Vol 29, No 4 (2021)

Introduction: NMDA receptors are involved in the pathogenesis of seizures, as it subunit is coded for by the GRIN1 gene. Different GRIN1 mutations are known in patients with different forms of epilepsy and encephalopathy. However, no data are available on the participation of the GRIN1 gene and its polymorphisms in the development of post-traumatic epilepsy (PTE).

Aim: To determine the influence of single-nucleotide rs1126442 polymorphism of GRIN1 on the risk of PTE formation.

Materials and methods: A total of 140 patients were examined, which included 69 patients with PTE and 71 patients with genetic epilepsy. All patients underwent a comprehensive examination, with evaluation of history, neurological status, electroencephalography (EEG) and neuroimaging results, and genotyping of blood samples by real-time polymerase chain reaction. The control sample for genetic examination was venous blood from 60 healthy individuals.

Results:  Focal seizures with transition to bilateral and tonic–clonic seizures were predominant in the PTE group. Neuroimaging revealed dystrophic, cystic, and cystogliotic alterations and signs of external hydrocephaly. EEG recorded interictal and ictal epileptiform activity and slowing of theta waves. Genotyping by rs1126442 polymorphism of GRIN1 revealed predominance of heterozygous G/A and homozygous A/A genotypes in patients with PTE in the codominant (odds ratio (OD)=3.43; 95% confidence index (CI) 1.56–7.55; p=0.0047), dominant (OR=3.24; 95% CI 1.57–6.68; p=0.0011), and superdominant (OR=2.90; 95% CI 1.36–6.22; p=0.0048) inheritance models. The carriage of heterozygous G/A rs1126442 genotype of GRIN1 was associated with an epileptiform activity in the EEG of all patients with epilepsy (OR=2.40; 95% CI 1.11–5.20; p=0.024).

Conclusion: The carriage of heterozygous G/A genotype and homozygous A/A rs 1126442 genotype of GRIN1 in the dominant and codominant inheritance models is associated with a high risk of development of epilepsy after craniocerebral trauma. The carriage of heterozygous G/A rs 1126442 genotype of GRIN1 is associated with an epileptiform activity in EEG.

Introduction: Currently, young Caucasian populations of different generations are living in the Magadan region (MR). The study of heart rate variability (HRV) in these samples will add to the modern understanding of the physiological mechanisms of adaptive restructures in those living in coastal and continental zones of the MR.

Aim: To study restructures of HRV in young Caucasians who were representatives of the zeroth, first, second, and third generations living in the coastal and continental zones of MR, with significant differences in the extremality of natural environmental factors.

Materials and methods: TThe study involved 870 young men aged 17–21 years. HRV parameters were analyzed using a Varikard device.

Results:  Compared with individuals of the same age living in the coastal zone, residents of the continental climatic zone were characterized by more evident predomination of the parasympathetic division of the autonomic nervous system. A tendency to the enhancement of the parasympathetic influence from the zeroth to subsequent generations was observed in both young men living in the coastal and continental zones.

Conclusion: The direction of adaptive shifts in the restructuring of HRV characteristics varied depending on the climatic zone where the examined individuals lived: in the continental climate of the MR, adaptive restructuring of HRV parameters occurs faster and already completed at the first generation in comparison with migrants, with no significant differences between representatives of the first and second generations. In young men living in coastal zones, restructures occur more slowly and continue upto the representatives of the third generation.

Background: To examine the pharmacoepidemiology of treatment for arterial hypertension (AH) in Russia, the PYTHAGOR study has been conducted since 2001, including PYTHAGOR I–II (2001–2002), PYTHAGOR III (2008), and PYTHAGOR IV (2013). Increasing the role of doctors of outpatient care in the pharmacotherapy of patients with AH creates prerequisites for conducting new pharmacoepidemiological studies.

Aim: To investigate the structure of prescriptions of antihypertensive drugs (AHD) by outpatient doctors at the regional level in comparison with the results of PYTHAGOR IV pharmacoepidemiological study.

Materials and methods: In 2018, a survey was conducted in the Voronezh region among 104 doctors, including 58 general practitioners (55.8%), 37 therapists (35.6%), and four cardiologists (3.8%). The average age of the doctors was 45.7 ± 13.5 years, the accumulated period of work was 21.0 ± 13.7 years, and the period of work in an outpatient clinic was 16.6 ± 12.4 years.

Results:  In the structure of doctors’ pREFERENCES in selecting free combinations of AHD, doctors preferred angiotensin-converting enzyme inhibitors (iACE; 90.3%), but they were prescribed more rarely than that in PYTHAGOR IV study (93.8%). The remaining AHD groups were used by doctors of the VR more often than in the PYTHAGOR IV study: beta-adrenoblockers, 89.4% (PYTHAGOR IV, 73.1%); diuretics, 88.4% (73.2%); calcium antagonists (CА), 86.5% (67.3%); angiotensin II receptor blockers (ARB), 81.7% (62.1%); imidazoline receptor agonists, 57.6% (13.3%). In the selection of fixed combinations of AHD: iACE or ARB with a diuretic was used in 71.9% and 36.4%, respectively, and iACE with CA in 46.2%. In the PYTHAGOR IV study, these combinations were used more rarely, i.e., in 33.3%, 28.0%, and 24.1%, respectively.

Conclusion: The data obtained indicate adherence of doctors to modern clinical guidelines for the pharmacotherapy of AH.

Introduction: As with many other surgical interventions, the implantation of a pacemaker may be associated with adverse outcomes in the immediate or distant period. The search for probable risk factors of adverse outcomes may promote the development of effective and safe management methods of patients with pacemaker postoperatively. One of the important directions in this field is the investigation of the effect of pacemaker implantation on the hemostasis system of these patients.

Aim: To evaluate the effect of the implantation of dual-chamber pacemaker on the hemostasis system of patients with different kinds of bradyarrhythmias and to determine probable risk factors for unfavorable outcomes in this groupof patients.

Materials and methods: The study was performed with the financial support of the Russian Foundation for Basic Research within the Scientific Project No. 19-315-90109. The prospective study (ClinicalTrials.gov ID, NCT04499612) enrolled 61 patients (men, 45.9%) with a mean age of 71.5 ± 8.8 years. The groupwho received surgical treatment included 23 patients with atrioventricular (AV) block and 25 patients with sick sinus syndrome (SSS), and the groupwith conservative treatment included 13 patients with AV blocks and SSS, but without indications for pacemaker implantation. Anticoagulant therapy was given to one patient with AV block, 12 patients with SSS, and five patients with conservative therapy. All the remaining patients received antiplatelet therapy. The surgical groupunderwent ultrasound examination of the veins of the upper and lower extremities and sampling of peripheral venous blood before and 7 days after pacemaker implantation to determine the level of fibrinogen (FI) and activity of blood coagulation factors VIII (FVIII) and IX (FIX), antithrombin III (AT III), and protein C. In the conservative group, a similar examination was conducted only on inclusion in the study.

Results:  In patients with AV block, a significant increase in blood fibrinogen was noted at 7 days after surgery (р=0.042). In the intergroupcomparison, the activity of AT III after the implantation was higher in the surgical groupthan in the conservative group(р=0.018 and р=0.006, respectively). After surgery, the activity of FVIII and FIX was lower in patients with SSS on anticoagulant therapy than in patients with antiplatelet therapy (р=0.048 and р=0.015, respectively). Based on the receiver operating characteristics analysis, the risk factors for lethal outcomes were reduced activity of AT III in patients with AV block and increased activity of FIX in patients with SSS.

Conclusions: The balance of the hemostasis system in patients with AV blocks on antiplatelet therapy was shifted toward hypercoagulation within at least 7 days after pacemaker implantation. The use of anticoagulants in patients with SSS caused a shift toward hypocoagulation. The reduced activity of AT III in patients with AV block and increased activity of FIX in patients with SSS are prognostic factors for lethal outcomes.

Introduction: The treatment strategies of patients with stenosis of the left main coronary artery (LMCA) and acute coronary syndrome (ACS) is being debated. One of the key problems is the selection of the optimal time for coronary artery bypass surgery (CABS) in these patients.

Aim: To analyze different periods of revascularization of the myocardium by CABS on a working heart in patients with LMCA stenosis and ACS.

Materials and methods: A prospective analysis of treatment of 112 patients with LMCA stenosis (> 50%) and ACS was performed. Patients were divided to three groups depending on the time of surgical treatment: upto 7 days after occurrence of ACS, 18 (16.1%, group1) patients; 8–14 days, 38 (33.9%, group2) patients; > 14 days, 56 (50%, group3) patients. The average time of ACS-CABS in all patients was 15 days. The groups were comparable in terms of the main preoperative parameters, except for EuroSCORE II and GRACE scale that were predominant in the early periods of CABS.

Results:  LMCA subocclusion (stenosis > 90%) with coexistence of anginal syndrome at rest was observed in more than half of patients with surgery upto 7 days (56%, p=0.019). The surgery duration, blood loss through drains, number of days in the resuscitation unit, duration of artificial lung ventilation, and use of vasopressor support were not significantly different. The revascularization index was higher in surgeries conducted within 7 days than in surgeries performed within 8–14 days (2.33 ± 0.59 versus 1.89 ± 0.65, p=0.02). The evaluation of the dynamics of the functional parameters of the myocardium showed a greater increase in ejection fraction in group1 when compared with group3 after surgery (p=0.036). In the evaluation of the end-diastolic volume of the left ventricle, the average reductions were 16 mL, 14 mL, and 8.5 mL, respectively, without any significant differences among the groups. The rate of intrahospital lethality was highest in group3 (.4%), followed by group2 (2.6%). No fatal outcomes were noted in surgeries conducted in upto 7 days (p> 0.050).

Conclusion: Early CABS performed upto 7 days have similar immediate results to delayed ones and considerably improves the contractile ability of the myocardium in patients with ACS and LMCA stenosis.

Background: Radiothermometry (RTM) is a breast examination method that permits, besides visualization of the pathological foci, to evaluate the quality of metabolism, which is important for the determination of the biological subtypes of breast cancer (BC) and the possibility of the evaluation of the degree of tumor aggressiveness before immunohistochemical analysis.

Aim: To study the potentials of modern RTM in the differential diagnosis of benign and malignant breast pathologies and in different biological subtypes of BC.

Materials and methods: Overall, 118 patients with different breast pathologies were examined using РТМ 01 РЭС computerized diagnostic complex. Measurements were performed in nine points: directly on the breast ― for the visualization of tumor, in two control points (in the region of the epigastrium and sternal xiphoid process), and in one point in the axillary zone on both sides ― for the identification of probable metastases. The examination time was 15–20 min for each woman. RTM results were compared with histological, ultrasound, mammographic, and clinical data.

Results:  The sensitivity and accuracy of RMT in the differential diagnosis of breast pathology were 96.9% and 74.5%, respectively. The specificity of RTM in the differentiation of aggressive and non-aggressive BC subtypes appeared to be low at 6.6%. In the evaluation of the temperature difference between the pathological and normal tissues, a tendency to a non-increase in the temperature above the tumor in comparison with the unaffected tissue was noted; however, no significant differences between the mean values for the healthy and affected breasts were obtained. No correlations were found between the proliferative index of BC and frequency of thermoasymmetry or extent of its evidence (r < 0.3).

Conclusion: RTM demonstrated effectiveness in the differential diagnosis of benign and malignant alterations of the breast; thus, it is not a method of choice in the evaluation of the spread and biological subtype of BC.

Introduction: The coronavirus 2019 (COVID-19) pandemic demonstrated a negative influence on many underlying diseases, their course, and prognosis. A combined course of active tuberculosis, human immunodeficiency virus (HIV) infection, and COVID-19 is a rare case in the routine clinical practice; therefore, it is of scientific and practical interest. In a 41-year-old patient with severe chronic disseminated pulmonary tuberculosis and HIV infection, presence of tuberculosis mycobacteria, resistance to streptomycin and isoniazid, chronic respiratory failure, cachexia, and immunodeficiency, COVID-19 was manifested only by the detection of SARS-Cov-2 virus from the nasopharynx and did not influence the treatment and prognosis of tuberculosis.

Conclusion: The described case of a combination of active tuberculosis with HIV infection and COVID-19 demonstrated that effective treatment of specific tuberculosis process is quite possible.

Introduction: According to the clinical recommendations of the Healthcare Ministry of Russia (2021), uterine artery embolization (UAE) in uterine fibroid is an alternative to surgical treatment in case of high surgical risk and absence of contraindications in women who do not desire pregnancy. The advantages of UAE are associated with lesser blood loss, shorter hospital stay, and recovery of the working capacity. Here, we present an analysis of the literature and our 14-year clinical experience in performing UAE in uterine fibroid. Screening and primary diagnosis of uterine fibroid and indications and contraindications of UAE in the current publications were analyzed. Different methods of EUA implementation were described, and the advantages of the transradial access (TRA) are demonstrated on the basis of the actual clinical experience.

Conclusion: The results obtained in the use of TRA revealed the reduction of radioscopy time and surgery time in general, which are beneficial in terms of the reduction of radiation exposure. Besides, an argument for the given access is a considerably lower frequency of serious complications at the access site. The main obstacles to the introduction and wide use of TRA are based on the lack of specialist experience, absence of specialized training programs, and use of unsuitable and traumatizing instruments. One of the unsolved questions is the absence of an anesthesia protocol, which must be developed with the participation of both gynecologists and specialists on X-ray endovascular diagnostics and treatment.

The article presents previously unpublished documents, comments, and materials that were directly related to significant events in the life and performance of a Russian scientist and academician P. K. Anokhin, such as the Lenin Prize award and the Pavlovian session. The text of P. K. Anokhin’s answer to the review of a corresponding member of the USSR Academy of Sciences E. A. Asratyan of P. K. Anokhin’s monograph “Biology and Neurophysiology of Conditioned Reflex” submitted to the competition for the Lenin Prize, was published. In 1972, P. K. Anokhin was awarded the Lenin Prize for the monograph “Biology and Neurophysiology of Conditioned Reflex”. P. K. Anokhin answered the accusatory statements of the reviewer concerning the “danger” of the functional system for the Pavlovian doctrine and the analytical nature of the scientific method of I. P. Pavlov and answered critical questions about the “synthetic” and “systemic” approach and the priority in the development of the theory of systems and feedback.

The work presented literature facts that the statements and questions of Asratyan were consistent with his accusatory comments about P. K. Anokhin at the Pavlovian session — the scientific session of the USSR Academy of Sciences and of the USSR Academy of Medical Sciences, dedicated to the physiological doctrine of academician I. P. Pavlov, which was held in Moscow in July–August 1950. At the session, P. K. Anokhin was accused of “revision” of the ideological foundations of Pavlov’s teachings and of detraction of the significance of Pavlov’s theory of the higher nervous activity.

After the Pavlovian session, P. K. Anokhin was dismissed from the post of the director of Institute of Physiology of the USSR Academy of Medical Sciences, dismissed from the Presidium of the USSR Academy of Medical Sciences, and appointed Professor of the Department of Physiology of Ryazan Medical Institute. Over the years, E. A. Asratyan persistently criticized P. K. Anokhin as the “opponent of I. PPavlov’s teaching” and actively rejected the theory of functional systems.

Conclusion: The presented documents have not lost their significance even now. These documents are important for understanding the ideological essence of the systemic approach and of the theory of functional systems and are interesting for the history of Russian physiological science and medicine.