The article describes the history of the first students enrolled and graduated from the St. Petersburg Women’s Medical Institute. The article describes how public organizations and various individuals helped women receive higher medical education. How Russian public reacted to the first graduation of students of the Institute. The fate of two graduates of 1902 is presented, based upon archival materials. 

Introduction. This article presents the experience of five years of using simulation modeling to optimize work in the field of healthcare organization. Works are considered on the example of organizing the process of a three-level system for organizing emergency medical care in the regions, and examples of the practical application of computer modeling to improve the work of an inpatient emergency department are presented.

The objective was to study various methods and approaches to the implementation of simulation modeling used in practice in the healthcare system. Consider the possibilities of simulation modeling on the FlexsimHC platform.

Methods and materials. The analysis of methods and software used to create a simulation model in the healthcare sector was carried out. The main possibilities of using process modeling on the FlexsimHC platform were considered on the example of designing work inside and outside the hospital.

Results. After a series of experiments in the virtual space, the data obtained were put into practice. On the example of the completed project of the simulation model of the region, a real way to optimize the emergency medical care in the region was proposed. Experiments were also carried out on models of an inpatient emergency department, the results of which revealed ways to optimize the workflow aimed at reducing the duration of stay inside the department, at an adequate distribution of patient flows, allowing timely implementation of all necessary medical and diagnostic measures without additional burden on medical personnel.

Conclusion. Simulation modeling is the key to solving the logical problems of modern planning, allowing to reduce the risks of logistics errors in real time. 

The article is devoted to summarizing the authors’ experience in the development of Russian-language versions of foreign quality of life questionnaires for cancer patients as well as their own questionnaires for studying various aspects of the quality of life in bone and soft tissue tumors of the musculoskeletal system. We briefly presented the results of the validation and testing of the modules of the «Cancer Quality of Life Questionnaire - Core 30» (EORTC QLQ-C30) developed by the Quality of Life Assessment Group at the European Organization for Research and Treatment of Cancer (EORTC) – «Fatigue» module (FA12), «Spiritual wellbeing» module (SWB32), «Bone Metastases» module (BM22), as well as the specialized Spine Oncology Study Group Outcomes Questionnaire (SOSG-OQ). We also presented the diagnostic tools developed by the authors’ themselves for studying the quality of life of patients with pelvic bone tumors and lower limb amputations due to cancer. The main objective of the article was to inform the scientific community, as well as practicing psycho-oncologists and oncologists about the existence of new diagnostic tools for assessing the quality of life of cancer patients. The article also outlines the prospects for development of diagnostic tools for quality of life of cancer patients. 

Introduction. Cognitive impairments are important components of the clinical picture of many neuropsychiatric disorders, and are in dire need of evidence-based pharmacotherapeutic approaches.

The objective was to test a model of delayed cognitive impairments due to neonatal administration of NMDA receptor antagonists (7th, 9 th, and 11 th days of life).

Methods and materials. Male Wistar rats were administered with phencyclidine, 10 mg/kg (Experiment 1), or (+)MK-801, 1 mg/kg (Experiment 2); then «2-choice serial reaction time task», or «reinforcement learning task based on response patterning under interval schedules of reinforcement» in the same adult rats were performed.

Results. Experiment 1: rats after neonatal NMDA-blockade performed operant tasks more accurately and made fewer missed attempts as compared to control. Experiment 2: switching to another schedule of reinforcement increased the pause after reinforced responses in both groups; in the experimental group, the duration of the post-reinforcement pause was shorter.

Conclusion. Neonatal NMDA receptor blockade affects inhibitory control and attention to sensory stimuli, which manifests, respectively, as increased impulsivity and hyperfocusing in limited-choice conditions. 

Introduction. Melatonin, being a powerful endogenous antioxidant, provides healthy course of pregnancy and childbirth. Decrease of melatonin levels in blood correlates with severity of preeclampsia. Currently, melatonin is viewed as a perspective antioxidant, able to improve mother’s condition during preeclampsia and protect fetus from unfavorable intrauterine environment.

The objective was to study melatonin effects on remodeling of chicken embryo heart tissue under normal conditions and under oxidative stress model.

Materials and methods. The study was performed using organotypic culture of heart tissue of 10–12-day-old chicken embryos. Oxidative stress was modeled by adding epinephrine 10^–4 М or homocysteine thiolactone 10^–3 М to culture medium.

Results. The trophotropic effects of melatonin was detected at a concentration of 10–6 M. Drug stimulated heart tissue explants’ growth on 20 %. Epinephrine showed cardiotoxic effects at concentrations of 10^–4 and 10^–6 М. Melatonin (10^–6 М) neutralized cardiotoxic effects of epinephrine (10^–4 M). Cardiotoxic effects of homocysteine thiolactone (10^–3 М) preserved in presence of melatonin (10^–6 М).

Conclusion. During embryonic period, melatonin neutralizes cardiotoxic effects of oxidative stress caused by a high concentration of epinephrine, but not by homocysteine thiolactone. 

Introduction. There is a problem in predicting the efficacy and safety of antipsychotic therapy. Dopamine receptor D1 is one of the targets of antipsychotics. Peripheral blood lymphocytes (PBL) are the research object of neurotransmission receptors.

The objective was to study DRD1 gene expression (mRNA, protein level) in PBL as a possible biomarker of olanzapine and haloperidol therapy prognosis.

Methods and Materials. Sample: 106 patients diagnosed with schizophrenic spectrum disorder. Study design: prospective longitudinal follow-up with drug administration by randomization. Assessment of mental status and development of Parkinsonism: Positive and Negative Syndrome Scale (PANSS) and Simpson-Agnus Scale (SAS), respectively. PBL was study material. DRD1 mRNA level was determined by real-time PCR. DRD1 protein concentration in PBL was measured by enzyme immunoassay.

Results. Haloperidol (but not olanzapine) treatment for 28 days, leads to DRD1 protein concentration decrease in PBL in a manner dependent on its initial level. DRD1 mRNA level in PBL remained unchanged during the treatment. Patients with effective therapy by olanzapine had lower DRD1 mRNA levels. Side effects of the therapy (Parkinsonism, weight gain) were not associated with studied DRD1 parameters.

Conclusions. Haloperidol treatment leads to a decrease of DRD1 protein concentration in PBL, which depends on the initial protein level. Effective olanzapine therapy is associated with reduced DRD1 mRNA level in PBL before the treatment. 

Introduction. Valproic acid and metamizole are widely used in the treatment of primary headaches. However, despite the drugs’ proven clinical efficacy, the neurophysiological mechanisms underlying their therapeutic action are poorly understood. The ventral posteromedial nucleus of the thalamus (VPM) serves as the highest suprasegmental relay center for transmitting ascending nociceptive information from the cranial structures to the cerebral cortex and is considered as a potential neuroanatomical target for anticephalalgic drugs.

The objective of the study was to evaluate the action of valproate and metamizole on the excitability of the VPM thalamic neurons.

Methods and materials. In acute controlled experiments on anesthetized rats (n=31), we studied the action of cumulative dosing (three fixed dose injections every 30 minutes) of intravenously administered valproate (n=8, 100 mg/kg x 3) or metamizole (n=16,150 mg/kg · 3) on extracellularly recorded background and dura mater electrical stimulation-evoked activities of the convergent VPM neurons. Results. In all experiments, intravenous valproate significantly inhibited both background activity of the VPM neurons and their responses to dural electrostimulation. Metamizole had a similar action in more than half of the cases, whereas 44 % of the examined thalamic cells (7 out of 16) did not react to its infusion.

Conclusion. One of the main neurophysiological mechanisms underlying anticephalalgic action of valproic acid and metamizole may be inhibition of the nociceptive transmission at the thalamic level due to the drugs-induced suppression of the meningeal-sensitive VPM neurons excitability. 

Introduction. The risk of developing Hodgkin lymphoma (HL) with HIV infection is higher than in the general population, and the course of the disease itself is more aggressive. Currently, there is no unified approach to the treatment of HIV-related HL, and data on its epidemiology in the Russian Federation are limited.

The objective was to study epidemiological characteristics, the used therapeutic tactics and the results of treatment for HIV-related HL.

Methods and materials. The multicenter retrospective study included 46 patients with HIV- related HL treated in 9 centers of the Russian Federation. Descriptive statistics methods were used, the analysis of overall survival (OS) and progression-free survival (PFS) was performed using the Kaplan–Meier method.

Results. HIV-related HL is more often represented by an advanced stage, B-symptoms, and extranodal lesions. The ABVD regimen was used as the first-line therapy in 60 % for HIV-related HL. The overall response to therapy was 81.6 %, and the 2-year OS and PFS were 85 % and 49 %, respectively. Factors that worsened OS were CD4+˂266 cells/mcL and general somatic status ECOG≥2. 

Relevance. The inflammatory process and endogenous intoxication of the patient’s body has a negative impact on the course of many malignant neoplasms, including salivary gland cancer.

The objective of the study was to determine the influence of some factors of systemic inflammation and endogenous intoxication in salivary gland cancer.

Methods and materials. A prospective study included the data of 59 patients with salivary gland cancer. The influence of peripheral blood parameters and relative indicators characterizing systemic inflammation on overall and disease-free survival was assessed.

Results. As a result of the multivariate analysis, it was revealed that an increase in the level of the relative number of peripheral blood neutrophils by more than 60.08 % increases the risk of death in patients from salivary gland cancer by 3.90 times (p=0.0456; HR 3.90: 95 % CI 1.03–14.79). The level of the absolute number of peripheral blood lymphocytes, not exceeding 1.49x109 /l, increases the risk of disease progression by 8.72 times (p=0.0002, R 8.72: 95 % CI 2.78–27.28).

Conclusion. Individual factors of systemic inflammation and endogenous intoxication, it is advisable to evaluate at the stage of planning the primary treatment of patients with salivary gland cancer, in order to determine the prognosis of the disease and optimize the choice of tactics for the primary treatment of patients. 

Relevance. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) makes it possible to treat severe malignant and non-malignant hematopoietic disorders system. Pulmonary complications (PC) occur in 40–60 % of patients after allo-HSCT. However to date, the effect of HSCT on functional and morphological pulmonary changes in recipients remains insufficiently studied.

The objective of current study was to evaluate risk factors affecting long-term survival in children and adolescents after allo-HSCT.

Methods and materials. The current study was both retrospective and prospective. The analysis included 362 patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), aged 5 months to 18 years, who received allo-HSCT at Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation in 2000–2018. All the patients underwent chest computed tomography (CT). When detecting CT changes, we performed fibrobronchoscopy (FBS) with microbiological examination of bronchoalveolar lavage (BAL).

Results. PC were diagnosed in 124 patients (64 %) who received allo-HSCT in 2014–2018. Decrease of overall survival (OS) is associated with PC development during the first year after allo-HSCT(р<0,001).The development of early PC in remission of the underlying disease significantly affected OS (p=0.001).The probability of PC development is 2.26 times higher in patients older than 9 years (p=0.006). When comparing the intensity of conditioning regimens (MACvsRIC) in remission of the underlying disease, we did not get significant differences in the incidence of PC (p>0.05). Graft source, donor type, HLA-compatibility, recipient gender did not affect the incidence of PC (p>0.05). When using graft-versus-host disease (GVHD) prophylaxis (ptCYvsATG), the 5-year OS in patients without PC was 78.8 % and 62.8 %respectively. The 5-year OS in patients with PC was 51.8 % and 42.4 % respectively (р=0.007). Decrease of OS in patients with PC is associated with chGVHD(58.3 %,) (р=0.03).

Conclusion. Pulmonary complications (infectious and non-infectious) in allo-HSCT recipients are more likely to occur in the first year after transplantation. Among bacterial pathogens, the predominance of Gr(-) flora remains. The incidence of pulmonary complications was significantly lower when using ptCY as a prevention of GVHD. 

The objective was to determine the concentrations of biomarkers of fibrosis and inflammation in the blood, parameters characterizing heart remodeling in patients with atrial fibrillation (AF) in combination with type 2 diabetes mellitus (T2DM).

Methods and materials. The study included 231 examined patients aged 35 to 65 years: patients with DM (n=99), of which 49 patients with AF, and the comparison group consisted of patients with AF without T2DM (n=54) and healthy examined patients (n=78).

Results. It was found that the concentration of profibrogenic biomarkers circulating in the blood of patients with AF and T2DM is higher than in patients with AF without T2DM: galectin-3 (13.4 (9.1–16.9) and 6.8 (4.6–12.8) ng/ml, p<0.001), TGF-beta1 (3032.5 (2468.5–4283.5) and 2339.7 (1813.3–3368.8) pg/ml, p=0.01), GDF-15 (2359.3 (1234.3–3465.1) and 1256.7 (889.9–2083.7) pg/ml, p><0.001), PINP (3625.4 (2462.1–4463.7) and 2451.3 (1842.0–2941.0) pg/ml, p><0.001) and PIIINP (92.8 (68.6–122.4) and 67.6 (47.9–93.3) ng/ml, p><0.001). Concentrations of proinflammatory cytokines CRP (3.5 (2.2–4.4) and 2.7 (1.4–7.1) mg/l, p=0.01) and CT-1 (1032.1 (667.6–1495.3) and 549.1 (411.9–960.1) pg/ml, p><0.001) in patients with AF and T2DM is higher than in patients with T2DM without AF. The levels of TNF-alpha, IL-6 in patients with AF and T2DM are comparable to the concentrations of these biomarkers of inflammation in patients with T2DM without AF. According to the results of echocardiography, it was revealed that the thickness of the epicardial adipose tissue in patients with AF and T2DM is greater than in patients with AF without T2DM and greater than in patients with T2DM without AF (7.1±0.4, 4.5±0.3 and 5.1±0.3, respectively, p><0.001). A strong positive correlation between GDF-15 and HbA1c was established according to the correlation analysis (r=0.617, p><0.0001) and regression analysis (β=0.586, p><0.0001). According to binomial logistic regression, it was found that T2DM in the examined cohort increased the risk of AF by 2.2 times (OR=2.2, 95 %CI 1.41–3.31, p=0.00004). Conclusion. The obtained new data on the increase in the concentration of profibrogenic factors in patients with AF in combination with T2DM indicate an important role of the formation of myocardial fibrosis in the development of this arrhythmia in these patients. Keywords: biomarkers, fibrosis, inflammation, atrial fibrillation, diabetes mellitus>˂0.001), TGF-beta1 (3032.5 (2468.5–4283.5) and 2339.7 (1813.3–3368.8) pg/ml, p=0.01), GDF-15 (2359.3 (1234.3–3465.1) and 1256.7 (889.9–2083.7) pg/ml, p˂0.001), PINP (3625.4 (2462.1–4463.7) and 2451.3 (1842.0–2941.0) pg/ml, p˂0.001) and PIIINP (92.8 (68.6–122.4) and 67.6 (47.9–93.3) ng/ml, p˂0.001). Concentrations of proinflammatory cytokines CRP (3.5 (2.2–4.4) and 2.7 (1.4–7.1) mg/l, p=0.01) and CT-1 (1032.1 (667.6–1495.3) and 549.1 (411.9–960.1) pg/ml, p˂0.001) in patients with AF and T2DM is higher than in patients with T2DM without AF. The levels of TNF-alpha, IL-6 in patients with AF and T2DM are comparable to the concentrations of these biomarkers of inflammation in patients with T2DM without AF. According to the results of echocardiography, it was revealed that the thickness of the epicardial adipose tissue in patients with AF and T2DM is greater than in patients with AF without T2DM and greater than in patients with T2DM without AF (7.1±0.4, 4.5±0.3 and 5.1±0.3, respectively, p˂0.001). A strong positive correlation between GDF-15 and HbA1c was established according to the correlation analysis (r=0.617, p˂0.0001) and regression analysis (β=0.586, p˂0.0001). According to binomial logistic regression, it was found that T2DM in the examined cohort increased the risk of AF by 2.2 times (OR=2.2, 95 %CI 1.41–3.31, p=0.00004).

Conclusion. The obtained new data on the increase in the concentration of profibrogenic factors in patients with AF in combination with T2DM indicate an important role of the formation of myocardial fibrosis in the development of this arrhythmia in these patients. 

Introduction. The endothelial system is an important component of vascular-platelet hemostasis, capable of actively responding to mechanical and inflammatory agents. Patients with congenital epidermolysis bullosa are prone to mechanical damage to the skin and the development of a chronic inflammatory syndrome with a high probability of endothelial dysfunction.

The study objective was to assess the state of the endothelial system and to reveal the dependence of endothelial dysfunction on the form of epidermolysis bullosa.

Methods and materials. The study used venous blood of 57 patients (27 men and 30 women) with congenital epidermolysis bullosa. In patients with simple and dystrophic forms of epidermolysis bullosa, the platelet count, P-selectin, fibrinogen, albumin, C-reactive protein, von Willebrand factor antigen concentration, and factor VIII activity were determined.

Results. Comparative results of endothelial dysfunction depending on the form of epidermolysis bullosa were represented and endothelial dysfunction’s dependence on the concentration of albumin, C-reactive protein, and platelet count was determined.

Conclusions. In patients with a dystrophic form of epidermolysis bullosa, endothelial dysfunction is accompanied by an increase in the expression of P-selectin, factor VIII activity, and the concentration of von Willebrand factor antigen. Chronic inflammation and impaired nutritional status with a decrease in albumin contribute to the development of endothelial dysfunction. 

Relevance. Evidence exists that infrarenal aortic aneurisms and aortoiliac occlusive disease in women are different than in men in terms of anatomical features and more severe clinical course. Gender differences in histopathology of abdominal aorta are not fully studied.

The objective was to study gender based differences in histopathology of abdominal aorta in patients with aortic aneurisms and aortoiliac occlusive disease.

Methods and materials. The study included 96 biopsy specimens from 71 patients with aorto-iliac lesions (23 women and 48 men). A number of morphological characteristics and expression of matrix metalloproteinase 9 (MMP-9) were analyzed. The data obtained were processed statistically.

Results. Adventitial infiltrate and medial sclerosis are more intense in the aneurysm than in occlusive-stenotic lesions, differences in the grade of fibrosis were proven only in men. Regardless of the patients’ gender, adventitial infiltration is denser in the aneurysmal body than in the neck; other changes in the anatomic parts of the aneurysm are similar. MMP-9 expression in the adventitia in the aneurysmal neck is higher in women, than in men. MMP-9 expression in the media and adventitia is higher in men with aneurysm, then with occlusive or stenotic lesion. Almost all indices of the aortic wall remodeling and MMP-9 expression correlate with each other in men with the aneurysm, in contrast to women.

Conclusion. Gender based features in histopathology of abdominal aorta and the degree of their correlation may determine differences in the anatomy and course of abdominal aortic aneurysm and aortoiliac occlusive disease in women and men. 

Introduction. Invasive Haemophilus influenza type b (Hib) infection often manifests as severe and complicated forms of purulent meningitis in children from birth to 6 years of age. Hib meningitis is the most commonly diagnosed invasive form, with a severe course. There is no generally accepted clinical classification of Hib infection. Along with meningitis, the infection is often manifested with purulent inflammatory foci of different localization.

The objective was to characterize the course of purulent Hib meningitis, including in combination with purulent foci, in young children.

Methods and materials. We analyzed 45 case histories of children (under the age of 3 years) who had an invasive Haemophilus infection with purulent meningitis. Hib meningitis (Group-1) was diagnosed in 17 patients and meningitis in combination with specific purulent foci was diagnosed in 28 patients (Group-2). The diagnosis in all patients was confirmed bacteriologically or serologically (Latex Agglutination Test).

Results. The combination of meningitis with purulent foci of Hib infection was characterized by late hospitalization (36 %), longer recovery of cerebrospinal fluid, longer duration of the disease, and the prevalence of severe and complicated disease, and often required surgical treatment (46.4 %). A burdened premorbid background is traditionally considered a condition for the development of invasive Hib infection. According to our data, only 40 % of children had a burdened premorbid background, which is confirmed by clinical cases.

Conclusion. Since Hib infection in young children is often combined with meningitis with purulent foci, is characterized by a severe and complicated course, and often requires surgical treatment, it is advisable to consider this form of infection separately.