Vol 100, No 2 (2019)

Theoretical and clinical medicine
Clinical and methodological aspects in the diagnosis of magnesium deficiency in patients with paroxysmal atrial fibrillation
Bozhko Y.G., Arkhipov M.V., Belokonova N.A., Kiseleva D.V.
Abstract

Aim. To determine magnesium deficiency in patients with paroxysmal atrial fibrillation using a comprehensive clinical and laboratory approach.

Methods. The prospective cohort study included 35 patients of the cardiology department of the Medical association «Novaya bolnitsa». The main group consisted of 22 patients with frequently recurrent paroxysmal atrial fibrillation, the control group - 13 patients without cardiac arrhythmias. The clinical status, Holter-monitoring of the electrocardiogram, the results of the clinical test for magnesium deficiency, laboratory parameters of calcium, magnesium in blood plasma and formed elements, magnesium in whole blood, free fatty acids and plasma osmolarity were evaluated.

Results. The clinical score of magnesium deficiency was significantly higher in patients from the main group compared to the control [16.5 (11÷21) vs 13 (8÷15), p <0.001]. In the main group, there was a decrease of magnesium in the whole blood [0.55 (0.5÷0.59) vs 0.61 (0.58÷0.54), p=0.002] and inside the blood cells [0.68 (0.53÷1.29) vs 1.38 (1.29÷1.44), p <0.001]. In patients with atrial fibrillation there is a shift of the ratio of calcium to magnesium in blood plasma [2.5 (2.5÷3) vs 2.9 (2.8÷3.15), p=0.029] and intracellularly [4.85 (2.62÷9.3) vs 1.7 (1.4÷1.95), p=0.002]. The redistribution of calcium and magnesium is influenced not only by the initial concentration of cations, but also by free fatty acids. The best redistribution was obtained when the concentration of free fatty acids was 900 µmol/l, magnesium 1 mmol/l, and calcium 3 mmol/l, which is consistent with the optimal value of cations in the blood plasma.

Conclusion. Patients with paroxysmal atrial fibrillation had a significantly lower magnesium content in whole blood and inside the blood cells; magnesium concentration in the cells and in whole blood closely correlated with the results of the clinical test for evaluating magnesium deficiency; intracellular magnesium content can be influenced by the complexing interaction with free fatty acids.

Kazan medical journal. 2019;100(2):197-203
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The relationship of cytokine status with left ventricular hypertrophy in patients with arterial hypertension
Zalova T.B., Polupanov A.G., Tsoy L.G., Rysmatova F.T., Sabirov I.S.
Abstract

Aim. To study the relationship of tumor necrosis factor α and interleukin-10 levels with the presence of left ventricular hypertrophy and myocardial remodeling in patients with arterial hypertension.

Metods. 156 patients with hypertension aged 40 to 75 years (mean age 55.8±7.5 years), including 57 women and 99 men were examined. All patients were divided into two groups. Group 1 included 83 patients without left ventricular hypertrophy (55.5±7.5 years), group 2 included 73 patients with left ventricular hypertrophy (56.2±7.8 years), established by echocardiographic signs. All patients in addition to the general clinical examination and biochemical studies had echocardiography and Doppler echocardiography performed, as well as measurement of the concentration of tumor necrosis factor α and interleukin-10 by solid-phase enzyme immunoassay using specialized «Cytokine-Stimulus-Best» kit (Novosibirsk, Russia).

Results. The concentration of tumor necrosis factor α in patients without left ventricular hypertrophy was 8.43±1.36 pg/ml and was comparable with the concentration of this cytokine in patients with left ventricular hypertrophy (8.54±1.58 pg/ml, p >0.05). This pattern was typical for both men and women. The concentration of interleukin-10 in both groups was also comparable (15.4±3.6 pg/ml in group 1 and 14.7±3.4 pg/ml in group 2, p >0.05). However, we identified gender-specific features in the relationship of interleukin-10 with the presence of left ventricular hypertrophy in patients with hypertension. Thus, while in women the concentration of cytokine in groups with/without left ventricular hypertrophy did not differ significantly, in men without hypertrophy the level of interleukin-10 of 15.7±3.6 pg/ml, was significantly higher than the value of the same indicator in the group of men with left ventricular hypertrophy (14.8±2.9 pg/ml, p <0.025). Multivariate regression analysis showed that tumor necrosis factor α and interleukin-10 concentrations correlated to left ventricular wall thickness in patients without left ventricular hypertrophy. No such pattern was revealed for patients with hypertrophy.

Conclusion. The results demonstrate the modulating role of tumor necrosis factor α and interleukin-10 in myocardial remodeling processes in arterial hypertension.

Kazan medical journal. 2019;100(2):204-213
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Relationship of psychological characteristics of the perception of illness and the coping strategies of patients with coronary artery disease with the indicators of their purpose-in-life orientation
Solodukhin A.V., Trubnikova O.A., Seryy A.V., Yanitskiy M.S., Barbarash O.L.
Abstract

Aim. To study the relationship of the perception of illness and coping strategies in patients with ischemic heart disease before coronary artery bypass grafting with purpose in life orientation.

Methods. The study included 108 males aged 45 to 73 years with a diagnosis of ischemic heart disease. Clinical and psychological diagnostics included the study of the patient's perception of illness using the Personal Questionnaire of the Bekhterev Institute, the coping strategies were assessed with the Ways of Coping scale developed by Lazarus and Folkman. To study the purpose in life orientation (formation of goals in life, the level of self-realization of a person, meaningfulness and saturation of life in the past and present, plans for the future), the «Purpose-in-Life Test» by D.A. Leont'ev was used.

Results. The study showed the predominance of adaptive variants of the perception of illness and moderate use of both productive and unproductive coping strategies in the studied group, as well as the preservation of aims and guidelines for the future in the situation of preparing for coronary bypass surgery. A positive relationship was found between the indicators of general meaningfulness of life, dedication, satisfaction with the process of activity and achievement of results with the indicators of adaptive variants of the perception of illness and productive coping behavior. Low levels of overall meaningfulness of life, inability to set goals and achieve them, as well as lack of satisfaction from past events, are associated with high rates of maladaptive variants of the perception of illness and the choice of unproductive coping strategies.

Conclusion. A high level of purpose in life orientation in patients with ischemic heart disease can lead to the formation of adaptive variants of the perception of illness variants and productive coping strategies, whereas a low level of purpose in life orientation probably leads to the risks of the formation of maladaptive perception of illness variants and coping strategies.

Kazan medical journal. 2019;100(2):214-220
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Primary prevention of the main dental diseases in children at different stages of orthodontic treatment with bracket systems
Bril’ E.A., Moiseenko S.A., Galonskiy V.G., Shishkov N.Y., Pustoshilova A.S., Bril’ V.I.
Abstract

Aim. Evaluation of the effective preventive methods of dental caries in children with dentoalveolar anomalies.

Methods. Orthodontic treatment was received by 50 children aged 12-14 years with dentoalveolar anomalies who were treated by an orthodontist using ligature bracket and who had a compensated form of dental caries before the beginning of the hardware treatment. In the first group of children (control, 25 subjects) professional oral hygiene twice a year was followed by the coating of all teeth with fluoride. Children of the second group (25 subjects) after professional oral hygiene twice a year had their teeth covered with tooth enamel around brackets with Clinpro XT Varnish (3M ESPE) material containing fluorine, calcium and phosphate compounds. Dental examination every three months included assessment of oral hygiene and the state of the gums, the presence of carious defects, fillings and removed teeth, followed by the calculation of the main dental indices.

Results. On the basis of studies of the dental status in children undergoing orthodontic treatment using brackets, the main dental indices such as DCF (decay/missing/filled), complex periodontal index, papillary-marginal-alveolar index were characterized at the stages of treatment. The analysis of the recorded values was performed in the comparison groups for each research method and the main statistically significant differences were identified. The study revealed that children from group 2 had positive dynamics of the state of periodontium within 18 months: the value of papillary-marginal-alveolar index among children from group 2 decreased by 5.4 times, the value of complex periodontal index decreased by 3.5 times. Children from group 2 had a significantly lower incidence of caries compared to the control group after 18 months of remineralizing therapy: the increase of complex periodontal index among children receiving orthodontic treatment with Clinpro XT Varnish coverage twice a year was only 1.42±0.16, incidence of caries of teeth surface reduced by 55%.

Conclusion. On the basis of these studies, a comparative characteristics of the dental indices was performed at the stages of treatment using the brackets, depending on the used primary preventive measures; dental status of children at the stages of orthodontic treatment have their features: special oral hygiene tools should be guided by hygiene indices and complemented by remineralizing drugs.

Kazan medical journal. 2019;100(2):221-225
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Oxidative protein modification of the temporal bone tissue in chronic otitis media
Dubinets I.D., Sinitsky A.I., Korkmazov M.Y., Chernykh E.I., Kukhtik S.Y.
Abstract

Aim. To study the role of oxidative protein modification of bone tissue proteins in the formation of destruction of temporal bone structures in chronic otitis media.

Methods. The study included 139 patients aged 16-75 years with a verified diagnosis of chronic otitis media, who are candidates for surgical treatment. Depending on the method of surgical treatment, patients are divided into four groups (by nosology and complications and reoperations): patients with tubotympanic otitis media and epitympanic antral otitis, without complications and with local or intracranial complications, after reconstructive sanitizing ear surgery. The state of the processes of oxidative modification of proteins was evaluated in the bone tissue of the middle ear cavities, obtained intraoperatively, by the content of carbonyl products with the use of spectrophotometry. The data were processed by descriptive statistics and were presented in the form of a median and a range between quartiles with an estimate of the reliability of the intergroup differences by the Mann-Whitney U-criterion.

Results. A comparison of the indicators characterizing the oxidative modification of bone tissue proteins of the temporal bone in patients with complicated and recurrent forms of chronic otitis media demonstrates a greater degree of free radical destruction of proteins, primarily markers of early stages of protein damage and an increase of aldehyde products, both at the basal level and in response to induction in a complicated course of the disease.

Conclusion. The obtained data allow drawing a conclusion about a high level of oxidative stress in bone tissue in destructive forms of chronic otitis media accompanied by relapses and complications, and about the perspectives of antioxidant pre-operative use taking into account the features of oxidative stress in bone tissue in patients with chronic otitis media.

Kazan medical journal. 2019;100(2):226-231
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Study of biochemical markers in newborns with necrotizing enterocolitis
Mekhtieva S.A., Nasirova S.R., Rakhimova N.D., Gafarov I.A.
Abstract

Aim. To study the level of biochemical markers to optimize the diagnosis and prognosis of necrotizing enterocolitis in newborns.

Methods. 110 newborns with necrotizing enterocolitis were observed in the intensive care unit at the age of 1 to 28 days. According to the stages of necrotizing enterocolitis, all examined newborns were divided into three groups. Group 1 consisted of 49 newborns (40.5%) with necrotizing enterocolitis stage I, group 2 included 48 newborns (39.7%) with necrotizing enterocolitis stage II and group 3 included 13 newborns (10.7%) with necrotizing enterocolitis stage III. In 40 newborns with necrotizing enterocolitis, matrix metalloproteinase-2, -9, -17, cathelicidin, transferrin in the blood and fecal calprotectin in the feces were measured by ELISA.

Results. Comparative analysis demonstrated that matrix metalloproteinase-2 was increased in newborns from group 1 by 6.9 times, in group 2 - by 8.3 times and in group 3 - by 10.7 times. Similarly, the level of metalloproteinase-9 was increased in group 1 by 3 times, in group 2 by 3.4 times, and in group 3 by 4.5 times compared to the newborns from the control group. The concentration of metalloproteinase-17 in newborns from groups 1 and 2 was almost the same and increased on average by 2.5 times, and by 3.6 times in group 3 compared to the control. In examined newborns, the highest level of cathelicidin and lowest level of transferrin were observed in necrotizing enterocolitis stage III, which indicates the more severe course of the disease and may be a predictor of changes in treatment tactics. So, taking into account the diagnostic value of fecal calprotectin (75%), it can be used as a noninvasive marker of inflammation in the intestine.

Conclusion. The established changes in the level of biochemical markers (metalloproteinases, cathelicidin and transferrin in the blood and fecal calprotectin in feces) have diagnostic and prognostic value in the diagnosis, prediction of outcomes and optimization of treatment tactics of necrotizing enterocolitis in neonatal practice.

Kazan medical journal. 2019;100(2):232-238
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Experimental medicine
Immunohistochemical evaluation of Ki-67, Cyclin D1 and β-catenin expression in the subtypes of triple negative breast cancer
Vashchenko L.N., Gudtskova T.N., Nepomnyashchaya E.M., Karnaukhov N.S., Kvarchiya M.V.
Abstract

Aim. To evaluate the expression levels of Ki-67 and cyclin D1 and β-catenin in the subtypes of triple negative breast cancer.

Methods. The study was conducted on the surgical material from 60 patients of clinical stage 2A (T1N1M0 or T2N0M0) who were treated at the Rostov Research Institute of Oncology from 2012 to 2015. For immunohistochemistry, antibodies to estrogen and progesterone receptors, cytokeratins 5/6, Ki-67, cyclin D1, β-catenin, HER2/neu and EGFR proteins were used.

Results. Triple negative breast cancer with the signs of basal epithelium was found to have a significantly higher expression level of Ki-67 compared to non-basal-like one. In some part of triple negative breast cancer samples overexpression of cyclin D1 was observed. The high level of cyclin D1 in the basal-like subtype was less common than in the subtypes without the signs of basal epithelium, but its average value was significantly higher. In triple negative cancer with cyclin D1 overexpression, the loss of β-catenin on the cell membrane and its abnormal accumulation in the cytoplasm was significantly more frequent. β-catenin translocation into the cell nucleus was observed only in basal-like triple negative cancer, and 2 times more often in case of cyclin D1 overexpression.

Conclusion. In triple negative breast cancer tumors with overexpression of cyclin D1 and abnormal expression of β-catenin are observed in some cases; these biomarkers can be considered as potential therapeutic targets for this group of tumors.

Kazan medical journal. 2019;100(2):239-244
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The mechanisms of sensitization of gastrointestinal stromal tumor cells to DNA topoisomerase II inhibitors
Dunaev P.D., Galembikova A.R., Boichuk S.V.
Abstract

Aim. To examine the ability of receptor tyrosine kinase inhibitors to modulate gastrointestinal stromal tumor cells sensitivity to DNA topoisomerase II inhibitors.

Methods. The following receptor tyrosine kinase inhibitors were used in the present study - imatinib, crizotinib, cabozantinib and sunitinib. An ability of the named medications to sensitize gastrointestinal stromal tumor cells to DNA topoisomerase II inhibitor (doxorubicin) was examined by using an MTS-based colorimetric assay. The expression of apoptotic, DNA damage and repair markers was assessed with western blotting by using the corresponding monoclonal antibodies. Proliferative activity was examined in a real-time by utilizing an iCELLigence system (ACEA Biosciences Inc., USA).

Results. We found that all above-mentioned receptor tyrosine kinase inhibitors were able to sensitize gastrointestinal stromal tumor cells to topoisomerase II inhibitors. This leads to the decrease of proliferative activity of tumors cells and enhancement of apoptotic cell death. Importantly, this effect was observed in imatinib-resistant gastrointestinal stromal tumor cells. One of the possible molecular mechanisms responsible for sensitization of these cells to topoisomerase II inhibitors was the ability of the target medications to inhibit the homologous recombination. This is evidenced by substantial decrease of Rad51 recombinase expression as a result of receptor tyrosine kinase inhibitor effect on the cells with DNA damage caused by topoisomerase II inhibitors.

Conclusion. Receptor tyrosine kinase inhibitors are able to sensitize imatinib-resistant gastrointestinal stromal tumor cells to topoisomerase II inhibitors by inhibiting DNA homologous recombination.

Kazan medical journal. 2019;100(2):245-251
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Accidental hypothermia as a factor of microcirculatory disorders
Lycheva N.A., Sedov A.V., Makushkina D.A., Shakhmatov I.I., Vdovin V.M.
Abstract

Aim. To study the dynamics of indicators of microcirculation during a single episode of hypothermia of moderate degree in rats, both immediately after cessation of cooling, and in different periods of posthypothermia.

Methods. The study was performed on 25 Wistar rats. The animals were subjected to a single immersion cooling in water at a temperature of 5 °C until reaching a rectal temperature of 27-30 °C. Analysis of the microvasculature was carried out immediately upon reaching a moderate degree of hypothermia, 2, 5, 10 and 14 days after the cooling. The microcirculation parameters were estimated using a laser analyzer of capillary circulation LAKK-02 (SMO «Lazma», Russia) at a wavelength of 0.63 μm. The main parameters of microcirculation were recorded, and the amplitude-frequency spectrum of blood flow oscillations was analyzed.

Results. Immediately after reaching a moderate degree of hypothermia, vasospasm was recorded, which was confirmed by a decrease in the rate of perfusion and wave amplitudes of all frequency ranges. 2 days after stopping the cooling perfusion index returned to baseline, a decrease in amplitude of endothelial, vasomotor and respiratory waves was observed with an increase in pulse waves. On day 5, perfusion increased by 5 times was observed along with decreased amplitudes of the waves of all ranges. By day 10, the level of blood flow returned to its original values, and the wave amplitudes of all frequency ranges remained at the same low level. By day 14, a progressive decrease of the factors of bloodflow modulation was associated by the decrease of perfusion.

Conclusion. Single cooling to a moderate degree of hypothermia leads to a progressive decrease of tissue perfusion and deep inhibition of active and passive factors of bloodflow modulation.

Kazan medical journal. 2019;100(2):252-256
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Time-dependent systemic hemostatic effects of fibrin monomer in controlled liver injury in the experiment
Vdovin V.M., Momot A.P., Orekhov D.A., Tolstokorov I.G., Shevchenko V.O., Krasyukova V.O., Shakhmatov I.I., Lycheva N.A., Belozerskaya G.G.
Abstract

Aim. To evaluate the hemostatic effect of fibrin monomer after its intravenous administration at different time periods in experimental trauma.

Methods. In the experiments, in a placebo-controlled study, hemostatic and hemostasiological effects of systemic use of fibrin monomer were studied at different time periods after its administration (in 5 min, 1 h and 3 h) in 97 male rabbits of the Chinchilla breed in the controlled liver injury model.

Results. A pronounced hemostatic effect was demonstrated for fibrin monomer used at a dose of 0.25 mg/kg demonstrated by a 6.3-fold decrease of blood loss volume (% of circulating blood volume) compared to placebo on the background of the intravenous preventive fibrin monomer administration 1 hour prior to controlled liver injury. Fibrin monomer administration at a stated dose was not accompanied by significant changes in haemocoagulative parameters including measurement of platelet count, activated partial thromboplastin time, prothrombin time, thrombin time, echitox time, fibrinogen concentration, level of soluble fibrin monomer complexes, D-dimer content, and antithrombin III activity. The effect of fibrin monomer is probably realized through some effectors, the nature of which has not yet been studied. The obtained results allow choosing the optimal interval between intravenous administrations of fibrin monomer and controlled liver injury for further study of the mechanisms of its hemostatic action.

Conclusion. Fibrin monomer in small doses (0.25 mg/kg) is able to exert a pronounced hemostatic effect with its systemic administration 1 hour prior to the injury without significant changes in haemocoagulative parameters.

Kazan medical journal. 2019;100(2):257-263
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Reviews
Current views on the possibility of cervical insufficiency correction
Yakovleva O.V., Glukhova T.N., Rogozhina I.E.
Abstract

The main role in spontaneous abortion in 2nd and 3d trimesters is assigned to cervical insufficiency. According to a number of researchers, bed rest, elevated lower limbs, restriction of physical activity, tocolysis, antibacterial therapy do not affect the prolongation of pregnancy and are ineffective for preventing premature spontaneous labor. Correction of cervical insufficiency can be carried out by a vaginal form of progesterone, cerclage, pessary. The use of vaginal progesterone is justified in women with recurrent miscarriage, a history of premature birth, and shortening of the cervix to less than 25 mm. Indications for surgical correction are limited to patients with habitual loss of pregnancy due to cervical weakness or a history of premature birth. In the absence of significant obstetric history, cerclage has no advantages over the use of progesterone. The optimal time for cerclage is up to 20 weeks of pregnancy. Unlike progesterone cerclage has complications, the frequency and severity of which are attributable to the timing and indications for correction. Transabdominal cerclage is performed only when there is a technical impossibility of vaginal access due to the absence of a vaginal part of the cervix or after unsuccessful attempts of vaginal cerclages. Most often, the use of a pessary is associated with the diagnosis of a short cervix in terms of more than 24 weeks of gestation in the absence of an aggravated history. The combined use of gestagens, pessary and cerclage does not increase the efficiency of carrying a singleton pregnancy. Methods for the prevention of preterm delivery in multiple pregnancy, such as the introduction of a specialized outpatient service, bed rest, antibacterial therapy, progesterone, preventive cerclage or the insertion of a pessary do not change the incidence and mortality of newborns.

Kazan medical journal. 2019;100(2):264-269
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Ovarian hyperstemulation syndrome as a private case of iatrogenic capillary leak syndrome
Kraevaya E.E., Petrosyan Y.A., Tapil'skaya N.I.
Abstract

Idiopathic capillary leak syndrome was first described in 1960 and later received its name in honor of the discoverer - Clarkson's Disease. However, in the past two decades, more cases have been reported than in the previous 35 years, most likely due to improved recognition, the widespread use of assisted reproductive technologies in the treatment of infertility and the emergence of targer therapy - monoclonal antibodies for the treatment of cancer and autoimmune diseases. Except for Clarkson's disease, capillary leak syndrome can occur in engraftment syndrome, differentiation syndrome after bone marrow transplantation, ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral infections, mostly hemorrhagic fevers, some autoimmune diseases, administration of recombinant interleukins, cytostatics, some monoclonal antibodies including treatment with the latest anticancer drugs - immune checkpoint inhibitors, snakebite envenomation, and ricin poisoning. This syndrome is characterized by a sharp increase in vascular permeability for fluid and protein molecules that leads to the loss of fluid into the interstitium, and presents with acute onset of severe edema, often asymmetric, hypotension, polyserositis, hemoconcentration and low blood protein level. In assisted reproductive technology programs, the introduction of gonadotropins results in an increase in estradiol levels, which leads to the development of immunopathological process, accompanied by leukocyte infiltration of blood vessels and secondary hypercytokinemia. Subsequently, the secondary «wave» of cytokines and vasoactive substances secreted in response to the introduction of human chorionic gonadotropin as an ovulation trigger, leads to disruption of interendothelial contacts and the development of ovarian hyperstimulation syndrome. It is necessary to conduct a further study of the pathogenesis of capillary leak syndrome, in order to develop promising methods for the prevention and correction of ovarian hyperstimulation syndrome in assisted reproductive technology programs.

Kazan medical journal. 2019;100(2):270-276
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Adrenal incidentaloma: management of patients with functionally autonomous cortisol synthesis
Chzhen T.R., Kiseleva T.P., Torosyan M.R.
Abstract

Over recent decades due to improved visualization (ultrasound, computer tomography and magnetic resonance imaging) prevalence of adrenal incidentaloma has increased. The term «adrenal incidentaloma» is generic and includes a group of tumors of various morphology and over 1 cm in diameter accidentally discovered during radiologic investigation. The found tumor can be hormonally inactive or actively releasing different hormones, malignant or benign, and originating from different adrenal zones or having non-specific organ origin. Based on the frequency of revealing and clinical significance the most noteworthy is functionally autonomous cortisol synthesis. It means changes of hypothalamic pituitary adrenal axis without classic clinically prominent signs of cortisol excess such as proximal myopathy, stretch marks, body fat redistribution and other metabolic changes related to cortisol. Currently a large number of recommendations on the management and tactics of treatment of adrenal incidentaloma can be found in the literature. Based on the analysis of these guidelines the conclusions were made about the diagnostic errors and incorrect approaches to the choice of treatment of such patients. Recently a lot of studies have been directed to the early detection of carbohydrate and lipid metabolism disorders, relation with obesity and type 2 diabetes mellitus, arterial hypertension and osteoporosis for preserved quality of life of such patients. Influence of hypercorticism is considered to worsen the course of these conditions but at the moment no effect of adrenalectomy on mortality and life duration was confirmed.

Kazan medical journal. 2019;100(2):277-287
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Late-onset hypogammaglobulinemia after rituximab therapy
Moskalets O.V.
Abstract

Development and implementation into practice of biologic agents has dramatically changed the approaches to the treatment of many severe diseases. But in the light of experience of their use more and more attention is paid not only to their efficacy but also to side effects. One of such medications is rituximab - a monoclonal chimeric antibody to CD20 antigen, which is expressed on the membrane of pre-B-lymphocytes and mature B-lymphocytes. In the literature more frequently are published the data about late-onset side effects of this medication, particularly hypogammaglobulinemia. The review presents the data on its prevalence after treatment of different diseases with rituximab, its severity, risk of infection. The possible mechanisms of the development of this phenomenon are discussed. Long-term hypogammaglobulinemia was shown to significantly delay the restoration of peripheral compartment of B cells, with over 90% of B cell population presented by naive B cells and significantly decreased concentration of B cells. Literature analysis demonstrates that the risk of hypogammaglobulinemia increases in multiple rituximab courses, preceding immunosuppression, decreased baseline immunoglobulin level. The need for detection of serum level of immunoglobulins before therapy with rituximab is pointed out by many authors, as the main disease can mask primary immunodeficiency, primarily common variable immunodeficiency, which requires life-term replacement therapy with intravenous immunoglobulins. The issue of administration of this therapy in secondary antibodies deficiency is not solved but severe hypogammaglobulinemia or severe infectious and inflammatory processes definitely require it. So to effectively detect hypogammaglobulinemia it is appropriate to perform monitoring of the level of immunoglobulins not only before but also during the treatment with rituximab as well as in several years after its completion.

Kazan medical journal. 2019;100(2):288-294
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Clinical significance of left ventricular longitudinal deformation in coronary heart disease and non-coronary pathology
Akramova E.G.
Abstract

The values of the global longitudinal systolic deformation of the left ventricle have sufficiently high diagnostic informativeness, preceding the reduction of the left ventricular ejection fraction, local contractility and increase of troponins. Its indicators reflect the early deformation disorders not only in coronary heart disease, but can serve as a sensitive parameter of the formation of systolic dysfunction in diseases of any origin. The study of the global deformation of the left ventricle with the preservation of traditional echocardiographic parameters within the norm (ejection fraction, local contractility, wall thickness, valve status, diastolic function, etc.) allows identifying a risk group for the subsequent targeted search for signs of coronary atherosclerosis. The sensitivity and specificity of longitudinal deformation by speckle-tracking echocardiography in the verification of myocarditis and cardiomyopathies are higher than those of magnetic resonance imaging. The prognostic value of the levels of deformation in the short and long term in relation to rehospitalization and death due to the progression of heart failure is proved. Dynamic observation of the global longitudinal deformation allows revealing the side cardiotoxic effects of drugs in patients with cancer and rheumatic diseases. Numerous studies show that the values of global longitudinal deformation in healthy individuals vary from -18 to -25% depending on the calculation program used, distinguishing this parameter from a number of other ultrasonic parameters. Illustrative color marking of numerical values of segmental systolic deformation of the left ventricle in the form of a «bull's eye» is much less reproducible than the value of the officially recommended global deformation. The differences in global and segmental longitudinal strain thresholds due to ultrasound scanner software and the lack of standardized clinical observations and statistical generalizations should stimulate further research in this area.

Kazan medical journal. 2019;100(2):295-302
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Social hygiene and healthcare management
The problem of routing of patients using psychoactive substances
Pichugin A.N.
Abstract

Alcoholism and drug addiction are concomitant or indirect causes of death in almost all subclasses of diseases, as well as frequent causes of violent death. In the field of detection, treatment, prevention and support of the studied group of patients, there is a huge number of problems, such as anosognosia, possible limitation of patients' rights, socially restrictive nature of addiction care, etc. As a result, patients taking psychoactive substances, have significantly reduced motivation to appeal to narcologists. There are many systemic organizational problems in the work of the addiction service, which significantly hamper the routing of patients, which differs from the routing of patients of somatic profile. In relation to this, scientific research aimed at optimizing drug addiction service is of particular relevance. In addition, each subject of the Russian Federation has a number of features (territorial, economic, i.e.), and this indicates the need to study certain types of specialized assistance, taking into account the characteristics of each specific region. There are several levels of patient routing, each of which includes certain tasks, components, and indicates the expected result. The routing of addictive patients has its own peculiarities, related both to temporary isolation of patients and to further long-term rehabilitation. As a result, the model of highly specialized care for patients using psychoactive substances does not allow involving the greatest possible number of people in need in each stage of therapy and does not contribute to solving the main public health problems. Despite the obvious availability of this type of assistance, for most potential customers it remains unattractive.

Kazan medical journal. 2019;100(2):303-309
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The modern state of specialized psychiatric service for the population of the Moscow region
Poslavskaya I.A.
Abstract

Aim. To perform the analysis of psychiatric service of the Moscow region and to determine the basic targerts to improve the availability of psychiatric service for the population of the Moscow region.

Methods. The study included the methods of retrospective statistical observation based on the data from the official statistical forms of annual reports (forms №14, №30, №36) of psychiatric institutions of the Moscow region in 2013-2017.

Results. The Moscow region is a territory of sustainable social economic development. In terms of fertility it takes the 1st place among the subjects of the Central Federal district, and 27th place in the Russian Federation. Specialized psychiatric care for the population of the Moscow region is provided in neuropsychiatric dispensaries, hospitals, day hospitals of psychiatric clinics, based on three principles: a differentiated approach to assist different patient cohorts, stepwise and continuity of care at different stages. Despite the restructuring of the psychiatric service and the widespread reduction of the number of beds in the Russian Federation, bed capacity of psychiatric hospitals in the Moscow Region remains at the same level, although there has been a negative dynamics in the work of the hospital bed from 354.3 days in 2013 to 329 in 2017. At the same time, the efficiency of day hospitals has increased: the length of stay of patients in the day hospital has decreased from 51 in 2013 to 39 days in 2017, the day bed turnover rate has increased from 5.5 to 5.9. In five years, the number of patients discharged from day hospitals has increased: 2 200 in 2013 and 2 521 in 2017. In the outpatient service there is a steady decrease in the number of dispensary patients (decreased from 71 413 to 69 364 in 5 years), and vice versa, the number of patients provided with counseling and treatment increased from 79 023 to 93 697. The number of diseases-related visits to a psychiatrist is decreasing. In 2013, 781 243 disease-caused and home visits occured, in 2017 - 496 540.

Conclusion. The results of the conducted study indicate both positive tendencies and negative sides of psychiatric service for the population of the Moscow region, which should be taken into account when planning reorganization and optimization of functioning of psychiatric service in the modern conditions: increased number of day beds, establishing medical rehabilitation departments, reduction of inefficient hospital beds.

Kazan medical journal. 2019;100(2):310-316
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Clinical observations
Treatment of ischemic stroke caused by dissection and occlusion of internal carotid artery in a young patient
Sazanov G.V., Belokon’ O.S., Krasnov A.Y.
Abstract

The type and etiology of stroke in young patients are known to differ from those in elderly patients, that influences the diagnosis and treatment. Dissection of cerebral arteries holds the top position in the structure of the causes of ischemic stroke in children and young people below 45 years. Currently no clear guideline on the proper treatment of this pathology exists. The article presents the case of acute ischemic stroke in a young patient (the stroke was caused by the occlusion due to dissection of the internal carotid artery) successfully treated with radiosurgical method - stenting of the cervical part of the artery with the transition to petrous segment of the left carotid artery using combined proximal and distal protection of cerebral vessels. The control of patient's state and results of angiography and ultrasound demonstrate the favourable immediate and medium-term prognosis for the patient.

Kazan medical journal. 2019;100(2):317-321
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Clinical experiences
The experience of pancreas transplantation with isolated splenic artery supply
Pinchuk A.V., Anisimov Y.A., Dmitriev I.V., Storozhev R.V., Balkarov A.G., Muslimov R.S., Khodilina I.V.
Abstract

Aim. To demonstrate the possibility of successful transplantation of pancreaticoduodenal complex with isolated splenic artery supply and to assess the quality of its perfusion.

Methods. 6 patients who underwent pancreas transplantation with isolated splenic artery blood supply were examined. The recipients were 3 men and 3 women, the median age was 36.5 [31; 42] years. To evaluate the state, quality of transplant perfusion and their function, the laboratory data, doppler ultrasound, measurement of blood flow volume (CT-perfusion) and treatment outcomes were assessed.

Results. Based on the results of investigations, adequate pancreatic graft blood supply through the splenic artery alone was detected. Pancreatic transplant function in all patients was satisfactory, blood glucose levels remained within normal values. Hospital mortality was 0%.

Conclusion. Successful transplantation of pancreaticoduodenal complex with isolated splenic artery supply is technically possible due to the presence of intraorganic arterial collaterals.

Kazan medical journal. 2019;100(2):322-326
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Esophageal-gastrointestinal-diaphragmatic murmur - a new objective sign of diaphragmatic hernias
Garanin A.A., Osadchuk A.M., Adyshirin-Zade E.E.
Abstract

Aim. To present a description and scientific substantiation of a new objective sign in patients with hiatal hernias.

Methods. The study included 127 patients with diaphragmatic hernia, who made up the group of patients, including 65 women and 62 men, mean age 56.2±11.4 years. The control group was represented by the results of a survey of 100 practically healthy people: 55 women and 45 men, the average age of 52.6±2.3 years. All patients included in the study group, underwent upper endoscopy and fluoroscopy of the esophagus and stomach with a suspension of barium sulfate, the results of which were compared with the data of auscultation of the chest.

Results. The description and scientific substantiation of the physical sign of diaphragmatic hernias was presented, which is pathological peristalsis at four points of auscultation on the thorax. The factors that led to the choice of localization of the points at which auscultation of esophageal-gastrointestinal-diaphragmatic murmur is carried out in this pathology, are presented. Pathophysiological mechanisms causing the appearance of pathological peristalsis of the esophagus and stomach, which is the essence of the proposed symptom of hiatal hernia, were found and substantiated. Sensitivity and specificity of a new method of detecting diaphragmatic hernia were calculated, the positive and negative predictive values were determined. High efficiency of auscultation of abnormal motility as a diagnostic method was demonstrated. The frequency of clinical symptoms in patients with hiatal hernia and their comparison with the world experience of observation of patients with this pathology are shown.

Conclusion. The proposed objective sign, which has a very high sensitivity and specificity, is an attempt to fill the currently existing «diagnostic gap» between the subjective sensations of a patient with diaphragmatic hernia and instrumental diagnostic methods that have certain limitations in application.

Kazan medical journal. 2019;100(2):327-332
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Prevention of recurrent bleeding from varicose veins of the esophagus and stomach among patients with decompensated liver cirrhosis
Onnitsev I.E., Bugaev S.A., Ivanusa S.Y., Dzidzava I.I., Khokhlov A.V., Kotiv B.N.
Abstract

Aim. To evaluate the efficiency of laparoscopic devascularization of the esophagus and stomach with endoscopic ligation of varicose esophageal veins in the prevention of esophageal-gastric bleeding among patients with decompensated liver cirrhosis.

Methods. The results of treatment of 73 patients with decompensated liver cirrhosis and high risk of bleeding were analyzed. To prevent recurrent bleeding from esophageal and gastric veins, all patients underwent endoscopic ligation at the first step of treatment. In case of inefficiency of ligation and recurrence of varicose veins of esophagus, laparoscopic devascularization of esophagus and stomach was performed. The efficiency of laparoscopic devascularization with intraoperative endoscopic ligation of varicose esophageal veins and ligation as an independent method of treatment for the prevention of upper gastrointestinal bleeding was estimated by comparison of the frequency of recurrence of esophageal and gastric bleeding and recurrence of esophageal varices according to upper endoscopy in comparison groups.

Results. In 6 months, 1 and 2 years after laparoscopic devascularization of the esophagus and stomach in combination with endoscopic ligation, the risk of bleeding is less compared to endoscopic ligation as an isolated treatment method (p=0.05; p=0.052; p=0.06). Laparoscopic devascularization with ligation reduces the risk of recurrence of esophageal varices during the first year after surgery by 20% (χ2=2.61; p=0.106), in 2 years by 23% (χ2=1.75; p=0.091) compared to endoscopic ligation only.

Conclusion. Patients with liver cirrhosis with decompensated hepatic failure satisfactorily postpone endovideosurgical interventions; laparoscopic gastric devascularization with the intersection of the main inflows to the esophageal varicose veins is an effective method to prevent esophageal-gastric hemorrhage among patients with decompensated liver cirrhosis after ineffective endoscopic ligation.

Kazan medical journal. 2019;100(2):333-339
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The experience of radiofrequency ablation of atrial tachycardia focus with the use of high-density myocardial mapping
Omelyanenko A.S., Mavlyudov T.I., Sapelnikov O.V., Cherkashin D.I., Islamova I.M., Nasibullina A.R.
Abstract

The article presents a case of successful treatment of focal atrial tachycardia by radiofrequency ablation using high-density myocardial mapping. The aim of the work was to evaluate the possibilities of high-resolution myocardial mapping by EnsitePrecision® navigation system in the treatment of complex arrhythmias. The analysis of clinical data and results of electrophysiological examination of a 29-year-old patient with continuous recurrent focal atrial tachycardia was carried out. The patient was admitted with complaints of heart rate disorders and frequent short attacks of palpitations. According to electrocardiography, frequent short paroxysms of focal atrial tachycardia were revealed. The patient was taken for electrophysiological examination and radiofrequency ablation of the focus of atrial tachycardia. The focus of atrial tachycardia was located in the anterior septal part of the left atrium, which is a rare localization. After radiofrequency ablation tachycardia was terminated, no complications and recurrences were registered. The patient was discharged with the sinus rhythm. Navigation system EnsitePrecision® enables conducting high-density myocardial mapping, which helps to accurately determine the localization of the source of tachycardia. The radiation load on the patient and ablation time are reduced, which reduces the frequency of complications from the procedure.

Kazan medical journal. 2019;100(2):340-344
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Possibilities of the use of shear wave elastography of the liver in pregnant women infected with viral hepatitis B and C
Saryeva E.G.
Abstract

Aim. To determine the diagnostic possibilities of using liver shear wave elastography in pregnant women with hepatitis B and C viral infection.

Methods. The study included 87 women with hepatitis B and C viral infections admitted to the Center of Clinical Medicine №1 and Educational and Therapeutic Clinic of Azerbaijan Medical University (basis of the department of obstetrics and gynecology 2 of Azerbaijan Medical University) in 2016 to 2017 aged 18-45 (average age 31.4±7.1 years), and 50 uninfected women with physiological pregnancy matched by the age (average age 30.6±6.8 years). Infected women were divided into two groups: 70 pregnant women (group 1) and 17 women (group 2), who were non-pregnant at the time of the study (average age 29.8±7.2 and 30.9±6.7 years, respectively). Women with physiological course of pregnancy were included into group 3 (average age 30.6±6.8 years). Groups of pregnant patients were matched by age, gestation age and parity (p ˃0.05). All patients underwent clinical and biochemical analyses and shear wave elastography of the liver. The obtained data were processed using the methods of variation statistics with calculation of mean and standard error (M±m), Mann-Whitney U-test, Spearman's rank correlation coefficient.

Results. In 52.9±6% of the examined pregnant women with viral hepatitis, hepatitis B was identified, in 47.1±6% - hepatitis C. According to the results of shear wave elastography, the average density of the liver in these patients was 7.2±1.0 kPa. An increase in liver density in pregnant women with viral hepatitis was not accompanied by changes in the size of the liver (only 1 patient had hepatomegaly). In 71.4±5.4% of the patients, F1 degree was revealed, in 20.0±4.8% - F2, in 5.7±2.8% - F3, in 2.9±2.0% - F4. İn comparison with infected patients without pregnancy, pregnant women with viral hepatitis B and C had more severe degree of fibrosis [F1 was significantly less frequent (p ˂0.05), and F2 was significantly more frequent (p ˂0.05)], and also had F4 degree, which was not observed in non-pregnant. In infected pregnant women, there was a positive correlation between liver echogenicity and density of its tissues (p=0.495; p <0.001).

Conclusion. In pregnant women with hepatitis B and C viral infection, the use of shear wave elastography allows detecting various degrees of liver fibrosis by a non-invasive method in the early stages, even in the absence of marked clinical and laboratory changes.

Kazan medical journal. 2019;100(2):345-350
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Application of adaptive tools in relaparotomy wound surgery
Izmaylov S.G., Ryabkov M.G., Leont’ev A.E., Beschastnov V.V., Izmaylov A.G., Lukoyanychev E.E.
Abstract

Aim. To evaluate the clinical effectiveness of the developed adaptive tools for mechanical treatment of wound surface and suturing of relaparotomy wounds.

Methods. 55 patients aged 43 to 79 years after relaparotomy operated on for various acute surgical diseases of the abdominal cavity were treated. In the main group (n=22. average age 63.5±4.75 years) in uncomplicated and complicated course of the wound process after relaparotomy for treatment of the wound surface and wound closure, adaptive tools were used as proposed by the authors. In the comparison group (n=33, average age 62±6 years; p=0.98) traditional mechanical methods of wound defect sanation and wound suturing (simple nodal, 8-shaped and U-shaped sutures) were used. Monitoring of relaparotomy wound healing was performed using an ultrasound method. The analysis of postoperative local complications in the discussed groups of patients was carried out according to Clavien-Dindo classification.

Results. In patients of the main group, the multiplicity of wound surface treatment decreased by 1.8 times compared to the comparison group. There were no cases of damage to the underlying tissues of the wound edges. Wound postoperative complications corresponded to severity grade I, II, and IIIa according to Clavien-Dindo classification: in the main group - 27.3% and in the comparison group - 54.5%. Suppuration occurred respectively in 9.1 and 33.3% of patients (p=0.049).

Conclusion. The developed adaptive tools are safe and effective mechanical means of prevention of wound postoperative complications after relaparotomy.

Kazan medical journal. 2019;100(2):351-357
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History of medicine
L.L. Fofanof: 140th anniversary of his birth. Contribution to science
Abdulganieva D.I., Kirillova E.R., Bombina L.K., Khusainova A.K., Bol'shakov N.A., Sabirova G.S.
Abstract

The article is dedicated to Professor L.L. Fofanof’s scientific activity. He headed the faculty therapeutic clinic of Kazan Imperial University in 1915-1920. Being a student L.L. Fofanov was interested in pathological anatomy and physiology. His dissertation «To physiology of n. depressoris» was dedicated to studying the vasomotor center. During his visit in Germany he worked a lot. In Charite together with Professor His he studied gout and its treatment with Radium emanation. In Halle clinic under Professor Schmidt’s supervision he studied assimilation of starch in normal and pathological digestion. L.L. Fofanov also made a contribution to tuberculosis treatment: with professor V.F. Orlovskiy he studied treatment of tuberculosis with simulated pneumothorax. In his research professor L.L. Fofanov paid great attention to the issues of pathogenesis and pathogenetic substantiation of the clinical manifestation and treatment. During the World War I and Civil War he fought against typhus epidemies: he saw patients, gave lectures, studied the features of myocardial involvement. He died in 1920 from typhus.

Kazan medical journal. 2019;100(2):358-363
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80th anniversary of the department of maxillofacial surgery and surgical dentistry in Kazan state medical university
Ksembaev S.S., Torgashova O.E., Ivanov O.A.
Abstract

The article highlights the main stages of formation and development of the Department of maxillofacial surgery and surgical dentistry of Kazan state medical University in 80 years of its activity. The article presents the information about the employees of the Department, starting from the first head of the Department associate professor I.M. Utrobin, the main directions of scientific research conducted under the leadership of the heads of the Department, the results of teaching, research and medical work. Special attention is paid to the achievements and contribution of the department staff to the clinical practice and work of the basic department of maxillofacial surgery in Kazan. The history of higher dental education in Kazan and training of specialists is inextricably linked with the activities of the department, whose representatives have made a significant contribution to the development of the national scientific school of dentistry and practical health care. The study of the history of maxillofacial surgery and surgical dentistry in Kazan, the study of ways and directions of its development, the study of the activity of the heads of the department, their achievements and scientific schools created by them, have traditionally been of interest not only among historians of medicine, specialists of surgical dental profile, as well as students of dental faculties, who decided to devote themselves to maxillofacial surgery or surgical dentistry. Today we are deeply grateful and proud to honor the memory of our teachers and predecessors, those who created Kazan dental school in the period of its formation and rapid development from the beginning of the 20th century to the present day by their glorious work and scientific discoveries.

Kazan medical journal. 2019;100(2):364-370
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Conferences
International seminar «Towards an International Network for Evidence-based Research in Clinical Health Research» (EVBRES: EVidence-Based RESearch) in Bergen, Norway
Ziganshina L.E.
Abstract

4–6 февраля в Университете прикладных наук Западной Норвегии (Берген, Норвегия) прошёл Международный семинар по научно-
обоснованным исследованиям в рамках программы действий CA17117 COST — Европейского сотрудничества в науке и технологиях: «Навстречу Международному сообществу по научно-обоснованным исследованиям в области клинических и биомедицинских исследований» [Towards an International Network for Evidence-based Research in Clinical Health Research — EVBRES COST Action Workshop in Bergen (EVBRES: EVidence-Based RESearch)].

Kazan medical journal. 2019;100(2):371-373
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Obituary
Professor Vladimir Petrovich Bulatov
 
Kazan medical journal. 2019;100(2):374
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Cochrane Review Summaries
Omega-3 intake for cardiovascular disease
 
Abstract

Вопрос обзора. Мы рассмотрели рандомизированные испытания (в которых участники имеют равные шансы быть определёнными в любую группу лечения), исследующие влияние увеличения потребления омега-3 жиров, полученных из рыбы и растений, на заболевания сердца и сосудов (называемые сердечно-сосудистыми заболеваниями, которые включают инфаркты миокарда и инсульт), на степень ожирения и на содержание жиров в крови [липиды, в том числе холестерин, триглицериды, липопротеины высокой плотности (ЛПВП - «хороший» холестерин) и липопротеины низкой плотности (ЛПНП - «плохой» холестерин)].

Kazan medical journal. 2019;100(2):375-376
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Omega-6 fats to prevent and treat heart and circulatory diseases
 
Abstract

Вопрос обзора. Мы рассмотрели рандомизированные испытания (участники имели равный шанс получить любое вмешательство), в которых изучалось влияние повышенного потребления омега-6 жиров на смертность и сердечно-сосудистые заболевания (ССЗ), в том числе инфаркты и инсульты.

Kazan medical journal. 2019;100(2):376
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