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Introduction. In most cases, in patients with hereditary fibrinogen deficiency, clinical manifestations are represented by bleeding of varying intensity and localization. However, the clinical picture of hereditary fibrinogen deficiency can also be represented by thrombosis.Aim — to characterize the detected mutations in fibrinogen genes and to analyze prothrombotic factors in patients with hereditary hypofibrinogenemia and thrombosis.Materials and methods. Forty-nine patients with hereditary hypofibrinogenemia were observed, of which 46 patients had no history of thrombosis and 3 patients had a confirmed history of thrombosis. These 3 patients made up the study group.Results. Heterozygous mutations were found in all 3 patients in the fibrinogen gamma chain gene (FGG), one of them had a previously undescribed deletion g.2653_2684+211del, p.(Asp167Glufs*2), which removes 32 terminal nucleotides of the fifth exon of the FGG gene and leads to the formation of a stop codon in place of amino acid 168. In two other patients, there were missense mutations c.1140T>A, p.(Cys365Ser) and c.1114A>T, p.(Asp356Val), which can determine the thrombogenic properties of the altered protein structure of fibrinogen. Other prothrombotic factors were also identified: genetic polymorphisms of low thrombotic risk, surgery, taking combined oral contraceptives.Conclusion. Hereditary fibrinogen deficiency does not play a protective role in relation to the development of thrombosis and may cause the development of thrombosis, which is associated with its multifunctional role in the hemostasis system. The pathogenesis of thrombosis in patients with hereditary hypofibrinogenemia is multifactorial and may be associated with the characteristics of the main protein defect and the coexistence of hereditary and acquired thrombotic risk factors (surgical interventions, taking combined oral contraceptives, etc.).

To assess the safety and efficacy of autologous haematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with dialysis-dependent renal failure.During a period from May 2010 to December 2016 fourteen MM patients with dialysis-dependent renal failure aged 48 to 65 years underwent auto-HSCT. After the induction therapy complete response, very good partial response, partial response were documented in 64, 29, 7% of patients, respectively. In no case was a renal response achieved. Haematopoietic stem cell mobilization in most patients (13/14) was performed according to the scheme: G-CSF 10 g/kg. Melphalan in 3 dosages was used as pre-transplant conditioning: 100, 140 and 200 mg/m2; 13 patients underwent a single and in one case underwent a tandem auto-HSCT against the background of hemodialysis. Evaluation of the antitumor and renal response was assessed on the 100th day after auto-HSCT. Subsequently, against the background of programmed hemodialysis and in the setting of high-dosed melphalan (100200 mg/m2), 13 patients underwent a single and one patient underwent a tandem auto-HSCT. At +100 days after auto-HSCT, an antitumor response and renal response were assessed.The period of agranulocytosis after auto-HSCT was from 5 to 12 days (median 8,5) and was accompanied by infectious complications, cardiac and neurological dysfunctions. At +100 days after auto-HSCT, the complete response was confirmed in 71% patients and very good partial response was confirmed in 29% patients. The minimal renal response was registered in 2 patients (14%), hemodialysis was stopped. The transplant-related mortality was absent. After a median follow-up of 53 months 5-year progression-free survival was 59%, and overall survival was 93%.Carrying out auto-HSCT in patients with dialysis-dependent renal failure contributed to the achievement of a minimal renal response in 14% of cases, which allowed these patients to stop hemodialysis. Patients whose conditioning regimen was performed using melphalan at a dose of 200 mg/m2showed more frequent complications in the early post-transplant period compared to patients who received a lower dose of melphalan (100140 mg/m2). Auto-HSCT in MM patients with dialysis-dependent renal failure is a feasible and effective treatment method, which in some cases contributes to independence from hemodialysis.Цель.Оценить безопасность и эффективность трансплантации аутологичных стволовых клеток (ауто-ТГСК) крови больным множественной миеломой (ММ) с диализ-зависимой почечной недостаточностью (ПН). Материалы и методы.В ретроспективное исследование включены 14 больных ММ с диализ-зависимой ПН в возрасте от 48 до 65 лет, которым с мая 2010 по август 2018 г. выполнена ауто-ТГСК. После индукционного этапа лечения полная ремиссия, очень хорошая частичная ремиссия, частичная ремиссия документированы у 64, 29, 7% больных соответственно. Ни в одном случае почечный ответ не достигнут. Мобилизация стволовых кроветворных клеток у большинства больных (13/14) проводилась по схеме Г-КСФ 10 мкг/кг. В качестве предтрансплантационного кондиционирования использовался мелфалан в 3 дозировках: 100, 140 и 200 мг/м2; 13 больным выполнена однократная и в одном случае тандемная ауто-ТГСК на фоне программного гемодиализа. Оценка противоопухолевого и почечного ответа проводилась на 100-й день после ауто-ТГСК. Результаты.Период миелотоксического агранулоцитоза после ауто-ТГСК длился от 5 до 12 сут (медиана 8,5 дня) и сопровождался инфекционными эпизодами, кардиальной и неврологической дисфункциями. На +100-й день ауто-ТГСК полная ремиссия диагностирована в 71% случаев, очень хорошая частичная ремиссия у 29% больных. Почечный ответ зарегистрирован у 2 (14%) больных, программный гемодиализ им отменен и возобновления заместительной почечной терапии не потребовалось в течение 24100 мес после ауто-ТГСК. Летальность, связанная с трансплантацией, отсутствовала. При медиане наблюдения 53 мес 5-летняя выживаемость без прогрессии составила 59%, общая выживаемость 93%. Заключение.Проведение ауто-ТГСК больным с диализ-зависимой ПН способствовало достижению минимального почечного ответа в 14% случаев, что позволило прекратить выполнение гемодиализа этим пациентам. У больных, предтрансплантационное кондиционирование которым проведено с применением мелфалана в дозе 200 мг/м2, отмечены более частые осложнения в раннем посттрансплантационном периоде по сравнению с пациентами, получившими меньшую дозу мелфалана (100140 мг/м2). Ауто-ТГСК является эффективным методом лечения больных ММ с диализ-зависимой ПН, в ряде случаев способствующим достижению независимости от гемодиализа.

Paraprotein is a laboratory biomarker of plasma cell tumors and other lymphoproliferative diseases. Its determination is necessary for diagnosing, monitoring and assessment of therapy effectiveness. The lecture presents the main methods of qualitative and quantative analysis of monoclonal proteins: gel electrophoresis, capillary electrophoresis, immunofixation and nephelometry features, possibilities and limitations are reviewed. The main sources of errors and artifacts during these studies are considered. Also the difficulties in the diagnosis and interpretation of the results of serum and urine tests are highlighted.Парапротеин лабораторный биомаркер плазмоклеточных опухолей и других лимфопролиферативных заболеваний, определение которого необходимо для диагностики, оценки эффективности проводимой терапии и мониторинга. В данной лекции приведены основные методы качественного и количественного анализа моноклональных белков: изложены особенности, возможности и ограничения гель- электрофореза, капиллярного электрофореза, иммунофиксации и нефелометрии. Рассмотрены основные источники ошибок и артефактов при выполнении этих исследований. Обращено внимание на трудности в диагностике и интерпретации результатов исследования сыворотки и мочи.

Aim: to determine serum free light chains (FLC) level by patients with multiple myeloma (MM) and dialysis - dependent renal impairment in which the amount Bence Jones (BJ) protein in the urine met the criteria of hematological response. Patients and methods: This study included 13 MM with dialysis - dependent renal impairment patients (estimated glomerular filtration rate < 10 ml/min), whose urine BJ protein content was less than 200 mg/day after antimyeloma therapy (including 11 patients whose urine BJ protein content was less than 100 mg/day). Results. The median serum concentration of monoclonal FLC was 608.7 (298-8380) mg/l. Thus, with trace amounts BJ protein in the urine serum content monoclonal FLC varied 28 times with the same degree of severity of renal failure. In patients with oliguria serum SLC content was significantly higher than in normal diuresis (1109 and 307 mg/L; p

The article considers economic menaces of demographic crisis of human resources in Russia induced by annual reduction of able-bodied population by 1 million. It is demonstrated that one of causes of crisis are cascade reactions due to decreasing fertility by 1 million of children from the early nineties. The inadequacy of common solutions for normalizing of established situation is stated. The possibility of annual increasing of numbers of able-bodied population up to 700-800 thousand is substantiated the expense of decreasing of disability and mortality. The innovative strategy of prevention of non-infectious and occupational diseases is developed based on management of health reserves in individuals with high risk. To implement this strategy a four-stage system ofpersonalized prevention is proposed that is implemented by doctors in polyclinics and by medical social workers in health offices on-the-job places. The important role of trade unions in supporting collective and individual health-improving activities at enterprises.

Contex. Angioimmunoblastic T-cell lymphoma (AITL) is a rare form of non-Hodgkins lymphoma, characterized by generalized lymphadenopathy, hepatosplenomegaly and dysproteinemia. Hypergammaglobulinaemia is revealed in 50-83% pts with AITL. However, the characteristics of immunoglobulinopathies observed in AITL are scarce. Objective: The aim of the study was to characterize quantitative and qualitative immunoglobulinopathies in patients with AITL at the onset of the disease. Patients and methods. 55 patients with newly diagnosed AITL were enrolled in the study, the male/female ratio was 30/25; median age was 61 (29-81) years. Diagnosis was based on standard WHO criteria. Immunochemical studies of blood serum included serum protein electrophoresis/immunofixation, nephelometric quantification of total immunoglobulins, serum free light chain assay. Results. Quantitative and qualitative immunoglobulinopathies were determined in 49 (89,1%) of 55 pts. Quantitative immunoglobulinopathies were revealed in 47 (85.5%) of 55 cases, qualitative - in 14 (25,5%). Combination quantitative and qualitative immunoglobulinopathies was observed in 12 (21,8%) of 55 pts. The detected immunoglobulinopathies were divided into 4 groups: polyclonal hypergammaglobulinaemia, hypogammaglobulinaemia, oligoclonal gammapathy, and monoclonal gammapathy. Polyclonal hypergammaglobulinaemia was marked in 41 (74.5%) of 55 pts, elevated level of IgG was determined in 27 (49,15%) of 55 cases, IgM - in 18 (32,7%) and IgA - in 21 (38.2%). Interestingly, polyclonal IgE hypergammaglobulinaemia was detected in 12 (48,0%) of 25 cases of performed studies. Hypogammaglobulinaemia was detected in 8 (14,5%) of 55 cases. Oligoclonal gammapathy was determined in 4 (7.3%) of 55 pts. Monoclonal gammapathy was revealed in 11 (20,0%) of 55 cases. The amount of monoclonal immunoglobulin varied from 2.6 to 14.1 g/l. Monoclonal immunoglobulin Gk was detected in 5 of 11 pts, Gλ - in 2, Mλ - in 2, Mk - in 2. Monoclonal gammapathy was accompanied by polyclonal hypergammaglobulinaemia in 9 of 11 cases, hypogammaglobulinaemia - in 2. Conclusions. Quantitative and qualitative immunoglobulinopathies are observed in most patients at the onset of AITL. Quantitative abnormalities were determined more often than qualitative. Monoclonal gammapathy can be a manifestation of lymphoproliferation and other concomitant disorders. The prognostic value of immunochemical parameters is still unclear and requires dynamic observation and study.

Aim. To explore preventive measures aimed at risk factors that affect the development of chronic non-communicable diseases of people working in enterprises.Materials and methods. The study was based on questionnaires completed by employers and leaders of trade union organizations.Results. Forms of preventive measures and incentives were suggested for employers to encourage workers to form and be committed to a healthy lifestyle.Conclusion. Implementing of preventive actions used in enterprises to promote and preserve health of people working in the territories of the South and North Caucasian FD is only possible when the employers and managers of the trade union organization have a responsible attitude to this issue.

Background: Angioimmunoblast T-cell lymphoma (AITL) is a rare T-cell lymphoproliferative disease that is accompanied by generalized lymphadenopathy, hepatosplenomegaly, intoxication symptoms and extranodal lesions. The extranodal manifestations of the disease frequently involve various skin changes. One of the first such manifestations is maculopapular rashes observed in about half of AITL patients and usually preceding the appearance of lymphadenopathy. Other forms of skin lesions accompany the disease considerably less frequently.Aim: To characterize the range of skin changes in patients suffering from AITL, to establish a correspondence between the nature of skin changes and their histological picture.Materials and methods: 54 AITL patients were being treated at the National Research Centre for Hematology from 2000 to 2017, with the male/female ratio being 30/24. The median age was 61 (29–81) years.Results: Changes in the skin were observed in 24 (44.4 %) of 54 AITL patients, out of whom 18 (75 %) and 6 (25 %) were male and female patients, respectively. Maculopapular rash was observed in 22 (91.7 %) out of 24 patients. The morphological and molecular investigations of skin biopsy specimens exhibiting maculopapular rash demonstrated nonspecific reactive changes. Patients with maculopapular rash demonstrated an increase in the level of total (polyclonal) IgE. Specific skin lesions detected in 8 (14.8 %) cases were represented by a ‘livedo reticularis’, focal skin hyperpigmentation, erythroderma, left eyelid tumour and tumour in 3, 2, 1, 1 and 1 cases, respectively.Conclusion: Maculopapular rash frequently observed in AITL patients is a reactive process not associated with a specific skin lesion. Specific skin lesions in AITL are much less common and can be represented by various forms. In some AITL cases, skin changes of the reactive and tumour nature can be simultaneously observed.

Afibrinogenemia is a rare congenital coagulopathy that leads to life-threatening bleeding. In afibrinogenemia, plasma fibrinogen levels are less than 0.1 g/L. The clinical manifestations of the disease can be both bleeding and thromboses of different localizations, which is determined by the multifunctional role of fibrinogen in hemostasis. The described cases demonstrate different clinical phenotypes of the disease. In both cases the diagnosis was confirmed by genetic examinations that revealed homozygous mutations in the fibrinogen A genes. The nature of the mutations assumes consanguineous marriages, as confirmed by the results of a genealogical analysis. Fibrinogen preparations are promising in treating afibrinogenemia in Russia.Афибриногенемия относится к редким врожденным коагулопатиям, приводящим к развитию угрожающих жизни кровотечений. При афибриногенемии уровень фибриногена плазмы составляет менее 0,1 г/л. Клиническими проявлениями заболевания могут быть как кровотечения, так и тромбозы различной локализации, что определяется многофункциональной ролью фибриногена в гемостазе. Описанные случаи демонстрируют различный клинический фенотип заболевания. В обоих случаях диагноз подтвержден генетическими исследованиями, в которых выявлены гомозиготные мутации в генах фибриногена А. Характер мутаций предполагает близкородственные браки, что подтверждено результатами генеалогического анализа. Перспективами лечения афибриногенемии в России являются препараты фибриногена.

Aim. Development of a model of strengthening and preservation of health to improve the activities of children’s and adult health centers.Methods. A statistical method was used: dynamic analysis of the number of population of Russian Federation in 2010-2015, analysis of budget funds received for preventive work by medical prevention centers in 2014. By the use of a modeling method the scheme of organizational support of children’s and adult health centers was developed.Results. Designed structure for children and adult health centers with a new direction of activity will contribute to more rational organizational support at various levels of health care, as well as improving the quality and effectiveness of preventive care. The proposed new titles of health centers (child center for health preservation; center for reproductive, family and personal health for adults) reflect the direction of their activities, basically provide improvement of family health at all stages of family development (childhood, youth, working-age and old people) and orientation to a healthy lifestyle. The peculiarity of the new direction of centers’ activity is greater attention to reproductive and mental health. Promoting mental health in adults should begin in childhood. Increased activity of children’s centers will strengthen health throughout life.Conclusion. Health center should be located in a medical organization; its name should reflect the direction of its activities; the basis of the center for the adults should become a family; strengthening of reproductive and sexual health will contribute to improvement of demographic situation in the country; it is necessary to increase funding for preventive care for the population.

Aim. To improve measures aimed at ensuring the continuity of the dynamic health monitoring of students on the basis of medical institutions of the University. Methods. On the basis of the technology «client-server», which is oriented on the management system of the Firebird databases, developed was an information-analytical system of dynamic observation of the health of students. Results. This system presumes a specific algorithm for the medical examination, first of all the screening methods: psychological testing, measurement of anatomical and physiological parameters, obtaining of the medical history, physical examination, cardiorhythmography and routine clinical and laboratory tests. With the help of original methods the medical information system provides a complex report on the state of health of the student and on the risks of the most common diseases in this age group. Conclusion. Health care providers of medical institutions of a University can use the developed system for dynamic monitoring of the health of the students.

To study morphofunctional condition of the kidneys in patients with hematological malignancies.Renal function, i.e. concentration ability, glomerularfiltration rate (GFR), concentration of electrolytes and beta2-microglobulin in blood serum and urine was studied at different stages of chemotherapy. Three cases are reported. All the patients have undergone transcutaneous fine-needle puncture biopsy of the kidney with histological and electron-microscopic study of biopsy specimens.Total urinalysis showed minimal changes. Concentration and filtration functions of the kidneys were impaired. Morphologically, glomerular damage was insignificant, there was dystrophy of tubular epithelium and focal interstitial sclerosis. Electron-microscopic examination revealed structural defects of the basal membrane of glomerular capillaries (focal thinning, focal insignificant thickening, the absence of three-layer structure at long distance) in all the patients. Dissection of the basal membrane was seen in one case. All the patients had cytoplasmic viruses: Epstein-Barr, cytomegalovirus, herpes simplex viruses type 1 and 2. In two cases mitochondria were affected with viruses. Dystrophic changes of podocytes and mitochondrial degradation were observed in all the cases.Chemotherapy may affect glomerular and tubular system of the kidney increasing probability of complications. Imbalance between cytolysis kinetics and natural clearance of the products of degradation of cells and drug metabolites may lead to nephropathy. Viral infection indicates immunodeficiency due to immunosuppression or is a direct cause of impairment of renal endothelium cells. No definite recommendations can be made still about therapeutic policy.

The status of the dermatological and venereological service in Moscow is analyzed and the epidemic situation for syphilis described for the period of 1992-1996. The activities of the service are assessed and its prospects for the nearest future outlined.

Based on vast comprehensive medical statistical database, the authors analyze the health status of the population and the efficacy of public health service in Moscow. The pre-crisis tendencies and the modern status of public health under modern socioeconomic conditions are noted.

In a major proportion (67%) of those examined (persons with stage-II hypertensive disease who took part in the elimination of the aftermath of the Chernobyl breakdown) with the aid of echocardiography, hypertrophy of the left ventricular (LV myocardium was revealed as was augmentation of the mass of the LV myocardium together with decline in the contractile function, while in other examinees (33%) all above parameters showed no deviation from the norm. This permits predicting probability of cardial complications in such patient populations.

Here, we report first results of the large-scale ongoing bioelectrical impedance body composition study in Russians. By the end of 2012, 216 out of 800 Russian Health Centres submitted raw bioimpedance data on 844,221 adults and children aged 5–80 years, representing nearly 0.6% of the Russian population, who were accessed cross-sectionally using the same type of bioimpedance meter, ABC-01 Medas. Estimates of overweight, obesity, and normal weight obesity prevalence in the general population, as well as characteristics of diagnostic sensitivity and specificity of the conventional WHO BMI-based criteria of obesity depending on age are obtained. The smoothed reference centile curves for percentage fat mass are constructed, and localized cut-offs for fatness and thinness are provided that can be used both at the individual and epidemiological levels.

Results are reported of treatment of 69 patients with vibration disease (VB) using hyperbaric oxygenation. Treatment course--10 sessions with an exposition of 40 minutes in the main regimen. Tests for choice of treatment regimens (1.3, 1.5, 1.8 atm.) were the dynamics of subjective and objective clinical signs, indices of the peripheral hemodynamics and thermoregulation. Hyperbaric oxygen treatment in persons with signs of vibration effects (preclinical stage) using a working pressure of 1.3 atm is justified. Presence of clinical manifestations of the disease (grade I-II degree of VB severity) justifies increase of the dose of hyperbaric oxygen to 1.5 atm.

Examination of 76 patients with pneumoconiosis (stage I) revealed that hyperbaric oxygenation is increasing the force of cardiac contractions, reduction of the general peripheral resistance and reduction of the lesser circulation hypertension. The therapeutic action of hyperbaric oxygenation is related to its ability to remove the sequels of oxygen.

In 4 patients with vibration disease hyperbaric oxygenation was included in the complex treatment and this resulted in an increase of blood supply to the extremity, increase of vascular reactivity, reduction of the peripheral vascular resistance. Inverse dependence of the hyperbaric oxygenation treatment and severity of vibration disease was found that was mainly determined by the initial lever of the peripheral hemodynamics.

The authors studied the influence of mountain climate (altitude: 2200 m) on the course of chronic dust-induced bronchitis, pneumoconiosis and vibration disease in 45 patients. It was found that a 1-month stay of patients with dust-induced bronchitis and pneumoconiosis in the mountains results in a positive clinical effect is accompanied by amelioration of the external respiratory function, positive changes of the hemodynamic values. Mountain climate treatment was ineffective in vibration disease.