Hereditary breast cancer: syndromes, tumour pathology and molecular testing.

Hereditary factors account for a significant proportion of breast cancer risk. Approximately 20% of hereditary breast cancers are attributable to pathogenic variants in the highly penetrant BRCA1 and BRCA2 genes. A proportion of the genetic risk is also explained by pathogenic variants in other breast cancer susceptibility genes, including ATM, CHEK2, PALB2, RAD51C, RAD51D and BARD1, as well as genes associated with breast cancer predisposition syndromes - TP53 (Li-Fraumeni syndrome), PTEN (Cowden syndrome), CDH1 (hereditary diffuse gastric cancer), STK11 (Peutz-Jeghers syndrome) and NF1 (neurofibromatosis type 1). Polygenic risk, the cumulative risk from carrying multiple low-penetrance breast cancer susceptibility alleles, is also a well-recognised contributor to risk. This review provides an overview of the established breast cancer susceptibility genes as well as breast cancer predisposition syndromes, highlights distinct genotype-phenotype correlations associated with germline mutation status and discusses molecular testing and therapeutic implications in the context of hereditary breast cancer.

Molecular Profile of Sensitization to Dermatophagoides pteronyssinus Dust Mite in Portugal.

BACKGROUND AND OBJECTIVES: To analyze component-resolved diagnosis of sensitization to Dermatophagoides pteronyssinus (Der p) in patients with respiratory allergy and the association between diagnostic findings and clinical severity in different geographical areas. METHODS: The study population comprised 217 patients (mean age, 25.85 [12.7] years; 51.16% female) selected from 13 centers in Portugal (5 from the North, n=65). All had allergic rhinitis with or without asthma and positive skin prick test results to at least 1 dust mite. Specific IgE (sIgE) to Der p, Dermatophagoides farinae, Lepidoglyphus destructor, Der p 1, Der p 2, Der p 10, and Der p 23 was determined using ImmunoCAP. The Mann-Whitney test was applied for the following comparisons: rhinitis vs rhinitis and asthma; mild vs moderate-to-severe rhinitis; North vs South. RESULTS: The prevalence of sensitization was 98.2% for Der p, and 72.4%, 89.4%, 9.7%, and 77% for Der p 1, Der p 2, Der p 10, and Der p 23, respectively. The corresponding median sIgE levels were 8.56, 17.7, 0.01, and 3.95 kUA/L. sIgE to all allergens was higher in patients with moderate-to-severe rhinitis and rhinitis with asthma (nonsignficant). Concentrations of sIgE to Der p 2 were significantly higher in the South than in the North (P=.0496). CONCLUSION: The most common sensitization in Portugal was to Der p. The highest prevalence and median sIgE level were observed for Der p 2. All sIgE values for molecular components were higher in more symptomatic patients (nonsignificant). Concentrations of sIgE to Der p 2 were higher in the South, probably because of the warmer temperature and/or the larger sample size.

Atopic Dermatitis Host and Environment Model: Revisiting Therapeutic Options.

Summary: Atopic Dermatitis affects both children and adults and is a serious health concern in many countries. AD is a complex disease with host and environmental factors underlying its pathology. Its treatment is multidimensional reflecting the diverse nature of its triggers and includes emollients, topical steroids and calcineurin inhibitors among others. Immunological dysfunction can be addressed broadly with systemic immunosupressors and specifically with monoclonal antibodies. Dupilumab, which targets IL-4 and IL-13 was granted approval for treatment of moderate-to-severe AD. Biologics targeting IgE/Th2 pathways may have its role in patients with overlapping AD and asthma. Psychological distress can exacerbate symptoms and is associated with increased severity of AD. Environmental triggers, such as, allergens can be addressed in selected cases with allergic immunotherapy. In this paper, we discuss AD treatment and propose a new step-by-step approach aiming at maintaining disease control and improving quality of life.

[Risk Assessment of Development of the Major Adverse Cardiac Events in Patients with Chronic Heart Failure with a Preserved and Intermediate Ejection Fraction in the Presence of a Bendopnea Symptom].

Aim To evaluate the risk of major cardiovascular complications (CVC) in patients with chronic heart failure (CHF) with intermediate and preserved ejection fraction (EF) depending on the presence of bendopnea symptom.Material and methods The study included 104 patients with stage II CHF and left ventricular EF ≥40 %. Mean age of the patients was 72.8±10.6 years. A test for detection of bendopnea symptom was performed for all patients. Two groups were formed: group 1, 69 patients with the bendopnea symptom and group 2, 35 patients with a negative test. Follow-up duration was 24 months. The composite endpoint (CEP) was death and hospitalization for any CVC.Results Mean time to the bendopnea symptom was 17.3±6.61 s. At two years of follow-up, the CEP was observed in 36 (34.6 %) patients, including 30 (43.5 %) patients in group 1 and 6 (17.1 %) patients in group 2. 12 patients died, and 9 of them had the bendopnea symptom. 21 patients of group 1 were hospitalized for CVC. Risk of CEP was significantly 1.7 times higher for men (relative risk, RR 1.7 [1.1; 2.6]) than for women. The presence of bendopnea symptom increased the risk of CEP 1.4 times (ОР 1.4 [1.1;1.9]) for women and 2.3 times (RR 2.3 [1.4; 3.6]) for men.Conclusion Results of the study demonstrated an unfavorable effect of bendopnea symptom on risk of CEP during the two-year follow-up of CHF patients with preserved and intermediate EF.

[Quality of life in patients with heart failure with preserved ejection fraction and the bendopnea symptom].

PURPOSE: The study of quality of life (QOL) in patients with CHF with preserved LVEF (left ventricular ejection fraction) and a symptom of bendopnea with different levels of salt intake. Materials and methods. The study included 66 patients. The main symptoms of CHF were edema in 54.5% of cases, dyspnea in 77% of cases, ascites was detected in only 2 patients, an enlarged liver in 7 patients. Abdominal obesity was detected in 53 patients. Quality of life was assessed by the SF­36 questionnaire, the level of salt intake was assessed by the Charlton: SaltScreener questionnaire. Results. On average, the time of occurrence of the bendopnea was 22.5±9.3 seconds, the minimum was 5 seconds. The absence of the effect of abdominal obesity on the risk of bendopnea (relative risk 1.18 [0.76; 1.83]) was revealed. According to the SF­36 questionnaire, a decrease in physical health indicators (median 31.3 points [20.7; 42.3]) and psychological health (average score 43.2±21.7) was found. In patients with bendopnea, QOL was reduced due to both physical and mental health, unlike patients without bendopnea: physical functioning (Physical Functioning - PF) 24.8±16.1 against 47±28.9 points, p=0.001 ; role­based functioning due to physical condition (Role­Physical Functioning - RP), 0 [0; 25] vs. 37.5 [0; 100] points, p=0.008; general health (General Health - GH) 29.9±15.8 against 50±14.2 points, p=0.0005, social functioning (Social Functioning - SF) 56 ± 38 against 78.9 ± 17.8 points ; p = 0.004. Multidimensional regression analysis revealed the relationship between the time of occurrence of the symptom bendopnea and the level of salt intake, physical and psychological activity (r2=0.25; p<0.009). The time of onset of the symptom of bendopnea in patients with CHF decompensation was significantly longer (18.9±8.7 vs. 26.2±8.5 seconds, p=0.003). The presence of diseases such as hypertension, COPD, IHD, atrial fibrillation, cerebrovascular disease did not significantly affect QOL (p> 0.05), while the presence of bronchial asthma or chronic kidney disease significantly reduced QOL of patients (p<0.05). Conclusion. The presence of the symptom bendopnea significantly reduces the quality of life of patients with CHF with preserved LVEF (left ventricular ejection fraction).

[Personalized approach for direct oral anticoagulant prescription: from theory to practice].

Data on possibilities of personalized approach for direct oral anticoagulants (DOAC) choice in patients with atrial fibrillation are presented in the article. We also review clinical and fundamental studies and future perspectives on pharmacogenetic and pharmacokinetic tests to predict the efficacy and safety of DOAC.

[Prevention of thromboembolic and hemorrhagic events in patients with atrial fibrillation undergoing elective surgery]. / Profilaktika tromboémbolicheskikh i gemorragicheskikh oslozhnenii u patsientov s fibrilliatsiei predserdii pri provedenii planovogo khirurgicheskogo lecheniia.

OBJECTIVE: To compare incidence of thromboembolic and hemorrhagic complications in patients with atrial fibrillation (AF) undergoing elective surgery on different schemes of perioperative anticoagulant therapy (ACT). MATERIAL AND METHODS: There were 86 patients (56 (65.1%) men and 30 (34.9%) women, mean age was 69 (64; 78) years) with non-valvular AF who underwent elective interventions. Forty (46.5%) patients underwent abdominal surgery, 34 (39.5%) - cardiovascular procedures, 12 (14.0%) patients underwent surgery for malignant diseases. We have analyzed incidence of thromboembolic and hemorrhagic events and compliance of perioperative ACT modes with current international guidelines. RESULTS: Thromboembolic and hemorrhagic events developed in 14 (16.3%) patients. Thromboembolic complications were noted in 6 (7.0%) patients, hemorrhagic events - in 8 (9.3%) cases. Maximum complication rate was observed in case of bridge-therapy (n=12, 20.0%). Cancellation of ACT was followed by 2 (9.5%) complications, bridge-therapy - by 4 (6.7%) thromboembolic complications. Hemorrhagic events were 2 times more common in case of this therapy (n=8, 13.3%). It was found that ESC guidelines for perioperative ACT were applied in less than half of patients (41, 47.7% patients with AF undergoing elective surgery). Half of complications (8 out of 16) occurred if unapproved modes of ACT were used (including 7 cases of bridge-therapy was not necessary). The causes of these complications were inadequate assessment of perioperative risk of thromboembolic and hemorrhagic events; unreasonable administration of bridge therapy. CONCLUSION: An unambiguous clinical effect of bridge therapy has not been confirmed in patients with high risk of thromboembolic complications. Cancer patients have higher risk of complications compared with others. These events occur mainly due to non-compliance with clinical guidelines and insufficient prevention of thromboembolic events.

[Factors associated with levels of interleukins -18, -8, and -6 in hypertensive patients at high and very high cardiovascular risk].

AIM: To identify the most significant factor influencing blood levels of cytokines in patients at high and very high cardiovascular risk. MATERIALS AND METHODS: A patient base from the "Management of chronic patients with multiple diseases" project was analyzed. 523 patients (mean age, 87±17.8) were included. Plasma samples were analyzed for concentrations of sodium, creatinine, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, and NT-proBNP. GFR was calculated using the CKD-EPI formula. Time-related CHF progression was assessed in one year; the time-related progression was considered an increase in CHF stage. Salt consumption was determined using the Charlton: SaltScreener questionnaire at the baseline visit and at one year. Low-salt diet containing 5 g of salt per day was recommended to all patients; 3.5 g of salt per day was recommended to patients with a documented diagnosis of CHF. Statistical analysis was performed using the Statistica 10.0 software. RESULTS: 52.2 % of included patients consumed 6-10 g of salt per day; 43.4 % of patients consumed 10 g of salt or more per day; and only 4.4 % of patients consumed 5 g of salt or less per day. 21 % of included patients were at high risk of cardiovascular complications whereas for the vast majority of patients (79 %), the risk was stratified as very high. Two clusters of patients were formed based on the grade of hypertension, one-year CHF progression, and plasma levels of IL-6, -8, and -18. The one-year progression of CHF most significantly influenced the levels of IL-18, -8, and -6. The IL-6 level was correlated with the NT-proBNP level; an approximately similar degree of correlation was found for NT-proBNP and BP. CONCLUSION: Therefore, the performed statistical analysis determined correlations between the following factors: IL-6 level, NTproBNP level, and one-year CHF progression.

[Correlations of IL-18 and IL-6 with sodium consumption in patients with arterial hypertension and diabetes mellitus].

AIM: To determine correlations of AH-associated interleukins (IL-18, IL-6) with sodium consumption in AH patients with and without DM. MATERIALS AND METHODS: The study included AH patients with and without DM (n=63) who were managed at the Municipal Clinic #64, Moscow Department of Health Care, Branch 1. Plasma levels of IL-6 and IL-18 were measured using ELISA kits (Bender Med-Systems). Salt consumption was determined using a Charlton: SaltScreener questionnaire. Statistical analyses were performed using the Statistica 10.0 software. RESULTS: Four groups were formed: Group 1, grade 2 AH and DM (n=19); Group 2, grade 2 AH and no DM (n=4); Group 3, grade 3 AH and no DM (n=28); and Group 4, grade 3 AH and DM (n=12). Group 2 was small and was excluded from further analysis due to impossibility of statistical treatment. All patients consumed more than 6 g of salt per day (approximately 10 g). Analysis of intergroup differences in selected parameters showed differences between groups in levels of cholesterol, triglycerides, LDL, and GFR. The following correlations were identified in the groups: Group 1, positive correlation of IL-18 with sodium consumption (r=0.65) and CRP level (r=0.52) and of IL-6 with LDL level (r=0.48); Group 3, positive correlation of IL-18 with IL-6 (r=0.66) and of IL-6 with CRP (r=0.52); Group 4, positive correlation of IL-18 with GFR (r=0.82) and of IL-6 with waist circumference (WC) (r=0.84) and IL-6 (r=0.73). CONCLUSION: Patients consuming more than 6 g of salt daily (approximately 10 g) with AH and DM had more pronounced inflammation, which promoted progression of kidney disease.

[Direct oral anticoagulants in atrial fibrillation patients aged 75 years or older: Efficacy and safety balance]. / Priamye peroral'nye antikoagulianty u patsientov s fibrilliatsiei predserdii v vozraste 75 let i starshe: balans éffektivnosti i bezopasnosti.

Atrial fibrillation (AF) is one of the most common heart rhythm disorders in the population. Researchers revealed a direct relationship between their incidence and a patient's age long ago. One of the most challenging issues of clinical practice in patients with AF is anticoagulant therapy used in the so-called very elderly patients aged 75 years and older when age itself is a risk factor for developing both thromboembolic and hemorrhagic events due to anticoagulants, regardless of the mechanism of action of the latter. However, scientific data regarding the treatment and prevention of thromboembolic events in elderly and senile patients with AF are very scarce and often uninformative. The data from the EURObservational Research Programme-Atrial Fibrillation Registry Pilot Phase (EORP-AF Pilot) and the randomized clinical studies RELY, ROCKET AF, ARISTOTLE, and AVERROES were analyzed to identify the most safe and most effective anticoagulant for elderly patients (over 75 years). Relying on the analyses of literature data, the authors propose an algorithm based on clinical characteristics for choosing the anticoagulant for patients older than 75 years.

[Anticoagulant therapy in patients with atrial fibrillation and reduced kidney function of diabetic and non-diabetic etiologies]. / Antikoaguliantnaia terapiia u patsientov s fibrilliatsiei predserdii i snizhennoi funktsiei pochek diabeticheskoi i nediabeticheskoi étiologii.

AIM: To evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and stages I-III chronic kidney disease (CKD). SUBJECTS AND METHODS: The cohort parallel-group study included 92 patients with AF and stages I-III diabetic and non-diabetic CKD, who were treated with DOACs (dabigatran, rivaroxaban, or apixaban) and vitamin K antagonists (warfarin). The follow-up duration was 12 months. RESULTS: Thromboembolic events and bleeding, which required patient hospitalization or blood transfusions, were not recorded during 1-year follow-up. There was no clinically significant progression of CKD in the groups of therapy with vitamin K antagonists or DOACs. Just the same, a more intense decrease in glomerular filtration rate and a high rate of hemorrhagic complications were revealed in the subgroup of patients with diabetes mellitus (DM) versus those with non-diabetic CKD. CONCLUSION: In patients with non-valvular AF and diabetic and non-diabetic CKD, the use of DOACs effectively and safely prevents thromboembolic events, irrespective of the stage of CKD. At the same time, in patients taking anticoagulants, CKD progresses more rapidly in the presence of DM than in its absence, regardless of a specific anticoagulant. Hemorrhagic complications are more common in patients with AF, DM, and CKD, which requires more frequent monitoring of their kidney function.

[The new 2017 European society of cardiology (ESC) guidelines: important changes for introduction into clinical practice]. / Novye rekomendatsii Evropeiskogo obshchestva kardiologov (ESC) 2017 g.: vazhnye izmeneniia dlia vnedreniia v klinicheskuiu praktiku.

The paper gives an overview of the European Society of Cardiology (ESC) guidelines updated in 2017. The revised and amended guidelines for areas, such as dual antiplatelet therapy (DAT), treatment of patients with ST-segment elevation myocardial infarction (STEMI), and management of patients with valvular heart disease and peripheral artery disease, were presented in late summer of this year. The authors of this paper present an independent analysis and discussion of new data on the key issues of diagnosis and treatment in patients in the above areas. The recommendations on DAT pay special attention to the timing of the therapy and to the choice of its drugs. The updated data on the treatment of patients with STEMI accurately determine the time to percutaneous coronary interventions, approaches to revascularization; the updates touch upon fibrinolytic therapy and new approaches to lipid-lowering therapy too. Recommendations for the management of patients with peripheral artery atherosclerosis propose for the first time a section devoted to the choice of antiplatelet therapy (an antiaggregant and/or an anticoagulant) depending on the clinical situation.

[The effect of the level of total sodium deposited in the myocardium on its stiffness]. / Vliianie urovnia obshchego natriia, deponirovannogo v miokarde, na ego zhestkost'.

AIM: To determine a relationship between the level of total sodium in the myocardium to its stiffness. SUBJECTS AND METHODS: The investigation enrolled 18 hypertensive patients who had suddenly died; their mean age was 40±10 years; mean waist circumference, 102±12.5 cm; height, 170±7.7 cm; myocardial mass, 319±53 g. RESULTS: The variation in the myocardial level of total sodium averaged 211.7±37.5 (min, 71.5; max, 226.17) mmol/l. The sodium level was ascertained to be affected to the greatest extent by myocardial mass (SS=3615.56; p=0.00029) and age at death (SS=1965.568; p=0.0029), whereas gender and smoking had a considerably lower impact (SS=778.584; p=0.03). A univariate regression analysis showed that there was a relationship between myocardial sodium levels and the thickness of the anterior wall of the left ventricle (ß=0.94; p=0.000001; r2=0.88), that of the anterior wall of the right ventricle (ß=0.82; p=0.000021; r2=0.66), and that of the interventricular septum (ß=0.94; p=0.000001; r2=0.89). The wall thickness of the myocardium was established to depend on its sodium level (SS=21813.89; p=0.000001; r2=0.88): the higher sodium amount in the myocardium, the thicker its walls. The average velocity of acoustic wave propagation was 6.24±0.51 m/sec. A significant correlation was observed between sodium concentrations in the myocardium and its stiffness (ß=0.72; p=0.00062; r2=0.49). CONCLUSION: The level of sodium deposited in the myocardium, which is directly related to dietary sodium intake, is significantly correlated with myocardial stiffness. It can be assumed that the elevated level of sodium deposited in the myocardium is an independent factor that changes the stiffness of the myocardium and appears to influence the development of its diastolic dysfunction.

Acute Hemorrhagic Edema of Infancy.

Acute Hemorrhagic Edema of Infancy is a small vessel leucocytoclastic vasculitis affecting young infants. It is characterized by large, target-like, macular to purpuric plaques predominantly affecting the face, ear lobes and extremities. Non-pitting edema of the distal extremities and low-grade fever may also be present. Extra-cutaneous involvement is very rare. Although the lesions have a dramatic onset in a twenty-four to forty-eight hour period, usually the child has a non-toxic appearance. In most cases there are no changes in laboratory parameters. The cutaneous biopsy reveals an inflammatory perivascular infiltrate. It is a benign and auto-limited disease, with complete resolution within two to three weeks leaving no sequelae in the majority of cases. No recurrences are described. We report a case of a 42-day old girl admitted at our hospital with Acute Hemorrhagic Edema of Infancy.

[WEAK COMBINED MAGNETIC FIELDS ADJUSTED TO THE PARAMETRIC RESONANCE FOR Ca2+ INTENSIFY DYSTROPHIN SYNTHESIS IN MDX MICE SKELETAL MUSCLES AFTER CELL THERAPY].

The mdx mice are an X-linked myopathic mutants, an animal model for human Duchenne muscular dystrophy (DMD). Mdx mice muscles are characterized by high level of striated muscle fibers (SMF) death followed by regeneration. As a result most SMFs of mdx mice have centrally located nuclei. The possibility of using stem cells therapy for the correction of DMD is actively being studied. One of the approaches to the usage of bone marrow stem cells for cellular therapy of DMD is the replacement of bone marrow after irradiation by X-rays. This method however does not give significant increase of dystrophin synthesis in mdx mice muscles fibers. We have tried to affect the mice after bone marrow transplantation by weak combined magnetic fields adjusted to the parametric resonance for Ca2+(Ca(2+)-MF) based on the data that the weak combined magnetic fields influence on tissues regeneration. We observed a significant increase in the proportion of dystrophin-positive SMFs in group of mdx mice radiation chimera 5 Gy and 3 Gy which was additionally exposed in Ca(2+)-MF in comparison with the control mdx mice and the group of mdx mice radiation chimera 5 Gy and 3 Gy which was kept in terrestrial magnetic field 2 months after chimera preparation--up to 15.8 and 18.3%, respectively. Also, there was an accumulation of SMFs without central nuclei. These data indicate a significanly increased efficacy of cell therapy in the case of additional exposition in Ca(2+)-MF. Thus, the efficiency of bone marrow transplantation mdx mice after both in doses 3 and 5 Gy was considerably enhanced by additional exposition to Ca(2+)-MF. Apparently, such magnetic field can intensify functioning of donor's nuclei which had been incorporated into muscle fibers.

[Impact of the dosing of basic drugs on the risk of rehospitalization in patients with chronic heart failure].

AIM: To investigate the impact of doses of the drugs, which have been achieved during adjustment and account for less or more than 50% of the maximal therapeutic ones on the risk of rehospitalization. SUBJECTS AND METHODS: The data of the Pavlov Register were used to assess the treatment of patients with chronic heart failure. To assess the risk of rehospitalization in relation of the dose of a drug, all the doses were represented in percentage terms depending on the maximum therapeutic one. RESULTS: The risk of hospitalization during 6 months in the patients receiving angiotensin-converting enzyme inhibitors at a dose of 25% or less of the therapeutic one was 21.18% (odds ratio (OR), 1.41; 95% confidence interval (CI), 1.13-1.76), that at doses of 50 and 100% of the therapeutic one was 16% (OR, 0.71; 95% CI, 0.56-0.88) and 34% (OR, 0.51; 95% CI, 0.43-0.60), respectively. The risk of rehospitalization in the patients taking ß-blockers at doses of 25, 50, and 100% of the therapeutic one was 26% (OR, 1.05; 95% CI, 0.94-1.17), 23% (OR, 0.902; 95% CI, 0.75-1.07), and 6.25% (OR, 0.19; 95% CI, 0.07-0.56), respectively. The combined analysis of the dose and use frequency of diuretics showed that the highest risk of rehospitalization turned was noted in the patients using a single dose of 100 mg of furosemide (4.2% of cases) once weekly and was as high as 39% (OR, 0.45; 95% CI, 1.04-1.98). CONCLUSION: The risk of rehospitalization is largely determined by the dosing factor in outpatient settings. Increasing the doses during adjustment reduces the risk of rehospitalization.

Dynamics of body burdens and doses due to internal irradiation from intakes of long-lived radionuclides by residents of Ozyorsk situated near Mayak PA.

This paper presents and discusses new autopsy results and other historic data from earlier autopsies and environmental monitoring linked to releases from the Mayak PA facilities in the Chelyabinsk oblast in the southern Urals. The focus is on residents of the town of Ozyorsk located near to Mayak PA and the dynamics of body burdens and radiation doses from inhalation of plutonium alpha and americium-241, and ingestion of strontium-90 and caesium-137. It is demonstrated that accumulation and exposure from these radionuclides was mainly due to unplanned releases in the 1950s and 60s. The mean content of plutonium alpha at the time of autopsy of people commencing residence in Ozyorsk from 1949 to 1959 was about 3.5 Bq, falling to 0.2 Bq in those arriving after 1990. A reducing trend was also seen for (241)Am. The highest (90)Sr content in Ozyorsk residents was measured in 1967. The (137)Cs body content of residents arriving in Ozyorsk at any time was in almost all cases below the limit of detection. The committed effective dose from internal exposure to these long-lived radionuclides which would have been accumulated in Ozyorsk residents if present from 1949 to 2013 is estimated to be 13 mSv. This dose is primarily attributed to intakes during 1949 to 1959 when the annual effective dose rate was approximately 1 mSv y(-1). The current value is about 0.1 mSv y(-1). This dose is about 20 times higher than the dose from global man-made fallout, which is about 0.005 mSv y(-1) at present, but much lower than that from natural background radiation, i.e. about 2 mSv y(-1). The experience gained from this work and continuing activities can contribute to the development of improved international guidance in legacy situations, particularly as regards the provision and use of monitoring data to test and thereby build confidence in prognostic models for radiation conditions and potential future exposures. The scope includes evidence for the rate of reduction in radionuclide concentrations in environmental media and in their bioavailability, resuspension of long-lived alpha radionuclides, uptake of (90)Sr and (137)Cs in the food-chain, and confirmation of cumulative uptake via autopsy and whole body counting measurements. Continuing investigations will thus support decisions on future planned releases and contribute to planning of remediation of other areas affected by historic releases.

[Curare-Like Camphor Derivatives and Their Biological Activity].

The synthesis and evaluation of muscle relaxant activity of series of dimeric camphor derivatives are described. Compounds in which the quaternary nitrogen atoms are separated by aromatic chain exhibited the highest efficiency as muscle relaxant. It was shown the screening of a charged atom and counter-ion does not have a significant role on the activity of the studied agents.

[The new methods in gerontology for life expectancy prediction of the indigenous population of Yugra].

The behavior of the state vector of human cardio-vascular system in different age groups according to methods of theory of chaos-self-organization and methods of classical statistics was investigated. Observations were made on the indigenous people of North of the Russian Federation. Using methods of the theory of chaos-self-organization the differences in the parameters of quasi-attractors of the human state vector of cardio-vascular system of the people of Russian Federation North were shown. Comparison with the results obtained by classical statistics was made.

[Effect of loop diuretics with different elimination half-lives on natriuresis changes and indicators characterizing the state of renal tubulointerstitial tissue].

AIM: To investigate the effect of loop diuretics with different elimination half-lives on natriuresis (NU) changes in patients with hypertensive disease (HD) and chronic heart failure (CHF). SUBJECTS AND METHODS: Fifty-six patients who had signs of progressive CHF and needed diuretic therapy were selected from a group of the patients who had participated in our previous study of the types of natriuretic curves. They all received torasemide SR or torasemide IR. RESULTS: It has been shown that the type of a natriuretic curve may be variable in the patients. In the toracemide IR group, NU worsens more frequently and earlier than in the toracemide SR group (p < 0.05). The type of the curve is associated with elevated Tamm-Horsfall protein (THP) levels, its transition from one to another type, and the duration of HD to the greatest degree. It has been found that the longer history of HD is, the higher effect of angiotensin II is. The probability of transition of the natriuretic curve from type 3 to 2 is 83.93% (odds ratio 11.667) from type 2 to 1 is 92.86% (odds ratio 120.00). CONCLUSION: With time and altered NU, there is a significant deterioration of sodium excretion, and an increase in THP excretion, which is a marker for progressive tubulointerstitial fibrosis, and angiotensin II activity increases, which gives proof to the necessity of monitoring NU.