, this process includes changes of the length (shortening) and consistency (softening) of uterine cervix. The latter from the clinical point of view is important not only for observation of pregnant women with normal course of pregnancy but also for predicting such states as an outcome of labor induction or preterm delivery. Traditionally, cervical elasticity has been estimated through digital examination and Bishop score, however, currently there are available imaging techniques, which are more objective and precise. Amongst these methods, elastography plays a special role. Elastography allows measuring the capacity of tissues to deform. The softer the tissues, the higher mentioned capacity under the applied pressure. Currently there are various methods of elastography, starting from real-time elastography, when the capacity to be deformed is registered under the influence of physiologic movements or minimal manual pressure, to shear wave elastography, when the velocity of propagation of shear waves is measured. Although there are number of methods of elastography and perspectives of their use in obstetric practice, at the present time there is no consensus on standardization of these methods. In the cervical elastography this task is even more complicated, because there is no reference tissue to be compared with, especially this is true for strain elastography. The aim of this study was comparative analysis of methods estimating cervical elasticity and underlining current problems from the clinical point of view.

Kazan medical journal. 2018;99(6):954-958
Mechanisms of the resistance of gastrointestinal stromal tumors to imatinib
Galembikova A.R., Boichuk S.V.

The review describes the modern concepts of the primary and secondary (acquired) resistance of gastrointestinal stromal tumors to the targeted drug imatinib. Gastrointestinal stromal tumors are the mesenchymal tumors of gastrointestinal tract that originate from interstitial cells of Cajal or their stem cell precursors. Up to 85 % of gastrointestinal stromal tumors have the mutations of KIT gene that lead to ligand-independent activation of this tyrosine kinase. Imatinib is an inhibitor of KIT tyrosine kinase which is hyperexpressed in 70-85 % of cases on the cell membrane of gastrointestinal stromal tumors. Despite the high effectiveness of imatinib in gastrointestinal stromal tumors, up to 15 % of patients do not respond to this therapy, and over 50 % of patients acquire the resistance to this drug 2 years after initiation of target therapy with imatinib. The mechanisms of primary resistance include basically the mutational status of KIT, PDGFRA and, rarely, mutations of SDH, NF1, BRAF, PI3K3CA, CBL, and KRAS. The mechanisms of secondary resistance of tumor cells to imatinib are not restricted to the secondary mutations of KIT and PDGFRA, but also might be due to the loss of KIT expression associated by overexpression of the alternative receptor- and non-receptor tyrosine kinases, such as MET, AXL, FGFR2α, FAK, etc. Alternative mechanisms of acquired resistance might be due to the mutations of BRAF gene.

Kazan medical journal. 2018;99(6):959-965
On-pump beating-heart coronary artery bypass grafting: a literature review
Borisov D.V., Zotov A.S., Troitskiy A.V., Khabazov R.I.

Coronary artery bypass grafting techniques have been unchangeable for many years, whereas development and enhancement of myocardial protection methods in coronary bypass grafting for patients with ischemic heart disease are still actual issues of current coronary surgery. Coronary artery bypass grafting techniques include the traditional/conventional technique with cardiopulmonary bypass, aortic cross-clamping and cardioplegia, off-pump and on-pump beating heart coronary artery bypass grafting. Coronary artery bypass grafting with cardiopulmonary bypass and cardioplegia remains the most common method of coronary revascularization. However the cardiac arrest inevitably leads to global cardiac ischemia, and current cardioplegias do not prevent ischemic damage to the myocardium in all cases, especially in high-risk surgical patients. Off-pump coronary artery bypass grafting allows preventing global myocardial ischemia (due to the constant native coronary blood-flow) and avoiding possible negative consequences of cardiopulmonary bypass use. The main limitations of this technique are associated with high risk of hemodynamic instability due to low cardiac output and systolic output caused by target arteries exposition. On-pump beating heart technique is a reasonable compromise between conventional on-pump coronary artery bypass grafting, cardioplegia and off-pump procedure. It is a safe and effective technique with outcomes that are equivalent or superior to the outcomes reported for conventional coronary artery bypass grafting in patients with unstable hemodynamics, low left ventricular ejection fraction and in high-risk patients. The literature review presents the results of on-pump beating heart coronary artery bypass grafting.

Kazan medical journal. 2018;99(6):966-972
Social hygiene and healthcare management
Social and age-related aspects of informativeness of indirect laboratory markers of alcohol consumption
Novikov D.G., Indutnyy A.V., Samuseva N.L.

Aim. To compare the diagnostic capabilities of indirect laboratory markers of alcohol consumption - alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltranspeptidase and carbohydrate-deficient transferrin, depending on the social status and age group of the subjects.

Methods. The activity of enzymes were assessed in the blood serum of socially adapted young subjects (18-25 years, 201 people) and adults (35-50 years, 121 people) by standard biochemical methods, and the level of carbohydrate-deficient transferrin was determined by capillary electrophoresis. With the use of questionnaires, the subjects were tested for alcohol abuse. Non-parametric criteria of statistical significance were used to evaluate the difference.

Results. No differences in the activity of enzymes associated with the level of alcohol consumption were found in the youth group (p = 0.911 for alanine aminotransferase, p = 0.669 for aspartate aminotransferase, p = 0.303 for gamma-glutamyltranspeptidase). Activity of gamma-glutamyltranspeptidase was significantly higher in adult group of alcohol abuse (p = 0.021), but individual values of enzyme activity of some subjects from this group fit into the population reference interval. Differences in the level of carbohydrate-deficient transferrin in the youth group, associated with the volume and frequency of alcohol consumption, were not revealed (p = 0.348), and all individual values were within the reference interval. In the adult group, values of this parameter were higher in high-dose alcohol drinkers (p = 0.019) but the diagnostic threshold of alcohol abuse was reached only in 2 subjects.

Conclusion. Indirect laboratory markers do not have sufficient diagnostic significance for screening of alcohol abuse among socially adapted young people and adults. Informativeness of carbohydrate-deficient transferrin may be sufficient if the diagnostic threshold corresponding to a definite social and age group replaces the standard population-established concentration limit.

Kazan medical journal. 2018;99(6):973-979
Damaging effects of ecologically unfavorable environmental factors on the health of descendants
Dudareva Y.A., Saldan I.P., Shoykhet Y.N., Kiselev V.I., Gur'eva V.A.

Aim. To determine the possible damaging effects of ecologically unfavorable environmental factors (radiation and chemical) on the health of descendants.

Methods. The cross-sectional study included 232 women of the Altai territory, who were divided into three groups: the first group included the descendants of persons who were in the area of radiation exposure, the second one - the descendants of chemical workers, the third group was the control group. As part of the expedition trip to the study areas, the collection of clinical and anamnestic data, the study of extragenital, gynecological morbidity, laboratory and functional methods of research were carried out.

Results. The data were obtained confirming the most damaging effect on reproductive health in the descendants of persons who were in the area of radiation exposure. It was the first group where the high frequency of extragenital and gynecological pathology was revealed. At the same time, the reproductive function of women, closely related to functional changes in the immune system, was disordered. The results of the study of a number of parameters of the immune system revealed changes in the functioning of cellular immunity, increase in the level of proinflammatory cytokines (tumor necrosis factor), mainly in the descendants of persons who were in the area of radiation exposure, in contrast to the descendants of workers of chemical production and control group.

Conclusion. A comparative assessment of some health parameters of descendants of persons exposed to radiation and chemical factors showed that the most damaging effect on the reproductive health of descendants is caused by radiation factor.

Kazan medical journal. 2018;99(6):980-985
Epidemiological features of acute and chronic hepatitis B in the Kyrgyz Republic over the 20-year period (1997-2017)
Tobokalova S.T., Bekenova D.S., Zairova G.M., Nurmatov Z.S., Nazarbaeva Z.N., Aytieva Z.T.

Aim. To determine epidemiological features of acute and chronic viral hepatitis B in the Kyrgyz Republic over the period 1997-2017. Меthоds. Analysis was performed on data bases of the National accounting forms on treated cases of acute and chronic hepatitis B cumulated by the Medical Information Centre of the Ministry of Health of Kyrgyz Republic for the period of 1997 to 2017 as well as 384 medical records of patients with chronic hepatitis B treated in the Hepatologic Centre “Tsadmir”.

Results. In the Kyrgyz Republic among all acute cases of acute viral hepatitides, hepatitis A comprises 60.5 %, hepatitis B - 16.9 %, the ratio of unverified non-A non-C viral hepatitis - 15.2%. With the introduction of HBV vaccination of children (2000) and improvement of infectious control in healthcare settings, a decline of acute HBV incidence is observed - from 26.7 0/0000 to 5.3 0/0000 due to the decrease of acute hepatitis B among children and adolescents to isolated cases, adults from risk groups. The highest incidence of acute hepatitis B is recorded in Osh and Bishkek, in Jalal-Abad and Chuy Regions. This can be explained by that in the southern and northern capitals of the Kyrgyz Republic and in the near lying areas with high population density, access to laboratory and instrumental methods of diagnosis of viral hepatitides is better, along with the higher awareness of its inhabitants regarding the prevention compared to other regions. At the same time an increase of chronic hepatitis B incidence is observed. Predominant modes of transmission are medical-parenteral exposure and household contact (60.9 %), with frequent formation of family clusters (23.8 %). Imperfections were found in the early detection, reporting and accounting of cases of chronic viral hepatitides as well as in examination of hepatitis B virus carriers.

Conclusion. The performed analysis of the incidence and prevalence of acute and chronic hepatitis B in the Kyrgyz Republic allowed assessing the dynamics of the epidemiologic situation in the country regarding this disease, revealed shortcomings in the detection and examination of viral hepatitis B carriers, contributed to development of a new guide for epidemiological surveillance of viral hepatitides.

Kazan medical journal. 2018;99(6):986-993
Clinical observations
A case of arterial thrombosis with formation of an atypical fibrin-rich thrombus
Khismatullin R.R., Shakirova A.Z., Peshkova A.D., Khuziakhmedov A.N., Khizriev S.M., Litvinov R.I.

Aim. To describe a case of arterial thrombosis with a thrombus that had atypical composition due to profound pathological changes in the cellular and protein composition of the blood.

Methods. Scanning electron microscopy of an ex vivo thrombus extracted from the common femoral artery.

Results. In the absence of platelets and leukocytes there was a significant prevalence of fibrin over other blood components in all layers of the arterial thrombus. There were no morphological signs of intravital contraction (retraction) characteristic for thrombi: single erythrocytes were not exposed compressive deformation, redistribution of fibrin and platelets within the thrombus toward the periphery. Formation of the atypical arterial thrombus in the vessel with atherosclerotic vessel damage is probably due to association with severe hyperfibrinogenemia and thrombocytopenia.

Conclusion. The structure of a thrombus depends not only on its vascular location (arterial or venous), but also on the cellular and protein composition of the blood. These factors support diversification of antithrombotic therapy, considering composition and properties of thrombi irrespective of the place and hemodynamic conditions of their formation.

Kazan medical journal. 2018;99(6):994-997
Clinical case of hereditary hemochromatosis
Solov’eva A.V., Kodyakova O.V., Nikitina I.N., Fomenko N.P., Rakita D.R.

The article presents a clinical case demonstrating the difficulties of timely diagnosis of hereditary hemochromatosis, presents data on modern diagnosis and approaches to the treatment of the disease according to existing clinical guidelines. The described clinical case of hereditary hemochromatosis is associated with a homozygous mutation of C282Y in HFE gene in a 58-year-old patient and his twin brother. Initially, signs of iron deposition in the liver were found on MRI of the abdominal cavity. In laboratory analyses, the patient was found to have an increased level of serum iron - 40 µmol/l and ferritin - 1340 ng/ml. Subsequently, the investigation of HFE gene mutations was carried out and a mutation of C282Y in homozygous form (genotype A/A) was found, which is a molecular genetic confirmation of hereditary hemochromatosis of type 1. At the same time, the patient's twin brother at the targeted examination had the serum iron level of 36 µmol/l, the ferritin level of 600 ng/ml, and also the mutation of HFE gene, the allelic variant of A/A. The results of liver fibroelastometry of the patient correlate with the degree of fibrosis F1 by Metavir scale. Timely started therapeutic phlebotomies led to improved clinical and laboratory parameters of iron metabolism while maintaining normal levels of red blood cells and hemoglobin.

Kazan medical journal. 2018;99(6):998-1003
Clinical experiences
Restorative minimally invasive interventions in patients with colostomy
Akhmetzyanov F.S., Valiev N.A., Daminov A.N., Bikbov B.S.

Aim. To show the benefits of performing mini-access restorative phase on the colon in patients with colostomy.

Methods. A retrospective analysis of the results of closure stomy operations in 2011-2017 in two emergency cancer departments of Republican Clinical Oncology Center MH RT was conducted. The inclusion criteria of the study were: 1) surgical intervention for acute intestinal obstruction in colorectal cancer performed in RCOC; 2) mandatory removal of the primary tumor during the first surgery; 3) the presence of a functioning intestinal stoma formed during the first surgery; 4) fixation of both stumps in one stoma. The exclusion criteria were refusal to restore the continuity of the colon for medical indications and the patient's refusal to undergo the surgery.

Results. The study included 11 males (44 %) and 14 females (56 %). The age interval was 49 to 81 years, of which 12 patients were over 70 years old (48 %), the average age was 67.7 ± 5.4 years. The tumor removed at the first stage was localized in the right parts of the colon in 5 patients (20 %), and in the left in 20 patients (80 %). By the stages of the malignant process, the patients were distributed as follows: stage B - 14 cases (56 %), stage C - 10 (40 %), stage D - 1 (4 %). The average duration of the surgery was 53 ± 14.38 minutes (40 to 123). The postoperative period was 10.8 ± 1.92 days on average (5 to 18).

Conclusion. Restoration of intestinal continuity through mini-paracolostomy access is technically rational, as due to the mini-access the patient undergoes minor surgical trauma; the anatomical proximity of the anastomosed bowel stumps excludes the difficulties associated with the search for the distal stump in the traditional method of recovery; the duration of the postoperative hospital stay decreases significantly.

Kazan medical journal. 2018;99(6):1004-1008
Justification of a new method of alternative treatment of high congenital hip dislocations in adolescents and adults
Abakarov A.A., Abakarov A.A.

Aim. Justofocation of a new method of hip joint stabilization in adolescents and adults with congenital hip dislocation by preserving its own bone structures.

Methods. The biomechanical substantiation of a new method of surgical correction of the proximal femur is presented. A primary analysis of the surgical treatment of congenital hip dislocation was performed on 101 patients (116 joints) aged 14 to 30 years (average age 21.3 ± 3.5 years) by creating an additional point of support for the pelvis according to the authors' method with 10 to 15-year follow up. The technique includes angulating elongating squamous oblique osteotomy of the thigh, which allows extending the limb simultaneously to 4 cm and restoring its biomechanical axis. All patients were evaluated clinically, radiologically and using Harris scale before and after the surgery.

Results. At the analysis of the treatment results 10-15 years after the operation in 56 patients, the average Harris score increased from 42.7 (from 40.1 to 45.3) to 81.1 (77.2-86.7). Valgus proximal hip and oblique intertrochanteric osteotomy allowed elongating the limb in one-side hip dislocation by 3.2 ± 0.8 (95 % CI 2.8-4.0 cm), shortening of the limb by 3 cm persisted in all patients with one-side hip dislocation. In 37 patients (43 joints) podographic examination revealed restoration of rhythmic walking and longer single-support time.

Conclusion. The suggested method of treatment of high congenital hip dislocation is an effective and minimally invasive method of stabilization of the hip joint in adolescents and adults. We discuss the question of possible reconstructive surgeries with preserved own bone structures in young patients aged 14 to 30 years, creating of bone mass in hip joint area for further joint replacement.

Kazan medical journal. 2018;99(6):1009-1015
Choice of minimally invasive method of treatment of pancreatic pseudocysts: a single center, retrospective study
Neledova L.A., Mizgirev D.V., Duberman B.L.

Aim of the study is to evaluate efficacy of different methods of minimally invasive treatment of pancreatic pseudocysts (PPC).

Methods. A single center retrospective study of patients with pancreatic pseudocysts (n = 17): 90 males (76.9 %), 27 females (23.1 %) aged 25 to 72 years. The patients underwent external percutaneous drainage (group 1, n = 96) or internal drainage (group 2, n = 21). The diagnosis of pseudocysts included clinical, laboratory (biochemical and bacteriological) and special investigation methods: radiological, endoscopic, ultrasound examination of hepatobiliary zone, computer tomography.

Results. Complications in the early postoperative period were observed in patients from both groups 1 and 2. They were related to inefficacy of cystodigestive anastomosis, which required percutaneous drainage in 2 cases (9.5 %), or to formation of pancreatic fistula. Lethal outcomes were not observed. Readmission to surgical department for removal of the drainage was required in 28 (23.9 %) patients from group 1. Internal drainage is considered more advantageous for PPC decompression compared to external one due to persistence of pancreatic fluid passage through gastrointestinal tract. External drainage is associated with frequent external pancreatic fistulae formation as well as prolonged hospital stay and treatment in an outpatient setting worsening the quality of life, but it is an intervention of choice in somatically severely ill patients, in fast growing cyst, imperfectly formed wall and threatening cyst rupture into abdominal cavity or abscess. These aspects prevent from refusal from external drainage for PPC treatment.

Conclusion. When choosing the optimal time and type of surgical intervention in PPC, the surgeon should evaluate localization, sizes, maturation of PC wall and its relation to pancreatic duct, somatic state and patient’s individual features.

Kazan medical journal. 2018;99(6):1016-1021
Clinical use of various endovascular stenting techniques in challenging coronary interventions
Sazanov G.V., Belokon' O.S., Pisarenko N.V., Krasnov A.Y.

Aim. Development of an algorithm of actions for stenting of artery stenosis during challenging percutaneous coronary interventions (PCI) based on the analysis of the results of different endovascular techniques.

Methods. We analyzed the experience of the department of radiologic endovascular diagnosis and treatment of Stavropol regional clinical hospital for endovascular surgical treatment of atherosclerosis of coronary arteries. The study included 317 cases of coronary interventions with technically impossible stent delivery to stenosis by standard method along the front-line guidewire and standard choice of the guide in case of distal TIMI 3 flow. For the study the patients were divided into 3 groups comparable by the number of subjects: 104, 113 and 100 respectively. For each group we determined different stages of enhancing support with consistent step-wise transition. The groups differed by the used methods of enhancing support and consistency of their use. Among other methods of support group 2 included the method of guide change and delivery of the second guidewire of enhanced support. At the same time groups 1 and 3 used these methods separately.

Results. The smallest number of unsuccessful interventions was observed in group 2 compared to those of groups 1 and 3. The relative risk indicators also demonstrate the high effectiveness of tactics used in the group 2.

Conclusion. The most preferable method for the necessary support when stent delivery distal to stenosis is impossible, is a choice of optimal guide and use of the second guidewire of enhanced support.

Kazan medical journal. 2018;99(6):1022-1027
Clinical bioethics on successful path
Kazan medical journal. 2018;99(6):1028-1031
Cochrane Review Summaries
Intervention for treating chronic prostatitis and chronic pelvic pain in men

Вопрос обзора. Каковы эффекты немедикаментозных видов лечения у мужчин с продолжительной болью, дискомфортом в области предстательной железы (простаты) и таза (хроническим простатитом / синдромом хронической тазовой боли (ХП / СХТБ)?

Kazan medical journal. 2018;99(6):1034-1035
Interventions to treat chronic infection of the prostate gland (chronic bacterial prostatitis)

Этот обзор показал, что фторхинолоны, такие как ципрофлоксацин, левофлоксацин, ломефлоксацин, офлоксацин или прулифлоксацин эквивалентны по эффективности и показателям успеха у пациентов с ХБП.

Kazan medical journal. 2018;99(6):1035
Screening for prostate cancer
Kazan medical journal. 2018;99(6):1035-1036
Alpha blocker treatment for men to increase chances to have urinary catheter successfully removed

Альфа-блокаторы (например, тамсулозин, альфузозин) - это группа лекарственных средств, известных своими положительными эффектами на мочевые симптомы, такие как слабый поток мочи. Считают, что их релаксирующий эффект на простату может также повысить шансы на возобновление свободного мочеиспускания после удаления катетера. Этот обзор оценил имеющиеся доказательства в поддержку описанной практики.

Kazan medical journal. 2018;99(6):1036-1037
Laser prostatectomy for obstruction caused by benign prostatic hypertrophy

Трансуретральная резекция простаты (ТУРП) считается лучшим лечением симптоматической ОДУП. ТУРП улучшает симптомы и мочеиспускание путем хирургического удаления ткани предстательной железы через мочеиспускательный канал. Однако побочные эффекты, появляющиеся примерно в 20 % всех ТУРП, включают в себя потерю крови, что требует переливаний, инфекции, стриктуры, нарушение половой функции, недержание мочи и задержку мочеиспускания. Лазерная простатэктомия, использующая лазер для разрушения ткани увеличенной простаты, приводящей к СНМП, является малоинвазивной процедурой, которая в настоящее время используется в качестве альтернативы ТУРП.

Kazan medical journal. 2018;99(6):1037
Index of authors
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Kazan medical journal. 2018;99(6):1038-1040

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