UDC 618.145-007.61

DOI: 10.20969/VSKM.2019.12(2).7-11

 RISK FACTORS AND PROGNOSTIC INDICATORS OF ATYPICAL ENDOMETRIAL HYPERPLASIA

AMIRASLANOV AKHLIMAN T., academician, D. Med. Sci., Head of the Department of oncology of Azerbaijan Medical University, Azerbaijan Republic, AZ1078, Baku, S. Vurgun str., 208, tel. (+994) 12541-59-77 (102)

SAFAROVA SAMIRA I., oncologist of the Oncology Clinic of Azerbaijan Medical University, Azerbaijan Republic, AZ1078, Baku, S. Vurgun str., 208, tel. (+994) 12541-59-77 (135)

Abstract. Aim. To study risk factors, prognostic indicators of atypical endometrial hyperplasia, as well as the methods for prevention of the disease. Material and methods. The study included 35 patients admitted to gynecology department at the oncology clinic with a diagnosis of atypical endometrial hyperplasia in 2016–2017. All of the patients with hyperplasia have undergone clinical and laboratory examination and diagnostic curettage. In our study the age of the patients with a diagnosis of atypical endometrial hyperplasia ranged from 39 to 56 years. Results and discussion. Atypical endometrial hyperplasia was diagnosed in 8 patients among 10 of menopausal and menopausal age upon the visit for uterine bleeding (80%). Most of the patients examined (28 patients, 80%) underwent planned surgical treatment. The remaining cases of hospitalization (7 patients, 20%) were the patients admitted to the hospital emergency with uterine bleeding. One of the typical symptoms in the history was meno- and metrorrhagia, which was observed in more than 1/2 cases of atypical endometrial hyperplasia. Among patients with atypical endometrial hyperplasia there were 11 (31,5%) with obesity, 13 (37,2%) with hypertension and 11 (31,5%) with diabetes. Pathological diffuse or focal proliferation, which leads to damage of the glandular structures and its stromal component to a lesser extent, occurs in endometrial hyperplastic processes. As a result, stromal swelling and gland enlargement might be developing. Conclusion. Prognosis and prevention of the disease depend on the etiological and genetic factors. Depending on the early diagnosis of the tumors of the female reproductive system organs, five-year survival is seen in 75%.

Key words: atypical endometrial hyperplasia, uterine cancer, endometrial cancer, risk factors.

For reference: Amiraslanov AT, Safarova SI. Risk factors and prognostic indicators of atypical endometrial hyperplasia. The Bulletin of Contemporary Clinical Medicine. 2019; 12 (2): 7–11. DOI:  10.20969/VSKM.2019.12(2).7-11.

REFERENCES

 ACTIVITY ANALYSIS FOR RENDERING OUTPATIENT SERVICE AT MEDICAL UNITS OF THE MINISTRY OF INTERNAL AFFAIRS OF THE RUSSIAN FEDERATION IN 2013–2017

BERSENEVA EVGENIA A., ORCID ID: 0000-0003-3481-6190; D. Med. Sci., the Head of the Center of the higher and additional professional education of National Research Institute of Public Health named after N.A. Semashko, Russia, 105064, Moscow, Vorontsovo Pole str., 12/1, tel. +7(916)216-84-59, e-mail: eaberseneva@gmail.com

MENDEL SERGEY A., ORCID ID: 0000-0001-7679-7106; C. Med. Sci., the Head of Clinical hospital of the Ministry of Internal Affairs of the Russian Federation in Moscow, Russia, 127299, Moscow, Novayа Ipatovka str., 3a, tel. +7(916)076-46-41, е-mail: 89160764641@mail.ru

TAIROVA RAISA T., ORCID ID: 0000-0002-4174-7114; C. Med. Sci., senior researcher of National research institute of cerebrovascular disorders and stroke of Pirogov Russian National Research Medical University, Russia, 117997, Moscow, Ostrovitianov str. 1, tel. +7(926)226-59-88, e-mail: tairova-r@mail.ru

SHKARIN VLADIMIR V., ORCID ID: 0000-0002-4009-9733; C. Med. Sci., the Head of the Department of public health and health management of faculty of physician advanced training of Volgograd State Medical University, Russia, 400131, Volgograd, Pavshih boytsov square, 1, tel. +7(902)311-83-66, e-mail: vlshkarin@mail.ru

KURAKOV DMITRY A., ORCID ID: 0000-0002-7753-2537; the Head of the Department of demographic policy of Health Committee of the Volgograd region, Russia, 400001, Volgograd, Raboche-Krestyanskaya str., 16,
tel. +7(927)252-52-31, e-mail: dkurakov@yandex.ru

SAVOSTINA ELENA A., ORCID ID: 0000-0002-2039-4639; D. Med. Sci., associate professor of the Department of medical statistics and informatics of Russian Medical Academy of Postgraduate Education, Russia,
123242, Moscow, Barrikadnaya str., 2/1, bild. 1, tel. +7(916)486-50-50, е-mail: eas-m@mail.ru

Abstract. Aim. Analysis of the outpatient activities at medical units of the Ministry of Internal Affairs of the Russian Federation for the period 2013–2017 was performed. Material and methods. The analysis was performed based on the indicators characterizing the serviced population and the volume of medical outpatient care. The indicators were composed according to dynamics and the regional aspects via lexical analysis of medical records. The data was generated on the basis of statistical reports generated at the medical units of the Ministry of Internal Affairs of Russia for the period 2013–2017. Results and discussion. An increase in the number of persons to be assigned for medical service was revealed (the figure exceeded 2,9 million people by the end of 2017, which was 90,1% compared to the number of persons in this group in 2013). Significant differentiation and multidirectional dynamics of medical outpatient care indicators were revealed at the medical units (subjects of the Russian Federation). A positive trend of the increase in the proportion of persons assigned for medical care, and of the total number of persons, who require medical care, is seen. Conclusion. The outpatient activities at the medical units of the Ministry of Internal Affairs of Russia in 2013–2017 were rendered in conditions of the increase in the number and proportion of the patients assigned for the medical care as well as in the number of the visits.

Key words: statistical accounting, outpatient care, medical unit, lexical analysis.

For reference: Berseneva EA, Mendel SA, Tairova RT, Shkarin VV, Kurakov DA, Savostina EA. Activity analysis for rendering outpatient service at medical units of the Ministry of Internal Affairs of the Russian Federation in 2013–2017. The Bulletin of Contemporary Clinical Medicine. 2019; 12 (2): 11–17. DOI: 10.20969/VSKM.2019.12(2).11-17.

1. Sidorenko VA, Sukhorukov AL, Kostin NA. Sovremennoye ambulatorno-poliklinicheskoye uchrezhdeniye MVD Rossii – vedushcheye zveno yedinoy sistemy okazaniyapervichnoy meditsinskoy pomoshchi prikreplennomukontingentu [Modern outpatient polyclinic institution of the Ministry of Internal Affairs of Russia is the leading element of the unified system of primary medical care for the assigned contingent]. Meditsinskiy vestnik MVD [Medical messenger of the Ministry of Internal Affairs]. 2016; 6: 9-12.

2. Sidorenko VA. Vedomstvennomu zdravookhraneniyu MVD Rossii – 95 let [Departmental Healthcare of the Ministry of Internal Affairs of Russia is 95 years old]. Vestnik sovremennoy klinicheskoy meditsiny [The Bulletin of Contemporary Clinical Medicine]. 2016; 9 (6): 9-12.

3. Sidorenko VA, Zubritskiy VF. Razvitiye vedomstvennoymeditsiny – osnova ukrepleniya zdorov’ya sotrudnikovorganov vnutrennikh del [The development of departmental medicine is the basis of health promotion for the officers of the internal affairs bodies]. Meditsinskiy vestnik MVD [Medical messenger of the Ministry of Internal Affairs]. 2017; 2 (87): 2-4.

4. Rosstat [Rosstat]. Zdravookhraneniye Rossii – 2015 god; Statisticheskiy sbornik [Healthcare of Russia – 2015; The statistical compilation]. 2016; http://www.gks.ru/bgd/regl/ b15_34/Main.htm

5. Rosstat [Rosstat]. Zdravookhraneniye Rossii – 2017 god; Statisticheskiy sbornik [Healthcare of Russia – 2017; The statistical compilation]. 2018; http://www.gks.ru/bgd/regl/ b17_34/Main.htm

6. Rosstat [Rosstat]. Demograficheskiy yezhegodnik Rossii [Demographic Yearbook of Russia]. 2018; http://www.gks. ru/wps/wcm/connect/rosstat_main/rosstat/ru/statistics/ publications/catalog/doc_1137674209312

7. Berseneva YeA, Kon’kov AV, Mendel’ SA, Savostina YeA. Osnovnyye napravleniya modernizatsii zdravookhraneniya MVD Rossii i puti ikh realizatsii [The main directionsof modernization of public health services of theMinistry of Internal Affairs of Russia and the ways of their implementation]. Voronezh: Perspektivy razvitiya sovremennoy meditsiny: sbornik nauchnykh trudov po itogam mezhdunarodnoy nauchno-prakticheskoy konferentsii (11 dekabrya 2017 goda) [Voronezh: Prospects for the development of modern medicine; Collection of scientific papers on the results of the international scientific-practical conference (December 11, 2017)]. 2018; http://izron.ru/articles/perspektivy-razvitiya-sovremennoy-meditsiny-sbornik-nauchnykh-trudov-po-itogam-mezhdunarodnoy-nauchn/sektsiya-26-obshchestvennoe-zdorove-i-zdravookhranenie-spetsialnost-14-02-03/ osnovnye-napravleniya-modernizatsii-zdravookhraneniya-mvd-rossii-i-puti-ikh-realizatsii/

8. Berseneva YeA, Mendel’ SA, Savostina YeA. Infor-matsionno-statisticheskoye obespecheniye meditsinskoy sluzhby ministerstva vnutrennikh del Rossiyskoy Federatsii [Information and statistical support of the medical service of the Ministry of Internal Affairs of the Russian Federation]. Sankt-Peterburg: Aktual’nyye voprosy meditsiny v sovremennykh usloviyakh; sbornik nauchnykh trudov po itogam mezhdunarodnoy nauchno-prakticheskoy konferentsii (11 yanvarya 2018 goda) [St Petersburg: Actual questions of medicine in modern conditions; Collection of scientific papers on the basis of the international scientific-practical conference (January 11, 2018)]. 2018; 5: 39-41.

9. Chechenin GI, Belyavskiy AI, Zhilina NM. Mediko-ekonomicheskaya i sotsial’naya effektivnost’ modeliekspertizy vremennoy netrudosposobnosti [Medico-economic and social effectiveness of the model for theexamination of temporary disability]. Sibirskiy nauchnyy meditsinskiy zhurnal [Siberian Scientific Medical Journal]. 2007; 1: 35-37.

10. Tairova RT, Berseneva YeA, Ushenin VV. Analiz kachestva okazaniya meditsinskoy pomoshchi naseleniyu Rossiyskoy Federatsii: vozmozhnyye puti optimizatsii [Analysis of the quality of medical care to the population of the Russian Federation: possible ways to optimize]. Vestnik sovremennoy klinicheskoy meditsiny [The Bulletin of Contemporary Clinical Medicine]. 2017; 10 (6): 75-80.

DOI: 10.20969/VSKM.2019.12(2).17-23

DOI: 10.20969/VSKM.2019.12(2).23-28

1. Shishlo LM, Prohorova VI, Zajcev LA. Osobennosti gemostaza pri pervichnom rake pecheni [Features of hemostasis in primary liver cancer]. Onkologicheskij zhurnal [Cancer Journal]. 2017; 11(13): 78-85.

2. Bilalova AR, Makashova VV, Aleshina NI. Osobennostisistemy gemostaza u bol’nyh hronicheskimi gepatitamii cirrozami pecheni [Features of hemostatic system in patients with chronic hepatitis and cirrhosis]. Infekcionnye bolezni [Infectious disease]. 2015; 13 (3): 37-45.

3. Morozov YuA, Mednikov RV, Charnaya MA. Narusheniyasistemy gemostaza pri patologii pecheni i ih diagnostika[Disorders of the hemostatic system in liver pathology and their diagnosis]. Gemorragicheskie diatezy, trombozy, trombofilii [Hemorrhagic diathesis, thrombosis, thrombophilia]. 2014; 1: 162–174.

4. Yagoda PV, Koroj PV. Patologiya pecheni i funkciya trombocitov (kliniko-patogeneticheskij analiz) [Liverpathology and platelet function (clinical and pathogeneticanalysis)]. Stavropol’: StGMA [Stavropol: StGMA]. 2008; 273 р.

5. Shklyaev AE, Malahova IG. Prognosticheskoe znacheniepokazatelej gemostaza pri zabolevaniyah pecheni[Prognostic value of hemostatic parameters in liver diseases]. Tromboz, gemostaz i reologiya [Thrombosis, hemostasis and rheology]. 2016; 67 (3): 462–464.

6. Rupasova AR, Sorokina AYu. Virusnye gepatity [Viral hepatitis]. Mezhdunarodnyj studencheskij nauchnyj vestnik [International student scientific Bulletin]. 2018; 4: 317–320.

7. Krutov IV, Davydkin IL, Hajretdinov RK, Kosyakova YuA, Nizyamova AR. Narushenie gemostaza u bol’nyhhronicheskim gepatitom i cirrozom pecheni virusnojetiologii (HCV), oslozhnennyh trombocitopeniej [Hemostasis disorders in patients with chronic hepatitis and liver cirrhosis of viral etiology (HCV) complicated by thrombocytopenia]. Vestnik RUDN, seriya Medicina [Bulletin of RPFU, series Medicine]. 2010; 3: 139–141.

8. Maleev VV, Polyakova AM, Kravchenko AV. Narusheniya gemostaza pri infekcionnyh zabolevaniyah [Hemostatic disorders in infectious diseases]. Moskva: De-Novo [Moscow: De-Novo]. 2005; 160 p.

9. Kozlovskij VI, Kovtun OS, Serouhova OP, Detkovskaya IN, Kozlovskij IV. Metody issledovaniya i klinicheskoe znachenie agregacii trombocitov; fokus na spontannuyu agregaciyu [Research methods and clinical significance of platelet aggregation; focus on spontaneous aggregation]. Vestnik VGMU [Bulletin of Voronezh state University]. 2013; 3: 79 –91.

10. Ruzov IV, Komarova LK, Krest’yaninov MV, Shchipanova EV, Nizamova LT. Ocenka agregacii trombocitov iperekisnogo okisleniya lipidov u pacientov perenesshihaortokoronarnoe shuntirovanie [Evaluation of plateletaggregation and lipid peroxidation in patients undergoingcoronary artery bypass grafting]. Ul’yanovskij Mediko – biologicheskij zhurnal [Ulyanovsk Medico – biological journal]. 2014; 2: 8–13.

11. Tugushev AS. Cirroz pecheni i tromboz [Cirrhosis of the liver and thrombosis]. Zaporozhskij medicinskij zhurnal [Zaporizhzhya medical journal]. 2010; 12 (3): 78–83.

12. Enaleeva DSh, Beshimova DT. Zavisimost’ aktivnostialaninaminotransferazy ot pola pacienta pri virusnyhgepatitah [The dependence of alanine aminotransferase on the gender of the patient with viral hepatitis]. Kazanskiy meditsinskiy zhurnal [Kazan Medical Journal]. 2012; 3 (93): 456–457.

13. Enaleeva DSh, Fazylov VH. Rol’ vrachej pervichnogozvena v diagnostike i dispanserizacii bol’nyh hronicheskimivirusnymi gepatitami V, S i D: Lekciya [The role of primarycare physicians in the diagnosis and clinical examinationof patients with chronic viral hepatitis B, C and D: Lecture]. Kazanskiy meditsinskiy zhurnal [Kazan Medical Journal]. 2014; 3 (95): 439-445.

14. Prati D, Taioli E, Zanella А. Updated definitions of healthyranges for serum alanine aminotransferase levels. Ann Intern Med. 2002; 1 (137): 1–10.

UDC 618.1-006-053.87

 INCIDENCE AND COMBINATION OF GENITALIA NEOPLASTIC PROCESSES IN POST-MENOPAUSAL PERIOD

GARASHOVA MINA A., C. Med. Sci., associate professor of the Department of obstetrics and gynecology No 1 of Azerbaijan Medical University, Azerbaijan, AZ1000, Baku, Kh. Shushinsky str., 24, tel. (+994) 215-49-01, e-mail: minagarashova@mail.ru

Abstract. Aim. The aim of the study was to assess the incidence and combination of genital tumors in post-menopausal period. Material and methods. The study included 306 women with benign and malignant genital tumors in the post- menopausal period. Mean age of the examined women was (59,3±0,4) years (48–83). The examination included clinical, functional, biochemical, hormonal, morphological, and radiological study methods, including position emission tomography. Results and discussion. In the post-menopausal period the women with genital tumors are most often being diagnosed with ovarian cancer (24,8%), endometrial hyperplastic processes (21,2%), endometrial cancer (16,3%), and uterine myoma (15,4%). The incidence of combined ovarian cancer with other genital neoplastic processes is 18,6%. In 72,2% of cases ovarian cancer is combined with uterine myoma. In 27,8% of cases it is combined with endometrial hyperplastic processes. The incidence of endometrial hyperplastic processes combined with other genital tumors is 35,4%. The most common combination of endometrial hyperplastic processes is with uterine myoma. The incidence of endometrial hyperplasia combined with uterine myoma is within 72,7% to 100%. In post-menopausal period the incidence of uterine fibroids combined with associated genital tumors is determined to be within 38,3%. Diffuse endometrial hyperplasia (83,3%), ovarian tumor masses (1,1%) and focal endometrial hyperplasia (5,5%) are most frequently detected in patients with uterine myoma. 69,2% of cases in women with postmenopausal cervical cancer are associated with genital tumors. Uterine fibroids are determined in 66,2%, while endometrial hyperplastic processes are seen in 33,3%. Conclusion. The study suggests that the post-menopausal period is associated with a high risk of reproductive system neoplastic process development.

Key words: post-menopausal period, uterine fibroids, ovarian cancer, endometrial cancer, endometrial hyperplasia, cervical cancer.

For reference: Garashova MА. Incidence and combination of genitalia neoplastic processes in post-menopausal period. The Bulletin of Contemporary Clinical Medicine. 2019; 12 (2): 28–32. DOI: 10.20969/VSKM.2019.12(2).28-32.

1. Breusenko VG, Savel’eva GM., Golova YuA. Techeniegiperplasticheskih processov endometriya v periodepostmenopauzy [The course of endometrial hyperplastic processes in the postmenopausal period]. Akusherstvo i ginekologiya [Journal of Obstetrics and Gynecology]. 2009; 4: 19-24.

2. Ahundova NE, Gasanova NN, Alieva EM, Sadyhova LI. Sostoyanie gipotalamo-gipofizarnoj sistemy u zhenshchin s hirurgicheskoj menopauzoj [The state of the hypothalamic-pituitary system in women with surgical menopause]. Saglamlyg [Health]. 2009; 4: 38-41.

3. Ragimova VV, Alieva EM, Sultanova SG. Osobennostiproyavlenij klimaktericheskogo sindroma u zhenshchin v postmenopauzal’nyj perid v sovremennyh usloviyah[Features of the manifestations of menopausal syndrome in women in postmenopausal periods in modern conditions]. Zdorov’e zhenshchiny [Health of a woman]. 2018; 1 (127): 68-72.

4. Rymashevskij AN, Vorob’ev SV, Andryushchenko YuA. Patogeneticheskie osobennosti razvitiya polipovendometriya u bol’nyh s ozhireniem v postmenopauze[Pathogenetic features of the development of endometrial polyps in patients with obesity in postmenopause]. Vestnik novyh medicinskih tekhnologij [Bulletin of new medical technologies]. 2011; 18 (4): 109-111.

5. Chestnova GP, Kulyushina EA, Abashin VG, Efimenko NA. Osobennosti diagnostiki giperplasticheskih processov vendometrii u zhenshchin v period dlitel’noj postmenopauzy[Features of diagnosis of hyperplastic processes in the endometrium in women in the period of prolonged postmenopause]. Klinicheskaya Medicina [Clinical Medicine]. 2013; 9: 46-47.

6. Cramer SF, Mann L, Calianese E, Daley J, Williamson K. Association of seedling myomas with myometrial hyperplasia. Am J Human Pathology. 2009; 40 (2): 218-225.

7. Imayama I, Alfano CM, Kong A, Foster-Schubert KE. Dietary weight loss and exercise interventions effects on quality of life in overweight/obese postmenopausal women a randomized controlled trial. Int J Behav Nutr Phys Act. 2011; 8: 118-121.

8. Freeman EW, Sammet MD, Lin H, Liu Z, Gracia CR. Duration of menopausal hot flushes and associated risk factors. Am J Obstet Gynecol. 2011; 117: 1095-1104.

9. Tsilidis KK, Allen NE, Key TJ, Dossus L, Kaaks R.Menopausal hormone therapy and risk of ovarian cancerin the European prospective investigation into cancer and nutrition. Am J Cancer Causes Control. 2011; 22: 1075-1084.

10. IARC. Biennial Report 2008-2009. Lyon: Am J International Agency for Research on Cancer. 2009; 145 p.

11. Vance S, Yechieli R, Cogan C, Hanna C. The prognostic significance of age in surgically staged patients with type II endometrial carcinoma. Am J Gynecol Oncol. 2012; 126: 16-19.

1. Dolgushina VF, Shishkova YuS, Grafova ED, et al. Struktura infekcionnoj patologii vlagalishha i shejki matki u zhenshhin v I trimestre beremennosti [The vagina and uteral cervix infectious pathology structure in women in I trimester of pregnancy]. Sovremennye problemy nauki i obrazovanija [Modern problems of science and education]. 2018; 1: 69.

2. Kurnosenko IV, Dolgushina VF, Sandakova EA. Infekcionnaja patologija reproduktivnogo trakta u beremennyh zhenshhin [Infectious pathology of the reproductive tract in pregnant women]. Chelovek; Sport; Medicina. [Human; Sport; Medicine]. 2017; 17 (1): 46-56.

3. Hamad’janov UR, Rusakova LA, Hamad’janova AU. Vnutriutrobnoe inficirovanie ploda: sovremennyj vzgljad na problemu [Intrauterine fetal infection: the present view of the problem]. Rossijskij vestnik akushera-ginekologa [Russian Bulletin of obstetrician-gynecologist]. 2013; 5: 16-19.

4. Hamoshina MB, Tulupova MS, Chotchaeva AI, et al. Korrekcija i profilaktika narushenij biocenoza vlagalishha u beremennyh [Treating and prevention of vaginal imbalance in pregnant women]. Doktor Ru [Doctor Ru]. 2012; 7 (75): 78-79.

5. Radzinskij VE, Ordijanc IM, Chetvertakova JeS, et al. Dvuhjetapnaja terapija vaginal’nyh infekcij [Two-stage therapy for vaginal infections]. Akusherstvo i ginekologija [Obstetrics and gynecology]. 2011; 5: 78-81.

6. Kira EF. Rol’ probiotikov v lechenii infekcij vlagalishha [Role of probiotics in the treatment of vaginal infections]. Rossijskij vestnik akushera-gignekologa [Russian Bulletin of obstetrician-gynecologist]. 2010; 5: 33-39.

7. Petersen EE, Magnani P. Efficacy and safety of vitamin C vaginal tablets in the treatment of non-specific vaginitis. A randomised, double blind, placebo-controlled study. Eur J Obstet Gynecol Reprod Biol. 2004; 117 (1): 70–75.

8. Kira EF, Artymuk NV, Savicheva AM, et al. Primeneniemolochnoj kisloty v sochetanii s glikogenom dlja lechenijabakterial’nogo vaginoza [The use of lactic acid in combination with glycogen in the treatment of bacterial vaginosis]. Ginekologija [Gynecology]. 2015; 02: 93-96.

9. Podzolkova NM, Sozaeva LG, Ivanycheva ID, et al. Vozmozhnosti odnojetapnoj terapii bol’nyh s bakterial’nym vaginozom: rezul’taty mnogocentrovogo otkrytogo prospektivnogo pilotnogo issledovanija [Possibilities of one-stage therapy in patients with bacterial vaginosis: results of a multicenter open-label, prospective, pilot study]. Rossijskij vestnik akushera-ginekologa gignekologa [Russian Bulletin of obstetrician-gynecologist]. 2015; 15 (3): 70-75.

10. Nivoliez A, Camares O, Paquet-Gachinat M, et al. Influenceof manufacturing processes on in vitro properties of theprobiotic strain Lactobacillus rhamnosus Lcr35®. Journal of Biotechnology. 2012; 160: 236– 241.

11. Mendling W, Weissenbacher ER, Gerber S, et al. Use of locally delivered dequalinium chloride in the treatment of vaginal infections: a review. Arch Gynecol Obstet. 2016; 293: 469-484.

12. Bashmakova NV, Volkova NJu, Gnatko EP, et al. Probiotik dlja profilaktiki recidivov vul’vovaginal’nogo kandidoza(rezul’taty mezhdunarodnogo mnogocentrovogo otkrytogoissledovanija revolakt) [Probiotic for the recurrencesof vulvovaginal candidiasis prevention (results of aninternational multicentre open-label study of revolakt]. Akusherstvo i ginekologija [Obstetrics and gynecology]. 2017; 6: 135-142.

13. Dan’kova IV, Chistjakova GN, Pestrjaeva LA, et al. Ocenka jeffektivnosti intravaginal’nogo preparata, soderzhashhegokul’turu laktobacill pri recidivirujushhem vul’vovaginal’nomkandidoze [Evaluation of the efficacy of an intravaginalpreparation containing a culture of lactobacilli in recurrentvulvovaginal candidiasis] .Ural’skij medicinskij zhurnal [Ural medical journal]. 2016; 11 (144): 9-11.

UDC 615.322(549.1)

 PAKISTANI MEDICINAL PLANTS: MIRACLE IN MEDICAL SCIENCE

NIAZI AKBAR KHAN, MBBS, the Chairman of Islamabad Medical & Dental College and Dr. Akbar Niazi Teaching Hospital, Pakistan, Islamabad, Bharakahu, Wadi-ul-Ilm Main Murree Road, tel. +92-314-224-34-15

MASTOI SHAH MURAD, MBBS, M. Phil, professor, the Head of the Department of pharmacology of Islamabad Medical & Dental College and Dr. Akbar Niazi Teaching Hospital, Pakistan, Islamabad, Bharakahu, Wadi-ul-Ilm Main Murree Road, tel. +92-314-224-34-15, e-mail: shahhmurad65@gmail.com

EJAZ FATIMA, associate professor of the Department of pharmacology of Lahore Medical Dental College, Pakistan, Lahore 53400, Tulspura, North Canal Bank

GHAFFAR ABDUL, CWO of Islamabad Medical & Dental College in Islamabad, Pakistan, Islamabad, Bharakahu, Wadi-ul-Ilm Main Murree Road

Abstract. Internal, plasma cholesterol is one of several clear risk factors in the development of atherosclerosis. There’s «bad» cholesterol, low density lipoproteins, and then there’s «really bad» cholesterol, oxidized low density lipoproteins. Oxidized low density lipoproteins are accumulated without restriction by macrophages, captured by scavenger receptors (e.g., CD36 and SR-A) and promotes differentiation to foam cells. This indicates that the generation of oxidants that oxidized low density lipoprotein is a critical step in the production of really bad cholesterol. Aim. This study was conducted to see hypolipidemic potential of two medicinal herbs. Material and methods. The research work was single blind placebo-controlled, conducted at Jinnah Hospital, Lahore It was conducted from January 2018 to June 2018. 75 already diagnosed primary and secondary hyperlipidemic patients were selected with age range from 17 to 65 years. All patients were divided in three groups (group I, group II, group III), 25 in each group. All participant’s baseline lipid profile data were taken and filed in specifically designed Performa, at start of taking medicine. 25 patients of group I were advised to take 10 grams of Flaxseeds in three divided doses after meal. 25 patients of group II were advised to take Ajwain seeds 10 grams in three divided doses after each meal for two months. 25 patients of group III were provided placebo capsules, (containing grinded rice), taking one capsule after each meal. All participants were advised to take these medicines for eight weeks. Their low density lipoproteins – cholesterol, and high density lipoproteins – cholesterol was determined at the hospital laboratory. Results and discussion. In two months therapy by Flaxseeds decreased low density lipoproteins – cholesterol from (195,11±2,110) mg/dl to (190,22±3,11) mg/dl, which is significant statistically. High density lipoprotein was increased from (34,53±1,65) mg/dl to (38,97±2,29) mg/dl, which is also significant change. In two months therapy by AJWAIN, low density lipoprotein-c reduced from (201,51±2,62) mg/dl to (197,11±2,66) mg/dl, which is significant statistically. High density lipoproteins – cholesterol increased by Ajwain from (36,97±3,32) mg/dl to (37,45±1,87) mg/dl, which is insignificant statistically. Conclusion. It was concluded from this study that Flaxseeds have more effect on high density lipoproteins-c but Ajwain has lowest effect on this parameter.

Key words: cholesterol, oxidized low density lipoproteins, Flaxseeds, Ajwain seeds.

For reference: Niazi Akbar Khan, Mastoi Shah Murad, Ejaz Fatima, Ghaffar Abdul. Pakistani medicinal plants: miracle in medical science. The Bulletin of Contemporary Clinical Medicine. 2019; 12 (2): 41–44. DOI: 10.20969/ VSKM.2019.12(2).41-44.

1. Anilakumar KR, Saritha V, Khanum F, Bawa AS. Ameliorative effect of ajwain extract on hexachlorocyclohexane-induced lipid peroxidation. Food Chem Toxicol. 2009; 47: 279-282.

2. Chialva F, Monguzzi F, Manitto P, Akgül A. Essential oil constituents of Trachyspermum copticum (L) and Lipid Metabolism. J Essent Oil Res. 2012; 5: 105-106.

3. Manhas A, Farmer JA. Hypolipidemic therapy and cholesterol absorption. Curr Atheroscler Rep. 2004; 6: 89-93.

4. Chialva F, Monguzzi F, Manitto P, Akgül A. Essential oil constituents of Trachyspermum copticum (L) Link fruits. J Essent Oil Res. 2010; 5: 105–106.

5. Nagalakshmi S, Shankaracharya NB, Naik JP, Rao LJM. Studies on chemical and technological aspects of ajowan (Trachyspermum ammi syn. Carum copticum). J Food Sci Technol. 2010; 37: 277–281.

7. Singh G, Maurya S, Catalan C. Chemical, antifungal, antioxidative studies of Ajwain oil and its acetone extract. J Agric Food Chem. 2009; 52: 3292-3296.

8. Choudhury S. Composition of the seed oil of Trachyspermum ammi (L) Sprague from northeast India. J Essent Oil Res. 2013; 10: 588–590.

9. Murthy PS, Borse BB, Khanum H, Srinivas P. Inhibitory effects of Ajwain (Trachyspermum ammi) ethanolic extract on A ochraceus growth and ochratoxin production. Turk J Biol. 2009; 33: 211–217.

10. Patenaude A, Rodriguez-Leyva D, Edel AL, Dibrov E, et al. Bioavailability of a-linolenic acid from flaxseed diets as a function of the age of the subject. Euro J Clin Nutri. 2009; 63: 1123–1129.

11. Krishnamoorthy V, Madalageri MB. Bishop weeds (Trachyspermum ammi): An essential crop for north Karnatka. J Med Aromat Plant Sci. 2010; 21: 996–

12. Ishikawah T, Sega Y, Kitajima J. Water-soluble constituents of ajowan. Chem Pharm Bull. 2011; 49: 840-844.

13. Rodriguez-Leyva D, Bassett CM, Mccullough R, Pierce GN. The cardiovascular effects of flaxseed and its omega-3 fatty acid, alpha-linolenic acid. Can J Cardiol. 2010; 26: 489-496.

14. Tzang BS, Yang SF, Fu SG, Yang HC, et al. Effects of dietary flaxseed oil on cholesterol metabolism. Food Chem. 2009; 114: 1450-1455.

15. Prasad K. Hypocholesterolemic and antiatherosclerotic effect of flax lignan complex isolated from flaxseed. Atherosclerosis. 2005; 179 (2): 269-275.

16. Arjmandi B, Khan D, Juma S, et al. Whole flaxseed consumption lowers serum LDL-cholesterol and lipoprotein (a) concentrations in postmenopausal women. Nutrition Research. 2011; 18 (7): 1203-1214.

17. Cho Y, Kwon E, Kim H, et al. Low trans structured fat from flaxseed oil improves plasma and hepatic lipid metabolism. Food and Chemical Toxicology. 2009; 47 (7): 1550-1555.

18. Choudhury S. Composition of the seed oil of Trachyspermum ammi (L) Sprague from northeast India. J Essent Oil Res. 2011; 10: 588-590.

19. Nagalakshmi S, Shankaracharya NB, Naik JP, Rao LJM. Studies on chemical and technological aspects of ajowan (Trachyspermum ammi syn Carum copticum). J Food Sci Technol. 2011; 37: 277–281.

20. Jenkins D, Kendall C, Vidgen E, et al. Health aspects of partially defatted flaxseed, including effects on serum lipids, and oxidative stress: a controlled crossover trial. American Journal of Clinical Nutrition. 2010; 69 (3): 395.

21. Kelley DS, Siegel D, Vemuri M, Mackey BE. Docosahe-xaenoic acid supplementation improves fasting andpostprandial lipid profiles in hypertriglyceridemic men. Am J Clin Nutr. 2007; 86: 324-333.

22. Shahidi F, Miraliakbari H. Omega-3 fatty acids in health and disease: Part1-cardiovascular disease and cancer. J Med Food. 2004; 7: 387-401.

UDC 615.357:577.175.722

DOI: 10.20969/VSKM.2019.12(2).45-53

 CLINICAL EVIDENCE OF BIOSIMILARITY OF RINSULIN® NPH (GEROPHARM, RUSSIA) AND HUMULIN® NPH (ELI LILLY, FRANCE) MEDICATIONS BY HYPERINSULINEMIC EUGLYCEMIC CLAMP PERFORMANCE IN HEALTHY VOLUNTEERS

NOSKOV SERGEY M., D. Med. Sci., professor, scientific consultant of Clinical Hospital No 3, Russia, 150007, Yaroslavl, Mayakovsky str., 61, e-mail: noskov03@gmail.com

NAGIBIN ROMAN M., C. Med. Sci., assistant of professor of the Department of internal medicine of Yaroslavl State Medical University, Russia, 150000, Yaroslavl, Revolutsionnaya str., 5, e-mail: nagibinrm@gmail.com

LUTSKOVA LYUDMILA N., C. Med. Sci., assistant of professor of the Department of internal medicine of Yaroslavl State Medical University, Russia, 150000, Yaroslavl, Revolutsionnaya str., 5, e-mail: lluckova@yandex.ru

DRAI ROMAN V., ORCID: 0000-0003-4594-6097; C. Med. Sci., Director of «Geropharm», Russia, 191144, St. Petersburg, Degtyarny lane, 11b, e-mail: roman.drai@geropharm.com

ANDEEVA OLGA I., ORCID: 0000-0002-6759-4283; C. Pharm. Sci., medical writer of the Department of сlinical trial of «Geropharm», Russia, 191144, St. Petersburg, Degtyarny lane, 11b, e-mail: olga.avdeeva@geropharm.com

MAKARENKO IGOR E., ORCID: 0000-0003-2308-0608; C. Med. Sci., the Head of the Department of pharmacology and early phase clinical trials of «Geropharm», Russia, 191144, St. Petersburg, Degtyarny lane, 11b, e-mail: igor.makarenko@geropharm.com

Abstract. Global incidence of diabetes in the 21st century has become pandemic. Insulin therapy is the main treatment for type I diabetes, as well as the one of the most important treatment options for type II diabetes. Due to the progress in genetic engineering in the eighties, manufacturing of the insulins, which are completely identical in structure and biological properties to human pancreatic insulin, has started. One of the first medications of human insulin manufactured in Russia was Rinsulin® NPH, which is biosimilar to Humulin® NPH medication. The program of clinical trials of biosimilar insulin medications includes pharmacological studies of pharmacokinetics, pharmacodynamics and clinical safety evaluation. Aim. Rinsulin® NPH (bioanalogue) and Humulin® NPH medication (original) biosimiliarity evaluation was performed in conditions of hyperinsulinemic euglycemic clamp in healthy volunteers. Material and methods. The studywas conducted on healthy male volunteers aged from 18 to 50 years. The study design is a double-blind, randomized, crossover study of comparative drug pharmacokinetics. The drugs were injected subcutaneously into the anterior abdominal wall at a dose of 0,4 IU/kg once. Duration of blood sampling performed to determine the pharmacokinetic parameters was 24 hours. Blood insulin was determined via enzyme immunoassay. Glucose infusion rate was adjusted according to glycemic level, the data of which were used to calculate the pharmacodynamic parameters. Results and discussion. Comparability of the main pharmacokinetic and pharmacodynamic characteristics of Rinsulin® NPH and Humulin® NPH medications was noted in conditions of hyperinsulinemic euglycemic clamp in healthy volunteers. The confidence interval for the logarithmically transformed ratio of Cins.max parameter values was 85,02–111,29%, and AUCins.0-12 – 88,10–118,66%, which compiles within 80–125% limits specified by the regulatory documents on drug comparability establishment. This confirms the high similarity of the reproduced Rinsulin® NPH drug to the original medication. Of particular clinical significance is synchronous onset of drug action, the time of the maximum effect onset and the duration of action. Adverse reactions were not recorded in terms of the study. Conclusion. According to the clinical study using the method of hyperinsulinemic euglycemic clamp in healthy volunteers, Rinsulin® NPH and Humulin® NPH can be considered equivalent.

Key words: genetically engineered human insulin; biosimilar; pharmacokinetics; pharmacodynamics; hyperinsulinemic euglycemic clamp.

For reference: Noskov SM, Nagibin RM, Lutskova LN, Drai RV, Avdeeva OI, Makarenko IE. Clinical evidence of biosimilarity of Rinsulin® NPH (Geropharm, Russia) and Humulin® NPH (Eli lilly, France) medications by hyperinsulinemic euglycemic clamp performance in healthy volunteers. The Bulletin of Contemporary Clinical Medicine. 2019; 12 (2): 45–53. DOI:10.20969/VSKM.2019.12(2).45-53.

1. Dedov II, Shestakova MV. Saharnyj diabet 2 tipa: ot teorii k praktike [Type 2 diabetes: from theory to practice]. Moskva: MIA (Meditsinskoye informatsionnoye agentstvo) [Moscow: MIA (Medical Information Agency)]. 2016; 576 p.

2. King P, Peacock I, Donnelly R. The UK prospective diabetes study (UKPDS): clinical and therapeutic implications for type 2 diabetes. British journal of clinical pharmacology. 1999; 48 (5): 643-648.

3. Kalinnikova AA, Strongin LG. Saharosnizhayushchij effekt insulinov Rinsulin R i NPH v sravnenii s insulinom Aktarpid i Protafan pri odnokratnom podkozhnom vvedenii: rezul’tatyodinarnogo slepogo aktivno kontroltruemogo klinicheskogoissledovaniya [Sugar-lowering effect of insulin Rinsulin R and NPH in comparison with insulin Aktarpid and Protafan with a single subcutaneous injection: the results of a single-blind, actively controlled clinical study]. Medicinskij Al’manah [Medical Almanac]. 2011; 5 (18): 172-174.

4. Ametov AS. Terapevticheskie zadachi i vozmozhnosti ih realizacii pri saharnom diabete tipa 2 [Therapeutic tasks and the possibilities of their implementation in type 2 diabetes mellitus]. Cons Medicum. 2003; 9: 484-486.

5. Avakova KA. Optimizatsiya metodov sovremennoy insulinoterapii pri lechenii sakharnogo diabeta 1-go tipa [Optimization of modern insulin therapy methods in the treatment of type 1 diabetes mellitus]. Moskva: Rossiyskaya meditsinskaya akademiya poslediplomnogo obrazovaniya [Moscow: Russian Medical Academy of Postgraduate Education]. 2009; 125 p.

6. Committee for Medicinal products for Human Use. Guideline on non-clinical and clinical development of similarbiological medicinal products containing recombinanthuman insulin and insulin analogues. European Medicines Agency. 2015; 12 p. https://www.ema.europa.eu/en/non-clinical-clinical-development-similar-biological-medicinal-products-containing-recombinant-human

7. Committee for Medicinal products for Human Use. Guideline on similar biological medicinal products. European Medicines Agency. 2015; 7 p. https://www.ema. europa.eu/en/documents/scientific-guideline/guideline-similar-biological-medicinal-products-rev1_en.pdf

8. Committee for Medicinal products for Human Use. Guidelineon the clinical investigation of the pharmacokineticsof therapeutic proteins. European Medicines Agency. 2007; 11 p. https://www.ema.europa.eu/en/documents/ scientific-guideline/guideline-clinical-investigation-pharmacokinetics-therapeutic-proteins_en.pdf

9. Committee for Medicinal products for Human Use. Guidelineon the clinical investigation of the pharmacokineticsof therapeutic proteins. European Medicines Agency. 2005; 10 p. https://www.ema.europa.eu/en/documents/ scientific-guideline/draft-guideline-clinical-investigation-pharmacokinetics-therapeutic-proteins_en.pdf

10. Committee for Medicinal products for Human Use. Guideline on the investigation of bioequivalence. European Medicines Agency. 2010; 27 p. https://www.ema. europa.eu/en/documents/scientific-guideline/guideline-investigation-bioequivalence-rev1_en.pdf

11. Committee for Medicinal products for Human Use. Guideline on Immunogenicity Assessment of Biotechnology-derived Therapeutic Proteins. European Medicines Agency. 2015; 23 p. https://www.ema.europa.eu/en/documents/ scientific-guideline/draft-guideline-immunogenicity-assessment-biotechnology-derived-therapeutic-proteins-revision-1_en.pdf

12. Reshenie No 89 ot 3 noyabrya 2016 goda «Ob utverzh-denii pravil provedeniya issledovanij biologicheskihlekarstvennyh sredstv Evrazijskogo ekonomicheskogo soyuza», glava 15.7 «Doklinicheskaya i klinicheskaya razrabotka bioanalogichnyh (biopodobnyh) lekarstvennyh preparatov, soderzhashchih rekombinantnyj insulin i analogi insulina» [Decision No. 89 of November 3, 2016 «On Approval of the Rules for Conducting Studies of Biological Medicines of the Eurasian Economic Union», chapter 15.7» Preclinical and clinical development of bioanalogical (bio-like) drugs containing recombinant insulin and insulin analogues «]. 2016.

13. Mironov AN, Merkulov VA, et al. Razrabotka bioanalogichnyh (biopodobnyh) lekarstvennyh preparatov, soderzhashchih v kachestve farmacevticheskoj substvancii genno-inzhenernyj insulin cheloveka ili analogi insulina cheloveka; Rukovodstvo po ekspertize lekarstvennyh sredstv; Tom IV. [Development of bio-analogous (bio-like) medicinalpreparations containing as a pharmaceutical subparty thegenetically engineered insulin of human or human insulin; Guidance on the examination of medicinal products; Volume IV]. Moskva: Poligraf-plyus [Moscow: Polygraphplus]. 2014; 172 p.

14. Heinemann L, Anderson JH. Jr. Measurement of insulin absorption and insulin action. Diabetes Technol Ther. 2004; 6 (5): 698-718. doi: 10.1089/dia.2004.6.698.

15. Heise T, Zijlstra E, Nosek L, Heckermann S, Plum-Mörschel L, Forst T. Euglycaemic glucose clamp: what it can and cannot do, and how to do it. Diabetes, Obesity and Metabolism. 2016; 18 (10): 962–972. doi: 10.1111/ dom.12703.

16. Hompesch M, Klaus Rave K. An Analysis of How to Measure Glucose during Glucose Clamps: Are Glucose Meters Ready for Research? J Diabetes Sci Technol. 2008; 2: 896–898. doi: 10.1177/193229680800200522.

17. Rabiee A, Magruder JT, et al. Accuracy and reliability of the Nova StatStrip® glucose meter for real-time blood glucose determinations during glucose clamp studies. Journal of diabetes science and technology, 2010; 4 (5): 1195-1201. doi: 10.1177/193229681000400519.

18. Lindquist KA, Chow K, West A, et al. The StatStripglucose monitor is suitable for use during hyperinsulinemiceuglycemic clamps in a pediatric population. Diabetes technology & therapeutics, 2014; 16 (5): 298-302. doi: 10.1089/dia.2013.0288.

19. Novikov VS. Otchet o klinicheskih issledovaniyah novyh lekarstvennyh form insulina (Insulin Chbio R, Insulin Chbio NPH), poluchennyh na osnove genno-inzhenernogo insulina cheloveka, proizvodstva RAO «BIOPREPARAT» [A report on clinical trials of new dosage forms of insulin (Insulin Chbio R, Insulin Chbio NPH), obtained on the basis of human genetically engineered insulin, produced by RAO BIOPREPARAT]. Sankt-Peterburg [St Petersburg]. 2000.

20. Heise T, et al. Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes. Diabetes. 2004; 53 (6): 1614-1620.

UDC 340.6:611.717.1

 AGE IDENTIFICATION BY SCAPULA MORPHOLOGICAL CHANGES

CHERTOVSKY ANDREY A., ORCID ID: orcid.org/ 0000-0003-1777-1752; C. Med. Sci., forensic doctor of Bureau of Forensic Medical Examination of the Department of Public Health of Moscow, Russia, 115516, Moscow, Tarny proezd, 3, e-mail: traumfilipp@mail.ru

TUCHIK EVGENIY S., ORCID ID: 0000-0003-4330-2327; D. Med. Sci., professor of the Department of Forensic Medicine of Russian National Research Medical University named after N.I. Pirogov, Russia, 117997, Moscow, Ostrovityanin str., 1, e-mail: rsmu@rsmu.ru

Abstract. Aim. The aim of the study was to identify changes that occur during life based on scapula morphometric study using obtained results to determine the age of a person. Material and methods. 108 acts (conclusions) of corps and scapula forensic investigations were used as a study material. Morphological and osteometric study methods were applied, along with mathematical ones using applied programs for data statistical processing.Results and discussion. Age-related changes in the scapula, including its articular cavity, have been studied. Individual scapula morphometric parameters, both qualitative and quantitative, allow one to reliably determine the age of a person by only this bone, using the correlation of age and quantitative and qualitative equivalents of the extent of individual parameters. Conclusion. Developed algorithm for age determination provides a wide range of opportunities in both skeleton and corpse identification in unknown persons with pronounced putrefactive changes. Low cost of the proposed osteological studies and a simple algorithm for problem solution via morphometry allows to reduce the range of actions performed by target material typing, which significantly reduces both economic and time costs.

Key words: morphometry, scapula, identification, anthropology, age.

For reference: Chertovsky AA, Tuchik ES. Age identification by scapula morphological changes. The Bulletin of Contemporary Clinical Medicine. 2019; 12 (2): 58–61. DOI: 10.20969/VSKM.2019.12(2).58-61.

1. Barinov EKh, Shcherbakov VV, Fedulova MV, Goncharova NN. Identifikatsiya lichnosti pri chrezvychaynykhproisshestviyakh s massovymi chelovecheskimi zhertvami[Identification of the person in case of emergency with mass human victims]. Kirov-Moskva: KOGUZ «Meditsinskiy informatsionno-analiticheskiy tsentr» [Kirov-Moscow: KOGUZ Medical Information Analytical Center]. 2008; 235 p.

2. Osipenkova-Vichtomova TK. Gistomorfologicheskaya ekspertiza kostey [Histomorphological examination of bones]. Moskva: «Meditsina» [Moscow: “Medicine”]. 2009; 152 p.

3. Alekseev VP. Osteometriya; Metodika antropologicheskikh issledovaniy [Osteometry; Methods of anthropological research]. Moskva: «Nauka» [Moscow: “Science”]. 1966; 251 p.

4. Alekseev VP, Debets GF. Kraniometriya; Metodika antropologicheskikh issledovaniy [Craniometry; Methods of anthropological research]. Moskva: «Nauka» [Moscow: “Science”]. 1964; 128 p.

5. Zel’tser A. Prichiny i formy proyavleniya uskorennogo rosta detey [Causes and forms of manifestation of accelerated growth of children]. Moskva: «Meditsina» [Moscow: “Medicine”]. 1968; 235 p.

6. Markosyan AA. Voprosy vozrastnoy fiziologii [Questions of age physiology]. Moskva: «Prosveshchenie» [Moscow: “Enlightenment”]. 1974; 223 p.

7. Miklashevskaya NN. Rost i razvitie rebenka [Growth and development of the child]. Moskva: Izdatel’stvo Moskovskogo universiteta [Moscow: Publishing House of Moscow University]. 1973; 220 p.

8. Roginskiy YaYa, Levin MG. Osnovy antropologii [Basics of anthropology]. Moskva: Izdatel’stvo Moskovskogo universiteta [Moscow: Publishing House of Moscow University]. 1955; 502 p.

9. Zvyagin, VN, Zamyatina AO, Galitskaya OI. Diagnostikamassivnosti skeleta i somatotipa cheloveka po kostyamkisti [Diagnosis of the massiveness of the skeleton and human somatotype on the bones of the hand]. Sudebno-meditsinskaya ekspertiza [Forensic medical examination]. 2003; 6: 19-25.

10. Pigolkin YuI, Fedulova MV, Zolotenkova GV. Opredelenie vozrasta cheloveka po kostnoy tkani [Determination of human age by bone tissue]. Sudebno-meditsinskaya ekspertiza [Forensic medical examination]. 2012; 1: 49-51.

11. Naynis IV. Identifikatsiya lichnosti po proksimal’nym kostyam konechnostey [Identification of the person by the proximal bones of the limbs]. Vil’nyus: Izdatel’stvo «Mintis» [Vilnius: Minthis Publishing House]. 1972; 158 p.

12. Koshelev LA. O polovom dimorfizme lopatok [On sexual dimorphism of the blades]. Sudebno-meditsinskaya ekspertiza [Forensic medical examination].1971; 4: 22-23.

13. Laptev ZL. Opredelenie pola i dliny tela po parametram lopatok [Determination of sex and body length by the parameters of the blades]. Sudebno-meditsinskaya ekspertiza [Forensic medical examination]. 1978; 3: 7-11.

14. Gurova NI. Vozrastnaya morfologiya grudnoy kletki cheloveka [Age morphology of the human thorax]. Moskva: «Prosveshchenie» [Moscow: “Enlightenment”]. 1965; 216 p.

1. Tsvetkova OA. Sostoyaniye sistemy provospalitel’nykhtsitokinov u bol’nykh khronicheskoy obstruktivnoybolezn’yu legkikh [The state of the system of pro-inflammatory cytokines in patients with chronic obstructive pulmonary disease]. Pul’monologiya [Pulmonology]. 2005; 3: 66-100.

2. Eisenhut M. Neopterin in Diagnosis and Monitoring of Infectious Diseases. Journal of Biomarkers. 2013; 2013 (196432): 10 p. doi: 10.1155/2013/196432

3. Yartsev MN, Yakovleva KP, Plakhtiyenko MV. Immunnaya nedostatochnost’ u detey: pervichnyye i vtorichnyye immunodefitsitnyye sostoyaniya, «immunokomprometirovannyy rebenok», podkhody k immunomoduliruyushchey terapii [Immune deficiency in children: primary and secondary immunodeficiency states, «immunocompromised child», approaches to immunomodulating therapy]. Tsitokiny i vospaleniye [Cytokines and inflammation]. 2005; 4 (3): 49-57.

4. Esposito S, Soto-Martinez ME, Feleszko W, Jones MH, Shen KL, Schaad UB. Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence. Current Opinion in Allergy and Clinical Immunology. 2018; 18 (3): 198– 209.

5. Luczak G, Plata-Nazar K, Kozielska E, et al. Serum neopterin level in children with lower respiratory tract infections. Med Wieku Development. 2007; 11 (4): 423-427.

6. Mildvan D, Spritzler J, Grossberg SE, Fahey JL, Johnston DM, Schock BR, Kagan J. Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection. Clinical Infectious Diseases. 2005; 40 (6): 853–858.

7. Murr C, Widner B, Wirleitner B, Fuchs D. Neopterin as a marker for immune system activation. Curr Drug Metab. 2002; 3 (2): 175-187.

8. Schaad UB, Mütterlein R, Goffin H, BV-Child Study Group. Immunostimulation with OM-85 in children with recurrent infections of the upper respiratory tract: a double-blind, placebo-controlled multicenter study. Chest. 2002; 122 (6): 2042-2049.

9. Veltishchev YuE. Immunnaya nedostatochnost’ u detey [Immune deficiency in children]. Rossiyskiy vestnik perinatologii i pediatrii [Russian Bulletin of Perinatology and Pediatrics]. 2004; 4: 10.

10. Samsygina GA. Chasto boleyushchiye deti: problemy patogeneza, diagnostiki i terapii [Often ill problems of the pathogenesis of diagnosis and therapy]. Pul’monologiya [Pulmonology]. 2005; 1: 66-73.

 MODERN UNDERSTANDING OF RENAL TRANSPLANT ISCHEMIC AND REPERFUSION INJURY PATHOGENESIS AND APPROACHES TO PREVENTION AND TREATMENT

ARTYOMOV DMITRIY V., ORCID 0000-0002-0753-967X; nephrologist of the Department of internal medicine No 1 of Consultative diagnostic center of Moscow Regional Research Clinical Institute named after M.F. Vladimirsky, Russia, 129110, Moscow, Shshepkin str., 61/2, bild. 1, tel.: +7(926)528-96-52, 8(495)681-36-76, e-mail: anatom555@yandex.ru

ZULKARNAEV ALEKSEY B., ORCID 0000-0001-5405-7887; D. Med. Sci., professor of the Department of transplantology, nephrology and artificial organs of faculty of advanced physician training of Moscow Regional Research Clinical Institute named after M.F. Vladimirsky, Russia, 129110, Moscow, Shshepkin str., 61/2, bild. 1, tel.: +7(926)528-96-52, 8(495)681-36-76, e-mail: anatom555@yandex.ru

Abstract. Aim. The aim of the study was to analyze the modern understanding of the pathogenesis, and approaches to prevention and treatment of renal graft ischemic and reperfusion injury. Material and methods. Literature review was performed. Results and discussion. Current article highlights the main pathogenetic factors for renal allograft ischemic/ reperfusion syndrome. Cellular, humoral, as well as non-specific mechanisms of renal damage development are being described. The main modern methods of exposure were identified. Reperfusion and ischemic damage to the allograft is a complex of multiple pathological processes that occur immediately after the onset of the reperfusion. This process is complicated by the time interval, since correction is limited to a time period in the range of 12–14 hours. Conclusion.Multiple cellular, humoral and nonspecific factors play an important role in the initiation of pathogenetic mechanisms of renal graft ischemic and reperfusion injury. It is necessary to unify treatment and prevention of ischemic-reperfusion injuries, since they may influence the long-term effective and efficient functioning of the renal allograft. Further study of these mechanisms and development of pathogenetically justified correction methods are the main vectors of the modern development in transplantology.

1. Morariu AM, Schuurs TA, Leuvenink HG. Early events in kidney donation: progression of endothelial activation, oxidative stress and tubular injury after brain death. Am J Transplant. 2008; 8 (5): 933-941.

2. Jayle C, Milinkevitch S, Favreau F. Protective role ofselectin ligand inhibition in a large animal model of kidneyischemia-reperfusion injury. Kidney Int. 2006; 69 (10): 1749-1755.

3. Nemoto T, Burne MJ, Daniels F. Small molecule selectinligand inhibition improves outcome in ischemic acute renalfailure. Kidney Int. 2001; 60 (6): 2205-2214.

4. Bilenko MV. Ishemicheskiye i reperfuzionnyye povrezhdeniya organov: molekulyarnyye mekhanizmy, puti preduprezhdeniya i lecheniya [Ischemic and reperfusion organ damage: molecular mechanisms, ways to prevent and treat]. Moskva: Meditsina [Moscow: Medicine]. 1989; 368 p.

5. Collard CD, Gelman S. Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology. 2001; 94 (6): 1133-1138.

6. Chok MK, Ferlicot S, Conti M. Renoprotective potency of heme oxygenase-1 induction in rat renal ischemia-reperfusion. Inflamm Allergy Drug Targets. 2009; 8 (4): 252-259.

7. Katori M, Anselmo DM, Busuttil RW, Kupiec-Weglinski JW. A novel strategy against ischem ia and reperfusion injury: cytoprotection with heme oxygenase system. Transpl Immunol. 2002; 9 (2-4): 227-233.

8. Rabb H, Daniels F, O’Donnell M. Pathophysiological role of T lymphocytes in renal ischemia-reperfusion injury in mice. Am J Physiol Renal Physiol. 2000; 279 (3): 525-531.

9. Krishnadasan B, Naidu B, Rosengart M. Decreased lung ischemia-reperfusion injury in rats after preoperative administration of cyclosporine and tacrolimus. J Thorac Cardiovasc Surg. 2002; 123 (4): 756-767.

10. Nakayama Y, Nonoguchi H, Kiyama S. Intranephron distribution and regulation of endothelin-converting enzyme-1 in cyclosporin A-induced acute renal failure in rats. J Am Soc Nephrol. 1999; 10 (3): 562-571.

11. Beiras-Fernandez A, Chappell D, Hammer C, Thein E. Influence of polyclonal antithymocyte globulins upon ischemia-reperfusion injury in a non-human primate model. Transpl Immunol. 2006; 15 (4): 273-279.

12. Takada M, Chandraker A, Nadeau KC. The role of the B7 costimulatory pathway in experimental cold ischemia/reperfusion injury. J Clin Invest. 1997; 100 (5): 1199-1203.

13. Furuichi K, Wada T, Iwata Y. CCR2 signaling contributes to ischemia-reperfusion injury in kidney. J Am Soc Nephrol. 2003; 14 (10): 2503-2015.

14. Katori M, Anselmo DM, Busuttil RW, Kupiec-Weglinski JW. A novel strategy against ischem ia and reperfusion injury: cytoprotection with heme oxygenase system. Transpl Immunol. 2002; 9 (2-4): 227-233.

15. Damman J, Daha MR, van Son WJ et al. Crosstalk between complement and Toll-like receptor activation in relation to donor brain death and renal ischemiareperfusion injury. Am J Transplant. 2011; 11 (4): 660-669.

16. Furuichi K, Kaneko S, Wada T. Chemokine/chemokine receptor-mediated inflammation regulates pathologic changes from acute kidney injury to chronic kidneydisease. Clin Exp Nephrol. 2009; 13 (1): 9-14.

17. El-Asir L, Wilson CH, Talbot D. Interleukin 2 receptor blockers may directly inhibit lymphocyte mediated ischaemia reperfusion injury. Transpl Int. 2005; 18 (9): 1116.

18. Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med. 2009; 37 (7): 186-202.

19. Bagnenko SF, Moysyuk YaG, Reznik ON. Pervyy opyt primeneniya apparatnoy perfuzii pochek, poluchennykh ot asistolicheskikh donorov, dlya uluchsheniya rezul’tatov transplantatsii [The fi rst experience of using hardware perfusion of kidneys obtained from asystolic donors to improve the results of transplantation]. Vestnik transplantologii i iskusstvennykh organov [Bulletin of transplantology and artificial organs]. 2006; 8 (3): 9-13.

 RESULTS OF THE EXPERT EVALUATION OF PAIN MANAGEMENT IN PATIENTS WITH BLOOD DISEASES

LEVCHENKO OLGA K., C. Med. Sci., senior researcher of Intensive care unit and therapy of National Medical Center of Hematology, Russia, 125167, Moscow, Novy Zykovsky proezd, 4, tel. 8(926)816-38-87, e-mail: levchenkokp@rambler.ru

BERSENEVA EVGENIYA A., D. Med. Sci., the Head of Center of higher and additional professional education of National Research Institute of Public Health named after N.A. Semashko, Russia, 105064, Moscow, Vorontsovo Pole str., 12, bild. 1

Abstract. Aim. The aim was to study the relevance of pain management implementation in hematological patients on the territory of the Russian Federation. Material and methods. Prospective multicenter study, including a survey on pain management performance by the hematologists undergoing advanced training at the Russian Medical Academy for Continuous Professional Education, was conducted. The inclusion criteria were: more than a 10-year professional experience in hematology acquired on the territory of the Russian Federation (including the regions), taking into account academic degrees and titles. Results and discussion. The study revealed a poor level of pain managementin hematological patients. Only 18% of the experts rated the effectiveness of pain relief as high, while others marked it as low or moderate. Unanimously, 100% of respondents consider it necessary to create specialized units (pain management service) in order to provide outpatient and inpatient care for such patients. In most cases (73%), the experts reported that such units are not developed or do not operate in the regions. Current guidelines on pain management are being followed only in 27% of cases (while the rest (72%) reported that they are partially or not followed). Among the suggestions of the experts, the most frequently proposed were: improvement of regulatory documents (more detailed, interdisciplinary, and interdepartmental); introduction of the standards for specialized pain management unit development (1 unit for a certain number of people); and increasing continuity between different specialists. Conclusion. The resultsof evaluation expert analysis confirm the relevance and the need to provide proper pain management for the patients with blood diseases. Strategic solutions have been proposed and described by a number of factors, allowing gradually establishing pain management service in hematological hospitals.

1. Niscola P, Tendas A, Scaramucci L, Giovaninni M, Cupelli L, De Sanctis V, Brunetti GA, Bondanini F, Palumbo R, Lamanda M, Battistini R, Cartoni C, Romani C, Arcuri E. Pain in malignant hematology. Expert Rev Hematol. 2011; 4 (1): 81-93.

2. Witkop M, Lambing A, Divine G, et al. A national study of pain in the bleeding disorders community: a description of haemophilia pain. Haemophilia 2011; 18 (3): 115-119.

3. Ionova TI. Aktual’nye voprosy issledovaniya kachestva zhizni v onkogematologii [Actual questions of the study of quality of life in oncohematology]. Byulleten’ SO RAMN [Bulletin of the SB RAMS]. 2013; 1: 82–89.

4. Srivastava AK, Brewer EP, Mauser-Bunschoten, et al. Guidelines for the management of hemophilia. Haemophilia 2013; 19 (1): 1–47.

5. Tran QK, Nguyen T, Tuteja G, Tiffany L, Aitken A, Jones K, Duncan R, Rea J, Rubinson L, Haase D. Emergency Providers Pain Management in Patients Transferred to Intensive Care Unit for Urgent Surgical Interventions. West J Emerg Med. 2018; 19 (5): 877-883.

6. Lecky F, Benger J, Mason S, Cameron P, Walsh C; IFEM Quality Symposium Working Group. The International Federation for Emergency Medicine framework for quality and safety in the emergency department. Emerg Med J. 2014; 31(11): 926-929.

7. Prikaz ot 15 noyabrya 2012 goda # 930n «Ob utverzhdenii poryadka okazaniya medicinskoj pomoshchi naseleniyupo profilyu «gematologiya» [Order of November 15, 2012 N 930n «On approval of the procedure for rendering medical care to the population in the» hematology «profile]. 2012.

8. Ukaz Prezidenta RF «O strategii nacional’noj bezopasnosti Rossijskoj Federacii» ot 31.12.2015 No683 [Presidential Decree «On the strategy of the national security of the Russian Federation» of 12/31/2015 # 683]. 2015.

9. Federal’nyj zakon «Ob osnovah ohrany zdorov’ya grazhdan v Rossijskoj Federacii» ot 21/11/2011 # 323-FZ (stat’ya 10) [Federal Law «On the Principles of the Protection of the Health of Citizens in the Russian Federation» of 21/11/2011 # 323-FZ (Article 10)]. 2011.

10. Prikaz Ministerstva zdravoohraneniya Rossijskoj Federacii ot 20 dekabrya 2012 goda # 1183n «Ob utverzhdenii Nomenklatury dolzhnostej medicinskih rabotnikov i farmacevticheskih rabotnikov» [Order of the Ministry of Health of the Russian Federation of December 20, 2012 # 1183n “On approval of the nomenclature of positions of medical workers and pharmaceutical workers”].

 PRINCIPLES IN ENDOSCOPIC SURGEON SHORT-TERM TRAINING: 25 YEAR EXPERIENCE

FEDOROV IGOR V., D. Med. Sci., professor of the Department of endoscopy, general and endoscopic surgery of Kazan State Medical Academy – the branch of Russian Medical Academy of Postgraduate Education, Russia, 420012, Kazan, Mushtari str., 11, tel. +7(966)260-40-05, e-mail: 2604005@list.ru

SLAVIN LEV E., D. Med. Sci., professor of the Department of endoscopy, general and endoscopic surgery of Kazan State Medical Academy – the branch of Russian Medical Academy of Postgraduate Education, Russia, 420012, Kazan, Mushtari str., 11

FEDOROV VLADIMIR I., physician of Republic Clinical Cancer Center, Russia, 420029, Kazan, Sibirskiy tract str., 29, e-mail: valdamedmed@gmail.com

Abstract. Aim. The aim of the study was to determine the outcomes of short-term intensive training in endoscopic surgery technologies. Material and methods. The study included 5712 doctors trained in «Endosurgery center» during the last 25 years. Retraining was carried out in the framework of following relevant medical specialties, such as abdominal surgery, operative gynecology, ENT, traumatology and orthopedics, urology, and cardiovascular surgery. Duration of the courses, depending on the specialty, ranged from 5 to 11 training days. Feasibility of the acquired knowledge and practical skills after the training, as well as the frequency and severity of perioperative complications, which are not supposed to exceed the mean level after the training, were considered as criteria of effectiveness of training in surgical specialties. Results and discussion. Telephone and e-mail survey was conducted in order to collect the information on professional experience of 2456 out of 5712 doctors (43%) trained in the Center. 1719 specialists out of 2456 respondents (70% of the respondents) reported on successful professional activities. During 6 months after training they began practicing endovideosurgery, applying the knowledge relevant to their specialty. However, the remaining 30% (737 of the surveyed) failed to apply their skills for multiple reasons. In 12% of cases it was related to the lack of endoscopic equipment required to perform minimally invasive interventions in the health center. In 8% of cases it was explained by the high competition in ones department. In 5% of cases it was related to the change of profession, place of work or to an illness of a specialist. In 5% of cases the insufficient number of patients was noted. Conclusion. Short-term intensive training in the field of new technologies can be considered very effective in endoscopic surgery specialist training. Such type of education allows retraining a significant number of doctors according to the modern requirements in health care for a short period of time. The effectiveness of training was determined by the feasibility of the acquired knowledge and practical skills acquired.

1. Olovyanny VE, Fedorov AV, Glantsev SP. Laparoskopicheskaya khirurgiya v Rossii [Laparoscopic surgery in Russia]. Arkhangel’sk: Izdatel’stvo Severno-go gosudarstvennogo meditsinskogo universiteta[Arkhangelsk: Publishing of Northern State Medical University]. 2017; 242 p.

2. Fedorov IV, Sigal EI, Odintsov VV. Shestnadtsatiletniy opyt kratkosrochnogo obucheniya vrachey Rossii i stran SNG endokhirurgicheskim tekhnologiyam [Sixteen years of experience in short-term education of doctors in Russia and the CIS countries on endosurgical technologies]. Vestnik sovremennoj klinicheskoj mediciny [The Bulletin of Contemporary Clinical Medicine]. 2009; 2 (2): 59-63.

3. Shine Moshe, Assalia Ahmad. Zdravyy smysl v neotlozhnoy abdominal’noy khirurgii [Common sense in emergency abdominal surgery]. Moskva: GEOTAR [Moscow: GEOTAR]. 2013; 649 p.

4. Fedorov IV. Dvadtsatidvukhletniy opyt kratkosrochnogo obucheniya vrachey endoskopicheskoy khirurgii [Twenty-two years of experience in short-term education of doctors of endoscopic surgery]. Moskovskiy khirurgicheskiy zhurnal [Moscow surgical journal]. 2015; 4: 29-31.

5. Galimov OV, Fazullin TR, Paltusov AI, Idrisova GA. Profilaktika posleoperatsionnykh oslozhneniy i voz-mozhnost’ laboratornogo kontrolya yeyo effektivnosti[Prevention of postoperative complications and the possibility of laboratory monitoring of its effectiveness]. Endoskopicheskaya khirurgiya [Endoscopic Surgery]. 2013; 2: 48-51.

6. Galimov OV, Khanov VO, Zanega VS, Bakirov AA. Vyborkhirurgicheskoy taktiki pri gryzhakh pishchevodnogootverstiya diafragmy v zavisimosti ot razmerov [The choiceof surgical tactics for hernias of the esophageal opening ofthe diaphragm depending on the size]. Meditsinskiy vestnik Bashkortostana [Medical Bulletin of Bashkortostan]. 2016; 3: 28-31.

7. Fedorov IV, Sigal EI, Burmistrov MV. Oslozhneniya endoskopicheskoy khirurgii [Complications of endoscopic surgery]. Kazan’: «Obraztsovaya tipografiya» [Kazan: “Exemplary Typography”]. 2017; 294 p.

8. Humphries LA, et al. Causes of dissatisfaction after laparoscopic fundoplication: the impact of new symptoms, recurrent symptoms, and the patient experience. Surgical endoscopy. 2013; 27 (5): 1537-1545.

9. Logvinov YI, Orlovskaya AI. Metodicheskoye soprovozhdeniye obrazovatel’noy deyatel’nosti v ramkakh simulyatsionnogo tsentra [Methodological support of educational activities in the framework of the simulation center]. Virtual’nyye tekhnologii v meditsine [Virtual technology in medicine]. 2018; 2: 10-12.

10. Ushmarov DI, Alekseenko SN. Opyt provedeniyaeksperimental’noy operatsii v programme obucheniyavrachey-ordinatorov khirurgicheskikh spetsial’nostey [Theexperience of conducting an experimental operation inthe training program for physicians-residents of surgical specialties]. Virtual’nyye tekhnologii v meditsine [Virtual technology in medicine]. 2018; 2: 41-43.

11. Semm K. Advances in pelvioscopic surgery (appendectomy). Curr Probl obstet gynecol. 1983; 5: 482.

 CLINICAL CASE OF LEFT LUNG UPPER LOBE ARTERIOVENOUS MALFORMATION IN A PREGNANT WOMAN

AINABEKOVA BAYAN A., D. Med. Sci., professor, the Head of the Department of internal medicine of Astana Medical University, Republic of Kazakhstan, 010000, Astana, Beybitshilik str., 49а

GUDYM STANISLAV I., C. Med. Sci., assistant of professor of the Department of internal medicine of Astana Medical University, Republic of Kazakhstan, 010000, Astana, Beybitshilik str., 49а

IMANGAZINOVA SAULE S., ORCIDID: 0000-0002-4848-5401; C. Med. Sci., associate professor of the Department of internal medicine of Astana Medical University, Republic of Kazakhstan, 010000, Astana, Beybitshilik str., 49а, tel. +7(701)435-34-14, e-mail: dr_iss@mail.ru

ASKAROVA KARASHASH M., ORCIDID: 0000-0001-6566-3663; C. Med. Sci., associate professor of the Department of internal medicine of Astana Medical University, Republic of Kazakhstan, 010000, Astana, Beybitshilik str., 49а

Abstract. Arteriovenous malformations, in particular in lung tissue, represent a congenital vascular disorder with a rare incidence from 1 in 2 350 to 1 in 39 000 people in the entire population. Aim. The aim of the study was to demonstratethe difficulties in lung tissue arteriovenous malformation diagnosis and differential diagnosis in a pregnant woman using the clinical case. Material and methods. The patient was admitted to pulmonology department with complaints of episodic dry cough, chest pain when coughing, and inspiratory shortness of breath on exertion. Comprehensive examination was conducted. Results and discussion. The disease manifested in woman as hemoptysis only during pregnancies. Computed tomography with contrasting allowed clarifying the diagnosis of lung malformation. Conclusion.Arteriovenous malformation can lead to a life-threatening complication for the mother and fetus in pregnant women, which is pulmonary bleeding. Favorable pregnancy is possible in patients with arteriovenous malformations when planning it knowing detailed localization and extensiveness of the pathologic process, as well as, performing vascular malformation surgical correction if necessary. The leading role in diagnosis verification belongs to computed tomography in angioregime.

1. Vasil’ev IS, Abushkin IA, Diomidov IA. Anomalii razvitiya sosudov: terminologiya, klassifikaciya [Anomalies of Vessel Development: Terminology, Classification]. Vestnik YuUrGU; Seriya «Ob obrazovanii, zdravoohranenii, fizicheskoj kul’ture» [Bulletin of SUSU; Series «On Education, Health Care, Physical Education»]. 2013; 13: 66-68.

2. Kolos AI, Sajgel’dina LL, Zhajnorov NE. Arteriovenoznye shunty legkih: trudnosti diagnostiki i lechebnoj taktiki [Arteriovenous shunts of the lungs: difficulties in diagnosis and treatment tactics]. Clinical Medicine of Kazakhstan. 2015; 4: 74-78.

3. Huan Yuan’fen. Klinika, diagnostika, hirurgicheskoe lechenie arteriovenoznyh mal’formacij legkih [Clinic, diagnostics, surgical treatment of arteriovenous malformations of the lungs]. Moskva: Rossiyskiy nauchnyy tsentr khirurgii imeni akademika BV Petrovskogo» [Moscow: Russian Scientific Center of Surgery named after academician BV Petrovsky]. 2015; 784 р.

4. Asher E, Pokrovskiy AV, ed. Sosudistaya hirurgiya po Hajmovichu [Vascular surgery in Haimovich]. Moskva: Binom, Laboratoriya znaniy [Moscow: Bean, Knowledge Lab]. 2017; 644 р.

5. Paleev NR. Bolezni organov dyhaniya [Diseases of the respiratory system]. Moskva: Medicina [Moscow: Medicine]. 2000; 699 р.

6. Radeckaya LS. Beremennost’ i mezenhimal’nye displazii (sindromy Marfana, Elersa-Danlo, Rendyu-Oslera) [Pregnancy and mesenchymal dysplasia (Marfan, Ehlers-Danlo, Rendu-Osler syndromes)]. Akusherstvo, ginekologiya i reprodukciya [Obstetrics, gynecology and reproduction]. 2015; 4: 74-85.