ORIGINAL ARTICLES. CLINICAL MEDICINE
Aim. The paper studies p63 expression in patients with seborrheic keratosis in the presence or absence of carbohydrate metabolism disorders.
Materials and methods. The study involved 130 patients with seborrheic keratosis. Following the endocrinologist’s consultation, the patients were divided into two groups. The fi rst group comprised 68 people: 44 patients with type 2 diabetes and 24 patients with impaired glucose tolerance. The second group was composed of patients without carbohydrate metabolism disorders (62 people). The authors performed a histological study and an immunohistochemical (IHC) test using monoclonal antibodies to р63. The results of the IHC test were analysed according to the number of stained tumour cells: 0 — no response or weak staining of less than 10% of the cells, 1 — from 10% to 30% of tumour cells are stained, 2 — staining of more than 30% of tumor cells; as well as according to the colour intensity: weak (+) and marked (++).
Results. The IHC test using monoclonal antibodies to р63 produced a positive reaction in 82.3% of cases. Sixty-fi ve seborrheic keratomas (SK) (50%) exhibited a diffuse pronounced expression of p63. Weak nuclear staining (10%–30% of cells) was recorded in 42 SKs (32.3%). The study revealed a high correlation dependence of p63 expression in SK on the presence of carbohydrate metabolism disorders in patients (R = 0.82, p = 0.0000001). Thus, in patients with carbohydrate metabolism disorders, overexpression of p63 in SKs was found to be signifi cantly higher — 89.7%, as compared to 6.4% in patients without impaired carbohydrate metabolism (p = 0.00001).
Conclusion. P63 overexpression in seborrheic keratosis correlates with the presence of chronic hyperglycemia in patients. Disruption of cellular metabolism leads to changes in the balance between p63 isoforms and plays an important role in the pathogenesis of seborrheic keratosis.
Aim: To determine the clinical features and analyse the concentration of the heart failure (HF) marker in patients with atrial fi brillation (AF) and chronic obstructive pulmonary disease (COPD).
Materials and methods: 120 patients were divided into the following groups: 1) experimental group including patients with chronic heart failure (CHF), AF and COPD (n = 29); 2) comparison group 1 including patients with COPD, but without cardiovascular diseases (CVD) (n = 28); 3) comparison group 2 consisting of patients with CHF and COPD, but without AF (n = 30); 4) comparison group 3 comprising patients with CHF and AF, but without COPD (n = 33). Clinical symptoms and tolerance to physical load were assessed for all patients with CHF using the clinical condition scale (CCS) and the 6 Minute Walk Test (6MWT), respectively. The severity of dyspnoea was assessed (mMRC scale) in the groups of patients with COPD. The concentration of NT-proBNP was analysed using a Biomedica NT-proBNP reagent pack (SK-1204).
Results: A comparative analysis of the CHF clinical manifestations (according to CCS) in the study groups showed higher median values in the group of patients with CHF, AF and COPD, as compared to the same indicator in patients with CHF and AF, but without COPD (p < 0.001). An intergroup analysis of the dyspnoea symptom using the mMRC scale showed the lowest degree of dyspnoea in the group with COPD and without CVD, which signifi cantly differed from the same indicator in patients with CHF and COPD, but without AF (p = 0.015). The 6MWT results did not reveal signifi cant differences between the groups (p = 0.017). In assessing the level of the HF marker, higher concentrations of NT-proBNP were found in the group of patients with CHF, AF and COPD, which exceeded its concentration in patients with CHF and COPD, but without AF (p = 0.0003), as well as in patients with CHF and AF, but without COPD (p = 0.01).
Conclusion: 1. Due to the presence of chronic bronchial obstructive syndrome, higher severity of clinical HF symptoms was established in patients with CHF, AF and COPD – as compared to the group including patients with CHF and AF, but without COPD. 2. A statistically signifi cant higher level of NT-proBNP was determined in patients with CHF, AF and COPD, which is associated with the presence of hemodynamic load on both ventricles of the heart under the mutual infl uence of AF and chronic bronchial obstruction on the hemodynamics of the pulmonary circulation.
Aim. The present article assesses the state of the central part of the auditory analyser in children with type 1 diabetes.
Materials and methods. The study included 71 children with type 1 diabetes mellitus who were treated at the Endocrinology Department of the Children’s Territorial Clinical Hospital from September 2017 to February 2018. The children’s age ranged from 7 to 15 years (8±2.6). Group A comprised 34 children who were fi rst diagnosed with type 1 diabetes, with the duration of clinical manifestations not exceeding 3 months; whereas group B included 37 children who had been suffering from type 1 diabetes for 1–5 years. The control group was represented by 30 children of the same age group without a somatic pathology (group K). The functional state of the central part of the auditory analyser was assessed when studying brainstem evoked potentials of short, middle and long latency.
Results. In the course of studying short-latency brainstem evoked potentials at a broadband-click stimulus frequency of 10 Hz and an intensity of 70 dB, the latent periods of peaks and peak-topeak intervals were analysed in groups A, B and K. Statistically signifi cant differences were observed for I and V latent periods of peaks, as well as for the I–V inter-peak interval. At a click stimulus intensity of 70 dB, peaks and peak-to-peak intervals of middle-latency brainstem evoked potentials revealed differences in the values of NO, PO, Na, Pa and NO–PO between the groups of patients with type 1 diabetes and the control group. Greater statistical differences, as compared to the control group, were observed in the latent periods of long-latency brainstem evoked potentials for interval P1 in group A and intervals P2 and N2 in group B (unfavourable course) during 100 dB stimulation at a repetition frequency of 1 Hz in a time window of 50 ms. The presence of differences between groups A and B in the parameters of peak P2 (p ≤ 0.07), as well as peak intervals P2–N2, N1–N2, N1–P1, N2–P2 and N1–P2, may indicate signifi cant differences in the centres of the auditory analyser (p ≤ 0.1). At the same time, the maximum activity of the studied parameters was found in the group of patients with newly diagnosed type 1 diabetes.
Conclusions. The study of different types of brainstem evoked potentials, characterising the central parts of the auditory analyser, in children with type 1 diabetes allowed the authors to register functional disorders both in the brainstem segment and in the cortical structures. This fact indirectly indicates initial manifestations of diabetic neuropathy in the studied category of patients and can be used in the future for diagnosing CNS disorders.
Aim. In this study, we set out to determine the informative value of multi-parametric ultrasound examination using ultrasound elastography in the differential diagnosis of thyroid nodular neoplasms.
Materials and methods. We analysed 229 multi-parametric ultrasound examinations of patients in the preoperative period in order to assess the effectiveness of strain elastography (SE) and shear wave elastography (SWE) drawing on the example of ARFI and Strain Ratio. Two patient groups were formed. The fi rst group (N1=93) included patients with thyroid cancer, whereas the second one (N2=136) was composed of patients with benign thyroid nodules (thyroid adenoma and follicular or colloid goitre). The control group consisted of 174 patients with unchanged thyroid parenchyma. SE visualised tissue elasticity as a colour map. Shear wave elastography (SWE) — ARFI and Strain Ratio techniques — was performed using the following ultrasonic apparatuses: Acuson S-2000 (Siemens, Germany), Ultrasonix SP (Sonix, Canada) and Mindray DC-8 (Mindray, China).
Results. According to the obtained data (SE technique), the parenchyma of the unchanged thyroid gland exhibited heterogeneous, uneven fi ne / moderately granular, symmetrical staining (96.6%). Thyroid cancer was characterised by a shear wave velocity (ARFI) of greater than 3.57 m/s, as well as a density ratio (elasticity modulus and Strain Ratio) of more than 1.56.
Conclusion. The study revealed that the application of ultrasound elastography is highly informative in the comprehensive diagnosis of thyroid nodular neoplasms and should be used when thyroid cancer is suspected to ascertain the size of nodules, as well as the tumour invasion into surrounding tissues.
Aim. The paper studies the dynamics of the indicators defi ning the antioxidant system (AOS) and endogenous intoxication in patients with microbial eczema (ME) prior to and following treatment.
Materials and methods. The experimental group consisted of patients with ME (n=30) and the control group comprising somatically healthy individuals (n=30). In this study, we determined the components of the antioxidant defence system in blood plasma and erythrocyte suspension, as well as assessed endogenous intoxication.
Results. The study revealed an imbalance of indicators refl ecting the severity of oxidative stress and endogenous intoxication in patients suffering from ME. Prior to receiving treatment, the experimental group, as compared to the control group, exhibited an increase in catalase activity (CAT) up to 35.93 [32.50; 38.22] mmol / (min • l) (p < 0.001) and glutathione peroxidase (GPx) up to 1194.27 [1069.50; 1375.78] μmol / (min • l) (p < 0.001). In addition, there was a decrease in the activity of superoxide dismutase (SOD) to 13.28 [11.35; 14.10] u/l (p < 0.001), glutathione reductase (GR) to 501.46 [479.77; 542.52] mmol / (min • l) (p < 0.001) and the concentration of reduced glutathione to 1.64 [1.59; 1.78] μmol / ml (p = 0.043). We observed no statistically signifi cant changes in the total antioxidant activity (TAA) of blood plasma (0.59 [0.55;0.62] mg/l; р = 0.375) and the sulphhydryl groups (0.44 [0.41;0.47] ODU; р =0.111). The patients with ME exhibited the syndrome of endogenous intoxication (SEI), accompanied by an increase in the content of medium and low molecular weight molecules in plasma to 12.19 [11.20; 13.37] arb. u. (p < 0.001), with their content in erythrocytes being relatively normal – 15.23 [14.26; 16.44] arb. u. (p = 0.005). Following the treatment, changes in the studied parameters were of a multidirectional character in relation to the control values. An increased level of CAT and GPx (р <0,001), as well as lower values of SOD and GR, continued to be observed (р < 0.001). The TAA in serum (p = 0.308), sulphhydryl groups (p = 0.111) and reduced glutathione (p = 0.107) did not differ signifi cantly from the control values. The treatment did not reverse the SEI: the content of medium and low molecular weight molecules continued to increase in both plasma and erythrocytes, as compared to the control values (p < 0.001 in both cases).
Conclusion. The obtained data confi rm the failure of mechanisms underlying antioxidant defence in patients with ME. Despite the attempt of its compensation by increasing the catalase activity, SOD control values were still not reached. An increase in the GPx activity along with a decrease in GR was observed, which could have lead, in turn, to a decrease in the concentration of reduced glutathione. The failure of the antioxidant defence mechanisms is also indicated by an increase in the content of medium and low molecular weight molecules, as well as by the development of the SEI, resulting from the excessive formation of reactive oxygen species and the inability of the antioxidant system to neutralise them.
ORIGINAL ARTICLES. MEDICAL AND BIOLOGICAL SCIENCES
Aim. The paper analyses the dynamics and structure of forensic medical examinations conducted by an expert panel in cases involving medical malpractice in the Krasnodar Krai (2010– 2018).
Materials and methods. The authors studied the annual reports along with the archived copies of expert panel reports on the cases of medical malpractice submitted in 2010–2018 by the Department for Complex and Expert Panel Examinations (Bureau for Forensic Medical Examination, Krasnodar). The obtained results were processed using Microsoft Excel 2010 and SPSS Statistics Data Editor v.17.0. In this study, the authors employed the following methods: retrospective, comparative and analytical.
Results. In 2010–2018, a total of 1,023 expert panel examinations were conducted in cases involving medical malpractice. A steady increase in the number of examinations (from 36 in 2010 to 245 in 2018) is associated with the growing number of citizens complaining about the poor quality of medical care, the interest of judicial and investigation authorities in looking into such offences, etc. A direct cause-and-effect relationship between imperfect and erroneous healthcare delivery and ensuing adverse effects was established in 212 cases, whereas indirect or no relationship was determined in 130 and 644 cases, respectively. The number of examinations pertaining to criminal cases amounted to 29.1%, showing an increase by 3.5 times (from 16 in 2010 to 57 in 2018); while the number of examinations related to civil cases and those conducted during pre-investigation checks came to 18.2% and 52.7%, respectively.
Conclusion. The study shows a steady increase in the number of examinations related to medical malpractice (including criminal cases), which reveal a direct cause-and-effect relationship between errors in healthcare delivery and clinical outcomes
Aim. In this article, the authors determine the severity (index) of histological activity (HAI) and fi brosis in various forms of alcoholic liver disease drawing on the autopsy material, as well as suggest a marker for detecting fi brosis.
Materials and methods. The authors studied 110 autopsies and histopathological studies of people who died from ethanol poisoning in the setting of various forms of alcoholic liver damage (95) and traumatic brain injury – control (15). Alcohol dehydrogenase (ADH) activity was studied through histochemical methods; values were estimated through the quantitative morphometry of the histochemical reaction product using the MORFOLOG program developed at the Department for Forensic Medicine (V.A. Porodenko, 1996). Statistical analysis was performed using the STATISTICA 10 software package and a created Exсel database. In order to determine the signifi cance between two compared values, the Student’s t-test was employed. Correlations were estimated using the Spearman’s rank correlation coeffi cient (r).
Results. The study revealed various degrees of histological activity and fi brosis in the setting of alcoholic steatosis, hepatitis and cirrhosis. The initial liver damage is characterised by minimal / weak activity and F0–F2 stage of fi brosis. With the progression of the pathological process in the liver, HAI is estimated as moderate and severe (F2–F4 stage of fi brosis). There is a correlation between the development of perisinusoidal and pericellular fi broses (r = –0.655), septae (r = –0.435), connective tissue in the portal tracts and around a vein (r = –0.517) and the number of medium caliber vessels in the liver, as well as between the portal vein diameter and the development of perisinusoidal and pericellular fi broses (r = 0.377). The authors noted high and moderate positive correlation between the ADH activity in zone 3 of the liver acini and the development of necroses and fi brosis, minor cholestases, expansion of the perisinusoidal spaces. The calculated index of fi brosis and ischemic liver damage correlates with its impaired morphofunctional state.
Conclusion. The obtained data indicate that fi brosis develops in the early stages of alcoholic liver damage, whose severity can be assessed using the proposed method for determining the index of fi brosis and ischemic liver damage, given that it refl ects both the structural and functional state of the organ.
REVIEW
Aim. The article presents information on modern urethral bulking agents used in the treatment of female stress urinary incontinence (SUI).
Materials and methods. The authors reviewed the current scientifi c literature on the topic (original articles, monographs, meta-analyses), whose relevance lies in the increasing interest of both clinicians and patients in the minimally invasive treatment of SUI.
Results. On the basis of available information on the use of urethral bulking agents, regulatory bodies prohibited the use of substances that did not meet the requirements of safety and effi cacy. Substances approved for clinical use are safe and show considerable effect, which makes them a suitable alternative to the surgical treatment of SUI.
Conclusions. This kind of treatment is characterised by a low rate of serious complications and a suffi ciently high level of patients’ satisfaction with the results, despite its lower objective cure rate. Further research in this area involves a search for the “ideal” urethral bulking agent, as well as the use of cell technologies.
Hypokalaemia is the most common electrolyte abnormality seen in cardiac patients, which represents a side effect of diuretic therapy or results from the overactivation of the renin-angiotensinaldosterone system and the sympathetic nervous system in heart failure. Hypokalaemia is known to contribute to an increased risk of ventricular arrhythmias whose mechanism is based on the dynamic interplay of the provocative trigger and the vulnerable substrate. A premature ectopic impulse acts as a provocative trigger, whereas the vulnerable substrate is created by the structural and functional myocardial changes that favour the impulse circulation within a closed conducting pathway, thus perpetuating the re-entrant activation. The premature ectopic impulse that serves as the initiating event for arrhythmia can be generated due to abnormal automaticity or triggered activity. Hypokalaemia facilitates abnormal automaticity by increasing the rate of spontaneous diastolic depolarisation in Purkinje fi bres, which then start to exhibit pacemaker activity that interferes with the regular activations set by the sinoatrial node. The triggered activity is attributable to the early and delayed afterdepolarisations in cardiac myocytes. The early afterdepolarisations are typically precipitated by an excessive lengthening of the cardiac action potential duration that results from the inhibition of the repolarising K+ currents in the setting of hypokalaemia. The delayed afterdepolarisations are related to calcium overload in cardiac cells, which is provoked by hypokalaemia via inhibition of the Na+-K+ ATPase on myocyte sarcolemma. This translates to the increased intracellular Na+ levels, which in turn activate the reverse mode of the Na+-Ca2+ exchange, leading to increased cytosolic Ca2+ concentration. With regard to creating a vulnerable substrate for re-entry, hypokalaemia is known to induce a non-uniform increase in the action potential duration in different myocardial regions, which amplifi es spatial heterogeneities in the recovery of ventricular excitability during the fi nal repolarisation phase. This sets favourable conditions for a unidirectional conduction block upon premature ectopic activation, which initiates the impulse propagation around a small area of refractory cardiac tissue. In addition, hypokalaemia slows cardiac conduction by inducing hyperpolarisation of the myocyte sarcolemma that results in markedly increased excitation threshold. The induced conduction delay in the re-entrant circuit then allows suffi cient time for recovery from refractoriness in the cardiac cells ahead of the excitation wavefront, which sustains re-entrant activation. The risk of ventricular tachyarrhythmia becomes particularly high when hypokalaemia is combined with the administration of cardiac glycosides or class III antiarrhythmic agents.
Aim. To review Russian and foreign literature of the recent years pertaining to the modern methods of diagnosis and management of children and adolescents suffering from cardiomyopathies.
Materials and methods. Russian and foreign literature was analysed using the following databases: RSCI, Scopus, Web of Science, Pubmed.
Results. There has been an increase in the proportion of non-specifi c myocardial lesions of non-infl ammatory origin in the structure of cardiovascular diseases in children and adolescents. Cardiomyopathies (CMP) constitute a group of myocardial diseases, which have been defi ned relatively recently and are increasingly attracting much research attention of cardiologists, morphologists, geneticists and cardiac surgeons. CMPs in children constitute a severe pathology and are characterised by a progressive course, resistance to therapy, as well as by an unfavourable prognosis. In this connection, a fundamentally new concept of CMP diagnosis, as well as its role in the structure of cardiovascular diseases, has been introduced, which is associated with the achievements in the spheres of medical genetics, immunology and molecular endocrinology. The article presents data from the Russian and foreign publications on paediatric aspects of metabolic CMP. In ths paper, we consider clinical, paraclinic and instrumental criteria for the diagnostics of non-coronary myocardial pathologies and associated pharmacotherapy, as well as some terminological issues.
Conclusion. The problem of effi cient CMP diagnostics remains to be solved; its complexity is explained by the absence of specifi c clinical disease markers and a long asymptomatic course. CMPs occupy a special place among myocardial diseases of various origins, thus requiring a common diagnostic algorithm, as well as a complex of preventive, therapeutic and rehabilitation measures to be used in the paediatric practice.
The present article summarises existing ideas about the sources of leprosy and the modes of its transmission. The authors cover the evolution of views on the origin of this infection along with the mechanism underlying its transmission. Special attention is paid to modern research trends and current achievements in the sphere of modern leprology.
CLINICAL CASE
Background. Hodgkin’s lymphoma (HL) is a malignant disease of lymphoid tissue, which is characterised by the appearance of giant Reed—Berezovsky—Sternberg cells in the lymph nodes affected by the pathological process. These cells can be detected through microscopic examination. Currently, HL is one of the most treatable oncological diseases. In recent years, the recovery rate in patients suffering from this pathology has increased (70–90%), almost reaching the recovery rate in patients starting treatment at the early stages. Given the above, the quality of life in these patients during remission is becoming more important, since most of them are women of childbearing age planning to have children. In this connection, it is of great importance to study the course of pregnancy and labour, along with their effect on the possibility of a relapse, in such patients.
Aim. In this paper, we set out to analyse the course of pregnancy and childbirth in a patient suffering from HL.
Materials and methods. We studied the medical records (including medical history and pregnancy records) of a patient whose pregnancy occurred in the setting of a severe oncological pathology – HL in remission. The patient underwent a thorough examination and the baby was successfully delivered.
Result. The outcome of pregnancy and childbirth for the patient and foetus was studied in the setting of a severe oncological pathology (HL in remission).
Conclusion. The pregnancy of a woman suffering from a serious oncological pathology (HL in remission) was prolonged to full-term and successfully completed. The patient was able to experience the joy of motherhood for the third time.
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