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Sechenov Medical Journal

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Vol 10, No 2 (2019)
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ORIGINAL ARTICLES 

5-13 905
Abstract
Aim. To study the immediate and long - term results of treatment of patients with a primary operable breast cancer, depending on the morphological and biological characteristics of the tumor. Materials and methods. The retrospective study included 974 patients aged from 30 to 82 years (a mean age of54.5 years) with a primary operable breast cancer (T1-2N0-1M0) observed from 2005 to 2012. The overall survival (OS) and disease - free survival (DFS) were studied depending on the histological type, molecular - biological subtype of breast cancer, axillary status, lymphovascular invasion, tumor histologic grade, proliferation index (by Ki-67 staining) and HER2 protein expression. Statistical data processing included a comparison of the frequencies of the studied traits, analysis of survival curves by the Kaplan-Meier method.Results. Indicators of a 5-year OS and 5 and 10-year OS and DFS were lower in carcinomas of mixed type compared with invasive carcinoma of no special type ( p =0.03) and invasive lobular carcinoma ( p =0.01). In the absence of metastases in regional lymph nodes, indicators of 5 and 10-year OS were higher compared with the macrometastatic involvement of one ( p =0.02) or two or more lymph nodes ( p =0.004): 96.0% and 89.3%; 95.4% and 79.0%; 88.9% and 79.3%, respectively. A similar trend has been noted for indicators of 5 and 10-year DFS. The OS in the absence of metastases in the lymph nodes was greater with the luminal B HER2-positive subtype and triple - negative breast cancer. The degree of malignancy of the tumor had no effect on OS. The probability of disease recurrence was significantly higher in patients with a degree of G3 compared with G1 ( p =0.00001) and G2 ( p =0.002): the rates of 5 and 10-year - old DFS were: 84.8 and 55.0%; 94.1 and 86.0%; 88.9 and 72.2%, respectively. The expression of HER2 and Ki-67 proliferation index influenced the DFS without affecting the OS.Conclusions. The morphological factors deteriorating the OS and DFS of patients with primary operable breast cancer are the presence of macrometastases in regional lymph nodes, the defeat of two or more lymph nodes, the presence of lymphovascular invasion, mixed histological form of breast cancer. The subtypes with a more aggressive course include: HER2-positive tumors, triple negative breast cancer.
14-20 335
Abstract
Aim. To study antitumor and anti - metastatic action of AKh-554, 2-Aminium-7-(Diethylamino)-4-(4-Metoxibenzo[d][1,3]dioxol-5-yl)-4H-chromene-3-carbonytril N-Acetylamino - ethanoate, on in vivo model of lung adenocarcinoma patient - derived xenograft model. Materials and methods. In 40 immunodeficient nu/nu BALB/c female mice with heterotopic patient - derived lung adenocarcinoma xenograft model antitumor and anti - metastatic effects of 2-aminochromene derivative, AKh-554 at dose 50 mg/kg intragastrically during 7 days, were explored. Laboratory animals were randomly designated into four groups - intact mice, control, referent drug and main group. We used Cyclophosphamide as referent drug. In the tumor tissue of the animals treated with the derivative through intragastric rout we quantitively detected TUBB3, ALK and c-MET/HFG levels.Results. AKh-554 more than 7.5 times decreases both the growth rate and size of xenograft tumor when compared with control group ( p =0.001), and possesses an anti - metastatic effect. Experimental treatment up to 103±2 days increases the lifespan of tumor carriers ( p =0.001 when compared with the control; p =0.03 when compared with cyclophosphamide), and induces remission in 60% of all cases. The established effect is due to activation of tumor cells apoptosis associated with decrease in tumor tissue ALK concentration (2.77±0.54 ng/ml; p =0.001 when compared with the control and cyclophosphamide). Experimental models demonstrate no signs of pharmacological resistance to AX-554, which is confirmed by the absence of differences of c-MET/HFG tissue level in all the studied groups (0.16±0.07 ng/ml - control; 0.09±0.03 ng/ml - Cyclophosphamide; 0.10±0.04 ng/ml - AKh-554).Conclusions. AKh-554 more effectively than Cyclophosphamide inhibits xenograft tumor growth and its metastatic activity. The compound increases more than 3.3 times when compared with the control the lifespan of experimental animals and induces remission of the malignant process in 60% of tumor carriers. The compound anticancer property is due to anti-ALK-mediated activation of tumor cells’ apoptosis and suppression of cell proliferation processes.
21-28 332
Abstract
Aim. To study changes in the concentration of neurospecific proteins (NSE and S100B) and neurological status in model of focal transient cerebral ischemia in rats with preventive and therapeutic administration of citicoline. Materials and methods. The work was performed on 51 male rats weighing 180-220 g. We investigated the effectiveness of intraperitoneal injection of citicoline (2000 mg/kg) in model of transient 60-minutes intravasal occlusion of the left MCA in preventive single (EP group, n=12) and daily therapeutic administration (ET group, n=14). The control group was represented by 25 animals, of which 8 were falsely operated (CWI group - control group without ischemia), 17 were simulated cerebral ischemia (CI group - control group with ischemia). In all subgroups was evaluated the neurological status according to the Bederson scale and the concentration of neurospecific proteins (NSE and S100B) in the blood plasma before and at 1, 3 and 5 days after modeling of cerebral ischemia. When comparing groups, the nonparametric Wilcoxon test and the Mann-Whitney U-test were used.Results. In the CI subgroup, on the first day after ischemia modeling, there was a significant increase in the level of NSE and S100B, respectively, to 232 and 309% from baseline ( p <0.01) with a subsequent tendency to a slight decrease. The average neurological score in this subgroup on the Bederson scale for all 5 days of observation was 2.5±0.1. In the ET subgroup, there was no statistical difference in the dynamics of changes in the concentrations of neurospecific proteins and neurological status in the first 5 days of the postischemic period compared to the CI subgroup. In rats of the EP subgroup, the dynamics of changes in NSE and S100B in compared with the initial level, was characterized by an increase in their concentration to 193 and 253%, respectively. In comparison with the subgroups of CI and ET, the increase in concentration was less pronounced ( p <0.01). The average neurological score in this subgroup for 5 days of observation was significantly lower than in the CI and ET subgroups and was 0.8±0.2 ( p <0.01).Conclusion. In model of cerebral ischemia in rats the effectiveness of citicoline is more pronounced with its preventive than the therapeutic using. Further clinical studies are needed on the efficacy of citicoline prophylactic use.
29-35 381
Abstract
Background. Anthropogenic human activity contributes to the inclusion of zinc compounds in the biological cycle in areas where there is pollution with this metal. This leads to the accumulation of the substance in organs and tissues, which can have a neurotoxic effect on the body. Aim. To evaluate the toxic effect of zinc succinate on the structure and function of the cerebral cortex of laboratory rats. Materials and methods. The study was performed on 12 Wistar male rats aged 2 months. The animals were divided into 2 groups: control and experimental, 6 rats each. Within 30 days, the animals of the experimental group were intragastrically injected with a solution containing zinc succinate in a dose of 100 mg/kg. The rats from group 1 served as intact controls. Fluorescent analysis of coenzyme activity of the brain was performed, for which excitation was used at wavelengths of 365 nm and 450 nm, which corresponds to the reduced form of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD); morphological analysis of the motor cortex of the cerebral hemispheres.Results. Analysis of fluorescence spectra demonstrated a statistically significant decrease in its intensity in the experimental group for the coenzyme NADH (0.855 [0.092]) compared with the control (0.709 [0.062]); p <0.05. Differences in the intensity of the fluorescence spectra for coenzyme FAD is not found. Morphological analysis revealed the presence of toxic and dystrophic processes in the cerebral cortex in animals of the experimental group: the vessels are predominantly full - blooded, in some places the expansion of the perivascular space is visualized, a small number of neurons in the form of shadow cells. Conclusion. The effect of zinc succinate on the structure of the cerebral cortex is characterized by a decrease in the fluorescence intensity of coenzyme NADH, and the absence of changes in the fluorescence of coenzyme FAD, which may indicate the initiation of mitochondrial dysfunction and impaired oxygenation of neurons. Morphological analysis demonstrates the development of dystrophic changes.
36-44 442
Abstract
Aim. Poisonings with ethanol and surrogate alcohols are preventable causes of morbidity and mortality posing a serious threat to population health. The aim of the study was to analyze the dynamics of the incidence of acute poisoning with ethyl and surrogate alcohols in the Irkutsk region for the period from 2010 to 2017, and to discuss it in the context of the regional and federal policy aimed at regulation of the alcohol - containing products. Materials and methods. The data of the statistical reporting form No. 12-15 “Information on the results of toxicological monitoring” in the Irkutsk region for the period from 2010 to 2017, the data of the Federal State Statistics Service RosStat on the incidence of acute chemical poisoning, and on incidence of acute poisoning with ethyl alcohol and surrogate alcohols were analyzed. Subsequent interpretation of the results in the context of the regional and federal alcohol control policy has been performed. Results. In the Irkutsk region, during the analyzed period of time there was observed a high incidence of acute poisonings with ethanol and surrogate alcohols with territorial differences within the region, and with positive dynamics of reduction of incidence by 38.7% in 2017 in comparison to 2010. Poisonings with ethanol occupy a leading place in the structure of the incidence in comparison with poisoning with other alcohols. The Irkutsk region was ranked 9th among all other subjects of the Russian Federation in 2017 by level of morbidity with alcohol poisonings. Among all cases of poisonings the proportion of the adult working age population was 89.1%, males - 77%, and unemployed population - 57.8%, which suggests that these categories of population are under the highest risk of acute poisoning with ethanol and surrogate alcohols. Conclusion. Strengthening control over the illegal distribution of ethyl alcohol and alcohol - containing products, especially in the territories situated along the Federal highways is seen as a priority area for action. Control of distribution of alcohols between 2010 and 2017 on the territory of the Irkutsk region allowed reducing incidence of poisonings by 38.7%. To maintain the positive dynamics of reducing morbidity and mortality from acute poisoning of alcohol etiology, to preserve the labor potential of the population of the Irkutsk region, it is necessary to further strengthen and reinforce control measures at the regional level.
45-53 300
Abstract
Aim. To study non - stationary and semi - stationary forms of health - improving services of multifunctional regional social welfare centers and determine satisfaction with their quality. Material and methods. The annual reports of state budgetary institutions of Territorial Centers for Social Welfare for 2017, projects to ensure healthy longevity. A survey of 210 respondents was conducted (average age - 71 years) of the participants in the Moscow Longevity project about satisfaction with the provision of recreational services of Territorial Centers for Social Welfare. Statistical analysis included the study of the absolute and relative values of the indicators obtained. Results. An analysis of the activities of 6 organizations of the Moscow Territorial Centers for Social Welfare revealed the implementation of all federal and regional programs, as well as two of them - local projects to stimulate active longevity. Women (68%) and persons with a higher education (48%) prevailed among the surveyed participants in the Moscow Longevity project. The frequency of chronic diseases and the attendance of medical care increased with age of the respondents. The average cost of purchasing drugs amounted to 25% of the monthly pension. Within one to three years, 54% of respondents used the services of Territorial Centers for Social Welfare. The analysis of satisfaction with the quality of social and health services showed high rates (4.7-4.9 points out of 5) for the criteria “Goodwill and competence of employees”, “Organization of educational, physical, leisure and social and cultural activity”. Average values (4.5-4.6 points) were obtained for the criteria “Openness and availability of information about the services provided” and “Comfort of conditions for the provision of services”. The lowest number of points - 4.2 - was obtained according to the criterion "Organization of medical and pharmaceutical care". Conclusions. In addition to federal and regional programs, organizations of the Moscow Territorial Centers for Social Welfare also implement local projects to stimulate active longevity. The majority of respondents use the services of Territorial Centers for Social Welfare for more than one year and positively evaluate their activities, but consider it expedient to increase the semi - stationary and non - stationary bases of the Territorial Centers for Social Welfare, create conditions for the provision of medical and medicinal care.
54-62 281
Abstract
Aim. To determine the frequency and study the risk factors of transient neonatal myasthenia (TNM).Materials and methods. The study included 194 cases of pregnancy in patients with Myasthenia Gravis, observed at the Research Center of Neurology from September, 2015 to January, 2019. For analysis, data from two cohorts were combined: retrospective (151 pregnancies) and prospective (43 pregnancies). TNM was diagnosed in 31 (16%) of newborns. A univariate analysis of the features of maternal myasthenia and the characteristics of newborns in groups with and without TNM was carried out. Student’s t - test and Pearson 2 were used to compare groups. Calculated: odds ratio (OR) and 95% confidence intervals (CI).Results. The risk of TNM is associated with maternal myasthenia with predominantly affected limb and axial muscles (OR 2.62; 95% CI 1.18-5.79), severe maternal myasthenia (IVA-B, V class of MGFA), an unachieved remission before the pregnancy, exacerbations of mother’s myasthenia in the third trimester (OR 4.72; 95% CI 2.09-10.69) and postpartum exacerbations. The average titer of autoantibodies to the acetylcholine receptor (anti-AChR-Abs) before the pregnancy was higher among mothers with a child affected by TNM than without it: 18.32 and 14.35 nmol/l, respectively ( p =0.002). In children with TNM, the mean gestational age and body weight at birth were lower than in children without TNM: 36.7 and38.7 weeks, 2814.8 and 3165.9 g, respectively ( p <0.001). The proportion of Ab’s to fetal form of AChR in cord blood among newborns with TNM was 28% of the total Abs titer, and in newborns without TNM (n=17) - 83% [54; 88]. Conclusion. The risk of TNM is associated with severe maternal myasthenia gravis, the absence of remission of the disease before pregnancy and a higher anti-AChR-Abs, exacerbation in the second half of pregnancy and postpartum, as well as predominantly affected limb and axial muscles in mother’s myasthenia. Prematurity and low birth weight are the risk factors for TNM, contributed by the newborn.
63-69 299
Abstract
Among the somatic pathology in young children, the most common is anemic syndrome. Until recently, the commonest method for correction of anemia was hemotransfusion, which allows to restore normal hemoglobin quickly, but has the high risk of complications. The main disadvantage of this method is the short - term positive effect and necessity of repeating donor red blood cell transfusions to prevent rapid progression of anemia. The currently available alternative is the use of an erythropoiesis - stimulating agent, which increases the level of hemoglobin and red blood cells in the blood by stimulating of erythropoiesis in the bone marrow. Modern erythropoiesis - stimulating agent and anti - anemic drug, registered in Russian Federation, is darbepoetin alpha. When developing this drug, a new approach was used to increase the number of sialic acid residues and the degree of glycolysis. This helped to achieve an optimal ratio between the activity and the half - life period of the drug and made possible to prescribe it with longer intervals between injections. Currently, there is evidence of effective and safe use of darbepoetin alpha in premature infants with low body weight, anemia, encephalopathy and chronic kidney disease.
70-76 368
Abstract
Introduction. Diverticulosis of the colon is one of the most common diseases of the intestine. In recent years, there has been an increasing tendency for diverticular disease (DD) to manifest itself at earlier age, as well as to the more frequent development of complications in young and middle - aged people. Most interventions for planned surgical treatment of DD complications are performed by two - stage access for laparotomy. One - stage laparoscopic intervention is a relatively new approach to treatment. Case report. 40-year - old man was hospitalized in the surgical department with complaints of air release during urination and aching pain in the lower part of abdomen. Outpatient examination excluded the pathology of the prostate gland and revealed infiltration between the urinary bladder and sigmoid colon. A complex examination, including cystoscopy, colonoscopy, multispiral computed tomography with contrast, showed the presence of chronic paracolic infiltration and blad - derntestinal fistula, which complicated the latent course of colon DD. Laparoscopic opening the abscess, resection of the sigmoid colon, the formation of descendo - rectal anastomosis was performed in one - step. Intra - and postoperative complications were not observed, dynamic observation and control examination after 6 months showed no symptoms. Discussion. One - stage laparoscopic surgery in the treatment of chronic inflammatory complications of colon DD is currently available procedure, which allows in a short time to relieve patients from symptoms and has good immediate and long - term results. The condition for the use of this technique is a sufficient experience of laparoscopic surgery of the abdominal cavity, retroperitoneal space and pelvis.


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