OBSTETRICS AND GYNAECOLOGY
Background. Spontaneous miscarriage is the most common complication of pregnancy. Obesity increases the risk of adverse pregnancy outcomes.
Aim of the study. To assess the cytokine profile as a marker of spontaneous miscarriage in women with metabolic disorders in the past medical history.
Materials and methods. A prospective study of 170 adolescent girls with metabolic disorders was conducted between 2000 and 2013. Assessment of menstrual and reproductive function was carried out in 86, pregnancy outcomes – in 72 women. The average age of women in reproductive age was 21.95 ± 0.2 years, BMI – 24.7 ± 3.9 kg/m2.
Results. In women with early pregnancy losses and metabolic disorders in past medical history, the predictor of an early pregnancy loss is an increase in the ratio of pro- and anti-inflammatory cytokines TNF-a/IL-10 in serum at 7–8 weeks of gestation (OR = 2.29). It was determined a significant correlation between the levels of pro- and anti-inflammatory cytokines of the same name in serum and chorion (IL-10 (p = 0.000) and TNF-α/IL-10 (p = 0.001), which indicates similar changes in chorion. The activity of NF-kB in chorion was 5.75 ± 0.51 pg/ml.
Conclusions. The findings suggest that the cytokine balance of pro- and anti-inflammatory cytokines in women with metabolic disorders in past medical history is an important component in the development of early pregnancy losses.
INTERNAL DISEASES
Aim of the research. To study the parameters of nutritional status of patients with acute and chronic coronary syndromes and symptoms of heart failure in conjunction with clinical, anthropometric, laboratory parameters, structural and functional characteristics of the heart.
Materials and methods. A cross-sectional study of 106 patients with acute and chronic coronary syndromes and symptoms of heart failure. All subjects underwent an integrated assessment of the nutritional status (anthropometric, caliperometric (caliper metric) indicators, CONUT scale (lymphocytes, total cholesterol, albumin), hormonal indicators (N-terminal brain natriuretic propeptide), structural changes in the myocardium using echocardiography, exercise tolerance by 6-minute walk test.
Results. Nutritional deficiency, according to CONUT scale, was found in 81.1 % of cases (86 patients). In the group of patients with the presence of malnutrition, there were significantly high level of fibrinogen and N-terminal brain natriuretic propeptide. The interpretation of changes in body composition showed a significant upward trend in the prognostic index of hypotrophy and a decrease in lean body mass as heart failure progresses. The dependence of nutritive insufficiency on the CONUT scale with laboratory parameters (creatinine, fibrinogen, brain natriuretic propeptide), structural and functional characteristics of the heart (diastolic and systolic dimensions of the left ventricle, ejection fraction, left ventricular myocardial mass index), a functional indicator of tolerance to the physical load (6-minute walk test) was determined.
Conclusion. An integrated analysis of nutritional status indicators of patients with heart failure revealed an increase of malnutrition signs with an increase of the severity of HF. Pathological effects of nutritional deficiency are associated with impaired left ventricular systolic function, reduced exercise tolerance.
GENETICS, PROTEOMICS AND METABOLOMICS
Background. An infant brain damage is an extremely urgent problem, this pathology is difficult to prevent, and subsequently it manifests itself with a variety of neurological consequences. Various mechanisms are involved in neurodamage; cytokines, as well as genes that control their activity, are under a great concern today. However, there is little data about their role as predictors of the brain damage among children after hypoxia.
Aim of the research. To identify the frequency of cytokine gene polymorphism: interleukin (IL)-1β(C-511T), IL-1β(C3953T), IL-4(C589T), IL-6(C174G), IL-10(C819T), IL-10(G1082A) among newborns with hypoxic events.
Materials and methods. The study involved 128 full-term newborn patients with hypoxic events: the first group (n = 48) included newborns who experienced chronic intrauterine hypoxia (CVH), the second group (n = 80) included newborns born in asphyxiation. Control group (52) included babies born without asphyxia and not suffering from CVH. A retrospective analysis of case-records was carried out. The material for molecular genetic analysis was DNA samples isolated from umbilical cord blood leukocytes using DNA Express Blood reagents (Scientific and Production Company LITECH, Moscow).
Results. Compared to the control group (p = 0.03) children born in asphyxia had their T allele IL-1β (C-511T) prevailed. The group of newborn who had CVH had their TT genotype (p = 0.04) and the T IL-1β allele (C-511T) (p = 0.01) prevailed compared to the control group. In the same study group while studying the polymorphism of the IL-1β gene, the T allele (p = 0.03) at the point C3953T prevailed, in contrast to the control group.
Conclusion. Due to the fact that cytokines are part of a reaction cascade leading to the secondary brain damage, under the action of hypoxia, it was found that among newborns undergoing asphyxia and chronic intrauterine hypoxia the increased frequencies of carriage of IL-1β-511TT and IL-1β-3953TT genotypes, and IL-1β-511T and IL-1β-3953T alleles increase the risk of neurodamage.
DEMOGRAPHY
Background. A hypothesis on the main role of factors of psychosocial and psychological distress in the formation of gender differences in mortality in the post-Soviet period is proposed.
Aim of the research. To identify the characteristics and main causes of changes in gender trends and indicators of sexual dimorphism in mortality of the population of the Irkutsk region in the post-Soviet period.
Methods. Statistical materials were obtained from the databases of the Federal State Statistic Service of the Russian Federation and from the Demographic Yearbooks of Russia. To establish the gender characteristics of irrevocable demographic losses, we analyzed the values of the male excess mortality index. It is defined as the ratio of the mortality rate of men to the corresponding indicator for women. We established the close connection between changes in the male supermortality index and the level of psychological distress of the population. The last index was determined by the suicide rate.
Results. During the 31-year period (1987–2017), the highest values of the male mortality index were observed in 1993– 1995 and in 2001–2005. An indicator of the frequency of suicides is proposed and applied as a specific socio-demographic criterion for the influence of the factor of psychological distress on the socio-demographic status of the population. The dependence of the male supermortality index on the level of psychological distress for the period from 1991 to 2017 is estimated. A strong positive relationship between these indicators was identified (r = 0.792; p < 0.0001).
Conclusion. Changes in the indicator of male supermortality largely depend on changes in the level of psychological distress. The indicator of sexual dimorphism of mortality (the index of male supermortality) can be used as an important indicator of pronounced changes in psychosocial and psychological distress and, accordingly, the quality of life of a society.
DISCUSSION PAPERS, LECTURES, NEW TRENDS IN MEDICAL SCIENCE
Cardiovascular diseases are among the major causes of mortality among aged people in most developed countries. Oxidative stress, which causes mutations of mitochondrial DNA and mitochondrial dysfunctions, was considered as the main mechanism of heart failure and other pathologies of old age. However, in recent years the prior paradigm of mechanisms of aging, oxidative stress and antioxidative defense was questioned and in some aspects even turned out to be wrong. In this review, we discuss the new data that led to the need to reconsider paradigms. We show that although the mitochondrial free radical theory of aging remains valid, the radical responsible for the aging is the protonated form of the superoxide radical, namely perhydroxyl radical, which was largely ignored all previous years. Perhydroxyl radical initiates the isoprostane pathway of lipid peroxidation (IPLP) of polyunsaturated fatty acids, which are part of the phospholipid core of the mitochondrial inner membrane. IPLP was discovered 30 years ago by Roberts and Morrow at the Vanderbilt University, but the mechanism of its initiation remained unknown. The IPLP causes formation of the racemic mixture of hundreds of biologically active products, named isoprostanes, and highly toxic molecules, first of all isolevuglandins. We distinguish two types of damages caused by IPLP during aging. The first one is associated with oxidative damages to cardiolipin and phosphatidylethanolamine (PEA), which result in disruption of polyenzymatic complexes of the oxidative phosphorylation system. The second type of dysfunctions is caused by the direct actions of toxic products on the lysine-containing proteins and PEA. To this type of mitochondrial damages evidently belongs the oxidative damage of the mitochondrial DNA polymerase, which results in a 20-fold increase in mutations of mitochondrial mtDNA.
INFECTIOUS DISEASES
Aim of the research. To study the epidemic manifestations of HCV infection in the Republic of Sakha (Yakutia) in order to develop recommendations for improving the effectiveness and quality of treatment and prevention measures.
Materials and methods. The paper uses materials from the official statistics of the Territorial Department of Rospotrebnadzor of the Republic of Sakha (Yakutia) for 1994–2018, and data from the electronic register «Chronic viral hepatitis in the RS (Ya)» (2019). Molecular and biological studies of the genotype of the hepatitis C virus were performed jointly on the basis of the Federal state budgetary Institution «Central research Institute of epidemiology» of Rospotrebnadzor (2007–2011, n = 75). To assess the epidemiological situation, the rate of increase in morbidity is calculated on the basis of data equalized by the method of least squares. Statistical processing was performed using the SPSS 17 program. The critical significance level is assumed to be 0.05.
Results. Thus, the study of long-term dynamics of the incidence of viral hepatitis shows that in the Republic of Sakha (Yakutia) a consistently high level of incidence of HCV with adverse trends in the development of the epidemic process remains. Analysis of the distribution of different variants of HCV genotypes allowed us to establish the prevalence of genotype 1b, which can determine the high frequency of cirrhosis and primary liver cancer. The current situation in the Republic regarding the incidence of viral hepatitis requires detailed monitoring, improvement of epidemiological surveillance and introduction of modern treatment methods. It is also necessary to improve the quality of health education among the population of the Republic.
CARDIOLOGY
Background. Coronary heart disease is the leading cause of death in the Russian Federation, causing social and economic damage to the state. Previously published studies showed the association of rs1800470 polymorphism of the gene of the transforming growth factor-β1 (TGF-β1) with the risk of developing coronary artery disease due to more severe atherosclerotic lesions of the coronary arteries.
Aim of the research. To study the association of single-nucleotide polymorphism rs1800470 of the TGF-β1 gene with the rate of progression of atherosclerotic coronary artery lesion.
Material and methods. The study included 89 men with myocardial infarction, a Caucasian race under the age of 65 years (51 ± 7.9). Genomic DNA was isolated from venous blood by the phenol-chloroform method. The rs1800470 polymorphism of the TGF-β1 gene was tested using real-time polymerase chain reaction (PCR) (TaqMan probes, AB 7900HT). Assessment of the severity of coronary lesion was carried out initially according to the standard polyprojection coronary angiography protocol with the Gensini score calculated, as well as in dynamics after 40.7 ± 29.7 months (from 5 to 103 months).
Results. Carrier of the rs1800470 allele A of the TGF-β1 gene is an independent risk factor for coronary heart disease and is associated with a more aggressive course of coronary atherosclerosis in men: a 20 % worsening of the Gensini score was observed after 7 months (p = 0.013), and by 30 % after 5 months (p = 0.003) from the initial coronary angiography. In addition, the homozygous genotype AA rs1800470 of the TGF-β1 gene is associated with the development of late stent restenoses in this group of patients after 12 months of observation (p = 0.002).
Conclusion. Identification of carriers of the rs1800470 allele A of the TGF-β1 gene can help identify patients at risk for more rapid progression of coronary artery atherosclerosis in order to conduct angiographic control in the early period – 6 months from the initial percutaneous coronary intervention.
MICROBIOLOGY AND VIRUSOLOGY
Background. To obtain reliable results of laboratory studies on the identification of Listeria, the presence of certified diagnostic agglutinating Listeria sera is required. An important step in the manufacturing process of such medical devices for in vitro diagnostics requires effective nutrient media for the accumulation of listeriosis microbe.
Aim of the research. To develop an effective nutrient medium for the accumulation of bacterial mass of Listeria.
Materials and methods. The object of the study was an experimental culture medium for Listeria cultivation. As a control, we used nutrient agar for the cultivation of microorganisms (fish meal hydrolysate, FMH-agar) and meat-peptone agar with 1 % glucose (MPA with 1 % glucose). The specific activity of nutrient media during cultivation of the test strain Listeria monocytogenes 766 was evaluated using a complex of microbiological methods.
Results. The optimal base of the nutrient medium for Listeria cultivation has been selected: pancreatic hydrolysate of river magpie fish (Rutilus rutilus lacustris) and hydrolysate of meat water production waste. The qualitative and quantitative composition of the nutrient medium has been developed, its physical, chemical and biological properties have been studied. It was found that after 24 hours of incubation at 37 °C, the nutrient medium provided the growth of typical Listeria colonies. The germination rate was 85 %, which is higher compared to the growth of the culture on MPA with 1 % glucose and GRM agar by an average of 21 % (p < 0,05).
Conclusion. The experimental culture medium for Listeria cultivation provided growth of colonies of the test strain L. monocytogenes 766 with the preservation of characteristic cultural, morphological and biochemical properties, and, in terms of germination and growth rate, exceeded the control media. The developed nutrient medium provides effective growth of Listeria and can be used as a medium for the accumulation of microbial mass.
OPHTHALMOLOGY
Background. The most common chronic cerebrovascular pathology is dyscirculatory encephalopathy, in which a decrease in blood supply due to damage to brachiocephalic vessels leads to damage to brain substances and analyzers, including visual, with the possible development of severe damage in the form of ischemic optic neuropathy. Many studies have been devoted to the relationship between atherosclerotic damage to the neck vessels and ischemic damage to the visual organ, but little attention has been paid to the study of the functional activity of the altered visual analyzer in patients with dyscirculatory encephalopathy, and the results are scattered.
Aim. To conduct a comparative analysis of changes in neurophysiological parameters of the brain and visual analyzer in patients with dyscirculatory encephalopathy and patients with a combination of dyscirculatory encephalopathy and ischemic optic neuropathy.
Materials and methods. 34 patients with the 2nd stage of dyscirculatory encephalopathy were examined and divided into two groups based on the presence/absence of ischemic optic neuropathy of various prescription periods. All patients underwent ultrasound scanning of neck vessels, visual fields determination, electroretinography, visual evoked potentials, and electroencephalogram.
Results. The results revealed changes in a number of indicators in the group of patients with a combination of two diseases: more pronounced atherosclerotic lesion of brachiocephalic vessels, a decrease in the amplitude and the alpharhythm prevalence index, a decrease in oscillatory potentials, a change in latency and amplitudes the visual analyzer according, lengthening of time indicators with a simultaneous decrease in amplitudes and depression of retinal sensitivity.
Conclusion. Patients with dyscirculatory encephalopathy complicated by ischemic optic neuropathy have a combined lesion of the brain and visual analyzer, which determines the severity of the detected changes and requires a comprehensive multidisciplinary approach to the treatment of these patients.
PEDIATRICS
A significant contribution to the morbidity and mortality of children is due to hereditary pathology, which is manifested by high mortality.
Aim of the research. To study the frequency of occurrence, structure and clinical and laboratory markers of hereditary metabolic diseases in children of the first half of the year with suspicion of this pathology.
Materials and methods. A retrospective analysis of case histories (form No. 003/y) and a face-to-face examination of patients directed to blood tests by tandem mass spectrometry, from Surgery Unit No. 2 for Newborns and Premature Babies and from the Unit of Pathology of Newborns, (Ivano-Matryoninskaya City Children’s Clinical Hospital, Irkutsk).
Results. In 2019, 21 children with suspected hereditary metabolic diseases were examined using the tandem mass spectrometry method in the above mentioned departments. All of them had at least one of the main clinical criteria for hereditary metabolic diseases: 67 % had hepatomegaly in combination with an increase in the level of liver enzymes, 43 % had a hereditary history and metabolic acidosis, 33 % showed a sudden deterioration after a period of normal development, 24 % had hypoglycemia, and 14 % had an abnormal urine or body odor, in 4.7 % of cases there was an increase in ketone bodies in the blood and (or) urine. All children identified from 3 to 7 additional criteria, which are indications for examination on the hereditary metabolic diseases.
The results of the study revealed 5 children with hereditary metabolic diseases namely amino acid metabolism. 90 % of them had a burdened hereditary history, 100 % had a concomitant pathology – hepatitis and cholestatic lesions of the liver, anemia, an open oval window and others.
Conclusion. Despite the obvious economic and medical significance of preclinical identification of patients with hereditary metabolic diseases, the screening problem contains many open questions that need to be addressed at all levels of the organization.
PSYCHOLOGY AND PSYCHIATRY
The article discusses modern problems of dimensional diagnosis of somatoform disorders including the vagueness of the criteria and the lack of reliance on pathogenetic differences in the selection of separate classification categories. An ongoing discussion on the necessity of revision of the boundaries and of “redistribution” of some somatoform disorders into different categories in accordance with their psychopathological relationship is associated with these problems. As a promising change in the diagnostic criteria of the DSM-V classification, the emphasis is shifted to psychological and behavioral characteristics, which is assessed as an actualization of the classical descriptive diagnostics methodology. As a confirmation of the significance of this, an analysis of the psychopathological study of Irkutsk psychiatrists of the first half of the 20th century, devoted to the delusion of obsession, is given. In 1935, the head of the Department of Psychiatry at the Irkutsk Medical Institute V.S. Deryabin and his student I.S. Sumbaev published a scientific work “Delirium of obsession and somatic sensations”. The authors substantiate the intimate relationship of traditionally understood sensual hysterical and ideatorial hypochondriacal mechanisms in the formation of an integral clinical picture of somatoform disorders. The use of descriptive diagnostics many decades before the introduction of ICD-10 proves the pathogenetic unity of hysterical (sensory) and hypochondriacal (ideatorial) formations within the psychosomatic register of disorders and the legitimacy of combining phenomenologically different states into a circle of somatoform
disorders.
SURGERY
Parathyroidectomy is the leading treatment for drug-refractory secondary and tertiary hyperparathyroidism in patients with chronic kidney disease. Difficulties in performing this surgery are mainly associated with the anatomical features of the parathyroid glands, in particular with the variability of their number and topographic anatomy. Ectopic parathyroid glands are one of the most common causes of persistence or recurrence of secondary hyperparathyroidism after surgery. One of the common variants of ectopia is the localization of the parathyroid gland in the anterior-superior mediastinum. The article discusses the features of surgical treatment of secondary hyperparathyroidism in patients with end-stage chronic kidney disease with this ectopia. A new method of treating hyperparathyroidism in patients with an atypical location of the parathyroid gland in the anterior-superior mediastinum is presented. This method is characterized by low invasiveness of access, ease of implementation without using special equipment and instruments. The proposed method was used in the treatment of a patient with secondary hyperparathyroidism due to chronic renal failure as a result of chronic glomerulonephritis. The duration of hemodialysis at the time of the surgery was more than 17 years. In the presented clinical case, ectopia of one of the pathologically altered parathyroid glands in the anterior-superior mediastinum was found at the preoperative stage. As a method of surgical treatment, we carried out total parathyroidectomy with autotransplantation of a fragment of parathyroid tissue into the brachioradialis muscle. Thanks to this method, it was possible to remove the atypically located parathyroid gland from the cervicotomy access and to discharge the patient within the standard terms for a given volume of surgery.
Background. Sporadic multiple gland disease in primary hyperparathyroidism occurs in 7 to 33 % of cases. The absence of specific risk factors, low sensitivity of imaging methods, and low efficiency of bilateral neck exploration and intraoperative monitoring of parathyroid hormone indicate the complexity of the diagnosis and treatment of this disease’s form.
Aim of the research. To analyze the results of surgical treatment of multiple lesions of the parathyroid gland in primary and secondary hyperparathyroidism.
Methods. There was retrospective study, which included 100 observations of surgical treatment for primary and secondary hyperparathyroidism in the thoracic department of Irkutsk Regional Clinical Hospital from May 2018 to September 2019. The main point was to identify the frequency of surgical treatment outcomes in patients with multiple parathyroid lesions. As part of the study, potential predictors of multiple gland disease in primary hyperparathyroidism were analyzed.
Results. Multiple gland disease in primary hyperparathyroidism occurs in 29 % of cases and causes persistence of the disease (p ≤ 0.01). Signs of multiple gland disease in primary hyperparathyroidism include the level of ionized calcium, parathyroid hormone (p ≤ 0.05), creatinine level and glomerular filtration rate (p ≤ 0.01). A negative result of intraoperative monitoring correlates with persistence of primary hyperparathyroidism in multiple lesions (χ2, p ≤ 0.05). Selective parathyroidectomy is associated with persistence of hyperparathyroidism in multiple lesions (χ2, p ≤ 0.05), while total parathyroidectomy is associated with remission of the disease (χ2, p ≤ 0.05). We did not find a statistically significant relationship between the results of surgical treatment for morphology of the parathyroid glands (χ2, p > 0.1).
Conclusion. Multiple gland disease is the main cause of persistence of primary hyperparathyroidism. This form of the disease corresponds to lower levels of calcium, parathyroid hormone, and kidney function. Persistence factors have been established: removal of less than four parathyroid glands and a negative result of intraoperative monitoring of parathyroid hormone. Bilateral neck exploration does not reduce the incidence of disease persistence.
Perioperative bleeding occupies a leading place among all surgical complications and, despite the rapid development of surgery, remains relevant to this day. In addition to an increase in mortality, bleeding can cause the development of other postoperative complications, which lead to disability of patients and to a decrease in the quality of life in all age groups. Most perioperative bleeding are caused by technical errors. This article reviews the problem of perioperative bleeding from the point of view of impaired coagulation capabilities of the body. The main etiopathogenetic features of hemostasis during the development of this complication are considered. The analysis of postoperative complications, which were directly or indirectly caused by bleeding during or after surgery, is presented. The prevalence of these complications in various areas of surgery has been demonstrated. More detailed study of the hemostasis system and the identification of predictors of hemostasis difficulties before the surgery may cause an improvement in the results of surgical treatment and reduce the number of postoperative complications and the duration of hospital stay. Accordingly, this will lead to a decrease in the cost of treatment and an increase in patient satisfaction with the medical care. In connection with the above, there is a great interest among surgeons and anesthesiologists in preventing the development of perioperative bleeding.
EXPERIMENTAL RESEARCHES
Background. Previously, we have shown that the polyhexamethylene guanidine hydrochloride hydrogel exhibits a pronounced wound healing. At the same time, no studies of the toxic effect of the hydrogel on animals have been conducted.
Aim of the research. In the framework of this work, the acute toxicity of the hydrogel polyhexamethylene guanidine hydrochloride was studied in laboratory animals with intragastric administration.
Materials and methods. The polyhexamethylene guanidine hydrochloride hydrogel was obtained by crosslinking the amino end groups with formaldehyde. An acute toxicity study was carried out (P 1.2.3156-13, GOST 32644-2014 and the Guidelines for conducting preclinical studies of drugs) in an experiment on outbred mice with a single addition of the test substance in different doses (1000, 3000, 5000, 8000 mg/kg) with fixing indicators (appearance, behavior, condition of the body hair coat, water and food consumption, excretion, body weight and its growth) during 14 days. After the animals were withdrawn from the experiment, autopsy, macroscopic evaluation and weighing of the internal organs were performed.
The results showed that with the introduction of the test substance into the animal organism, death during the observation period (14 days) did not occur. It was not possible to determine the semi-lethal dose for the test compound.
Conclusion. The conducted studies allow us to conclude that this substance is practically non-toxic and can be classified as hazard class V. Further research will be directed to the formation of hydrogel compositions with medicinal substances.
HISTORY OF MEDICINE AND ANNIVERSARIES
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