[Receptive status of the endometrium in patients with benign ovarian tumors before and after organ-preserving operations]. / Retseptivnyi status endometriya pri dobrokachestvennykh opukholyakh yaichnikov do i posle organosokhranyayushchikh operatsii.

Background. Benign ovarian tumors (BOT) occupy the 2nd place in the structure of diseases of the female genital organs. In 20% of women of reproductive age, BOT are associated with infertility. One of the causes of infertility caused by ovarian tumors is morphofunctional inferiority with impaired endometrial receptivity. OBJECTIVE: To reveal the morphological and functional features of the endometrium and the level of receptivity to sex hormones in patients with BOT before and after organ-preserving operations. MATERIAL AND METHODS: The study included 77 patients with epithelial ovarian tumors (EOT) - I group, 52 with mature teratomas (MT) - II group. Before and 6-12 months after laparoscopic cystectomy aspiration biopsy of endometrium was performed in the middle stage of secretory phase. The percentage and degree of maturity of pinopodes were determined, and the level of expression of estrogen (ER) and progesterone (PR) receptors in the glands and stroma of the endometrium was assessed. RESULTS: At the preoperative stage, a decrease in the number of mature pinopodes in patients with EOT was revealed. Normal levels of ER were determined in glands and stroma of endometrium, PR was reduced both in stroma and glands of uterine mucosa. In patients with MT all markers corresponded to those of healthy women. In the postoperative period an increase in the number of developed pinopodes on the apical surface of endometrium in patients of I group was found. The ER level did not differ from control values, PR remained reduced in stroma. In II group a persistent decrease in quantity of mature pinopodes, ER in stroma, PR in glands and stroma of uterine mucosa was recorded. CONCLUSION: The presence of BOT and unintentional intraoperative removal of healthy ovarian tissue lead to indirect disorders of the morphofunctional state and endometrial receptivity.

[The use of reamberin in antishock therapy in severely burned patients]. / Ispol'zovanie reamberina pri provedenii protivoshokovoi terapii u tiazheloobozhzhennykh.

A 51-year-old severely burned woman had hospitalized at the Clinic of Thermal Injuries of the S.M. Kirov Military Medical Academy with a diagnosis: flame burn in a surface area of 40% (11%)/II-III b degrees of head, neck, trunk, limbs. Inhalation injury of moderate severity. The infusion drug of the combined action reamberin, which has a volemic and antihypoxic effect, had added to the complex antishock therapy. The presented clinical observation demonstrates the favorable course of burn shock: stopping of burn shock 28 hours after injury.

[Comparative assessment of the expression of Muc 2, Muc 5AC, and Muc 6 in serrated neoplasms of the colon]. / Sravnitel'naia otsenka ékspressii Muc 2, Muc 5AC i Muc 6 v zubchatykh novoobrazovaniiakh tolstoi kishki.

In the course of the serrated pathway of carcinogenesis, there are changes in the expression of mucins with a characteristic immunophenotypic sign, such as a late loss of intestinal differentiation and an increase in gastric differentiation. OBJECTIVE: To comparatively assess the expression of Muc 2, Muc 5AC, and Muc 6 in hyperplastic polyps (HPs), sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs) of the colon for determination of their role in differential diagnosis. MATERIAL AND METHODS: Sixty-five serrated masses from 52 patients were examined. Among them, there were 26 SSAs, 26 HPs, and 13 TSAs. A histological examination was done using hematoxylin and eosin staining; periodic acid-Schiff reaction in combination with alcian blue, as well as immunohistochemistry with anti-Muc 2, anti-Muc 5AC, and anti-Muc 6 antibodies were used. Genetic testing of the specimens for KRAS and BRAF mutations was also carried out. RESULTS: All the serrated neoplasms of the colon exhibited a pronounced expression of Muc 2. A marked Muc 6 expression in the dilated crypt bases was found in 76.9% of SSAs, while no reaction was seen in 92.3% of HPs and in 100% of TSAs. SSAs were characterized by an intense Muc 5AC expression in the whole length of the crypts and in the surface epithelium in contrast with HPs and TSAs, where the expression of the marker was focal. Comparison of the response of the markers and the presence of gene mutations identified that the SSAs with BRAF mutation intensely expressed along the length of the crypt for Muc 5AC and Muc 6; and the TSAs with KRAS mutation had a moderate focal Muc 5AC expression in the crypt bases in 100% of cases. CONCLUSION: For differential diagnosis of the types of serrated adenomas of the colon, it is useful for a pathologist to apply the immunohistochemical markers Muc 2, Muc 5AC, and Muc 6 in his/her practice.

[The clinical and anatomical aspects of preeclampsia: current features of its course]. / Kliniko-anatomicheskie aspekty preéklampsii: sovremennye osobennosti techeniia.

Preeclampsia is the most menacing complication of pregnancy and childbirth worldwide and remains one of the leading causes of maternal and perinatal morbidity and mortality. It is characterized by a complex etiopathogenesis with specific clinical and laboratory changes (hypertension, proteinuria and edema), as well as by the morphological pattern of target organ damage and uteroplacental blood vascular lesions. However, the triad of clinical signs of preeclampsia is not encountered in all cases now. OBJECTIVE: to study the clinical and anatomical aspects of preeclampsia at the present stage. MATERIAL AND METHODS: 17 maternal deaths due to preeclampsia were studied at the medical institutions of the Moscow Healthcare Department from 2012 to the first half of 2017 through postmortem examination at City Clinical Hospital Thirty-One, Moscow Healthcare Department. RESULTS: This analysis showed the atypical course of preeclampsia (without substantial blood pressure elevations, with mild/moderate proteinuria, but almost always with edema). The characteristic feature is a laboratory sign, such as thrombocytopenia and liver enzyme dysfunction. Morphological examination of deceased patients showed that almost half of the cases had brain hemorrhages of different localization and size; in most cases, renal changes corresponded to the pattern of a shock kidney with endotheliosis and frequently with cortical necroses. The liver was characterized by a considerable increase in size with the development of fatty dystrophy, centrolobular necroses and hemorrhages; there were metabolic damage foci in the heart in almost half of the cases, as well as signs of disseminated intravascular coagulation with numerous hemorrhages in the organs and tissues. CONCLUSION: Characteristic uteroplacental artery morphological changes in both the surgical and autopsy material render a leading assistance in the diagnosis of preeclampsia/eclampsia.

[Morphological and immunohistochemical features of severe gastric dysplasia and early gastric cancer]. / Morfologicheskie i immunogistokhimicheskie osobennosti tiazheloi displazii i rannego raka zheludka.

AIM: to investigate the morphological and immunohistochemical features of severe gastric dysplasia (SGD) and early gastric cancer (EGC). MATERIAL AND METHODS: The fragments of gastric tumor tissue with adjacent mucosal portions from 50 patients aged from 34 to 79 years (mean age 63.8 years), which had been removed during organ-sparing endoscopic surgery, were histologically, histochemical, and immunohistochemically (IHC) examined. RESULTS: In EGC, there was a preponderance of intestinal-type cancer; the adjacent mucosal areas showed foci of SGD and colonic metaplasia in 100%. Cancer emboli were absent in the lumen of blood and lymphatic vessels in EGC at a рТ1а stage. Relapse of cancer occurred in 10% of the patients with EGC within 6-24 months after endoscopic dissection. CONCLUSION: Complex morphological and IHC examination allows timely diagnosis of SGD and EGC, namely: the ability to assess the histologic type and depth of invasion of EGC, the presence or absence of cancer emboli in the blood and lymphatic vessels, which is crucial in determining treatment policy and prognosis. The immunophenotype of SGD and EGC with a number of antibodies (Abs) (cytokeratins 7, 8/18, mucins 1, 2 and 5AC, and p53) was assessed, the most significant ones of which were, in our opinion, Abs to p53 and mucin 5AC.

[Serrated adenomas of the colon: Clinical, morphological, and molecular genetic characteristics]. / Zubchatye adenomy tolstoi kishki: kliniko-morfologicheskaya i molekulyarno-geneticheskaya kharakteristika.

AIM: to investigate the clinical, morphological, and molecular genetic characteristics of serrated adenomas of the colon. MATERIAL AND METHODS: The study included 82 colon adenomas from 63 patients aged 29 to 81 years, who underwent colonoscopy with biopsy or polypectomy. The mean age of men was 63.3 years; that of women was 56.8 years. Comprehensive clinical, morphological, immunohistochemical, and molecular genetic examinations were made. RESULTS: The histological examination showed that sessile serrated adenomas (SSA) of the colon were most common (46.4%), while hyperplastic polyp (HP) and traditional serrated adenoma (TSA) were found less often and with the same frequency (26.8%). The most typical location of SSA was the right colon; that of TSA was the left one. HP was detected equally on both sides of the colon. The immunohistochemical examination of the subtypes revealed no significant differences in the expression of markers. An analytical panel of antibodies against Desmin, Podoplanin (D2-40), CK20, CD34, Ki-67, Muc2, CEA, and CDX2 was used when identifying dysplasia areas, suspecting malignancy with invasion into the muscular layer of the mucous membrane and when determining the possible presence of emboli in blood and lymph vessels. BRAF gene mutation was identified in half of SSA cases; genetic BRAF mutation was observed in 41.7% of HP cases; genetic KRAS mutation was seen in 16.6%. The patients with TSA showed KRAS and BRAF mutations in 58.4 and 8.3% of cases, respectively. Mutations of these genes were absent. CONCLUSION: The study revealed that the subtypes of serrated adenomas substantially differ by sex, age, localization, and molecular genetic characteristics.

[Dose-Response Dependences for Frequency of RET/PTC Gene Rearrangements in Papillary Thyroid Carcinoma after Irradiation. Simple Pooling Analysis of Molecular Epidemiological Data].

On the basis of all possible publications on the theme included in the previously formed base of sources on molecular epidemiology of RET/PTC rearrangements in thyroid papillary carcinoma a pooled analysis ("simple pooling data") on determination of the dose-effect dependences for RET/PTC frequency in radiogenic carcinomas of various irradiated groups was performed. (They are groups subjected to radiotherapeutic exposure, residents near the Chernobyl nuclear power plant (CNPP) and victims of nuclear bombing). The tendency to Pearson linear correlation (r = 0.746; p = 0.148) between the frequency of RET/PTC and the estimated dose on thyroid in the regions affected by the CNPP accident was revealed. But this tendency was recognized to be random owing to abnormally low values of the indicator for the most contaminated Gomel region. The method tentatively called "case-control" showed reliable differences in thyroid dose values for carcinomas with RET/PTC and without those. The versatility of changes was found: the lack of RET/PTC for radiotherapeutic impacts was associated with higher doses, whereas in case of the CNPP accident and for nuclear bombing victims it was the opposite. Probably, in the first case the "cellular cleaning" phenomenon after exposure to very high doses took place. Search of direct Pearson correlations between average/median thyroid doses on groups and RET/PTC frequency in carcinomas of these groups showed a high reliability for the dose-effect dependences- at the continuous dose scale (for RET/PTC in total and RET/PTC1 respectively: r = 0.830; p = 0.002 and r = 0.906; p = 0.0003); while there was no significant correlation received for RET/PTC3. When using the weighting least square regression analysis (proceeding from the number of carcinomas in samples), the specified regularities remained. Attempts to influence the strength of correlation by exception ofthe data of all the samples connected with the accident on the CNPP did not significantly reduce the strength of associations for RET/PTC in total. On the basis of ordinal scale doses (background, "low" (0.1 Gy), "middle" (0.1-1 Gy) and "large" (1-10 Gy) dose) also found was a significant correlation (Spearman) with the dose for the frequency RET/PTC in total (r = 0.736; p = 0.0098), but for certain types of rearrangements the results were reverse to the previous analysis (the effect was significant only for the RET/PTC3: r = 0.731; p = 0.024). The linear dose-response trends of the Cochrane-Armitage-test for the frequency of RET/PTC in total, RET/PTC1 and RET/PTC3 depending on the dose to the thyroid in the ordinal scale were registered (p, respectively: < 0.0001 < 0.0001 and 0.007). Thus; after more than 20 years of the molecular and epidemiological research of RET/PTC in thyroid radiogenic carcinomas the comprehensive evidence of the dose-effect dependence existence indicating a real relationship between the studied parameters and a radiation factor was obtained for the first time.

OUR EXPERIENCE OF OPTIMIZATION AND LEGITIMIZATION OF HEART TEAM WORK (MEDICAL CONSULTATION FOR DETERMINATION OF TREATMENT MANAGEMENT IN PATIENTS WITH ISCHEMIC HEART DISEASE).

The article raises the problem of optimization and legitimization of work of the Heart Team. It also described the background and international experience, provided an overview of the recent international guidelines in relation to management of revasculization in patients with stable coronary artery disease. The article presents an experience of the I. P. Pavlov First Saint- Petersburg State Medical University.

[Pooled Analysis of RET/PTC Gene Rearrangement Rate in Sporadic and Radiogenic Thyroid Papillary Carcinoma].

The database of publications on molecular epidemiology of RET/PTC rearrangements in sporadic and radiogenic thyroid papillary carcinoma has been formed (197 sources at the end of 2014; coverage of 100%). Based on this database a pooled analysis of data on the rates of RET/PTC1, RET/PTC3 and RET/PTC in total was conducted. Statistical approach involves a simple pooling, as well as calculations on the models of random and fixed effects. Since almost all the strata were characterized by heterogeneity, simple pooling and random effect models were adequate. Calculations using both models led to almost identical results. For rates of RET/PTC1, RET/PTC3 and RET/PTC in total with respect to formed carcinoma striations the following values (pooling, in %) were obtained: sporadic, total--13.2; 8.9; 21.2; sporadic, adults--13.3; 9.9; 21.1; sporadic, children--22.4; 17.5; 44.5; radiogenic, total--20.9; 20.3; 40.4; radiotherapy (exposure in childhood)--31.1; 11.8; 42.5; children affected after the Chernobyl accident--19.9; 23.6; 46.1; radiological incidents (exposure in adulthood)--19.9; 7.7; 18.4. Statistically proven is the reliability of differences of carcinoma indicators for children compared with adults (both sporadic and radiogenic tumors) and for radiogenic cancer compared with sporadic. The greatest increase in rate after irradiation was found for RET/PTC1, previously characterized in vitro as one of radiogenic types of RET/PTC.

[RET/PTC Gene Rearrangements in the Sporadic and Radiogenic Thyroid Tumors: Molecular Genetics, Radiobiology and Molecular Epidemiology].

A review of molecular genetic, radiobiological and molecular epidemiological studies of gene (chromosome) rearrangements RET/PTC in the cells of the thyroid gland as well as the laws in relation to radiation exposure in vitro, in vivo and human populations identified with them are submitted. The data on the c-RET gene and its chimeric constructs with the gene-donors (RET/PTC rearrangements) are considered. The information about the history of the RET/PTC discovery, their types, carcinogenic potential and specificity both to tumor and non-tumor thyroid disease especially for papillary thyroid carcinoma are provided. The data (seven studies) on the induction of RET/PTC after irradiation of tumor and normal thyroid cells in vitro and mice are reviewed. The mechanisms of RET/PTC induction may be associated with DNA double strand breaks and oxidative stress. Some information (three publications) about the possibility of RET/PTC induction by low doses of radiation with low LET (to 0.1 Gy) is given and it is concluded that their potential evidentiary is generally weak. The achievements in the molecular epidemiology of RET/PTC frequency for exposed and unexposed cohorts are stated. At the same time it is noted that, despite the vast array. of data accumulated from 30 countries of the world and more than 20 years of research, the formed provisions are weakly confirmed statistically and have no base corresponding to the canons of evidence-based medicine. The possibility of use of the RET/PTC presence or their frequencies as markers of the papillary thyroid carcinomas and, specifically, their radiogenic forms, is considered. In the first case the answer may be positive, while in the second, the situation is characterized by uncertainty. Based to the above mentioned we came to a conclusion about the need of a pooled or meta-analysis of the totality of the published data.

The risk of radiation-induced cerebrovascular disease in Chernobyl emergency workers.

The paper deals with estimating radiation risks of non-cancer diseases of the circulatory system among the Chernobyl emergency workers based on data from the Russian National Medical and Dosimetric Registry. The results for the cohort of 61,017 people observed between 1986 and 2000 are discussed. These are essentially updated results for the similar cohort that was studied by authors earlier in 1986-1996. Newly discovered is the statistically significant dose risk of ischemic heart disease [ERR Gy = 0.41, 95% CI = (0.05; 0.78)]. Confirmation is provided for the existence of significant dose risks for essential hypertension [ERR Gy = 0.36, 95% CI = (0.005; 0.71)] and cerebrovascular diseases [ERR Gy = 0.45, 95% CI = (0.11; 0.80)]. In 1996-2000, the assessed ERR Gy for cerebrovascular diseases was 0.22 with 95% CI = (-0.15; 0.58). Special consideration is given to cerebrovascular diseases in the cohort of 29,003 emergency workers who arrived in the Chernobyl zone during the first year after the accident. The statistically significant heterogeneity of the dose risk of cerebrovascular diseases is shown as a function of the duration of stay in the Chernobyl zone: ERR Gy = 0.89 for durations of less than 6 wk, and ERR Gy = 0.39 on average. The at-risk group with respect to cerebrovascular diseases are those who received external radiation doses greater than 150 mGy in less than 6 wk [RR = 1.18, 95% CI = (1.00; 1.40)]. For doses above 150 mGy, the statistically significant risk of cerebrovascular diseases as a function of averaged dose rate (mean daily dose) was observed: ERR per 100 mGy d = 2.17 with 95% CI = (0.64; 3.69). The duration of stay within the Chernobyl zone itself, regardless of the dose factor, had little influence on cerebrovascular disease morbidity: ERR wk = -0.002, with 95% CI = (-0.004; -0.001). The radiation risks in this large-scale cohort study were not adjusted for recognized risk factors such as excessive weight, hypercholesterolemia, smoking, alcohol consumption, and others.

Time trends of thyroid cancer incidence in Ukraine after the Chernobyl accident.

The rate of childhood thyroid cancer incidence observed in northern Ukraine during the period 1986-1998 is described as a function of time-since-exposure, age-at-exposure, and sex. Conclusions are drawn for the excess absolute risk per dose: after a minimal latency period of about three years it shows a linear increase with time-since-exposure for at least nine years. It is roughly constant in age-at-exposure, up to 15 years. For girls exposed very young it is about a factor 2 larger than for boys. For children exposed at age 16-18 this ratio increases to about 5. The thyroids of young children are not more sensitive to radiation dose than those of older ones in absolute risk in northern Ukraine in the currently used data set. As the background is increasing with age, a constant absolute risk gives a decreasing relative risk.

Specific features of electron distributions at altitudes of 400 km.

New experimental data obtained on the orbital station 'MIR' in 1991 during solar maximum are discussed. Electron fluxes with Ee>75 keV were registered for three different directions as well as for electrons with Ee>300 and 600 keV. Spatial and time distributions of electron fluxes in the trapping region are presented. In the inner radiation belt an additional maximum is observed at L=1.25-1.35, and the fluxes in the 22-05h MLT interval are 2-3 orders of magnitude smaller, than during other local times. In this region a flattening of the electron spectrum is observed. The results obtained were compared with the AE-8 model.

Leukaemia and thyroid cancer in emergency workers of the Chernobyl accident: estimation of radiation risks (1986-1995).

This work focuses on the direct epidemiological assessment of the risks of radiation-induced leukaemia and thyroid cancer in emergency workers (EW) after the Chernobyl accident. The Russian National Medical Dosimetric Registry (RNMDR) contains data for 168,000 EW as of January 1, 1996. The analysis relates to 48 leukaemias and 47 thyroid cancers, diagnosed and verified. Radiation risks are estimated by comparing the EW data with national data for a male population of the same age distribution. For leukaemia, an excess relative risk per Gy (ERR/Gy) of 4.30 (95% CI: 0.83, 7.75) is obtained, while the excess absolute risk per 10(4) person-years (PY) Gy (EAR/10(4)PY Gy) is found to be 1.31 (95% CI: 0.23, 2.39); for thyroid cancer an ERR/Gy of 5.31 (95% CI: 0.04, 10.58) is obtained, and an EAR/10(4)PY Gy of 1.15 (95% CI: 0.08, 2.22).

Thyroid cancer among "liquidators" of the Chernobyl accident.

In 1986, immediately after the Chernobyl accident, the USSR Ministry of Health adopted a large scale programme of establishing an All-Union Distributed Registry of persons affected by radiation due to the accident. The registry was based at the Medical Radiological Research Centre of the Russian Academy of Medical Sciences (MRRC RAMS). In 1992, when the USSR was dissolved, this registry database contained information on 659,000 persons, including 284,000 Chernobyl accident emergency workers ("liquidators"). Currently, the Russian National Medical Dosimetric Registry (RNMDR) contains data on 435,276 persons, including 167,862 liquidators. This paper reviews the data for 47 verified thyroid cancers in the liquidator subgroup of the RNMDR. Analyses show that there is an excess relative risk of thyroid cancer per Gy of 5.31 (95% confidence intervals 0.04 and 10.58) and an excess absolute risk of thyroid cancer per 10(4) person-years per Gy of 1.15 (95% confidence intervals 0.08 and 2.22).

Succinyl phosphonate inhibits alpha-ketoglutarate oxidative decarboxylation, catalyzed by alpha-ketoglutarate dehydrogenase complexes from E. coli and pigeon breast muscle.

Effects of a set of alpha-ketoglutarate phosphoanalogues on the activity of alpha-ketoglutarate dehydrogenase (EC 1.2.4.2) complexes from E. coli and pigeon breast muscle, as well as on alpha-ketoglutarate dehydrogenase isolated from the pigeon breast muscle, have been studied. alpha-Ketoglutarate phosphoanalogues (succinyl phosphonate and its monomethyl ester) were found to be effective inhibitors of alpha-ketoglutarate oxidative decarboxylation, catalyzed by both muscle and bacterial alpha-ketoglutarate dehydrogenase complexes, as well as muscle alpha-ketoglutarate dehydrogenase. The ability of glutamate phosphoanalogues to inhibit alpha-ketoglutarate oxidative decarboxylation has been shown in E. coli extract and a model system.

Inhibition of pigeon breast muscle alpha-ketoglutarate dehydrogenase by phosphonate analogues of alpha-ketoglutarate.

Succinylphosphonate (SP) is a powerful inhibitor of alpha-ketoglutarate dehydrogenase (KGD). Methylation of the phosphonate reduces its inhibitory effect. The complex of KGD with SP undergoes a kinetically slow transition similar to the process observed during catalysis. alpha-Ketoglutarate binds to the enzyme-inhibitor complex, preventing its isomerisation.