Wiadomości Pamięci Lekarskie dra Władysława Czasopismo Polskiego Towarzystwa Lekarskiego Biegańskiego

Redaktor naczelnyTom LXVIII, 2015, Nr 4 Pediatria Rok założenia 1928 Prof. dr hab. med. Władysław Pierzchała Prof. dr hab. med. Ewa Małecka-Tendera (SUM Katowice) (SUM Katowice) Zastępca redaktora naczelnego Dr hab. med. Tomasz Szczepański Prof. zw. dr hab. n. med. Aleksander Sieroń (SUM Katowice) (SUM Katowice) Położnictwo i ginekologia Sekretarz redakcjiECOLOGY & HUMAN HEALTHProf. dr IN hab. THE med. Jan NORTH Kotarski Joanna Grocholska (UM Lublin) VI CONGRESS WITH INTERNATIONALProf. dr hab. med.PARTICIPATION Andrzej Witek Redaktor statystyczny (SUM Katowice) Ewa Guterman 12-14 November 2015 Yakutsk,Stomatologia Russia Rada naukowa Prof. dr hab. Maria Kleinrok Redaktorzy tematyczni: (UM Lublin) Chirurgia Polskie Towarzystwo Lekarskie Prof. dr hab. med. Krzysztof Bielecki Prof. dr hab. med. Jerzy Woy-Wojciechowski (CMKP Warszawa) (Prezes PTL) Prof. dr hab. med. Stanislav Czudek Prof. emerytowany dr hab. med. Tadeusz Petelenz (Onkologickié Centrum J.G. Mendla Czechy) (O. Katowicki PTL) Prof. dr hab. med. Marek Rudnicki (University of Illinois USA) Editors of issue:Kontakt z redakcją i wydawnictwem Petrova Palmira Georgievna, DMS, professor, Choroby wewnętrzne Joanna Grocholska director of Medical Institute NEFU, Head ofe-mail: Department [email protected] of Physiology Prof. dr hab. med. Marek Hartleb, gastroenterologiaBorisova Natalia Vladimirovna, DMS, (SUM Katowice) professor of Department of Physiology,Wydawca Medical Institute NEFU Prof. dr hab. med. Jacek Dubiel, kardiologia Blue Sparks Publishing Group Sp. z o.o. (CM UJ Kraków) ul. Obornicka 15/4, 02-948 Warszawa Prof. dr hab. med. Zbigniew Gąsior, kardiologia tel. (22) 858-92-53 (SUM Katowice) Zarząd: dr Anna Łuczyńska − prezes Prof. dr hab. med. Jerzy Korewicki, kardiologia Reklama i marketing: Agnieszka Rosa (Instytut Kardiologii Warszawa) tel. 662-116-020 Dr hab. med. Antoni Wystrychowski, nefrologia e-mail: [email protected] (SUM Katowice) Zamówienia na prenumeratę: Prof. dr hab. med. Ryszarda Chazan, pneumonologia e-mail: [email protected] i alergologia (UM Warszawa) Aluna Publishinglub tel. (22) 858-92-53 Prof. dr hab. med. Tadeusz Płusa, pneumonologia i alergologia (WIM Warszawa) Projekt okładki: Dorota Cybulska Choroby zakaźne Opracowanie gra czne: Tomasz Białkowski 441 Prof. dr hab. med. Andrzej Gładysz (UM Wrocław) Nakład: do 6000 egz. Epidemiologia © Copyright by Blue-Sparks Publishing Group Prof. dr hab. med. Jan Zejda (SUM Katowice) Wydanie czasopisma Wiadomości Lekarskie w formie papierowej jest wersją Neurologia i neurochirurgia pierwotną (referencyjną). Redakcja wdraża procedurę zabezpieczającą ory- Prof. dr hab. med. Krystyna Pierzchała, neurologia ginalność publikacji naukowych oraz przestrzega zasad recenzowania prac (SUM Katowice) zgodnie z wytycznymi Ministerstwa Nauki i Szkolnictwa Wyższego. Prof. dr hab. med. Henryk Majchrzak, neurochirurgia Czasopismo indeksowane w: (SUM Katowice) Medline, EBSCO, MNiSW (6 pkt), Index Copernicus, PBL.

WL_1_2013.indb 1 27.03.2013 12:23 442 © Aluna Wiadomości Wiadomości Lekarskie 2015, tom LXVIII, nr 4 Pediatria Prof. dr hab. med. Ewa Małecka-TenderaPamięci Lekarskie (SUM Katowice) dra Władysława RedaktorCzasopismo naczelny Polskiego Towarzystwa Lekarskiego Dr hab. med. Tomasz Szczepański Biegańskiego (SUM Katowice) Prof. dr hab. med. Władysław Pierzchała (SUM Katowice) Położnictwo i ginekologia Redaktor naczelny Pediatria Prof. drZastępca hab. med. redaktora Władysław naczelnego Pierzchała Prof. dr hab. med. Jan Kotarski Prof.(UM dr hab. Lublin) med. Ewa Małecka-Tendera (SUM Katowice)Prof. zw. dr hab. med. Aleksander Sieroń (SUM Katowice) (SUM Katowice) Prof. dr hab. med. Andrzej Witek Zastępca redaktora naczelnego Dr hab.(SUM med. Katowice) Tomasz Szczepański Redaktor wydania (SUM Katowice) Prof. zw. dr hab. n. med. Aleksander Sieroń Stomatologia Petrova Palmira Georgievna, (SUM Katowice) Położnictwo i ginekologia Yakutsk, Republic of Sakha (Yakutia) Prof. dr hab. Maria Kleinrok Sekretarz redakcji Prof.(UM dr hab. Lublin) med. Jan Kotarski Borisova Natalia Vladimirovna, (UM Lublin) Joanna Yakutsk,Grocholska Republic of Sakha (Yakutia) Prof. dr hab. med. Andrzej Witek Redaktor statystyczny Polskie Towarzystwo Lekarskie Redaktor statystyczny (SUM Katowice) Prof. dr hab. med. Jerzy Woy-Wojciechowski Ewa GutermanMgr Ewa Guterman Stomatologia(Prezes PTL) Rada naukowaRada naukowa Prof.Prof. dr hab. emerytowany Maria Kleinrok dr hab. med. Tadeusz Petelenz Redaktorzy tematyczni: Redaktorzy tematyczni: (UM Lublin)(O. Katowicki PTL) Chirurgia Chirurgia Prof. dr hab. med. Krzysztof Bielecki Polskie Towarzystwo Lekarskie Prof. dr hab. med. Krzysztof Bielecki Kontakt z redakcją i wydawnictwem (CMKP Warszawa) Prof. dr hab. med. Jerzy Woy-Wojciechowski (CMKP Warszawa) Anna Łuczyńska Prof. dr hab. med. Stanislav Czudek (Prezes PTL) [email protected] Prof. dr(Onkologickié hab. med. Stanislav Centrum J.G.Czudek Mendla Czechy) Prof. emerytowany dr hab. med. Tadeusz Petelenz (Onkologickié Centrum J.G. Mendla Czechy) www.wiadomoscilekarskie.pl Prof. dr hab. med. Marek Rudnicki (O. Katowicki PTL) Prof. dr(University hab. med. of Marek Illinois RudnickiUSA) Wydawca (University of Illinois USA) Choroby wewnętrzne KontaktWydawnictwo z redakcją Aluna i wydawnictwem ChorobyProf. wewnętrzne dr hab. med. Ryszarda Chazan, pneumonologia i alergologia Joannaul. PrzesmyckiegoGrocholska 29 Prof. dr(UM hab. Warszawa) med. Marek Hartleb, gastroenterologia e-mail:05-510 [email protected] Konstancin-Jeziorna (SUM Katowice)Prof. dr hab. med. Jacek Dubiel, kardiologia Wydawcawww.aluna.waw.pl (CM UJ Kraków) Prof. dr hab. med. Jacek Dubiel, kardiologia Blue Sparks Publishing Group Sp. z o.o. (CM UJ Kraków)Prof. dr hab. med. Zbigniew Gąsior, kardiologia ul. ObornickaKoordynatorzy 15/4, 02-948 projektu Warszawa Prof. dr(SUM hab. Katowice)med. Zbigniew Gąsior, kardiologia tel. (22)Agnieszka 858-92-53 Rosa dr n. med. Lesia Rudenko (SUM Katowice)Prof. dr hab. med. Marek Hartleb, gastroenterologia Zarząd:tel. 694dr Anna778 068 Łuczyńska − prezestel. 888 251 102 Prof. dr(SUM hab. Katowice)med. Jerzy Korewicki, kardiologia [email protected] i marketing: Agnieszka [email protected] Rosa (InstytutProf. Kardiologii dr hab. Warszawa) med. Jerzy Korewicki, kardiologia tel. 662-116-020 Prenumerata Dr hab.(Instytut med. Antoni Kardiologii Wystrychowski, Warszawa) nefrologia e-mail: [email protected] [email protected] (SUM Katowice)Dr hab. med. Krzysztof Łabuzek, farmakologia kliniczna, diabetologiaZamówienia na prenumeratę: (SUM Katowice) www.wiadomoscilekarskie.pl/prenumerata Prof. dr hab. med. Ryszarda Chazan, pneumonologia e-mail: [email protected] i alergologiaProf. dr (UM hab. Warszawa) med. Tadeusz Płusa, pneumonologia i alergologia lub tel.Opracowanie (22) 858-92-53 graficzne (WIM Warszawa) Prof. dr hab. med. Tadeusz Płusa, pneumonologia Piotr Dobrzyński (www.poligrafia.nets.pl) i alergologiaDr hab. (WIM med. Warszawa) Antoni Wystrychowski, nefrologia Projekt okładki: Dorota Cybulska (SUM Katowice) Choroby zakaźne OpracowanieNakład do gra6 tys. czne: egz Tomasz Białkowski Choroby zakaźne Prof. dr hab. med. Andrzej Gładysz (UM Wrocław)Prof. dr hab. med. Andrzej Gładysz Nakład: do 6000 egz. (UM Wrocław) © Copyright by Aluna Publishing Epidemiologia Epidemiologia © Copyright by Blue-Sparks Publishing Group Prof. drProf. hab. dr med. hab. Janmed. Zejda Jan Zejda Wydanie czasopisma Wiadomości Lekarskie w formie papierowej jest wersją (SUM Katowice) pierwotną (referencyjną). Redakcja wdraża procedurę zabezpieczającą (SUM Katowice) Wydanieoryginalność czasopisma prac Wiadomości naukowych Lekarskieoraz przestrzega w formie zasad papierowej recenzowania jest wersją zgodnie NeurologiaNeurologia i neurochirurgia i neurochirurgia pierwotnąz wytycznymi (referencyjną). Ministerstwa Redakcja Nauki wdraża i Szkolnictwa procedurę Wyższego. zabezpieczającą ory- Prof. drProf. hab. dr med. hab. Krystynamed. Henryk Pierzchała, Majchrzak, neurologia neurochirurgia ginalność publikacji naukowych oraz przestrzega zasad recenzowania prac (SUM Katowice)(SUM Katowice) zgodnie z wytycznymi MinisterstwaCzasopismo Nauki indeksowane i Szkolnictwa w: Wyższego. PubMed/Medline, EBSCO, MNISW (6 pkt), Prof. drProf. hab. dr med. hab. Henrykmed. Krystyna Majchrzak, Pierzchała, neurochirurgia neurologia Czasopismo indeksowane w: (SUM Katowice)(SUM Katowice) Medline, EBSCO, MNiSWIndex Copernicus, (6 pkt), Index PBL, ScopusCopernicus, PBL. 443

WL_1_2013.indb 1 27.03.2013 12:23 Instructions for authors

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444 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

SPIS TREŚCI/contents

Asekritova A.S., Kylbanova E.S., Emelyanova E.A., Borisova E.P. Ga str o es o p h a ge a l re f l u x d ise a se in a ss o ci a ti o n w it h lipid-m et a b o l ic i n d ic a t o rs a t t h e y a k u ts k 449

Borisova E.P., Kylbanova E.S., Asekritova A.S. Fe a t u res o f clinical-f u n cti o n a l m a n i f est a ti o n s o f c h r o n ic o b str u cti v e l u n g d ise a se in c o m b i n a ti o n w it h m et a b o l ic s y n d r o m e in et h n ic gr o u ps o f t h e y a k u ts a n d t h e r u ssi a n s 454

Borisova N.V., Petrova P.G. Ad a pti v e re a cti o n s o f i n d ige n o u s p o p u l a ti o n o f y a k u ti a 458

Sleptsovа s.S., Borisovа n.V. Th e r o l e o f v ir a l h ep a titis in t h e m ec h a n is m o f l i v er c a n cer f o r m a ti o n a m o n g t h e f a r n o rt h i n d ige n o u s i n h a b it a n t s 464

Stepanova G.K., Ustinova M.V. Ps y c h o l o gic a l a n d v eget a ti v e c h a r a cteristics o f st u d e n ts – y a k u ts w it h d i f f ere n t e d u c a ti o n a l s u cces s 469

Sleptsova S.S., Semenova V.K., Dyatchkovskaya P.S., Nikitina S.G. Bre a d t h spre a d i n g o f v ir a l h ep a titis m a r k ers in t h e ris k gr o u ps in t h e rep u b l ic o f s a k h a (y a k u ti a ) 476

Kershengolts B.M., Sydykova L.A., Shаrоykо V.V., Anshakova V.V., Stepanova A.V., Varfolomeeva N.A. Lic h e n s ’ β-o l ig o s a cc h a ri d es in t h e c o rrecti o n o f m е t а b o l ic d is o r d ers in t y pe 2 d i а b е t е s m e l l it u s 480

Avvakumova N.V., Chibyeva L.G., Vasiliev N.N. Clinical a n d m o rp h o l o gic a l c h a r a cteristics o f t h e c h r o n ic g a stritis w it h f u n cti o n a l d y spepsi a in t h e rep u b l ic o f s a k h a (y a k u ti a ) 483

Alekseeva S.N., Antipina U.D., Arzhakova L.I., Protodyakonov S.V. Ne w a pp l ic a ti o n s o f a d a pt o ge n s t o re d u ce r a d i a ti o n si d e e f f ects 487

Aprosimov L.A., Chichakhov D.A. Th e sit u a ti o n w it h st a f f i n g in pe d i a tric ser v ices o f t h e rep u b l ic o f s a k h a (y a k u ti a ) 490

Akhremenko Y.A., Cheremkina A.S., Tarasova L.A., Ushnitsky I.D. Micr o b i o ce n o sis in i n f l a m m a t o r y pr o cesses o f m a rgi n a l g u m a m o n g c h i l d re n 493

Borisova N.V., Markova S.V., Antipina U.D., Sivtseva T.P., Savvina I.L. Th e a n a l y sis o f m a j o r ris k f a ct o rs o f c a r d i o v a sc u l a r d ise a ses a m o n g i n h a b it a n ts o f t h e n o rt h regi o n 496

Gerasimova V.V., Maksimova N.R., LevakovaI A., Zhebrun A.B., mukomolov S.L. Epidemiological f e a t u res o f c h r o n ic v ir u s h ep a titis b a n d c in t h e rep u b l ic s a k h a (y a k u ti a ) 502

Neustroeva V.,Kylbanova E., Simonova G., Tatarinova O., Scherbakova L. Ch a r a cteristic o f a ct u a l f o o d a t e l d er l y a n d se n i l e a ge d p o p u l a ti o n o f y a k u ti a 508

445 Spis treści/Contents

Tobohov A., Nikolaev V. Res u l ts o f c o l o n c a n cer s u rgic a l tre a t m e n t 512

Guryeva A.B., Alekseyeva V.A., Petrova P.G. Ge n d er f e a t u res o f t h e a n t h r o p o m etric , cep h a l o m etric a n d b i o i m pe d a n ce p a r a m eters in t h e st u d e n ts o f y a k u ti a 513

Daybanyrova L.V., Shevchenko O.P. Clinical significance l e v e l s o f c-re a cti v e pr o tei n a n d cer u l o p l a s m i n in p a tie n ts w it h isc h e m ic h e a rt d ise a se 517

Baisheva N.S., Duglas N.I., Pavlova T.Yu., Yakovleva E.B., Rad Ya.G. Su per e a r l y pre m a t u re b irt h in ter m s o f t h e n e w st a n d a r d o f l i v e b irt h in t h e rep u b l ic o f s a k h a (y a k u ti a ) 520

Egorova A., Garmayeva D. Mo rp h o l o gic a l a ssess m e n t o f n a ti v e m a l e s u b j ects ’ t h y r o i d b o d y in t h e rep u b l ic s a k h a (y a k u ti a ) in d i f f ere n t se a s o n s 523

Epanov V.V., Palshin G.A., Epanova A.A., Komissarov A.N., Tomsky M.I., Sedunov V.F., Egorov P.L. 526 X-r a y d e n sit o m etr y a n d f r a x m o d e l in pre d icti n g t h e ris k o f o ste o p o r o sis a n d l o w -e n erg y f r a ct u res in p o st m e n o p a u s a l w o m e n Ivanova A.A., Kakorina E.P., Timofeev L.F., Potapov A.F., Aprosimov L.A. Regi o n a l tre n d s in t h e w o r k i n g -a ge p o p u l a ti o n m o rt a l it y r a te in t h e rep u b l ic o f s a k h a (y a k u ti a ) in 1990-2012 529

Ivanova O.N., Argunova, E.F., Alekseev S.N., Ystugina T.V., Varfolomeev A.R., Troev I.P, Kononova I.V., Egorova V.E. Ad a pti v e m ec h a n is m s o f t h e i m m u n e s y ste m in c h i l d re n in f a r n o rt h 534

Kirillina M.P., Loskutova K.S., Lushnikova E.L., Nepomnyaschih L.M. Im m u n o h ist o c h e m ic a l a n a l y sis o f m a m m a r y epit h e l i a l ce l l s a t t u m o r a l gr o w t h in rep u b l ic o f s a k h a (y a k u ti a ) 537

Lineva Z.E., Gulyaeva N.A., Romanova M.V., Dyachkovskaya P.S. Th e r o l e o f c a n d i d a in i n testi n a l d y s b a cteri o sis f o r m a ti o n 543

Shamaeva S.K., Portnyagina U.S., Edelstein M.V., Kuzmina A.A., MalogulovaI S., Varfolomeeva N.A. Res u l ts o f m o n it o ri n g m et a l l o -b et a -l a ct a m a se -pr o d u ci n g str a i n s o f pse u d o m o n a s a er u gi n o s a in a m u l ti -pr o f i l e h o spit a l 546

Lineva Z.E., Zorina S.P. Th e r o l e o f m e d ic a l a n d s o ci a l f a ct o rs in pre d icti n g disability t u b erc u l o sis 549

Dmitrieva T.G., Munkhalova Ya.A. , Argunova E.F. , Alexeyeva S.N., Egorova V.B., Alexeeva N.N. Th e pre v a l e n ce o f c h r o n ic v ir a l h ep a titis in c h i l d re n a n d a d o l esce n ts in y a k u ti a 553

Popova T.E., Tappahov A.A., Shnaider N.A., Petrova M.M., Nikolaeva Т.Y., Konnikova E.E., Kozhevnikov A.A., Ammosov V.G., Vinokurova N.E. Di a g n o stics a l g o rit h m o f d i a b etic p o l y n e u r o p a t h y in pre d icti o n o f clinical c o u rse 557

Palshina A.M., Bannaev I.F., Palshin G.A., Shamaeva S.Kh., Yadrikhinskaya V.N., Komissarov A.N., Krivoshapkina A.G. Th e i n f l u e n ce o f u ri n a r y tr a ct i n f ecti o n s o n tre a t m e n t o f f r a ct u re o f pr o x i m a l f e m u r in p a tie n ts w it h s y ste m i v o ste o p o r o sis 562

роtapov A.F., Matveev A.S., Ignatiev V.G., Ivanova A.A., Aprosimov L.A. Simulation o f ge n er a l a n est h esi a o n t h e «si m m a n 3g» a n d its e f f icie n c y 565

Lebedeva N.A., Seyalova A.S., Irintseev A.A., Cheldieva E.I., Poselskaya N.V. Th e morbidity o f u pper a ir w a y s a n d e a r in i n d u stri a l regi o n s o f t h e rep u b l ic s a k h a (y a k u ti a ) 567

Protopopova A.I., Tobokhov A.V., Gogolev N.M. Ex peri m e n t a l i n v estig a ti o n 569

Savvina V.A., Varfolomeyev A.R., Nikolayev V.N., Tarasov A.Yu, Vasilyev Ye.P., Grigoryev V.A., Sleptsov A.A., Grigoryeva L.A., Kolmogorov V.V., Sofronova M.S., Koryakina A.D. Su rger y o f c o n ge n it a l m a l f o r m a ti o n s in n e w b o r n s 578

Vinokurov M.M., Saveliev V.V., Gogolev N.M. Yalynskya T.V. Immunomodula ti o n a n d tre a t m e n t o f a c u te d estr u cti v e p a n cre a titis in a multidisciplinar y s u rgic a l h o spit a l 582

Savvina V.A., Tarasov A.Yu., Varfolomeyev A.R., Nikolaev V.N., Petrova N.E., Emeliynova Z.E., Grigoriev V.A., Sleptsov A.A. Ex perie n ce o f tre a t m e n t o f c o n ge n it a l d i a p h r a g m a tic h er n i a a m o n g b a b ie s 587

Sleptsova S.S., Duglas N.I., Shek L.A. Clinical c a se o f c o n d u cti n g preg n a n c y a n d c h i l d b irt h a t t h e w o m a n w it h c h r o n ic v ir a l h ep a titis b in t h e rep l ic a ti v e f o r m 591

446 Spis treści/Contents

Filippova R.D., Stepanova N.R., Nikiforova V.N. He a l t h st a t u s o f preg n a n t w o m e n 596

Tobohov A., Nikolaev V. Su rgic a l tre a t m e n t o f n ec k a n d retr o ster n a l g o iter , clinical c a se 598

Chibyeva L.G., Balanova O.P., Vasilev N.N. Descripti o n o f g a str o es o p h a ge a l re f l u x d ise a se in d i f f ere n t et h n ic gr o u ps , living in t h e n o rt h 600

Chugunova S.A., Nikolaeva T.Y., Semenov A. Co n tri b u ti o n o f cere b r a l v a sc u l a r a n o m a l ies in h e m o rr h a gic str o k e str u ct u re in d i f f ere n t r a ci a l gr o u ps o f y a k u ti a 604

Troev I.P., Petrova P.G. Osadchuk A.V., Osadchuk L.V., Kleshchev M.A., Gutorova N.V. Regi o n a l pec u l i a rities in se m e n q u a l it y a n d ser u m h o r m o n a l c o n ce n tr a ti o n s o f citi z e n s f r o m y a k u ti a 608

447 448 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Ga str o es o p h a ge a l re f l u x d ise a se in a ss o ci a ti o n w it h lipid-m et a b o l ic i n d ic a t o rs a t t h e y a k u ts k

Asekritova A.S., Kylbanova E.S., Emelyanova E.A., Borisova E.P. f s a e i h p e “n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v ” y a k u t s k , r u s s i a .

ABSTRACT Aim: to estimate interrelations of gastroesophageal reflux disease with lipid-metabolic indicators at the Yakutsk. Materials and methods: a one-stage investigation of 100 patients of the Yakut nationality with gastroesophageal reflux disease (GERD) is carried out. For estimating the association of GERD clinical symptoms with lipid-metabolic indicators a method of binary logistical regress with compulsory inclusion of predictors has been used. Results: according to results of the comparison most statistically significant distinctions of metabolic indicators are revealed at GERD esophageal (eructation) and extra-esophageal symptoms (night cough), dyspepsia (distention, epigastric heaviness), as well as snoring. Logistical regression analysis has confirmed interrelation of clinical symptoms with lipid-metabolic indicators, as waist circumference, a level of arterial pressure and blood lipid (triglycerides, lipoprotein cholesterol of low and high density). Conclusions: thus, the estimation of interrelation of GERD clinical symptoms with MS criteria at the Yakutsk has revealed the influence of MS components, especially abdominal adiposity, arterial hypertension and triglycerides on the development of dyspepsic symptoms (distention, epigastric heaviness), GERD esophageal (eructation) and extra-esophageal manifestations (night cough).

Key words: gastroesophageal reflux disease, metabolic syndrome, Yakutia.

Wiad Lek 2015, 68 (4), 449-453

INTRODUCTION of the Republican hospital №2-Emergency medical aid and Study of comorbidity is one of the most actual problems gastroenterology of the Yakutsk clinical hospital within 2010- of modern medicine as it is necessary to diagnose timely the 2013, who corresponded to criteria of inclusion in the research. characteristics of combined pathologies and determine a 100 patients with GERD of the Yakut nationality were included certain treatment approach. The metabolic syndrome М( S) in the research, of them 50 people being with МS, no MS was and abdominal adiposity aggravate a current of many chronic noted for the rest 50 people. The men amounted to 37 %, and non-infectious diseases [1, 2], also they can be accompanied by women – 63 %, with middle age of 46, 92 (11, 35). cardiovascular complications which, in turn, result in fatal cases. The study was conducted within the research project «Metabolic In this connection while studying the combined pathologies at syndrome and chronic non-infectious diseases among inhabitants МS, scientist focus on cardiovascular diseases. At the same time, of Yakutia». The research report was approved by the local the researches published for the last years concern the problem committee on bioethics at the Yakutsk scientific center of complex of comorbidity and testify to associativity MS with characteristic medical problems of the Siberian branch of the Russian academy of gastroenterological symptoms [2-4]. of medical sciences. All patients gave the informed consent for Clinical-morphofunctional features of gastroesophageal participation in the research in accordance with the Helsinki reflux disease (GERD) were studied in various age and ethnic declaration (report №24 from June, 29, 2010). groups of the population of Yakutia [5-8]. However, now there Preliminary verification of GERD diagnosis was conducted are no works devoted to the comorbidity of reflux disease sand according to recommendations of the Mayo clinic and the Montreal МS at the Yakutsk. consensus (2006) at obligatory presence, giving trouble to a In this connection, the aim of the present work is the patient including heartburn and / or regurgitation once a week estimation of association of gastroesophageal reflux disease and more often within the last 6 months. For definition of a and lipid-metabolic indicators at Yakutsk with the metabolic damage degree of the esophageal mucous in order to establish a syndrome. HERD clinical-endoscopic type and reveal its complications and accompanying pathology of the mucous gastroduodenal zone MATERIALS AND METHODS the investigation with the flexible endoscope «OlympusXQ-40» A set of a clinical material was conducted by an unselected from the beginning of the treatment was conducted in fasting method of inclusion of all inpatients of the Emergency department state with preliminary anesthetic 10 %-s’ lidocaine solution. The

449 Asekritova A.S., et al degree of erosive esophagitis was estimated by Savary-Miller interrelation with WC, the level of arterial pressure (SAP/DAP) modified classification (1978). and only with one lipid profile indicator – TG (tab. II). The metabolic syndrome was diagnosed on the basis of When estimating the GERD extra-esophageal symptoms recommendations of the All-Russia scientific organization of the distinctions between night cough and indicators of arterial cardiologists from 2009. The basic sign: central (abdominal) pressure (SAP/DAP) were revealed. At patients suffering from adiposity type – waist circumference (WC) more than 80 cm night cough SAP/DAP average values had the highest levels at women and more than 94 cm at men. Additional criteria: in comparison with patients without the extra-esophageal arterial hypertension (AP ≥ 130/85 mm. of Mercury); increase symptom (tab. I). The logistical regression analysis has confirmed in triglycerides (TG≥1,7 mmol/l); low cholesterol of high density the relationship of night cough with SAP/DAP indicators, it lipoprotein (HDLC<1,0 mmol/l at men;<1,2 mmol/l at women); remaining at exception of the patients taking antihypertension high cholesterol of low density lipoprotein cholesterol (LDLC)> preparations (tab. II). 3,0 mmol/l; hyperglycemia in fasting state (glucose in blood At the patients surveyed by us with epigastric heaviness more plasma ≥ 6,1mmol/l); impaired glucose tolerance (glucose in negative distinctions on WC, AP levels, TG values and HDL blood plasma in 2 hours after the glucose infusion within ≥7,8 and (tab. I) were found out in comparison with the patients without ≤11,1 mmol/l). The central adiposity and two additional criteria the given symptoms. According to the results of the logistical were the basis for diagnosing the metabolic syndrome. regression (tab. III) we have confirmed that the development Laboratory methods of the research were carried out on such of the symptom as heaviness in epigastria is interrelated with a certified equipment as the biochemical analyzer «Olympus the indicators WC, SAP, DAP, TG and LDLC. AU 400» (Beckman Coulter, the USA) under instructions of At patients with complaints to stomach distention the higher manufacturers after standardization. Indicators of lipid spectrum rate of AD and WC was noted than at the patients without and glucose levels were defined in blood test from the median distention (tab. I) observed. At the regression analysis (tab. III) cubital vein after 12 hours of starvations. we have revealed the positive association of distention with WC, Statistical processing and the analysis of the data were performed AP indicators and blood lipids (TG, HDLC). with use of the package IBM SPSS Statistics 19. Measures of the central tendency and dispersions of quantitative variables are presented as DISCUSSION M (SD) – an average value (standard deviation) and Me (Q25-Q75) In our research, we have found out the interrelation of dyspepsic – a median (25 and 75 quartile distributions). For selection of symptoms (distention, epigastric heaviness), GERD esophageal the statistical criterion of checking the normal distribution law of (eructation) and extra-esophageal symptoms (night cough) with quantitative signs the Kolmogorov-Smirnov test with amendment of lipid-metabolic indicators such as WC, AP indicators, TG levels, Lilliefors and Shapiro-Wilk statistics was used. Based on the results LDLC and HDLC. It is necessary to note that these indicators of testing nonparametric criteria were applied when comparing the are MS diagnostic criteria. The results of the interrelation of independent groups. The pair comparisons were conducted by means GERD clinical symptoms with lipid-metabolic indicators at of the Mann-Whitney criterion. For estimation of the interrelation the Yakuts will be coordinated with the researches carried out of HERD clinical symptoms with components MS the method of in other countries where overweight, namely the index of body binary logistical regression with compulsory predictor inclusion has weight are shown as strong independent risk factors of more been used. As a dependent variable clinical symptoms were serially frequent and severe symptoms of GERD and erosive esophagitis taken, where as independent variables comprise lipid-metabolic [9-12]. There is also a growing tendency of the central adiposity, indicators (waist circumference (WC), systolic arterial pressure the increase of waist circumference instead of the general body (SAP), diastolic arterial pressure (DAP), TG, HDLC, LDLC, glucose weight index, it considered as a strong risk factor of GERD in fasting state and postprandial). Quality of binary classification was development and its complications [4, 13, 14]. Also in the study estimated by the area of ROC-curve. Critical value of significance conducted among the Chinese pensioners by means of models point (p) was equal 5%. of the logistical regression, researchers revealed that the arterial hypertension and TG high level in blood are interrelated with RESULTS substantial growth of GERD risk [15]. According to the results of the comparison, the most statistically significant distinctions of metabolic indicators were revealed at CONCLUSION GERD esophageal (eructation) and extra-esophageal symptoms In conclusion, the estimation of interrelation of GERD clinical (night cough), dyspepsia symptoms (distention, epigastric symptoms with lipid-metabolic indicators at the patients of the heaviness) (tab. I). Yakut nationality has revealed the influence of MS components, As for the esophageal symptoms, only in eructation the following including the abdominal adiposity, arterial hypertension and distinctions on average values WC, SAP/DAP, TG and HDL triglycerides on the development of dyspepsic symptoms (distention, (tab. I) were revealed. However, at the same time, at application epigastric heaviness), GERD esophageal (eructation) and extra- of the logistical regression analysis the eructation had positive esophageal symptoms (night cough).

450 Gastroesopha g e a l re f l u x d i s e a s e in association w i t h lipid-m e t a b o l i c i n d i c a t o r s a t t h e ya k u t s k 0,214 0,825 0,134 0,368 0,097 0,001 0,001 <0,001 Indicators –average value; value; –average M 80 84 79 76 N o 119 120 6,72 7,20 5,20 3,19 5,34 3,12 1,28 1,27 1,23 1,07 (1,25) (1,05) (0,31) (0,57) (7,58) (3,58) (0,95) (20,87) (72-97) (60-90) (100-130) (4,62-6,10) (5,77-7,65) (2,34-3,85) (1,06-1,45) (0,79-1,49) distention 98 84 132 130 6,25 5,90 5,40 3,66 5,40 1,30 3,42 1,37 1,57 1,39 87,5 100,5 (1,39) (1,26) (0,48) (0,92) (8,26) (0,95) (18,19) (13,17) (80-90) (120-140) (78-110,5) (4,46-6,20) (5,29-7,25) (2,81-4,10) (1,12-1,56) (0,87-2,17) Distention р 0,059 0,147 0,036 0,814 0,013 0,027 0,005 <0,001 o 84 80 78 76 N 122 120 6,91 5,23 5,00 3,08 3,18 1,28 1,04 1,30 1,18 (1,34) (0,99) (0,29) (0,55) (1,02) (17,00) (12,72) (20,82) (73-96,5) (110-140) (4,40-6,02) (2,26-3,83) (0,74-1,45) (60,0-90,0) (1,12 -1,51) 7,53 (6,25-7,70) epigastricheaviness ) 30 83 85 102 1 130 5,60 6,15 3,75 5,53 3,50 1,35 1,23 1,51 99,5 1,64 14,63 (1,27) (1,22) (0,95) (0,51) (0,93) (9,79) (80-90) (17,84) ( (120-140) (4,80-6,20) (2,79-4,23) (1,05-1,50) (0,91-2,30) (79,0-112,0) 5,80 (5,40-6,50) E pigastricheaviness р 0,634 0,851 0,705 0,810 0,017 0,263 0,068 0,023 90 80 80 124 120 6,54 6,20 5,20 3,28 5,39 1,28 3,26 1,34 1,37 1,17 78,51 (1,31) (1,12) (1,02) (0,42) (0,79) (18,75) (18,01) (11,89) (70-90) (75-103) (110-140) (5,60-7,65) (4,67-6,18) (2,49-3,94) (1,11-1,50) (0,77-1,72) o night cough N 99 90 137 103 135 6,06 6,02 5,55 3,36 5,25 3,31 1,25 1,34 1,52 1,44 85,63 (1,49) (1,11) (0,96) (0,35) (0,69) (17,58) (19,21) (10,31) (80-90) (123-149) (83,5-113) (5,05-7,32) (4,24-6,10) (2,88-4,10) (0,97-1,50) (1,01-2,05) N ight cough р 0,794 0,075 0,010 0,368 0,001 <0,001 <0,001 <0,001 o 84 78 76 80 N 6,3 121 120 7,00 5,10 5,22 3,06 3,13 1,32 1,29 1,02 1,16 (0,5) (1,49) (1,05) (0,28) (1,02) (17,39) (19,29) (12,67) (73-97) (60-90) (110-130) (5,47-7,63) (4,35-5,85) (2,21-3,82) (1,14-1,52) (0,71-1,44) eructation 86 90 133 102 130 6,10 5,65 6,48 3,82 5,60 3,59 1,21 1,76 1,67 103,5 (1,25) (1,17) (0,91) (7,44) (0,91) (14,67) (16,40) (80-90) (96-113) (120-140) 1,34 (0,55) (5,46-7,62) (4,83-6,20) (2,89-4,18) (1,03-1,49) (1,02-2,30) E ructation M e M e M e M e M e M e M e M e M (SD) M (SD) M (SD) M (SD) M (SD) M (SD) M (SD) M (SD) (Q25-75) (Q25-75) (Q25-75) (Q25-75) (Q25-75) (Q25-75) (Q25-75) (Q25-75) l / , l l S components at patients of the Yakut nationality Yakut of the patients at and M S components GERD clinical symptoms Indicators , , / / , , , , см SAP DAP mmol LDLC , PPGL HDLC mm of mm of WC mmol/l mmol/l mmol mmol M ercury M ercury Glucose TG able I. T level; glucose PPGL–postprandial cholesterol; lipoprotein density high HDLC- cholesterol; lipoprotein density low - LDLC –triglycerides; TG pressure; arterial DAP–diastolic pressure; arterial systolic SAP- circumference; waist - WC Note: M e - a median; Q25-Q75 - 25 and distribution quartiles; of distinctionsthe groups deviation; significance comparison of statistical SD – standard at р – anobtained level

451 Asekritova A.S., et al

Table II. Association of GERD clinical symptoms with MS components (binary logistical regression). ROC –curve 95% CI for Exp (B) Indicators В(SE) р Exp (B) AS 95% CI SE р lower upper S Lower Upper Eructation WC, cm 0,056 (0,013) 0,000 1,058 1,031 1,086 0,76 0,66 0,86 0,05 <0,001 SAP, mm of Mercury 0,040 (0,013) 0,003 1,040 1,014 1,068 0,69 0,59 0,79 0,05 <0,001 DAP, mm of Mercury 0,091 (0,024) 0,000 1,096 1,044 1,150 0,73 0,63 0,83 0,05 <0,001 TG,mmol/l 1,148 (0,331) 0,001 3,152 1,648 6,029 0,71 0,61 0,82 0,05 <0,001 HDLC, mmol/l 0,131 (0,500) 0,794 1,140 0,428 3,034 0,45 0,33 0,57 0,06 0,37 LDLC, mmol/l 0,557 (0,229) 0,015 1,745 1,114 2,733 0,66 0,55 0,77 0,06 0,01 Glucose, mmol/l 0,318 (0,191) 0,096 1,375 0,945 2,000 0,61 0,49 0,72 0,06 0,08 PPGL, mmol/l 0,050 (0,278) 0,859 1,052 0,610 1,814 0,47 0,26 0,69 0,11 0,79 Night cough WC, cm 0,026(0,015) 0,072 1,027 0,998 1,056 0,64 0,49 0,79 0,08 0,07 SAP, mm of Mercury 0,040(0,017) 0,015 1,041 1,008 1,076 0,69 0,55 0,83 0,07 0,03 DAP, mm of Mercury 0,064(0,030) 0,035 1,066 1,005 1,131 0,67 0,53 0,82 0,07 0,03 TG, mmol/l 0,231(0,328) 0,482 1,259 0,662 2,396 0,59 0,44 0,74 0,08 0,26 HDLC, mmol/l -0,666(0,818) 0,416 0,514 0,103 2,555 0,52 0,35 0,68 0,08 0,81 LDLC, mmol/l 0,052(0,281) 0,854 1,053 0,607 1,828 0,53 0,37 0,69 0,08 0,71 Glucose, mmol/l -0,125(0,254) 0,622 0,882 0,537 1,451 0,52 0,35 0,68 0,08 0,85 PPGL, mmol/l -0,283(0,357) 0,427 0,753 0,374 1,516 0,56 0,29 0,83 0,14 0,64 Note to Tables 2 and 3: WC- waist circumference; SAP –systolic arterial pressure; DAP - dyastolic arterial pressure; TG - triglycerides; HDLC - low density lipoprotein cholesterol; HDLC - high density lipoprotein cholesterol; PPGL –a postprandialglucose level; B– regression ratio; SE - standard error; р – an obtained level of statistical significance of distinctions; Exp (B) - odd ratio; CI - confidential interval; S – ROC-curve square; AS 95 % CI – asymptomatic 95 % confidential interval.

Table III. Association of GERD clinical symptoms with MS components МС (binary logistical regression). Epigastric heaviness WC, cm 0,050 (0,013) 0,000 1,051 1,025 1,077 0,73 0,63 0,83 0,05 <0,001 SAP, mm of Mercury 0,023 (0,012) 0,048 1,023 1,000 1,047 0,63 0,52 0,74 0,06 0,03 SAP, mm of Mercury 0,054 (0,019) 0,005 1,055 1,016 1,096 0,66 0,55 0,76 0,06 0,01 TG, mmol/l 0,866 (0,309) 0,005 2,377 1,297 4,355 0,65 0,54 0,75 0,06 0,01 HDLC, mmol/l 0,289 (0,502) 0,565 1,335 0,499 3,573 0,49 0,37 0,60 0,06 0,81 HDLC, mmol/l 0,432 (0,217) 0,046 1,541 1,008 2,356 0,63 0,51 0,74 0,06 0,04 Glucose, mmol/l 0,249 (0,187) 0,182 1,282 0,890 1,848 0,58 0,47 0,69 0,06 0,15 PPGL, mmol/l -0,487 (0,319) 0,127 0,614 0,329 1,148 0,70 0,49 0,91 0,11 0,06 Distention WC, cm 0,041(0,012) 0,001 1,042 1,018 1,067 0,63 0,43 0,84 0,10 0,22 SAP, mm of Mercury 0,042(0,013) 0,001 1,043 1,017 1,071 0,70 0,60 0,81 0,05 0,001 DAP, mm of Mercury 0,064(0,020) 0,001 1,067 1,026 1,109 0,68 0,57 0,78 0,06 0,002 TG, mmol/l 0,622(0,290) 0,032 1,863 1,056 3,287 0,60 0,48 0,71 0,06 0,09 HDLC, mmol/l 0,608(0,540) 0,260 1,837 0,637 5,295 0,55 0,44 0,67 0,06 0,37 LDLC, mmol/l 0,307(0,209) 0,147 1,354 0,899 2,039 0,59 0,47 0,70 0,06 0,13 Glucose, mmol/l 0,048(0,181) 0,792 1,049 0,735 1,496 0,51 0,39 0,63 0,06 0,83 PPGL, mmol/l -0,282(0,291) 0,332 0,754 0,426 1,334 0,63 0,43 0,84 0,10 0,22

452 Gastroesopha g e a l re f l u x d i s e a s e in association w i t h lipid-m e t a b o l i c i n d i c a t o r s a t t h e y a k u t s k

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ADDRESS FOR CORRESPONDENCE: Asekritova A.S. Russia, Republic of Sakha (Yakutia), 677000, Yakutsk city, 58, Belinsky street, [email protected]

453 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Fe a t u res o f clinical-f u n cti o n a l m a n i f est a ti o n s o f c h r o n ic o b str u cti v e l u n g d ise a se in c o m b i n a ti o n w it h m et a b o l ic s y n d r o m e in et h n ic gr o u ps o f t h e y a k u ts a n d t h e r u ssi a n s

Borisova E.P., Kylbanova E.S., Asekritova A.S. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k.a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT Aim: studying features of clinical-functional manifestations of chronic obstructive lung disease in the combination with metabolic syndrome in the Yakut ethnic group. Materials and methods: the basic group consisted of 39 patients of Yakut nationality with chronic obstructive lung disease (COLD) in the combination with metabolic syndrome (MS), middle age of them being 53,4±1,17 years. The comparison group comprised 40 patients of Russian nationality with COLD and МS with middle age 53,1±1,21 years. Features of clinical manifestations and respiratory functions are studied. Results: cough and sputum were noted in dynamics for 3 years by 64,1 % of Yakut patients and 85 % of the Russians, р=0,033; the intensity of cough was marked at 30 % of patients of Russian nationality and 15,4 % of patients of the Yakut nationality, р=0,016. The morning sputum and daily sputum within 3 months a year at the Russians in comparison with the Yakuts was marked in 95 % vs 74,4 %, p=0,011; 80,0 % vs 56,4 % р=0,024, accordingly. According to Medical Research Council (mMRC) Dyspnea Scale (Mahler et al., 1985) dyspnea has been 2,2±0,09 points at the Yakuts vs 2,7±0,09 points at Russian, p=0,002. At patients of the Yakut nationality more often exacerbations were registered 2 times a year (53,8 %), at patients of Russian nationality noted 3 times a year (55 %). Respiratory function manifestations have been at patients of the Yakut nationality with COLD and МS, in comparison with similar Russian patients:

forced expiratory volume for a first second (FEV1) – 64,0±2,30 % vs 56,8±2,69 %, р=0,026; forced vital capacity of lungs (FVC) – 65,0±2,45 vs 65,0±3,70,

р=0,733; FEV1/FVCL ratio being 102,5±2,81 vs 87,3±3,30, р=0,000, accordingly. Conclusions: regardless of ethnicity the phenotype “D” has higher prevalence rate of clinical phenotype COLD in the combination with metabolic syndrome, thus at the Russians the clinical COLD is characterized by severe clinical manifestations in comparison with the Yakuts, and also in both ethnic groups expiratory

dysfunctions in the form of decreasing FEV1, decreasing FVC and increases of ratio FEV1/FVC> 70 % are marked.

Key words: metabolic syndrome, chronic obstructive lung disease, expiratory function, the Yakuts, the Russians.

Wiad Lek 2015, 68 (4), 454-457

INTRODUCTION forecast at patients with COLD as compared with the control Chronic obstructive lung disease (COLD) and metabolic group [3, 4, 5]. syndrome (MS) are considerable problems of public health service However, for the moment there are still very few individual of the 21st century and society as a whole. Now the metabolic researches considering features of clinical-functional manifestations syndrome (МS) is considered as ‘a 21st century pandemic’ by of COLD in the combination with MS, and we have not found WHO experts. Its prevalence among adult population of Russia out such data concerning the Yakut ethnic group. according to the All-Russia scientific organization of cardiologists The aim of the research was studying features of clinical- (2009) amounts 20-40 % and it is marked more frequently at functional manifestations of chronic obstructive lung disease the middle and senior aged. The indicator of MS prevalence with metabolic syndrome in the Yakut ethnic group. by criteria of the International diabetic federation among the native population of Yakutia averages 8,8 % [1]. MATERIALS AND METHODS Within the last decade, the COLD concept has been generally A complex of clinical-functional, instrumental method of identified as diseases with systematic manifestations including examination of 79 patients based on the acute medical unit of cardiovascular pathology, cachexia, muscular dysfunction, the Republican Hospital №2 – the Emergency medical aid center osteoporosis, anemia, clinical depression, metabolic disorders of Yakutsk from 2009 for 2013 was carried out. The research was and endothelial dysfunction [2]. The epidemiological data conducted within the research project « Metabolic syndrome and testifies that some accompanying diseases, including diabetes chronic non-infectious diseases among inhabitants of Yakutia». are marked much more often and connected with the worst All patients signed the informed consent for being examined

454 Fe a t u r e s o f clinical-f u n c t i o n a l manifestations o f c h r o n i c obstructive l u n g d i s e a s e in combination w i t h m e t a b o l i c s y n d r o m e in e t h n i c g r o u p s according to the Helsinki declaration of the World association on recommendations of the All-Russia scientific organization «Ethical principles of carrying out scientific medical researches of cardiologists from 2009. with participation of the person». There has been approval by The patients survey was conducted with the account of the the local ethical committee based on Yakutsk scientific center developed questionnaire approved by ethical committee which of complex medical problems of the Siberian branch of the contained a list of questions: socially-demographic characteristic, Russian academy of medical sciences. anamnesis data, heredity research, behavior and health, a validated The basic group included 39 patients of the Yakut nationality questionnaire according to respiratory symptoms, a scale of COLD with COLD in the combination with МС. Middle age was equal symptoms (Paggiaro P.L., 1998). The spirometery was conducted 53,4±1,17 years, on the basis of sexual composition: men of 35,9 %, on the program complex “Valenta” (St.-Petersburg) for carrying women of 64,1 %, regular smokers were 35,9 %, the smoking out functional researches. The following postbronchodilatatory index has amounted 11,2±2,67 pack-years. The COLD severity volume and high-speed indicators of expiratory function s (EF): level was distributed as follows: easy degree – 7,7 %, average forced expiratory volume for the first second (FEV1), forced degree – 74,4 %, heavy – 18,0 %. vital capacity of lungs (FVC), and also the relation of these two

The comparison group included 40 patients of Russian indicators (FEV1/FVC). Statistical processing and analysis of the nationality with COLD in the combination with МS. Middle data were carried out with a use of package SPSS (19 version). age corresponded to the age group of patients of the Yakut Quantity indicators in the research groups were characterized nationality (53,1±1,21 years). On the basis of sex composition: by means of average values (M) and an average standard error men and women were 50,0 %, while 37,5 % of patients were (m). Distribution laws of quantity indicators were checked by regular smokers, the smoking index has made 18,3±3,26 pack- Kolmogorov-Smirnov’s criterion. The results have confirmed years. On COLD severity level: easy severity level was noted that distribution of many quantity indicators did not submit at 6,9 %, average degree – 58,6 %, heavy degree – 34,5 %. All to the normal law. Therefore, for the comparative analysis of patients involved into the research in the comparison group quantity indicators a nonparametric Mann-Whitney test was were new arrivers, with average term of residing in the north applied. The research of interrelations of qualitative signs was 35,6±1,58 years. conducted by means of Pearson chi-square standard criterion. When comparing the investigated groups authentically did For a threshold level of significance of all applied statistical not differ on age, sex composition, number of regular smokers, criteria the value р <0,05 was accepted. smoking index and COLD severity level. ‘Chronic obstructive lung disease’ was diagnosed based RESULTS on complaints, anamnesis of the disease, objective inspection, Cough and sputum has been noted in dynamics for 3 years by spirometer data, according to «Global strategy of diagnostics, 64,1 % of Yakut patients and 85 % of Russians, р=0,033 (tab. I); the treatment and prevention of chronic obstructive lung disease» intensive cough was marked at 30 % of patients of Russian nationality revision in 2011. ‘Metabolic syndrome’ was established based and 15,4 % of patients of the Yakut nationality, р=0,016.

Table I. Characteristics of cough syndrome and character of sputum discharge at patients of Yakut and Russian population with COLD and MS, %. COLD+MS, the Yakuts COLD+МS, the Russians Signs p* n=39 n=40 Progress of cough and sputum for 3 years 64,1 85,0 0,033 no 7,7 0,0 0,042 Light 33,3 15,0 0,042 Intensity of cough moderate 43,6 55,0 NS High 15,4 30,0 0,042 Morning sputum discharge 74,4 95,0 0,011 Daily sputum discharge during 3 months a year 56,4 80,0 0,024 Sputum production no 12,8 2,5 least 48,7 60,0 0,307 moderate 35,9 32,5 0,307 Sputum color large 2,6 5,0 0,307 transparent 0,0 2,5 0,307 white-grey 46,2 25,0 0,106 light-yellow 25,6 47,5 0,106 green 28,2 25,0 0,106 Note: *р – authenticity of distinctions of Pearson chi square criteria

455 Borisova E.P., et al

Table II. Syndrome of dyspnea and a number of recurrence at patients of Yakut and Russian population with COLD and MS, %. COLD+MS, the Russians Signs COLD+MS, the Yakuts n=39 p* n=40 Rattles and whistles in breast 61,5 85,0 0,018 Dyspnea with sensation of ‘rattles’ 41,0 65,0 0,033 no 2,6 0,0 NS Intensity of dyspnea at moderate load 74,4 42,5 0,016 at light load 20,5 50,0 0,016 at minimum load 2,6 7,5 NS till 1 17,9 7,5 NS The number of recurrence a year 2 and more 53,8 37,5 NS 3 and more 28,2 55,0 0,044 Note: *р – authenticity of distinctions of Pearson chi square criteria

Table III. Indicators of spirography at patients of Yakut and Russian population with COLD and MS, %. COLD+MS, the Yakuts n=39 COLD+MS, the Russians n=40 FIR index p* M±m M±m FVC 65,0±2,45 65,0±3,70 0,733 FEV1 64,0±2,30 56,8±2,69 0,026 FEV1/FVC 102,5±2,81 87,3±3,30 0,000 Note: *р – authenticity of distinctions of Mann-Whitney criteria

On character of sputum statistically significant distinctions whereas at patients of Russian nationality in most cases there are noted in such parameters as morning sputum n (74,4 % of were 3 cases a year (55,0 %). patients of the Yakut nationality vs 95 % of patients of Russian When comparing indicators of the respiratory function nationality, p=0,011) and daily sputum within 3 months a year in the groups surveyed we revealed that at patients of the (56,4 % of patients of the Yakut ethnic group vs 80,0 % of patients Yakut nationality with the combination COLD and МS the of Russian ethnic group, р=0,024). On intensity of sputum and lower indicator of FEV1 has been noted and amounted for color reflecting the intensity of inflammatory changes of the 64,0±2,30 % that is statistically significant higher than in the bronchopulmonary system, no statistically significant distinctions group of Russian patients with COLD and МS – 56,8±2,69%, between the investigated groups are revealed. р=0,026 (tab. III). In our research FVC is lower in both When analyzing the syndrome of shortness of breath we groups surveyed – 65,0±2,45 % at Yakuts and 65,0±3,70% revealed (tab. II) that at Yakut patients with COLD and МS at Russians. Also statistically significant distinctions of the rattles and whistle in the thorax (61,5 % vs 85,0 %, р=0,018) and indicators FEV1/FVC in groups with the combination of COLD dyspnea with «rattles» (41,0 % vs 65,0 %, р=0,033) authentically and МS the Yakut and Russian nationalities were revealed for were less often marked. The analysis of a degree of dyspnea has the account of greater decrease FEV1 among the patients of shown that at the patients of Yakut nationality with COLD and Russian nationality are revealed: 102,5±2,81 % vs 87,3±3,30% МS the intensity of short wind has appeared less intensive as (р=0,000), accordingly. compared with similar patients of Russian nationality. So, at patients of the Yakut nationality in 77,0 % of cases the dyspnea DISCUSSION was at moderate loading, light loading – in 20,5 %, at minimum Thus, in the combined COLD andМ S current the group «D» loading – in 2,6 %. The reverse picture has developed at patients with ‘the higher index of symptoms and high risk of exacerbation’ of Russian nationality: in half of all cases the patients complained is noted at patients regardless of ethnicity (GOLD, 2011). And of dyspnea at light loading, in 42,5 % – at moderate loading, in a prevailing clinical phenotype COLD is the phenotype with 7,5 % – at the minimum loading. frequent exacerbations. At the same time, patients of the Yakut Some distinctions in frequency of exacerbation are revealed nationality have more favorable clinical picture in comparison in the groups as well. At patients of the Yakut nationality more with patients of Russian nationality. The results obtained by us often the exacerbations were registered 2 times a year (53,8 %) correspond to the literary data according to which the native

456 Fe a t u r e s o f clinical-f u n c t i o n a l manifestations o f c h r o n i c obstructive l u n g d i s e a s e in combination w i t h m e t a b o l i c s y n d r o m e in e t h n i c g r o u p s people of the North have acquired resistance to extreme climatic in comparison with the Yakuts. In both ethnic groups in the geographic conditions by formation of biological adaptation [6]. the combination COLD and МS the obstruction of external The features of morphological and biochemical parameters can respiratory impairment is marked accompanied by the decrease be marked at the native people: somatotype; pre-natal formation FEV1, FVC and the increases of relation FEV1/FVC >70%. of «northern lung»; metabolism (prevalence of a protein-fatty type of metabolism); membranes of blood cells; blood chemical REFERENCES compound, features of functioning and regulation of various 1. osakovskiy V.L. Metabolicheskiy sindrom u aborigennogo naseleniya Yakutii. / V.L. systems. Also at the Northern indigenous population difficult Osakovskiy, L.G. Gol’dfarb, T.M. Klimova [et al.] // Yakutskiy meditsinskiy zhurnal , 2010, airway of bronchial tubes and insignificant obstruction of large No. 2. P. 98-102. bronchi are noted as a compensatory structural-functional 2. Tkacova R. Systemic Inflammation in ChronicO bstructive Pulmonary Disease: May Adipose component protecting fabrics from overcooling [7]. While Tissue Play a Role? / R. Tkacova // Review of the Literature and Future Perspectives. at the arrived population who have lived for more than 10- Mediators Inflamm., 2010, Vol. 5, P. 859-889. 15 years, adaptable reserves appear to be already possible . 3. Cazzola M. Prevalence of comorbidities in patients with chronic obstructive pulmonary Therefore physical overloads, excessive smoking, could cause disease. / M. Cazzola, G. Bettoncelli, E. Sessa [et al.] // Respiration, 2010, Vol. 80, P. the higher rate of hypoxemia and development of destructive 112-119. changes of the lung tissue. It causes in turn, higher prevalence 4. Paggiaro P.L. Multicentre randomised placebo controlled trial of inhaled fluticasone and severe current of acute and chronic pathological processes propionate in patients with chronic obstructive pulmonary disease. P.L. Paggiaro, R. in respiratory organs [8]. Dahle, I. Bakran [et al.] // Lancet, 1998, Vol. 351, № 9105, P. 773-780. At the same time, adiposity also influences lung functions and 5. Sode B.F. Myocardial infarction and other comorbidities in patients with chronic obstructive pulmonary volumes as it is related with reduction of expiratory reserve pulmonary disease: a Danish nationwide study of 7.4 million individuals. / B.F. Sode, volume and functional residual capacity due to extrapulmonary M. Dahl., B.G. Nordestgaard // Eur. Heart J., 2011, Vol. 32, P. 2365-2375. restrictive components [9, 10]. At the combination of COLD and 6. manchuk V.T. Sostoyanie i tendentsii formirovaniya zdorov’ya korennogo naseleniya МS in both ethnic groups decrease in key parameters of pulmonary Severa i Sibiri. / V. T. Manchuk., L.A. Nadtochiy // Byulleten’ SO RAMN – Bulletin SB RAMS, 2010, Vol. 30, no. 3, P. 24-32. ventilation FEV1, FVC is registered and accordingly the relation 7. Agadzhanyan N.A., Ermakova N.V., Kutsov N.A. Ekologo-fiziologicheskie i konstitutsional’nye FEV1/FVC amounts 70 % and over, getting nearer to 100 %. Similar associations between the central adiposity and obstruction of osobennosti korennogo i prishlogo naseleniya Severa. / N.A. Agadzhanyan., N.V. Ermakova., respiratory ways are described also in a number of researches. So, N.A. Kutsov // Kontseptsiya sokhraneniya zdorov’ya cheloveka na Kraynem Severe: K-B.H. Lam et al. (2010) have shown that abdominal adiposity Materialy nauchno-prakticheskoy konferentsii. Noril’sk, 1994, P. 50-51. is associated with obstruction of respiratory ways irrespective of 8. Avtsyn A.P., Zhavoronkov A.A., Marachev A.G., Milovanov A.P. / Patologiya cheloveka smoking status: OR 1,43, 95 % DI 1.09-1.88 [11]. In the research na Severe. Moscow, Meditsina, 1985. 416 p. of N. Leone et al. (2009) МS and abdominal adiposity are closely 9. Gifford A.H. Respiratory function in an obese patient with sleep-disordered breathing. / A.H. Gifford., J.C. Leiter., H.L. Manning // Chest, 2010, Vol. 138, P. 704-715. connected with low FEV1 and FVC, irrespective to possible interfering factors [10]. Adiposity is connected with restriction of respiratory 10. Leone N. Lung function impairment and metabolic syndrome the critical role of abdominal excursion of lungs with decrease of FEV and increase of relation obesity. / N. Leone., D. Courbon., F. Thomas., [et al.] // Am. J. Respir. Crit. Care Med., 2009, Vol. 179, P. 509-516. FEV1/FVC> 70% [12]. 11. Lam K-B.H. Airflow obstruction and metabolic syndrome: the Guangzhou Biobank CONCLUSION Cohort Study. / K-B.H. Lam., R.E. Jordan., C.Q. Jiang., [et al.] // Eur. Respir J., 2010, Vol. Regardless of ethnicity the phenotype ‘D’ is considered the 35, P. 317-323. most common clinical phenotype of COLD in the combined 12. Nakajima K. A possible association between suspected restrictive pattern as assessed current with metabolic syndrome, however at the Russians the by ordinary pulmonary function test and the metabolic syndrome. / K. Nakajima., Y. COLD clinic is characterized by severe clinical manifestations, Kubouchi., T. Muneyuki., [et al.] // Chest, 2008, Vol. 134, no. 4, P. 712-718.

ADDRESS FOR CORRESPONDENCE: Borisova E.P. Russia, Republic of Sakha (Yakutia), 677013 Yakutsk city, 27, Oyunsky street Ph. 8914 2206769 [email protected]

457 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Ad a pti v e re a cti o n s o f i n d ige n o u s p o p u l a ti o n o f y a k u ti a

Borisova N.V., Petrova P.G. f s a e i h p e “n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v ” y a k u t s k , r u s s i a .

ABSTRACT Introduction: the researches of organism’s adaptive possibilities of indigenous population of the Arctic region are extremely important in modern conditions of the development of northern territories. The functional reserve of basic physiological systems and their interaction define «the health’s resources», its potential level. Aim: this research has substantiated the adaptive reactions of organism of the North inhabitants on the basis of medical-physiological results. Materials and methods: physical development was estimated by the standard anthopometrical method: the height and body mass were measured, index of body mass (BM), Quetelet’s index, Rohrer’s index were defined, area of body surface was calculated. Carbon dioxide in the air was defined by portable infra-red gas analyzer of firm “Fudji” for measurements indoors and outdoors. The parametres of blood acid-base state (ABS) were analyzed by standard procedures with microevaluator application ABL-330 (Denmark). Computer spirometry was done on the hardware-software diagnostic complex (HSDC) for analyses of external respiration function (NSRIMT – Russia) and «Pneumoscrin-2» of Erih Eger company (Germany). Arterial pressure was measured by Korotkov’s method. Results: the inhabitants of the North irrespective of ethnicity have conditions for more effective lung ventilation to satisfaction of the high metabolic requirements of the organism. Conclusions: stability of arterial pressure among indigenous population, microcirculation optimisation and transcapillary tissues exchange, conserves steady level of metabolism that testifies a high level of adaptation of the person to severe climate- geographic North conditions.

Key words: indigenous population of the North, Arctic regions, adaptation, the North, Yakutia, adaptive reactions.

Wiad Lek 2015, 68 (4), 458-463

INTRODUCTION northern territories are developed, is extremely actual nowadays The problem is important because ecological-physiological [2-4]. mechanisms of adaptation of the human body to various life Aim: The research purpose is substantiation of adaptive reactions conditions are defined by the possibility of models of control, of students’ organism on the basis of medical-physiological results behaviour correction and preventive disadaptive conditions. In and development of the scientifically-proved recommendations spite of diversity, the development of adaptation processes has directed on conservation and strengthening of health in extreme some laws caused by both environment influence and specific conditions of Yakutia. features of the organism. Sharply continental climate of Yakutia causes sharp annual MATERIALS AND METHODS temperature drops and presence of two expressed seasons: winter The choice of methods and volume of researches were defined lasts 3/4 of the year and almost immediately passes into summer by the work purpose. The examinees have been informed on which proceeds from the end of May till August. The power the general character of forthcoming influences according and cost of functional reserves of the organism are known to to the standard rules of the man’s examination. Full safety of be estimated by unsuccessful factors, loads, and “the adaptation examination and noninvasive manipulations has been guaranteed price” by degree and value of physiological reactions of the to all examinees before the research. At the moment of the person in inadequate and sometimes extreme conditions. The research all examinees were at the age of 17-19 years old, had results of several fundamental researches testified the existence no signs of diseases and had been recognized almost healthy. of ethnic distinctions of the major physiological organism’s The general characteristic, volume and research methods are constants in functioning of not only separate systems, but also presented in table I. adaptive alterations in various inhabitancies [1, 3]. Physical development was estimated by the standard Thus, the research of adaptive possibilities of the natives’ anthopometrical method: the height and body mass were organisms of the Arctic region when economic and mental measured, index of body mass (BM), Quetelet’s index, Rohrer’s potential of Russia are defined by quantitative and qualitative index were defined, area of body surface was calculated. The height characteristics of health which the population possesses today was measured by means of vertical auxanometer in a standing when new state long-term programs on intensive development of position without footwear. Measurement was made within 0,5 cm.

458 Ad a p t i v e r e a c t i o n s o f i n d i g e n o u s p o p u l a t i o n o f y a k u t i a

Table I. General characteristic, volume and research methods. Number of the examined, № Direction of researches Research methods people 1st investigation phase (seasons winter-summer) 1. Questioning 296 2. Anthropometry 190 3. Medical-physiological researches Assessment of indexes of peripheric hemodynamics 296 4. Research of function indexes of external respiration system 296 5. Research of indexes of acid-base state of blood 296 2nd research phase 6. Ecological-physiological Research of the carbon dioxide content in atmosphere

Scales for body mass measurement were positioned on a rigid carried out by the standard methods with package use «SPSS floor. 13». Mean sizes Mean (M), standard mean error (m), standard Carbon dioxide in the air was defined by portable infra-red deflections Standard Deviation (SD) and 95 % of confidence interval gas analyzer of firm “Fudji” for measurements indoors and were calculated. Correlation analysis was done on Spearman's outdoors. and also one-dimensional dispersion analysis with the use of The parametres of blood acid-base state (ABS) were analyzed criterion F- Fisher was made. The assessment of reliability of by standard procedures with microevaluator application ABL-330 distinctions between the data received in the examined groups, (Denmark). Studying of features of blood gas content included was made on Student’s t-criterion. Normal distribution laws analyses of the following indexes of arteliazic capillary blood: were carried out by Kolmogorov-Smirnov’s criterion. In cases

рН, partial strain of carbon dioxide in blood (рСО2, mm hg), of allocation difference from normal, nonparametric Mann- partial strain of oxygen (рО2, mm hg), bicarbonates of plasma Whitney criteria were used for the analysis. The method of twin - (НСО3 ), standard bicarbonates (SВ, mEq/l), true surplus of the correlation analysis with coefficient calculation correlation (r) bases (АВ, mEq/l), deficiency of the buffer bases (ВЕ, mEq/l), was used for detection of communication closeness between haemoglobin oxygenation (SatО2, %), and also the haemoglobin studied signs. content (Нb, GM). Population’s examination was done with ethical standards Computer spirometry was done on the hardware-software stated in the Helsinki declaration and Instructions of the European diagnostic complex (HSDC) for analyses of external respiration community (8/609 EU) (2000). function (NSRIMT – Russia) and «Pneumoscrin-2» of Erih Eger company (Germany). The analyses of external respiration function RESULTS AND DISCUSSIONS included the following parametres: vital capacity of lungs (VCL), Yakutia is a unique region in the world with sharply continental forced vital capacity of lungs (FVCL), respiratory capacity (RC), climate where the voltage of temperature variations of air exceeds respiratory minute volume (RMV) and respiration rate (RR, 100°С (+40°С in summer and -60°C in winter). The mean annual respiration/minute). The indexes of trachea- bronchial patency temperature of air variates from-16°C (in the northeast) to were defined: maximum volume air flow rate of lungs fullness in +10°С (in the south). The season with temperatures below 0 lasts

75, 50 and 25% (PEFR75, PEFR50 and PEFR25) accordingly. External 6-7,5 months (from October till April). It is actually possible respiration indexes were defined in absolute numbers and in % to mark out two contrast seasons of year – short, hot summer concerning their due values (Knudson R.J. et al., 1976). and long, cold winter. The following indexes have been studied: heart rate (HR, Deep and frequent amplitudes of fluctuations of partial SG/min), systolic pressure (SP, mm hg), diastolic pressure (DP), density of oxygen for short time intervals (in 6-8 hours) reaching sphygmic pressure (SP), average dymanic pressure (ADP), cardiac 35-40 g/m3 are observed in the air in the north of Yakutia that index (CI, l/m²), general peripheric vascular resistance (GPVR, is displayed in weather anomaly – hypoxia and hyperoxia are dyne cm sec-5), double product (DP, RVU), a vegetative Kerdo’s observed. index (VKI, RVU), medium blood pressure (MBP, mm hg). The soil breath is known to reach its maximum in the autumn- Arterial pressure was measured by Korotkov’s method. The winter season that leads to atmosphere enrichment by carbon estimated integrated index characterising adaptive reserves of dioxide (СО2). The gas which is collected under chilled high blood circulation system – АP (adaptive potential) were defined layer of soil is thrown out in atmosphere in clamping period for complex assessment of health level and revealing of possible of seasonal thawing and long frozen ground by frost fractures. adaptive disorders (Ermakova N.V., Berseneva A.P., 1994). Frost of seasonal thawing soil which is strongly sated by carbon Research data and preprocessing were made in original dioxide, there is its squeezing from freezing through soil solution database Microsoft Excel 2002. Statistical data processing was in the inferior departments. When clamping of two fronts of

459 Borisova N.V., Petrova P.G. the frozen soil happens there is its almost full degassing of the profile located over permafrost and the collected carbonic acid gets to atmosphere by fractures and again remains not claimed neither vegetation, nor the frozen aqueous ecosystems [5, 6].. The data analysis has shown that in Yakutsk the maximum values of carbon dioxide in the air was 475±5 ppm and were fixed in November and December, and minimum – 343±4 ppm in June and the beginning of July. It was established that СО2 content indoors in winter season variates during the day. So, in the morning during practical lessons with 10-17 students the maximum rise of СО2 in the air was 1067±5 ppm, and at night values of carbon dioxide equaled to 371±3 ppm and gas concentration were equal in the air in the street. Similar essential fluctuations ofСО 2 in atmosphere indoors in air basin testified system changes in many parts of natural and anthropogenic Fig. 1. рСО dependence in capillary blood in the examined from рСО level in the air biocenoses going in parallel directions. 2 2 during various seasons of the year (in winter and summer). Thus, it is possible to assume that there is a possibility of influence of carbon dioxide excess on the health state of people with insufficiency of breath and blood circulation function. It is necessary to note also that such influence may have positive character as physiological effects of influence on the organism, as a rule, stimulating breath and blood circulation influence. cold climate conditions similar anthopometrical distinctions In the cold conditions similar effects can render beneficial predetermine size of functional reserves and adaptedness of the effect on processes of adaptation of the human body to low organism to climate-geographical characteristics of the place temperatures. of constant residing of people. The influence of severe climate of high widths on the human The research results of indexes of gas and acid-base state of body, including – cold and dry air on the bronchi-pulmonary system, blood corresponded to the data taken over across Russia, except causes significant morphofunctional changes – a bronchospasm, рО2 which has appeared reduced (tab. II). disorder of drainage function of bronchi and other changes SatО2 indexes approach to the inferior border of normal of lungs function even in almost healthy people. The hypoxia range. All examined has рН decrease in the sour side without has the mixed character and includes ventilation-perfusion depending on the season, especially in winter it was connected disorders and damage of cellular membranes by products of with chronic hypoventilation while cold air aspiring. Thus, peroxide oxidation of lipids. partial strain of carbon dioxide in blood capillaries came nearer Seasonal fluctuations of gas exchanges in people have adaptive to the highest border of normal range, the tendency to decrease character and are caused by organism adaptation to changed in level of the buffer bases that speaks about the compensated conditions of environment. The question is to study carefully gas acidosis. the mechanism of these seasonal changes and use the received The relative analysis of results has shown that strain of oxygen knowledge for the prevention of diseases. and saturation of capillary blood by oxygen in the examined in The 1st examined group were Caucasians (Russian, Ukrainians), winter season tends to decrease. We’ve revealed that values of the 2d group –Yakuts. carbon dioxide strain in capillary blood among the examined was

The relative analysis of anthopometrical characteristics of the lower in winter and СО2 level in the air – in summer (р <0.05). examined groups has shown distinctions in some parametres: Anatropic correlation link between values of СО2 strain in capillary height, body mass index, Rohrer’s index. Mean indexes of age and blood and СО2 level in free air was thus revealed: coefficient of body mass between the examined have no reliable distinctions twin correlation has compounded r =-0,4. In winter (December), that testifies the correctness of the examined groups. Length when level СО2 in the air was high among the examined strain and area of body surface is significantly above (р <0,05) in the СО2 was lower in capillary blood than in summer (June) when examined of the 1st group, and body mass index, Rohrer’s index carbon dioxide content in free air falls (fig. 1). – in the second group. The body mass index is the important Carbon dioxide is known to have direct and reflex exciting physiological parametre characterising constitutional features effect on the respiratory centre, causing increase and deep breath of the person, its physical development degree and level of its that promotes СО2 washing away from blood in winter. energy metabolism. Body mass index is known to be capable One of the major functions of working capacity of the to carry out substantially a role of prognostic criterion of the organism is breath function. Indexes of respiratory function assessment of compensatory -adaptive possibilities of the organism can be divided in two components: characteristics of respiratory (Kutsov G. M, 1994). Rohrer’s index reflects both degree of organ and gaseous exchange parametres in the lungs, reflecting physical development and level of energy metabolism of the transport of gases in the blood, heart work and state of tissue organism. So, it is obvious that people with big body mass index breath. Considering that fact that pathology among students will be more stable to low temperatures because of possibility of Yakutia are mostly respiratory organ diseases, studying of to increase heatproduction proportionally to body mass. In the cardio-respiratory systems, revealing and assessment of disorders

460 Ad a p t i v e r e a c t i o n s o f i n d i g e n o u s p o p u l a t i o n o f y a k u t i a

Table II. Dynamics of indexes of gas and acid-base state of blood during different seasons of the year (M+m). Seasons of the year Winter Summer Indexes 1group 2 group 1group 2 group PH, unit 7,373± 0,004 7,379±0,002 7,388±0,003 7,397±0,002*

pO2, mm hg 69,9±0,6 74,9±0,8* 77,8±0,5 81,1±0,8*

рCO2, mm hg 39,9±0,3 40,3±0,3 42,4+0,5 41,2+0,4* Hb, GM 144,1±1,1 146,5±1,2 146,8±1,2 148,4±1,4*

SatO2, % 92,9±0,2 93,9±0,2* 94,3±0,2 95,5±0,3* SB, mEq/l 23,6±0,1 23,7±0,1 23,7±0,2 23,9±0,2 BE, mEq/l -0,72±0,19 -0,61±0,14 -0,58±0,19 -0,36±0,13 Notes: The 1st group – examined – Caucasians The 2nd group – Yakuts Distinction is statistically significant in comparison with the 1st group, р <0,05

Table III. External respiration indexes during contrast seasons of the year (М+m). Seasons of the year Indexes Winter Summer 1 group 2 group 1 group 2 group VC, (l) 4,54±0,06 4,32±0,04 4,65±0,05 4,49±0,03* RVC, (l) 4,79±0,04 4,62±0,03 4,77+0,04 4,64±0,03 VC from RVC, % 94,7±1,2 93,5±1,1 97,5+1,2* 96,8±1,0* RR, breath/minute 17,1±0,5 16,9±0,4 16,2±0,4 15,8±0,3* BC, (l) 0,63±0,02 0,61±0,01 0,72±0,02* 0,71±0,01* RMV, (l) 10,7±0,2 10,3±0,3 11,7±0,3* 11,2±0,2* Notes: The 1st group – examined- Caucasians The 2nd group –Yakuts Distinction is statistically significant in comparison with the 1st group, р <0,05

of external respiration function allow us to make diagnostic Observable changes of frequency-volume correlation of lung process more qualitative and to estimate disease severity more ventilation towards relative prevalence of respiration rate in winter adequately. season among students can specify in decrease in functional The relative analysis of VC values among respondents has reserves of external respiration at this time of the year (fig. 2). shown reliable increase of this index in summertime of the year, The cause of RMV and LVC among the examined in winter in comparison with winter (p <0,05) that will be co-ordinated season can be connected with cold narrowing of bronchi and with the data of other authors. Thus students-Caucasians have bloodstream centralisation. Whereas the respiration rate increase

VC value reliably higher than representatives of the Yakut in winter season is possibly bound to raised СО2 content in nationality (p <0,05). atmosphere which includes chemoceptors, centres and effector As diffusion capacity of lungs is proportional to their part of chemical contour of breath regulation. volume, so VC volume is an index reflecting functionality of Analyses of trachea-bronchial patency (tab. IV) have shown external respiration system as a whole. Thus, inhabitants of that MEFV among the examined of both groups exceeds Central Yakutia irrespectively of ethnic nationality, conditions for more European age norms in 4-8 %, especially in summer (all indexes effective lung ventilation to satisfaction of the raised metabolic are given in percentage due to Knutson’s values). In summer season requirements of organism are created due to increased VC. the reliable increase of bronchi patency among respondents- Besides, VC increase is possibly compensatory adaptive reaction, Caucasians (р <0,05) was observed. allowing to improve parametres of air-conditioning of inhaled It has been found out that people of the Yakut nationality had air among inhabitants of the North. patency of various parts of trachea-bronchial tree lower, than

461 Borisova N.V., Petrova P.G.

their resistance, raises intrathoracic pressure and substantially forces work of respiratory organs, invoking additional strain. At the same time narrowing of bronchi increases cardiovascular system load. Thus, dynamics of indexes of external respiration function during contrast seasons of the year among examined Caucasians were higher that testified functional strain of regulatory systems in winter season of the year. Distinctions in indexes of respiratory system should affect cardiovascular system function. The cardiovascular system is the indicator of adaptive reactions of the whole organism. Fig. 2. The correlation of LVV and RR during various seasons of the year. Statistical analysis results of seasonal dynamics of cardiovascular Notes: The 1st group – examined – Caucasians. system indexes among the examined also essentially differed The 2d group – examined of the Yakut nationality. during contrast seasons of the year (tab. 5). So, frequency of heart rate in rest were reliably higher during winter time among Caucasians and minute volume of blood circulation – in summertime among Yakuts (р <0,05). among Caucasians people (р <0,05). It was probably compensatory Seasonal MBV changes among Yakut students were higher than structurally functional component carrying out function of tissue among Caucasians. At the same time, indexes of arterial pressure protection of lung from overcooling and reflecting physiological (SP, DP, ADP and GPVR) in healthy examined had no reliable mechanisms of regulation of heat emission through respiratory distinctions during contrast seasons of the year that testified ways. On the other hand, narrowing of respiratory ways increases more expressed inertness and stability of these indexes.

Table IV. Some indexes of trachea – bronchial patency in the examined students during contrast seasons of the year (М+m). Seasons of the year Indexes Winter Summer 1 group 2 group 1 group 2 group MEFV, % 105,8±1,6 104,3±1,4 108,1±1,6 106,3±1,6 PEFR25, % 102,6±2,1 101,8±2,3 105,6±2,6 104,3±2,5 PEFR50, % 89,5±1,3 87,3±1,9 103,4±2,7* 98,3±1,6* PEFR75, % 91,3±1,9 87,5±2,1 102,9±2,1* 99,8±1,5* Notes : The 1st group – examined- Caucasians. The 2d group –Yakuts. Distinction is statistically significant in comparison with the 1st group, р <0,05.

Table V. Some indexes of cardiovascular system during contrast seasons of the year (М±m). Seasons of the year Indexes Winter Summer 1 group 2 group 1 group 2 group SP, mm hg 121,7±1,1 119,7±1,1 118,3±1,3* 118,2±0,9 DP, mm hg 79,4±1,1 77,6±0,9 76,6±0,8* 74,8±0,8* ADP, mm hg 93,9±0,9 91,7±0,6 90,5±0,8* 90,6±0,7 HR, ud/min 78,1±0,9 76,7±0,7 73,1±0,5* 71,8±0,8* MBV, l/min 4,49±0,05 4,55±0,06 4,59±0,04* 4,72±0,06* GPVR, dyne cm sec -5 1679±55 1610±61 1549±33* 1519±32 DP, RVU 95,5±1,1 91,8±0,9 87,4±0,7* 84,9±0,9* Notes : The 1st group – examined- Caucasians. The 2d group –Yakuts. Distinction is statistically significant in comparison with the 1st group, р <0,05.

462 Ad a p t i v e r e a c t i o n s o f i n d i g e n o u s p o p u l a t i o n o f y a k u t i a

Very important index characterising function of blood by functional state and interaction of the basic physiological circulation is double product (DP) which reflects haemodynamic systems, and also degree and character of their interaction for load level on cardiovascular system. The analysis has shown that homeostasis determination after load. the highest DP values were observed in group of Caucasians in winter, basically because of SP increase, and low among Yakut REFERENCES nationality in summer that testified more economic functioning 1. Borisova N.V. Ecological substantiation of formation of functional reserves among of blood circulation system in this season. indigenous people of Republic of Sakha (Yakutia) / N.V. Borisova, P.G.Petrova // Science and education. – 2008. – №2 (50). – P. 55-61. CONCLUSIONS 2. Gorbanev S.A. Monitoring of inhabitancy with natural and technogenic factors / Thus, stability of arterial pressure optimises microcirculation S.A.Gorbanev, V.G.Maimulov, L.V.Vorobieva // Materials of Х All-Russian congress of and transcapillary exchange in tissues, conserving steady level hygienists and sanitary inspectors (book II). – Moscow, 2007. – P. 634-638. of metabolism that testified more high level of adaptivity of the 3. Еrmakova N.V. Ecological portrait of the person in the north and questions of ethnic person to severe climate geographic conditions of Republic of physiology / Ermakova N.V. // Materials of XI International symposium «Ecological- Sakha (Yakutia). physiological problems of adaptation» – М: Publishing house RUDN, 2003- P.183. Adaptive abilities of the human body substantially depend 4. Nefedov B. N. Some ecological-technological risks of building of large hydraulic engineering on reserve possibilities. The functional reserve of the basic objects in the north of Siberia / Nefedov B. N // Materials of IX International symposium physiological systems and their interaction define «the health on the cold regions development. – Yakutsk, 2010. – P.42. reserves», its potential level. Among almost healthy people with 5. Panin L.E. Homeostasis of the person in the conditions of high widths / L.E.Panin // 13 united mean “normal” values of the basic physiological parametres International congress of subpolar medicine. – Novosibirsk, 2006. – P.12-13. it is possible to evolve group of people with different reserve 6. modern state and epidemiological forecast on natural-focal and especially dangerous possibilities by the adaptive approach and, hence, with different infection contaminations in terrain of Yakutia in the conditions of intensive industrial level of health up to borderlines between health and illness. region (megaprojects) and global climate change / N.G.Solomonov, etc. // Materials of IX Specific features of adaptive abilities of the person are defined International symposium on the cold regions development. – Yakutsk, 2010. – P. 228.

ADDRESS FOR CORRESPONDENCE: Petrova P.G. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street [email protected]

463 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Th e r o l e o f v ir a l h ep a titis in t h e m ec h a n is m o f l i v er c a n cer f o r m a ti o n a m o n g t h e f a r n o rt h i n d ige n o u s i n h a b it a n ts

Sleptsovа s.S., Borisovа n.V. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT Introduction: Yakutia is a region of high prevalence of viral hepatitis B, C and D. The rating and ranking of risk factors for the formation of cirrhosis and primary liver cancer in patients with chronic viral hepatitis (CVH) B, C and D in the Republic of Sakha (Yakutia) (R S(Y)), it is a serious medical problem. Aim: studying of the main reasons for the progression of chronic viral hepatitis B, C and D to cirrhosis and liver cancer in the Far North. Materials and Methods: materials of official statistics of the Territorial Rospotrebnadzor and official registration of Mthe inistry of Health of RS (Y); serological and molecular biological research methods to the studying of HCV genotype B, C, D. Results: on the basis of long-term morbidity of chronic viral hepatitis B, C and D and their outcomes in Yakutia defined a role in the progression to cirrhosis and primary liver cancer, ethnicity and genotype of HBV and HDV. Established fact of viral replication in cirrhosis and primary liver cancer under adverse social and environmental factors, genetically determined increased concentration of acetaldehyde due to impaired activity of alcohol dehydrogenases (ADH) and aldegiddegirogenases (AlDG) at the indigenous inhabitants of the republic proves the need for targeted therapy of complex events. Conclusions: the regions of Yakutia are the most affected by the virus of hepatitis B, C and D with progressive course of the disease to cirrhosis and cirrhosis liver cancer, defined by genotype hepatitis B & D, in which significantly usually occurs primary liver cancer, also noted that the combined mixed-replicating virus hepatitis is a risk factor for primary liver cancer.

Key words: chronic hepatitis, liver cirrhosis, liver cancer, replicative activity, genotypes.

Wiad Lek 2015, 68 (4), 464-468

INTRODUCTION RESULTS AND DISCUSSION The relevance of chronic viral hepatitis (CVH) B, C and D in Republic of Sakha (Yakutia) is the largest subject of the Russian the Republic of Sakha (Yakutia) (RS (Y)), as a whole, the Russian Federation and is located in the north-east of Russia. According to Federation (RF), is determined by the prevalence of chronic the State Statistics Committee of Russia (2000), Yakutia occupies viral hepatitis, a significant role in the formation of unfavorable 3103.2 thousand km2 which is 18% of the territory of the Russian outcomes (cirrhosis and cancer) and frequent registration among Federation. In the area of permafrost beyond the Arctic Circle young adults [1, 2, 3]. The level of registration of chronic viral about 40% of the territory of the republic is located. The climate of hepatitis has no downward trend, the rate of prevalence in Yakutia is sharply continental and dry. The absolute minimum of 2011 was 1502.5 per 100 thousand population, according to the air temperature recorded in Oymyakon district is -71,2 ° C and the reference center for surveillance of viral hepatitis, is the highest absolute maximum in Yakutsk is + 38 °C [5] .Considering given main in the Russian Federation (RF). complex criteria discomfort in the lives of climatic and geographical, Aim: the purpose of research: studying of the main reasons environmental, social-economic, medical-demographic factors for the progression of chronic viral hepatitis B, C and D to for studying prevalence of disease, 35 administrative territories cirrhosis and liver cancer in the Far North. of Yakutia conventionally are subdivided into six medical and geographical zones. These are Polar, Eastern Yakutia, Western MATERIALS AND METHODS Yakutia (Viluiskiy group of districts), Southern (Verkhnelensky), Data of official statistics of the Territorial management of Central and the large towns zones. [6] Sickness rate of the first time Rospotrebnadzor of the Territorial of Sakha (Yakutia), materials established forms CVH B and C in the Sakha Republic (Yakutia) of official registration of MoH RS (Y), information about the in the period of observation is much higher than in Russia, and population of patients in the republic. The observation of patients this trend can be seen throughout the observation period, with besides clinical examination included biochemical, serological the greatest difference being in 2003-2005 (Fig. 1). On results and molecular biology survey methods. of 2013 in the Republic of Sakha (Yakutia) were registered 701 For the statistical analysis of obtained data in this research cases of chronic hepatitis, the incidence rate was 73.1 per 100 used a system STATISTICA for Windows (version 8). thousand of population.

464 Th e r o l e o f v i r a l h e p a t i t i s in t h e m e c h a n i s m o f l i v e r c a n c e r f o r m a t i o n a m o n g t h e f a r n o r t h i n d i g e n o u s inhabitants

Along with the manifest forms of hepatitis B (HB), the higher incidence of liver cancer was observed in the western 0 0 causative agent is stored concealed circulation, which leads (19,7±4,44 /0000) and polar areas of Yakutia (16,05±4,06 /0000). to the formation of difficult to diagnose of infection variants. The low incidence of liver cancer were recorded in the eastern 0 Official statistics before 1999 did not account for chronic hepatitis area (5,5 ± 2, 35 /0000) and at the residents of large towns (10,4 0 0 caused by hepatitis B virus, the number of virus carriers of ± 3, 22 /0000), the South of Yakutia (8,1 ± 2, 85 /0000, р<0,05). HBsAg in the RS (Y) was greater than in some years the Russian For a full analysis of the incidence of HBV in the republic indicators in 3.0-3.5 times, which reflects the intensity of the from September 2012 was implemented an automated program epidemic process as a whole in the territory of region. As it is to integrate people with chronic viral hepatitis (CVH) in the shown in Fig. 2, since 2002, there is a significant decrease in region. Fig. 3 shows the incidence of HBV, C and D and their this indicator (p = 0,0303). By 2011, the level of HBsAg carrier outcomes (cirrhosis and liver cancer) on medical-geographical state in the Sakha Republic (Yakutia) has decreased in 8.3 times zones of the republic on the basis of data register "Chronic (32.8 per 100 thousand population) compared to 2000 (272,6 viral hepatitis in the Sakha Republic (Yakutia)". In December per 100 thousand population), rank correlation coefficient (rsp 2013 according to the population register of the country on = -0.99) between the level of vaccination and HBsAg carrier is the account are composed 13,098 people, without taking into authentic (p <0,001). account hepatitis B virus carriers, of which CVH – 12,609 (B – The analysis of the spread of HBsAg carriers of health- 6109, C – 5008, D – 671, mixed – 624 specified etiology – 197), geographical zones in the Republic of Sakha (Yakutia) showed with the liver cirrhosis (LC) are registered in the republic 422 that significantly meaningful intensive indices were noted in the patients, with primary liver cancer (PRP) – 67 people. This 0 0 polar zone (182,2±13,5 /0000) and large towns (127,2±11,3 /0000), unfavorable epidemiological situation is connected with the values of 1.8 and 1.2 times, respectively, exceeded the average climatic and geographical features of the Far North, with significant 0 value (100,8±10,0 /0000). The high level of HBsAg carrier among prevalence of immunodeficiency disorders, the frequency of the inhabitants of polar zones is explained by conducting in some which is increased considerably due to unfavorable environmental years of mobile medical screening and discovery expeditions of conditions, particularly, it is characteristic for the Republic of immunological laboratories in some areas (Verkhoyansk, Ust- Sakha (Yakutia). Jansky, Bulunsky). High rates of HBsAg carrier are constantly High incidence of chronic viral hepatitis and their outcomes recorded in areas with a high incidence of acute hepatitis, chronic in the areas of central, polar and western Yakutia is explained hepatitis, cirrhosis of the liver, because “carriers” HBsAg are the by insufficient provision of rural indigenous populations living main reservoir of infection, contributing to the formation of in these regions, and qualified health-care and preventive care. family homesteads around CHB patients [7]. The prevalence We obtain reliable coefficients of rank correlation (p <0,05) of antibodies to the virus carrier of hepatitis C by the medical between the incidence of chronic viral hepatitis B, C and D as and geographical areas had uneven character, high figures were a whole with the outcome of cirrhosis (rsp = + 0,94) and liver 0 recorded in large towns (119,2±10,9 /0000), which was in 1.7 times cancer (rsp = + 0,83), as well as between D chronic hepatitis 0 greater than the average national value (70,3±84 /0000). with cirrhosis (rsp = + 0,94) and liver cancer (rsp = + 0,89), A comparative analysis of the incidence of primary liver cancer separately for CHC and CHB statistically significant association from 2001 to 2010 years in medical-geographical zones of the was not revealed. republic has shown that the highest sick rate in the population was Conducted researches of immunological monitoring of recorded in the central zone of Yakutia, which was significantly population in Viluysk region (western zone), confirm the role in 1.7 times higher than the average republic value (23,2 ± of changes of the immune system in the progression of chronic 0 4,82 versus 13,8±3,71 /0000, р<0,05). A statistically significantly viral hepatitis [8]. Thus, in the process of studying of the state

Fig. 1. The first time established incidence of chronic viral hepatitis in the R S(Y) and RF according to official registration.

465 Sleptsovа s.S., Borisovа n.V.

Fig. 2. The morbidity of HBV and HBsAg carrier state in the Republic of Sakha (Yakutia) from 2000-2013 years on the background of vaccine prevention of hepatitis B.

Fig. 3. The morbidity of chronic viral hepatitis B, C, D and their outcomes (CL, PLC) on medical and geographical zones in the Republic of Sakha (Yakutia).

466 Th e r o l e o f v i r a l h e p a t i t i s in t h e m e c h a n i s m o f l i v e r c a n c e r f o r m a t i o n a m o n g t h e f a r n o r t h i n d i g e n o u s inhabitants of nonspecific immunological resistance among residents of replication and DNA-HBV – 35,3%, in liver cirrhosis mixed- certain localities in the western zone of Yakutia showed signs replication of HBV and HDV was found in 63% of cases, mono- of immunosuppression of T-cell stored in the comparative HDV replication in 37% of patients with HDV-infection. Thus, systems of immunity, reduction of the three main classes of the mixed HDV and HBV replication leads to the liver cirrhosis immunoglobulins with the weakening of the phagocytic activity reliably (p <0,05) more often. Among patients with CHB DNA- of neutrophils. The reduction of resistance is confirmed by the HBV in PCR detected in 76.9% of cases, the replication-HCV shift in immunochemical terms – increasing of titles P-proteins RNA was preserved at all patients with liver cancer in CHC (a high percentage of the residents of destabilization Nurba and (100%). The results suggest the need for antiviral therapy in Suntar districts), CEC (a high percentage of the residents of patients with liver cancer in the outcome of CVH [9]. Among the destabilization in Mirny, Nurba and Suntar districts). The scale indigenous peoples was identified a high frequency of “atypical” of disease and features of CVH course, especially in Nyurbinsky, isoform of alcohol dehydrogenases – ADH2 combined with Verkhnevilyuisk and Vilyuysky districts confirm the role of a lack AlDG1, i.e. high probability of increasing the ratio of the immune system and system of nonspecific detoxification ADH to AlDG and accumulation of highly toxic acetaldehyde of the liver in liver pathology, as well as in lowering of general above the critical concentration, which can be the basis of the resistibility of organism to pathogens influence. progressive course of the disease [10]. The native inhabitants of During the observation period, the morbidity of PLC among the republic c CHB at hepatocirrhosis stage the level of AlDG the rural population was higher in relation to the level of urban amounted 0,85 ± 0,03 mmol / (L-min), which is significantly residents and the sickness rate was 1:2, that was respectively different from the activity AlDG among Europeoids with the the 0 (12,9±1,4) and (27,4±2,8) /0000. On average, the sick rate of same diagnosis – 1,05 ± 0,19 (p <0.01). The ratio of the activity of liver cancer of indigenous nationality was in 2 times higher ADH and AlDG in both groups were also significantly different than among non-indigenous. (p <0,01). In the control group there are significant differences We observed 2,700 patients with chronic viral hepatitis, in the activity of ADH (p <0,001) and AlDG (p <0,001), and the including 1712 patients (63.4%) with chronic hepatitis B and 988 ratio of activity of ADH and AlDG (p <0,01) in Europeans (1,0 patients with liver cirrhosis (36.6%). On the basis of serological ± 0,03) and persons of indigenous nationality (1,3 ± 0,2), which and molecular biological studies, patients with chronic viral confirms the data on the availability of initially modified ADH hepatitis in the stage of the CPU (n = 354) were divided into 3 isozyme spectra and AlDG among the indigenous population. groups: patients with chronic hepatitis B – 68 (19.2%); with the The ratio of the activity of ADH and AlDG is directed toward chronic hepatitis D – 143 people (40.4%) with chronic hepatitis increasing the concentration above normal in the organism of B – 143 (40.4%), which represented in table 1. Among these acetaldehyde which, provoking covalent modification of proteins patients were revealed 53 cases of PLC, 95% confidence interval, by subjecting the organism the autoimmune processes. Moreover, calculated on the basis of the angular conversion of Fisher, it was it is known that acetaldehyde has a genotoxic effect [11], and 11,2% ÷ 8,9%. The frequency of liver cancer in the CHD was its excessive accumulation is associated with an increased risk 18.9% and significantly (p <0.05) higher than in CHB and CHC of malignant transformation of the liver [12]. – 14.7% and 11.2%, respectively. There were identified 24 cases of viral replication, which amounted to 45.3%; 95% confidence CONCLUSION interval, calculated on the basis of the angular conversion of It is noted uneven distribution of morbidity of chronic viral Fisher, was 32,2% ÷ 58,7%. Replicative chronic hepatitis virus hepatitis in various territories of the republic, which is directly activity in primary liver cancer was observed more frequently related to the living conditions of the population, the state of with CHD – 55.6%, which was significantly (p <0.05) higher the immune system and the remoteness from major population than the frequency of replication at CHB and CHC and was centers, not only with modern equipped laboratories, but also 40% and 31.2%, respectively. secured by all kinds of medical and social care, the need for all Analysis of the molecular structure of biological viruses zones of the Republic. showed that among examined patients on the background of Among the natives of polar, central and western zones of the formation of the PLC remained replicative virus activity: in Yakutia is observed the highest incidence of cirrhosis and primary 67.4% of the patients with the CHD activity showed RNA-HDV, liver cancer. Among patients with chronic viral hepatitis with in one third of the cases was discovered the mixed-HDV RNA the formation of liver cancer, remains high replicative activity of

Table I. The number of patients with chronic hepatitis B at cirrhotic stage with a diagnosis of primary liver cancer. Chronic hepatitis virus Revealed primary liver cancer Frequency of replication Total number of patients at cirrhoitic stage (abs.ch. / in %) (abs.ch. / in %) Chronic hepatitis B 68 10/14,7 4/40,0 Chronic hepatitis D 143 27/18,9 15/55,6 Chronic hepatitis C 143 16/11,2 5/31,2 Total 354 53/14,9 24/45,3

467 Sleptsovа s.S., Borisovа n.V. hepatitis viruses B, C and D. It was found that liver cancer more 6. Ivanov P.M. Hepatology North / P.M. Ivanov [et al.]. – Yakutsk: Sphere, 2012. – P. often develops at patients with HBV-infection with genotype D, 304. HDV-infection – and genotype I HCV-infection – genotype Ib. 7. Alekseeva M.N. Viral hepatitis in the Republic of Sakha (Yakutia): Dis. ... Dr. med sciences: The progressive nature of the disease is caused by unfavorable 14.00.10 / Martha N. Alekseev. – St. Petersburg, 2002. – P. 285. climatic and geographical factors, phenotypic features of isoenzyme 8. Petrova P.G. Ecological and physiological aspects of human adaptation to the conditions spectra of ADH and AlDG at the indigenous inhabitants of of the North / P.G. Petrova. // – Yakutsk: Dani Almas, 2011. – P. 272. the republic. 9. Rakhmanova A.G. Outcomes of liver transplantation in patients with cirrhosis and cirrhosis-cancer due to hepatitis B, C and D / Rakhmanova A.G., Sleptsova S., Tichonova REFERENCES N. // Journal of Hepatology. – 2014. – April. – Vol.60. – Issue.– P. 205. 1. Abdurakhmanov D.T. / Chronic hepatitis B and D. – M .: GEOTAR Media, 2010. – P. 10. Kershengolts B.M. Ethnogenetic particularly resistant to alcohol in the populations of 288. the North / B.M. Kershengolts, T.V. Chernobrovkina, O.N. Kolosovа // The Interregional 2. Rakhmanova A.G., Yakovlev A.A. / Chronic viral hepatitis and HIV infection. – SPb., scientific-practical conference with international participation «Ecology and human 2011. – P. 164. health in the North», dedicated to the 55th anniversary of higher education in Yakutia. 3. Barazani Y. Chronic viral hepatitis and hepatocellular carcinoma / Y. Barazani, J.R. Hiatt, November 10-11, 2012. – P. 172-180. M.J. Tong [et al.] // World J. Surg. – 2007. – Vol. 31. – P. 1245–1250. 11. Wang M. Identification of DNA adducts of acetaldehyde /M .Wang, E.J. McIntee, G.Cheng, 4. Sleptsova S.S. Viral hepatitis in the Republic of Sakha (Yakutia): Abstract. Dis. Dr. med. Y.Shi, P.W.Villalta, S.S. Hecht // Chem. Res. Toxicol. – 2000. – Nov. – Vol. 13(11). – P. Sciences: 14.01.09, 14.02.03 / Snezhana Spiridonovna Sleptsova. – S.-Pb., 2013. – P. 1149-1157. 44. 12. Seitz H.K. Acetaldehyde as an underestimated risk factor for cancer development: role 5. maksimov G.N. Native Yakutia: nature, people, nature / G.N. Maksimov; ed. MY Jury. – of genetics in ethanol metabolism / H.K. Seitz, F. Stickel // Genes Nutr. – 2010. – Jun. Yakutsk Bichik, 2003. – P. 168. – Vol.5 (2). – P. 121-128.

ADDRESS FOR CORRESPONDENCE: Sleptsova S. S. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street Ph. 8-914-2718770 [email protected]

468 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Ps y c h o l o gic a l a n d v eget a ti v e c h a r a cteristics o f st u d e n ts – y a k u ts w it h d i f f ere n t e d u c a ti o n a l s u ccess

Stepanova G.K., Ustinova M.V. f s a e i h p e “n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v ” y a k u t s k , r u s s i a

ABSTRACT Consideration of ethnic features of adaptation of students to educational activity in high school is needed as to optimize the learning process and to preserve the functional reserves of the organism. We investigated the characteristics of the psychological status and correlated them with the heart rhythm variability in students Yakuts with varying different effectiveness of educational success. Regression analysis of the relationship of personality psychological characteristics of students with indicators of the spectral power of heart rate showed that more adaptive resource autonomic regulation of the heart have people with an average level of introversion and of personal anxiety indicators corresponding to the transition from moderate to high degree and also in individuals with an average levels of neuroticism. Revealed higher effectiveness of examinations students introverted compared to extroverts and students with high personal anxiety relatively to persons with moderate personal anxiety. High efficiency of intellectual activity of students is achieved through high tension mechanisms vegetative regulation of the heart.

Key words: Yakuts, heart rate, personal characteristics, effectiveness of educational success.

Wiad Lek 2015, 68 (3), 469-475

INTRODUCTION MATERIALS AND METHODS The centuries-old adaptation of indigenous peoples to the The study involved 46 healthy young men – students NEFU harsh climatic conditions shaped adaptive type, allowing providing 18-21 years. It was recorded in the first ECG standard lead using ecologically balanced human activity in the environment. However, the hardware-software complex “Valens” (“Neo”, St. Petersburg). the rapid changes in human ecology in the North led to social and 200 cardio intervals recorded after a 10-minute rest in the supine stress-reduction and adaptive qualities of the native population, as position. Registered ECG checked for the presence of artifacts. evidenced by the deterioration of their health [1]. Comparison of Estimated time characteristics cardio intervals: the average the results of social-hygienic and economic standards of living of the duration of RR-intervals (ms) for the entire period under review; working population in Yakutia with the level of trait anxiety showed SDNN, ms – the standard deviation of the values of RR-intervals, significant inverse relationship [2]. In Yakutia students marked reflecting the total activity of the regulatory mechanisms of higher level of personal and situational anxiety than students in cardiac rhythm; RMSSD, ms – the square root of the sum of the other climatic zones [3]. Among the numerous studies on various differences of successive RR-intervals, reflecting the activity of aspects of adaptation of students, a lot of attention is paid to the status the parasympathetic division; pNN50, % – the number of RR- regulatory mechanisms of cardiac rhythm. Complex investigations of intervals differing by more than 50 ms; AM0, % – the frequency heart rate variability (HRV) and personal psychological characteristics of the most common values of cardio intervals (Mо), expressed of students with different levels of adaptation to the educational as a percentage of the total number of cardio. Stress index (SI, process [4, 5, 6]. The Yakut universities comes the young, educated cond. units) was calculated using the formula: SI = AM0 / 2M0 to a certain ethnic environment that affects its adaptation to training * x, x where variation range, sec – the difference between in high school. However, the problem of accounting for the ethnic the maximum and minimum values of cardio intervals duration characteristics of the adaptation of Russian students to educational of△ the test△ the dynamic series. activity in high school rose in isolated [3, 7, 8]. In modern conditions From the parameters of the spectral analysis considered the of economic transformation in Yakutia important study adaptive following indicators: HF, ms2 – high-frequency oscillations of capabilities of students, part of the social and labor potential of heart rate (HR), LF, ms2 – low frequency oscillations SR. the region. Personality structure was assessed by the test H Eysenck The purpose of the study was to investigate the characteristics [9], trait anxiety (TA) of BH Spielberger [10]. The criterion of of the psycho-physiological status and correlated them with heart success of training is the average score is calculated from the rate variability in the Yakut students with varying effectiveness delivery of the four exams in the spring exams students’ second of educational activity. year medical school.

469 Stepanova G.K., Ustinova M.V.

Considering that the distribution of the HRV parameters is TA have been not identified. In our studies, the mean score TA not described by a normal distribution, the data are presented as (48.8 ± 1.1 points) for all of the students coincides with the data median, 25th and 75 percentiles. Comparison of data between obtained during the examination of students of first course of the groups surveyed was performed using Wilcoxon test for two Yakutsk State University medical school in 2001 [12]. Thus, over independent groups. To establish links between the individual the past decade, the level of TA in medical students of junior and typological characteristics and parameters of HRV, as well as courses remains high, which probably reflects both the personal between performance of educational activity and spectral indices qualities of students who choose to become a doctor, and about were HR equation least square regression, polynomial trend intensity of psychosocial adaptation to the students. and the reliability of these trends expressed by the coefficient Table II shows the values of HRV parameters in the examinees of determination. with different individually-typological characteristics. The table shows that introverts x is of great importance compared RESULTS AND DISCUSSION to extroverts: x [Z ( x introverts and x extroverts) = Testing students on Eysenck revealed belong 54.3% of them 1.28, P = 0.19]. It was also△ found that the smaller the value to the extroverts, and 45.7% – to introverts (Table I). The value of introverts extraverts△ △ relative SI: SI [Z (SI△ introverts and SI of the average neuroticism in the subjects was 10.9 ± 0.67 points. extroverts) = -1.59, P = 0.11]. It is believed that the observed 52% of the subjects were low levels of neuroticism (Ne), which differences x and SI values reflect a lesser degree of stress apparently is a component of the mechanism of adaptation regulatory mechanisms of cardiac rhythm in relatively due genotype and phenotype ethnic northerners to extreme introverted △extroverts. environmental factors. Self-control, restraint of emotion – a To determine the relationship between the values of introns characteristic quality social type Yakuts [11]. and extroversion, and the power spectrum of HRV, it was The test results showed a high level of TA from 68.3% surveyed built according to the spectral components of HRV on the a moderate level of TA – at 31.7%. Individuals with low levels of level of extraversion introns (IE) subjects presented on the

Table I. Distribution of surveyed youths as belonging to extra- and introversion and anxiety levels. Extraversion (n=25) 54.3% Introversion (n=21) 45.7% The level of neuroticism Low Medium High Low Medium High 40% 28% 32% 61.9% 23.8% 14.3% (n=10) (n=7) (n=8) (n=13) (n=5) (n=3)

Table II. HR and HRV in extra- and introverts (M ± m; M (25-75). Р Indicators Extraverts (n=25) Introverts (n=21) Extra-introverts RR, ms 860(740-930) 880(830-940) - HR, beats / min 71±2.4 68±1.5 - ∆X, s 0.27(0.21-0.42) 0.35(0.27-0.44) 0.19 RMSSD, ms 38(28-64) 44(30-69) - pNN50, % 23(12-44) 32(11-61) - SDNN, ms 60(50-70) 70(50-70) - АМ0, % 41(32-49) 38(30-50) - SI, rel. u 76(59-113) 59(38-72) 0.11 HF, ms 2 453(268-785) 589(333-1070) - LF, ms 2 157(112-345) 216(130-314) -

470 Ps y c h o l o g i c a l a n d v e g e t a t i v e characteristics o f s t u d e n t s – y a k u t s w i t h d i f f e r e n t educational s u c c e s s charts figure 1. The scale was divided evenly IE 6 slots, each of TA2 + 407 TA – 8653. The correlation coefficient between the which found median HF, LF and SDNN, trend and statistical experimental points and model parabolas above 0.9. Thus, all evaluation of the boundary interval (variance) values HF. The 3 charts show that the general vegetative tone higher in young distribution of HF asymmetrically with respect to median – men surveyed the level of trait anxiety that is in the middle of shifted to lower values. Values shown LF to HF via scale factor. the scale, “moderated – high trait anxiety.” Configuration curves connecting median HF, LF and SDNN Our results are consistent with published data on the lesser repeats each other. The absolute values of these indices are of the total power of HRV spectrum in students with high trait maximal in subjects with an average level of introversion (8 anxiety compared with the students, characterized by low- and points on a scale of IE). middle-TA [6]. Low spectral power of HRV in patients with high The above data on the trend toward large values x, lower values TA indicates a high tension regulation system, the consequence of SI, as well as several large spectral power of HRV in introverts, of which may be a reduction in adaptive capacity and reserve extraverts respect, according to the predominance△ of functional capacity of the organism. reserve of the autonomic regulation of the examinees, personal Using regression analysis, we have traced the relationship psychological qualities which correspond to introversion. between the level of neuroticism and HRV. Fig. 3 shows graphs To establish the relationship between the level of TA and showing changes in median values HF, SDNN, SI, and statistical cardiac output spectrum used regression analysis (Fig. 2). Scale TA evaluation of the boundary interval HF young men with different was divided into five intervals, as in the construction of previous levels of neuroticism (Ne). The regression equations presented graphs for each interval found medians SDNN, wave power HR parabolic dependence and boundary interval statistical evaluation HF. Higher values SDNN = – 0.76 Ne2 + 14 Ne + 131; HF = – 1.3 Ne2 + 40 Ne + of the power spectrum of HRV observed in patients, the level 304; SI = Ne2 – 25 Ne + 254. The correlation coefficient between of trait anxiety that is 43-49 points, coinciding with the center the model and experimental point’s parabolas 0.9 above except of the scale “moderate – high TA” for the values of TA, beyond HF (Ne), where it is 0.33. these limits, the value of SDNN, HF- and power LF- waves The maximum values of HF, SDNN were observed in students subside, and, to a greater degree in the subjects with high levels with average levels of neuroticism. This graph median SI is out of TA. Regression equations of the spectral components of HRV of phase with the spectral curves of indicators SR. High power level TA expressed parabolic dependence: SDNN = – 1.98 TA2 vegetative regulation and low values SI in patients with moderate + 183 TA – 3668; HF = – 0.075 TA2+ 6.61 TA – 81; LF = -4.35 neuroticism show higher reserve possibilities of the organism

Fig. 1. The relationship between the values ​​of HF, LF, SDNN and surveyed youths belonging to the intro- extroverts.

471 Stepanova G.K., Ustinova M.V.

Fig. 2. The relationship between the values ​​of HF, LF, SDNN and the level of trait anxiety in youths surveyed.

Fig. 3. The relationship between the values ​​of HF, SDNN, SI and the level of neuroticism have surveyed youths.

472 Ps y c h o l o g i c a l a n d v e g e t a t i v e characteristics o f s t u d e n t s – y a k u t s w i t h d i f f e r e n t educational s u c c e s s

Table III. Effectiveness of examinations of students in groups with a variety of personal and psychological characteristics. Trait anxiety, Effectiveness Neurotism, n (%) Extra Intro n (%) Average wert, n (%) wert, n (%) Exam. rating Low Medium High Medium High rating «4» и «5» 4.38± 5(50) 5(50) 4(40) 3(30) 3(30) 2(20) 8(80) n=10 0.091 «3» и «4» 3.38± 13(48) 14(52) 15(55.6) 7(25.9) 5(18.5) 9(41) 13(59) n=27 0.042 «5» 5.0 1(25) 3(75) 3(75) - 1(25) 2(50) 2(50) n=4 «2» 2.0 5(100) - 1(20) 2(40) 2(40) 3(60) 2(40) n=5

in comparison with the patient, the level of emotional stability, According to AP Okoneshnikova [11] introversion – typical which corresponds to the values located at the beginning and characteristic of social quality of the Yakuts. It is believed that the end of the scale “neuroticism.” introverted type is a typical feature of the social Yakut, which is In order to identify the possible connection with the effectiveness necessary for adaptation to the harsh climatic conditions [16]. of training activities individually-typological features explored Yakut introverted qualities of students appear in the educational the results of examinations of students with a variety of psycho- activity, as evidenced by the tendency to systematize the teaching physiological characteristics (Table. 3). material, careful, unhurried work performance, pre-thinking It sets significantly higher average exam score in introverts response [16]. extraverts relative (P = 0.036), which is consistent with the To study the effectiveness of training activities due to the baseline literature [6, 13]. We also showed a trend (P = 0.19) to higher of the spectral parameters of HRV analysis used regression analysis. achievement among students with high levels of trait anxiety, All the students were divided into 5, approximately equal to the compared with those of medium TA. The students, who passed number of surveyed (7-10), groups with different success of training exams at the «4» and «5» (average score of 4.38 ± 0.091), the (Fig. 4). Since the majority of students (n = 27) received an average same number of extra- and introverts, the incidence of people score of 3.38, the duration of the intervals on the scale of «progress» with low levels of neuroticism – 40%, and those with a high TA (USP) was different. The graph shows the median values of HF – 80%. Among the students who reach the highest achievements and statistical evaluation of the boundary interval (25%, 75%), (honors), introverts incidence was 75%, those with low levels of distribution of the variables HF asymmetrically relative to the neuroticism, too, 75% of the study on the relationship between median, as in the previous chart – skewed toward lower values. The the success of training and psycho-physiological characteristics highest values of power HF-wave spectrum detected in young men of young men-Moscow students found a group of people who showed satisfactory knowledge (average score of 3.25 – 3.5). Students have high results achieved in examinations combined low showed good and excellent knowledge (GPA 4-4.75), characterized neuroticism and high TA [14]. Young men with the lowest by a lower amount of power HF- waves. The regression equation is success of educational activity (not admitted to examinations as represented by a parabolic dependence: HF = -373 GPA 2 + 2674 not to execute the program) – all extroverts, characterized by a GPA – 3857. The correlation coefficient between the experimental high (40%) and medium (40%) levels of neuroticism, medium points and the model parabola above 0.65. (60%) and high (40%) levels TA. The low level of psychological In the future, for the study of the relationship of individual HRV and emotional stability of these students obviously associated each student with their academic performance scale “performance” with learning disabilities. was defeated by 2 to 5 points with divisions of 0.25 points (Fig. 5). According to the above data, the most significant differences In the interval of “2 points” HRV parameters included students not were found between the psycho-physiological characteristics of admitted to the session. As in the previous chart, showed a trend the students who showed the best and worst results of educational toward lower values of​​ HF, LF, SDNN with the improvement of the activity. If honors appeared mostly introverts, all students who are results of the examination session. Thus, the physiological value not admitted to the session – extroverts. If, among the standouts of the educational activities of students who passed the session occurrence emotionally balanced (low neuroticism) was 75%, with an average score of 4.38 is higher than that of students with while among non-admitted students for the session – only 20%. an average score of 3.38. High academic success is associated with Significantly lower rates of neuroticism of students with good high voltage systems, autonomic control of cardiac activity, which academic performance compared with students who have shown can lead to a decrease in the reserve capacity of the organism, a satisfactory level recorded in RP Karasev [15]. and the quality of health of students.

473 Stepanova G.K., Ustinova M.V.

, Trend

Fig. 4. The relationship between the values ​​of HF, LF, SDNN and the level of trait anxiety in youths surveyed.

Fig. 5. The relationship between the values ​​of HF, SDNN, SI and the level of neuroticism have surveyed youths.

474 Ps y c h o l o g i c a l a n d v e g e t a t i v e characteristics o f s t u d e n t s – y a k u t s w i t h d i f f e r e n t educational s u c c e s s

CONCLUSION 4. Bulatetsky S.V. Physiological mechanisms of successful training cadets of educational We surveyed students set high incidence of people with a institutions the Russian Interior Ministry. / Bulatetsky S.V. // Dr. med. Sci. diss. Ryazan; high level of trait anxiety (68.3%). High values of TA (48.8±1.08, 2008 (in Russian). points) coincided with those of 10 years ago [12]. 5. Dmitriev D.A. Influence of exam stress and psycho-emotional features on blood pressure Regression analysis of the relationship personal and and heart rate regulation in students. / Dmitriev D.A., Dmitriev A.D., Karpenko Y.D. [et psychological qualities of the students with the values of total al.] // Human Physiology. 2008; 5: P. 96 – 89 (in Russian). spectrum power (SDNN), low (HF) and high-frequency (LF) 6. Aghajanian N.A. Comparative features of heart rate variability in students living in waves of cardiac rhythm revealed a tendency to the predominance different climatic regions. / Aghajanian N.A., Batotcirenova T.E., Severin A.E. [et al.] // of adaptive resource autonomic regulation of the heart in young Human Physiology. 2007; 6: P. 60 – 66 (in Russian). men with an average level of introversion, with indicators of 7. Buduk-ool L.K, Ethnic peculiarities of psychosocial adaptation of students to learn in trait anxiety, corresponding to the transition from a medium high school. / Buduk-ool L.K. // Vestn. Tomsk. State. ped. University. 2011; issue. 6 (108) to high degree (43 to 49 points) and in the middle-surveyed : P. 180 – 176 (in Russian). neurotism (12 points). 8. Rusalov V.M. A new type of adaptation personality test EPI. / Rusalov V.M. // Jurnal Study links individually-typological features to performance Psychological. 1987; 1: P. 118 – 113 (in Russian). examinations revealed significantly higher performance in boys, 9. Hanin Y.L. / A Brief Guide to the application of the scale reactive and personal anxiety compared with introverts and extroverts tend to be more successful BH Spielberger. L .: LNIIFK; 1976 (in Russian). learning in young men with high TA, relating to persons with 10. okoneshnikova A.P. / Interethnic perception and understanding of other people. Perm; medium TA. YSU. 1999 (in Russian). In the initial state (before the session) more economically 11. FedorovA A.I. Psychological status of 1st year students. / FedorovA A.I., Osinskaya A.A., consumed regulatory potential of the young men who showed Sergina E.P. // In: Problems of identity formation in the modern university: mes. Conf. a satisfactory performance in examinations in comparison with Repub. Intercollege. conf. Yakutsk, 2001; P. 27 (in Russian). the students passed the session as “good” or “excellent.” The 12. Degtyarev V.P. Adaptive capacity of students with different individual-typological effectiveness of the intellectual activity of the students, showing characteristics. Psychological and psychoanalytic studies 2010-2011. / Degtyarev V.P. high-quality knowledge on exams, achieved through higher // M: Institute of Psychoanalysis. 2011: P. 120 – 114 (in Russian). voltage functional reserves with respect to students with lower 13. Degtyarev V.P. The role of trait anxiety in the formation of a successful educational productivity of the session. activity of students. Herald Peoples’ Friendship University. / Degtyarev V.P., Torshin V.I. // A series of “Medicine”. 2010; 3: P. 102 – 98 (in Russian). references 14. Dzhebrailova T.D. Students knowledge level computer testing result and individual 1. manchuk V.T. Status and trends shaping the health of indigenous peoples of the North specificity of purposeful activity vegetative support. / Dzhebrailova T.D., Suleimanova and Siberia. / Manchuk V.T., Nadtochy L.A. // Bull. SB RAMS. 2010; 3: P. 32 – 24 (in R.G., Ivanova L.I. [et al.] // Human Physiology. 2012; 5: P. 66 – 58 (in Russian). Russian). 15. Karasev R.P. / The ratio of psychodynamic characteristics and indicators of functional 2. Egorova A.G. Psychosocial factors and their association with dyslipidemia in the working lateralization in the systemic organization of purposeful human behavior at age population. / Egorova A.G., Krivoshapkina Z.N., Matveeva N.P. [et al.] // Yakut Medical different levels of mental and emotional stress. Dr. med. sci. diss. Ryazan; 2009 Journal. 2009; 4: P. 60 – 57 (in Russian). (in Russian). 3. Nikolaeva E.N. Psychophysiological features of adaptation of students while studying at 16. Ptitsina O.N. / Features of self-organization of the Yakut students in learning activities. university in the North. / Nikolaeva E.N // Dr. biol. Sci. diss. Yakutsk; 2006 (in Russian). Dr. ped. Sci. diss. Yakutsk; 1995 (in Russian).

ADDRESS FOR CORRESPONDENCE: Stepanova G.K. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street [email protected]

475 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Bre a d t h spre a d i n g o f v ir a l h ep a titis m a r k ers in t h e ris k gr o u ps in t h e rep u b l ic o f s a k h a (y a k u ti a )

Sleptsova S.S.1, Semenova V.K.1, Dyatchkovskaya P.S.1, Nikitina S.G.2 1f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a 2scientific r e s e a r c h i n s t i t u t e o f h e a l t h «n o r t h -e a s t e r n f e d e r a l u n i v e r s i t y n a m e d a f t e r m.k. a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT Introduction: republic of Sakha (Yakutia) is a hyperendemic region of Russian Federation for spreading of parenteral viral hepatitis B, C and D. In risk groups of these diseases are firstly medical personnel, who contacting with infection carriers including latent infections family and members of families of chronic viral hepatitis carriers. Aim: to reveal the breadth of spreading of viral hepatitis markers in the risk groups. Materials and methods: the level of HBV- and HC- infection were determined in medical staff of large multi specialty hospital and family members of people with viral hepatitis B and C. Epidemiological, clinical, serological and molecular biology methods of viral hepatitis diagnostics were applied in this study. Results: results of this study showed that the staff at surgery and hematology departments and all nursing staff belong to the high-risk of HBV-infection groups. Therefore, they are a priority for active immunization. Attention is paid on the fact that infectivity of medical staff is not equally distributed in dependence on type of department and position of medical staff. Rate HBV-marker detecting in «family hearths» was dependent on degree of interrelationship with infection source. According received information, in families of patient with chronic hepatitis B spreading of infection was higher (77,6%) then in families of patients with acute hepatitis B (39,7%). At primary examination of families an anti-HCV was detected in 9,3±1,8% cases, i.e. the spreading of HCV was at low-activity. Conclusions: results of our study on spreading of hepatitis B and C in Yakutia showed the high rate of appearance of HCV and HBV markers in the risk groups.

Key words: viral hepatitis, hepatitis markers, nidus of infection in families, infection.

Wiad Lek 2015, 68 (3), 476-479

INTRODUCTion RESULTS AND DISCUSSION According the opinion of director of Labor Medicine Institute High-risk groups of hepatitis B, C, and D viruses infection of academic N.F. Izmerov (2005), in the beginning of XXI century identical by many parameters cause by common paths of spreading. situation with healthcare of medical staff is not satisfactory, Important role in nosocomial infectious process of medical staff because we have trend to growing of cases of incidents and [2,3,4,5]. We have reasons to consider viral hepatitis B and C professional diseases. Causes of this are to due close contact as professional disease of medical staff [2,6,7]. 70% of nurses with contagious patients and specific working environment. and 40-50% of medical doctors have had diagnosis of HBV at Also, factors which maintain epidemic and infectious process retirement, like in previous years [8]. of viral hepatitis spreading are diversity of natural transmission According by Rospotrebnadzor statistics, in 2005-2013 rate paths and high spreading of hemocontact viral hepatitis among of HBsAg marker in serum of medical staff were fluctuated people of childbearing age with forming of «family hearths» from 3,7% (2005) to 3,4% (2013). Maximal level was detected and «mild» clinical course [1]. in 2007 (5,2%). Anti-HCV founded in 1,6% (2005) and reached Aim: to reveal the infectivity degree and intensity of HBV to 3,2% (2013) with maximum at 2007 – 4,1%. and HBC viruses circulation in the risk groups: medical staff of Most part of medical staff with serologic markers of HBV large multi specialty hospital and in the family hearths. and HCV-infection are staff of surgical, urological, obstetrical, anesthesiological, dentistry and infectious departments and MATERIALS AND METHODS paramedics of ambulance – average 88,2%-96,6%. Official statistics of Yakutian department of Rospotrebnadzor Degree of medical staff of National Medical Center of Yakutia was used for epidemiologic analysis. The level of HBV and HCV involvement in epidemical process was evaluated by results of infection of medical staff at the National Medical Center (1067) serologic tests. HBV markers – 1067, including 414 doctors and and their HBV-infected family members were examined (121). 653 nurses were measured. HBsAg, anti-HBc summary and Epidemiological, clinical, serological and molecular methods of anti-HCV were detected by enzyme-linked immunosorbent diagnostics of viral hepatitis were used in this study. assay (Table I, II).

476 Br e a d t h s p r e a d i n g o f v i r a l h e p a t i t i s m a r k e r s in t h e r i s k g r o u p s in t h e r e p u b l i c o f s a k h a (y a k u t i a )

Table I. Frequency of HBV markers detection in medical staff of National Medical Center of Yakutia. HBV-markers Examined Department HBsAg anti-HBc Total Category Amount Abs. % Abs. % Abs. % Doctors 122 4 3,3 22 18,0 22 18,0 Surgery Nurses 248 5 2,0 36 14,5 38 15,3 Doctors 138 1 0,7 12 8,7 13 9,4 Therapeutical Nurses 198 2 1,0 46 23,2 47 23,7 Doctors 32 1 3,1 3 9,4 3 9,4 Hemotranfusion Nurses 79 2 2,5 34 43,0 36 45,6 Doctors 122 - - 6 4,9 6 4,9 Obstetrical and gynecological Nurses 128 2 1,6 44 34,4 45 35,1 Total 1067 17 1,6 203 19,0 210 19,7

Table II. Frequency of HCV markers detection in medical staff of National Medical Center of Yakutia. Examined anti-HCV Department Category Amount Abs. % Doctors 122 3 2,5 Surgery Nurses 248 5 2,0 Doctors 138 3 2,2 Therapeutical Nurses 198 5 2,5 Doctors 32 1 3,1 Hemotranfusion Nurses 79 5 6,3 Doctors 122 - - Obstetrical and gynecological Nurses 128 2 1,6 Total 1067 24 2,25

210 people (19,7%) have HBV-infection markers, 44 doctors infection in nurses was 45,6%, in departments of obstetrical (10,6%) and 25,4% of nurses have HBsAg and/or anti-HBc total, and gynecological – 35,1%. HCV-infection in hemotransfusion 24 members of medical staff (2,25%) haveа nti-HCV, including service was maximal – 6,3%, in therapeutical departments – 7 doctors (1,7%) and 17 nurses (2,6%). 2,5%, surgical departments – 2,0%. Most part of medical staff suffered by latent infection. This fact in In doctors of the National Medical Center maximal level of agreement with data of previous researches [3,7,9]. Higher prevalence total anti-HBc was detected in surgeons (18%), minimal – in of HBV infection was found in medical staff of hemotransfusion gynecologists (4,9%). The connection with level of infection (35,1%) and obstetrics (20,4%) depatrments. and duration of work at hospitals was found. Most people with Rate of HBsAg detection was maximal in surgeons – 3,3%, hepatitis B was detected in-group with working experience of and doctors and nurses of hemotransfusion service – 3,1% and 11-15 years – 28%, 6-10 years – 23% and 16-20 years – 22%. In 2,5%, respectively. HBsAg was not detected in gynecologists, groups with more than 20 years and 3-5 years – 12 and 11%, general practitioners had minimal values – 0,7% (Table II). less than 3 years – 4%. Most higher level of HCV-infection was detected in staff of Important to note the fact: nurses with work stage less than hemotransfusion service (5,4%). Rate of detection was maximal 5 years did not have HCV markers, if stage more than 10 years in doctors of hemotransfusion service – 3,1% and surgeons – rate was 1,3%. Rate of HCV marker in doctors with stage less 2,5%. Anti-HCV was not detected in gynecologists, in general than 5 years – 5,7%, with stage more than 10 years anti-HCV practitioners – 2,2%. detection increases in 1,8 times – 10,6%. During analysis most risk of infection in nurses was found Also, 62 epidemic niduses of HBV-infection in families (25,4%). In blood transfusion department total rate of HBV- with 121 people (including 11 children until 14 years, 15 teens

477 Sleptsova S.S., et al. and 95 adults) was observed. First group – 22 niduses of acute In families, which mother is nidus of infection, children hepatitis B with 63 people. Second group formed from niduses infected in 16 cases (40%). In this, 7 cases (43,7%) with expressed with chronic hepatitis B infection – in 40 niduses with 58 people clinical presentation and replication markers in serum of children examined. blood: HВeAg in 3 (18,7%), DNA-HBV in 6 (37,5%), HВeAg During observation, epidemiologic anamnesis were collected with HBV-DNA in 1 (6,25%). In case of father’s chronic infection and serological enzyme-linked immunosorbent assay and PCR (in 50% with liver cirrhosis), HBV infection markers of children markers were determined. Different forms of HBV-infection founded in 20,0%. In families with children primary infection were found. In children, HBV markers registered in 45,5%; HВsAg were detected in 40% in siblings. in adults – 55,8%; in teens – 80,0% of cases detected HBsAg Results of this study shows a key role of HBV transmission and anti-HBcIgG (Table III). In this way, contagious people in family: total amount with HBV markers is 57,8%. Our data involved in latent epidemic process of hepatitis B is 45,5-80%. regarding high epidemiological dangerous of people with According S.S. Pershin (1997) in examination of niduses of chronic hepatitis B in agree with similar results obtained by infection in families hearths is 44,5% different HBV-infection other researches [11, 12]. Risk of infection in family hearths markers founded [10]. with founded HBV-DNA was higher in 1,5 times than sources Generally, subclinical hepatitis B founded in 57,8% of contagious without replication. people. This fact indicates to intensive virus circulation in current Examined with anti-HCV detection and collection of group (Table III). epidemiologic anamnesis 110 niduses of infection in families 22 families with acute hepatitis B examined. HBsAg found with HCV-infection, formed by 84 people with acute hepatitis in 12 (19,0%), anti-HBcIgG – in 33,3% (Table IV). In 14 people C and 32 people with chronic hepatitis C. 259 people was under (22,2%) siblings is potential niduses of infection, in 6,3% – nidus our observation – 197 from acute hepatitis C nidus and 62 from is mother. In 6,3% of cases was sexual path of transmission. chronic hepatitis C including 115 men and 144 women. In 58 members of 40 families of people with chronic hepatitis primary examination of family anti-HCV founded in 9,3±1,8%. B were examined. In total, HBV markers founded in 77,6% Herewith, in acute hepatitis C niduses 7,1% seropositive people (45 people), including 25 (43,1%) with HBsAg, 29 (50%) with was founded, in chronic hepatitis C – 16,1%. Anti-HCV in anti-HBcIgG. 35,1±7,9% of cases was founded in spouses. In group of parents

Table III. Frequency of HBV-infection in people, who living in niduses of infection in families. Including

Age Examined (Abs.) HBV- markers HВsAg HBsAg + Anti-HBcIgG Anti-HBcIgG Children (0 -14 years) 11 5 1 3 1 Teens (15-19 years) 15 12 3 4 5 Adults (20-60 years) 95 53 16 10 27 Total 121 70 (57,8%) 20 (16,5%) 17 (14,0%) 33 (27,3%)

Tab. IV. Frequency of HBV markers in epidemic niduses, with formed by people with acute and chronic hepatitis B. HBV markers Including Amount of Amount of examinated Infection source HBsAg, sources people Abs. % HBsAg аnti-HBcIgG Anti-HBcIgG Acute HB 22 63 25 39,7 4 8 13 Chronic HB 40 58 45 77,6 16 9 20 Total 62 121 70 57,8 20 17 33

478 Br e a d t h s p r e a d i n g o f v i r a l h e p a t i t i s m a r k e r s in t h e r i s k g r o u p s in t h e r e p u b l i c o f s a k h a (y a k u t i a ) and children аnti-HCV was founded in 14,9% of children. Like 3. ogarkov P.I. Epidemiologic characteristics of medical staff hepatitis B vaccination/ this, spreading of this infection in families was low active. P.I.Ogarkov, A.V.Smirnov, V.S.Tokmakov //Thesis of conference “Clinical perspectives in Immunization in Yakutia implemented during «Vaccinal infectology”. – S.-Pb., 2001. – P. 146-147. prevention» republican program, in this moment – in federal 4. Rakhmanova A.G. Chronic viral hepatitis and liver cirrhosis: Doctors’ guideline/ A.G. program “Health”. On 31.12.2014 total amount of HBV-vaccinated Rakhmanova, A.A. Yakovlev, E.N. Vinogradova [et al.] S-Pb..: «SpetsLit», 2006. – P. 413. people is 548349 (97% of republic population), 99,6% of medical 5. Khrapunova I.A. Risk of nosocomial hepatitis B and C infection and prophylactics in staff and 84,4% of people in niduses in families. Moscow hospitals / I.A. Khrapunova, P.A. Huhlovich, L.D. Zhukova [et al.] // Hepatitis B, C and D. Problems of research, diagnostics, treatment and prophylactics: thesis of. – М., CONCLUSIONS 1997. – P. 234-235 High risk of HBV-infection enter to city hospitals founded. 6. mikhaylov M.I. Hepatitis viruses / M.I.Mikhaylov // Clinical hepatology – 2009. – №1. This fact promotes to formation of HBV-infection epidemic – P.15-24. niduses in large hospital. Duration of work in hospital and rate 7. Rakhmanova A.G. Viral hepatitis: ethiopathogenesis, epidemiology, clinics, diagnostics of HBV/HCV infection is directly depends: increase of duration and therapy / A.G. Rakhmanova, V.A. Neverov, G.I, Kirpichnikova [et al.] // Koltsovo, results to increasing of infection rate. 2003. – P. 57. Chronic carriers in families forming sustain niduses of 8. Shakhgyldyan I.V. Epidemiological characteristics of chronic hepatitis B and C in Russian infection and promotes to spreading. High intensity of HBV Federation / I.V. Shakhgyldyan [et al.] // Information statement World of viral hepatitis epidemic process, due by natural transmission pathways, – 2008. – № 5. – P.11-13. promotes to persistence of virus in contagious person. In- 9. Savelyev S.I. Parenteral viral hepatitis as one of major professional diseases of medical family transmission of HCV possible too, but activity of this staff /S.I. Savelyev, I.A. Tschukina, I.A.Khodyakova [et al.] //Actual problems of modern lesser, than HBV infection. virology. – Ekaterinburg, 1995. – P. 275-282. 10. Sleptsova S.S. Viral hepatitis in Republic of Sakha (Yakutia): Ph.D. dissertation synopsis: REFERENCES 14.01.09, 14.02.03./ Sleptsova Snezhana Spiridonovna. – S.-Pb., 2013. – 44 p. 1. Yakupova F.M. Immunoprophylatics of hepatitis B perinatal infection in niduses of 11. mukomolov S.L. Modern epidemiologic essentials of viral hepatitis B /S.L.Mukomolov, I.A. infection in families / Yakupova F.M, Fazylov B.H. // Practical medicine – 2012. -№ 7 Levakova, V.A. Vasilyeva //Thesis of VII Russian conference “Viral hepatitis: epidemiology, (83). – P.133-136. diagnostics, treatment and prophylactics” / World of viral hepatitis. – 2009. – № 3. – P. 19. 2. Akimkin V.G. Epidemiologic features of hepatitis B and C spreading in patients and 12. Nechaev V.V. Epidemiology and prophylactics of viral hepatitis with parenteral transmission personnel of large / Akimkin V.G., Skvortsov S.V., Vytsar B.N. [et al.] // C hepatitis pathways in hospitals: guidelines / V.V.Nechaev, G.M. Valegova, G.V. Hromova [et al.] (Russian consensus): Thesis of conference, 26-27 Sept. 2000 – М., 2000. – P. 6-7. // В.В. –S.-Pb.., 1993. – 19 p.

ADDRESS FOR CORRESPONDENCE: Sleptsova S.S. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street Ph. 8-914-2718770 [email protected]

479 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Lic h e n s ’ β-o l ig o s a cc h a ri d es in t h e c o rrecti o n o f m е t а b o l ic d is o r d ers in t y pe 2 d i а b е t е s m e l l it u s

Kershengolts B.M.1,2, Sydykova L.A.2, Shаrоykо V.V.1,3, Anshakova V.V.2, Stepanova A.V.2, Varfolomeeva N.A.2 1f g b i s “i n s t i t u t e o f b i o l o g i c a l p r o b l e m s o f cryolithozone s b r a s ”, y a k u t s k 2f g b i s h p e “n o r t h -e a s t e r n f e d e r a l u n i v e r s i t y , n a m e d a f t e r m.k. a m m o s o v ”, y a k u t s k 3f g b i s h p e “s a i n t p e t e r s b u r g s t a t e u n i v e r s i t y ”, i n s t i t u t e o f c h e m i s t r y, s a i n t p e t e r s b u r g

ABSTRACT Introduction: lichens of the genus Cladonia are used as medicinal plants in folk medicine. Biologically active food supplement (BAFS) on the basis of lichens p. Cladonia was derived by mechanical-chemical biotechnology in the Educational-Research-Engineering Laboratory “Mechanical-Chemical Biotechnology” of the North-Eastern Federal University (NEFU). As a result of biotech impact, the solid β-glycoside bonds are destructed on β-oligosaccharide molecules, and other groups of lichen BAS is mobilized. The content of hydrolysable carbohydrates in samples of lichen increased 8 times after mechanical activation. Aim: the aim of investigation was to study the effects of BAFS “Yagel-Detox” in patients with type 2 diabetes mellitus (DM 2). Materials and methods: the 150 patients (group 1 – 100 patients receiving “Yagel-Detox”, group 2 – 50 patients receiving placebo) with a diagnosis DM 2 were examined. The research included: general clinical and instrumental examination, biochemical and clinical blood tests. “Yagel-Detox” was used 1 capsule 3 times a day, the rate of admission was 3 months. Results: clinical trials have shown that 3-month intake of BAFS “Yagel-Detox” reduces the concentration of blood glucose 1.3÷1.6 times (in the control group – 1.2÷1.4 times), glycosylated hemoglobin – from 9.8÷11.4% to 7.6% (in the control group – 1.0%). The concentration of low-density lipoprotein (LDL) reduced on 1.3 % through 6 months. Patients of both groups were on the similar tablet glucose-lowering therapy (randomized treatment), which have not been adjusted. Conclusions: the obtained results allow us to recommend BAFS “Yagel-Detox” as an additional remedy to normalize blood glucose concentration in patients with DM 2.

Key words: lichens, oligosaccharides, diabetes mellitus, type 2.

Wiad Lek 2015, 68 (4), 480-482

INTRODUCTION was found in the hyphae of lichens. The amount of lichenin By the definition of the International Diabetes Federation and reaches 50-70% of dry matter. As a result of it hydrolysis, 98- WHO, diabetes mellitus (DM) is characterized as an epidemic, so, 99% D-glucose is formed, the remains of which are related in prevention, treatment of DM, and its complications is one of the lichenin two ways – 73% by β-glycosidic bonds between the 1st primary tasks of biomedical science and public health. Therefore, and the 4th, and 27% by β-glycosidic bonds between the 1st and despite the presence in the pharmaceutical market plurality of 3rd carbon atoms [3]. Synthesis of lichenin in vitro is not yet drugs for treating diabetes, a search for new therapeutic options done. A human body does not assimilate lichenin. Lichenin is is actively conducted. It is known that in folk medicine the absorbed in organism of reindeer due to hydrolysis by bacteria plants with hypoglycemic actions are commonly used (Coccinia found in their digestive tract. Theβ -polysaccharides cover the indica, Silibum marianum and others) [1]. In particular, one hyphae of lichens, forming a 3D matrix, in which cells there of the most widely used drugs in type 2 DM – Metformin, was are other biologically active substances (BAS) in «immobilized» derived from the plant Galega officinalis (French Lilac). form. Mechanical activation process destroys the cortical layer, To expand the range of plant material used for correction of formed by dense tangle of fungal hyphae, between which are metabolic disorders in diabetes, biologically active food supplements located the cells of fikobiont and algal area with high content of (BAFS) on the basis of lichens p. Cladonia [2] were derived by BAS, for example, a wide range of metabolites with antibacterial mechanical-chemical biotechnology in the Educational-Research- action. As a result of such biotech impact, the solid β-glycoside Engineering Laboratory “Mechanical-Chemical Biotechnology” bonds are destructed on β-oligosaccharide molecules, and other of the North-Eastern Federal University. Lichens of the genus groups of lichen BAS is mobilized [4]. Cladonia are medicinal plants used in folk medicine to treat many Analysis of water-soluble carbohydrates by «reducing diseases. A polysaccharide lichenin, called even lichen starch, tip» method in extracts of the lichen genus Cladonia after a

480 Li c h e n s ’ β-o l i g osaccharides in t h e c o r r e c t i o n o f m е t а b o l i c d i s o r d e r s in t y p e 2 d i а b е t е s m e l l i t u s rough grinding or mechanical activation, confirmed the partial Table. I. Informed consent was prospectively obtained from all patients destruction of β-glycosidic linkages in lichen β-polysaccharides. – participants of study. Theβ -oligosaccharide molecules are produced due to mechanical Group 1 Group 2 Index activation. The content of hydrolysable carbohydrates in samples (N=100) (N=50) (comparison) of lichen genus Cladonia increased 8 times and after mechanical HbA1c, % 9,8±1,6 9,2±2,1 activation was 33.48 mg/g of dry material (and 4.61 mg/g of Fasting venous plasma 10,2±1,8 11,6±2.2 dry sample milled on the mixer KMS-50 before mechanical glucose, mmol/l activation). Total cholesterol, mmol/l 7,2±1,2 6,8±0,8 Previously, the ability of hydroalcoholic extract from the LDL cholesterol, mmol/l 3,1±1,02 2,8±1,05 lichen genus Cladonia, pre-treated with carbon dioxide in a HDL cholesterol, mmol/l 0,9±0,12 0,9±0,22 supercritical fluid state – BAFS “Yagel” [5], to improve insulin Triglyceride, mmol/l 2,1±0,12 2,2±0,82 secretory function of clonal β-cells of rat insulinoma INS-1 BP systolic, mm Hg 145±10 149±15 (clone 832/13), was studied [6]. The results of pre-clinical studies, BP diastolic, mm Hg 45±8 38±12 obtained in these experiments, allowed us to conduct clinical BMI, kg/m² 32±2,8 30±1,8 trials of “Yagel-Detox” in order to reduce blood glucose in patients with type 2 DM. According to the classification, proposed by the US National Institutes of Health, these clinical trials are glycated hemoglobin decreased in both groups of the study (Fig. classified as “quality of life trials”, which are held to explore 1). However, a statistically significant reduction was observed only ways to improve the quality of life of patients, suffering from in group 1, getting “Yagel-Detox” for 3 months, with retention chronic diseases [7]. of a good result on this indicator within 6 months. Aim: the aim of our investigation was to study the effects of Indicators of fasting blood glucose have also demonstrated BAFS “Yagel-Detox” in patients with type 2 diabetes mellitus statistically not significant, but a considerable decrease in 3 (DM 2). months in group 1 (Fig. 2). Improved indicators in the control group, getting placebo, can be explained by more frequent self- MATERIALS AND METHODS monitoring of the patients and their lifestyle modification. BAFS “Yagel-Detox” and placebo in capsule form for using per os, were produced in the laboratory of the NEFU by mechanical- chemical biotechnology. The research program of “Yagel-Detox” included comprehensive treatment and examination of 150 patients (group 1 – 100 patients receiving “Yagel-Detox”; group 2 (comparison) – 50 patients receiving placebo) with a diagnosis of type 2 DM, and getting the standard glucose-lowering tablets therapy. The research included: general clinical and instrumental examination, biochemical and clinical blood tests, as well as the determination of HbA1c (glycated hemoglobin). Baseline characteristics of the study groups are shown in Table. I. Correction of prior hypoglycemic therapy was not conducted, “Yagel-Detox” administered separately. “Yagel-Detox” was used 1 capsule 3 times a day, the rate of admission was 3 months. Indications for use were type 2 diabetes and metabolic disorders. Fig. 1. Dynamics of average HbA1c, %. Typical instrumental and laboratory signs, showing on metabolic disorders were: Hyperglycemia (fasting venous plasma glucose > 6.1 mmol/l, HbA1c > 6.5%); Dyslipidemia (total cholesterol > 4.5 mmol/l, LDL cholesterol > 2.6 mmol/l, HDL cholesterol < 1.0 mmol/l (men), HDL cholesterol < 1.2 mmol/l (women), TG > 1.7 mmol/l); Hypertension (BP > 130/80 mm Hg); Overweight and obesity (BMI > 25 kg/m²). Clinical and laboratory monitoring to assess the effectiveness of the BAFS was conducted in 3 and 6 months. The results of study were processed using StatSoft Statistica v.6.0, SPSS 9.0 statistical software.

RESULTS AND DISCUSSION Dynamic observation showed that the patients stood supplement “Yagel-Detox” well, side effects were not observed. The level of Fig. 2. Dynamics of average fasting venous plasma glucose, mmol/l

481 Sleptsova S.S., et al.

Table II. Dynamics of the blood pressure in study groups, mm Hg. Groups Initial In 3 months In 6 months Group 1 145±10 45±8 140±18 45±15 142±16 38±12 Group 2 149±15 38±12 142±12 40±8 144±22 38±18

Fig. 3. Dynamics of lipid spectrum indicators, mmol/l. Fig. 4. Dynamics of body mass index (BMI), kg/m².

A significant improvement in total cholesterol indicators in REFERENCES the group 1, due to reducing triglyceride level and increasing 1. mark D.A. Chromium picolinate supplementation attenuates body weight gain and HDL, were revealed (Fig. 3). In group 2 (placebo) analysis, after 3 increases insulin sensitivity in subjects with type 2 diabetes // Diabetes Care. 2006 and 6 months, no significant dynamic changes were showed. Dec; 29(12):2764. Control of blood pressure dynamics found no significant 2. Biologically active food supplement “Yagel-Detox” // certificate of state registration changes in indicators in both groups over the study period RU.77.99.11.003.E.003704.05.13. (Table. II). 3. Dembitsky V.M., Tolstikov G.A. Organic metabolites of lichens. Novosibirsk: Publishing Average body mass index (BMI) after 3 months of the study house “Geo”, 2005: 135 p. decreased on 1 indicator from the initial figure in both study 4. Anshakova V. The mechanochemical technology for producing of biocomplexes based groups. The retention result was revealed in group 1. In group on lichen material // Russian Journal of Biopharmaceuticals. 2011. V. 3(5):P.33-42. 2 the index returned to the original value (Fig. 4). 5. Biologically active food supplement “ Yagel “ // certificate of state registration RU.77.99.11.003.E.051236.11.11. CONCLUSIONS 6. Churkina E.V., Kershengolts B.M., Sharoiko V.V. Effect of the BAFS “Yagel” from thalli of Thus, analysis of the results of the study showed the efficacy lichen genus Cladonia on insulin secretion // Far East Medical Journal. 2011. V. 2:67-70. of natural raw materials from lichen, processing by mechanical- 7. http://www.webcitation.org/61BHrqVfM (02/20/2015) chemical biotechnology, as an additional remedy for the correction of metabolic disorders in treatment of type 2 diabetes mellitus. A positive effect on carbohydrate and lipid metabolism in patients ADDRESS FOR CORRESPONDENCE: with type 2 diabetes was noted. There were no adverse effects Sydykova L. on blood pressure and weight gain of patients. BAFS “Yagel- Russia, Republic of Sakha (Yakutia), Detox” should be given 1 capsule 3 times a day for 3 months 677000, Yakutsk, 20, Kulakovski Street, flat 15 courses 1-2 times a year. Ph. 8(924)5931550, 8(964)4213932 [email protected]

482 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Clinical a n d m o rp h o l o gic a l c h a r a cteristics o f t h e c h r o n ic g a stritis w it h f u n cti o n a l d y spepsi a in t h e rep u b l ic o f s a k h a (y a k u ti a )

Avvakumova N.V.1, Chibyeva L.G.1, Vasiliev N.N.2 1f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a 2y a k u t s k c i t y clinical h o s p i t a l

ABSTRACT Introduction: chronic gastritis with syndrome, functional dyspepsia (SFD) is one of the most pressing problems in medicine. Certain scientific and practical interest is the elucidation of the frequency and clinical manifestations of functional dyspepsia in patients hospitalized in the gastroenterology department YAGKB and frequency combinations of chronic gastritis (including H. pylori) with functional dyspepsia. Aim: the aim of the study was to investigate the clinical and morphological features of the chronic gastritis with syndrome pattern of functional dyspepsia in native-born and people of the Republic of Sakha (Yakutia), an d to assess the effectiveness of treatment, depending on the gastric acid and H.pylori. Materials and methods: this study examined 105 patients with functional dyspepsia, including 41 patients with epigastric pain syndrome and 64 patients with postprandial distress syndrome. Considered groups of patients were homogeneous for age, gender, by ethnicity. Of the 105 patients included in the study, I group were 57 indigenous people (80% of them – Yakutia), II group – 48 people visiting (Caucasians). Results: clinical presentation and course of chronic gastritis with functional dyspepsia in the Republic of Sakha (Yakutia) have a number of distinctive features: epigastric pain syndrome occurs in 26,8% of patients and 73,2% of the indigenous population of the visitor, the intensity of pain in the root is much lower than that of visitors – 12 and 85% respectively. Postprandial distress syndrome was diagnosed in 71,9% of patients and 28,1% of the indigenous newcomers. At endoscopy in all patients with functional dyspepsia diagnosed chronic gastritis. The native inhabitants of the most common mixed gastritis (54,5%), the newcomers – superficial gastritis (66,7%). Conclusions: the found features of a current of functional dyspepsia can be further the basis for the individualized and differentiated approaches to treatment of this disease.

Key words: A syndrome of functional dyspepsia, epigastric pain syndrome, posprandialny distress syndrome, gastric mucosa, Helicobacter pylori.

Wiad Lek 2015, 68 (4), 483-486

INTRODUCTION of Sakha (Yakutia), remain, gives reason to believe that their Chronic gastritis with syndrome, functional dyspepsia (SFD) study is relevant. is one of the most pressing problems in medicine. Prevalence SFD The aim of the study was to investigate the clinical and is considered very high, but the exact static data, not, as many morphological features of the chronic gastritis with syndrome patients do not seek medical help. In recent years, a growing pattern of functional dyspepsia in native-born and people of interest in functional dyspepsia. This is due primarily to the the Republic of Sakha (Yakutia), and to assess the effectiveness fact that this pathology along with other functional disorders of treatment, depending on the gastric acid and H.pylori. of the digestive system causing significant economic losses to society, taking after acute respiratory infections second place MATERIAL AND METHODS in the list of most important causes of disability [2, 5, 6, 7]. This study examined 105 patients with functional dyspepsia, Gastrointestinal complaints are the cause of 4-5% of all cases including 41 patients with epigastric pain syndrome and 64 of complaints of patients to general practitioners. In this case, patients with postprandial distress syndrome. Considered groups the share of organic dyspepsia accounts for only 35-40% of of patients were homogeneous for age, gender, by ethnicity. Of the all cases of this syndrome, and the proportion of functional 105 patients included in the study, I group were 57 indigenous dyspepsia – 50-60% [1, 3, 4]. people (80% of them – Yakutia), II group – 48 people visiting Certain scientific and practical interest is the elucidation of the (Caucasians). Considered groups of patients were homogeneous frequency and clinical manifestations of functional dyspepsia in for age and sex. Group I included 22 men, 35 women, in the patients hospitalized in the gastroenterology department YAGKB II group – 28 men, 20 women. The control group consisted of and frequency combinations of chronic gastritis (including H. 30 healthy individuals. The range of initial evaluation included pylori) with functional dyspepsia. Thus, many of the issues esophagogastroduodenoscopy. The study was combined with related to the study of functional dyspepsia in the Republic biopsy, which was taken at least 2 pieces: from the antral mucosa

483 Avvakumova N.V., et al. of the stomach body, in the presence of erosions of the mucous superficial gastritis. The group of patients visiting more common membrane – at least 4 pieces of the erosion. superficial gastritis, which is combined with duodenogastric Intragastric pH-metry was performed using autonomous reflux (table 1.). In 105 patients with the syndrome of functional atsidogastrometra “Gastroskan-24” (source system, Russia), dyspepsia, which included 51 men and 54 women aged 18 to 65 which will record the pH automatically within 24 hours. years, we have analyzed the degree of contamination H. pylori To determine the Helicobacter pylori in the gastric mucosa and gastric mucosa. Lower degree of colonization of the gastric the degree of contamination using histological, immunological mucosa of the patients diagnosed in the indigenous population and biochemical (rapid urease test) methods. – (50,9%), moderate – (25,5%) and high – (23,6%). In patients visiting the degree of contamination is slightly higher than the RESULTS AND DISCUSSION root: low – (26%), moderate – (30%) and high – (44%). In the analysis of clinical symptoms of functional dyspepsia A significantly greater degree of contamination H. pylori patients identified with postprandial distress syndrome 64 (61%) (P <0,05) was found in patients with epigastric pain syndrome and epigastric pain syndrome, 41 (39%). The main clinical compared with postprandial distress syndrome can suggest that H. manifestations of the syndrome of functional dyspepsia patients pylori infection plays a role in the genesis of pain in PD. Probably, described by the group was the pain localized in the epigastric H. pylori causes dysmotility of the upper gastrointestinal tract region, which was detected in 56,1±6,6% of patients with the and increased visceral perception, which leads to the appearance indigenous population and 62,5±7,0% – the visitor (p>0,05). of clinical symptoms of functional dyspepsia [2, 3]. Along with pain in patients with indigenous populations were The average pH of the stomach body was determined by observed more severe diarrheal disorders: nausea – at 38,6±6,4%, the results of the 24-hour pH-metry in patients with epigastric vomiting – at 14,0±4,6, heartburn – at 21,1±5,4, regurgitation pain syndrome, postprandial distress syndrome, functional “odor of rotten eggs» – 29,8±6,1, bloating and fast saturability dyspepsia. after taking even a small amount of food – from 31,6±6,2% of The syndrome of epigastric pain hyperacidity was 51,2% (n-21), patients. Disorder observed in stool 12,3±4,4% as constipation normatsidnost – 26,8% (n-11), hypoacid – 22,0% (n-9) cases. and 24,6±5,7% of patients – in the form of diarrhea. In clinical When postprandial distress syndrome of functional dyspepsia manifestations of functional dyspepsia patients of this group hyperacidity observed in 25% (n-16) of cases normatsidnost – dominated dyspeptic symptoms, predominantly in combination, in 56,2 (n-36), hypoacid – in 18,8% (n-12) of cases. (table 2.). such as: weight after meal with a sense of early saturation, bloating, Feature of gastric acid syndrome in patients with epigastric pain rumbling, belching, nausea, vomiting. In the group of immigrants indigenous acid production is continuous and Hyperacidity – 4 were more common: pain syndrome – 62,5±7,0% of patients with (9,8±4,6%) cases normatsidnost – 3 (7,3±4,1%), hypoacid – 4 localization in the pyloroduodenal area and epigastric heartburn (9, 8±4,6%). From visiting patients gastric acid level somewhat – at 54,2±7,2, burping – from 20,8±5, 9, early feeling of saturation higher: Hyperacidity was observed in 17 (41,4±7,7%) patients – at 18,7±5,6, constipation – at 37,5±7,0% (p <0,05), and other normatsidnost – in 8 (19,5±6,2%), hypoacid – in 5 (12,2±5 , symptoms of dyspepsia were observed less frequently. Thus, in 1%) patients (p <0,02). For postprandial distress syndrome in patients with various functional dyspepsia in history can not be patients with indigenous populations were characterized by: isolated only factors determining the development of clinical normatsidnost – in 29 (45,3±6,2%), hypoacid – in 10 (15,6±4,5%), symptoms. Seems to play a role here summation pathogenic hyperacidity recorded at least – in 7 (10 9±3,9%) patients. From effects, that is, the disease is multifactorial in nature. visiting patients with postprandial distress syndrome is more At esophagogastroduodenoscopy in patients indigenous common in hyperacidity, in 9 (14,1±4,4%), normatsidnost – in most common mixed gastritis, focal atrophic gastritis and less 7 (10,9±3,9%), hypoacid – in 2 (3,1±2,2%) patients (p <0,01).

Table I. Endoscopic picture of the various options syndrome functional dyspepsia. Epigastric pain syndrome Postprandial distress (n – 41) syndrome (n – 64) Endoscopic picture 1 group 2 group 1 group 2 group Р Р (n – 11) (n – 30) (n – 46) (n – 18) 2 1 Pathology wasn’t found – – – – (6,7±4,6) (2,2±2,2) 2 16 15 12 Endogastritis >0,01 <0,02 (18,2±11,6) (53,3±9,1) (32,6±6,9) (66,7±11,1) 3 5 11 2 Focal atrophic gastritis >0,05 >0,05 (27,3±13,4) (16,7±6,8) (23,9±6,3) (11,1±7,4) 6 7 14 2 Mixed gastritis <0,02 <0,04 (54,5±15,0) (23,3±7,7) (30,4±6,8) (11,1±7,4) 2 Duodenogastric reflux – – – 5 (10,9±4,6) <0,03 (11,1±7,4)

484 Clinical a n d m o r p h o l o g i c a l characteristics o f t h e c h r o n i c g a s t r i t i s w i t h f u n c t i o n a l d y s p e p s i a in t h e r e p u b l i c o f s a k h a (y a k u t i a )

Table II. The degree of colonization of the gastric mucosa Hp patients in different ethnic groups. The degree Including Altogether (n-105) Р of contamination HP 1 group (n-57) 2 group (n-48) H. pylori + 40 (38,1±4,7) 13 (22,8±5,6) 22 (45,8±7,2) <0,03 H. pylori ++ 30 (28,6±4,4) 16 (28,1±6,0) 14 (29,2±6,6) <0,01 H. pylori +++ 35 (33,3±4,6) 28 (49,1±6,6) 12 (25,0±6,3) <0,03

Thus, the syndrome of continuous epigastric pain and acid expressed dyspeptic complaints were recorded in 4 patients production Hyperacidity recorded more frequently in patients (6,25%), moderate dyspeptic complaints in 12% (18,75%), mild visiting – 17 (41,4±7,7%), and in patients with the indigenous dyspeptic complaints – in 10 patients (15,63%). Only 3 days population – 4 (9,8 ± 4,6%) cases (p < 0,01). When postprandial of treatment dyspeptic syndrome was arrested in 38 (59,37%) distress syndrome in patients with more common indigenous of 64 patients who complained of stomach indigestion before normatsidnost – 29 (45,3±6,2%), from visiting patients Hyperacidity treatment. On day 5 of treatment expressed dyspeptic symptoms – 9 (14,1±4,4%) (p <0,05). were observed, moderate dyspepsia occurred in 4 (6,25%), When comparing the average pH of the body of the stomach dyspeptic syndrome of low intensity – in 6 patients (9,38%). in two groups of patients with functional dyspepsia with the On day 7, treatment of dyspeptic complaints did not show any following results: the average pH in patients with epigastric of the patients. pain syndrome was equal to 2,15 u, with postprandial distress When FD with epigastric pain syndrome and postprandial syndrome – 5,1 units. distress syndrome after a month of treatment has been good The highest acid production accounts for evening and night progress. hours (20.00 to 04.00) – 1,4±0,2, which requires the use of Thus, the results of medical treatment of patients with antisecretory drugs with the biorhythm of acid. functional dyspepsia led to the following conclusions. We evaluated the relationship of acid-forming function of In the presence of patients with functional dyspepsia of pain the stomach and pain intensity in patients with various forms in the epigastric region, and 3,1 symptoms of discomfort in of functional dyspepsia. Of the 41 patients with epigastric pain advanced gastric hyperacidity effectively destination 7–10 – days syndrome in 30 (73,2±6,9%) had hyperacidity, and the pain of therapy with proton pump inhibitors (omeprazole 20 mg 2 syndrome was detected in 10 (33,3%), moderate in 14 (46,7%) times a day), somewhat less effective in treatment of such patients and the smaller – in 6 (20%) patients. In patients with moderate therapy blockers H2-receptor antagonists, 150 mg two times a and mild pain was identified normatsidnost and hypoacid – in day (longer terms of treatment of pain and heartburn). 5 (12,2±5,1%) and 6 (14,6±5,5%), respectively. Consequently, To eliminate a large number of clinical symptoms, usually the presence of pain in functional dyspepsia is significantly combined into a single term “discomfort”, require a comprehensive correlated with increased acid production in the stomach therapy including antisecretory agents in combination with (p <0,05), and when and hypoacid normatsidnyh states equally prokinetics, in some cases with enzymatic preparations. often present pain of moderate and low intensity. Combined use of blockers of histamine H2-receptor with Treatment of functional dyspepsia symptoms associated prokinetics, and some patients with the enzyme preparation with great difficulties, because so far not developed effective showed high efficiency in the treatment of pain, and a large number therapies different variants of this syndrome. The variety of of diarrheal illness in patients with functional dyspepsia. pathophysiological mechanisms of the syndrome of functional A high level of eradication is achieved at the 10-day treatment dyspepsia requires an individual approach to drug therapy in of patients with chronic H. pylori gastritis with functional these patients. In this regard, there is still no consensus on the dyspepsia blockers, H2-receptor antagonists in combination issue. with two antibiotics (amoxicillin and tetracycline), which also Patients with hyperacidity (n=31) was obtained as antisecretory should take note. therapy proton pump inhibitors – omeprazole (n=14), and Thus, functional dyspepsia is one of the most common rabeprazole (Pariet) (n=17). syndromes of the upper digestive tract, where there are various Patients with normatsidnostyu and hypoacid H. pylori-negative options for chronic gastritis with frequent persistence of H. received a prokinetic drug motilium 10 mg 3 times a day. pylori, a violation of the evacuation of the gastrointestinal tract. In the presence of H. pylori infection in all patients as a In the treatment of this syndrome have been used successfully therapy of H. pylori received clarithromycin and amoxicillin H. pylori and antisecretory agents, with postprandial distress for 7-day scheme. syndrome –prokinetics, and the detection of Hyperacidity When postprandial distress syndrome in 64 patients before designate antisecretory agents. treatment dyspeptic complaints reported 46.9% of patients (n=30) of them are dominated by moderate dyspeptic complaints – 18 CONCLUSION (28,1%) compared with severe (n=13, 20,3%) and mild (n=3, Clinical presentation and course of chronic gastritis with 4,7%), dyspeptic complaints. On the 3-rd day of therapy, functional dyspepsia in the Republic of Sakha (Yakutia) have a

485 Avvakumova N.V., et al. number of distinctive features: epigastric pain syndrome occurs REFERENCES in 26,8% of patients and 73,2% of the indigenous population of 1. Ivashkin V.T. Recommendations for evaluation and treatment of patients with dyspepsia the visitor, the intensity of pain in the root is much lower than syndrome: A guide for physicians./V.T. Ivashkin, A.A. Sheptulin // – M.: 2001. – P. 30. that of visitors – 12 and 85% respectively. Postprandial distress 2. Sheptulin A.A. Discussion of the problem of Helicobacter pylori infection in the European syndrome was diagnosed in 71,9% of patients and 28,1% of Gastroenterology Week/ A.A. Sheptulin, O.A. Mordanova // Rus. Journal. Gastroenterol., the indigenous newcomers. At endoscopy in all patients with Gepatol., Koloproktol. – 2007. – T. 14. – № 2. – P. 88–92 functional dyspepsia diagnosed chronic gastritis. The native 3. Drossman D.A. The functional gastrointestinal disorders and the Rome-III process. / inhabitants of the most common mixed gastritis (54,5%), the D.A. Drossman // Gastroenterology. – 2006. – Vol. 130 (5). – P. 1377–1390. newcomers – superficial gastritis (66,7%). The syndrome of 4. Longstreth G.F. Functional bowel disorders / G.F. Longstreth, W.G. Thompson, W.D. Chey continuous epigastric pain and acid production Hyperacidity [et al.] // Gastroenterology. – 2006. – Vol. 130 (5). – P. 1480–1491. detected more often in immigrants (41,4%) than in the indigenous 5. Tack G. Functional gastroduodenal disorders. / G. Tack, N.G. Talley, M. Camillery [et al.] population (9,8%). When postprandial distress syndrome in // Gastroenterology. – 2006. – Vol. 130 (5). – P. 1466–1479. indigenous normatsidnost more common (45,3%), the visitors 6. Hall W. Gastric mucosal mast cells are increased in Helicobacter pylori-negative – Hyperacidity (14,1%). The syndrome of epigastric pain more functional dyspepsia / W. Hall, M. Buckley, P. Crotty, C.A. O’Мorain// – Clin Gastroenterol effective was the appointment of H. pylori and antisecretory Hepatol – 2003 Sep. – 1(5).-P. 363-369. drugs, and at postprandial distress syndrome – prokinetic in 7. Loreno M. Pattern of gastric emptying in functional dyspepsia. An ultrasonographic identifying Hyperacidity therapy should supplement antisecretory study/ M. Loreno, A. M. Bucceri, F.Catalano [et al]//.-Dig Dis Sci – 2004 Mar. – 49(3). agents. – P.404-407.

ADDRESS FOR CORRESPONDENCE: Avvakumova N. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, Yaroslavsgogo St. 30, quarter 16. Ph.8-924-870-15-50 [email protected]

Within scientifically research work of Public Educational Institution of Higher Professional Training Severo-Vostochny federal university to them M. K. Ammosova “Physiological and medical aspects of health protection of various age groups of the population of the Republic of Sakha (Yakutia)”.

486 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Ne w a pp l ic a ti o n s o f a d a pt o ge n s t o re d u ce r a d i a ti o n si d e e f f ects

Alekseeva S.N., Antipina U.D., Arzhakova L.I., Protodyakonov S.V. m e d i c a l i n s t i t u t e o f t h e n o r t h -e a s t e r n f e d e r a l u n i v e r s i t y , y a k u t s k , r u s s i a

ABSTRACT One of the live medical issues today is to find medication to prevent adverse effects of ionizing radiation on the immune and hematopoietic systems. In Yakutia where in most of its regions the overall environmental situation is getting worse due to the development of natural deposits including radioactive deposits, this problem remains vital. The purpose of this work is to study radioprotective properties of adaptogens in the case of the hematopoietic system under irradiation. The studies were conducted on certain groups of hybrid mice. We used the methods of radiation exposure by a radiological apparatus RUM-25 on hybrid mice followed by studying the cellularity of bone marrow, spleen and thymus. The functional activity of all compartments of early hematopoiesis (bone marrow hematopoiesis) was identified by the exogenous colony forming method. The study found that the extracts of reindeer and moose antlers have a stimulating effect on the functional activity of the hematopoietic precursors in response to radiation. The study medication stimulates regeneration processes in the thymus and bone marrow after irradiation. Further, the adaptogens stimulatory effect on CFU functional activity was identified. The most pronounced effect has the extracts of reindeer antlers “Epsorin”.

Key words: hematopoiesis, adaptogens, radioprotectors, radiation.

Wiad Lek 2015, 68 (4),487-489

INTRODUCTION One of the live medical issues today is to find medication The wide scale of peaceful application of nuclear energy to prevent adverse effects of ionizing radiation on the immune in a number of areas like energy sector, medicine, agriculture, and hematopoietic systems. In Yakutia where in most regions industry, space exploration, as well as the ongoing threat of a the overall environmental situation is getting worse due to the military conflict involving nuclear weapons pose a potential development of natural deposits including radioactive deposits, risk for present and future generations. The number of people this problem remains vital [2] exposed to ionizing radiation sources will continue to grow. The radiological environment is one of the important priorities For over 30 years scientists have known radioprotective among the environmental factors in the Sakha Republic (Yakutia). properties of certain chemicals and their study is conducted for The slow elimination process of products of nuclear weapons tests public health protection. It is self evident that there is the need conducted in the late 20th century from the stratosphere remains to to protect people from exposure to ionizing radiation in the be the main contamination source. Settling on the area the radioactive aftermath of accidents at nuclear installations and in case of a products of those explosions pollute water and soil [3,4]. military conflict involving nuclear weapons. Further penetration Goal of research: To study the radioprotective properties of into space is also inconceivable without the development of extracts of reindeer and moose antlers, ginseng tincture on the appropriate radioprotective measures. hematopoietic system in response to radiation exposure. Radiation protection in a broad sense includes any action aimed Objectives: 1. To study the effect of adaptogens in the process at reducing the risk of radiation injury. These primarily include of exogenous and endogenous CFU colony formation. 2. To all the preventive measures in the field of radiation safety in the compare the effects of the study medications on the regeneration units with ionizing radiation [1]. Recommendations (№ 26) of processes of the hematopoietic and immune systems in response the International Commission on Radiological Protection were to radiation exposure. published in 1977. In 1982 the International Atomic Energy Agency in Vienna published basic safety rules for radiation protection. MATERIALS AND METHODS Upon contact to ionizing radiation of high power the practical The studies were conducted in the Department of Experimental protection measures might include: a) mechanical shielding of Immunology of the Institute of Clinical Immunology SB RAMS a part or all of the body during exposure; b) dose fractionation on hybrid mice (SVAhS57V1 / 6) F1. by rotation during works in contaminated areas and outside; c) One control group of mice, three groups of experimental radioprotective agents prescription before irradiation. mice, before and after the radiation exposure they received

487 Alekseeva S.N., et al. respectively: Group 2 – “Epsorin”, Group 3 – extract from moose It was found that the most pronounced effect was obtained antlers, Group 4 – ginseng tincture (comparator). with the use of "Epsorin" and the extract from moose antlers. So Radiation exposure techniques were followed by study of the the number of CFUs with the administration of these medications cellularity of bone marrow, spleen and thymus. The functional exceeded the performance of the irradiated control about 1.7 and activity of all compartments of early hematopoietic progenitor 1.6 times, respectively (firm p <0.001). With the administration (bone marrow hematopoiesis) was identified by the exogenous of ginseng this figure exceeds the control approximately 1.3 colony forming method. The hybrid mice were irradiated using times (firm p <0.02). RUM-25 at a dose rate of 0.5 Gy / min, a voltage of 130 kW, a Thus, the use of adaptogens after exposure has a stimulating current of 10 mA. The radiation dose was 500 roentgen. The effect on the growth of spleen endo-colonies that demonstrates mice were killed 8-9 days after exposure. The extracted spleens radioprotective properties of these drugs. Apparently, their effects were placed in Carnoy or Telesnitsky solutions and 24 hours can be related to their anti-stress effect when such a stress factor later the colonies on the spleen surface were counted [5]. is radiation. Administered adaptogens that have the ability to activate the body defenses, seems to provide a higher recovery RESULTS rate of CFUs in a spleen. From the data of Figure 1 it is clear that the studied medications At the first stage of the study medications were administered in increase (firm, p <0.05) the number of splenic endo-colonies. a volume of 0,2 ml orally daily for 5 days. After drug administration, It was found that in the control group, the number of endo- animals were exposed to the total X-ray irradiation at a dose of 5 Gy colonies per spleen was 4,5 ± 0,6. The experimental groups: in the once. On the 9th day the bone marrow cellularity was counted. group treated with "Epsorin" prior to irradiation the endo-colonies According to our data (Fig. 3) it was found that the cell number on the spleen were 7,96 ± 0,8; in the groups treated with an of the femur in the control group was 4,8 ± 0,9 x 106. In the extract from the northern moose antlers and ginseng the number experimental groups, in Group 1 in animals treated before of endo-colonies were 8,7 ± 1,3 ± 1,2 and 10 respectively. irradiation with "Epsorin", in group 2 treated with the extract According to the experiment, the greatest effect is seen in the from northern moose antlers, in group 3 treated with the ginseng extract of moose antlers, it increases the growth of endo-colonies tincture, these data were respectively: 8,41 ± 1,2 x 106; 16,55 ± 2 times as contrasted with the control group (firm, p <0.01). 4,7 x 106; 11,96 ± 2,4 x 106. "Epsorin" and ginseng increase the growth of endo-colonies in 1.7 and 1.8 times (respectively) as compared to the control group (firm, p <0,002 and p <0,001). Thus, it was found that administration of adaptogens before irradiation leads to a significant increase in the release of endogenous colonies in the experimental groups, suggesting the positive effect on the function of blood stem cells after radiation exposure. Increasing the number of CFUs they contribute to the rapid recovery of hematopoiesis. [2] Epsorin According to this study when administered after exposure the study medications increase the release of endo-colonies (Fig. 2). According to our data, the number of CFUs in the control group was 6 ± 0,5, in the group treated with "Epsorin" and moose antlers extract this data accounted to 10,6 ± 0,8 and 10,2 ± 1,0 respectively. In the group receiving ginseng tincture Fig. 2. The effect of adaptogens on the process of endogenous colony formation in mice endo-colonies number was 8,3 ± 0,6. when administered after irradiation at a dose of 5 Gy.

Epsorin Epsorin

Fig. 1. The effect of adaptogens on a process of endogenous colony formation in mice Fig. 3. Bone marrow cellularity in mice when administered adaptogens before irradiation when applied prior to a radiation dose of 5 Gy. at a dose of 5 Gy.

488 Ne w applications o f a d a p t o g e n s t o r e d u c e r a d i a t i o n s i d e e f f e c t s

As seen from the results the study medications increase (firm CONCLUSIONS p <0.05) bone marrow cellularity in mice when administered 1. Adaptogens (the extracts from reindeer and moose prior to irradiation. antlers, ginseng tincture) stimulate the functional activity of The most pronounced effect was obtained in the case of SCFUs, it is identified by the exogenous and endogenous colony an extract from moose antlers. Compared with the control forming method, they have a stimulating effect on the entire group of mice experienced bone marrow cellularity increased compartment of the early precursors of hematopoiesis (CFUs-5 approximately 4 times (firm p <0.05). "Epsorin" and ginseng CFUs-8 CFUs-11). increase this figure compared with the control 1.7 and 2.7 times 2. The study medications contribute to the restoration of respectively (firm p <0.05). cellularity of bone marrow and thymus in mice after exposure The second stage of the study the drugs were administered in to radiation while using these medications before and after the same mode, after irradiation of animals in a dose of 5 Gy. exposure to ionizing radiation. The comparative characteristics The experiment revealed that the studied drugs increase show that the most pronounced effect has the extract from (not firm p> 0.05) bone marrow cellularity. In the case of extract reindeer antlers. from northern moose antler compared to the control the bone Thus, our study reveals new possibilities for the use of these marrow cellularity increased 1.6 times. "Epsorin" and ginseng medications to reduce the side effects of radiation and can be increase the baseline in 1.6: and 1.3 times respectively. widely used for the selective protection of the hematopoietic system It is found that the most pronounced effects of these three cells in radiation therapy of tumors, and can be recommended medications are observed in case of administration of adaptogens for the recovery of hematopoiesis after exposure to ionizing before irradiation (firm p <0.05) rather than when administered radiation. after irradiation. The medications can be used as a means of prevention to The use of such medications increases thymic cellularity in reduce the pathological effects of radiation on the immune and both cases of adaptogens administration. "Epsorin" increases hematopoietic systems of the body, which is essential for the (not firm in both cases, p> 0.05) thymic cellularity compared regions with high radiation pollution which is undoubtedly with the control group. The extract of moose antlers increases highly important for our region. the number of thymocytes (firm p <0.05) when administered Our results help to expand the existing understanding of before and (firm p <0.01) after irradiation. The ginseng tincture the pharmacological properties of the studied adaptogens. To increases (firm p <0.02) thymic cellularity when administered the well-known antioxidant and immunomodulatory effects before and after irradiation. of “Epsorin” we can add radioprotective properties. It should be noted that the studied medications are produced from local DISCUSSION materials. It was determined that “Epsorin” has the most pronounced radioprotective effect in the case of immune and hematopoietic REFERENCES systems (increases the cellularity of bone marrow and thymus, 1. Tsybulko N.N. Radiation protection of the population of Belarus after the Chernobyl increases the number of hematopoietic progenitor cells in the accident. / Tsybulko N.N. // Radiation and risk. -2014. -Tom.23. – №2. – P. 112-122. bone marrow and spleen) compared with the moose antler 2. Alekseev S.N. Influence of adaptogens on the immune and hematopoietic systems and extract or the ginseng tincture. conditions of radionuclide cytostatic effects. . / Alekseev S.N. //- Abstract ... diss. cand. It is shown that “Epsorin” has a stimulating effect on the of med. sci.- Novosibirsk, 1996. –P. 25. functional activity of all compartments of early hematopoietic 3. Petrova P.G. Ecological and physiological aspects of human adaptation to northern progenitor (hematopoiesis of the bone marrow) [6] ensuring the conditions. / Petrova P.G. //- Yakutsk: Dani Almas, 2011. – P. 12-15. successful course of the initial stages of erytropoiesis, myelopoiesis 4. Savinov D.D., Petrova P.G. [et al.] // The habitat and human health in the North. – Nauka, and lymphopoiesis. The adaptogens stimulating effect on the Novosibirsk, 2005. –P. 288. functional activity of CFUs (CFUs-5, CFUs-8, CFUs-11) was 5. Verfaille C.M. // Blood. 1993. v 82. N 7. P. 2045-2053. revealed. 6. Vykhodtsev J.V. The effect of immunomodulator “Epsorin” on the state of immunological Thus, study medications increase bone marrow cellularity reactivity in patients with malignant tumors of the maxillofacial region in the posto- when administering them before and after irradiation. They perative period / Vykhodtsev J.V. // Vestnik of the North-Eastern Federal University. are most effective when administered before irradiation, which -2010. -№1. –P. 47-52. suggests that the use of these medications leads to improvement of regenerative processes in the hematopoietic system, making the critical radiosensitive hematopoietic system to become capable of ensuring a stable level of bone marrow cellularity for a certain ADDRESS FOR CORRESPONDENCE: period of time. Alekseeva S.N. These results suggest that the study medications have a positive Russia, Republic of Sakha (Yakutia), effect on the regeneration of the thymus, bone marrow after 677013, Yakutsk city, 27, Oyunsky street irradiation. [email protected]

489 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Th e sit u a ti o n w it h st a f f i n g in pe d i a tric ser v ices o f t h e rep u b l ic o f s a k h a (y a k u ti a )

Aprosimov L.A., Chichakhov D.A. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT Introduction: at present, the public health in the Republic of Sakha (Yakutia) (RS(Y)) is a powerful state structure with an extensive network of prevention and treatment facilities. Since medical service density is the most generalized criterion of the medical service level, its analysis represents special interest to any regional system of public health. Aim: to analyze the dynamics of availability of doctors of all fields, of pediatricians, including pediatric surgeons, pediatric endocrinologists, and pediatric oncologists in 1995-2013. Materials and methods: the analysis is done to reveal the dynamics of availability of doctors: of all fields, pediatricians, including pediatric surgeons, pediatric endocrinologists, and pediatric oncologists to the population of Yakutia in 1995-2013. A statistical and comparative analysis of the data has done. Results: as a whole, in the studied period, RS(Y) witnessed an increase in the availability of doctors of the pediatric profile to the child population. Both in the Russian Federation and in the RS(Y) in particular, the increased availability of pediatricians was mainly due to the reduction of the child population and, to a lesser degree, to an increase in the number of doctors. Conclusions: the survey revealed the increased availability of pediatricians in RS(Y) only in densely populated areas and the continuing lack of pediatric services in the areas with low population density.

Key words: human resources for health, provision with doctors, pediatric division.

Wiad Lek 2015, 68 (4), 490-492

INTRODUCTION to any regional system of public health. It should be noted that At present, the public health in the Republic of Sakha (Yakutia) the most complex processes are currently taking place at the (RS(Y)) is a powerful state structure with an extensive network regional health level. The tense staffing situation in medical of prevention and treatment facilities. It has made a significant organizations at the regional level occurs because it is the regions contribution to the stabilized demographic indicators for the that face most problems of a systemic nature. region. The health care system of the RS(Y) has rearranged its Objective: to analyze the dynamics of availability of doctors of resources, thus enabling its further enhancement. However, at the all fields, of pediatricians, including pediatric surgeons, pediatric same time, the population health indicators, the slow population endocrinologists, and pediatric oncologists per 10,000 people growth, and the lack of the health system effectiveness require of the total population, the child population (0-17 years old) investments into resources, especially to human ones. in 1995-2013. In their study of the medical service density in the areas populated by indigenous peoples in the Republic Sakha (Yakutia), MATERIALS AND METHODS T. E. Uvarova and T. E. Burtseva [5] noted the continuing decline A statistical analysis of the availability of doctors of all in the core resources (number of health facilities, number of beds, fields, of pediatricians, including pediatric surgeons, pediatric staff, etc.). This reduction happened in the sparsely populated endocrinologists, and pediatric oncologists per 10,000 people areas of the RS(Y) with “excessive”, compared to the average of the total population, the child population (0-17 years old) federal, availability indicators throughout the republic. This in 1995-2013is done basing on the data from Rosstat (Russian situation demonstrates the inadequacy of the staffing standards, Statistics Agency) and Yakut Republic’sMedical Information- based on the number of residents, which is a violation of the Analytical Center (YMIAC). A comparative analysis of the data constitutional right of citizens of the Russian Federation (RF) to is done with those from the Far Eastern Federal District (FEFD) the access to health care. This is true not only for the Far North, and the Russian Federation. To conduct the survey, given the but also for other sparsely populated areas in Siberia [3,4], for medical and economic zoning of the RS(Y) [1], we divided central regions of Russia [2], and others. the regions of the republic into 6 groups: central, across the Since medical service density is the most generalized criterion river from Yakutsk, industrial, Vilyuisk (Western), Northern, of the medical service level, its analysis represents special interest and Arctic. The calculations were performed using software

490 Th e s i t u a t i o n w i t h s t a f f i n g in p e d i a t r i c s e r v i c e s o f t h e r e p u b l i c o f s a k h a (y a k u t i a ) packages Statistica 6 and Excel. For the analysis, we identified the doctors. By the end of 2013, the number of pediatriciansin the factors most significantly associated with the studied parameters RS(Y) per 10,000 of the child population was significantly lower –the availability of doctors of all fields and pediatriciansto the (p = 0.023) than the average for the Russian Federation – 24.3 population of RS(Y). doctors per 10,000 children (RF in 2012 – 31.1). In general, in the period 1995-2013, the RS(Y) witnessed an RESULTS AND DISCUSSION increase of the availability of pediatricians to the child population FEFD and RS(Y) enjoy significantly better availability of from 15.5 to 24.3 per 10,000 of the child population, or by doctors of all fields than the Russian average: the availability 56.7%. of doctors of all fields in Yakutia before 2001 was significantly In 2013, health institutions of the RS(Y) employed 427 (p=0.045) lower than in the Russian Federation; afterwards, pediatricians and neonatologists. However, there are significant there has been a steady growth –in 2011, the number of doctors differences in the groups of regions in terms of the availability in the Republic of Sakha (Yakutia) was significantly (p = 0.012) of pediatricians and neonatologists (Fig. 3). more than in Russia, but less than in the FEFD. Over the past 20 years, in the Russian Federation, the increase in the number of doctors of all fields was 15.1%, in FEFD – 18.8%, in the Republic of Sakha (Yakutia) – 34.3% (Fig. 1). The structure of health worker positions to ensure the availability of skilled medical service differs from the Russian average. The doctor-to-nurse ratio is 1:2.7, which is slightly lower than the optimal value – 1:3. The current ratio in the republic is due to the need to provide primary medical care to the population in remote localities, decreasing funding of ambulance aviation, as well as the introduction of new technologies in medicine. The number of active pediatricians, including pediatric surgeons, pediatric endocrinologists, and pediatric oncologists in the Republic of Sakha (Yakutia) has always been lower than in the whole of Russia, although there was an increase in the availability of pediatricians in 1999-2008. Over the past 20 years, the availability of pediatricians to the child population of the Russian Federation has undergone a rapid growth: in Russia, the number of pediatricians has gone up by 1.3 times;in the RS(Y) for the same period – by 1.6 times (Fig. 2). The increased availability of pediatricians, both in the Russian Federation Fig. 2. Availability of pediatricians, including pediatric surgeons, pediatric endocri- and in the RS(Y), was mainly due to the reduction of the child nologists, and pediatric oncologists per 10,000 of the population (according population and, to a lesser extent, to the increased number of to Rosstat, in 2013 - according YMIAC).

Fig. 1. Availability of doctors of all fields per 10,000 of the population (according Fig. 3. Availability of pediatricians and neonatologists in the groups of regions per to Rosstat, 2013 - according to YMIAC). 10,000 of the population (according YMIAC).

491 Aprosimov L.A., Chichakhov D.A.

Almost in all the groups of regions the availability of (the availability totaled to 54.6 per 10,000 of the population, pediatricians and neonatologists to the populations did not with 4 working pediatricians). exceeded the republic’s average value of the index and only in Over the surveyed 20 years, the lowest availability of pediatricians two of them it was higher for several years – in the industrial and and neonatologists was reported in 1997 in Amga region – 5.1 Arctic groups. The indicator was most unstable in the Northern per 10,000 of the population (2 working pediatricians). and Arctic regions. In 2009, the Arctic group of regions had the highest availability of pediatricians, whereas in 1997 – the lowest CONCLUSION (30.3 and 13.0 per 10,000 of the child population, respectively). The The shortage of pediatricians in the rural and remote Northern Northern group also demonstrated fluctuations of the indicator: settlements imposes a unique imprint on the organization the maximum availability was observed in 2009, the minimum – in of pediatric services to the child population. In general, it is 1997 (20.0 and 10.6 per 10,000 of the population, respectively). organized primarily on residence-based consulting principle, When assessing the availability of pediatricians and neonatologists but differs from the urban arrangement, since patients have in these regions, one should take into account the fact that the immediate access to medical services at rural health posts by availability indictor, calculated per 10,000 of the population, doctors of non-pediatric profile, who are able to provide first is uninformative because these groups encompass 14 regions aid, prehospital and emergency aid. Pediatric services, as well as with the lowest population density. Thus, in the Arctic group, specialized medical care can be obtained, in most cases, only in which includes five regions: Anabarsky, Bulunsky, Ust-Yansky, regional centers. The survey revealed the increased availability Allaikhovsky,and Nizhnekolymsky, in 2009, there worked 21 of pediatricians in RS(Y) only in densely populated areas and doctors, and in 1997 – 15 doctors. In the Northern group of the continuing lack of pediatric services in the areas with low 9regions, in 2009, there worked 30 doctors, in 1997 – 17, while population density. some areas did not have pediatricians at all. During the studied 20 years, the availability of pediatricians REFERENCES and neonatologists in the republic has increased by 11.0% (from 1. Chichakhov D.A. Detskoje naselenie Respubliki Sakha (Yakutia): problem sokrachenija 15.4 in 1995 to 17.1 in 2013). The highest availability was observed predotvratimych poter / Chichakhov D.A., Aprosimov L.A. // [pod red. d.m.n. Timofeeva in 2005 (23.0 per 10,000 of the population, mostly due to staffing L.F.]. Yakutsk: izdatelsko-poligraficheskiy kompleks SVFU, 2011,150 p. in the Arctic group of regions with the indicator at 24.0). 2. Golikov V.E. Osobennosti anesteziologicheskoj sluzhby v territorijach s nizkoj plotnostju. The highest growth rates of the availability of pediatricians / Golikov V.E., Slepyh N.I. // Problemy socialnoj gygieny, zdravoochranenija I istorii and neonatologistsin 1995-2013was observed in the group of mediciny, 2010, №3, P. 21-26. regions across the river from Yakutsk: the increase made 57.8% 3. Kagirova G.V. Osobennosti okazanija medicinskoj pomoschi detjam v regione c nizkoj (from 8.3 to 13.1 per 10,000 of the population, respectively). plotnostju naselenija / Kagirova G.V., Repina L.V., Haustova I.V. [et al.] // Sbornik materialov The lowest rates observed in the Arctic group of regions – an IX Kongressa pediatrovRossii “Aktualniye problemi pediatrii”. M: 2007, 265 p. increase of 1.4% (from 13.9 to 14.1 per 10,000 of the population, 4. Solomatin T.V. Organizatcija vyezdnoj medicinskoj pomochy naseleniju severnych ra- respectively). jonov Sibiry. / Solomatin T.V. // Zdravoochranenie Rossiyskoy Federacii, 2007, № 2, P. In the period 1995-2013, the highest availability of pediatricians 19-21. and neonatologists was seen in 2005 in Ust-Maya region (with 5. Uvarova T.E. Dynamika osnovnych pokazatelej medicinskoj obespechennosti naselenija 9 working pediatricians, the availability amounted to 36.4 per v rajonach prozhivanija korennych malochislennych narodov Severa. / Uvarova T.E., 10,000 of the population); and in 2009, in Allaikhovsk region Burtseva T.E. // Jakutskij medicinkij zhurnal, 2011, №1, P. 73-74.

ADDRESS FOR CORRESPONDENCE: Aprosimov L.A. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street Ph. 8(4112) 36-34-89, [email protected].

492 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Micr o b i o ce n o sis in i n f l a m m a t o r y pr o cesses o f m a rgi n a l g u m a m o n g c h i l d re n

Akhremenko Y.A., Cheremkina A.S., Tarasova L.A., Ushnitsky I.D. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT Introduction: the development of gingivitis among children remains actual problem in modern dentistry due to high prevalence, disorders of dental-alveolar functions and development of parodontium diseases at the older age. The microorganisms occupying dental chamfer play the leading role in parodontium tissues damage. Aim: research of microbial spectrum of dental chamfer and assessment of etiology significances of the revealed microorganisms in gingivitis among children of school age. Materials and methods: bacteriological research of dental chamfer in 30 children of secondary school age with gingivitis of slight and severe level. Inoculations have been done on the chocolate agar incubated in air-locked containers with gas generators for anaerobic atmosphere «GENbag Anaer» and inoculations on bloody gemagar – with gas generators for microaerophiles «GENbag Microaer» (bioMerieux) within 24-48 hours. Infections were precipitated out on the Saburo medium. Identification of discharged cultures was carried out on the microbialogic evaluator «Vitek II Compact» (bioMerieux). Results: microflora of dental chamfer in the examined children has been presented by three groups of microorganisms: gram-positive cocci (63,3 %), gram- negative nonfermentative bacteriums (63,3 %) and yeast Candida fungus (30 %). Among gram-postitive cocci representatives of normal microflora of oral cavity Streptococcus oralis (26,6 %) were dominated. Neisseria (N. sicca, cinerea et animaloris) were dominated most often in the group of gram-negative nonfermentative bacteriums (23,3 % of children), yeast Candida fungus have been presented by two kinds – C. dubliensis (at 20 % of children) and C. аlbicans (at 10 %). The mean content of all discharged microorganisms has compounded 5,7 lg КОЕ that supposes their etiology role in development of marginal gum inflammation. Conclusions: received results showed us some mechanisms of development of inflammatory diseases of parodontium tissues which will allow us to develop new approaches of treatment and gingivitis prevention among children of school age.

Key words: flora of the gingival groove, gingivitis in children, inflammation of marginal gum, microaerophilic streptococci, Neisseria, yeast-like fungi

Wiad Lek 2015, 68 (3), 493-495

INTRODUCTION optimisation of etiotropic and pathogenetic gingivitis therapy The development of gingivitis among children remains actual and prevention. problem in modern dentistry due to high prevalence, disorders Aim: research of microbial spectrum of dental chamfer and of dental-alveolar functions and development of parodontium assessment of etiology significances of the revealed microorganisms diseases at the older age. in gingivitis among children of school age. As show the researches made in the north, the most often pathology of parodontium tissues among children of 7-14 years MATERIALS AND METHODS old is gingivitis of chronic catarrhal type. The prevalence of this Bacteriological research of dental chamfer in 30 children of pathology happens with the age. This index is at the level of 40 secondary school age with gingivitis of slight and severe level. % in group of children of 7 years old, in group of 14-year-old The material from the inflammatory locus has been received children it compounds 85% [1]. by means of a tampon which was placed in transport medium Nowadays a series of etiology factors of development of tissues with coal. Primary material inoculation was made on anaerobic parodontium inflammation is known. Unsatisfactory hygiene blood agar, “chocolate” agar and Saburo medium. Incubation of of oral cavity, periodontium trauma, insufficient functional inoculation was carried out at 370С within 24-48 hours. Cups load of dental-alveolar systems, condtition of immune system with anaerobic gemagar was incubated in air-locked containers of the macroorganism [2, 3]. Also the resident microorganisms for atmosphere with gas generators for anaerobic atmosphere of oral cavity occupying dental chamfer, forming tooth plaques «GENbag Anaer» (bioMerieux). Inoculation on «a chocolate» agar plays the important role. were also placed in hermetic containers, but with gas generators Microflora analyses of dental chamfer in gingivitis among for microaerophils «GENbag Microaer» (bioMerieux). children in the north has not been made, however it’s extremely The quantity of microorganisms in the inoculation material was actual for understanding of mechanisms of development of calculated by Melnikova-Tsareva’s method: a tampon inoculated inflammatory processes in parodontium tissues in children, material on the 1st sector of Petri’s dish with a nutrient medium.

493 Akhremenko Y.A., et al.

Table I. The Calculation table for detection of quantity of bacteria in the examined materia. Number of colonies by sectors Quantity, КОЕ Sector 1 Sector 2 Sector 3 1-6 No growth No growth <1000 (до 103) 8-20 No growth No growth 1000 (103) 21-30 No growth No growth 5000 (103-4) 31-60 No growth No growth 10.000 (104) 70-80 No growth No growth 50.000 (104-5) 100-150 5-10 No growth 100.000 (105) A lot 20-30 No growth 500.000 (105-6) A lot 40-60 No growth 1.000.000 (106) A lot 100-140 10-20 5.000.000 (106-7) A lot A lot 30-40 50.000.000 (107) A lot A lot 60-80 100.000.000 (108) A lot A lot 80-140 1.000.000.000 (109)

After that a bacteriological loop of 3 mm diameter made 4 shaped DISCUSSION inoculations from the1st sector to the 2nd, similarly from the On the basis of the conducted research it is possible to 2nd sector in the 3rd, burning a loop after reinoculation of each assume etiological importance of three groups of discharged sector. Quantity of bacteria in material was defined in table 1. microorganisms, it’s yeast-like Candida fungus, Streptococcus Identification of discharged cultures was carried out by oralis and neisseria. morphological, tinctorial and biochemical properties. Unguentums, Leading position in frequency of seeding belongs to yeast- coloured by Gram’s method were taken from evolved colonies. like Candida fungus which were found in 9 (30 %) examined Pure growth was accumulated in the conforming medium in children. The yielded sort includes more than 100 kinds, the suitable atmosphere, then identified on the microbialogic evaluator basic pathogen is C. albicans. However quite often there are «Vitek II Compact» with application of identification cards also other kinds. «Vitek 2 GN», «Vitek 2 GP», «Vitek NH», «Vitek 2 YST», «Vitek As a rule, the candidiasis develops as a typical autoinfection and 2 ANC» (bioMerieux). is concomitant disease or complication of any pathology leading to immunodeficiency state [4]. Vitamin deficiency, endocrinopathy RESULTS and irrational antibacterial therapy of intercurrent diseases, Microflora of dental chamfer in the examined children has and also application of antibacterial additives in preventive been presented by three groups of microorganisms: gram-positive tooth pastes promote the raised Candida vegetation on oral cocci (63,3 %), gram-negative nonfermentative bacteriums (63,3%) cavity mucosa. and yeast Candida infections (30 %). The second place in frequency occupy gram-positive Among gram-postitive cocci representatives of normal microaerophil α- haemolytic group of streptococci «mitis» (by microflora of oral cavity Streptococcus oralis were dominated classification of Facklam R., 2002) which have been evolved in 8(26,6 %) patients, also Kocuria rosea et kristinae were met among 8 (26,6 %) children. in 4 patients (13,3 %) and Granulicatella adiacens et elegans Streptococcus oralis is the resident of oral cavity of the in 4 examined children(13,3 %). In other cases other kinds of human, however has property of synthesis of extracellular streptococci, rotia and leuconostoc have been revealed. polysaccharides participating in formation of tooth plaques, Neisseria (N. sicca, cinerea et animaloris) were dominated possesses neuraminidase and IgA1 proteases activity. It is the most often in the group of gram-negative nonfermentative most dangerous pathogen from the group of green streptococci bacteriums (23,3 % of children), the same frequency Aeromonas as it is capable to invoke endocarditis and septicemia among salmonicida was met. In other cases there were bacteria of immunecompromise patients [5]. Sphingomonas, Oligella and Pasterella. The third group of microorganisms, were neisseria which were Yeast Candida fungus have been presented by two kinds – found in 7 (23,3 %) children. All neisseria – gram-negative aerobic C. dubliensis in 6 (20%) et C. аlbicans in 3 children (10%). cocci. The sort is presented by 22 species of microorganisms, Monocultures of gram-positive and gram-negative 2 of which pathogenic, other refer to conditional-pathogenic microorganisms have been received in 9 (30 %) children. In and saprophytic microorganisms. The kinds identified by us other cases bacterial and bacterial-fungic associations took were neisseria, N. sicca, N. cinerea and N. animaloris, they place. were normal inhabitants of nasopharynx of the human that can The microflora spectrum of dental chamfer in the examined cause quinsy, otitis, kerato-conjunctivitis, septicemia and even children is presented in fig. 1. meningitis. They differ from each other by enzymatic activity.

494 Microbiocenosis in inflammatory p r o c e s s e s o f m a r g i n a l g u m a m o n g c h i l d r e n

Fig.1. A microflora spectrum of dental fillet in inflammation of marginal gum among children

From the point of view of inflammation development of gum Mean concentration of all discharged microorganisms tissues the most dangerous is presence N. sicca which possesses compounds 5,7 lg КОЕ that may assume their etiologic role in ability to formation of acids from sugar series, in particular inflammation development in marginal gum tissues. sucrose, and also possesses proteoclastic activity [6]. The received results dilate our representations about mechanisms The mean content of all discharged microorganisms has of development of inflammatory parodontium diseases which will compounded 5,7 lg КОЕ that may assume their etiological role allow developing new approaches to treatment and prevention in development of inflammation of marginal gum. of gingivitis among children of school age. Our research of dental chamfer microflora among children of secondary school age in chronic catarrhal gingivitis of slight REFERENCES and severe level allows assuming that tissue inflammation of 1. Ushnitsky I.D., Zenovsky V.P, Vilova T.V. Dental diseases and their prevention among marginal gum begins because of unsatisfactory hygiene of the inhabitants of the North // Moscow: Science, 2008. 172 p. oral cavity, as promoting factors are traumas of periodontium 2. Кukushkina E.A. Influence of immune therapy on indexes of immunodefence and tissues, intercurrent diseases leading to immunodeficiency state nonspecific resistance of patients with parodontium: thesis abstract ..candidate of and also irrational antibacterial therapy. These factors promote Medical sciences. // Chita, 2004. 19 p. the raised formation of dental patch, vegetation of yeast-like 3. К�������������������������������������������������������������������������������������ukharenko Y.V. Pathogenetic substantiation of pharmacological correction of microcir- fungus and oral streptococci in dental chamfer. Production of culatory disorders and peroxide status in chronic gingivitis: thesis abstract ..candidate exopolysaccharides by oral cavity streptococci initiates formation of Medical sciences. // Chita, 2005. 22 p. of tooth plaques, process progressing is promoted by the mediated 4. Babichev S.А. Chapter 70. The Pathogenic fungi. In book: Korotyaev A.I., Babichev S.A. adhesion of gram-negative cocci and other concomitant microflora Medical microbiology, immunology, virology // St.-Petersburg: Special lit, 2008. P. of oral cavity and nasopharynx. 608-631. All microorganisms are representatives of aerobic microflora 5. Ryapis L.A., Briko N.I., Eshchina A.S., Dmitriev N.F. Streptococci: general characteristic and of oral cavity. Strict anaerobes have not been revealed. It means methods of laboratory diagnostics // Moscow: Medical news agency, 2009. 196 p. that inflammatory process occurs in surface layers of gum tissues 6. marusina N.E., Lapshin G. N, Naumov A.M., Shulaeva M. L. Research of bronchial lavage and more often defines its intensity as slight and middle severity in bacteriological diagnostics of nonspecific diseases of lungs in children. In book: level. The anaerobic microflora meets in inflammatory-destructive conference materials «Modern problems of epidemiology, diagnostics and treatment processes of parodontium tissues which basically more often of infectious and allergic diseases». // Kazan; 2000; P. 32-33. occurs among adults.

CONCLUSIONS ADDRESS FOR CORRESPONDENCE: Three groups of microorganisms in gingivitis of slight and Akhremenko Y. A. severe level are most often found in children of school age in Russia, Republic of Sakha (Yakutia), dental chamfer: gram-postive microaerophil cocci – 63,3%, 677013, Yakutsk city, 27, Oyunsky street gram-negative non-fermenting aerobic bacteria also – 63,3% Ph. +7 924 1753177 and yeast-like Candida fungus – 30%. [email protected]

495 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Th e a n a l y sis o f m a j o r ris k f a ct o rs o f c a r d i o v a sc u l a r d ise a ses a m o n g i n h a b it a n ts o f t h e n o rt h regi o n

Borisova N.V., Markova S.V., Antipina U.D., Sivtseva T.P., Savvina I.L. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT Last years the problem of organism’s adaptation to severe climate-environmental conditions of the Far North has been intensively developed. The Republic of Sakha (Yakutia) is the most northern republic of the Russian Federation. People have created a unique way of life, language, original culture on this cold part of the earth and have carried centuries later. This unique experience has been saved up throughout many centuries and generated in natural environment of habitation and passed from generation to generation. Last years the changes of living conditions of indigenous population, urbanization and globalisation, deterioration of ecological conditions exhausted reserve possibilities of organism. Among the indigenous population health change has menacing character, especially among the children’s population. The analysis of major risk factors of the development of cardiovascular diseases among the indigenous population of the north has been carried out in this research.

Key words: the North, health, ecology, cardiovascular diseases, risk factors.

Wiad Lek 2015, 68 (4), 496-501

INTRODUCTION Diseases of blood circulation, respiratory and digestive The population of the Republic of Sakha (Yakutia) is affected systems, being a principal cause of diseases, physical inability by the influence of some unfavorable factors as natural (climatic and death rate of the population occupy the leading place in heliogeophysical and geochemical conditions) and anthropogenic chronic non-infectious diseases. Deterioration of ecological character (ecological problems) [2, 4]. There is the increase of conditions, changes of lifestyle of people cause the prevalence ecologically caused diseases leading to pathology of the major of risk factors of chronic non-infectious diseases [6]. functional systems, oppression of immunobiological reactance and other pathologies. Reserves of compensatory-adaptive possibilities MATERIALS AND METHODS of the human body in the conditions of anthropobiosphere have Data of scientific-practical expedition of NEFU Medical started to drop and demonstrated considerable increase of indexes institute to Nurba region in five settlements: Маlykai, Huty, of the general diseases, disability and death rates, reduction of mean Maldzhagar, Egolzha and Chukar. lifetime. Many health problems have deep social and economic Medical examination of population was made by adult roots, including regional aspects of living conditions, change of population’s appealability. The analysis of the following data traditional way of life and food habits of indigenous peoples of has been carried out: presence of risk factors of ischemic heart the Republic predetermining significant strain of population- disease, arterial hypertension, age, sex, hereditary predisposition, demographic processes among ethnic groups, prompt increase obesity, smoking, hyperlipidemia, hyperglycemia; anthropometrical of sharp ecological and social problems [1, 3, 5]. The health methods of research (weight, height, waist circumference), arterial state of north population with extreme climatic factors and pressure, frequency of heart rate. worsening ecological conditions has taken over menacing Bodymass index (BMI) was counted by formula body mass (kg) character, especially among children, women and indigenous / height (m2). Optimum values were BMI in interval > 18 <25 kg/m2. population. The deterioration of food quality here has played Overweight was > 25 <30 kg/m2. Obesity was > 30 kg/m2 a significant role. Meat, milk, eggs, sugar and other products (WHO, 1999). has contracted two and more times per head over the last ten A man smoking 1 cigarette a day was considered regular years in many regions of the Republic. smoker. Non-smoker was of smoking stop not less than 12 The influence of risk factors on population’s health is displayed in months (WHO, 1978). processes of human’s adaptation, changes of immune, biochemical, The analysis of lipid spectrum, blood glucose was made in physiological status and concrete nosological disease forms of the NEFU clinic by the doctor according to clinical recommendations, population, demographic processes, physical development [1]. 2013.

496 Th e a n a l y s i s o f m a j o r r i s k f a c t o r s o f cardiovascular d i s e a s e s a m o n g inhabitants o f t h e n o r t h r e g i o n

RESULTS AND DISCUSSION females of them (76,1%) and 28 males (23,9%) were registered. Non-modified risk factor of cardiovascular diseases is the Obesity of the 1st degree –78 people (66,7 %), 2 degree – 27 female age older 65 years which was in 39 patients (10,3%) people (23,1%), 3 degree – 12 people (10,3%). Patients with among the examined population. Among them 19 (48,7 %) abdominal obesity had essential hypertension – 23 patients (19,7 humans had essential hypertension (EH), ischemic heart disease %), ischemic heart disease – 3 patients (2,6%), hypertension and (IHD) – 8 (20,5%), EH and IHD were revealed in 12 (30,1%). ischemic heart disease were diagnosed in 60 patients (51,3%) Male’s risk factor was the age older 55 years which was found with obesity (tab. II). in 44 (11,7 %) patients. Among them EH was revealed in 21 Such risk factor as smoking, has been revealed in 73 patients humans (47,7%), 20 (45,5%) had EH and IHD. that has compounded 19,4% from total examined, 39 males Non-modified risk factors of cardiovascular diseases were (53,4%) and 34 females (46,6%). Among smoking patients, 11 referred to the males which was 28,6% among the examined people suffered from hypertension – (15,1%), ischemic heart population. Among males, 11 suffered from EH (10,2%), IHD disease – 4 people (5,8 %), 26 people (35,6 %) suffered from – 9 (8,3%), EH and IHD – 42 (38,9%). essential hypertension and ischemic heart disease. The data is Hereditary predisposition of arterial hypertension (АH) presented in tab. III. was among 67 examined (17,8 %), 51 patients of them were Detection of lipid profile and blood glucose has been made diagnosed with AH (76,1%); 14 patients (3,7%) had heredity in 193 people. Results of detection of triglycerides level are ischemic heart, 6 patients (42,9 %) were diagnosed with IHD. presented in tab. IV, V and VI. 3 examined patients (0,8 %) had diabetes heredity, 2 patients As you can see in the table 5, 119 females (67,6%) and males – 57 (66,7%) of them were diagnosed with diabetes. (32,4%) had normal level of triglycerides. The high level of triglycerides Obesity and smoking referred to modified risk factors of was observed in 14 females (82,4%), 3 males (17,6%). cardiovascular diseases. Potentially corrective risk factors were 66 patients (37,5 %) of 50-59 years old age category were hyperlipemia, dislipoproteinemia. marked with normal level from total triglycerides level. The The overweight body mass was among 131 patients (34,7%), same age category had 11 patients (64,7 %) with the high level males – 40 (30,5%), females – 91 (69,5%). The data is presented of also. in tab. I. Thus, the high level of triglycerides was revealed in 17 persons 117 persons had high percent of abdominal obesity that (8,8%), males – 3 (17,6%) and females – 14 (82,4%). 11 patients compounded 31 % from total number of the examined, 89 (64,7%) of 50-59 years old age category prevailed among patients

Table I. Quantity of patients with overweight body mass among the examined population in five settlements of Nurba region. Settlement Males Females Total Маlykai 21(33,9%) 41(66,1%) 62(47,3%) Huty 5(26,3%) 14(73,7%) 19(14,5%) Maldzhagar 3(27,3%) 8(72,7%) 11(8,4%) Egolzha 5(27,8%) 13(72,2%) 18(13,7%) Chukar 6(28,6%) 15(71,4%) 21(16,0%) Total 40(30,5%) 91(69,5%) 131(100%)

Таble II. Quantity of patients with obesity among the examined population in five settlements of Nurba region.

Settlement Sex 1 degree, n(%) 2 degree, n(%) 3 degree, n(%)

М 9(11,5%) 3(11,1%) 1(8,3%) Маlykai F 23(29,5%) 12(44,4%) 9(75%) М 2(2,6%) - - Huty F 7(9%) 2(7,4%) 1(8,3%) М 3(3,8%) 1(3,7%) - Maldzhagar F 4(5,1%) 6(22,2%) 1(8,3%) M 2(2,6%) - - Egolzha F 6(7,7%) 1(3,7%) - M 7(9%) - - Chukar F 15(19,2%) 2(7,4%) - Total 78(66,7%) 27(23,1%) 12(10,3%)

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Table III. Quantity of smoking patients among the examined population. Table IV. Indexes of triglycerides among the examined population. Settlement Quantity of smoking patients by sex structure Triglycerides Settlement Мales, n(%) Females, n(%) 0,68-1,88 mmоl/l ↑1,88 mmоl/l Маlykai 18(46,2%) 15(44,1%) Маlykai, n 99 8 Huty 3(7,7%) 4(11,8%) Huty, n 16 2 Maldzhagar 4(10,3%) 6(17,6%) Maldzhagar, n 22 2 Egolzha 6(15,4%) 1(2,9%) Egolzha, n 16 2 Chukar 8(20,5%) 8(23,5%) Chukar, n 23 3 Total 39(53,4%) 34(46,6%) Total, n 176 17

Таble V. Indexes of triglycerides by sex structure. Triglycerides Settlement 0,68-1,88 mmоl/l ↑1,88 mmоl/l М, n F, n М, n F, n Маlykai 37 62 1 7 Huty 4 12 - 2 Maldzhagar 6 16 - 2 Egolzha 3 13 1 1 Chukar 7 16 1 2 Total 57 119 3 14

Таble VI. Indexes of triglycerides in different age categories. Nurba region Age categories Triglycerides 20-29 years, n 30-39 years, n 40-49 years, n 50-59 years, n 60-69 years, n 70 years and older, n 0,68-1,88 mmоl/l 4 22 38 66 33 13 ↑1,88 mmоl/l - - 1 11 4 1

with high level of triglycerides. Among patients with high value Thus, laboratory data of 193 examined, HDL low level was of triglycerides, EH and IHD were diagnosed among 8 patients revealed in 6 patients (3,1%), males – 2 (66,7%) and females – 4 (47,1%) and only EH – 7 people (41,2%). (33,3%), more often at the age of 60-69 years (50%). Among Results of analyses of detection of general cholesterol level these patients were diagnosed: IHD – 2 patients, EH and IHD are presented in tab. VII, VIII and IX. – 4 patients. As you can see in the table 7, the majority of the examined Results of the analysis of low-density lipoproteins are presented patients had a high level of general cholesterol – 124 (64,2%), in tab. XIII, XIV and XV. normal level of cholesterol was in 69 patients (35,8%). As you can see in table 15, 39 (31,2%) patients with normal Normal level of cholesterol was noted in 48 females (69,6%) LDL values in age-group of 50-59 years old. Among the same and 21 males (30,4%). 84 females (67,7%) and 40 males (32,3%) category of patients there were more patients with high LDL had high level cholesterol. level – 38 (55,9%). Thus, laboratory data of 193 patients showed the high level of Thus, high LDL level was revealed in 68 patients (35,2%), males general cholesterol in 124 patients (64,2%), males – 40 (32,3%) – 20 (29,4%) and females – 48 (70,6%), more often patients with and females – 84 (67,7%), high index of cholesterol were met high LDL values were met in age-group of 50-59 years old – 38 more often in age-group of 50-59 years – 56 people (45,2%). (55,9%). Among these patients EH was diagnosed in 14 patients Among these patients with high level of general cholesterol were (20,6%), IHD – 9 (13,2%), EH and IHD- 22 patients (32,4%). diagnosed: 18 patients with EH (14,5%), IHD – 10 (8,1%), EH Results of sugar blood test are presented in tab. XVI, XVII, and IHD – 47 patients (37,9%). XVIII.

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Таble VII. Indexes of general cholesterol among the examined population. Table VIII. Indexes of the general cholesterol on a sex structure. Settlement General cholesterol General cholesterol Settlement 0-5,20 mmоl/l ↑5,20 mmоl/l 0-5,20 mmоl/l ↑5,20 mmоl/l М, n F, n М, n F, n Маlykai, n 51 56 Маlykai 17 34 22 34 Huty, n 5 13 Huty - 5 4 9 Maldzhagar, n 4 20 Maldzhagar 1 3 5 15 Egolzha, n 4 14 Egolzha 2 2 2 12 Chukar, n 5 21 Chukar 1 4 7 14 Total, n 69 124 Total 21 48 40 84

Table IX. Indexes of general cholesterol in different age categories. Nurba region Age categories

General cholesterol 20-29 years, n 30-39 years, n 40-49 years, n 50-59 years, n 60-69 years, n 70 years and older, n 0-5,20 mmоl/l 3 16 16 20 7 7 ↑5,20 mmоl/l - 7 24 56 30 7

Table X. HDL Indexes among the examined population. Таble XI. HDL Indexes by sex structure among the examined population. High-density lipoprotein High-density lipoprotein Settlement Settlement ↑0,77 mmоl/l 0,77-1,83 mmоl/l ↑0,77 mmоl/l 0,77-1,83 mmоl/l Маlykai, n 2 105 М, n F, n М, n F, n Huty, n - 18 Маlykai, n - 2 38 67 Maldzhagar, n - 24 Huty, n - - 4 14 Egolzha, n 4 14 Maldzhagar, n - - 6 18 Chukar, n - 26 Egolzha, n 2 2 2 12 Total, n 6 187 Chukar, n - - 28 18 Total, n 2 4 58 129

Таble XII. HDL Indexes in different age categories. Nurba region Age categories HDL 20-29 years, n 30-39 years, n 40-49 years, n 50-59 years, n 60-69 years, n 70 years and older, n ↑0,77 mmоl/l - - 1 2 3 - 0,77-1,83 mmоl/l 4 22 38 75 34 14

Table XIII. LDL Indexes among the examined population. Тable XIV. LDL Indexes in different age categories. Low-density lipoproteins Low-density lipoproteins Settlement Settlement 0-3,36 mmоl/l ↑3,36 mmоl/l 0-3,36 mmоl/l ↑3,36 mmоl/l Маlykai, n 84 23 М, n F, n М, n F, n Huty, n 10 8 Маlykai 28 56 7 16 Maldzhagar, n 9 15 Huty 1 9 3 5 Egolzha, n 1 17 Maldzhagar 2 7 4 11 Chukar, n 21 5 Egolzha 1 - 3 14 Total, n 125 68 Chukar 5 16 3 2 Total 37 88 20 48

499 Borisova N.V., et al.

Таble XV. LDL Indexes in different age categories. Nurba region Age categories LDL 20-29 years, n 30-39 years, n 40-49 years, n 50-59 years, n 60-69 years, n 70 years and older, n 0-3,36 mmоl/l 4 20 30 39 21 11 ↑3,36 mmоl/l - 2 9 38 16 3

Table XVI. Indexes of sugar in blood among the examined population. Table XVII. Indexes of sugar in blood by sex structure. Glucose Glucose Settlement 3,88-5,83 mmоl/l ↑5,83 mmоl/l Settlement 3,88-5,83 mmоl/l ↑5,83mmоl/l Маlykai, n 95 12 М, n F, n М, n F, n Huty, n 17 1 Маlykai 33 62 5 7 Maldzhagar, n 24 - Huty 4 13 - 1 Egolzha, n - 2 Maldzhagar 6 18 - - Chukar, n 23 3 Egolzha 4 12 - 2 Total, n 175 18 Chukar 5 18 2 1 Total 52 123 7 11

Table XVIII. Indexes of sugar in blood in different age categories. Nurba region Age categories Glucose 20-29 years, n 30-39 years, n 40-49 years, n 50-59 years, n 60-69 years, n 70 and older years, n 3,88-5,83 ммоl/l 4 21 37 68 32 13 ↑5,83ммоl/l - 1 2 10 4 1

As you can see in table 16, 175 examined had normal level heredity, obesity, hyperlipemia, smoking. 377 examined patients of glucose (90,7%), 18 (9,3%) patients had high level of glucose were detected on lipid spectrum and glucose of blood, where among the examined. 17 people (8,8%) had hypertriglyceridemia, 8 humans (47,1%) As you can see in table 17, 123 females (70,3%) had normal of from suffered from hypertension and ischemic heart disease, level of glucose, males – 52 (29,7%). 11 females (61,1%) and 7 7 (41,2%) – hypertension. 124 examined patients (64,2%) had males (38,9%) were with high sugar level. hypercholesterolemia, 18 (14,5%) – hypertension, 10 (8,1%) – As you can see in table 18 data, patients with normal glucose ischemic heart disease, 47 (37,9%) patients – hypertension and level in blood compounded the age-group of 50-59 years old – ischemic heart disease. 6 (3,1%) patients were diagnosed with 68 (38,9%). Patients with high level of sugar in blood prevailed low level of high density lipoproteins, 2 patients with diagnosis also in the same group – 10 (55,6%). «Ischemic heart disease», 4 patients – «Hypertension and ischemic Thus, high level of glucose in blood was revealed in 18 (9,3%) heart disease”. The high level of low density lipoproteins were patients, males – 7 (38,9%) and females -11 (61,1%), more among 68 (35,2%) persons, 14 (20,6%) – hypertension, 9 (13,2%) often patients with high sugar level were met in age-group of – ischemic heart disease, 22 (32,4%) – hypertension and ischemic 50-59 years old – 10 (55,6%). 4 (22,2%) examined patients had heart disease. The high level of glucose in blood was revealed diabetes among these patients. in 18 patients (9,3%), 4 (22,2%) of them were diagnosed with diabetes. CONCLUSION Thus, the secondary prevention of cardiovascular diseases is Results of medical examination of the population in based on the assessment of risk degree of cardiovascular diseases expeditionary conditions have revealed the basic modifying risk in the nearest future for the appropriate tactics and intensity factors of IHD, such as arterial hypertension, age factor, male sex, preventive and therapeutic interventions.

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REFERENCES 4. Borisova . N.V. Ecological substantiation of functional reserves among indigenous 1. Boitsov. S.A. Prevention of chronic non-infectious diseases / S.А. Boitsov, A.G.Chuchalin population of the Republic of Sakha (Yakutia) / N.V. Borisova, P.G. Petrova // Science // Recommendations. – Moscow, 2013. – P. 89-95. and education. – 2008. – №2 (50). – P. 55-61. 2. Ivanov. K.I. Modern approaches to preventive methods and treatment of arterial hyper- 5. Recommendations of experts of All-Russian science foundation of cardiologists // tension in Yakutia / K.I. Ivanov, T.M. Klimova // Methodical recommendations. – Yakutsk, Arterial hypertension. – 2001. – V 7, №1. 2002. – P. 12-13. 6. Savvinov. D.D. Habitant and health of the person in the north: Ecological-medical aspect 3. Kuznetsov. A.N. Classifications and symptoms of inner illnesses: manual /А .N. Kuznetsov / D.D. Savvinov, P.G. Petrova, F.A. Zakharova, others. – Novosibirsk: Science, 2005. – P. // N.Novgorod, 2013. – P. 65-73, 79-82. 111-130.

ADDRESS FOR CORRESPONDENCE: Borisova N.V. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street borinat@yandex. ru

501 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Epidemiological f e a t u res o f c h r o n ic v ir u s h ep a titis b a n d c in t h e rep u b l ic s a k h a (y a k u ti a )

Gerasimova V.V.1, Maksimova N.R.1, LevakovaI A.2, Zhebrun A.B.2, mukomolov S.L.2 1f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a 2f b s i r e s e a r c h i n s t i t u t e o f e p i d e m i o l o g y a n d m i c r o b i o l o g y o f p a s t e u r, s t .-p e t e r s b u r g

ABSTRACT High disease burden of chronic virus hepatitis B and C of population in the Republic Sakha (Yakutia) is subject to referring it to endemic territories due to these infections. For a 15-year-old period the disease has been registered at higher rates in the Russian Federation.

Key words: virus hepatitis, disease, morbidity, genotypes.

Wiad Lek 2015, 68 (4), 502-507

INTRODUCTION 96,3) and 20-29 years (13,7 and 52,6), and in age groups of 40- Virus hepatitis is a serious problem of public health services 49 years has made 13,4 and 52,9 and 50-59 years 13,2 and 33,3 all over the world, Russia and its regions. It is determined by its on 100 thousand population. The greatest levels of morbidity widespread prevalence among various groups of the population, HBV and HCV, ( the total number of patients identified and variety of clinical forms and outcomes. According to WHO data registered on December 31, 2013), are revealed in age groups [1, 2, 3], about 50 million people in the world annually have of 30-39 years (259,9 and 755,2 on 100 thousand accordingly), hepatitis virus B, and the hepatitis virus C infects almost 3 % 40-49 years (226,1 and 516,8) and 20-29 years (169,9 and 459,9 of the worldwide population. Almost all lethal outcomes are on 100 thousand population). caused by activators of haemocontact virus hepatitis at patients Issues on prevalence and factors of synchronization of with acute clinical courses, and also all cases of formation of virus hepatitis among indigenous and arrived population of liver chronic diseases, including cirrhosis and primary cancer the Republic Sakha (Yakutia) are considered by only individual [4, 5, 6]. researches [7,11,9,12] which testify to a higher level of prevalence The republic Sakha (Yakutia) is considered to be a region of virus hepatitis B and C in the republic territory and in further of high risk of the disease and a carrier of haemocontact virus erious additional epidemiological and laboratory researches hepatitis activator with constant excess of similar indicators of are required. the whole Russian Federation in 2-3 times [7, 8, 9]. Considering Aim of this research was study of prevalence rate of the results of 2013 in the Republic Sakha (Yakutia) HBV has haemocontact virus hepatitis B and C in Yakutia for the last made 27,8 on 100 thousand population, and HCV was 43,2 on 15 years. 100000, and their shares in structure of chronic virus hepatitis was distributed as follows: 38,9% HBV, 60,4 % HCV. Only at a MATERIALS AND METHODS small amount of patients (0,7%) it was not possible to establish In the work materials of official statistics of the Territorial etiology of chronic hepatic defeat [10]. Directorate of the Republic Rospotrebnadzor (Russia Directorate Thereupon it is necessary to notice that in some certain for Consumer Rights and Health Protection) are used. The territories there are high indicators of the disease burden, and disease burdens of chronic virus hepatitis B and C from 1999 also physical inability and death rate etiologically associated to 2014 have been analyzed. with activators of haemocontact virus hepatitis B and C. When diagnosing epidemiological, clinical, biochemical In the Russian Federation for the last 15 years the CVH has data, specific serologic markers of virus hepatitis and molecular- prevailed more than in 2,2 times: from 23,6 (1999) to 51,7 per biological methods of the research were taken into account. 100 thousand population (2014).The higher disease burden of chronic virus hepatitis is caused by triple increase of chronic RESULTS AND DISCUSSION hepatitis C: from 12,9 (1999) to 39,9 per 100 thousand population. The epidemic situation in the Republic Sakha (Yakutia) (2014), chronic hepatitis B has increased in 1,3 times: from concerning the diseases of chronic virus hepatitis B and C continues 8,9 to 11,3. Higher indicators of HBV and HCV in 2013 were to be threatening. In Yakutia the diseases of chronic virus hepatitis registered in age groups of 30-39 years (accordingly 21,6 and since their registration (1999) and till 2014 increased in 2,4

502 Ep i d e m i o l o g i c a l f e a t u r e s o f c h r o n i c v i r u s h e p a t i t i s b a n d c in t h e r e p u b l i c s a k h a (y a k u t i a ) times: from 28,3 (1999) to 67,4 (2014) , these parameters being Similar changes have occurred in dynamics of the diseases higher (51,7) as compared with the whole Russian Federation of chronic virus hepatitis B and chronic virus hepatitis C (fig. territories on 24 %. In RS (Y) there was high disease burdenof 2). From 1999 till 2006 the disease burden of chronic hepatitis B chronic hepatitis C in 3,5 times: from 11,3 (1999) to 39,1 (2014) was higher than the chronic hepatitis C, since 2007 till now more and chronic hepatitis B in 1,6 times from 15,2 (1999) to 28,0 patients for the first time registered with chronic hepatitis C have per 100 thousand population (2014). been noted than patients with chronic hepatitis B annually. Changes in etiologic structures of the chronic virus hepatitis In RS (Y) HBV has made 42 % in the general structure of throughout the analyzed period are reflected on fig. 1. Since CVH in 2014. HBV prevalence rate (28,0 per 100 thousand 1999 till 2004 the share of the chronic hepatitis in the structure population) is in 2,5 times higher than in the Russian Federation of all chronic virus hepatitis B reached a maximum rate (62 %) (11,3 per 100 thousand). Throughout all the analyzed 15-year-old in 2001. In 2005-2006 the ratio of HBV and HCV has become period (1999-2014) HBV in RS (Y) was higher than as a whole equal , and since 2007 in the structure of chronic virus hepatitis on the country, and in certain years (2003-2004) this parameter the chronic hepatitis C has been prevailing rated 61 % in 2013 differed in 4 times (fig. 3.). The following years the disease HBV and 58 % in 2014. It is necessary to note, also, decrease in a share gradually decreasing, has reached the indicator 28,0 per 100 of unexplained chronic hepatitis (UCH) in the structure of all thousand population that in 2,5 times higher as compared with chronic virus hepatitis from 11,3 % in 2000 to 0,3 % in 2014. the parameters in the Russian Federation, registered in 2014.

Fig. 1. Etiologic structure of chronic virus hepatitis in the Republic Sakha (Yakutia) in 1999-2014.

Fig. 2. Dynamic sof disease burdenofc hronic virus hepatitis Band C in the Republic Sakha (Yakutia) in 1999-2014.

503 Gerasimova V.V., et al.

Fig. 3. Dynamics of disease burden of chronic virus hepatitis B in the Republic Sakha (Yakutia) in 1999-2014.

Fig. 4. CVH sickness rateinse parateage groups of the populationin 2009-2013 (average indicators) and the total number of HBV (morbidity) in different age groups, registered December 31, 2013 in the RS(Y).

Fig. 5. Dynamics of disease burden of chronic virus hepatitis C in the Republic Sakha (Yakutia) in 1999-2014.

504 Ep i d e m i o l o g i c a l f e a t u r e s o f c h r o n i c v i r u s h e p a t i t i s b a n d c in t h e r e p u b l i c s a k h a (y a k u t i a )

Fig. 6. HCV sickness ratein separate age groups of the population in 2009-2013 (average indicators) and the total number of HCV (morbidity) in different age groups, registered December 31, 2013 in the RS(Y).

Fig. 7. Distribution of districts RS(Y) on groups according to indications.

505 Gerasimova V.V., et al.

HBV indicators for the first time the revealed in 2013 in CONCLUSION different territories of the republic had essential distinctions. Due to HBV and HCV high levels among the population of On the majority of the territories (30 %) the disease was from the Republic Sakha (Yakutia), it refers to endemic territories on the 20,0 to 50,0 per 100 thousand population. Indicators of the given infections. Throughout the 15-year-old period of the trial disease from 50,0 to 100,0 per 100 t.p. were registered at 20 % the registered sick rate remains higher than the indicators of the of the territories. At the same time in 7 areas of the republic Russian Federation. It concerns, first of all, to HBV which in RS (Y) CHB primary cases were not registered, and in two districts in 2014was in 2.5 times higher than in the Russian Federation. (Srednekolymskiy, Churapchinskiy) high indicators of the disease The analysis of HBV and HCV dynamics in RS (Y) from (103,3 and 150,8 per 100 thousand accordingly) were revealed. 1999 to 2014 reveals 2 periods: the first period (1999-2005) with HBV indicators in separate age groups of adult population for HBV leading position, it comprising 61 % of all CVH, and the the last five years (2009-2013) had no great distinctions (fig. 4) second period (2007-2014) with HCV leadership. and were within the limits of 40,0-49,0 per 100 thousand HBV and HCV disease burden in separate age groups of the population. HBV high indicator (2009-2013) was registered at population has distinctions. The maximum indicator of HBV patients of 30-39 years (51,7 per 100 thousand population) and is registered at patients of 30-39 years, and HCV at persons of 50-59 years (49,6 per 100 thousand population). HBV highest 60 years and senior. indicators among the republic population were registered at CVH morbidity in separate areas RS (Y) varies greatly from 20,0 patients of 50-59 years (1197,6 per 100 thousand) and 30-39 per 100 thousand to 4000,0 per 100 thousand population. years (1172,0 per 100 thousand population). Considering the epidemic importance of chronic virus hepatitis, In HCV general structure registered in RS (Y) in 2014, it is possible to offer the following recommendations: HCV was diagnosed at 58 %. The analysis of the long-term - To continue the all-round population screening , parti- data on HCV in RS (Y) and the Russian Federation (fig. 5) cularly in remote areas of the republic, on markers of shows that HCV prevalence rate in the republic was higher haemocontact virus hepatitis, first of all, of the population than in the Russian Federation during all period of the trial. from risk groups; HCV decrease tendency outlined in 2012 in the republic has - To use molecular-genetic methods widely that will al- allowed to reach39,1 per 100 thousand population for the first low: time in 2014, that parameter being the lowest morbidity rate a) to reveal primary circulation of certain genotypes of in the Russian Federation. viruses Band C in different social groups of the popu- HCV sick rate and morbidity in separate age groups of the lation and in various territories, population of the republic is presented on fig. 6. HCV indicators b) to find out causes of formation of sites of these infections consistently increase with the years, reaching the highest level in epidemically significant establishments, particularly, at patients of 60 years and senior. The age group of 30-39 years medical aid services, is to be noted, its average index are higher than at patients of - To create and to expand information base of the existing 40-49 and 50-59 years. The similar picture of HCV sick rate is register of patients with the diagnosed chronic virus he- revealed in separate age groups. patitis in separate territories of the republic. The analysis of CVH morbidity allows to estimate a level of distribution of this chronic pathology. These indicators reflect REFERENCES not only the registered level of CHV distribution, but also 1. onischenko, G.G. About actions directed on stabilization of disease burden of parenteral include a level of their diagnostics, quality of health survey virus hepatitis in the Russian Federation / G.G. Onischenko // Decision of chief sanitary and registration. officer of the Russian Federation. – 2013. – № 9. HBV morbidity indicators are higher than HCV in all age groups 2. Shahgildjan, I.V. Parenteral virus hepatitis (epidemiology, diagnostics, prevention) / of the population, except patients aged 60 years and senior. Their I.V. Shahgildjan, M.I. Mihajlov, G.G. Onischenko // -М, 2003. – P. 384. distinction is particularly seen in age groups of 15-19 years - in 3. Dore, G.J. Hepatitis C disease burden and strategies to manage the burden (Guest 4 times, (HBV - 162,7 per 100 thousand, HCV - 37,7) and 20-29 Editors Mark Thurse, Gregory Dore and John Ward / G.J. Dore, J. Ward, M. Thursz // J. years - in 2 times, (HBV - 701,1 per 100 thousand, HCV - 371,8 Viral Hepat. – 2014.-Vol. 21. – P. 1 4. per 100 thousand). The maximum indicators of HCV morbidity 4. onischenko G.G. Disease burden of infections able to manage by means of specific are registered in the senior age groups: 50-59 years - 1012,4 per prophylaxis in the Russian Federation and problems on its decrease and liquidation / 100 thousand and 1142,2 per 100 thousand population. The G.G.Onischenko // – 2003. – № 2. – PP. 16-28. highest indicators of UCH morbidity rates are registered at the 4. Lupinacci, RM. Hepatocellular carcinoma, from monitoring to treatment / RM. Lupinacci, population aged 50 years and senior - 54,2 %. F.Menegaux, C. Tresallet // Soins.- 2013.-Vol. 3.-P.5-7. On the map (fig. 7.) the territory of the Republic Sakha 5. Wallace, MC. The evolving epidemiology of hepatocellular carcinoma: a global perspec- (Yakutia) is divided into 5 groups depending on the morbidity tive / MC. Wallace, D. Preen, GP Jeffrey, LA. Adams // Expert Rev Gastroenterol Hepatol. indicators registered on it with their increase. CVH prevalence – 2015. – Vol.1.-P.1-15. in the republic territory has considerable distinctions from 174,8 6. AlekseevaM.N. Virus hepatitis in the Republic Sakha (Yakutia): abstr .diss. …cand. per 100 thousand in Eveno-Bytantajsky district to 3865,6 per med. sciences / Alekseeva Marfa Nikolaevna // – St.-Petersburg, 2002. – P. 37. 100 thousand population in Ust-Aldanskiy district. Particularly 7. Zotova A.V. Distribution of virus hepatitis B and C among reindeer breeders-nomads high indicators of the morbidity are registered in central areas in the Republic Sakha (Yakutia) / A.V.Zotova, O.E.Popova, K.K.Kjuregjan, [et al] // Virus of the republic, the northeast Arctic zone and the western areas hepatitis, its epidemiology, diagnostics, treatment and prevention. Materials of 7th adjoining on Krasnoyarsk region and the Irkutsk region. scientific-practical conference. –М – 2007.- PP. 28-29.

506 Ep i d e m i o l o g i c a l f e a t u r e s o f c h r o n i c v i r u s h e p a t i t i s b a n d c in t h e r e p u b l i c s a k h a (y a k u t i a )

8. Semenov S.I. Virus hepatitis disease burden in the Republic Sakha (Yakutia) / S.I. Semenov, 10. SavvinR.G.Monitoringand epidemiological importance of geographical distribution of R.G. Savvin, V.G. Krivoshapkin [et al.] // Materials of II East-Siberian gastroenterologicconf. parenteral virus hepatitis markers in conditions (in the territory) of the Republic Sakha “Clinical-epidemiological and ethnic-environmental problems of diseases of digestive (Yakutia):abstr. diss. … cand.med.sciences/ SavvinR. G. – Irkutsk, 2008. organs”, May, 15-17th, 2002 – Abakan, 2002. – P. 123-124. 11. Sleptsova S.S. Chronic virus hepatitis / S.S. Sleptsova, V.K. Semenova, S.G. Nikitin [et 9. About sanitary and epidemiologic state in the Republic Sakha (Yakutia) in 2013.: State al.] // Yakut Medical Journal.-2013.- № 1.-P.52-55. report. – Yakutsk: Directorate for Consumer Rights and Health Protection on the Republic Sakha (Yakutia), 2013. – P. 282.

ADDRESS FOR CORRESPONDENCE: Gerasimova V.V. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street [email protected]

507 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Ch a r a cteristic o f a ct u a l f o o d a t e l d er l y a n d se n i l e a ge d p o p u l a ti o n o f y a k u ti a

Neustroeva V.1,Kylbanova E.1, Simonova G.3, Tatarinova O.2, Scherbakova L.3 1f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k.a m m o s o v », y a k u t s k , r u s s i a 2r e p u b l i c a n h o s p i t a l №2 - c e n t e r o f e m e r g e n c y m e d i c a l a i d , y a k u t s k , r u s s i a 3r i o f t h e r a p y a n d p r e v e n t i v e medicine s b r a m s ,novosibirsk , r u s s i a

ABSTRACT Aim: to conduct estimation of actual food among in digenous and arrived population of Yakutia of elderly and senile ages. Materials and methods: in the work results of epidemiological research with analysis of actual food of the population of Yakutia at the age of 60 years and over are presented. On the basis of a list of candidates with use of random selection a representative sample of men and women of Yakutsk at the age of 60 years and more has been generated. In total 775 foreheads were surveyed, the middle age has made 75,7±9,4 years. For the analysis of actual food 575 people (244 men and 331 women) have been included. Among the surveyed there were 244 respondents of the in digenous population (the Yakuts) and 331 arrived respondents (the Russians, the Ukrainians, the Byelorussians, the Poles, the Germans, the Jews). The estimation of actual food is conducted by means of a frequency questionnaire. Results: high content of general fat, sated fat acids, polyunsaturated fat acids and refined sugar due to low consumption of general carbohydrates is revealed. At the analysis of food package of the indigenous population in comparison with the newly arrived some distinctions in consumption of following products are revealed: fresh, tinned and frozen vegetables, potatoes, eggs, horsemeat, venison, koumiss, fresh fruit and berries, oil and fats, bean, juice and drinks, sugar, chocolate and confectionery products. Conclusions: daily food intake of the indigenous population of elderly and senile ages is notable for lower daily caloric content, greater general fat, SFA, less consumption of refined sugar on the background of significantly lower content of general carbohydrates, starch and food proteins. In diets at the Yakuts there is considerably lower consumption of fresh and tinned vegetables, potatoes, eggs, fresh fruit and berries, bean, nuts, sugar, chocolate and confectionery products and higher consumption of meat products (horsemeat, venison), oil and fats.

Key words: food, macronutrients, elderly, senile age, epidemiology.

Wiad Lek 2015, 68 (4), 508-511

INTRODuCTION Thus, estimation of the nutrition of the indigenous population The republic Sakha (Yakutia) is a region with extreme living of Yakutia is of great significance for studying modern conditions conditions with long winter and short hot summer, long periods of adaptation to the North living conditions. of high atmospheric pressure, critically lower partial pressure of oxygen in the atmosphere, strengthened geomagnetic activity. MATERIALS AND METHODS Besides, light regime distinctions assume an extremely high On the basis of a list of candidates with use of random selection degree of adaptation of the indigenous population in conditions a representative sample of men and women of Yakutsk at the of high latitudes [1]. age of 60 years and over has been generated including long- Food factors can influence the development of human livers, all of them having been examined during the one-stage adaptable changes in conditions of high latitudes, being one of population researches of risk factors of chronic noncommunicable the bases of human health formation [2, 3]. In a traditional diet diseases. of any person living in the Far North, decline of energy content In total 775 foreheads were surveyed, the middle age has of carbohydrates and increase of fats are noted with a lower made 75,7±9,4 years.575 people have been included in a database degree of proteins. Besides, fat-soluble vitamin requirements are for the analysis of the actual food (244 men and 331 women). revealed rather than water-soluble ones, i.e. a so-called protein- Among the surveyed 244 respondents were the Yakuts (the lipid type of food is formed [4]. indigenous population) and 331 respondents –the Europeans: However, changes of lifestyle of the indigenous people of Yakutia (the Russians, the Ukrainians, the Byelorussians, the Poles, the have led to changes of their traditional protein-lipid character of Germans, the Jews (non-indigenous). food [5], it causing a higher incidence rate of atherosclerosis and Standard epidemiological methods of the research are used. other cardiovascular diseases (CVD) among them [6, 7, 8]. The research has been approved by local ethical committee at

508 Ch a r a c t e r i s t i c o f a c t u a l f o o d a t e l d e r l y a n d s e n i l e a g e d p o p u l a t i o n o f y a k u t i a the Yakutsk scientific centre of complex medical problems SB RAMS. All surveyed give informed consent for the participation in the research. The survey was conducted with use of a validated assay and questionnaires, including socially-demographic data. The estimation of the actual food is conducted by a frequency questionnaire. By means of a specially constructed mathematical model (E.G.Verevkin – founder, cand. biol. sciences) and schedules of chemical compound of food substances the information on the content in daily dietary intake of nutrients is obtained: general proteins, fats, including saturated (SFA), monononsaturated (MNSFA) and polynonsaturated fat acids (PNSFA), general, complex and simple carbohydrates, vitamins and macrocells, Fig. 1. The macronutrient structure of a daily dietary intake at men and women of Yakutsk and also daily ration of food energy value. Food value of the diet aged60 years and over, as regards ethnicity; *р<0,05; ** р<0,01. calculated with use of standard caloric factors in kcal on 1 gram: 4 kcal for proteins and carbohydrates, 7 kcal for alcohol and 9 kcal for fats. A food consumption share of basic substances in % from the general caloric content of the daily dietary intake has been defined. At the analysis of actual food the norms of physiological requirements for food substances and macronutrients have been used regulated by WHO recommendations (2002). The statistical processing and analysis of data were carried out by means of the software package SPSS (11,5 version). Results are presented in a form of average value and a standard error of average value (М±m). The authenticity of sample differences was revealed by a nonparametric method (test Mann-Whitney U) for two independent samples. The criterion of statistical authenticity was accepted by р<0,05.

RESULTS It is established that the food value of the dietary intake in the Yakut ethnic group has made 1747,1±38,2 kcal per day, in Fig. 2. The fat structure in food intake of men and women at the age of 60 years and the European group - 1883±41,5 kcal per day. over in Yakutsk as regards ethnicity; * р<0,05 Protein content in diet of the indigenous population was 59,6±1,2g per day, 64,0±1,4g per day at the arrivers (Figure 1). Bakeries, dishes from flour and groats, meat, dairy and fish products were basic protein sources in the diet of the surveyed. General fat intake in the natives’ food ration has made 79,5±2,0 g per day, 84,2±2,2/at the arrivers. The share of general fat consumption in the diet of the indigenous population has structure of carbohydrates the higher rates of protein bakeries, amounted to 40,8±0,4% and 39,6±0,4%of energy at the arrivers flour and cereal products, sugar, chocolate and confectionery (Figure 2). products were noted. The energy share of SFA was 15,8±0,2 % of energy value of When analyzing the food package, we found out that the the dietary intake at the Yakuts, 15,01±0,2% of energy at the indigenous and no indigenous population consume as the basic Europeans. The parity of MNSFA/PNSFA has made 0,5%. Meat products: fresh vegetables (76,7 and 120 g/d), potatoes (93,9 and and dairy products were found out the basic fatty sources in 104,5 g/d), tinned, frozen vegetables (73,0 and 123,8 g/d), eggs the food ration. (78,3 and 116,3 g/d), horsemeat (164,7 and 47,1 g/d), venison General carbohydrates were 194,3±4,7g at the natives, (180,0 and 20,0 g/d), koumiss at the Yakuts (5,5 g/d), fresh 217,4±4,9 g/d at the arrivers (Figure 1). Thus, the consumption fruit and berries (73,0 and 123,6 g/d), oil and fats (107,3 and of refined sugar among the Yakuts was 62,4±2,5 g/d (13,9% of 93,2 g/d), bean (68,0 and 127,2 g/d), juice and drinks (64,4 and energy) and at Europeans – 84,3±2,8 g/d (17,5% of energy). 133,2 g/d), sugar, chocolate and confectionery products (84,9 In the Yakut ethnic group dietary fibers in a food pattern and 112,9 g/d), accordingly. are revealed to be lower 14,6±5,2 g/d, as compared with the arrivers -18,5±5 g/d. The trial showed the surveyed rations of DISCUSSION the Yakut group contained cellulose (1,2 % of energy), starch According to our research it is established that energy value (28,5% of energy), at the arrived population cellulose being 1,5% of the dietary intake in the Yakut ethnic group is lower, than in of energy, starch 26,5% of energy. In food sources of all the the European one (р=0,013), possibly, due to the high content

509 Neustroeva V., et al. of carbohydrates. Venison is characterized by the higher protein content as well as It is established that the protein content in the indigenous the lower fat intake and at 5-10 times rich with vitamin C [10]. population’s dietary intake was significantly lower as compare, For the last years the actual food of the indigenous and no PNSFA with the arrivers (Figure 1). But at the same time, the indigenous able-bodied population of the Far North has been protein share essentially did not differ in the studied groups. The characterized asimbalanced concerning its basic nutrients, vitamins, ethnicity-related analysis of the food package has not revealed mineral substances, it having atherogenic orientation [5]. In the any differences. food pattern less protein products have been noted characterized The general fat intake in the dietary intake has revealed no by carbohydrate-lipid content due to the lower content of vitamins, distinctions in both groups. However, the share of the general fat minerals, food fibers and other vital nutrients [4, 5]. consumption in the indigenous population’s diets was considerably Food imbalance leads to the development of metabolic higher than at the arrivers, р=0,029 (Figure 2). dysaptation [11], causing the prevalence of risk factors of The share of SFA energy was higher in the Yakut ethnic noncommunicable and alimentary-dependent pathologies [7]. group than at the Europeans, р=0,000. Over the last 5 years in the republic the high incidence rate of At the same time, no authentic distinctions in the level of endocrine and immune systems has been marked, as well as MNSFA, PNSFA consumption are revealed (Figure 2). The metabolism at 22%, blood circulation system at 45,6 % [11]. parity PNSFA/SFA has made 0,5 and testified to higher content The general fat consumption in the population of elderly of animal fats in the dietary in take both at the natives and at and senile ages of Yakutia exceeded the same parameter of the arrivers as well. adult population of the USA in 1994-1996 [12]. At the same The general carbohydrate content at theYakutsis lower than at time, a share of fat from the general caloric content of the the Europeans (Figure 1). Thus, the refined sugar consumption ration at elderly population of Yakutia exceeded the general among the Yakutsis significantly lower in comparison with the fat consumption in population of adult population of the USA similar parameter of the Europeans (р=0,000). In the Yakut as well as in Russia [13]. ethnic group the food fiber content in the food pattern is lower in At the population of Yakutia at the age of 60 years maintenance comparison with the arrived population (р=0,000). The rations also is more senior did not differ from consumption level in surveyed in the Yakut group contained less cellulose (р=0,000), Russia, thus was more than adult population of the USA in however the starch content was higher in comparison with the 1999-2000 [14]. Europeans, р=0,000. The trials carried out among the Evenks of Siberia and Eskimos As for the carbohydrate food structure, we revealed the of the North America have shown rather high level of the basic higher rate of bakeries, flour goods and cereal products, sugar, metabolism at persons keeping traditional way of life and its chocolate and confectionery products which did not differ in lower rate among urban groups [15]. Previous researches have both studied groups. shown that in the Inuits the traditional products were rich in Comparing the food package of the indigenous population fats of animal origin with high content of ω-3 PNSFA while the with the arrivers we have revealed distinctions in the basic Inganasans had - ω-6 PNSFA. Thus, the Nganasans’ daily rations products consumption: fresh vegetables, potato, tinned, frozen had the carbohydrate character of food [16]. vegetables, eggs, horsemeat, venison, koumiss at Yakuts, fresh According to epidemiological researches concerning the fruit and berries, oil and fats, except for animal fats, bean, juice actual food conducted by the Institute of therapy SB RAMS in and drinks, sugar, chocolate and confectionery products. Thus, Chukotka, among inhabitants of the coastal areas consuming a the consumption of these products is significantly lower in the considerable quantity of fish and sea products, atherogenic changes Yakut ethnic group in comparison with the Europeans, with of blood and atherosclerosis had much smaller degree than in the exception of horsemeat, venison, oil and fats that in the Novosibirsk and Moscow. Also in the investigated population structure of carbohydrates that was proved in earlier researches death rate from myocardium heart attack approximated 10 times in Yakutia. lower as compared with others [13]. The research of all the food Characterizing ethnic features of the food ration of the natives pattern has shown that fat has been presented mainly by SFA, of the Far North of Yakutia, it is necessary to note the special type MNSFA, in less degree by PNSFA. The ratio PNSFA/SFA in the of food notable for specific assortment of products, but also a ration was very low and equaled 0,3. The shares MHSFA and certain ratio of the basic components in the daily ration [3]. The PNSFA were authentically lower in Chukchi population than in traditional ration of the indigenous population was based on population of Novosibirsk. In spite of the fact that in the group considerable amount of meat (horsemeat, venison, beef, fowl) of indigenous population there were lower rates of MNSFA and and dairy dishes with addition of fish which is usually consumed PNSFA as a part of fat acids of blood, various PNSF acids more in a raw state, as well as wild berries and plants for tastiness favorable for metabolism have been defined. It is confirmed improvement. Dairy products of the Yakuts were the traditional with the results of CVD prevalence rates among the Eskimos foodstuff satisfying nutrient requirements of an organism in the of Greenland in comparison with populations of the Eastern severe environmental conditions. Valuable qualities of koumiss Europe and the North America [15, 17]. are caused by its structure: proteins, lactose, enzymes, vitamins A, groups B, D, Е, C and mineral elements. Products of animal origin CONCLUSION were used by the indigenous population in significant amounts The daily food ration of the indigenous people at the age of [5]. High prevalence rate of such kind of food as horsemeat is 60 years and over differs from the nonindigenous people’s lower noted among the Yakut population due to its unique value [9]. daily caloric content by the greater share of general fat, SFA,

510 Ch a r a c t e r i s t i c o f a c t u a l f o o d a t e l d e r l y a n d s e n i l e a g e d p o p u l a t i o n o f y a k u t i a smaller consumption of refined sugar on the background of 8. Argunov, V.A. Age dynamics of atherosclerosis of aorta and coronary arteries at men much lower general carbohydrates, starch and food fibers. In the of Yakutsk and its evolution for 40 years / V.A.Argunov // Atherosclerosis. - 2010. - Т. 6, portion at the Yakuts there is considerably smaller consumption № 1. - P. 20-24. of fresh and tinned vegetables, potato, eggs, fresh fruit and 9. Hygienic safety and food value of Yakut horsemeat / A.A.Martynov, Z.A.Gabysheva, V.V. berries, bean, nuts, sugar, chocolate and confectionery products Uvarovsky [et al.] // the Yakut medical journal. - 2013. - № 1 (41). - P. 47-48. and bigger consumption of meat products (horsemeat, venison), 10. Meat efficiency and food value of venison of Yakutia / A.F.Abramov, M.P.Neustroyev, oil and fats. K.M.Stepanov [et al.]. - М, 2011. – P. 117. 11. Metabolic adaptation of the Yakuts (Sakha) / D.Snodgrass, V.R.Rove, L.A.Tarsky [etc.] REFERENCES //the Yakut medicaljournal. - 2011. - № 2 (34). - P. 11-14. 1. mechanisms of adaptation of a person in conditions of high latitudes / V.P.Kaznacheev, 12. Did fat intake in the United States really decline between 1989-1991 and 1994-1996? V.J.Kulikov, L.E.Panin, [et al].; edited by V.P.Kaznacheeva. - L: Medicine. - 1980. – P.199. / P. Chanmugam, J.F. Guthrie, S. Cecilio [et al.] //J. Am. Diet. Assoc. - 2003. - Vol.103, 2. Food asa basis of primary prevention of diseases in the north / edited by L.E.Panin. – №7. - P. 867-872. Novosibirsk. - 1987. – P. 100. 13. Quality of life in Siberia (population and clinical researches): coll. theses / edited by 3. Krivoshapkin V.G. Food as a basis of formation of human health in the north / V.G.Krivoshapkin// G.I.Simonova. - Novosibirsk: the Parallel, 2008. – P. 139. Science and education. - 2002. - № 1. - P. 57-60. 14. Briefel, R.R. Secular trends in dietary intake in the United States / R.R. Briefel, C.L. 4. Eganjan, R.A. Characteristic of food of inhabitants of the Far North Russia (the literature Johnson //Annu. Rev. Nutr. - 2004. - Vol. 24. - P. 401-431. review) / R.A.Eganjan //Preventive medicine. - 2013. - Т. 16, № 5. - P.41-47. 15. Dyerberg, Y. Prevalence of chronic noncommunicable diseases in population of Greenland 5. Klimov Т. M. Actual food of indigenous small population of the Republic Sakha (Yakutia) and North America / Y. Dyerberg //Philos. Trans. Soc. London. - 1981. - Vol. 294. - P. / Т. M.Klimov, M.E.Baltahinova, V.I.Fedorova [et al.] // Bulletin of the Russian university 373-386. of people’s friendship. - 2008. - № 7. - P. 306-310. 16. Metabolic profile in two physically active Inuit groups consuming either a western or 6. Ivanov K.I. Cardiovascular pathology in Yakutia / K.I.Ivanov // the Russian cardiological traditional Inuit diet / T. Munch-Andersen, D.B. Olsen, H. Sondergaard [et al.]//Jnt. J. journal. - 2006. - № 1 (57). - P. 52-57. Circumolar Health. - 2012. - Vol. 71. - P. 17342. 7. manchuk V.T. State and tendencies of formation of indigenouspopulation’s health of 17. Diabetes prevalence, incidence, complications and mortality among Alaska Indigenous the North and Siberia / V.T.Manchuk, L.A.Nadtochy // the Bulletin SB RAMS. - 2010. - Т. people 1985-2006 / M.L.Narayanan, C.D. Sahraer, L.R. Bulkow [et al.]//Jnt. J. Circumolar 30, № 3. - P.24-32. Health. - 2010. - Vol. 69, № 3. - P. 236-252. 18. Dietary habits in three central and eastern European countries: the HAPIEE study / S. Boylan, A. Welch, H. Pikhart [et al.] //BMC Public Health. - 2009. - № 9. - P. 439.

ADDRESS FOR CORRESPONDENCE: NeustroevaV.N. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Ojunsky street Ph. 89246616635 [email protected]

511 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Res u l ts o f c o l o n c a n cer s u rgic a l tre a t m e n t

Tobohov A., Nikolaev V. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT In recent decades in the Republic of Sakha (Yakutia) there was a growth of the colon cancer, so the problem of its early diagnosis and treatment currently acquired great importance. The article is devoted to one of the most common cancers – the colon cancer and considersissues of the differentiated approach to its integrated treatment. We achieved the best results of the five-year survival in patients with colon cancer at Stage A.

Key words: the colon cancer, diagnosis of colon cancer, surgery

Wiad Lek 2015, 68 (4), 512

INTRODUCTION At the present time, in our opinion, in patients with cancer In recent decades in the Republic of Sakha (Yakutia) there of the colon there is no alternative to surgical treatment [2]. was a growth of the colon cancer, so the problem of its early Radiation and chemotherapy, laser treatment are only auxiliary diagnosis and treatment currently acquired great importance [1]. ones. Resection volume depends mainly on the tumor location The article is devoted to one of the most common cancers – the and the distribution process. When the local process, we used colon cancer and considersissues of the differentiated approach standard techniques. In the presence of distant metastases, in to its integrated treatment. We achieved the best results of the recent years we adhere to the active surgical tactics. The tumor of five-year survival in patients with colon cancer at Stage A. the segmented intestine mostly metastasizes to the liver. Under isolated metastases,regional, wedge resection or lobectomy of METHODS the liver can be successful. In case ofcarcinomatosisweperform We analyzed the observations of 119 patients with malignant cytoreductive surgery to reduce the tumor mass followed by the tumors of the colon and rectum, being on treatment and examination application of radiation and polychemotherapy. at the National Center of Medicine of the Republic of Sakha (Yakutia) from 2007 to 2014. The patients were at theageof 27 CONCLUSION to 86 years including57 women and 62 men. Bariumenema It should be noted that the 5-year survival rates are clearly combined with endoscopy colon tumor biopsy, followed by correlated with the stages of the disease. Thus, the best results histological examination of tissuewere the most efficientdiagnosis. were obtained in patients who have undergone radical surgery CT, ultrasound provided insights on the prevalence of tumors for Stage A. A 5-year survival rate is 90%. At the Stage B, the and metastases. 5-year survival rate is 70%. In patients with damage of perienteric lymph nodes (Stage C1), the 5-year survival rate is about 52%. RESULTS In presence of metastatic disease (stage D) it is also possible to Localization of the process: the tumor located inascending achieve a 5-year survival, especially in patients with isolated colonandblindgutin 17% of cases, in transverse colon – 10%, in distant metastases of small size (15%). descending colon – 4%, in sigmoid – 29% and in rectum – in 40% of cases. By microscopic structure we have established the REFERENCES following types of malignant epithelial tumors: 1. Adenocarcinoma 1. Ivanov P.M. // Tomsk MI PD Karataev Malignancies in Yakutia at the turn of the century. forming 87% of cases, including 36% of highly differentiated Yakutsk, 2008.268 p. one, 45% of moderately differentiated and 19% of low-grade 2. Perevodchikova N.I. // Guide chemotherapy of tumor diseases. Moscow, 2005.230 p. one. 2. Mucous adenocarcinoma accounted 1%. 3. Signet ring cell carcinoma – 1%. 4. Squamous cell carcinoma – 2%. 5. Undifferentiated carcinoma – 9%. The most common tumors ADDRESS FOR CORRESPONDENCE: of the colon had a structure of adenocarcinoma. According to Nikolaev V. N. the Dukes classification, patients were distributed as follows: Russia, Republic of Sakha (Yakutia), StageA – identified in 3% of patients, Stage B – 17%, Stage C1 677013, Yakutsk city, 27, Oyunsky street – 28%, Stage C2 – 39%, Stage D – in 13% of cases. [email protected]

512 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Ge n d er f e a t u res o f t h e a n t h r o p o m etric , cep h a l o m etric a n d b i o i m pe d a n ce p a r a m eters in t h e st u d e n ts o f y a k u ti a

Guryeva A.B., Alekseyeva V.A., Petrova P.G. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT To establish the anthropo-ecological portrait of the current population of Yakutia, it is necessary to study the regularities of the variability of physical status in different gender groups and develop regional standards of the physical development of different age-sex groups of the population with regard to the peculiarities of the environment. The aim of this study is to do research on the gender features of anthropometric, cephalometric and bioimpedance parameters in the students of Yakut ethnicity. The measures of 228 Yakut girls and 168 Yakut youths born and permanently resident in Yakutia were analyzed. Anthropometric measurements were performed using the method of V.V. Bunak (1941), somatotyping – using the Rees-Eysenck index (1945). Head type was determined by the cephalic index, face type – by the upper facial index. Bioelectrical impedance analysis with the use of ABC – 01 Medass analyzer was performed to estimate body composition. Adipose tissue mass (AM), skeletal muscle mass (SMM), lean mass (LM), active cell mass (ACM) and phase angle (PA) were determined. Obtained material was processed by the method of variation statistics with the use of SPSS 17.0 software package. Overall measures of the soma of the examined groups have gender features of body organization that are expressed in the significantly higher values of all measured parameters in the youths of Yakutia. In our study, the sexual dimorphism in the distribution of somatotypes by the Rees-Eysenck index has not been identified. The analysis of cephalometric measures has revealed reliably higher parameters of absolute head sizes in the youths. Gender differences in the distribution of head and face types have not been found in the examined ethno-age group. Significantly larger absolute amount of AM has been established in the girls. The measures of SMM, ACM and LM are reliably higher in the youths. The values of active and reactive tissue resistance are reliably higher in the girls. Gender features of the anthropometric, cephalometric and bioimpedance parameters of the students have been established. The conducted study presents the anthropo-ecological image of this age-sex group of the population of Yakutia.

Key words: anthropometry, cephalometry, bioimpedance, Yakutia.

Wiad Lek 2015, 68 (4), 513-516

INTRODUCTION of the population of Yakutia in different age and ethnic groups To ensure the full development of an individual or the humanity with the identification of overall, component indices and body at large, modern medicine was confronted with a number of types [2, 3, 4 etc.] was defined. However there is not enough issues, one of which is to determine the characteristics of the research on bioimpedance and cephalometric parameters in physical development of a person in the specific environmental, the adolescent age group, which determines the relevance of climatic and geographical and social living conditions [1]. The this study. Sakha Republic (Yakutia) is a region with harsh natural and The aim of this study is to do research on the gender features climatic conditions for human habitation. Undoubtedly, such of anthropometric, cephalometric and bioimpedance parameters specific living conditions influenced the formation of the physical of the junior students of Yakut ethnicity attending Ammosov status of the population. To establish the anthropo-ecological North-Eastern Federal University. portrait of the current population of Yakutia, it is necessary To attain the aim, we set the following objectives: to study the regularities of the variability of physical status in To make anthropometric, cephalometric and bioimpedance different gender groups and develop regional standards of the examination of the girls and youths studying at NEFU. physical development of different age-sex groups of the population To identify gender features of anthropometric, cephalometric with regard to the peculiarities of the environment. From 1996 and bioimpedance characteristics of the examined groups. onwards North-Eastern Federal University in cooperation with Krasnoyarsk State Medical University has conducted research MATERIALS AND METHODS on the assessment of the physical status of the population of To attain the stated aim we have made anthropometric Yakutia. As a result of the conducted research, the physical status examination of 396 students of the city of Yakutsk. We have

513 Guryeva A. B., et al. analyzed the measures of 228 girls and 168 youths of Yakut Biotabs® with Ag/AgCl coating and tip area of 528 mm2 were ethnicity. All the examined students were born and permanently used. ABC01_036 software recorded the data of the subject, the resident in Yakutia. In accordance with the age periodization of final protocol was automatically generated after bioimpedance human ontogenesis, adopted at the 7th All-Union Conference measurement. Adipose tissue mass (AM), skeletal muscle mass on Age Morphology, Physiology and Biochemistry of the USSR (SMM), lean mass (LM), active cell mass (ACM) and phase angle Academy of Sciences (1965), examined students fell into adolescent (PA) were determined. The phase angle values were calculated period (16-20 for girls, 17-21 for youths). Ethnic affiliation was as the arctangent of the ratio of bioimpedance components: determined on the basis of a survey, miscegenation in three PA=arctg(Xc/R), where Хс is the reactive resistance, R is generations was excluded. The study has been pursued after the active resistance. PA values were assessed as follows: less receiving a favorable decision of the local ethics committee than 4.40 — significantly below normal, from 4.40 to 5.390 – subject to clear exclusion criteria, namely the presence at the decreased, from 5.40 to 7.80 – the norm, over 7.80 – increased time of the examination of acute diseases or acute exacerbation of [9]. Instrument status was monitored every 50 measurements chronic diseases, pregnancy, and refusal of examination survey, with a special board of the DUMMY biological object simulator with the written consent of the participants. The principles of coming with the analyzer. voluntariness, the rights and personal liberties of the examined Obtained material was processed by the method of variation persons were respected. The examination of the students was statistics with the use of SPSS 17.0 software package. We determined conducted at the NEFU multidisciplinary scientific laboratory the pattern of each feature distribution with subsequent calculation Natural and Human Evolution in the North. of value M and its error m, the root-mean-square deviation δ, Anthropometric measurements were performed using the coefficient of feature variation V. The Kolmogorov-Smirnov the classic method of V.V. Bunak (1941) [5] adopted at the test was used to assess the normality of data distribution [10]. We Research Institute of Anthropology, Moscow State University used the methods of parametric and nonparametric statistics, (1981), in accordance with the requirements for anthropometric the evaluation of intergroup differences was made using the measurements using a standardized anthropometric instrument Student’s t-test and the Mann-Whitney U-test. The differences set (metal rod Martin anthropometer, medical scales, rubber were considered statistically significant at p <0.05. measuring tape, sliding caliper, spreading caliper). After every 100 measurements the accuracy of instruments was checked RESULTS with a special calibration block. The measurement results were The analysis of the body overall measures has revealed that registered in an individual record of anthropometric examination. the body length of the girls is on the average 160.62±0.23 cm, We determined the overall body dimensions (body length, body the body weight is 52.93±0.30 kg. The body length of the youths weight, transverse thoracic diameter, waist and hip circumference). is 173.67±0.59 cm, and the body weight is 63.83 ±0.93 kg. TTD All the examined students underwent somatotyping by the Rees- of the girls was 24.25±0.08 cm, of the youths – 28.05±0.21 cm. Eysenck index (1945) [6] according to the formula: I=BL*100/ The waist circumference of the girls was 66.02±0.32 cm, the (TTD*6), where BL represents the body length (cm), TTD hip circumference – 90.28±0.21 cm. The same measures of represents the transverse thoracic diameter (cm). Persons with the youths were 73.32±0.80 and 88.74±0.66 cm respectively. an index value of up to 96 belong to the pyknic somatotype, from The waist-to-hip ratio in the girls was significantly lower at 96 to 106 – normosthenic and over 106 – asthenic somatotype. 0.74±0.002, in the youths it was 0.81±0.005. The comparative To determine the head type we measured the longitudinal and analysis of the ratio between somatotypes has shown that the transverse diameters of the head with subsequent calculation of asthenic body type prevailed in both studied groups (84.6% of the cephalic index (74.9 or less – dolichocephaly, from 75.0 to the girls and 70.8% of the youths). The normosthenic type in 79.9 – mesocephaly, over 80.0 – brachycephaly). To determine the girls was registered in 13.9%, in the youths – 26.2%. The the face type we calculated the upper facial index representing pyknic type was detected in only 1.5% of the girls and 3.0% of the ratio of the upper facial height to the bizygomatic diameter the youths. in percentage terms (49.9 or less – eurens, from 50.0 to 54.9 – Gender differences of the cephalometric measures were mezens, over 55.0 – leptens) [7]. expressed in significantly (р<0.001) larger values of longitudinal To assess the body composition based on the electrical (19.08±0.10 cm – youths, 17.64±0.09 cm – girls), transverse properties of body tissues we performed bioelectrical impedance (14.81±0.09 cm – youths, 14.14±0.08 cm – girls) diameters, analysis using the analyzer of body composition and body fluid upper facial height (7.81±0.09 cm – youths, 7.43±0.05 cm – girls), compartments balance ABC – 01 Medass (validation certificate bizygomatic (14.44±0.09 cm – youths, 13.97±0.06 cm – girls) of the Federal Service on Surveillance in Healthcare and Social and bigonal (11.64±0.08 cm – youths, 11.07±0.05 cm – girls) Development No. FSR 2007/01219 of 26.11.2007). diameters in youths. According to the data of the transverse- Impedance analysis was performed by tetrapolar method longitudinal cephalic index of the examined youths and girls, with the probe sinusoidal current at the constant frequency the mesocephalic head type was found in a higher percentage of 50 kHz, with a strength of not more than 1mA within the of cases (48.4% – youths, 43.8% – girls). Dolichocephaly and range of measured impedance values of up to 1000 ohms, in a brachycephaly in the youths are found with the same frequency supine position. We used two measure electrodes placed on the of 25.8%. In the girls, brachycephaly is observed significantly dorsum of the right hand and right foot in the wrist and ankle (p <0.001) more often than dolichocephaly (40.9% and 15.3%, joints, and two current electrodes placed 4-5 cm distal of the respectively). The study of the distribution of face types has measure ones [8]. Disposable bio-adhesive electrodes Schiller shown that the leptoprosopic face type is the most common

514 Ge n d e r f e a t u r e s o f t h e anthropometric , cephalometric a n d bioimpedance p a r a m e t e r s in t h e s t u d e n t s o f y a k u t i a for adolescents of both sexes (71.5% girls, 74.1% of youths). climatic, socioeconomic, etc.). The measures of SMM, ACM Europrosopic and mesoprosopic face types were defined much and LM are reliably higher in the youths. SMM depends on more rarely, in the girls it was 13.9 and 14.6%, respectively, in the fitness level and eating behavior and serves as a measure the youths – 8.7 and 17.2%, respectively. of the body’s adaptive reserve [13]. Lean mass is a necessary As a result of bioimpedance analysis the gender difference of measure in the assessment of the basal metabolic rate, i.e. energy some body components has been revealed. Body AM in the girls consumption of the body. ACM measure gives a quantitative is reliably (p<0.001) higher than that in the youths (16.01±0.23 estimation of the metabolically active tissues in the body. We kg in the girls and 12.51±0.38 kg in the youths). The absolute have also identified gender differences in the values of active measures of SMM had reliable gender differences that were and reactive resistance of the tissues. These measures are reliably expressed in higher measures in the youths – 29.9±0.26 kg (in higher in the girls. According to the literature data, the greatest the girls – 19.07±0.10 kg). Similar gender features are typical of value of active and reactive resistance of the tissues is observed LM (53.42±0.35 kg – youths, 39.2±0.16 kg — girls). The sexual in the adolescent age period [14]. With age, these measures in dimorphism of ACM is manifested in higher values in the youths both men and women tend to decrease with the preservation – 32.1±0.25 kg (23.2±0.1 kg). The analysis of bioimpedance of gender features. Thus, the set aim and objectives of the study measures has found that active resistance at the frequency of are achieved. 50 kHz was 562.95±5.1 ohms in the youths and 688.10±3.49 ohms (р<0.001) in the girls. Reactive resistance at the same CONCLUSIONS frequency was 73.09±0.71 ohms in the youths and 88.11±0.86 We have established the gender features of anthropometric, ohms (р<0.001) in the girls. It has been established that the PA cephalometric and bioimpedance parameters of the junior students value in both examined groups was within the normal range of Yakut ethnicity attending Ammosov North-Eastern Federal and made 7.36±0.08 in the girls and 7.48 ±0.07 in the youths University. and was not significantly different. Analyzing the anthropometric measures of the soma, it is possible to state that the overall body dimensions and absolute DISCUSSION measures of cephalometry have gender differences that are Analyzing the data of the overall measures of the soma manifested in reliably larger parameters in the youths. The of the examined groups, it is possible to state that there are sexual dimorphism has not been identified in the distribution gender features of body organization that are expressed in of somatotypes by the Rees-Eysenck index, head and face types the significantly higher values of all measured parameters in in the studied ethno-age group. The absolute measures of SMM, the youths of Yakutia. Similar results are also observed in the LM, and ACM had reliable gender differences that were expressed studies of anthropologists of various regions of the world [11]. in higher measures in the youths. Similar gender features are In anthropology, the length and weight of the body are the main typical of the values of active and reactive resistance of the parameters of the physical development of an individual. These tissues. The PA value has no reliable gender differences. The indices are most available in the measurement and along with conducted study enables, on the basis of the average measures other anthropometric parameters underlie the calculation of of a sample, to present the anthropo-ecological image of this the indices of the assessment of human physical development. age-sex group of the population of Yakutia. Due to the simplicity and availability, somatotyping by the Rees-Eysenck index is widely used in medicobiological and REFERENCES anthropological studies. In our study, the sexual dimorphism 1. Petrova, P.G. Ekologo-fiziologicheskiye aspekty adaptatsii cheloveka k usloviyam in the distribution of somatotypes by the Rees-Eysenck index Severa . / Petrova, P.G. // Yakutsk: Dani AlmaS, 2011. has not been identified. 2. Guryeva, A.B. Antropometricheskaya kharakteristika fizicheskogo statusa zhenshchin- The analysis of cephalometric measures has revealed reliably yevropeoidov 36-75 let Respubliki Sakha (Yakutiya). / Guryeva, A.B. // Dal’nevostochnyy higher parameters of absolute head sizes in the youths. Gender med. zhurn. 2011, No. 4, P. 80-82. differences in the distribution of head and face types have not 3. Alekseyeva, V.A. Etnicheskiye, vozrastnyye i konstitutsional’nyye osobennosti razvitiya been found in the examined ethno-age group. vtorichnykh polovykh priznakov devochek i devushek Respubliki Sakha (Yakutiya). / As a result of bioimpedance analysis the gender difference Alekseyeva, V.A. // Candidate of Medicine thesis. Krasnoyarsk, 2009. of some body components has been revealed. Significantly 4. Degtyaryova, T.G. Nekotoryye aspekty anatomo-antropologicheskikh issledovaniy larger absolute amount of AM has been established in the girls. muzhskogo naseleniya Respubliki Sakha (Yakutiya). / Degtyaryova, T.G., Guryeva, A.B. The comparative analysis of the AM measures of the girls of // Sovremennyye problemy nauki i obrazovaniya, 2015, No. 3. Yakutia with the same measures of the girls of Eastern Siberia 5. URL: www.science-education.ru/123-19333 (Krasnoyarsk, Tyva, Khakassia, Buryatia) has elucidated ethno- 6. Bunak, V.V. // Antropometriya. Moscow: Narkompros RSFSR, 1941. regional features. According to L.V. Sindeyeva [12] the girls of 7. Rees L., A Factorial Study of Some Morphological and Psychological Aspects of Human the Khakass ethnic group had the highest absolute and relative Constitution. / Rees L., Eysenck, H.J.// in J. Mental Sci. 1945, Vol. 91, pp. 219-232. values (15.12±0.41 kg, 27.40±0.50%) among the examined girls 8. Tegako, L.I. Osnovy sovremennoy antropologii. / Tegako, L.I., Salivon, I.I. // Minsk: of Eastern Siberia. Our study has shown that the Yakut girls Univer. Izd-vo, 1989. living in Yakutia have reliably higher (р<0.001) absolute amount 9. Nikolayev, D.V., Smirnov, A.V., Bobrinskaya, I.G. // Bioimpedansnyy analiz sostava tela of AM than the Khakass girls. This distinction of the body fat cheloveka. Moscow: Nauka, 2009. component may be associated with the ethnic characteristics 10. orlova, N.V., Chukayeva, I.I. Organizatsiya i funktsionirovaniye tsentrov zdorov’ya. and living conditions in Yakutia (environmental, natural and Moscow: RGMU, 2010.

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11. Glantz, S. Medico-Biological Statistics. Translation from English. Moscow: Praktika, 1998. 14. Godina Ye. Z. Osobennosti sostava tela u detey i podrostkov raznykh etnicheskikh grupp, 12. Peshkov, M.V., Sharaykina, Ye.P. // Pokazateli massy tela studencheskoy molodezhi: / Godina Ye. Z., Zadorozhnaya, L.V., Khomyakova, I.A. [et al.] // Aktual’nyye voprosy i sovremennoye sostoyaniye problemy, in Sibirskoye meditskinskoye obozreniye. 2014, dostizheniya sovremennoy antropologii: sb. nauch. trudov. Novosibirsk, 2008, P. 21- No. 4, P. 49-56. 24. 13. Sindeyeva, L.V. //Etnicheskiye osobennosti zhirovoy massy devushek Vostochnoy Sibiri po 15. Nikolayev, D.V. Bioimpedansnyy analiz: osnovy metoda, protokol obsledovaniya i inter- dannym antropometrii i bioimpedansometrii, in Diagnostika i lecheniye narusheniy regulyatsiy pretatsiya rezul’tatov. / Nikolayev, D.V, Rudnev, S.G. // Sportivnaya meditsina: nauka i serdechno-sosudistoy sistemy: tr. XIII nauch.-prakt. konf. Moscow, 2011, P. 202-209. praktika. 2012, No. 2, P. 29-36.

ADDRESS FOR CORRESPONDENCE: Guryeva A.B. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 34 Kulakovskogo St., Ph +7(924)6638386, [email protected]

516 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Clinical significance l e v e l s o f c-re a cti v e pr o tei n a n d cer u l o p l a s m i n in p a tie n ts w it h isc h e m ic h e a rt d ise a se

Daybanyrova L.V.1, Shevchenko O.P.2 1f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a 2”r u s s i a n n a t i o n a l r e s e a r c h m e d i c a l u n i v e r s i t y . p i r o g o v “, m o s c o w

ABSTRACT Introduction: the study examined the relationship of levels of ceruloplasmin and CRP in patients with coronary heart disease and assessed the possibility of their use for diagnosis and prediction of developing complications. Aim: the study investigated the relationship of levels of ceruloplasmin and CRP in patients with coronary heart disease and their potential use in the diagnosis and prediction of complications. Materials and methods: examined 117 patients with ischemic heart disease at the age of 39 to 80 years (median age +13.9 61.7 years), among them 56 were women and 61 men. Assessment of prognosis in patients with ischemic heart disease was conducted based on the two-year observation. Results: the reverse relationship between the levels of ceruloplasmin and CRP was identified. When comparing the survival curves without adverse events using the log-rank analysis in patients with levels of CPU of more than 0.2 grams per liter and CRP of less than 6.0 mg / l, the prognosis was significantly better than in patients with simultaneously detected low levels of the CPU (less than 0.2 g / l) and high levels of CRP (more than 6.0 mg / l) in the blood (p <0.05), Conclusions: highly sensitive measurement method of levels of c-reactive protein in patients with coronary heart disease combined with measurement of levels of ceruloplasmin, gives an opportunity to assess the activity of vascular inflammation that can be used to predict the development of acute coronary events.

Key words: acute coronary syndrome, ceruloplasmin, C-reactive protein, inflammation.

Wiad Lek 2015, 68 (4), 517-519

INTRODUCTION fibrinogen, serum amyloid A and other acute-inflammation The main cause of coronary heart disease (CHD) is phase proteins in the liver [3, 6, 7, 15]. atherosclerotic disease of the coronary arteries, which is The modern concept of involvement of inflammation in the observed in 95% of patients with CHD. According to current pathogenesis of coronary heart disease provides a new insight data, the indolent inflammatory process in the intima of the on the processes underlying the development of acute coronary coronary arteries involved in the initial change, contributes events and represents an important approach to the study of to the progression and development of complications [10,13], new markers and factors indicating the risk of coronary events. and plays a major role at all stages of the pathogenesis of C-reactive protein (CRP) in the blood, as measured by a highly atherosclerosis . sensitive technique, is the most significant prognostic marker Based on the results of recent studies the concept of “thin- among new and cardiovascular risk factors. The role of other skinned atherosclerotic plaque” explaining the mechanism acute-phase proteins in atherogenesis, such as ceruloplasmin, of the development of atherothrombotic complications was was notinvestigated enough. developed. According to this concept, the transition of the Ceruloplasmin (CP), as well as CRP, refers to proteins of the stable atherosclerotic plaque into the state of “thin-skinned” acute phase. It is a natural regulator of the oxidative balance and is based on the activation of the inflammatory process. The is involved in the oxidation of lipids, iron and copper metabolism, existence of a thin-skinned plaque is the main indication of blood clotting, and other. The clinical significance of ceruloplasmin the likelihood of damage and possible development of acute content in the blood of patients with coronary artery disease coronary syndrome shortly afterwards [11, 12]. remains unexplored. With the increase of inflammation, the cells of monocyte- The purpose of this study to determine the clinical significance macrophage system rapidly migrate in atherosclerotic plaques.. of ceruloplasmin and CRP in patients with coronary heart disease Macrophageselicit pro-inflammatory cytokines IL-6, TNF-α, and to evaluate the possibility of their use in the diagnosis and etc., which cause increased formation of C-reactive protein, prediction of complications.

517 Daybanyrova L.V., Shevchenko O.P.

MATERIALS AND METHODS respectively, p <0, 01), and the mean CRP levels are lower than The work is based on analysis of data obtained from the in the total group of patients (2.8 + 1.1 and 8.7 + 6.5 mg / l, survey of 117 CHD patients aged 39 to 80 years (mean age respectively, p <0.05). 61.7 13.9 years), with 56 female and 61 male population. Stable Comparative analysis of the CPU levels in patients with angina was in 70 patients (PRS), unstable angina (UA) – in various forms of ischemic heart disease found that the level of 32 patients, and acute myocardial infarction (MI) segment CP was significantly higher in the group of patients with stable elevation ST in 15 patients. The comparison group consisted angina – 0.20 + 0.1 g / l, compared with a group of patients with of 20 healthy subjects, aged 20 to 47 years (mean age – 31.6 + myocardial infarction – 0.12 + 0 , 1 g / l (p = 0.006). Ceruloplasmin 9.1 years). The diagnosis of myocardial infarction was based levels in patients with unstable angina and myocardial infarction on the identification of characteristic clinical signs, elevated patients were not statistically significant. levels of blood CPK MB and troponin T, as well as characteristic CRP levels were significantly higher in patients with myocardial changes in myocardial infarction electrocardiogram (ECG).In infarction compared to patients with stable angina – 7.7 + 3.1 patients with unstable angina were observed reduced tolerance mg / l and 5.1 + 4.6 mg / l (p = 0.004). CRP levels in patients to stress and the appearance of angina at rest, with no persistent with stable angina were significantly higher than in healthy ST-segment or T wave, increased levels of creatine kinase MB individuals – 2.8 + 1.1 mg / l and 5.1 4.6 mg / l (p <0.05), whereas and troponin T. in patients with unstable angina and patients with myocardial The diagnosis of stable angina was based on the identification infarction are not statistically significant 6.4-9.3 mg / l and 7.7 of typical angina, which occurred during physical exercise and + 3.1 mg / l (p> 0.05). stopped after taking nitroglycerin, and the appearance of changes In the study of the correlation between the concentrations of transient ST-segment during ECG after the exercise test. of C-reactive protein in the blood plasma and ceruloplasmin The study did not include patients with severe heart (LVEF the significant inverse relationship in the blood of patients with <30%), renal (creatinine levels> 3 mg / dl) and liver failure, coronary artery disease; r = -0,4, p <0.05 was found. In the analysis malignant hypertension with decompensated diabetes, as well based on CPU performance levels and levels of PAPP-A were as those with acute infectious, inflammatory or autoimmune significantly inverse relationship (r = -0,37, p = 0,001), while disease for at least 4 weeks after the complete clinical and CRP levels were not associated with the levels of PAPP-A in laboratory remission, persons younger than 20 years old, and patients with coronary heart disease (r = – 0,03, p = 0,62). pregnant.General clinical examination of the patient included When correlating the levels of CRP and ceruloplasmin with clinical assessment of state, general and biochemical blood tests, demographic and clinical data, the study revealed that their a blood test for lipids, ECG 12-lead, a study exercise (bicycle content was not associated with age, sex, body mass index, lipid ergometry), echocardiography. The prognosis in patients with levels of blood plasma, the presence of diabetes and hypertension, coronary artery disease was conducted on the basis of the two- and smoking. Reduced levels of CP in combination with high year follow-up. concentrations of CRP in the blood plasma of patients with Measuring the concentration of C-reactive protein via coronary heart disease after angioplasty and stenting of the a highly sensitive technique was performed using the latex coronary arteries is a poor prognostic sign for the occurrence of immunoturbidimetry strengthening and building kits production restenosis. [4]. Patients with reduced preoperative level CPU in «Orion», Findlyandiya. Ceruloplasmin concentration measurement combination with high or normal levels of CRP have developed was performed using immunoturbidimetry in microplate format the most severe postoperative complications, i.e.r Reducing with the help of the kits manufactured by “Aptec Diagnostics the concentration of CP, revealed before surgery may be an nv», Belgium. Measurement of the concentration of endogenous additional criterion for the selection of patients with a higher marker destruction – pregnancy-associated plasma protein A risk of postoperative complications. [5]. (PAPP-A) was determined by ELISA kits production «Diagnostic Out of the 117 patients included in this study, the prognosis Systems Laboratories INC», USA. for two years was estimated via monitoring of 105 patients (8 The significance of differences of quantitative parameters in patients were excluded from the analysis because of the loss of the two groups was determined by t-test. The significance of contact with researchers, one patient died of a lung abscess, differences was determined by qualitative attributes construct complications of pneumonia, three patients were hospitalized contingency tables and analysis using the criterion c-square. To for reasons not related to cardiovascular diseases). The study assess the correlation of quantitative traits the methods of linear identified 24 adverse events associated with cardiovascular disease: regression and correlation (Pearson correlation coefficient) were three patients died of recurrent myocardial infarction, three used. To assess the adverse event-free survival regression analysis patients had non-fatal myocardial infarction segment elevation Kaplan-Meier method was used. Comparison of survival without ST, seven were hospitalized with unstable angina, eleven patients adverse cardiovascular events was determined via lograngovogo showed a reduction in exercise capacity (progressive angina). (log-rank) test. One patient was hospitalized with recurrent acute stroke. When comparing survival curves with no adverse events, RESULTS AND DISCUSSION with a log-rank analysis showed that patients with high levels In the study of the concentration of inflammatory markers of CPU (> 0.2 g / L) had a significantly better prognosis than in healthy persons and the total group of patients with coronary patients with low levels of CPU levels (<0.2 g / L) (p <0.05) heart disease found that in healthy individuals the average levels When comparing survival curves with no adverse events, with of CP was significantly higher (0.33 ± 0.1 and 0.16 ± 0.1 g / l, a log-rank analysis, the study revealed that patients with CRP

518 Clinical significance l e v e l s o f c-r e a c t i v e p r o t e i n a n d ceruloplasmin in p a t i e n t s w i t h ischemic h e a r t d i s e a s e levels less than 6 mg / l had a better prognosis than patients with with coronary heart disease. Thus, the highly sensitive method CRP levels more than 6 mg / l, and this difference is statistically of measuring the levels of C-reactive protein in patients with significant (p <0.05). coronary heart disease in combination with the measurement In patients with levels of CPU up to 0.2 g/l and CRP less of the levels of ceruloplasmin, gives an opportunity to assess the than 6.0 mg/l the prognosis was significantly better than in activity of vascular inflammation, which can be used to predict patients with low levels of CPU (less than 0.2 g/l) and high the development of acute coronary events. levels of CRP (more than 6.0 mg/l) in the blood (P<0.05) detected simultaneously when comparing the survival curves REFERENCES without adverse events using the log-rank analysis . It should 1. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease // N Engl J be emphasized that the percentage of patients (CRP> 6 mg/l Med. 2005. – Vol. 352. – P. 1685-1695. and LC <0.2 g/l) was the highest in the group of patients with 2. Ross K. Atherosclerosis – an inflammatory disease / / N.Engl. J. Med. – 1999. – Vol. MI 31%. In all groups, the proportion of these patients was 104. – P. 115-126. 19%, in the group with stable angina 18% and in the group 3. Koenig W. Biomarkers of Atherosclerotic Plaque Instability and Rupture. Arterioscler. with unstable angina 20%. Thromb. Vasc. Biol., / Koenig W., Khuseyinova N. // January 1, 2007. – Vol. 27 (1). – P. 15 – 26 CONCLUSION 4. Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. // The results of the study allow to conclude that the amount Circulation. 2001. – Vol. 104. – P. 365-372. of ceruloplasmin levels in blood of patients with coronary heart 5. Hasonov E.L. C-reactive protein, a marker of inflammation in atherosclerosis (new data) disease is lower and levels of C-reactive protein is higher than / Hasonov E.L., Panukova E.B., Aleksandrova E.H. // Cardiology. -2002. – № 7. -P. 53-62. in healthy individuals, but the values of​​ concentration does not 6. Apple F.S. Future Biomarkers for Detection of Ischemia and Risk Stratification in Acute depend on exercise tolerance. In patients with acute coronary Coronary Syndrome Apple F.S., Wu A.H., Mair J., Ravkilde J. [et al.] // Clinical Chemistry. syndrome, the levels of C-reactive protein, determined by a highly – 2005. – Vol. 51. – P. 810-824. sensitive technique, were significantly higher, and ceruloplasmin 7. Cannon C.P. High-sensitive C-reactive protein is a impotant predictor of long-term levels are lower than in patients with stable angina, which confirms mortality in 3225 patients with acute coronary syndrome: results from OPUS-TIMI the involvement of inflammation in the development of acute 16 / Cannon C.P., MsSade C.H., Bently J. [et al.] // Circulation. – 2000. – Vol. 102. P. processes in coronary heart disease. The relationship between 11-499. ceruloplasmin levels of CRP and PAPP-A in patients with coronary 8. Zouridakis E., Markers of inflammation and rapid coronary artery disease progression artery diseas confirms the involvement of inflammation and in patients with stable angina pectoris / Zouridakis E., Avanzas P., Arroyo-Espliguero oxidative disturbances in the development of coronary heart R. [et al.] // Circulation. – 2004. – Vol. 110. – P. 1747-1753. disease. The presence of reduced levels of ceruloplasmin in 9. mazaev B.P. Proteins of acute phase and the risk of restenosis in the coronary arteries the blood plasma of patients (<0.2 g / l) and elevated levels of in patients with coronary heart disease / Mazaev B.P., Shevchenko O. A. // Laboratory. C-reactive protein (> 6 mg / l) indicates poor prognosis in patients -2001. – 4. -P. 3-7.

ADDRESS FOR CORRESPONDENCE: Daybanyrova L. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street Ph. 89241734446 [email protected]

519 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Su per e a r l y pre m a t u re b irt h in ter m s o f t h e n e w st a n d a r d o f l i v e b irt h in t h e rep u b l ic o f s a k h a (y a k u ti a )

Baisheva N.S.1, Duglas N.I.1, Pavlova T.Yu.2, Yakovleva E.B.1, Rad Ya.G.1 1f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a 2t h e ministry o f h e a l t h c a r e o f t h e r e p u b l i c o f s a k h a (y a k u t i a ), y a k u t s k , r u s s i a

ABSTRACT Premature birth is a serious problem of public health around the world owing to the high frequency of complications and perinatal losses [1]. According to the WHO recommendations by gestation terms the premature birth divides into: super early premature birth (SEPB) in the term of 22-27 weeks, early PB in the term of 28-33 weeks and PB in the term of 34-37 weeks. Preterm born infants make 85%, and in the neonatal mortality structure make more than 55%. It is necessary to consider that in recent years the number of women in the premature birth development risk group has increased, to which patients with a uterus scar, extragenital pathology, supporting reproductive technology treatment pregnancy [2,3] are related.

Key words: super early premature birth, Cesarean section, amniorrhea, preterm discharge of amniotic fluid, perinatal mortality.

Wiad Lek 2015, 68 (4), 520-522

INTRODUCTION RESULTS AND DISCUSSION The share of premature birth in the world makes 5-10% in During the period of 2009-2011 for the purpose of preparation recent years, and across Russia 15-20%. In the Republic of Sakha for to live birth new criteria changes, organizational events had (Yakutia) this indicator has made 3,3% in 2011. Since 2012 in been held from 2012 in the Sakha Republic.The three-level system connection with a change of new live birth standards in 2012, of healthcare delivery for newborns and women during pregnancy there was an expected increase of this indicator, it made 6,9%, and childbirth had been created.The first group of establishments 6,5% in 2013 and 6,9% in 2014. All this approves that preterm is 31 small delivery rooms of the central regional hospitals, the birth is one of serious problems for Yakutia as prematurity second group contains 6 city scale maternity departments, the represents an important social problem due to big expenses Perinatal Center makes the third group. In the republic the connected with nursing and rehabilitation of newborns, and list of pregnant women routing considering a perinatal risk is also considerable share of disabled and children with chronic approved in addition to the decree by Ministry of Healthcare pathology among them. This article presents the analysis of of the Russian Federation from November 1, 2012 No.572n, by super early premature birth structure in the Sakha Republic which an indications for hospitalization of pregnant women during 2012-2014 on the basis of the Perinatal Center of State in obstetrical establishments are regulated. The Ministry of Budgetary Institution RS (Ya) “RB№1 National Medical Center” Health of Yakutia decreed from February 21, 2012 No.01-8\4-22 for 2012-2014. “About introduction of clinical protocols” according to which Purpose of work: To develop a forecasting criteria for super the clinical protocol approved by the methodical letter of Health early preterm birth and recommendations to decrease their Ministry and SR Russian Federation No.15-4/10/2-12700 from quantity in groups of risk in the Republic of Sakha (Yakutia). 16.02.2011 for health care delivery to women with PB; the clinical protocol approved by the methodical letter of Ministry and SR MATERIALS AND METHODS RF No.15-0/10/2-11336 from 16.11.2011 for health care delivery Research is conducted in two stages. At the 1 stage all cases of to newborn, intensive therapy and nursing of children with an premature birth in the Sakha Republic for 2012-2014 are analysed. extremely low body weight (ELBW) which is 750-999 grams At the 2nd stage the retrospective analysis of 82 stories of super and very low body weight less than 1000-1499 grams. early premature births on the basis of the Perinatal Center of the The perinatal help regionalization in Yakutia was made to State Budgetary Institution RS (Ya) “RB№1 National Medical improve the rendering quality of medical care to prematurely Center” for 2012-2014 is made. born infants since January 2012. In 2012 there were approved

520 Su p e r e a r l y p r e m a t u r e b i r t h in t e r m s o f t h e n e w s t a n d a r d o f l i v e b i r t h in t h e r e p u b l i c o f s a k h a (y a k u t i a )

Fig. 1. Premature birth by levels of obstetric aid establishments.

Fig. 2. An indicator of perinatal mortality in RS(Ya)

20% of women with premature birth in maternity departments of the 1 level, 51,5% in obstetric establishments of the 2 level, 28,5% in those of the 3 level. As a result of the routing of women with preterm birth in 2014 the specific weight of premature had raised from 8,4 to 13,0 for 1000 born alive and dead. In births in the Perinatal Center had increased to 41,1% and had 2013 and 2014 this indicator had made 10,8 and 10,0. decreased in obstetric establishments of levels 2 to 43,6% and The retrospective analysis of 82 stories of women with super level 1 to 15,3%. early premature birth in the Perinatal Center of State Budgetary There were delivered 496 premature births in total across Institution RS RB No.1 for 2012-2014 was carried out. From the Republic of Sakha in 2012, a share of super early premature them 26 in 2012, 22 in 2013 and 34 in 2014. births makes 22,7% of them. In 2013 528 premature births The analysis revealed that in structure of super early premature were delivered, a share of super early made 17,6% of them. In birth hospitalization for three years women of rural area made 2014 these indicators made 1160 and 6,12%. Data provided 54,66%, urban 46,34%. Most often super early premature births in table I. were observed at the age of 19-28 years, making 42,46%. Studying Following the results of 2012-2013 the obstetric hospitals of the social status of these women it was revealed that women levels 2 are leading by the volume of provided medical care to with secondary education making 42.2% and married making women with super early premature birth, in 2014 the majority 55,06% prevail. From 82 women 31(37,8%) are smokers. The of super early premature births were delivered in the Perinatal early appearance for dispensary till 12 weeks of pregnancy has Center. Data provided in table II. made 60,97%. Studying the anamnesis revealed that 35,75% of In connection with changes of live birth new criteria from women had medical abortions, 28,1% had spontaneous abortions, January 1, 2012 the indicator of perinatal mortality in RS(Ya) antenatal death of fetus at 4 (4,87%) and premature birth at

Table I. Super early premature births in RS(Ya) for 2012-2014. 2011 2013 2014 Total Total number of preterm births in Yakutia 496 528 1160 2184 Super early 113 93 71 277 % 22,7% 17,6% 6,12% 12,68%

Table II. Super early premature birth in RS(Ya) by levels of establishments of obstetric aid. 2012 2013 2014 abs % abs % Abs 1 level 11 9,7% 13 13,97% 8 2 level 76 67,2% 58 62,36% 29 3 level 26 23% 22 24% 34 Total 113 100% 93 100% 71

521 Baisheva N.S., et al

13 (15,85%) respondents. Extragenital diseases in group of death of fetus in 3 (75%) cases, 1(25%) case of intranatal death. examined women were revealed in all cases, thus the majority From 24 born alive 1 (4,16%) had died in the early neonatal had some nosological forms. The following was revealed: diseases period. The survival had made 95,83%. of urinary tract had 75,6% of women, diseases of cardiovascular Totally 42 cases of childbirth in the term of 27 weeks of system at 54,87%, diseases of digestive tract at 36,58%, anemia pregnancy, from them 1(2,38%%) deadborn, from them antenatal at 19,51%, respiratory system diseases at 8,53%, endocrinopathy death of fetus in 1(100%) case. From 41 born alive 6 (14,63%) at 2,43%. Chronic diseases of female genital had 68,3%. Sexually had died in the early neonatal period. The survival had made transmitted infections were revealed almost at every woman, and 85,36%. some were revealed to have mixed infections: cytomegalovirus Extremely low body weight was revealed at 77,33% of newborns, infection at 32,92% of women, mycoplasmal at 24,39%, HSV very low body weight at 22,96%. at 19,51%, an ureaplasmal infection at 18,29% and chlamydial infection at 17,07%. At entering an obstetric hospital 55,06% CONCLUSION of women had a heavy state, from them concerning a heavy In the Republic of Sakha (Yakutia) the group of risk for preeclampsia of 87,33%. The reasons of super early premature super early premature birth consists of women with chronic birth were: preterm discharge of amniotic fluid in 42,6% of cases, diseases, perinatal losses in anamnesis, with a carriage of antenatal death of fetus in 18,6% of cases, a premature separation sexually transmitted infections. The main reason for such of placenta in 14,23% of cases, cervical incompetence in 6,06% childbirth are: preterm discharge of amniotic fluid and the and threat of fetus asphyxia in 9,13% of cases. emergency birth delivery concerning a heavy preeclampsia. Independent childbirth at 18,74%, an operational birth by The survival of newborns with super early premature birth Cesarean section at 81,26%. Urgent birth delivery at 13,41%. in the term of 22-24 weeks had made 20%, and in the term Studying recommendations to the emergency birth delivery has of 27 weeks was higher by 4 times – 85,36%. As one of the revealed that the main indications for an early birth delivery in main reasons for super early premature birth is infection, it is the term of 22-27 weeks were: heavy preeclampsia at 38,63%, necessary to introduce obligatory free preconception inspection separation of normally located placenta at 19,1% and preterm for sexually transmissible infections. In cases of probable early discharge of amniotic fluid at 16,23%. birth forecast owing to the complicated course of pregnancy Prevention of a respiratory distress syndrome was fully of probable premature birth – obligatory hospitalization to carried out to 85%. hospital of the third level, to create conditions for prevention In the analysis of perinatal outcomes of 82 cases of super of respiratory distress syndrome of fetus and rendering the early premature birth it was revealed that a still birth are 12 newborn of medical care of proper level. Long dispensary (14,64%) cases, the antenatal death of fetus made 8 (66,66%) supervision of women of childbearing age with preeclampsia of them, the intranatal death of fetus made 4 (33,33%) cases. and premature birth in anamnesis, their rehabilitation and From 70 born alive early neonatal mortality in 11 (15,71%) family planning are also necessary. cases. The survival had made 84,28%. The detailed analysis of outcomes of super early premature REFERENCES birth on terms showed the following. Totally 12 cases of childbirth 1. Sidelnikova V.M. “Premature birth. Prematurely born child”. / V.M. Sidelnikova, A.G. at the term of 22-24 weeks of pregnancy, from them 7 (58,33%) Antonov // Publishing group “GEOTAR-Media”-2008. stillborn, from them 3 (42,85%) a cases of intranatal death of 2. Khodzhaeva Z.S. “Effectiveness of application of new diagnostic tests for definition of fetus and antenatal death in 4 (57,14%) cases. From 5 born alive birth activity start and preterm discharge of amniotic fluid” / Z.S. Khodzhaeva, V.M. 4(80%) had died in the early neonatal period. The survival had Sidelnikova // Questions of gynecology, obstetrics and perinatology, 2007, t.6, No.1, made 20%. 47-51 Totally 28 cases of childbirth at the term of 25-26 weeks of 3. Sukhorukova O.I. “Prevention of premature birth” / O.I.Sukhorukova // Obstetrics and pregnancy, from them 4 (14,28%) stillborn, from them antenatal gynecology, 2012, No.7

ADDRESS FOR CORRESPONDENCE: Baisheva N. S. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Ojunsky street Ph. 8-924-6610093 [email protected]

522 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Mo rp h o l o gic a l a ssess m e n t o f n a ti v e m a l e s u b j ects ’ t h y r o i d b o d y in t h e rep u b l ic s a k h a (y a k u ti a ) in d i f f ere n t se a s o n s

Egorova A., Garmayeva D. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT Morphological analysis of macro-, microstructures of native male subjects’ thyroid gland in the Republic Sakha (Yakutia) in different seasons has been conducted. Macromorphometric indicators of native male subjects’ thyroid gland(specific weight, total capacity, linear indicators were specified in summer and winter seasons. Micromorphometric characteristics of structural components of native male subjects’ thyroid gland tissue was given in relation to different seasons. In this case native male subjects’ thyroid gland was as curtained as normoplastic mixed type of structure, indicators of outer and inner thyroid gland follicles diameter in winter period were slightly bigger than in summer period. The same tendency was observed when thyroid gland follicular-colloidal index was calculated. On the data obtained the attempt to assess season temperature factor impact on the thyroid gland structural indicators were made. This assessment might be used as morphological equivalent of the body adaptation processes in northern regions.

Key words: macromorphometry, micromorphemetry, thyroid gland, year seasons.

Wiad Lek 2015, 68 (4), 523-525

INTRODUCTION available scientific references the data referring to the study of Republic of Sakha (Yakutia) is one of the biggest territory body’s season adaptation on the basis of morphological indicators of the Russian Federation by its territory. By its natural and of native male subjects’ thyroid gland has not been found. territory conditions the republic is not comparable to any other Purpose of the study: to give season histomorphological regions of the world. More than 40% of the territory is situated characteristics of thyroid gland structural organization of native beyond the north of the Arctic Circle. male subjects in the Republic of Sakha (Yakutia). Almost all continental territory of the Republic Sakha (Yakutia) is based on integral centuries-long permafrost [7]. MATERIALS AND METHODS Natural environmental and climatic conditions of Yakutia are In order to support objectives of this search thyroid glands of mainly characterized as extreme one. Sharply continental climate 45 dead male bodies, representatives of indigenous nationality is specified by long winter and short summer periods. One of the on the territory of the Republic of Sakha (Yakutia) have been main exogenous factors of the northern latitudes which might evaluated for the period January 2007 to August 2012. According cause ambrosia of regulatory and compensatory mechanisms, to human ontogenesis age periodization adopted at the VIIth dyscrasia, and metabolic disturbance of the body as the integral All-Soviet Union Conference on Age Morphology Problems, whole is cold. In these conditions, health preservation of the Physiology and Biochemistry (1965) the second adulthood age population of the Sakha Republic, theoretically based preventive has been assessed. measures directed to optimize the adaptation process in cold Died as a result of a violent and sudden death with no injuries regions of the world are still urgent questions to be considered of neck have been the subjects of the research. and worked out. Material samplings were done in summer (June, July, August) Neuroendocrine system where thyroid body is one of the time and winter (December, January, February) time on the base considerable components fulfills specific functions in adaptation of State Budget Establishment “Bureau of Forensic Medicine coping reactions of the body. The importance of the latest is proved and Mortem Department of Republican Hospital№1- National by the fact that under hypothyroidism of endogenous iodinated Medical Center of the Republic Sakha (Yakutia). thyroid hormone the intensity of metabolism decreases as well as Autopsy was conducted during the first 12-24 hours after the body temperature when the hyper function of thyroid body death. Information about the samplings was obtained from causes opposite effect [4,5]. In accordance to this the thyroid protocols, personal data. According to reports none lifetime and disease is to be studied as the marker of ecological trouble. In postmortem pathology of thyroid gland was diagnosed.

523 Egorova A, Garmayeva D.

Fig.1. Diagram of indigenous people micromorphometric parameters of thyroid gland in summer and winter seasons.

Thus, all studied bodies were divided into 2 groups: Thyroid gland morphometry was studied by its structural 1st group – persons who died in summer time from mechanic and functional components’ quantitative assessment referring injuries incompatible with life and who did not have any pathology to recommendations given in scientific references [6]. Thyroid of thyroid gland during their lifetime; gland structural components’ analysis (average outer and inner 2ndgroup – persons who died in wintertime from mechanic diameter of the follicle, the average height of follicular thyrocytes, injuries incompatible with life and who did not have any pathology follicular thyrocytes area, area of colloid, the core area of follicular of thyroid gland during their lifetime. thyrocytes)was conducted with licensed software, specialized for Macromorphometric method of research: during the postmortem morphometric histologic research of specimen «Screen Meter». examination of a corpse thyroid gland was properly separated, Secondary indicators were calculated basing on first indicators. its topographic and anatomic characteristics were registered Colloid accumulation index (CAI) indicator, follicular colloid- (perspective view and sectional). Thyroid gland was weighed on index (FCI) indicator, nuclear – cytoplasmic index (NCI) indicator the scales ВЛКТ-500 up to 0,01 gr. Further linear parameters of were determined. both lobes were measured (height, width, thickness).Absolute mass (AM) (gr) and relative weight (RW) of thyroid gland were RESULTS AND DISCUSSION determined. The formula RW(TB) = Absolute mass (AM), gr/ Thyroid gland macro morphometric data of indigenous people in mass, kg x 100% was used. For thyroid gland dynamics study we summer and winter periods: The thyroid gland is typically located determined thyroid volume with the formula: V= а·b·с·0,479,where on the front surface of the trachea and consisted of two lateral a – length, b- width, c – thickness of thyroid body shares, 0,479– lobs connected by an isthmus. Sometimes pyramidal process was correction ellipsoid factor. defined. The thyroid gland was surrounded by visceral fascia of the Histomorphometric method of research: pieces of thyroid gland neck and enclosed in a dense fibrous capsule. The thyroid gland tissue the size of 10 x 10 x 5,0mm were excised from middle part of was smooth to the touch and had elastic consistence. The tissue on both lobes(right and left at the same level). The material was fixed in the cut was light chocolate brown. After linear dimensions of the 10% neutral formalin during 24 hours, then embedded in paraffin thyroid gland we restudied the average values were determine. As block with the unit «Leica EG 1150H». Four five micron thick thyroid gland weight is one of the it’s morphologic state indicators, sections were made from paraffin blocks with the sledge microtome we determined average thyroid gland (TG) absolute weight (AW) «Leica SM 2010R». The sections were deployed in water bath and indicator. So for indigenous people in summer period it was replaced to the micro slides. The sections for histologic research were 24,90±1,96 gr and in winter period 22,48±0,61 gr. The calculation colored with hematoxylin and eosin. When histologic specimen we of the average value of relative weight (RW) was in summer period restudied the type of thyroid gland structure was determined, as well 39, 00±2, 73%, in winter period 39,09±1,58% [3]. as its structural components which are morphological equivalents Thyroid gland micromorphometric data of indigenous people in of thyroid gland functional state. summer and winter periods: Microscopic examination of thyroid

524 Mo r p h o l o g i c a l a s s e s s m e n t o f n a t i v e m a l e s u b j e c t s ’ t h y r o i d b o d y in t h e r e p u b l i c s a k h a (y a k u t i a ) in d i f f e r e n t s e a s o n s gland tissues in study groups showed that their histologic structure CONCLUSION belongs to normoplastic mixed, middle follicular type. According to The data obtained proves the statement that thyroid gland the author GrigorievaV.A. (1970) [2], thyroid gland of normoplastic possesses specific plasticity when human body adapts to the mixed type is not fully mature and corresponds to inverse growth environmental conditions [6]. When thyroid gland histomorphologic where there is regular development in one parts and suppression analysis of indigenous people of the Republic Sakha (Yakutia) was with negative environmental impact in other parts. conducted we detected that thyroid gland microstructure reacts The shapes of the follicles were mostly round, ovoid and irregularly to the seasonal temperature. It was proved by increase of such rounded shape. The average thyroid gland outer diameter of the indicators as height, thyrocytes nuclei area, thyrocytes inner and follicle of indigenous people in summer period was 57,01±2,33 mkm, outer diameter follicles, follicular colloid index in winter time that is 1,05 times less than in winter period 60,87±1,42 mkm. The in comparison with summer time. Where in the increase of the average thyroid gland inner diameter of the follicle in summer follicular colloid index indicator can be explained as functional period was proved to be less 37, 92±1, 89 mkm, than in winter tension of thyroid gland which is necessary for maintenance of season of the year41, 68±1, 38 mkm. Thyroid gland follicular proper activity level in this season of the year [1, 7, 8]. epithelium had cubic form. Average height of the latest in summer period was 5, 84±0, 19 mkm, and in winter period 4,80±0,21mkm REFERENCES (р<0,05). The study of medium-sized areas of follicular thyrocytes 1. Khmel’nitsky O.K. Metodologicheskiye podkhody k morphologicheskim issledovaniyam of indigenous people in summer period was 3, 19±0, 10%, that endokrinnoy systemy cheloveka. / Khmel’nitsky O.K. Medvedev Y.A. // Arkhiv patologii.- is 1, 14 times bigger than in winter season of the year. Thyroid 1969.-T.21.-№ 5. -P. 15-26. gland cell nuclei thyrocytes were predominantly round, oval, 2. Kaznacheev V. P. // Sovremennye aspect adaptacii. – Novosibirsk, -P. 1980.-190. monochrome, located centrally in summer period 1,04±0,04%, 3. Panin L.E. Izmeneniye psychosomaticheskogo statusa cheloveka v usloviakh vakhtovogo in winter period 0,86±0,05% (р<0,05). The calculation of average truda. / Panin L.E. Valov R.P. Chukhrova [et al.] // Physiologia cheloveka. -1990.-T.16.- indicator of nuclear – cytoplasmic index (NCI) showed equal values №3-P. 107-113. in summer and winter seasons of the year. Follicles were filled with 4. Savvinov D.D. Ecologicheskaya besopasnost’ – element suverenizacii respubliki Sakha homogeneous eosinophilic colloid. When the average indicator (Yakutia) / Savvinov D.D // Nauka RS (Y): sostoyaniye, resultaty, problem. Nauchn. red. of colloid area was calculated, the result in summer period was Petrova P.G.: sb. nauch. st. –Yakutsk, 2001. –P. 196. 1,05 times less than in winter period. Average indicator of thyroid 5. Yegorova A.I. Macromorphometriya sh’itovidnoy zhelezy vsroslogo naseleniya Yakutii gland follicular colloid index (FCI) that determines functional NII morphologii cheloveka. / Yegorova A.I. Garmayeva D.K. // Moskva, 2014.-P.96-99. activity of thyroid gland among indigenous people in summer 6. Grigorieva V. A. // Materialy po vosrastnoy morphologii sh’itovidnoy zhelezy g. Kalinina season was 5,94±0,52, that is significantly lower than in winter avtoref. dis. kand. med. Nauk . Kalinin.1970. 24p. season (9,07±0,65) (р<0,05). When colloid accumulation index 7. AvdeenkoY.L. // Morphoecologicheskaya kharakteristika sh’itovidnoy zhelezy vsro- (Brown’s index) of indigenous people was assessed, it was defined slogo naseleniya Sankt-Peterburga. avtoref. dis.kand. med. nauk. Sankt – Peterburg that this indicator does not change and constitutes 11,13±0,51 2003.12p. (Fig.1). 8. Khmel’nitsky O. K. Morphoecologicheskaya kharakteristika zabolevanii sh’itovidnoy zhelezy v razlichnykh regionakh Rossii i Belorussi po dannym operacionnogo materiala / Khmel’nitsky O. K. Tretyakova M. S. Kiselev A.V. [et al.] // Arkh. pat.-2000.-T.62.-№ 4. -P.19-27.

ADDRESS FOR CORRESPONDENCE: Egorova A. Russia, Republic of Sakha (Yakutia), 677000, Yakutsk city, 36 Kulakovskogo St., Ph. 89841006527 [email protected]

525 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

X-r a y d e n sit o m etr y a n d f r a x m o d e l in pre d icti n g t h e ris k o f o ste o p o r o sis a n d l o w -e n erg y f r a ct u res in p o st m e n o p a u s a l w o m e n

Epanov V.V., Palshin G.A., Epanova A.A., Komissarov A.N., Tomsky M.I., Sedunov V.F., Egorov P.L. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a .

ABSTRACT 88 people of 50 years of age and older were put in this cross-sectional study. The main risk factors for osteoporosis and bone fractures were obtained using questionnaires. X-ray absorptiometry of the distal forearm was carried out with the help of Osteometer DTX-200. The FRAX tool was used for calculation of the 10-year absolute risk of major osteoporotic fractures. In the 50-59 year age group osteoporosis was found only in 30% of women but with increasing age its occurrence increases dramatically approaching 70% in women 70 years of age and older. The higher the age of women, the lower bone mineral density (r = -0,44, p <0,001).

Key words: osteoporosis, osteopenia, the risk of osteoporotic fractures, cross-sectional study.

Wiad Lek 2015, 68 (4), 526-528

INTRODUCTION exposure and the development of vitamin D in the body, which Currently, the systemic osteoporosis is one of the most common impairs the absorption of consumed calcium. In healthy children diseases of great medical and social concern. According to and adolescents in Yakutia in winter the average vitamin D level epidemiological studies in most countries the fracture frequency is 14 ng / ml. However in winter vitamin D deficiency is seen normalized to age in both sexes during the last 50 years increases. in 60% of healthy children and in 10% of children in summer Considering the rate of increase of this parameter to be constant [2]. Regional retrospective study analysis on the epidemiology and taking into account the increase in life expectancy, we can of fractures holds potential for the organization of targeted expect double increase in the annual number of fractures by therapeutic and preventive measures in high-risk groups against 2025. the background of osteoporosis [3]. The studies were conducted The incidence of osteoporosis in women over 50 steadily with the help of the development program of NEFU. increases with age, by age 80 70% of women suffer from osteoporosis, Goal of research: To examine the state of bone mineral density and osteopenia is found in 27%. During the non-serial densitometry in postmenopausal women living in Yakutsk. study of the distal forearm in 673 residents of Cheboksary at the age of 50 and older, OP was identified in 16.3% of cases, while a MATERIALS AND METHODS severe form of OP was found in more than one in three patients Based on gender sampling a group of 88 women of 50 years with OP (36.7%), the proportion of osteopenic syndrome was of age and older residing in Yakutsk. All of the women were 32.2%. People with normal BMD were significantly younger postmenopausal. In the framework of this study we carried out than patients with reduced BMD (58,4 ± 6,3 versus 62,7 ± 7,8 a double X-ray absorptiometry of the distal forearm of the non- years, χ2 = 20,28, pK-W <0,0001) [1]. dominant hand using densitometer DTX-200 («Osteometer», However, a particular group in the age structure of disease Denmark, United States). To identify risk factors for osteoporosis is people of young age. In this regard, the study of osteopenic we provided questioners taking into account all risk factors syndrome in this category of people is of particular importance, including the factors used to calculate FRAX model. The FRAX as a decrease in bone mineral density is the most important factor model calculates the absolute ten-year probability of typical in the development of osteoporotic fractures later. Though... «to osteoporotic fractures. To interpret the results when evaluating judge the prevalence of osteoporosis and fractures associated with BMD in postmenopausal women of 50 years of age and older we it in Russia according to official statistics is almost impossible. used the WHO densitometric classification. According to the Patients with fractures of the proximal femur may not seek WHO recommendations (1994) the results of densitometry were medical care at all. There are no registers of patients with evaluated as “normal” at T-score +2,5 SD to -0,9 SD of peak bone osteoporotic fractures in Russia» [4]. Yakutsk is located at 62° mass; “osteopenia” at T-score of -1,0 SD to -2,4 SD; “osteoporosis” north latitude where winter duration is up to 7 months with at T-score -2.5 or less SD. And “severe osteoporosis” at T-test -2,5 its short daylight hours and it is not conducive to adequate sun SD and below with a history of one or more marker fractures.

526 X-r a y densitometry a n d f r a x m o d e l in p r e d i c t i n g t h e r i s k o f osteoporosis a n d l o w -e n e r g y f r a c t u r e s in postmenopausal w o m e n

Statistical analysis is performed using standard statistical software package Statistica 6.0 and MS Excel 2007 of Windows XP. The quantitative data are presented as the mean (M) ± SD. Student-t criterion (p) was used. The calculations were performed using Statistica 6.0

RESULTS The average age of the surveyed women was 63,0 ± 6,9 years. The frequency of complaints by women aged 50 and older showed that the increased frequency of complaints starts in the 55-59 year age group, n-15 (17%), the frequency of complaints reaches its peak in the 60-64 year age group, n-30 (34%), followed by a Fig. 2. The share of OP and osteopenia syndrome in surveyed women residing in decrease in the 65-69 year age group, n-17 (19.3%). Yakutsk. The prevalence of OP and osteopenia of the distal forearm in women of 50 years of age and older is shown in Fig. 1. According to the results of densitometry of distal forearm BMD reduction was found in 71 women (81%). Thus, osteoporosis was diagnosed in 54% of women; the proportion of osteopenic syndrome was 27%. 19% were people with normal BMD and they were significantly younger than patients with reduced BMD. According to available data in the literature in postmenopausal women of 50 years of age and older, the processes of destruction of bone strengthens and only by 65 years it is reduced [5]. In the 50-59 year age group osteoporosis was found only in 15% of women, but with the increase age its occurrence increases dramatically approaching 70% in women of 80 years of age and older [7]. In this regard, to assess the prevalence of OP and osteopenia in women after the menopause in 10-years age subgroups was of great interest. According to the results of our study in the 50-59 year age Fig. 3. Status of the IPC in those 50 years of age and older with the BMI group 30% of women were diognosed with OP but with increasing age it increases dramatically approaching 70% in women of 70 years of age and older. The higher the age of women, the lower the BMD (r = -0,44, p <0,001). Low body weight (low BMI) is recognized as an indicator of low BMD and fracture predictor [5]. OP detected significantly It must be noted that virtually every third patient having a more often in patients with a lower body mass r = 0,528, body weight less than 57 kg, and / or BMI of less than 20 kg/m2, p <0.001 Fig. 3. already had a history of previous fractures associated with minimal trauma usually after falling from their own height. According to the results of previous studies “Osteoskrining Russia” 76% of women have more than one risk factor for osteoporosis and osteoporotic fractures. Risk factors such as BMI<20 were found in 2% of women; history of fractures in 31%; smoking in 6%; alcohol in 0.3% [6]. Clinical osteoporosis risk factors were identified in almost all the surveyed women (99.7%), the average rate of one woman of 50 year of age and older accounted for 3,1±1,4. In our study the risk factors such as low BMI, history of fractures, alcohol abuse, smoking are more common than during the social program “Osteoskrining Russia” [6]. In accordance with the results of densitometry and standard assessment of OP risk factors in 75% of cases the antiresorptive

therapy and combined calcium and vitamin D3 is required. The revealed correlations between age and BMD, between Fig. 1. The prevalence of OP and osteopenia in women of 50 years of age and older (based age and the 10-year absolute risk of major osteoporotic fractures on densitometry of distal forearm). Fig. 4.

527 Egorova A, Garmayeva D.

density, which requires a more in-depth study of the endocrine system. Thus, the need for further regional studies of bone tissues remodeling, the epidemiology of fractures associated with osteoporosis and bone mineral density among residents living in the Far North.

CONCLUSION 81% of surveyed women had a deficit of the bone mineral density of varying severity, with osteoporosis diagnosed in every second woman (54%). The follwing risk factors for osteoporosis such as BMI <20 kg/m2, the previous low-energy fractures, Fig. 4. Correlation between age and BMD, and between age and 10-year absolute risk of early menopause are more common than others. The diseases major osteoporotic fractures of kidney, gastrointestinal tract, endocrine system take leading positions among somatic diseases. The higher the age of women, the lower the BMD (r = -0,44, p <0,001) and the higher the 10-year absolute risk of major osteoporotic fractures (r = 0,37, p<0,001). Up to 75% of surveyed women are in need of drug assignment to treat and prevent osteoporosis.

Studying the correlative relationship of BMD, the age of REFERENCES surveyed women and FRAX data showed a direct correlation: 1. Bashkova I.B. The prevalence of osteoporosis and osteopenia of distal forearm and the the older the age, the lower bone mineral density (-0.44; p risk of osteoporotic fractures in the residents of Cheboksary over the age of 50 years. <0.001) and the higher risk of major osteoporotic fractures (0.37, / Bashkova I.B., Madyanov I.V., Markova T.N. [et al.] // Bulletin of the University of p <0.001) and the risk of fractures of the proximal femur (0.44; Chuvashia. Natural and engineering sciences. – 2012. – №3. – P. 296-303. p <0.0001). 2. Lesnyak O.M. An audit of the problem of osteoporosis in the Russian Federation / Lesnyak O.M. // Preventive Medicine, 2011. – № 2. -P.7-10 DISCUSSION 3. Krivoshapkina D.M. Specifics of calcium – phosphorus metabolism in minor orthopedic The results indicate high incidences of osteoporosis and pathology in children / Krivoshapkina D.M. // Yakutsk Yakutsk Medical Journal. – № 4. osteopenia syndrome among women of 50 years of age and – 2003. – P.10-13. older residing in Yakutsk, it is most likely due to the climatic 4. Krivova A.V. The dynamics of the incidence of fractures of the proximal femur. / Krivova A.V., and geographical peculiarities of the region where the short Rodionova S.S. // Osteoporosis and osteopathy, 2007. – №1, Volume 1. – P. 2-5. daylight hours and critically low temperatures limit physical 5. Lesnyak O.M. Osteoporosis. Diagnosis, Prevention and Treatment: Clinical guidelines / activities and contribute to hypodynamia and as a consequence edited. Lesniak O.M., Benevolensky L.I.// M.: GEOTAR Media, 2010. P. 272. lead to deficiency in the processes of bone tissues remodeling. 6. melton L.J. Perspectives: how many women have osteoporosis now? / Melton L.J. // The study results confirm that the older a woman, the lower J. Bone Miner. Res. 1995. V. 10. Р. 175-177. bone mineral density. At the same time some patients were 7. Nikitinskaya O.A. The social program “Osteoskrining Russia” in action. / Nikitinskaya O.A., I-III degrees obese and showed normal indices of bone mineral Toroptsova N.V. // Farmateka. 2012, № 6. – P. 100-103.

ADDRESS FOR CORRESPONDENCE: Epanov V. V. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street Ph. 89241770273 [email protected]

The studies were conducted with the help of the development program of NEFU

528 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Regi o n a l tre n d s in t h e w o r k i n g -a ge p o p u l a ti o n m o rt a l it y r a te in t h e rep u b l ic o f s a k h a (y a k u ti a ) in 1990-2012

Ivanova A.A., Kakorina E.P., Timofeev L.F., Potapov A.F., Aprosimov L.A. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a , n. a. s e m a s h k o n a t i o n a l r e s e a r c h i n s t i t u t e o f p u b l i c h e a l t h , r u s s i a

ABSTRACT Regions of the Russian Federation differ in climatic-geographic, medical-demographic and social-economic situations [1]. One of the regions with distinct peculiarities is the Republic of Sakha (Yakutia). Ranking first by the territory (3,103.2 thousand sq.km), Yakutia is on the 81th place by the population density among regions of the Russian Federation (0.3 people per 1 km2). Yakutia is one of the most isolated and inaccessible regions of the world: 90% of the territory lacks all-the-year-round transportation. Regions of the republic, as well, differ significantly in the climatic conditions and the levels of social-economic development, which influences the population health indicators, including mortality. This survey aimed to study the trends of mortality in the working-age population in different groups of regions. To do this, basing on the statistical data, we compared the levels, trends and structure of mortality in 1990-2012. It was established that the different groups of regions show a significant variation in the working-age population mortality, depending on the social-economic conditions. Since 2000, the Arctic group of regions has demonstrated higher mortality in working-age men and women, especially of cardiovascular and digestive system diseases, and external causes. Lying beyond the Arctic Circle, these regions have severe conditions and a relatively low level of social-economic development. As for the rural regions, despite the relatively favourabe situation, they also show a high level of mortality of external causes. The industrial regions are characterized by higher social-economic development, better transport infrastructure, a satisfactory material base of medical institutions. They also have sufficient resources of health institutions, including the staff and modern equipment for treatment and diagnostics, as well as, which is critical, the full range of medical specialists. Thus, these regions demonstrate lower population mortality; however, there is still mortality of infectious diseases, neoplasms, and respiratory diseases.

Key words: working-age population, mortality, causes of mortality.

Wiad Lek 2015, 68 (4), 529-533

INTRODUCTION (Yakutia), published by the Territorial Unit of the Federal State One of the regional features of the Republic of Sakha (Yakutia) Statistics Service in 1994-2012; demographic yearbooks of the is that along with the favourable situation with the birth rate Republic of Sakha (Yakutia); reports on mortality in 2000-2012. and natural population increase, premature mortality is an The continuous method was used to characterized the level, acute problem: there is a high human loss in young-age groups structure and trends of mortality in the working-age of the and the working-age group [2]. The mortality rate in children republic’s population, and there was done a comparative analysis of 0-17 years (1.2 per 1,000 people of the relevant age) is 25% of the parameters by different medical-economic groups: Arctic, higher than the index for the Russian Federation (0.9‰); infant industrial, and rural. The groups of regions were formed basing mortality (9.6 per 1,000 of born alive) – by 14.6% (8.2‰); in on the medical-economic zoning of administrative-territorial working-age population – by 12.0% (649.4 and 575.7 per 100 units of the republic [4]. thousand people, respectively). Different groups of the republic’s regions show significant differentiation in the mortality rates RESULTS AND DISCUSSION due to their social-economic conditions, territorial differences The annual loss of the working-age population in the republic in the supply of resources, and the medical and preventive aid makes over 40%of the total: in 1990 – 44.2%, in 2010 – 46.9%, provision [3]. Aim: to study peculiarities of the mortality trends in 2012 – 43.0%. The evolution of the working-age population in the working-age population in different groups of regions of mortality rate in Yakutia in 1990-2012 is presented in Table I. the Republic of Sakha (Yakutia) in 1990-2012. In general, over the studied period (1990-2012), the working- age population mortality rate in the republic remained stably high MATERIALS AND METHODS without reliable (t observed < t-critical, with the significance level The main sources of information were the reports on the 0.05). Statistically significant changes of the indicator (Student’s age and sex composition by regions of the Republic of Sakha t-test, t observed = 8.1 at critical t = 1.972) were seen in 1994,

529 Ivanova A.A., et al.

Table I. Dynamics of the working-age population mortality rate in the Republic of Sakha (Yakutia) (per 1,000 people of the relevant age). Republic of Sakha (Yakutia) Russian Federation Years Both genders Men Women Both genders 1990 4.9 7.5 2.0 4.9 1991 5.0 7.4 2.3 5.0 1992 6.2 9.5 2.5 5.8 1993 7.1 11.0 2.8 7.4 1994 8.0 12.3 3.1 8.4 1995 8.0 12.8 3.2 8.0 1996 7.4 11.2 3.2 7.1 1997 6.7 10.2 2.9 6.3 1998 6.6 9.9 3.0 6.1 1999 7.2 10.9 3.3 6.8 2000 7.3 11.3 3.2 7.3 2001 7.9 12.2 3.4 7.5 2002 7.8 12.1 3.5 6.8 2003 7.7 12.0 3.4 7.2 2004 7.7 12.0 3.4 7.2 2005 7.0 11.0 3.2 8.3 2006 7.2 11.1 3.3 7.5 2007 6.8 10.6 2.9 7.0 2008 7.2 11.2 3.1 6.9 2009 7.3 11.1 3.2 6.4 2010 7.2 11.2 3.1 6.3 2011 6.8 10.3 3.0 6.0 2012 6.5 10.0 2.7 5.7

and 1995 (the rate per 1,000 people 8.0±0.07), and in 2001 causes led to the death of almost every second died man in the and 2005 (7.8-7.9 per 1,000 people). Further, until the end of working age (42.1%) and every third died woman (28.7%). This 2010, there was stagnation of the figures without any significant problem largely stems from excessive drinking and alcoholism, changes. As of 2012, the parameters decreased, yet they remain as well as a deteriorated criminal situation both in the in the higher than the 1990 figures by 24.6% for the both genders, by country as a whole and the republic. The analysis of the causes 25% for men, and by 26% for women. The trend curve for the related to alcohol abuse (accidental poisoning, alcohol addiction, working-age male mortality rate echoes the one for the both alcoholic psychosis, and hepatic cirrhosis due to alcohol abuse) genders, which shows that the male supermortality determines also signals that working-age men are the category that is the the high level of the working-age mortality rate; the working- age female mortality rate in the period 1996-2011 remained almost the same (Fig. 1). Over the entire studies period, injuries and poisoning (38- 39%) ranked first among the causes of death in the working-age population, followed by cardiovascular diseases and neoplasms; the situation was different in 2010, only, when the mortality rate of cardiovascular diseases exceeded all other causes (Table II). In 1990-2012, in the causes distribution, there has been an increase in the mortality rate of certain infectious and parasitic diseases – by 35.6%, cardiovascular diseases – by 2 times, respiratory diseases– by 53.3%, digestive diseases – by over than 2 times, external causes – by 1.8%. As for the gender differences, the working-age male mortality rate exceeded the female mortality rate in the same age group by 4 times. In 2012, men made 80.3% of the total number of Fig. 1. Working-age mortality rate trend in the Republic of Sakha (Yakutia in 1991- the dead in the working age (four in every five dead). External 2012.

530 Re g i o n a l t r e n d s in t h e w o r k i n g -a g e p o p u l a t i o n m o r t a l i t y r a t e in t h e r e p u b l i c o f s a k h a (y a k u t i a ) in 1990-2012

Table II. Mortality indices for the working-age population by main and particular causes in the Republic of Sakha (Yakutia) (per 100,000 of working-age people). Causes of death 1990 1995 2000 2005 2010 2011 2012 Died of all causes 487.5 818.3 737.9 773.6 725.5 679.0 649.4 Some infectious and parasitic diseases 11.8 20.9 18.6 17.5 12.5 16.9 16.0 Neoplasms 78.6 87.2 78.4 79.0 64.2 67.1 73.9 Cardiovascular diseases 108.4 206.0 193.2 264.2 260.3 231.0 218.9 Respiratory diseases 15.2 27.1 28.4 30.5 23.4 24.6 23.3 Digestive diseases 18.7 56.0 40.9 43.9 55.9 46.7 42.7 External causes, 324.2 291.7 252.9 240.1 225.2 221.3 including: - road accidents 350.1 24.0 28.6 19.6 26.3 23.8 - suicides 68.9 67.0 56.1 56.0 55.0 - homicides 74.8 70.5 47.7 39.7 40.0

most vulnerable to alcohol abuse. With the general increase of group – in 2005, only; in the industrial group – in 1994-1995 the morality rate due to this group of causes (from 11.0 cases (t-observed 11.1 at t-critical = 1.972, р<0.05). per 100,000 of people in 1990 to 65.9 cases in 2010), the relevant With the working-age mortality index lowest in the Arctic indices for the working-age male mortality rate made 25.2 and regions in 1990, starting from 2000, this index significantly 118.6 cases, respectively; in women – 6.5 and 33.1 exceeded those of the rural and industrial groups and the republic In the individual causes of death distribution, the working as a whole (Table III). age group share is a dominant one. For instance, among people In 1990, the rural group of regions demonstrated the highest died of tuberculosis, the working-age ones account for 73.0%; level in the republic (5.4 per 100 thousand of the working-age mental disorders – 50.0%; external causes – 82.5%; suicides – population); by 2012, it had increased to 7.0‰ (by 30%), which 87.1% (Fig. 2). is 43.0% less than in the Arctic group, and by 17.0% more than The retrospective analysis of the working-age people mortality in the industrial one. rate in the Arctic, rural and industrial groups of regions of the It is worth noting that the Arctic regions show the highest republic shoed significant variations in the indices. Thus, the mortality indices in the republic in both men and women of figures of the working-age mortality rate in the studied period the working age (Table IV). According to the 2012 data, the increased in all the compared groups: the rural group – by 29.6%, mortality index of working-age men in the Arctic zone was Arctic – by 152.5%, industrial – by 18.4%, over the republic – by 26.2% higher than that of the rural group, and by 37.9% of the 32.7%; with the statistically reliable increase noted in the Arctic industrial one; the mortality index of women was by 44.2% and group (t-observed 11.3 at t-critical = 1.972, р<0.05), in the rural 55.8% higher, respectively. In the beginning of the study, the rural group had the highest mortality index of working-age men (8.0 per 100 thousand people) in the compared groups, but in 2012, it became less than in the Arctic group by 35.5% (10.7 and 14.5. respectively). The mortality index of working-age women remained almost the same over the period 1990-2012 (2.8 and 2.9 per 100 thousand working-age people); however, as of 2012, it exceeded the republic’s average by 6.9%. Almost over the entire studied period, the industrial group had the lowest working-age mortality rate for both genders and a relatively slow growth speed (by 18.0%); since 2000, these regions have had the most favourable situation with the working-age male and female mortality. The share of the dead in the working age makes 41.8%; (in the rural – 42.8%, in the Arctic – 53.6%). The analysis of the main classes of mortality causes in the working-age population revealed that the Arctic regions still face a pressing problem with cardiovascular diseases, digestive diseases, and external causes (Table V). For example, the mortality index of cardiovascular diseases Fig. 2. Share of the working-age dead of individual causes. exceeds the same indices of the rural and industrial groups by 1.6

531 Ivanova A.A., et al.

Table III. Working-age mortality rate in different groups of regions of the Republic of Sakha (Yakutia) (per 1,000 people of the relevant age and gender). Groups of regions 1990 1995 2000 2005 2006 2007 2008 2009 2010 2012 Rural 5.4 7.3 6.9 7.9 6.8 7.2 7.4 7.9 7.5 7.0 Arctic 4.0 8.3 8.9 11.3 9.9 10.2 11.3 11.0 11.8 10.1 Industrial 4.9 8.3 6.8 7.0 6.9 6.1 6.5 6.4 6.6 5.8 Republic of Sakha (Yakutia) 4.9 8.0 7.3 7.8 7.2 6.8 7.2 7.3 7.2 6.5

Table IV. Mortality indices of men and women of the working age in different groups of regions in 1990-2012 (per 1,000 people of the relevant gender and age). 1990 1995 2000 2005 2010 2012 Groups of regions men women men women men women men women men women men women Rural 8.0 2.8 10.9 3.3 11.3 3.2 12.2 3.3 11.4 3.2 10.7 2.9 Arctic 7.0 2.4 12.3 3.7 12.6 4.4 17.1 4.8 17.2 5.7 14.5 5.2 Industrial 7.3 2.2 12.8 3.2 10.4 3.0 11.0 2.9 10.5 2.7 9.0 2.3 RS (Y) 7.4 2.3 12.2 3.3 10.4 3.2 12.2 3.2 11.2 3.0 10.0 2.7

Table V. Mortality indices of the working-age population of certain main causes in different groups of regions (per 100,000 people of the relevant gender and sex).

Infectious Cardiovascular Respiratory External Groups of regions Neoplasms Digestive diseases All causes diseases diseases diseases causes Rural 10.0 70.3 216.0 20.6 37.7 284.0 696.5 Arctic 7.0 71.1 345.7 14.7 56.4 404.5 1012.6 Industrial 20.0 75.0 204.2 27.0 43.0 176.4 581.4 RS (Y) 16.0 73.9 218.9 23.3 42.7 225.2 649.4

times, of digestive diseases – by 1.5 and 1.3 times, respectively, people share and the continuing migration loss of the working- of external causes – by 1.4 and 2.3 times. age people, it has a negative impact on formation of the labour The working-age population mortality in the rural group due force of the republic. to the main causes is comparable to the average republic’s figures, except for external causes, whose index is 20.7% higher than the REFERENCES: regional one and 37.9% than that of the industrial regions. 1. Shchepin, O.P. Sovremennaya medico-demograficheskaya situatsiya v Rossii (Current The industrial group showed relatively high mortality rates medical-demographic situation in Russia) / O. P. Shchepin, V. B. Belov, A. G. Rogovina of infectious diseases, neoplasms, and respiratory diseases. // Problemy sotsialoi gigieny, zdravookhraneniya i istorii meditsiny (Probl Sotsialnoi Gig Istor Med). – 2009. – № 6. – P. 3–8. CONCLUSION 2. Ivanova A.A. Mediko-demograficheskaya situatsiya v arkticheskikh rayonakh Respubliki Therefore, the republic still has the high mortality rate in Sakha (Yakutia) (Medical-demographic situation in the Arctic regions of the Republic the working-age population of both genders due to preventable of Sakha (Yakutia)) / A.A. Ivanova, L.F. Timofeev, A.F. Potapov, L.A. Aprosimova // causes (external causes, cardiovascular, digestive, respiratory, and Byulleten NII obshchestvennogo zdoroviya RAMN (Bulletin of the Research Institute infectious diseases). Given the growing trend of the pension-age of Public Health, RAMS), 2012. – Issue 4. – P.57-60.

532 Re g i o n a l t r e n d s in t h e w o r k i n g -a g e p o p u l a t i o n m o r t a l i t y r a t e in t h e r e p u b l i c o f s a k h a (y a k u t i a ) in 1990-2012

3. Ivanova, A.A. Sravnitelny analiz obshchei smertnosti naseleniya razlichnykh grupp 4. Timofeev, L.F. Zdarookhranenie territoriy s nizkoi plotnostiyu naselenuya: na primere rayonov Respubliki Sakha (Yakutia) v 2010 g. (Comparative analysis of the total mortality Respubliki Sakha (Yakutia) (Healthcare on territories with low population density; the rate in different groups of regions in the Republic of Sakha (Yakutia) in 2010) / A.A. case of the Republic of Sakha (Yakutia)) / L.F. Timofeev, V.G. Krivoshapkin. – Novosibirsk: Ivanova, L.A. Aprosimova, A.F. Potapov, L.F. Timoeev // Dalnevostochny meditsinsky Nauka, 2006. – 211 p. zhurnal (Far-Eastern Medical Journal). – 2012. – № 4. – P. 109-111.

ADDRESS FOR CORRESPONDENCE: Ivanova A., Russia, Republic of Sakha (Yakutia), 677000, Yakutsk city, 12, Sverdlov street, Ph. 8-924-762-2916 [email protected]

533 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Ad a pti v e m ec h a n is m s o f t h e i m m u n e s y ste m in c h i l d re n in f a r n o rt h

Ivanova O.N., Argunova, E.F., Alekseev S.N., Ystugina T.V., Varfolomeev A.R., Troev I.P, Kononova I.V., Egorova V.E. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT This article is devoted to the probleme of modern Pediatrics pathology of the immune system in children with complicated viral infections. The aim of this study was to investigate the immune and cytokine status in children with complicated acute respiratory viral infections. The study included 100 children are often ill respiratory virus infections ( more than 8 times per year) from age 0 to 7 years, and 30 children with upper respiratory tract infection; no more than 1 time per year-the control group. The standards of indicators developed by the staff of Immunological laboratory Diagnostic center of the Ministry of health of Republic Sakha (Yakutia ) together with the Institute of health of the Republic Sakha (Yakutia). Statistical calculations made on the basis of applied programs “SAS” and “SPSS” In the analysis of contingency tables (estimates of the correlation of the characteristic and evaluation of significance of differences between groups) used the criterion of 2 (Pearson and likelihood ratio and Fisher’s exact test. Comparison of mean values was performed univariate analysis of variance using T-student criterion for assessing the equality of mean F-Fisher test to assess equality of variance. Extreme climatic conditions of the far North have an impact on immunological mechanisms. In the analysis of changes of the immune status revealed the greatest decline in T-cell level and components of complement in children with complications of viral respiratory infections. In children with complicated respiratory viral infections reduced cellular immunity (CD3+, CD4+, CD8+, CD+, СD 22+). In children with complicated respiratory viral infections decrease levels of cytokines (IFN-γ FNO-ά), indicating about the risk of the formation of complications of respiratory viral infections. As a result of drug therapy of broncho-vaxom marked improvement in immune status and the absence of recurrence of respiratory viral infections within the next 3 months after therapy.

Key words: immunity, immunotherapy, viral infection, cytokines, immune status, Pediatrics, children, components of complement, complications, disease.

Wiad Lek 2015, 68 (4), 534-536

INTRODUCTION Determination of subpopulations of T – and b-lymphocytes Complications of viral respiratory infections in children are was performed by flow cytometry using the “Navios” using caused by abnormal immune system. The functional state of immune monoclonal antibodies. cells and the ability to form intercellular cooperation determine Determination of immunoglobulins was carried out on the the possibility of resistance to the immune system. Deficiency unit immolate. of these parts of the immune system develop complications of The level of IL-1, IL-13, FNO, IFN in serum were determined viral respiratory infections. using ELISA method, according to the instructions supplied with Question effective immunomodulation in children with the kits antibodies. Kits for the determination of interleukins viral respiratory infections attracts the attention of clinicians. by ELISA kits reagents “Pro Con IL-1”, “Pro Con IF gamma” The main objective is to reduce the number of viral respiratory (LLC “Protein contour” St. Petersburg). Principles of solid- infections. phase ELISA based on the fact that the enzyme horseradish The study of immunomodulation is an important task of peroxidase, covalently attached to antibodies, while maintaining contemporary pediatrics [1, 2, 3, 4]. the biological activity (the ability to interact with the substrate by binding with immobilized immune complex formed on MATERIALS AND METHODS “sensitized” holes, which were incubated your samples and The study included 100 children are often ill respiratory standard reagents. virus infections ( more than 8 times per year) from age 0 to 7 Statistical calculations made on the basis of applied programs years, and 30 children with upper respiratory tract infection; no “SAS” and “SPSS” In the analysis of contingency tables (estimates of more than 1 time per year-the control group. The standards of the correlation of the characteristic and evaluation of significance indicators developed by the staff of Immunological laboratory of differences between groups) used the criterion of 2 (Pearson Diagnostic center of the Ministry of health of Republic Sakha and likelihood ratio and Fisher’s exact test. Comparison of mean (Yakutia) together with the Institute of health of the Republic values was performed univariate analysis of variance using Sakha (Yakutia) (tab. I shows the age of children 0 to 7 years). T-student criterion for assessing the equality of mean F-Fisher All studies were conducted in the period of low temperatures test to assess equality of variance. The relationship between (winter). parameters was assessed using coefficients of the linear and rank

534 Ad a p t i v e m e c h a n i s m s o f t h e i m m u n e s y s t e m in c h i l d r e n in f a r n o r t h

Table I. Indicators of immune status in children of Sakha (Yakutia) in children group long-term and frequently sick. The performance Standards indicators Group children with respiratory tract Сhildren are rarely ill respiratory Indicators of Sakha (Yakutia) for children infection tract infection (n = 300) M ± m (n = 100), M ± m (n = 30) M ± M СD3+ 52,6 ± 1,7 21,3 ± 1,02* 26,1 ± 1,2* СD4+ 26,3 ± 0,7 13,2 ± 0,9* 24,4 ± 0,2 СD8+ 22,5 ± 0,23 15,2 ± 1,1 21,1 ± 1,2 СD16+ 23,2 ± 0,54 7,6 ± 1,1* 19,4 ± 1,3 IRI 1,18 ± 0,64 0,8 ± 0,02 1,1 ± 0,02 IgA 2,34 ± 0,69 1,4 ± 0,3* 1,9 ± 0,2* IgG 13,3 ± 0,16 10,2 ± 0,7 12,4 ± 1,3 IgM 1,6 ± 0,03 1,2 ± 0,09 1,06 ± 0,03* СD22+ 19,8 ± 0,16 10,9 ± 1,9 12,98 ± 1,54 С3 0,67 ± 0,12 0,21 ± 0,02* 0,42 ± 0,06 С4 0,34 ± 0,05 0,12 ± 0,02* 0,28 ± 0,04 CIK 96,8 ± 0,132 198,2 ± 1,5* 160,1 ± 2,4* IL-1 0,52 ± 0,03 0,41 ± 0,001 0,34 ± 0,09* IFN-γ 0,53 ± 0,02 0,16 ± 0,01* 0,48 ± 0,03* FNO-ά 1,12 ± 0,04 0,3 ± 0,01* 1,26 ± 0,008 *p < 0.05 between the standards and indicators obtained in each group.

Table II. Indicators of immune status in children of Sakha (Yakutia) in children group long-term and frequently sick after children with complication of respiratory viral infection drug therapy of broncho-vaxom.

Indicators of Children group with respiratory Indicators of Children group with respiratory Indicators viral infection before the drug therapy viral infection after the drug therapy of broncho-vaxom (n = 30) M ± M of broncho-vaxom (n = 30) M ± M

СD3+ 21,3 ± 1,02* 34,1 ± 1,2* СD4+ 13,2 ± 0,9* 27,4 ± 0,2 СD8+ 15,2 ± 1,1 19,1 ± 1,2 СD16+ 7,6 ± 1,1* 19,4 ± 1,3 IRI 0,8 ± 0,02 1,1 ± 0,01 IgA 1,4 ± 0,3* 1,6 ± 0,23* IgG 10,2 ± 0,7 17,4 ± 1,32 IgM 1,2 ± 0,09 1,06 ± 0,03* СD22+ 10,9 ± 1,9 18,98 ± 1,54 С3 0,21 ± 0,02* 0,42 ± 0,06 С4 0,12 ± 0,02* 0,28 ± 0,04 CIK 198,2 ± 1,5* 90,1 ± 2,4* IL-1 0,41 ± 0,001 0,64 ± 0,09* IFN-γ 0,16 ± 0,01* 0,52 ± 0,03* FNO-ά 0,3 ± 0,01* 1,25 ± 0,008 *p < 0.05 between the standards and indicators obtained in each group.

correlation. To assess the relative risk of each of the indicators RESULTS AND DISCUSSION of risk factors and their distant shades, as well as to select the Extreme climatic conditions of the far North have an impact most meaningful combinations of risk factors used logistic on immunological mechanisms. In the analysis of changes regression (univariant analysis for each of the characteristics of the immune status (table 1) revealed the greatest decline separately and multiple step-by-step method for the totality of in T-cell level and components of complement in children symptom). with complications of viral respiratory infections. Average

535 Ivanova O. N., et al. concentration of the components of complement C3 and CONCLUSIONS C4 in children with complications of acute respiratory viral 1. In children with complicated respiratory viral infections infections, lower than in healthy children of the control group. reduced cellular immunity (CD3+, CD4+, CD8+, CD+, CD 22+). In children with complicated viral respiratory infections. In children with complicated respiratory viral infections above the level of the CIK than in healthy, reduced the content decreased levels of cytokines (IFN-γ FNO-ά), indicating that the of IFN-γ FNO-ά. The IgA level decreased in the group of decrease in antiviral defense and about the risk of the formation children with complications of viral respiratory infections. of complications of respiratory viral infection. The level of IgM, IgG did not differ significantly in compared groups 2. As a result of drug therapy of broncho-vaxom marked Similar changes: the decrease in the level of IFN-γ FNO-ά shows improvement in immune status and the absence of recurrence a decline in antiviral defense. of respiratory viral infection within the next 3 months after The analysis of the level of cytokines revealed the greatest therapy. reduction in the level of IFN-γ FNO-α in children with complicated acute respiratory viral infections, indicating that the decrease REFERENCES in antiviral defense. 1. Balabolkin I. I. Dermo-respiratory syndrome in children / Balabolkin I. I // Children’s 30 of the surveyed children long-term and frequently sick doctor.-2000.-№2.-P. 24-26. children with complication of respiratory viral infection medication 2. Nigmatullina G. N. Virus-induced diseases of the respiratory system / Nigmatullina G. used broncho – vaxom representing liofilizat of bacteria that N., Enikeeva E. G. // Proc. Dokl. 13th National Congress on respiratory diseases. – SPb., inhabit bronchial tract. Therapy was carried out by a ten day – 2003. course (1 caps per day) for three months. Upon completion of the 3. Vogralik M. V. Secondary immunodeficiency States. Immune blood disease / M. V. course of therapy of broncho-vaxonom conducted monitoring Vogralik, L. V. // Educational-methodical manual. – Bitter, GMI them. S. M. Kirov, – immune status and revealed the following results. 2000.-S. 25-67. As a result of drug therapy of broncho-vaxom marked 4. markova T. P. // A Practical guide to Clinical Immunology and Allergology. -M. -2003.-Pp. improvement in immune status and the absence of recurrence 31-45. of complicated respiratory viral infections within the next 3 months after therapy.

ADDRESS FOR CORRESPONDENCE: Ivanova O.N. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street [email protected]

536 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Im m u n o h ist o c h e m ic a l a n a l y sis o f m a m m a r y epit h e l i a l ce l l s a t t u m o r a l gr o w t h in rep u b l ic o f s a k h a (y a k u ti a )

Kirillina M.P., Loskutova K.S., Lushnikova E.L., Nepomnyaschih L.M. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a “r e s e a r c h i n s t i t u t e o f m o l e c u l a r p a t h o l o g y a n d pathomorpholo g y ” novosibirsk

ABSTRACT The analysis of results histological examination of surgical material of breast cancer from 294 women with subsequent immunohistochemical determination of estrogen (ER) – and progesterone (PgR) – receptors, proliferative activity (Ki-67), expression of the mutant suppressor gene (p53) and gene-inhibitor apoptosis (bcl-2) was carried out.The obtained data testify that IHC-research of the tumor progression markers is a defining part in the forecast of course, optimization of therapeutic approaches with an individualization of chemo-, hormonal and beam therapy of mammary cancer, the decision of a question of medicamentous and/or surgical shutdown of the ovaries, based on the research results of the biological activity markers of the tumor.

Key words: breast, cancer, immunohistochemistry.

Wiad Lek 2015, 68 (4), 537-542

INTRODUCTION MATERIALS AND METHODS Currently one of the most urgent problems not only in oncology In our research work the material from 294 women who were but also health care in general is the prevention of breast cancer held surgical treatment and / or puncturing biopsy in Yakutsk (BC), due to the rapid, steady growth and widespread incidence Republican Oncology Center and 2nd surgical department of the of this form of cancer, which became on top of the structure of Clinical Center SBD Sakha (Yakutia) “Republican Hospital № 1 morbidity for women with malignant neoplasms [1]. – National Medical Center” was investigated. In our research, as Immunohistochemistry (IHC) is the method of pinpointing indigenous were considered Yakuts, Evens and Evenki people, as the precise localization of particular cell or tissue antigen, non-indigenous – all persons of other nationalities, who arrived allowing to carry out the immunoassay of tissue sections while at different times from regions of Russia and CIS countries. There maintaining the cell morphology. Thus, the most important were 118 (40.1%) of indigenous women and 176 (59.9%) women biological characteristics of tumors having a value in the forecast of non-indigenous nationalities. All studies were performed with of disease include proliferative activity (PA) (antigen Ki-67) of the approval of the Local Committee on Biomedical Ethics “Yakut tumor cells, their differentiation level, hormone receptor status, Scientific Center of complex medical problems” SB RAMS. intensity of apoptosis (as markers of bcl-2 and p53 ), which are Histological processing of the material was carried out according determined by immunohistochemical methods [2]. to conventional techniques. Immunohistochemical study was Despite the widespread adoption of immunohistochemical performed on serial paraffin sections., Staining was performed techniques in the diagnosis of cancer, it should be noted that by indirect immunoperoxidase method after unmasking the in this area theknowledge about the changes in expression of antigenic determinants.Sections were incubated for 40 – 60 certain markers of proliferation, differentiation and cell death min with primary monoclonal antibodies to the antigens of is still being accumulated. Most of the studies evaluated the estrogen (ER), progesterone (PgR), Ki-67, p53, bcl-2 (used RTU- expression of a limited number of markers, which does not allow ER-6F11, RTU-PGR-312, RTU-Ki-67 -MM1, RTU-p53-DO7, us to identify the most informative predictors of malignancy RTU-bcl-2/100/D5, «Novocastra», UK). Staining was performed amplification.It is also important to note the need for diagnostic according to the manufacturer’s instructions. examinations considering ethnicity, since When evaluating the results of the research for the ER and It is also important to point out, that there is a need of PgR were performed determination of the fraction of stained diagnostic examinations considering ethnicity, since ethnic and cells in points [4,5]: 0 – total absence of nuclear staining, 1 – 10% genetic factors play significant role for many types of cancers, of the cells in the investigated material have nuclear staining, 2 including breast cancer [3]. – 1/3 of the cells with nuclear staining, 3 – from 1/3 to 1/2 of the The goal of research is to examine expression patterns of cells with nuclear staining, 4 –from 1/2 to 2/3 of the cells with molecular biologicalmarkers for breast cancer, depending on age nuclear staining, 5 – from 2/3 to 100% of the cells with nuclear and ethnicity on the example of Republic of Sakha (Yakutia). staining.Determination of antibody expression intensity was

537 Kirillina M.P., et al. also performed in points: 0 – complete absence of expression (percentage) receptor-positive breast cancer with increasing in the nuclei of tumor cells, 1 – weak nuclear staining, 2 – mild the age (Fig. 3). Thus, in a group under 39 years old, they made nuclear staining, 3 – strong nuclear staining. Upon receiving 56.7% and in the group over 70 years old – 75.6%. At the same the total result which is less than or equal to 2, the reaction was time, in both groups receptor-positive breast cancer profile considered negative (-), 3 or more – a positive (+). prevailed (correspondingly 48.3 and 54% of cases in indigenous Index of Ki-67 positive cells (proliferative activity – PA) was and non-residents); receptor-negative breast cancer profile was determined by analysis of at least 100 nuclei by the following less frequent (correspondingly 38.1 and 32.9% of cases). formula: The connection between the age of patients and the expression of ER (p = 0.03). If under the age of 39 years, the average total P= ‘‘the number of ki – positive cells x 100’’ score estimates of the proportion of positive cells and the intensity ‘‘the total cell number’’ level of ER expression was equal to 3.2, the following age groups indicated a steady rise in these indicators up to 3.7 points at Low PA corresponded to Ki-67 index of less than or equal patients with breast cancer who were older than 70 years. In to 15%; high PA – with Ki-67 index of more than 15%. assessing the changes in the level of expression of PgR similar Low expression of p53 was detected in the presence of linear relationship is not detected (p = 0.54). expression of less than 25% of the cells; high expression of p53 By the statistical analysis of the data according to ethnicity – in the presence of expression of more than 25% of tumor cell we have revealed differences among the indigenous women and nuclei (nuclear stain). women of non-indigenous nationalities. There was a tendency Low expression of bcl-2 was detected in the presence to a slight increase in the expression level of ER of indigenous ofexpression of less than 25%; High expression of bcl-2 – in women with the age, while increase of the expression level of ER of the presence of expressionof more than 25% of tumor cells women of non-indigenous nationalities was statistically significant (cytoplasmic staining). (r = 0,20, p = 0,01).Other authors have also noteddifferences Statistical analysis was performed using the statistical package in the content of hormones in the blood of women of different SPSS STATISTICS 17.0 (SPSS Inc.). ethnic groups in Siberia, in particular, higher levels of estradiol of indigenous (Tyva, Hakass, Buryat) at a lower the incidence RESULTS AND DISCUSSION ofbreast cancer [8]. A comparison of the degree of malignancy The average age of the operated women was 54,2 ± 12,1 years, of tumors with the presence of ER and PgR (Fig. 4). most were women over 50 years old – 96 women (32.6%), 60 – The obtained data demonstrate certain dependence of 69 years old – 64 women (21.8%), in ages of 40 – 49 years – 60 histological grade of breast cancer on receptor profile of tumor women (20.4%), and under 39 years old – 37 women (12.6%), cells (χ2 = 20.40, df = 6, p = 0.002). Thus, G1 at the receptor- and over 70 years old – 37 women (12.6%) (Table I). positive tumors was detected 2 times more frequently (40.8% of It should be noted that the breast cancer, which is traditionally the tumors in this group) than in the receptor-negative (21.3%) considered as a disease of women older than 50 years, today and only the ER-positive tumors (26.1%) and PgR positive became much “younger” – there are cases of disease of women (37.5%).G2 was detected equally often in receptor-positive and of forty and thirty years old, and even women in their twenties receptor-negative breast cancer (48 and 49.5%, respectively), [6]. This tendency was observed in our research. For example, while it was the vast majority of tumors with only ER-positive there are twice more women aged over 50 years than those (56.5%) and only PgR-positive (56.2%) profile. Though G3 under 50 years (197 versus 97), the largest number recorded is in the general totality was diagnosed more than 2 times less significantly more frequent in the age group of 50 – 59 years than remaining degrees, it constituted 29.1% of tumors with old (96 cases or 32.6% of total surveyed) . In second place in a receptor-negative profile and 11.2% – with a positive profile frequency of our research is the age group of 40 – 49 years old and was found in only 17.4% with ER-positive, and 6.2% of the (60/20, 4%).Also, studies were conducted in women aged under PgR-positive profile. 39 years (37/12, 6%) and women aged over 70 years (37/126%). Thus, by increasing the degree of malignancy receptor-negative These results are comparable to those of developed countries, tumors are significantly more observed (p <0.05), while receptor- where about 75% of cases of breast cancer occur among women positive rate decreases. in postmenopause [7]. Proliferative activity of breast tumor cells was determined To determine ER and PgR immunohistochemical examine was using a universal proliferation marker Ki-67, which is expressed carried out (Fig. 1, 2) and 4 groups with various combinations in almost all phases of the mitotic cycle and reflects the value of of steroid receptors in tumor cells were allocated: ER + / PGR- the proliferative tumors pool [9]. In our research Ki-67 expression (7,8%), ER-/PGR + (5,4%), ER -/PGR- (35%), ER + / PGR + was detectedin 272 cases (92.5%) – less than 15% of tumor cells (51,7%). (low PA). We observed Ki-67 expression in 22 women (7.5%) – Collectively receptor-positive tumor cells in breast cancer more than 15% of tumor cells (high PA) (Fig. 5-6). were significantly higher than the receptor-negative (p <0.05) Analysis of the expression pattern of Ki-67, depending on – 191 cases (64.9%) of the total number of studies: aged under the age revealed that the expression level of Ki-67 antigen was 50 years – 60 cases (31, 4%), over 50 years – 131 cases (68.6%). independent of age (χ2=4.1, df=4, p =0.39). High PA of tumor Analysis of the dynamics of change of the receptor status of cells occurs in both elderly patients and younger aged ones. In breast cancer according to age revealed no statistically significant aggregate indicators in groups of indigenous and non-indigenous differences (p = 0.14), but set a trend toward increased frequency population in breast cancer statistically significant correlations

538 Im m u n o h i s t o c h e m i c a l a n a l y s i s o f m a m m a r y e p i t h e l i a l c e l l s a t t u m o r a l g r o w t h in r e p u b l i c o f s a k h a (y a k u t i a )

Fig. 1. Infiltrative ductal breast cancer.x200. Fig. 2. Infiltrative ductal breast cancer x200. The immunohistochemical reaction with the monoclonal antibody to ER. Immunohistochemical reaction with monoclonal antibodies to PgR. Proportion of stained cells in scores = 5 (from 2/3 to 100% of the cells with nuclear Proportion of stained cells in scores 4 = (½ to 2/3 of the cells with nuclear staining), the staining), the intensity of expression in scores = 3 (strong nuclear staining), the sum intensity of expression in scores = 3 (strong nuclear staining), the sum score = 7. Result: score = 8. Result: ER-positive breast cancer. PgR-positive breast cancer.

Fig. 3. Dynamics of changes in receptor status of breast cancer according to age. Fig. 4. Distribution of degrees of malignancy (by Elston& Ellis) at various hormone profile of breast cancer.

Fig. 5. Infiltrative ductal breast cancer X200. Fig. 6. Infiltrative ductal breast cancer x200. The immunohistochemical reaction with the monoclonal antibody Ki-67. Expression The immunohistochemical reaction with the monoclonal antibody Ki-67. Expression of 20%. of 90%.

539 Kirillina M.P., et al.

Fig. 7.Dependence of histological degree of malignancy on the level of Ki-67 expression. Fig. 8. Invasive breast cancer x200. The immunohistochemical reaction with monoclonal antibodies to p53. Expression of 15%.

Fig. 9. Infiltrative ductal breast cancer X200. Fig. 10. Dependence of histological grade on the level of p53 expression. The immunohistochemical reaction with monoclonal antibodies to p53. Expression of 100%.

Fig. 11. Invasive papillary breast cancer x200. Fig. 12. Dependence of bcl-2 expression on the degree of malignancy. The immunohistochemical reaction with the monoclonal antibody bcl-2. Expression of 98%.

540 Im m u n o h i s t o c h e m i c a l a n a l y s i s o f m a m m a r y e p i t h e l i a l c e l l s a t t u m o r a l g r o w t h in r e p u b l i c o f s a k h a (y a k u t i a )

Table I. Distribution of material by age and ethnicity. Indigenous Non-indigenous In total Age group the number the number the abs. / rel. average age abs. / rel. average age abs. / rel. average age under 39 15/12,7 33,7+5,3 22/12,5 33,8+3,6 37/12,6 33,7+4,3 years old 40 – 49 28/23,7 45,3+2,9 32/18,2 45,0+2,8 60/20,4 45,1+2,9 years old 50 – 59 31/26,3 54,8+2,7 65/37,0 54,1+2,9 96/32,6 54,3+2,9 years old 60 – 69 25/21,2 63,4+2,6 39/22,1 62,9+3,1 64/21,8 63,1+2,9 years old over 70 19/16,1 74,2+2,9 18/10,2 73,3+3,3 37/12,6 73,8+3,2 years old Total number: 118/100 54,8+12,9 176/100 53,8+11,5 294/100 54,2+12,1

with PA ethnicity has not been found (χ2=1.6, df=1, p=0.20). By immunohistochemical study of the expression of anti- Numerous studies have shown that PA of tumor cells in breast apoptotic tumor-suppressor gene bcl-2 we found low expression cancer is directly correlated with the histological degree of of bcl-2 in 142 cases (48.3%), high expression – in 152 cases malignancy [10,11]. The results obtained in our study indicate (51.7%) (Fig. 11). that the expression of Ki-67 antigen significantly differ between Data analysis based on ethnicity did not reveal differences the different histological variants of breast cancer (χ2=3.58, df=1, in the frequency of cases with low and high expression of bcl-2 p=0.05): there was a tendency of increasing the histological (χ2=0.23, df =1, p=0.64). Low expression of bcl-2 in indigenous degree of malignancy while increasing the expression of Ki-67 and non- indigenous women most frequently was recorded at (Fig. 7). the age of 50 – 59 years (respectively 33.9 and 36.1%). High These results do not contradict to the literature data on the expression of bcl-2 was more common among indigenous women Ki-67 antigen as a marker of adverse outcome of the disease aged 60 – 69 years (27.1%), in non- indigenous women – aged [12,13,14]. Importantly, PA of tumor cells serves as an independent 50 – 59 years (37.6%). prognostic indicator of relapse, overall and disease-free survival According to the literature, bcl-2 is a tumor-suppressor gene [15], as well as a predictive factor in determining the sensitivity to affecting cell death mechanisms and suppressing apoptosis [18]. radiotherapy and chemotherapy [16, 17]. Our analysis confirmed According to many authors, the increased expression of bcl-2 the dependence between the degree of histological malignancy is associated with increased survival of patients after adjuvant and proliferative activity of tumors, which proves the necessity therapy. Perhaps this is due to the close relationship between of accounting PA of tumor cells in the evaluation of malignant the expression of bcl-2 and the expression of ER and PgR, potential and prognosis of breast cancer. and low PA. However, bcl-2 is not an independent prognostic In immunohistochemical study of mutant tumor suppressor factor [15]. We have established a negative correlation between gene p53 low expression (less than 25% of tumor cells) was the expression of bcl-2 antigen, and the degree of histological observed in 197 (67.0%) cases, whereas high expression (more malignancy of tumor (r = -12.9, p=0.03), i.e. tumors with a high than 25% of tumor cells) – 97 (33 0%) cases (Fig. 8, 9). degree of malignancy were characterized by low expression of In the analysis of this indicator based on ethnicity, we have bcl-2, which describes by preserving the regulation of apoptosis established that indigenous women have statistically significant in normal levels (Fig. 12). weak positive correlation (r = 0,21, p = 0,02) between age and Thus, the data of comparative immunohistochemical study the expression of p53. Low expression of p53 was observed of some molecular biological markers for breast cancer analysis in indigenous women aged 40 – 49 years (27.2%), while non- of their expression levels showed: indigenous – aged 50 – 59 years (36.7%). In aggregate indicators - According to clinical and morphological analysis, bre- in both groups statistically significant age differences were not ast cancer develops most often in representatives of found (χ2 = 1,8, df = 4, p = 0.76). The positive relationship non-indigenous nationalities of the Republic of Sakha between the level of p53 expression and increased histological (Yakutia) (60%) than those belonging to indigenous tumor grade was found (χ2=7.9, df =2, p=0.01), which proves the nationalities (40%). With the highest rate recorded in need to consider the severity of the process of cell apoptosis in women of indigenous and non-indigenous nationali- evaluating the malignant potential of the tumor and prognosis ties in the age group 50 – 59 years (32.6%) and 60 – 69 of breast cancer (Fig. 10). years (21.8%).

541 Kirillina M.P., et al.

- In breast cancer tumors with the presence of steroid hor- 6. Pisareva L.F. Hormonal status of women of different ethnicities in the region of Siberia mone receptors are predominant (65%). and the Far East. / L.F. Pisareva, I.N. Odintsov, O.A.Ananina / / Siberian Journal of - With increasing age tumor cells of breast cancer the level Oncology. – 2011. – № 2 (44). – P. 5 – 10. of ER expression increases (p = 0.03). 7. Uporov A.V. Immunohistochemical study of breast cancer cells using a variety of pro- - Tumors with a high degree of malignancy are characterized liferation markers / A.V. Uporov, V.F. Semiglazov, K.M. Pozharissky // Archives of by low expression of estrogen receptors and progesterone Pathology. – 2000. – № 2. – P. 26-30. receptors (p <0,05). 8. Anderson W.F. Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, - The tendency of tumor grade increasing by increasing the and the Results database / W.F.Anderson, N.Chatterjee, W.B.Ershler // Brawley Breast expression of p53 and Ki-67 is found. cancer Res.Treat. – 2002.– Vol. 76. – P.27-36. - The level of expression of bcl-2 antigen and its prevalence 9. Buchholtz T.A. Chemotherapy-induced apoptosis and bcl-2 levels correlate with breast is positively correlated with the presence of ER and PgR cancer response to chemotherapy / T.A.Buchholtz, D.W.David, D.J.McConcey et al. // receptors on tumor cells and low-grade tumors. Cancer. – 2003. – Vol.9/ – P.33-41. - The most informative criteria of increasing breast cancers 10. Costarelli L. Hormone-dependence and C-ERBB2: relationship between estrogen receptor are the decrease in expression of estrogen and progestero- expression, estrogen-regulated proteins, and C-ERBB2 in breast carcinoma / L. Costarelli, ne receptors, increased expression of Ki-67 and p53 and F.R. Piro, L. Fortunato // SupplTumori. – 2005.- Vol.4.- P.171. decreased expression of bcl-2. 11. Choi D.H. Immunohistochemical biomarkers in patients with early-onset breast carcinoma - The most informative criterias of increasing of breast tumors by tissue microarray / D.H. Choi, S.Kim, D.L. Rimm et al.// Cancer J.- 2005.-Vol.ll(5).- malignancy are the decrease in expression of estrogen and P.404-411. progesterone receptors, increased expression of Ki-67 and 12. Ferrara N. The role vascular endothelial growth factor in pathological angiogenesis / p53 and decreased expression of bcl-2. N. Ferrara // Breast Cancer Res. Treast. -1995. – Vol.36, №36, №2. – P.127-137. 13. Hoonkop A.H. Prognostic role of clinical, pathological and biological characteristics REFERENCES in patients with locally advanced breast cancer/ A.H.Hoonkop ,P.J.van-Diest // Br. J. 1. Berstein L.M. Modern endocrinology of hormone-depended tumors / / Problems of Cancer. – 1998. – Vol.77. – P. 621 – 626. Oncology. – 2002. – V.48, № 4. – P. 496 – 503. 14. Imamura, H. MIB 1 determined proliferative activity in intraductalcomponentsand 2. Loskutova K.S. Immunomorphological characteristics of the hormonal status of primary prognosis of invasive ductal breast carcinoma / H.Imamura, S.Haga, T.Shimizu et al. // breast cancer in the Republic of Sakha (Yakutia) / K.S. Loskutova, V.A. Argunov / / Yakut Jpn. J. Cancer Res. – 1997. – Vol. 88. – P. 1017 – 1023. Medical Journal. – 2009. – № 1. – P. 46 – 49. 15. Keshgegian A. Proliferation markers in breast carcinoma: mitotic figure count, S-phase 3. Pozharissky K.M. Value of immunohistochemical techniques to determine the nature fraction, proliferating cell nuclear antigen, Ki-67 and MIB-1 /А. Keshgegian, А. Cnaan// of the treatment and prognosis of tumor diseases / K.M. Pozharissky, E.E. Leenman / / Am. J. Clin. Pathol. – 1995. – Vol. 104. – P. 42 – 49. Archives of Pathology. – 2000. – № 5. – P. 3 – 11. 16. Kronqvist P. Predicting aggressive outcome in TINOMO breast cancer / P.Kronqvist, Т. 4. Petrov S.V. Guidelines for immunohistochemical diagnosis of human tumors / S.V. Kuopio, M. Nykanen, H. Helenius// Br. J. Cancer. – 2004. – Vol. 91 (2). – P. 277 – 281. Petrov, N.T. Reichlin // – Kazan, 2004. – P. 452 17. Rozan, S. No significant predictive value of c-erbB-2 or p53 expression regarding / S.Rozan, 5. Pisareva L.F. Epidemiological features of breast cancers in the region of Siberia and the A. Vincent-Salomon, B.Zafrani et al. // Int. J. Cancer. – 1998. – Vol.79. – P.27-33. Far East. / L.F. Pisareva, I.N.Odintsov, A.A.Shivit-ool, A.K. Sirazitdinova // – Tomsk Univ. 18. Jacobson M.D. Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA / M.D.Jacobson, University Press, 2006. – P. 10. J.F.Burne, M.P.King et al.// Nature. – 1993. – Vol.361. – P.365 – 368.

ADDRESS FOR CORRESPONDENCE: Kirillina M.P. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Ojunsky street Ph. +79142716881 [email protected]

542 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Th e r o l e o f c a n d i d a in i n testi n a l d y s b a cteri o sis f o r m a ti o n

Lineva Z.E., Gulyaeva N.A., Romanova M.V., Dyachkovskaya P.S. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT Introduction: in modern TB chemotherapy until today retains a leading role in the treatment of tuberculosis patients, and specific nature of the inflammatory process, its course and symptoms include the duration and continuity of chemotherapy. It is known that prolonged chemotherapy naturally leads a large majority (92.0%) of patients in the development of intestinal dysbiosis, where the leading role in the microbial imbalance is a deficiency or complete absence of bifidobacteria, it creates conditions for the settlement of fungi Candida, also plays a major role in microbial associations. Aim: examine the role of candida in intestinal dysbacteriosis formation. Materials and methods: the 500 patients with various forms of pulmonary tuberculosis were examined for reveal intestinal dysbiosis, which conducted bacteriological examination of feces for intestinal dysbiosis method RV Epstein-Litvak FL Vilshanskoy. Results: in great majority of patients (92%), the long chemotherapy naturally leads to conclusions development of intestines dysbacteriosis. The leading value in a microbial imbalance belongs to deficiency or total absence of the bifidobacterium, which creates conditions for Candida, and plays the main part in microbial associations. There was noted a high therapeutic efficiency of the pathogenic agents antifungal drugs, allowing to eliminate Candida intestinal dysbacteriosis of patients suffered from pulmonary tuberculosis.

Key words: dysbacteriosis, Candida, chemotherapy.

Wiad Lek 2015, 68 (4), 543-545

INTRODUCTION efficiency of the pathogenic agents antifungal drugs, allowing to In modern TB chemotherapy until today retains a leading eliminate Candida intestinal dysbacteriosis of patients suffered role in the treatment of tuberculosis patients, and specific nature from pulmonary tuberculosis. of the inflammatory process, its course and symptoms include the duration and continuity of chemotherapy [1]. DISCUSSION It is known that prolonged chemotherapy naturally leads a The leading value in a microbial imbalance belongs to deficiency large majority (92.0%) of patients in the development of intestinal or total absence of the bifidobacterium, which creates conditions dysbiosis, where the leading role in the microbial imbalance is for Candida, and plays the main part in microbial associations. a deficiency or complete absence of bifidobacteria, it creates There was noted a high therapeutic efficiency of the pathogenic conditions for the settlement of fungi Candida, also plays a agents antifungal drugs, allowing to eliminate Candida intestines major role in microbial associations. dysbacteriosis of patients suffered from control of intestines Aim: examine the role of candida in intestinal dysbacteriosis microflora state in 3-5 months of chemotherapy, especially formation. at massive an antibiotic – and hormone therapy application with using of parenteral methods of tuberculostatic drugs MATERIALS AND METHODS administration. The 500 patients with various forms of pulmonary tuberculosis The nature of the inflammatory process, its course and were examined for reveal intestinal dysbiosis, which conducted manifestation of tuberculosis include the duration and continuity bacteriological examination of feces for intestinal dysbiosis of chemotherapy (AG Khomenko, 1984, MV Shesterina 1985 method RV Epstein-Litvak FL Vilshanskoy. monograph Mishin), therefore, in addition to evaluating the effectiveness of causal activity of chemotherapy, have to also RESULTS consider the complications which may appear under the influence in great majority of patients (92%), the long chemotherapy of them on the macro-organism. naturally leads to conclusions development of intestines Under the influence of a broad and long-term using of dysbacteriosis. The leading value in a microbial imbalance antibiotics, chemotherapy drugs, which are the powerful belongs to deficiency or total absence of the bifidobacterium, factor of macroorganisms biological variation, and also under which creates conditions for Candida, and plays the main part the influence of macroorganism’s metabolism products, the in microbial associations. There was noted a high therapeutic process of different biological properties’ variability of bacterial

543 Kirillina M.P., et al. population strongly increases: change the numerical composition, change of typical colibacilli total number, existence of lactose- destroy the intercourse between the normal microflora and defective escherichias, emergence of haemolytic colibacilli, macroorganisms and microbial biocenoses, damage a variety of and significant deficiency of bifidobacterium , and increasing physiological functions of the microbial cell: change the number of numbers of putrefactive, pusforming and fungoid species of of members, violated the established evolutionary relationship bacteria in the majority of observed patients. between the normal microflora and macroorganism , destroyed On this background, the intestinal dysbacteriosis is formed vnutrimikrobnye biocenoses develop goiter, damaged a variety in the first 2-3 months of treatment, because of adaptative, of physiological functions of the microbial cell (AG Khomenko, shielding, compensatory mechanisms frustration, and because of IR Dorozhkova, L.G.Selina 1984 monograph). the long-term chemotherapy, the macroorganism is not able to The local character’s confounding factor, leading to intestinal produce effective shielding mechanisms from toxic substrata, due dysbacteriosis formation, can be the affect of mucous membrane to this, there occur intestinal dysbiosis disruption, emergence and subsequent decline of epithelium barrier function, which of Candida in 58-72% of cases. occurs the direct effects of tuberculostatic drugs, mainly at oral The great concern was represented by patients suffered from use. Chemotherapy drugs, damaging the epithelium of the diabetes with varying severity of intestinal dysbacteriosis. Those gastrointestinal tract, create favorable conditions for germination patients, observed in both groups, had intestinal dysbacteriosis of steady microbes. before having chemotherapy, in 100,0% cases. Thus, in 80,0% and It is well known that the oral using of chemotherapy drugs 82,0% of cases, most patients had intestinal dysbiosis disruption and antibiotics’ could be cause of more evident changes in of 2-3 degree. intestines microflora, than parenteral using determined by It should be noted that at mainly oral using of tuberculostatic created tuberculostatic drugs concentration. drugs, it occurs oppression of many species of microbial activity It is known that during parenteral administration of certain and it favors Candida procreation. antibiotics, their antibiotic concentration is in 20-30 times lower Apart from long-term oral using of tuberculostatic drugs, than during oral administration. Antibiotics, chemotherapy especially rifampicin, which is a broad-spectrum antibiotic, the drugs, being administered intravenously or intramuscularly, aggravating factor in formation of candidal intestinal dysbacteriosis have an insignificant effect on intestines microflora, and which is the using of mild corticosteroids in complex treatment on some taken orally lead to qualitive and quantitive changes to its patients suffered from pulmonary tuberculosis. Suppression of formulation. all immunity indicators was usually noted in such patients. During the chemotherapy, the dysbiotic disturbances occur It is known that there is a close interrelation between a not only in the intestines microflora, but also in other areas of condition of immunity and candidiasis, candidiasis can be the human body. both a consequence and the reason of immune insufficiency It is known that chemotherapy may cause eliminations from that favors generalization of a candidal infection. It is observed a mouth, which is an obligatory gram-positive microflora, and in patients suffered from diabetes and in patients who took also may lead to procreation of colibacilli and candida. Due corticosteroids, added to comprehensive treatment. The given to this, the physiological barrier function of the oral cavity data shows that the using of immunocorrectors, as well as the microflora is reduced and gastro-intestinal tract becomes patulous antifungal drugs, is obligatory to be corrected disbiotic disruptions to potentially pathogenic microorganisms [2]. in this category of patients. Microflora imbalance leads to disruption of digestion, The polymorphous manifestations were a distinctive feature absorption and all types of metabolism [3, 4]. of clinical presentation of mycotic leasion. Candidiasis of Serious bacterial changes are accompanied by functional mucous membranes often involved a mouth cavity and was impairment and inflammatory processes of major organs. characterized as a hyperemia of mucous membrane with emergence However, the pathogenetic role of intestinal disbiosis hasn’t of a grayish-yellow fur on a tongue, internal surfaces of cheeks, been found out yet, and cannot be considered as the consequence and seldom involved tonsils, emergence of the mycotic lumps in of only gastrointestinal tract pathology. a phlegm. Patients complained of anorexia, the general weakness, Specification and clarifications of the intestinal dysbacteriosis a weight loss, periodic stomac-aches of various character and pathogenetic significance o in patients with pulmonary tuberculosis intensity, mainly round a navel, a burning sensation, heaviness in conditions of prolonged use of tuberculostatiс drugs is an in the epigastrium, flatulence, a frequent, semi-liquid feces important problem in improving ways of correction. with slime. It is known that in the chemotherapy and the rifampicin In the course of chemotherapy, intestines microflora state are being as the main tuberculostatic drug, which is mainly continued to get worse, especially in patients suffered from used orally during 5-8 months, besides, rifampin is a broad- pulmonary tuberculosis complicated by diabetes who had spectrum antibiotic. significant amelioration of intestines microflora before having According to our research, 500 patients with different clinical chemotherapy. During treatment, intestines microflora disruption forms of pulmonary tuberculosis, who took rifampin orally caused serious changes to the intestines biocenosis, characterized in comprehensive treatment have the dysbiotic disruption of by total absence of bifidobacteria, microbic association with a biocenosis with predomination of Candida, it is the absolute predominating role of Candida majority of observed patients ( -72.0%) 58.0. Decrease of all immunity evidence was usually observed in Constant pathological shifts in intestines microecology were such patients. It is known that there is a close connection between observed after 2-3 months of the chemotherapy, characterized by immunity state and candidiasis, candidiasis can be a result and

544 Th e r o l e o f c a n d i d a in i n t e s t i n a l dysbacteriosis f o r m a t i o n a cause of immune insufficiency, as at profound changes of Well-timed bacteriological control, identification, prevention microflora structure, microbes’s activity is suppressed, and it and treatment of candidal dysbacteriosis should let eliminate an leads to avitaminosis, enzymatic activity disorder, that reduces aggravating influence of Candida on immunological reactivity, body resistance considerably and aggravates the seriousness of a clinical progression, and a minimization of adverse reactions dysbiotic disruption. In these conditions there occur smooth in patients suffered from pulmonary tuberculosis procreation and activation of Candida owing to which the candidal infection is formed. CONCLUSION When studying antibiotic sensitivity of Candida , there 1. In great majority of patients (92%), the long chemotherapy distinguished the tendency to increase an antibiotic resistance in naturally leads to development of intestines dysbacteriosis. 65% of patients or full resistance formation to all known antibiotics 2. The leading value in a microbial imbalance belongs to in 35.0% of patients suffered from pulmonary tuberculosis, deficiency or total absence of the bifidobacterium, which create complicated by diabetes. conditions for Candida population, and plays the main part in Medical treatment of Candida dysbiosis is particularly difficult microbial associations. in this respect, the therapy should be comprehensive, the basic 3. In most cases, more serious disbiotic disruptions are principles of which should be: stated in patients, who suffered from pulmonary tuberculosis 1. The inclusion of antifungal drugs to comprehensive che- and complicated by diabetes, which had generalization of a motherap for patients suffered from pulmonary tuber- candidal infection. culosis; 4. There was noted a high therapeutic efficiency of the 2. It is mandatory to conduct the nonspecific pathogenic pathogenetic agents antifungal drugs, allowing to eliminate therapy; Candida intestinial dysbacteriosis in patients suffered from 3. The prescription of immunomodulatory drugs and me- pulmonary tuberculosis. dicine, which reduce the mycotic sensitization. 5. For prevention of candidiasis it is necessary to conduct In our opinion, the most effective remedies of candidal bacteriological control of intestines microflora state in 3-5 dysbacteriosis treatment were the following antifungal drugs: months of chemotherapy, especially at massive an antibiotic nystatin, levorin, amphoglucaminum. Levorin should be considered – and hormonotherapy application with using of parenteral as the most effective remedy and more sensitive to fungus, methods of tuberculostatic drugs administration. than nystatin. We intentionally refused to administer other antifungal drugs, such as nizoral, amphotericinum, because REFERENCES of their high toxicity aggravated in a combination to specific 1. Lineva Z.E. Intestinal dysbiosis and methods of its correction in patients suffered from chemotherapy. pulmonary tuberculosis. /Lineva Z.E. // Publishing house of NEFU , 2012.150 p. Proceeding from immune protection suppression at 2. Kashkin K.P. Immune responsiveness and antibacterial therapy. Kashkin K.P., Karayev candidal dysbacteriosis, it is reasonable to include drugs Z.O. //– М., 1984. 200 p. of immunomodulatory effect – methyluracil, pentoxyl, 3. Krasnogolovetz V.N. Intestinal dysbacteriosis. Krasnogolovetz V.N. //- М. Москва, stimulating the production of antibodies, phagocytic activity, 1989. 206 p. leukopoiesis, and also the drugs, stimulating indicators of 4. Dorofeychuk V.G. Intestinal dysbiosis and its role at the present stage in the pathogenesis of T-lymphocytes. several diseases in children, dis. Dr.med.Scienes. / Dorofeychuk V.G.: // M., 1978. 146 p.

ADDRESS FOR CORRESPONDENCE: Lineva Z.E. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Ojunsky street Ph. 89248681529

545 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Res u l ts o f m o n it o ri n g m et a l l o -b et a -l a ct a m a se -pr o d u ci n g str a i n s o f pse u d o m o n a s a er u gi n o s a in a m u l ti -pr o f i l e h o spit a l

Shamaeva S.K.1, Portnyagina U.S.1, Edelstein M.V.2, KuzminaA.A.3, MalogulovaI.S.3, VarfolomeevaN.A.3 1r e p u b l i c a n h o s p i t a l n o 2 – c e n t r e f o r e m e r g e n c y m e d i c a l a i d o f t h e r e p u b l i c o f s a k h a (y a k u t i a ), r u s s i a 2antimicrobial chemotherapy r e s e a r c h i n s t i t u t e o f s m o l e n s k s t a t e m e d i c a l a c a d e m y o f t h e ministry o f h e a l t h c a r e a n d s o c i a l development o f t h e r u s s i a n f e d e r a t i o n , s m o l e n s k 3f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

aBSTRACT The authors present the results of long-term monitoring of metallo-beta-lactamase (MBL) producing strains of Pseudomonas aeruginosa in the Republican Hospital No 2 of Yakutsk, Russian Federation. Hospitals across Russia, as well as the rest of the world, face a rapid appearance and a virtually unchecked spread of multiresistant and panresistant nosocomial pathogens. Especially prevalent are multidrug-resistant isolates of P. aeruginosa, most often found among the patients of intensive care and intensive therapy units, as well as surgery departments. The aim of this study is to investigate the prevalence of metallo-beta- lactamase-producing strains of P. aeruginosa in a multi-profile hospital. 2,135 isolates ofP. aeruginosa were studied, collected during a time span of seven years (2008-2014) from clinical specimens of hospitalised patients in acute surgery, purulent surgery, neurosurgery, otolaryngology, coloproctology departments, intensive care and intensive therapy, burn units, as well as intensive care unit for patients with acute cerebrovascular accidents and coronary care unit. Strains were identified and re-identified using established methods, NEFERMtest 24 (MICROLATEST) biochemical microtest and API (bioMerieux) test systems were used. For all carbapenem-resistant strains a phenotype screening for MBL was performed using the double-disks method with EDTA. In order to identify VIM-type and IMP-type MBL genes a real-time multiplex polymerase chain reaction was used. Among the investigated strains the largest number of P. aeruginosa – 35.6% (761 isolates) was found in patients at intensive care and intensive therapy units. Clonal expansion of extensively drug-resistant strain P. aeruginosa ST235 (VIM-2) was determined, the resistance mechanism of which is connected to MBL. Sensitivity determination of MBL-producing isolates of P. aeruginosa has shown that isolated strains have a high level of resistance (100%) to all tested antibacterial agents: piperacillin, piperacillin-tazobactam, ceftazidime, cefepime, cefoperazone-sulbactam, aztreonam, imipenem, meropenem, doripenem, gentamicin, netilmicin, amikacin, ciprofloxacin, levofloxacin, fosfomicin.

Key words: Pseudomonas aeruginosa, antibiotic resistance, metallo-beta-lactamase

Wiad Lek 2015, 68 (4), 546-548

INTRODUCTION (downregulation of the porin protein OprD), active movement Hospitals all over the world face a rapid appearance and a of antibiotics out of the cell (activation of efflux systems), and virtually unchecked spread of multiresistant and panresistant production of serine-β-lactamases with carbapenemase activity. nosocomial pathogens [1]. Especially prevalent are multidrug- However, of highest clinical and epidemiological importance resistant isolates of Pseudomonas aeruginosa, most often found is the production of acquired MBLs. IMP-type and VIM-type among the patients of intensive care and intensive therapy units, as MBLs hydrolyse virtually all β-lactams including carbapenems, well as surgery departments. P. aeruginosa is one of the principal with the exception of aztreonam. Therefore, effective treatment causative agents for pyoinflammatory processes, especially in of infections caused by P. aeruginosa is a serious clinical issue hospital conditions. The properties of this microorganism include and requires adequate microbiological controls and an obligatory fast development and high level of resistance to many broad- investigation of their sensitivity in vitro [5]. spectrum antibacterial agents, which are usually prescribed for Aim: Investigation of prevalence of metallo-beta-lactamase- empiric treatment of nosocomial infections [2]. Multiresistance producing strains of P. aeruginosa in a multi-profile hospital. of P. aeruginosa is a significant issue in healthcare, leading to a greater number of inadequate initial antibacterial therapy MATERIALS AND METHODS prescriptions. This, in turn, results in longer hospitalisation 2,135 isolates of P. aeruginosa were studied, collected during of patients, greater incidence of complications and lethality, a time span of seven years (2008-2014) from clinical specimens multifold increase in the number of invasive diagnostic and (bronchial lavage fluid, phlegm, tracheal aspirate, urine, wound treatment procedures and the cost of therapy [3, 4]. exudate) of hospitalised patients in acute surgery (ASD), purulent P. aeruginosa has different characteristic resistance mechanisms: surgery (PSD), neurosurgery (NSD), otolaryngology (OD), reduction of cell membrane permeability to antibiotics coloproctology departments (CPD), intensive care and intensive

546 Re s u l t s o f m o n i t o r i n g m e t a l l o -b e t a -l a c t a m a s e -p r o d u c i n g s t r a i n s o f pseudomonas a e r u g i n o s a in a m u l t i -p ro f i l e h o s p i t a l therapy (ICU), burn units (BU), as well as intensive care unit number tandem repeat analysis (MLVA). The number of tandem for patients with acute cerebrovascular accidents (ICACA) and repeats was evaluated in six Variable Number Tandem Repeat coronary care unit (CCU) of Republican Hospital No 2 – Centre (VNTR) loci. Six VNTR-loci were amplified using multiplex PCR for Emergency Medical Aid of the Republic of Sakha (Yakutia) (two separate reactions for each isolate). Analysis of the size of (RH No 2 – CEMA). amplification products of six VNTR-loci was done using the method Strains were identified and re-identified using established of capillary electrophoresis with fluorescence detection (fragment methods in accordance with normative documents regulating the analysis) on ABI-310 Genetic Analyzer (Applied Biosystems) work of bacteriological laboratories. Furthermore, NEFERMtest automated sequencer. Cluster analysis of MLVA profiles was 24 (MICROLATEST) biochemical microtest and API (bioMerieux, completed in Bionumerics v.6.6 (Applied Maths) software using France) test systems were used. categorical values of VNTR-loci lengths and the algorithm of The study was conducted as part of the National Programme for building dendrograms of minimal distances. Molecular genetic Monitoring the Spread of Strains of Gram-negative Microorganisms testing was carried out in Laboratory of Molecular Microbiology Producing Metallo-Beta-Lactamases in Russia (METALL) at Antimicrobial Chemotherapy Research Institute of Smolensk in cooperation with Antimicrobial Chemotherapy Research State Medical Academy of the Ministry of Healthcare and Social Institute of Smolensk State Medical Academy of the Ministry of Development of the Russian Federation. Healthcare and Social Development of the Russian Federation Input, statistical processing and analysis of data was done (ACRI), Interregional Association for Clinical Microbiology and using Microsoft Excel (version 7.0 for Windows 2000) and Antimicrobial Chemotherapy (IACMAC), Research Guidance WHONET 5.6 software. Centre for Antimicrobial Resistance (RGCAR), and Republican Centre for Monitoring Antibiotic Resistance of RH No 2 – RESULTS CEMA. Among the investigated strains the largest number of P. Sensitivity to 15 antibacterial agents was tested using the disk aeruginosa – 35.6% (761 isolates) was found in patients at intensive diffusion method on Mueller-Hinton agar in accordance with care and intensive therapy units. The ratio of identified strains МУК 4.2.1890-04. Quality control was completed using the P. of P. aeruginosa in other departments of the hospital was as aeruginosa ATCC 27853 and E. coli ATCC 25922 control strains. follows: BU – 23.7% (506), PSD – 16.4% (351), NSD – 4.3% The results were interpreted in accordance with recommendations (93), ASD – 4.9% (105), ICACA – 8.1% (163). and criteria of CLSI/NCCLS (2010-2011). Of the 2,135 strains, using the double-disks with EDTA method, For all carbapenem-resistant strains a phenotype screening 976 (45.7%) were identified as MBL-producing carbapenem- for MBL was performed using the double-disks method with resistant P. aeruginosa strains. Analysis of monitoring MBL- EDTA [6]. producing P. aeruginosa strains shows that during the analysed In order to identify VIM-type and IMP-type MBL genes a period their number has increased slightly from 33.2% in 2008 real-time multiplex polymerase chain reaction (PCR) was used to 45.4% in 2014 (Table I). (28 poly-resistant clinical isolates of P. aeruginosa). Amplified The next stage of the study involved a molecular genetic fragments of blaVIM and blaIMP genes were identified by determining testing of 28 carbapenem-resistant P. aeruginosa strains. All their melting temperature (~80°C for blaIMP and ~85°C for blaVIM) 28 isolates are confirmed to have VIM-type MBL according to in the presence of intercalating fluorescent dye SYBR Green I. PCR analysis results. Additionally, melting profiles of test specimens were compared Using RFLP method, we established the identical structure to melting profiles of positive control strains. For evaluating of integrons carrying the MBL gene in these isolates and VIM-2 the structure of integrons carrying MBL genes RFLP method coding integrons with a set of gene cassettes aacA7-blaVIM-2- (restriction fragment length polymorphism) was used. Variable dhfrB5-aacC-A5 (GenBank Acc. No. DQ52233), previously regions of class 1 integrons are amplified with the help of primers described in P. aeruginosa strains from Russia [1]. to 5’ (intI1) and 3’ (qacE∆1 or tniC/Tn5090) conservative segments of integrons in pairs with internal primers to blaVIM genes and DISCUSSION are restricted by TaqI enzyme. Resulting restriction profiles of Typing of P. aeruginosa using MLVA shows that all 28 MBL- PCR fragments were compared with corresponding profiles of positive strains of P. aeruginosa are related and belong to a known MBL coding integrons used as controls. single clonal complex (CC235) (Figure 1). This widespread Epidemiological typing of carbapenem-resistant isolates of sequence-type 235 (ST235) is epidemic and has been found in P. aeruginosa was completed using the multiple-locus variable hospitals of 27 cities in Russia, Belarus and Kazakhstan (National

Table I. Monitoring of MBL-producing P. aeruginosa strains. 2008 2009 2010 2011 2012 2013 2014 Total identified strains 328 349 237 341 298 294 288 Number of MBL-producing strains 109 175 82 146 170 163 131 % 33.2 50.1 34.5 42.8 57 55.4 45.4

547 Shamaeva S.K. et al.

Spread of poly-resistance to antibacterial agents among P. aeruginosa isolates in clinical departments of RH No 2 – CEMA can be explained by the identification in them of one of the most widespread mechanisms of antibiotic resistance, connected with metallo-beta-lactamase production. MBL-producing P. aeruginosa isolates are found in all clinical specimens and in virtually all departments of the multi-profile hospital RH No 2 – CEMA. Appearance of poly-resistant MBL-producing strains and dangerous epidemic clones of P. aeruginosa requires the development of measures for infection control aimed at timely identification and limitation of expansion of MBL-producing P. aeruginosa isolates into hospital departments and other medical institutions; introduction of an obligatory permanent monitoring of antibiotic resistance; epidemiological marking Fig. 1. Clonality of P. aeruginosa strains based on MLVA typing of carbapenem-resistant isolates. REFERENCES 1. Li J., Brunner A.M., Shevchenko O., Meilan R., Ma C., Skinner J.S., Strauss S.H. Shevchenko O.et al. Efficient and stable transgene suppression via RNAi in field-grown poplars // Programme for Monitoring the Spread of Strains of Gram- Transgenic Research, 2007; 17(4):679-694. negative Microorganisms Producing Metallo-Beta-Lactamases 2. Reshedko G.K., Ryabkova E.L., Faraschuk A.N., Rosnet research group. Non-fermenting in Russia (METALL). gram-negative agents of nosocomial infections in intensive care units of Russia: issues of Sensitivity determination of MBL-producing isolates of P. antibiotic resistance // Klin. Microbiol Anitmicrob Chemother, 2006; 8(3):243–259. aeruginosa has shown that isolated strains have a high level of 3. Hirsch E.B. & Tam V.H. Impact of multidrug-resistant Pseudomonas aeruginosa infection resistance (100%) to all tested antibacterial agents: piperacillin, on patient outcomes // Expert Review of Pharmacoeconomics & Outcomes Research, piperacillin-tazobactam, ceftazidime, cefepime, cefoperazone- 2010; 10 (4): 441–451. sulbactam, aztreonam, imipenem, meropenem, doripenem, 4. Lambert M.-L. et al. Clinical outcomes of health-care-associated infections and antimicrobial gentamicin, netilmicin, amikacin, ciprofloxacin, levofloxacin, resistance in patients admitted to European intensive-care units: a cohort study // fosfomicin. Isolates are found to be sensitive only to colistin Lancet Infect Dis, 2011; 11(1):30–38. and polymyxin B. 5. Yakovlev S.V. Hospital-acquired infections caused by resistant gram-negative microorganisms: clinical significance and modern possibilities for therapy // Infections and antimicrobial CONCLUSIONS therapy, 2004; 6(4):16–18. In conditions of the multi-profile hospital RH No 2 – CEMA 6. Edelstein M.V. Methods of identifying metallo-beta-lactamases in gram-negative there is a clonal expansion of extensively drug-resistant strain non-fermenting bacteria // Methods of Clinical Laboratory Research. Vol. 3. Moscow: of P. aeruginosa ST235 (VIM-2). Labora, 2009. – P. 404-411.

ADDRESS FOR CORRESPONDENCE: Shamaeva S.K. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street Ph. +7 924 6612751 [email protected]

548 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Th e r o l e o f m e d ic a l a n d s o ci a l f a ct o rs in pre d icti n g disability t u b erc u l o sis

Lineva Z.E., Zorina S.P. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a . r e s e a r c h c e n t e r “p h t h i s i o l o g y ” y a k u t s k , r u s s i a .

ABSTRACT In persisting study are considered social, epydemiological and clinical features by sick tuberculosis lungs with for the first time installed by disability. On the grounds of got result are revealled main criteria of the forecasting to disability on tuberculosis lungs. Disability of pulmonary tuberculosis is an important medical and social problem and is dependent on the social and clinical factors. The study of disability reveals the main reasons for poor prognosis in tuberculosis, which leads to a more chronic course with frequent exacerbations and relapses. In Russia, the dynamics of disability for tuberculosis does not tend to decrease. Unfavorable epidemiological disability tuberculosis remains high in the structure of the primary disability in Yakutsk and Sakha (Yakutia) (2.8%, 2.5% – respectively).

Key words: tuberculosis, disability, the criteria for predicting

Wiad Lek 2015, 68 (4), 549-552

INTRODUCTION MATERIALS AND METHODS In persisting study are considered social, epidemiological The research is based on the results of medical and social and clinical features by sick tuberculosis lungs with for the analysis of 178 adult patients with pulmonary tuberculosis living first time installed by disability. On the grounds of got result in Yakutsk and its suburbs, divided into 2 groups of observations. are revealled main criteria of the forecasting to disability on The first group of observations (118 patients) was formed from tuberculosis lungs. patients with pulmonary tuberculosis receiving receive a primary Disability of pulmonary tuberculosis is an important medical disability. The second group of observations (60 patients) consisted and social problem and is dependent on the social and clinical of patients who are transferred after effective treatment in group factors. The study of disability reveals the main reasons for poor III clinical supervision. prognosis in tuberculosis, which leads to a more chronic course Statistical data processing and analysis were performed using with frequent exacerbations and relapses [1,2]. In Russia, the IBM-compatible computers class «Pentium» and applications dynamics of disability for tuberculosis does not tend to decrease Microsoft Excel 2003; StatSoft Statistica v6.0; SAS ® 9.2 Software [3]. Unfavorable epidemiological disability tuberculosis remains for Windows. Based on the analysis of 27 predictors identified high in the structure of the primary disability in Yakutsk and the most significant signs of disability in pulmonary tuberculosis. Sakha (Yakutia) (2.8%, 2.5% – respectively). Each feature has been coded in several ways. The purpose of Primary disability pulmonary tuberculosis is an indicator of multivariate analysis was to identify the factors of the number treatment failure patients identified in the phase of disintegration, of available, have a significant impact on the development of smear, as well as with acutely progressive process [5,6,7]. According disability in patients with pulmonary tuberculosis. The study to different authors with disabilities due to tuberculosis, are persons groups were analyzed in comparison with each other. Measured with reduced quality of life, low income and educational level the contribution of each feature and calculated ratios. To develop [1, 2, 3]. This situation requires the development of prediction predictive models of disability with pulmonary tuberculosis methods for the prevention of disability of patients with pulmonary method was used logistic regression, which is a statistical method tuberculosis, for an individual approach to the registration of for determining the effects of several factors to a pair of outcomes, patients with identified signs of disability. in this case the outcome was “disabled” and “not disabled.” The purpose of this study was to develop predictive models As an indicator of the actual distribution of the consent of disability in patients with pulmonary tuberculosis based on of the observations and the forecast used the percentage of the available medical and social factors. correct reclassification based on logistic regression equation Aim. The development of predictive models of disability (Concordant), as well as the value of the coupling coefficient according to medical and social characteristics of TB patients D-Sommer (Somers’D). in the study group and approval of the model obtained in the The significance level for inclusion (exclusion) of the predictors control group supervision. in the regression equation were asked so that the current level

549 Lineva Z.E., Zorina S.P. of statistical significance of the Wald x2 (Pr> Chi-Square) for In persisting study are considered social, epydemiological each predictor after stepwise procedure did not exceed 10%. and clinical features by sick tuberculosis lungs with for the The critical level of significance for statistical tests was assumed first time installed by disability. On the grounds of got result to be 0.05. are revealled main criteria of the forecasting to disability on tuberculosis lungs. RESULTS AND DISCUSSION Disability of pulmonary tuberculosis is an important medical The analysis has been allocated eight of disability, which and social problem and is dependent on the social and clinical suggests that the difference between the outcomes of “disabled factors. The study of disability reveals the main reasons for poor person” and “not disabled” is defined by a sufficiently large prognosis in tuberculosis, which leads to a more chronic course range of indicators. The coincidence of fact and calculations by with frequent exacerbations and relapses [1, 2]. In Russia, the gradations signs of “disabled” and “not disabled” in the arms dynamics of disability for tuberculosis does not tend to decrease of the study was achieved in 95.2% of cases (Concordant), the [3]. Unfavorable epidemiological disability tuberculosis remains coupling coefficient (Somers’D) was 0.905, which is quite a high high in the structure of the primary disability in Yakutsk and rate of reliability. The results are presented in Table I. Sakha (Yakutia) (2.8%, 2.5% – respectively) To work with a model drawn Coding table (Table II), Primary disability pulmonary tuberculosis is an indicator of which presents a set of 8 selected features, factor codes and treatment failure patients identified in the phase of disintegration, components for each trait. Individual features highlighted smear, as well as with acutely progressive process [5,6]. According the probability of “disabled/not disabled”, the coefficient of to different authors with disabilities due to tuberculosis, are persons which was – 7.0783. with reduced quality of life, low income and educational level To illustrate further examples of calculating the probability [1, 2, 3]. This situation requires the development of prediction of graduation “disabled” and “not disabled.” methods for the prevention of disability of patients with pulmonary

Table I. Symptoms affecting the development of the primary disabilitydue to pulmonary tuberculosis. № Standardized Predictor (Estimate Standard Error Wald Chi-Square Pr > ChiSq п/п Estimate 1 Probability forecast „disabled / not disabled” -7,0783 1,8331 14,9102 0,0001 - 2 Material living conditions in -1,4690 0,7769 3,5755 0,0586 -0,3734 3 Is the homeless -4,8232 1,4893 10,4890 0,0012 -0,8040 4 Pernicious habits 0,7515 0,3778 3,9566 0,0467 0,3437 5 The method of identifying 0,8258 0,4064 4,1298 0,0421 0,3548 6 The diagnosis on the registration of 0,7046 0,2821 6,2381 0,0125 0,4536 7 The volume of lesions in the lungs 0,8145 0,3749 4,7193 0,0298 0,4894 8 Phase contamination 1,7964 0,7289 6,0732 0,0137 0,4958 9 ESR level in the primary study 0,1526 0,0403 14,2985 0,0002 1,7549

Fig. 1. Based on the data in Table 1 a mathematical model to predict the outcome of the high reliability of "disabled" or "not disabled" for each individual patient with tuberculosis.

550 Th e r o l e o f m e d i c a l a n d s o c i a l f a c t o r s in p r e d i c t i n g disability tuberculosis

Table II. Coding table tuberculosis, for an individual approach to the registration of Number patients with identified signs of disability. factor Symptom Code (X) sign The purpose of this study was to develop predictive models of disability in patients with pulmonary tuberculosis based on social characteristics the available medical and social factors. Material conditions: Based on the data in Table 1 a mathematical model to predict 1 -1,4690 q not satisfactory 0 the outcome of the high reliability of “disabled” or “not disabled” for each individual patient with tuberculosis (Fig. 1) q satisfactory 1 Рatient A., 36 years old. Material living conditions in (X1)

Is the homeless: – 1; whether homeless (X2) – 0; habits (X3) – 1, the method of 2 -4,8232 q no 0 detection (X4) – 2, diagnosed with the registration of (X5) – 4, the amount of destruction in light (X ) – 3, phase contamination q yes 1 6 (X7) – 1, the level of ESR at baseline (x8) – 25 (mm / h). In Bad habits: solving the regression beta = 4,7291, the probability p (beta)> 0,5. 3 0,7515 q no 0 Based on this result, we can conclude that patients at risk for the outcome of «disabled.» In fact, this patient a year after taking on q is 1 the dispensary registration diagnosed with infiltrative tuberculosis Epidemiological characteristics of the right lung in a phase of decay and contamination, with The method of identifying: an inefficient outcome of primary chemotherapy, set II of q physical 1 disability. Patient B., 31 years old. Material living conditions in (X ) 4 0,8258 q on negotiability 2 1 – 1; whether homeless (X2) – 0; habits (X3) – 1, the method of q from prison 3 detection (X4) – 1; diagnosis of the registration of (X5) – 4, the

q by contact 4 amount of destruction in light (X6) – 1, phase contamination (X ) – 0, the level of ESR at baseline (x ) – 10. In this case, Characteristics of tuberculosis 7 8 beta = -3,9249, the probability p (beta) <0,5, indicating no The diagnosis on the registration of: risk outcome «invalid» in this patient. In fact, the patient B. q tuberculoma 1 established clinical cure of pulmonary tuberculosis in 2.5 years q focal tuberculosis 2 after taking on the dispensary registration and transferred to the inactive group III records. q disseminated tuberculosis 3 The resulting regression model of disability has been tested on 5 0,7046 q infiltrative tuberculosis 4 41 patients with pulmonary tuberculosis, 16 of which are under q cheesy pneumonia 5 the supervision of a group III dispensary – «People with inactive tuberculous process after clinical cure ', and 25 are disabled on q fibro-cavernous tuberculosis 6 tuberculosis and still contain the active group dispensary (Table 3). q TB segmental bronchi 7 Proper distribution of «disabled / not disabled» when you use q cavernous tuberculosis 8 this method in the tested groups was 90.2%. The volume of lung injury: CONCLUSION q 1-2 segments 1 The proposed method has a high reliability of forecasting the 6 0,8145 q share 2 development of disability. The implementation of this method into practice TB facilities will enable the early prediction of q one lung 3 disability in order to design individual treatment plan for each q both lungs 4 patient with tuberculosis and thus increase the effectiveness of Phase of colonization: treatment and reduce the incidence of primary disability. 7 1,7964 q no contamination 0 q is sowing 1

8 0,1526 ESR level at initial study - Table III. The effectiveness of the method Distribution after Proper To get the value [beta] calculates the probability [p] by the actual graduation the application distribution formula shown in Figure 2. For p> 0.5, the patient is likely to distribution develop disability, p <0,5 likelihood of disability not. of the model in% invalid 25 23 92,0 Not disabled 16 14 87,5 (III DGG) Fig. 2. The formula for calculating the probability of [beta] only 41 37 90,2

551 Lineva Z.E., Zorina S.P.

REFERENCES 4. Grishina L. P. Trends in primary disability of the adult population in the Russian Federation 1. Vishnevskaya L. К. The causative factors of disability due to pulmonary tuberculosis / L. for 2001-2005. / L. P. Grishina, Lunev V.P, Bayrakov V.I. // health of the Russian Federation. К Vishnevskaya // The problems of tuberculosis and lung diseases. – 2005.- № 7.– P. – 2006. – № 6. –P. 30-32. 13-15. 5. Klochikha А. V. Medical and social characteristics of the population of primary disability 2. Gorbach L. А. The quality of life of patients with pulmonary tuberculosis / L. А. Gorbach due to tuberculosis in the Omsk region / А. V. Klochikha, Zapariy S.P., Kalashnikova S.N. // Belarusian Medical Journal. – 2002. – № 1. – P. 43-46. // Omsk Scientific Bulletin. – 2006. – № 10. –P. 72-74. 3. Gnezdilova Е. V. Social characteristics of people with pulmonary tuberculosis / Е. V. 6. Khudushina Т. А. Influence of various factors on the disablement of new TB cases / Т. А Gnezdilova // The Eighth National Congress on Respiratory Diseases: a collection. sum- Khudushina, М. G. Маslakova // The problems of tuberculosis. – 1994. – № 5. – P.17- mary. – М., 1998. –276p. 19. 7. Perelman М.I., Коryakin V.А. Diagnosis and treatment of tuberculosis of the respiratory system. Manual for physicians. М.: «Health and Life». 2003 -48p.

ADDRESS FOR CORRESPONDENCE: Lineva Z. E. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street Ph. 89248681529

552 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Th e pre v a l e n ce o f c h r o n ic v ir a l h ep a titis in c h i l d re n a n d a d o l esce n ts in y a k u ti a

Dmitrieva T.G1., Munkhalova YA.A. 1, Argunova E.F. 1, Alexeyeva S.N. 1, Egorova V.B. 1, Alexeeva N.N. 2 1f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a 2i n s t i t u t e o f f o r e i g n p h i l o l o g y a n d r e g i o n a l s t u d i e s

ABSTRACT Chronic hepatitis in children represents a serious health and social problem. Under the conditions of the high prevalence of viral hepatitis in Yakutia epidemiological process has a number of peculiarities. In children chronic hepatitis often occurs with minor clinical manifestations, which complicate diagnosis. The study of the epidemiological, clinical and laboratory data is an important task. The aim of the study was to investigate the epidemiological characteristics of chronic hepatitis in children and adolescents living in hyper-endemic region. Materials and Methods: the study included 1568 patients’ data, registered in the dispensary with a diagnosis of chronic hepatitis in the period from 2000 to 2012. Epidemiological history data of 304 patients with chronic hepatitis were analyzed. The data from official statistics were used for epidemiological analysis. Processing of clinical and laboratory studies was performed using the statistical package IBM SPSS STATISTICS 19. Result: CH epidemiological features were identified, including the prevalence of HBV-infection in etiological structure, the high incidence of the disease among the indigenous population, a high risk of intra-familial infection with hepatitis B virus , high frequency of perinatal infection with hepatitis C virus. It was proposed to maximize screening tests for markers of viral hepatitis and to improve quality control of vaccination. Conclusions: The epidemic process of viral hepatitis in children and adolescents in Yakutia is characterized by domination of HBV-infection in the structure of chronic hepatitis. The predominance of the indigenous nationalities among patients with chronic hepatitis B and the leading role of family contact in the routes structure of infection transmission indicates the importance of ethnic and social factors in contraction of the disease.

Key words: hepatitis, children, adolescents.

Wiad Lek 2015, 68 (4), 553-556

INTRODUCTION from 2000 to 2012 Epidemiological history data of 304 patients Viral hepatitis (VH) is a socially significant disease of a human with chronic hepatitis were analyzed. The group of patients with being and is a major cause of chronic liver disease. According to chronic hepatitis B (CHB) made 50.3% (153 children), of whom the World Health Organization (Inf. Bull. № 164, WHO, 2012) in 122 patients HBsAg was allocated ,in 31 patients (9.9%) in there are more than 500 million people infected with hepatitis the presence of a-NVsor and DNA HBV, HBsAg and a-HBsAg B virus and approximately 150 million – with hepatitis C virus were not detected . The group with chronic hepatitis C included [3,4,10]. Emphatic success in the treatment of chronic hepatitis 116 patients (38.4%). The group of patients with mixed-hepatitis (CH), especially chronic hepatitis C (CHC) has been achieved included 35 patients, accounting for 10.9%. Of these CHB + C [8, 9]. Despite considerable progress in diagnosis, treatment was set in 18 patients (6%), CHB + D in 15 (5%) CHB + C + and prevention of hepatotrophic viral infections, this problem D in 2 (0.7%). For epidemiological analysis we used data from is far from being solved [1, 2, 11]. official statistics of the Territorial Rospotrebnadzor of Sakha Only a few studies were devoted to the problem of the prevalence (Yakutia), the Federal State Health Care “Center for Hygiene and factors of chronic viral hepatitis among native and alien and Epidemiology in the Republic of Sakha (Yakutia)”. When the population of the Republic of Sakha (Yakutia) ( RS (Y)). CH diagnosis was made we took into account the epidemiological, problem In children has not been studied at all [5, 6, 7]. The aim clinical, biochemical data, serological and molecular biological of this study was to investigate the epidemiological features of markers of viral hepatitis. Processing of clinical and laboratory CH in children and adolescents living in hyper-endemic region studies was performed using the statistical package IBM SPSS on the example of the Republic of Sakha (Yakutia). STATISTICS 19.

MATERIALS AND METHODS RESULTS The studies were conducted on the basis of the Pediatrics Clinic The Republic of Sakha (Yakutia) always belonged to the of Republican Hospital №1 of National Center of Medicine and hyper-endemic regions. The incidence of viral hepatitis in SHI of Republic Sakha (Yakutia), “Children’s City Clinical Hospital Yakutia population of all the years of observation exceeded №2». The study included data of 1568 patients who were in the that of the national average. In recent years there has been dispensary with a diagnosis of chronic hepatitis in the period significant reduction in the incidence of viral hepatitis, especially

553 Dmitrieva T.G., et al. acute forms. However, long term epidemiological disadvantage residence. In the regions of the Arctic and Subarctic only 5.3% formed a significant layer of the chronically ill patients, who are of patients lives (Table. I). a constant source of infection due to the fact that CH is a long Significant morbidity among adults in Alaykhovsky district 0 0 lasting chronic disease that goes unnoticed for many years. The with CHB – 601.3 /0000, with CHC – 556.20 /0000; Bulunsky district 0 0 prevalence of the disease, especially among adolescents remains with CHB – 259.90 /0000, with CHC – 183.30 /0000; Nizhny Kolyma 0 0 unclear. On the basis of indirect evidence it can be judged as district with CHB – 179.3 /0000, with CHC – 200.4 /0000 and the 0 sufficiently high risks of CH infection in children and adolescents. incidence of primary liver cancer in the region (16,05 /0000) indicate Thus, the proportion of pregnant women with HBs-antigenemia a high level of hepatotrophic viruses infection in population . for 2000-2011 was 3.29%, while the dynamics was not tended But due to the objective situation people seek treatment only to decrease. The frequency of infection with hepatitis C virus when there are serious health problems. At the same time, cases was 1.1% [11]. In childhood there is an extremely high risk of of chronic hepatitis in children and adolescents in these districts perinatal infection transmission. A large spread of CH in the have not been identified. adult population of Sakha (Yakutia) (from 120.1 per 100 thousand In many regions of the country, thanks to the introduction of population in 2003 to 88.4 per 100 thousand of population of hepatitis B vaccine into the national immunization schedule, in 2011) indicates about the broad contacts of children and the incidence and forms of acute and chronic HBV-infection adolescents with these sick people. were significantly reduced. This trend is observed in our country In our study we identified several problems of early diagnosis (Fig. 2), but despite good immunization coverage of children of VH in pediatric practice. These include primarily minimal under 14 years (since 2006 more than 90%) and a decrease in clinical disease manifestations in the early stages. In most cases, the number of new cases of hepatitis B in the Sakha Republic the diagnosis was made by chance, when examining a patient (Yakutia), CHB is diagnosed in more than half of children and with another disease – in 189 patients, accounting for 62.6%. adolescents with chronic hepatitis (67.1%). In 57 cases (18.9%) diagnosis was put during the examination In analyzing the distribution of patients with chronic hepatitis of the child’s contact with the CVH sick person. The survey, B, chronic hepatitis C and mixed hepatitis according to age we scheduled on the complaints of a patient,revealed CH in 56 revealed a statistically significant difference (p <0.05). In the group patients (18.5%). A serious problem is a weak diagnostic base of mixed-hepatitis the proportion of patients older than 14 years in the districts of the Republic. Hepatitis viral marker analysis was significantly lower than mono-hepatitis. The distribution often detects only HBsAg. This may explain much larger number of patients by sex was similar for all hepatitis and statistically of new cases of CHV under examination in the Medical and significant differences were detected (p> 0.05) (Table. II). Preventive Treatment Facilities compared with CHB (15.3% The special features of the epidemiological process of CH and 46.8%, respectively). In addition, in our study we have in children and adolescents in the Republic of Sakha (Yakutia) shown that the inclusion of a-HBcor screening can detect are undoubtedly include the ethnicity of patients. Statistically patients with HBsAg-negative CHB. According to our data significant differences in the frequency of detection of CHB, the proportion of such patients is 6.8% of all patients with CHC and mixed-hepatitis in patients of different ethnicities CHB. The absence of a specialty “Children’s Infectious Disease (p <0.05) (Table. III) were revealed. Physician” leads to the fact that children with chronic hepatitis The table shows that in most cases the patients with CH are are not subjected to regular medical check-up in a dispensary representatives of the indigenous nationalities. According to the and are not observed properly. This is especially characteristic latest census the proportion of indigenous peoples (the Yakuts of Arctic and Subarctic regions of the country, where a number and the Indigenous small –numbered peoples of the North) in of objective factors (low population density, remoteness and the RS (Y) does not exceed 47%, but among children with chronic small size of settlements, a complicated transportation scheme, hepatitis, it is 71.1% of cases. CHB is much more common in often nomadic or semi-nomadic way of life) make it difficult for children and adolescents of the indigenous nationality – in 75.2% people to access, not only to the specialist, but also in general of cases. Whereas, with a comparable frequency of CHC detected to health care institutions. This conclusion is confirmed by the in children and adolescents, and indigenous and non-indigenous: analysis of the distribution of patients with chronic hepatitis 58.7% and 41.3%, respectively. This indicates the presence of who are registered with a doctor-hepatologist, by region of ethnic epidemiological peculiarities of viral hepatitis.

Table I. The distribution of patients with chronic hepatitis b, chronic hepatitis c, hepatitis b and mixed by region of residence. CHC Mixed-hepatitis CHB (n = 153) (n = 116) (n = 35) HbsAg (+) HbsAg (-) n % n % N % n % Arctic 11 9.1 1 1.6 4 3.4 0 0 Subarctic 11 9.1 1 1.6 8 6.9 2 5.7 Far North 100 37.9 29 11 104 39.4 33 94.2

554 Th e p r e v a l e n c e o f c h r o n i c v i r a l h e p a t i t i s in c h i l d r e n a n d adolescents in y a k u t i a

Table II. The distribution of CH patients by age groups. CHB (n = 153) CH C (n = 116) Mixed-hepatitis (n = 35) Age HbsAg (+)(n = 122) HbsAg (-) (n = 31) n % n % N % n % Up to 1 year 2 1/6 0 >0.05 5 4.3 2 5.7 1-3 years 7 5.7 1 >0.05 3 2.6 6 17.1 4-6 years 6 4.9 5 16.1 18 15.5 2 5.7 7-10 years 22 18 3 9.7 18 15.5 6 17.1 11-14 27 22.1 8 25.8 27 23.3 15 42.8 Older than 14 years 58 47.5 14 45.2* 44 37.9 3 8.5* * The difference is statistically significant p <0.05.

Table III. Distribution of patients with chronic hepatitis B, chronic hepatitis C and mixed hepatitis by nationality. chronic hepatitis B (n = 153) chronic hepatitis C (n = 116) Mixed-hepatitis (n = 35) Nationality HbsAg (+) (n = 122) HbsAg (-) (n = 31) n % n % n % n % Yakut (n = 195) 86 70.5* 22 71* 64 55.2* 24 68.5* Russian (n = 77) 24 19.6* 8 25.8* 36 29.6 9 25.7 Indigenous (n = 11) 7 5.7 0 0 4 3.4 0 0 Others (n = 20) 5 4.1 1 3.2 12 10.3* 2 5.7* * The difference is statistically significant p <0.05.

In the analysis of the possible ways of infection the leading of the North) in the RS (Y) does not exceed 47%, but among role of family contact was determined. The presence of the children with chronic hepatitis, it is 71.1% of cases. Also, it was CH in the patient’s family was noted in 41.4% of children and defined that the family contact occupied the leading place in adolescents with chronic hepatitis. There is a direct correlation the structure of routes transmission. The maximum number of family contact depending on the child’s age (p <0.001) and of chronic hepatitis cases was found in adolescents.The risk the etiology of the process (p <0.05) (Table. IV). of infection dramatically increases in adolescence, due to the CH is often diagnosed in adolescents in the age group over spreading of infection tract. Smoking, piercing, tattoos, sex 14 years – 45.4%. At this age the highest number of patients are added to usual childhood blood-borne infection path in diagnosed for the first time CHB was recorded. later period of life. In addition, at the age of 16 young men had thorough medical examination including serological diagnosis DISCUSSION during the Commission before military conscription. The results This study is the first one devoted to the research of the showed the value of ethnic and social factors in causing the prevalence and factors of chronic viral hepatitis in children and disease. adolescents in the Republic of Sakha (Yakutia). These incidence of VH prevalence of VH markers among blood donors and CONCLUSION pregnant women in the complex, allow sufficiently objectively 1. The epidemiological process of chronic hepatitis in children assess the epidemiological situation of СH among the adult and adolescents in the Republic of Sakha (Yakutia) at present population. Evaluation of the same frequency of VH among has a number of peculiarities. CHB is still the most frequent children and adolescents is carried out only on the basis of diagnosis in children and adolescents with chronic hepatitis, diagnoses registration, which creates objective difficulties in the accounting for 67.1%. A significant role in the structure of analysis of the epidemiological situation. However, taking into CH transmission paths in children and adolescents plays a account the direct and indirect data, we have identified some family member. The frequency of family contacts of patients epidemiological peculiarities of CH in children and adolescents with chronic hepatitis B was 43.8% ,with CHC- 33.6% and living in Yakutia. These include a large share of HBV-infection in mixed-hepatitis – 57.6%. There were significant differences in the structure of chronic hepatitis. There is the predominance of the structure of CH in children and adolescents of different the indigenous nationalities among patients with chronic hepatitis. nationalities. The proportion of indigenous nationalities among According to the latest census the proportion of the indigenous patients with chronic hepatitis B is 75.2%, CHB + D – 93.3%. peoples (the Yakuts and the Indigenous small-numbered peoples The most common disease of CH is detected in adolescence:

555 Dmitrieva T.G., et al.

Table IV. Family contact and the age of patients with chronic hepatitis. Age Family contact With with several members P With mother With father siblings of the family n 4 0 0 0 Up to 1 year <0.001 % 57.1 0 0 0 n 10 0 0 3 1-3 years >0.05 % n 76.9 0 0 23.1 4-6 years >0.05 % 8 3 3 1 n 26.7 10 10 3.3 7-10 years >0.05 % 7 1 1 1 n 15.9 5.2 5.2 2.9 11-14 years >0.05 % 10 10 10 2.9 n 22 22 22 13 Older than 14 <0.05 % 27.7 16.1 16.1 9.5

CHB in 69.9% of cases, chronic hepatitis C – 61.2%, the mixed 4. Uchaikin V.F. Cirrhosis of the liver in children. / Uchaikin V.F. Chuelov S.B., Rossina .A.L hepatitis – 82.9%. [et al] //Pediatrics. 2008; 87 (1): 11-19p. 2. To ensure the availability and quality of care for children and 5. Kirillova T.A. Risk analysis of vertical transmission of hepatitis C in children. / Kirillova, adolescents with chronic hepatitis it is necessary for improvement T.A., Grobovetskaya N.A. Khabudaev V.A.[ et al.] // Infectology Journal. 2011; 3, Appendix of CH primary prevention quality in children to put into practice N 3: 54-55p. CHB vaccination of family members of patients with newly 6. Elisofon S.A., Hepatitis B and C in children: current treatment and future strategies. / diagnosed chronic hepatitis B in out-patient departments at the Elisofon S.A., Jonas M.M. // Clin. Liver Dis. 2006; 10 (1): 133-148p. level of primary health care; to improve the quality of secondary 7. Sokal E.M. Management of chronic hepatitis B in childhood: ESPGHAN clinical practice prevention of CH in children and adolescents research on BBM guidelines: consensus of an expert panel on behalf of the European Society of Pediatric must be included into medical examinations, to make it mandatory Gastroenterology, Hepatology and Nutrition. / Sokal E.M., Paganelli M., Wirth S. [et al.] for planned and emergency hospitalization in various fields. To // J. Hepatol. 2013; 59 (4): 814-829p. expand the screening by including a-HBcor and a-HBs. 8. Strokova T.V. The natural course of chronic HBV + HCV infection in children. / Strokova T.V., Mashulan I.V., Sentsova T.B. [et al ]//Clin. Gastroenterology. 2013; REFERENCES 1: 29-33. 1. Ponomarenko T.N. Clinical and laboratory features of acute hepatitis C in people of 9. Semenov S.I.// Epidemiological features and clinical characteristics of viral hepatitis B, middle age. / Ponomarenko T.N. // World of viral hepatitis. 2009; 1: 26. C and delta in the Republic of Sakha (Yakutia): Abstract. Dis. .... Doc. Med. Sciences. M .; 2. Zhdanov K.V. Saint-Petersburg. / Zhdanov K.V., Gusev D.A. Lobzina Y. Viral Hepatitis. //: 2007. 48 pp. Tome; 2011. 304 p. 10. Fedoseyeva, L.R. // Clinical and epidemiological characteristics of hepatitis B virus in 3. Baranov A.A. Incidence of chronic viral hepatitis in the child population of the Russian pregnant women in the Republic of Sakha (Yakutia). : Author. Dis. .... PhD. Med. Sciences. Federation for the period 2003-2012. / Baranov A.A., Namazova- Baranova L.S. , Volynets M .; 2008. 23 pp. G.V. [et al.]// M .: “Ultra Print”; 2012. 46 pp. 11. Sleptsova S.S. Peculiarities of chronic viral hepatitis in Yakutia. / Sleptsova S.S., Tikhonova N.N., Samsonova V.K.,Djachkovskaya P.S. // J. Infectious Diseases. 2011; 9: 343p.

ADDRESS FOR CORRESPONDENCE: Munhalova Y. A. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street [email protected]

556 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Di a g n o stics a l g o rit h m o f d i a b etic p o l y n e u r o p a t h y in pre d icti o n o f clinical c o u rse

Popova T.E.1, Tappahov A.A.1,3, Shnaider N.A.2, Petrova M. M2, Nikolaeva Т.Y.1, Konnikova E.E.1, Kozhevnikov A.A.2, Ammosov V.G.1, Vinokurova N.E.4 1f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a 2krasnoyarsk s t a t e m e d i c a l u n i v e r s i t y n a m e d a f t e r p r o f . v.f.v o i n o -y a s e n e t s k y, r u s s i a 3r e p u b l i c h o s p i t a l №2 –c e n t e r o f e m e r g e n c y, r u s s i a 4y a k u t s k municipal clinical h o s p i t a l , r u s s i a

ABSTRACT Aim: to estimate the importance of new algorithm introducing of PDP diagnostics in practice of NEFU medical institute Clinic in detection of severity level and predicting of clinical course. Materials and methods: 50 people with sensory-motor PDP form among patients with 2 type diabetes were examined on the basis of Clinic of NEFU medical institute. Patients have been divided into 2 groups by disease duration: the first groups were patients with duration of disease till 10 years, the second group – more than 10 years. Diagnostics methods: clinical neurologic, neurophysiological. Results: patients underwent polymodal sensitivity analysis, computer pallesteziometry, stabilometry, electroneuromyography. The dependence of clinical neurophysiological PDP parametres from severity of the duration of type 2 diabetes has been revealed. Conclusion: thus, dependence of clinical-neurophysiological parametres of PDP severity from the duration of 2 type diabetes has been revealed. The new algorithm raised efficacy of clinical-neurophysiological PDP diagnostics and helped the predicting of the clinical course.

Key words: diabetic polyneuropathy, diagnostics, computer pallestesiometry, stabilometrics, electroneuromyography.

Wiad Lek 2015, 68 (4), 557-561

INTRODUCTION medical institute Clinic for severity level detection and predicting Prevalence of diabetes mellitus (DM) all over the world last of clinical course. years has compounded 2,8 %. By 2030 the quantity of patients with DM will reach 366 million persons (4,4 % of the general MATERIALS AND METHODS population) [1]. In Russia for the last 15 years the number of Clinical-laboratory researches were made on the basis of Clinic patients with DM has reached 2-4 % of population in some of medical institute of «The North-Eastern federal university regions [2]. Approximately 30-60 % of patients with DM develop named after M.K.Ammosov» (Yakutsk) from January till April, peripheric diabetic polyneuropathy (PDP)[3]. Distal symmetric 2015 within the partner complex researches with employees of polyneuropathy is most often met PDP form and compounds Krasnoyarsk state medical university named after Prof. V.F.Voino- 75 % of all diabetic neuropathy [4], 30 % of patients with DM Yasenetsky (Krasnoyarsk) with the topic: «Epidemiological, genetic are diagnosed with it in-patient department and 25% of the and neurophysiologic aspects of diseases of the nervous system patients are observed it in out-patient department [5, 6]. (central, peripheral and vegetative) and preventive medicine» Among neurophysiological methods of PDP diagnostics (гregistration 0120.0807480). The object of research was a group the most significant are electroneuromyography (ENMG) and of patients with PDP with 2 type DM. All patients passed careful computer pallestesiometry [7-12] which allow to verify degree preliminary anamnestic and clinical selection which was carried and character of affection of peripheral nerves and also to estimate out by stratified randomization method with the use of criteria efficacy of therapeutic treatment. of incorporation and exception, developed according to the In 2012-2013 new advanced algorithm of polyneuropathy purpose and problems of the present research. diagnostics with modern highly informative neurophysiological The volume of neurophysiological examination included methods, including computer pallestesiometry, stabilometrics, computer pallestesiometry, stabilometrics, ENMG. Computer ENMG was developed on the basis of the neurologic centre pallestesiometry was made on domestic diagnostic equipment of University clinic in Krasnoyarsk state medical university “Vibrotester-MBN” VT-02-1 with the use of the original device (Krasnoyarsk) together with colleagues from the North-Eastern for mount “Vibrotester-MBN” VT-02-1 (patent №83906 in federal university (Yakutsk) and scientific Centre of neurology 6/27/2009) [2, 9]; stabilometrics – by means of diagnostic platform (Moscow) [7, 9-12]. Aim: to estimate the importance of new “Mera” (Moscow) in Romberg’s posture by European variant of algorithm introducing PDP diagnostics in practice of NEFU feet installation in 2 phases: with opened (ОE) and closed (CE)

557 Popova T.E., et al. eyes [13]; stimulation ENMG – on device “Neirosoft” (Ivanovo), The sensitive disorders of polyneurotic type dominated in including research of speed impulses by motor fibers (SI) and clinical PDP pattern, paresthesia were most often marked (in the SI by sensitive fibers (SIs) of median, fibular and tibial nerves. 1st group –74,1%, in the 2nd group – 82,6%) and hyperesthesia The critical level of tests’ importance has been defined at p ≤ (55,6% and 78,3% accordingly). Tactile sensitivity has been 0,05. Statistical processing of results was made by means of applied reduced among 22 (81,5%) patients of the 1st group and 23 programs packages Statistica 7.0 (StatSoft, USA). Statistical data (100%) patients of the 2nd group. Muscle strength decrease processing and interpretation of the received results considered in the 1st group has been revealed in 1 patient (3,7%), in the modern international requirements to representation of results second –2 (8,6%). Thus, patients with PDP mainly were noted of statistical analysis in articles and dissertations. sensitive neuropathy type, more expressed in the 2nd group of the examined. Vegetative PDP manifestations were revealed RESULTS AND DISCUSSION in 1/3 patients. The clinical characteristic of patients with PDP In total 50 persons with 2 type DM at the age from 36 till 77 Computer pallestesiometry years old, median age – 57 [50,75; 64] years old. All examined The comparison of indexes of vibrating sensitivity from outside patients have been divided into 2 groups depending on 2 type anklebones and styloid processes among PDP patients with DM duration: the first group – patients with duration of disease reference corridors norms for healthy volunteers of middle age till 10 years; the second group – patients with duration of disease has given the data testifying the vibrating sensitivity damage that over 10 years. was caused by development of demyelination of thick myelinated The 1st group included 27 patients, median age of 56 years fibres βA type of peripheral nerves (fig. 1-2). old [50; 61], males – 8 (29,6%), females – 19 (70,4%); the 2nd The comparative analysis of pallestesiometry results from group – 23 patients, median age of 62 years old [55; 66], males outside anklebones has revealed that patients suffering from – 5 (21,7%) and females – 18 (78,3%). Prevailed persons of the DM for more than 10 years, statistically significant increase of Yakut ethnic group: in the 1st group – 81,5 %; in the 2 group corridor borders in all investigated frequencies that testified – 74%. The median age of a debut has compounded in the 1st damage progressing of vibrating sensitivity has been noticed. group – 50 years old [42; 56], in the 2nd group – 40 years old At the same time the similar analysis of pallestesiometry results [35; 50] (р=0,003). In the 1st group there were 6 people (22,2 %), didn’t have statistically different distinctions from styloid processes in the 2nd group – 13 people (31,6 %) (р <0,001) had physical that could be a cause of later involving of nerves of the upper inability. extremities. Insulin in the 1st group was received by 13 people (48,1 %), in 2 group – 17 people (73,9%); peroral hypoglycemia drugs – the Stabilometrics 1st group – 14 people (51,9%), and in the 2nd group – 6 people The pressure centre position in frontal plane was not displaced, (26,1%). Level of glycemia on empty stomach in the 1st group in sagittal – was displaced forward (anteropulsion) by stabilometrics has compounded 8,6 [6,98; 12] mmol/l and in the 2nd group – results in both examined groups. Indexes of speed of pressure 9,1 [7; 11,6] mmol/l (р=0,94). Level of glycemia haemoglobin centre displacement did not exceed standard sizes as a whole. was 7,3 [6,1; 8,7] and 7,3 [6,7; 9,7] (in the 1st and 2nd groups The statokineziogram area in both groups exceeded standard accordingly) (р=0,72). sizes in both phases of research that was caused by presence of

Fig. 1. Results of computer pallestesiometry among PDP patients of the1st group in distal departments of the lower and upper extremities (A - outside anklebone, B – styloid process) in comparison with control (red line– patients with chronic inflammatory demyelinated polyneuropathy; green line– healthy volunteers).

558 Di a g n o s t i c s a l g o r i t h m o f d i a b e t i c polyneuropathy in p r e d i c t i o n o f clinical c o u r s e

Fig. 2. Results of computer pallestesiometry among PDP patients of the 2nd group in distal departments of the lower and upper extremities (A - outside anklebone, B – styloid process) in comparison with control (red line– patients with chronic inflammatory demyelinated polyneuropathy; green line– healthy volunteers).

centre moving per 1 sec; QR –Romberg’s quotient; ОE – data for a phase with open eyes; CE –data for a phase with close eyes.

Stimulation electroneuromyography The signs of axoanalis – demyelinated affection in both groups were revealed in research of motor and sensitive fibers of median nerves and demyelinated changes have been expressed in the 2nd group in a greater degree. The analyses of motor fibers of fibular nerves also revealed presence of axoanalis – demyelinated affection in both groups, however the big expressiveness of both axoanalis and demyelinated changes was marked in the 2nd group. Similar changes, but to a lesser degree, were observed and in sensitive fibers of fibular nerves. The axoanalis – demyelinated affections were found in motor and sensitive fibers of tibial nerves according to ENMG, more expressed among patients of the 2nd group (tab. 1).

CONCLUSION Computer pallestesiometry and ENM allow to estimate Fig. 3. Indexes of stabilogrammas with PDP in two examined groups in comparison with objectively degree of affection of nerve fibrils and their standard indexes. character among patients with PDP. There is time connection between expressiveness of changes and duration of disease and pathological changes are more expressed in peripheral nerves of the lower extremities. Stabilometrics elicits the fact patients with DM of both cortical and sensitive ataxia. Power of postural damages and their character, estimates involving inputs exceeded standard values in both phases of research, degree of proprioceptive evaluator reflecting affection of thick especially among patients of the 2nd group. However statistically myelinated fibres of the lower extremities in PDP. The received significant distinctions between two examined groups has not results of neurophysiological researches were co-ordinated with been revealed by all stabilometric indexes during research. increase of neurologic semiology while carrying out polymodal Notations: X – centre position of pressure centre in frontal research of sensitivity. Thus, the offered algorithm of PDP plane; Y – centre position of pressure centre in sagittal plane; S – diagnostics can be more widely used for PDP objectification statokineziogram area; Ei – power index; V – speed of pressure and assessments of its severity degree.

559 Popova T.E., et al.

Table I. Results of stimulation ENMG. 1st group (n=27) 2nd group (n=23) p-value Median nerves, motor fibers Motor nerve action potential Normal 18 (66.7%) 18 (78.3%) < 0.001* Some to half 8 (29.6%) 5 (21.7%) More than half 1 (3.7%) - Motor nerve conduction velocity on the segment “wrist-elbow” Normal 20 (74.1%) 11 (47.8%) 0.09 Some to half 7 (25.9%) 12 (52.2%) More than half - - Motor nerve conduction velocity on the segment “elbow- the lower third of the shoulder” Normal 21 (77.8%) 12 (52.2%) < 0.001* Some to half 5 (18.5%) 11 (47.8%) More than half 1 (3.7%) - Median nerves, sensory fibers Sensory nerve action potential Normal 21 (77.8%) 16 (69.6%) < 0.001* Some to half - - More than half 6 (22.2%) 7 (30.4%) Sensory nerve conduction velocity on the wrist Normal 15 (55.6%) 4 (17.4%) 0.13 Some to half 7 (25.9%) 14 (60.9%) More than half 5 (18.5%) 5 (21.7%) Peroneal nerves, motor fibers Motor nerve action potential Normal 11 (40.7%) - 0.07 Some to half 8 (29.6%) 7 (30.4%) More than half 8 (29.6%) 16 (69.6%) Motor nerve conduction velocity on the segment “tarsus-head of the fibula” Normal 25 (92.6%) 11 (47.8%) < 0.001* Some to half 2 (7.4%) 10 (43.5%) More than half - 2 (8.7%) Motor nerve conduction velocity on the segment “head of the fibula-the lower third of the thing” Normal 22 (81.5%) 10 (43.5%) < 0.001* Some to half 4 (14.8%) 11 (47.8%) More than half 1 (3.7%) 2 (8.7%) Peroneal nerves, sensory fibers Motor nerve action potential Normal 10 (37%) 5 (21.7%) 0.005* Some to half - - More than half 17 (63.%) 18 (78.3%) Motor nerve conduction velocity on the rear foot Normal 9 (33.3%) 5 (21.7%) 0.002* Some to half - - More than half 18 (66.7%) 18 (78.3%)

560 Di a g n o s t i c s a l g o r i t h m o f d i a b e t i c polyneuropathy in p r e d i c t i o n o f clinical c o u r s e

Table I. Cont. Tibial nerves, motor fibers Motor nerve action potential Normal 10 (37%) 5 (21.7%) < 0.001* Some to half - - More than half 17 (63.%) 18 (78.3%) Motor nerve conduction velocity on the segment “tarsus-popliteus” Normal 14 (51.9%) 4 (17.4%) < 0.001* Some to half 13 (48.1%) 17 (73.9%) More than half - 2 (8.7%) Tibial nerves, sensory fibers Motor nerve action potential Normal 19 (70.4%) 7 (30.4%) 0.78 Some to half - - More than half 8 (29.6%) 16 (69.6%) Motor nerve conduction velocity on the lateral malleolus Normal 21 (77.8%) 9 (39.1%) 0.16 Some to half - - More than half 6 (22.2%) 14 (60.9%) * - significant differences

REFERENCES 8. Коvrazhkina E.A. Demyelinizing forms of polyneuropathy among patients with diabetes 1. Wild S. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030 and chronic alcoholic intoxication / Коvrazhkina E.A. // Journal Neurology and psychiatry / Wild S., Roglic G., Green A. [et al.] // Diabetes Care – 2004. Vol. 27. – P. 1047-1053. named after S.S.Korsakova. – 2012.–V. 112, № 5. – P. 41–45. 2. Balabolkin M. I. Diabetology // – M: Medicine 2000. – 671 p. 9. Popova T.E., Dynamics of changes of vibrating sensitivity according to computer 3. Tavakoli M. Management of painful diabetic neuropathy / Tavakoli M., Malik R.A. // pallestesiometry in acqiured and genetically determined forms of polyneuropathy Expert OpinPharmacother – 2008. – Vol. 17. – P. 2969-2978. of myelinopathy class / Popova T.E., Shnaider N.A., Petrova M. M., [et al.] // Siberian 4. Bansal V. Diabetic neuropathy / Bansal V., Kalita J., Misra U.K. // Postgrad. Med. J. – medical review. – 2014. – № 5. – P. 12-16. 2006. – Vol. 82. – P. 95-100. 10. Popova T.E., Principle of diagnostics polyneuropathies in the general medical practice / 5. Turbina L.G. Diabetic neuropathy: epidemiology, pathogeny, clinic, diagnostics, treatment Popova T.E., Shnaider N.A., Petrova M. M., [et al.]// Manual of the general practitioner. / Turbina L.G., Gordeev S.A., Zusman A.A. // Journal Neurology and psychiatry named – 2014. – № 11. – P. 18-32. after S.S.Korsakova – 2010. – V. 110, №11. – P. 56-62. 11. Popova T.E., Mainly sensitive chronic inflammatory demyelinizing polyneuropathy in 6. Ziegler D. KORA Study Group. Prevalence of polyneuropathy in prediabetes and diabetes practice of the neurologist: new approach to diagnostics / Popova T.E., Shnaider N.A., is associated with abdominal obesity and macroangiopathy: the MONICA/KORA Augsburg Petrova M. M., // Consiliummedicum. – 2014. – № 9. – P.27-31. Surveys S2 and S3 / Ziegler D., Rathmann W., Dickhaus T. [et al.] // Diabetes Care. – 12. Shnaider N.A., Sensitivity computer pallestesiometry in distal departments of the 2008. – Vol. 31. – P. 464-469. upper extremities in hereditary neuropathy of Charcot-Marie-Tuta / Shnaider N.A., 7. Schneider N.A. Diagnostics diabetic neuropathy: Monography // Editor N.A. Schneider, Glushchenko E.V. // Modern medical technologies – 2011. – № 6. – P. 65-67. M.M. Petrova // М: Publishing house Medic, 2014. – 288 p. 13. Skvortsov D.V. // Stabilometric research. – М: Maska, 2010. – 176 p.

ADDRESS FOR CORRESPONDENCE: Popova T.E. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street

561 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Th e i n f l u e n ce o f u ri n a r y tr a ct i n f ecti o n s o n tre a t m e n t o f f r a ct u re o f pr o x i m a l f e m u r in p a tie n ts w it h s y ste m i v o ste o p o r o sis

Palshina A.M.¹, Bannaev I.F.², Palshin G.A.¹, Shamaeva S.Kh.², Yadrikhinskaya V.N.¹, Komissarov A.N.², Krivoshapkina A.G.¹ ¹f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a ²s b i “r e p u b l i c h o s p i t a l №2 – t h e c e n t e r o f e m e r g e n c y m e d i c a l c a r e , y a k u t s k

aBSTRACT In the structure of intrahospital infections the infections of urinary tract make up from 20 to 40%. This problem represents special medical-social significance for trauma departments as patients with trauma are being in forced situation for a long time. 380 patients older than 60 years (average age 73.6±9.2 years) with a fracture of proximal femur against background of the systemic osteoporosis having in-patient treatment in the trauma department of the Republic Hospital №2 were being examined and treated from 2011 to 2013. Urinary tract infections were diagnosed in 130 (34.2%) patients (average age 77.3±8.3 years). Women (80%-82%) with the average age 77.7±8.2 years prevailed by gender signs. From them 40 (30.8%) patients admitted with prehospital urinary tract infections and intrahospital urinary tract infections were diagnosed in 90 (69.2%) patients. In etiological structure of urinary tract infections the part of gram-negative microorganisms made up 47.4%, the leading role belonged to the family of Enterobacteriaceae. Escherichia coli (23.3%) and Klibsiella pneumonia (12%) were the most significant from them. Gram-positive microorganisms 44% were sown in the second place.M ore frequently Enterococci (33.6%) were separated such as Enterococcus faecium (18.1%) and Enterococcus faecalis (15.5%). Intrahospital urinary tract infections resistant to antimicrobial therapy were observed in 6.7% patients with systemic osteoporosis and fracture of proximal femur. The average duration of preoperative preparation and in-patient treatment of patients with fracture of proximal femur and concomitant urinary tract infections is much more (3.9 days and 5.4 bed-days correspondingly) higher than the average indications of all operated patients in the department.

Key words: urinary tract infection, fracture of femur

Wiad Lek 2015, 68 (4), 562-564

INTRODUCTION has appeared against background of the systemic osteoporosis Considerable spreading of infectious diseases of urinary tract in patients older than 60 years. is one of the most important problems of the health services [2]. Specific weight of urinary tract infections (UTI) in the MATERIALS AND METHODS infectious structure connected with giving medical help makes 380 patients older than 60 years (average age 73.6±9.2 years) up from 20 to 40%. Considerable economic expenses connected with a fracture of proximal femur against background of the with UTI were conditioned by the increasing of expenses on systemic osteoporosis having in-patient treatment in the trauma diagnostics, treatment and hospitalization period [3]. Despite department of the Republic Hospital №2 (RH№2) were being successes in diagnostics and treatment of UTI of the last years examined and treated from 2011 to 2013. All patients have got the problem of achievement of clinical-laboratory recovery with fractures when falling from height of own growth. Patients with pathogen eradication is being of great interest [4]. The most a tumor of the bone have been excluded. UTI was diagnosed frequent pathogen is Escherichia coli in old age and association in 130 (34.2%) patients (average age 77.3±8.0 years). Patients of microbes is in 20% of cases [4]. Elderly patients may have with UTI were divided into 2 groups. There were 40 (30,8%) the change f pathogen and the development of poly-resistant patients with UTI in anamnesis: 32 (80%) women, average forms during the illness. It is also characteristic of relapsing and age 77.7±8.2 years and 8 (20%), average age 76.6±6.6 years more serious course of the illness [4]. The most serious medical- in the 1st group. There were 90 (69.2%) patients without UTI social consequences among fractures against background of in anamnesis: 74 (82.2%) women, average age 77.4±7.9 years the systemic osteoporosis are conditioned by the fracture of and 16 (17.8%) men, average age 75.1±9.0 years in the second proximal femur (FPF) [1]. group. The diagnosis was mde ccording to the clinical-laboratory Object: To study the influence of urinary tract infections examination during hospitalization and in-patient treatment. on the treatment results of the fracture of proximal femur that General clinical investigations of blood and urine, ultrasound

562 Th e i n f l u e n c e o f u r i n a r y t r a c t i n f e c t i o n s o n t r e a t m e n t o f f r a c t u r e o f p r o x i m a l f e m u r in p a t i e n t s w i t h s y s t e m i v osteoporosis investigations of abdominal cavity and kidneys were carried out. positive microorganisms 44% were sown in the second place. Standard methods were used to separate and identify isolated Psuedomonas aeruginosa in 5 (4.3%) tests and Acinetobacter strains. The sensitivity of isolated strains to antibiotics was baumannii in 3 (2,6%) tests were separated considerably rare. determined by disc-diffusive method on the Muller-Hinton Gram-positive microorganisms 44% (51 isolated strains) medium. Testing and estimation of the results were carried out have got the second place. Enterococci (39 strains – 33,6%) were according to MI 4.2.1890-04. separated more frequently such as Enterococcus faecium 21 (18.1%) and Enterococcus faecalis 18 (15,5%) strains. In 12 samples RESULTS Staphylococci were separated such as Staphylococcus aureus 3 In the 1st group of patients, leucocytoria in the urine sediments (2.6%). Staphylococcus saprophyticus 1 (0.9%), Staphylococcus were revealed in 25 (62.5%) patients at admitting and acute epidermidis 8 (6.9%) strains. Fungi – Candida spp. were separated condition of UTI occurred in 7 (17.5%) patients during in- in 10 (8.6%) samples. patient treatment. Slight proteinuria less than 100 mg/l had 8 Sensitivity analysis to antimicrobial drugs of more frequently (20%) patients, the average level was 34.1±8.6 mg/l, moderate sowed gram-negative microorganisms revealed that Escherichia coli proteinuria more than 100 mg/l had 7 (17.5%) patients with had 100% of sensitivity to meropenem, fosfomycin trometamol, the average level 190±103.2 mg/l. norfloxacin, nitrofurantoin. Then the sensitivity on the decrease Luecocytoes with the shift of luecocyte formula to the left made up to amikacin 95.5%, ceftrazidime 88.9%, cefepim 80%, till 12.2±5.1% had 11 (27.5%) patients, the average level was ceftriaxone 73.4%, ciprofloxacin 72.3%, amoxicillin/clavulanat 12.9±2.4x/l. Increase of ESR had 24 (60%) patients with the 62.0%, cefatoxime 61.2%. average level 32.5±9.2 mm/h at admitting. When determining the sensitivity of Klibsiella pneumaniae Surgical treatment of FPF was made to 25 (62.5%) patients. to antibiotics it was revealed that 100% of sensitivity was to Preoperative preparation was 8.4±7.4 days. The average duration meropenem, then on the decrease it was to amikacin 85,8%, of in-patient treatment was 19.8±7.5 bed-days. ceftriaxone 78.6%, nitrofurantoin 77%, cefepime and fosfomicin 15 patients had got conservative treatment, the average trometamol 71.5%, ceftazidime 66.7%, norfloxacin 64.3%. duration of hospitalization was 16.7±12.1 bed-days. At discharge according to urinalysis the recovery was marked DISCUSSION in 15 (37.5%) patients and improvement in 21 (52.5%) ones. The frequency among elderly patients with FPF is 34,2% 4 patients having contraindication to surgical treatment were and it is within specific weight of UTI (20-40%) connected with discharged without positive dynamics to treatment in the somatic rendering medical help (3). Women (80%-82%) with the average department. The average duration of hospitalization of these age 77.7±8.2 years prevailed by gender signs among patients patients was 3.5±2.1 bed-days. with FPF against background of the systemic osteoporosis and In the 2nd group of patients with UTI, Luecocytorium was concomitant urinary tract infections. At admitting to the hospital registered in 39 (43.3%) patients and joining of UTI during patients of the 1st group half as often than the 2nd group of in-patient treatment occurred in 51 (56.7%) patients. Slight patients have clinical-laboratory signs of UTI (62.5% and 43.3% proteinuria had 43 (47.8%) patients with the average level respectively). On the contrary the frequency of intrahospital UTI 46.0±28.8 mg/l. Moderate proteinuria had 9 (10%) patients with in patients with FPF statically and validly (p=0.0005) prevails the average level 240±104 mg/l. One patient had short-term over the second group of patients (61.1% and 17.5% respectively). increase of proteinuria till 1650 mg/l. The factors of risk intrahospital UTI in patients with FPF are Luecocytoes had 27 (30%) patients with average level 14.1±4.6x/l forced lying position of the patients with FPF, which results in in hospitalization. The shift of luecocyte formula to the left decline in the quality of personal hygiene, incomplete evacuation (8.3±3.1%) had 18 (20%) patients. Also in hospitalization 55 of urinary bladder, neurogenic urinary bladder, catherization (61.1%) patients had acceleration of ESR, the average level was of urinary bladder. 34.8±14.2 mm/h. Statically significant difference according to laboratory In the 2nd group 71 (80%) patients were made surgical treatment indications between groups was not observed: the frequency of FPF. Preoperative preparation was 8.5±6.2 days, the average and the level of luecocytes, the shift of luecocyte formula to the duration of hospitalization was 20.5±9.5 bed-days. left, acceleration of ESR, proteinuria more 100 mg/l. At the same The average time of in-patient treatment was 15,3±7.6 bed- time proteinuria less 100 mg/l among the 2nd group of patients days in 18 (20%) patients. was statically and validly higher (p=0.0006). At discharge according to urinalysis the recovery was marked Indications of the average time of preoperative preparation in 49 (54.4%) patients and improvement in 35 (38.9%) ones. (8.4±6.3 and 8.5±5.9 days) and the average time of in-patient 6 (6.7%) patients with the average duration of hospitalization treatment (19.8±5.6 and 20.5±4.8 bed-days) haven’t the differences 6.2±2.4 bed-days had not considerable positive dynamics. but appropriate average indications prevail over all operated Urine sowing on microflora was made and 116 strains were patients in the trauma department for the period of 2011-2013 separated in all patients from both groups with UTI. In etiological (4.7± 3.1;3.7±2.2;3.2±1.7 days and 15.4±3.7;15.3±3.9;13.5±2.6 structure of UTI the part of gram-negative microorganisms bed-days respectively). Increasing of preoperative preparation of made up 47.4% (55 isolated strains), the leading role (47 isolated patients with FPF, concomitant UTI on the average for 3.9 days strains – 40.5%) belonged to the family of Enterobacteriaceae. and in-patient treatment for 5.4 bed-days has been observed. Escherichia coli 27 (23.3%) and Klibsiella pneumonia 14 (12%) In etiological structure of UTI in patients with FPF as in isolated strains were the most significant from them. Gram- the general population microorganisms from the family of

563 A.M. Palshina et al.

Enterobacteriaceae (Escherichia coli, Klebsiella pneumonia), Analysis according to Nechiporenko from 13th of January Staphylococcus (Staphylococcus aureus, Staphylococcus epidermidis) 2013 is 435 000 leucocytes, 1000 erythrocytes in 1 ml. and fungi of Candida genus prevail. General blood analysis on dynamics is Hb – 93 g/l, Ht – The determination of sensitivity showed that more active in 36.0%, Le – 10,8x109/l, b/n – 8%, ESR – 46 mm/h. relation to the basic uropathogens are carbapenems (meropenem), Blood sowing on culture doesn’t give the growth. fosfomycin trometamol, cephalosporins of the 3d and 4th generations In bio-chemical blood analysis urea is 4,9 mmol/l, creatinine (ceftrazidime, ceftriaxone, cefepim), aminoglycoside (amikacin), – 87 mcmol/l, blood sugar – 5,2 mmol/l. The rate of glomerular beta-lactams (amoxicillin / clavulanat), fluoroquinolones filtration is 88 ml/min. (ciprofloxacin). After repeated analysis on microflora frotmth 4 of December At discharge from the hospital the minimal per cent of the 2013 it is sown Escherichia coli sensitive to amikacin, gentamicin, recovered (according to the results of urinalysis) was (p=0.11) fosfomycin. among the 1st group of patients. Patients discharged with By recommendations of a clinical pharmacologist it is prescribed improvement were more in the 1st group, but the difference amikacin sulphate 0.5 x 1 time per day №7, fluconazol 50 mg 1 statically was unreliable (p=0.21). time per day №7, lavage of the urinary bladder with antiseptic An example of resistant to antimicrobial therapy of intrahospital solution. urinary tract infections in a patient with FPF against background In urinalysis considerable pyuria and proteinuria till 80 of systemic osteoporosis is given. mg/l remain. In general blood analysis there are Hb – 88 g/l, The patient V. (70 years old) admitted to trauma department on Ht – 31.1%, Le – 4,.4x109/l, b/n – 2%, ESR – 50 mm/h. the 20th of November 2013 with the diagnosis: systemic osteoporosis, Because of the developed resistance of UTI to antimicrobial therapy closed fracture of the left femur neck with displacement. The principal the patients is transferred to specialized urology department for method of the operative treatment in patients of old age at medical the subsequent treatment by the urologist recommendations. fractures of the femur neck is total endoprosthesis of coxal joint. In anamnesis the patient had pulmonary tuberculosis at CONCLUSION youth age. She denies the fact of urinary tract infections. 1. Women with the average age (77.7±8.2years) prevail in At hospitalization protein is absent in urinalysis; luecocytes the gender structure of patients with the fracture of proximal are 4-5-6, unchanged erythrocytes are 3-2-1 in the field of vision; femur against background of the systemic osteoporosis and mucus +; bacteria +. concomitant urinary tract infections. General blood analysis are hemoglobin (Hb) – 105 g/l, 2. Fracture of proximal femur results in urinary tract hematocrit (Ht) – 35,4%, leucocytes (Le) – 5,8x109/l, bacillus- infections. nuclear (b/n) – 1%, ESR – 37 mm/h. 3. Resistant to antimicrobial therapy course of intrahospital Operative treatment is planned after pre-examination and urinary tract infections is observed in 6.7% patients with systemic documents registration on high technological medical help. osteoporosis and fracture of proximal femur. The operation is abolished by anesthetist, as urine with pus has 4. Urinary tract infections increase the duration of preoperative been taken in catheterization of urinary bladder. After repeated preparation and in-patient treatment of patients with the fracture investigation of urinalysis it is revealed that urine is turbid, of proximal femur. protein is 1650 mg/l, leucocytes are everywhere, unchanged and changed erythrocytes are in considerable quantity. Mucus – +++; REFERENCES lots of bacteria. It is prescribed sowing of urine on microflora 1. Pashinyan A.G. Therapeutics of urinary tract infections / Pashinyan A.G. // Maedical and sensitivity analysis to antibiotics. advice. 2011. №34. – P. 46-47. Empiric therapy starts with ceftriaxone 2.0 i/v 1 time per 2. Stamm W.E. Management of urinary tract infections in adults / Pashinyan A.G. W.E. day, metronidazole into 0.5 x 3 times per day. Stamm, T.M. Hotton // N/ Engl. J/ Med. – 1993/ – Vol. 329. – P. 1328-1334. The results of urine sowing are Enterobacter sp. Sensitive 3. Pegushina O.G. Characteristics of urinary tract microflora in patients of cardio-surgical to amikacin, gentamicin, meronem, norfloxacin, ceftazidime, hospital / Pegushina O.G., Felbdblum I.V., Maslov Y.N. [et al.] // Medical anthology. – ciprofloxacin. 2011. – №5. – P. 207-209. Taking into account sensitivity of microflora it is carried out 4. Sigitova O.N. Differentiated approach to antimicrobial therapeutics of pyelonephritis / Sigitova the course of etiotropic therapy cyprofloxacin 0.5 x 2 times per O.N., Arhipov E.V., Mitrofanova E.I. // Practical medicine. – 2011. – №7. – P. 29-31. day №7, ceftrazidime 1.0 x 2 times per day i/m №7. 5. Lesnyak O.M. Clinical recommendations. Osteoporosis. Diagnostics, preventive inspection In dynamics pyuria, slight hematuria, proteinuria till 100- and treatment / edited by Prof. O.M. Lesnyak, Prof. L.I. Benevolsky. – M.: GEOTAR-Media, 120 mg/l remains in the patient urine analysis. 2012. – 272 p.

ADDRESS FOR CORRESPONDENCE: Palshina A. M. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street Ph. 89142265939 [email protected]

564 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Simulation o f ge n er a l a n est h esi a o n t h e «si m m a n 3g» a n d its e f f icie n c y

роtapov A.F., Matveev A.S., Ignatiev V.G., Ivanova A.A., Aprosimov L.A. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

aBSTRACT In recent years in medical educational process new innovative technologies are widely used with computer simulation, providing the reality of medical intervations and procedures. Practice-training teaching with using of simulation allows to improve the efficiency of learning material at the expense of creating imaginary professional activity and leading barring material to practical activity. The arm of the investigation is evaluation of the students training efficiency at the Medical Institute on the topic “General Anesthesia with using a modern simulation “SimMan 3 G”. The material of the investigation is the results, carried out on the basis of the Centre of Practical skills and medical virtual educational technologies (Simulation Centre) at the Medical Institute of NEFU by M.K. Ammosov. The Object of the investigation was made up by 55 students of the third (3) course of the Faculty of General Medicine of the Medical Institute of NEFU. The investigation was hold during practical trainings (April-May 2014) of the General Surgery Department on the topic “General Anesthesia”. A simulation practical course “General Anesthesia” consisted of 12 academic hours. Practical training was carried out using instruments, equipments and facilities to install anesthesia on the SimMan 3G with shooting the process and further discussions of the results. The methods of the investigations were the appreciation of students background know ledge before and after practical training (by 5 points scale) and the analysis of the results. The results of the investigation showed that before the practical course only 23 students (41,8%) had dot positive marks: “Good” – 7 students (12,7%) and “Satisfactory” – 16 (29,1%) students. The rest 22 (58,2%) students had bad results. The practical trainings using real instruments, equipments and facilities with imitation of installation of preparations for introductory anesthesia, main analgesics and muscle relaxants showed a patients reaction on the virtual trainer SimMan 3 G. Students were divided into anesthetic team, co-assisting of an anesthesiologist, an assistant and nurses anesthetist, who conducted general anesthesia (the mask anesthesia, intravenous anesthesia, endotracheal anesthesia). After finishing the practical course 16 students (29,1%) got 5 marks (Excellent), 35 students (63,6%) – 4 (Good) and 4 students (7,3%) – 3 mark (Satisfactory).

Key words: general anesthesia, simulation methods, patients simulator, teaching (training) efficiency.

Wiad Lek 2015, 68 (4), 565-566

INTRODUCTION increase the efficiency of leaning material creating the imitation Leading worlds experience in the medical education shows of professional activity and approaching learning material to that increasing in efficiency of practical training is possible with practical activity. Aim: evaluation of training effectiveness of using new innovative training technologist. More perspective the 3-rd (third) course students of the Medical Institute on the technologist in Medicine are those which allow to form and topic “General Anesthesia” using the modern patients, simulator improve students and specialists professional knowledge and SimMan 3G. skills using special wax works, phantoms and trainers as well as virtual (computer) simulators, providing the creation of real MATERIALS AND METODS medical interventions and prosedures [1, 2, 3, 4, 5]. The material of the investigation were result of the prospective Simulation methods reached more development in surgical investigation, carried out on the basrs of Practical Skill Centre professions where mistakes during trainings on real patients can and Medical Virtual educational technologies (Simulaton Centre) lead to fatal complications with subsequent legal investigation of the Medical Institute of NEFU by M.K. Ammosov. and big financial expenses. The Object of the investigation was made up by 55 students Using medical trainers and simulations without any risk for of the third (3) course of the Faculty of General Medicine of the patients life one can get necessary practical skills and improve Medical Institute of NEFU. The investigation was hold during them. Apart from that practice training with simulators allow to practical trainings (April-May 2014) of the General Surgery

565 роtapov A.F., et al.

Department on the topic “General Anesthesia”. A simulation It is necessary to notice, that the discussion of the results had practical course “General Anesthesia” consisted of 12 academic great interest in compari son with a common lecture-room class. hours. The students were more emotional, they exchanged their own Practical training was carried out using instruments, equipments impressions, made an analysis and discussion of the material and facilities to install anesthesia on the SimMan 3 G with covered. shooting the process and further discussions of the results. The methods of the investigations were the appreciation CONCLUSION of students background know ledge before and after practical The evaluation of background know ledge on Anesthesiology training (by 5 points scale) and the analysis of the results. showed that 23 (41,8%) students had positive marks: “Good” – 7 (12,7%) students and “Satisfactory” – 16 (29,1%) before the RESULTS practical course. Evaluation of background knowledge on Anesthesiology Practical training using real anesthesiological tools and before practical course revealed that only 23 students (41,8%) had equipments, anesthesia imitation on the simulator SimMan positive marks: “Good” – 7 students (12,7%) and “Satisfactory” 3G improves the results of learning material. Thus 16 (29,1%) – 16 (29,1%) students. The rest 22 students (58,2%) had bad students gained practical skill for 5 goints (“Excellent”), 35 results. We should notice, that according to curriculum there (63,6%) students – for 4 points (“Good”) and only 4 (7,3%) for are 2 lectures on the topic “Local anesthesia”, and “General 3 points (“Satisfactory”). Anesthesia”, each for 2 academic hours. Methods of simulation training using modern simulators of a The testing checked of the students know components patient allows to increase practice oriented approach in teaching, of general anesthesia (anesthesia, analgesia, neurovegetative motivates and improves the best mastering of theoretic knowledge, protection, mioplegii, auxiliary methods) and preparations, increase the level of students practical preparation. which are used during general anesthesia. Practical training were carried out with using real instruments, REFERENCES equipments and facilities for installation anesthesia (airducts, 1. Bokeria L.E. Modern approach in training speacialists in Cardiovascular Surgery and endotracheal tubes, laryngeal mask, laryngoscope, Ambu bad, in related specialities / L.E.Bokeria, I.N. Stupakov, S.M. Krupyanko, S.G. Khydaev, O.A. anesthesia apparatus “Polinarkon-5”). The following actions Manerova, M.A. Afonina, S.S. Volkov, I.N. Nefedova // Virtual technologies in Medicine. were imitated: the installation of preparations for introductory – 2013. – №2. P. 36. anesthesia, main analgetics and muscle relaxants, which allowed 2. Gorshkov M.D. Returnson virtual training of laparoscopy / M.S. Gorskov, A.B. to see a patients reaction on the virtual trainer of the third Fedorov// Medical education and professional developments. – 2011. – №3. – generation SimMan 3G. p.136 – 141. The students were divided into anesthetic team, consisting 3. Dosmagamletova R.S. Recommendations on implementation of training on the basis of an anesthesiologist, an assistant and anesthetist nurses and of simulation technologies in the educational process at the Medical Instite / R.S. under the teachers instruction they carry out general anesthesia Dosmaqamdetova, A.S. Kusainova, V.P. Riklegs// Medical Education and professional (mask, intravenous, endotracheal). The process of installation development// 2011. – №3. – p.74 – 84. the anesthesia was shooted for subsequent discussion. 4. Kolganov A.V. Virtual technologies in modern Medical Education/ A.V. Kolganov, S.S. The results of know ledges evaluation after finishing the Chaplygen, A.S. Voronin. // Bulletin of Sam S.U. 2011 №4 (85). – p.250 – 254. course of practical trainings in Simulation Centre showed the 5. Cooper J.B. Design and Evaluation of Simulation Scenarios for a Program Introducing following: 16 (29,1%) students got practical skill evaluated for 5 Patient Safety, Teamwork, Safety Leadership, and Simulation to Healthcare Leaders points (“Excellent”), 35 (63,6%) students – for 4 points (“Good”) and Managers / J.B. Cooper, S.J. Singer, J. Hayes, [et al.] //Simul. Health. 2011,6:231- and 4 (7,3%) students – for 3 points (“Satisfactory”). 238.

ADDRESS FOR CORRESPONDENCE: Potapov A.F. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street [email protected]

566 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Th e morbidity o f u pper a ir w a y s a n d e a r in i n d u stri a l regi o n s o f t h e rep u b l ic s a k h a (y a k u ti a )

Lebedeva N.A.¹, Seyalova A.S.¹, Irintseev A.A.¹, Cheldieva E.I.¹, Poselskaya N.V.² ¹f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a ²i n s t i t u t e o f r e g i o n a l s t u d i e s a n d f o r e i g n p h i l o l o g y n e f u , y a k u t s k , r u s s i a

ABSTRACT The analysis of morbidity of upper airways and ear in industrial areas of the Republic Sakha (Yakutia) – Aldanskiy, Mirninskiy and Nerungrinsky regions is presented in the article. The main tendencies in dynamics of morbidity of inflammatory diseases and cancer are revealed. The reasons of increasing pathology of upper airways and ear in the studied industrial regions are defined.

Key words: morbidity, upper airways, industry.

Wiad Lek 2015, 68 (4), 567-568

INTRODUCTION RESULTS AND DISCUSSION Aldan, Mirninsky and Neryungrinsky regions are the The higher incidence of upper airways and ear for the last largest industrial centers of the Republic of Sakha (Yakutia). years has been noted. Among the adult and teenage population in About 90% of all Russian diamonds, 47% of coal and 24% of mobidity patterns ear and mastoid diseases have prevailed in70,1 gold are mined there. Certainly, all mining productions and in Aldan and 60,9 in Mirninsky region (per 1000 population), conditions impacting harmfully to workers (noise, vibration, sinusitis prevail (32,4 on 1000 population in the Neryungrinsky microclimate of the production environment), have a major region). The children’s and teenage population living in conditions role in pathogenesis of professional relative deafness and ENT of increased air pollution are more subject to illnesses of ENT- pathology [3]. Environmental enhancement in connection organs particularly ear diseases on the background of reduced with the increase of technogenic pollution prevailing in immune reactivity and unfavorable climatic and natural factors recent years is the priority direction in the state, political, owing to various reasons [2]. Among the children’s population economic and nature protection activity [5]. The climate is in morbidity patterns of ear and mastoid the higher prevalence sharply continental: annual temperature falls reach 60-65 is noted (on 1000 population – 65,4 in Aldan, 62,2 B Mirninsky degrees. A higher level of pollution of the atmosphere in and 64,4 in Neryungrinsky regions). these areas is noted. According to routine observations of the Oncological situation. In Mirninsky region 13 patients have state monitoring of FSBI the Yakutsk Hydrometeorology and been registered: of them 2 patients diagnosed for the first time, Environmental Monitoring average concentration exceeds 11 repeated patients. Middle age – 60,8 years. 46,2% (6 people) the standards of maximum allowable concentration for the were disabled: of them the group 2 – 30,8% (4 people), the group content of polluting substances: formaldehyde by 4,7 times, 3 – 15,4% (2 people). Generally oncological incidence is presented suspended materials by 2,3 times in Aldan, formaldehyde by by throat cancer (46,2%). In Aldan region there were 7 patients 4,1 times, suspended materials by 1,5 times in Mirninsky, registered. Middle age – 66,4 years. The incidence is presented by formaldehyde by 8,3 times, benzapyrene twice, nitrogen throat cancer – 2, oropharyngeal cancer – 2, salivary gland tumor – 1, dioxide twice in Neryungrinsky region [1]. Aim: study of nose cavity and paranasal sinus cancer – 2. In Neryungrinsky region morbidity patterns of upper airways and ear in industrial 16 patients have been registered: of them 7 patients diagnosed for regions of the Republic of Sakha (Yakutia). the first time, 9 repeated ones. Middle age – 63,8 years. Generally the oncological incidence is presented by throat cancer (62,5%). MATERIALS AND METHODS The analysis of the morbidity of upper airways and ear CONCLUSION according to the State Budgetary Institution RS (Ya) “Aldan Thus, in the structure of incidence of ENT-organs in industrial central regional hospital” and SBI RS (Ya) “Mirninskaya central regions of RS (Y) the higher prevalence of ear and mastoid diseases regional hospital” was carried out. (mainly in Aldan and Mirninsky areas) as well as sinusitis and

567 Lebedeva N.A. et al. tonsillitis have been revealed, throat cancer among oncological 2. Sineva E.L. Prevalence and structure of diseases of ENT organs at children of industrial diseases being more frequent. A large amount of the cases of regions / E.L. Sineva, V. B. Pankova, E.O. Sarancha // Bulletin of otorhinolaryngology. ear and mastoid diseases is presented by acoustic occupational – 2015. – No. 2. – P. 48-52. neuritis as a result of noise exposure and vibration [4]. The higher 3. Sineva E.L. Working conditions and occupational diseases of ENT organs. / E.L. Sineva, incidence rate is explained by climatic features, development B. V. Ustyushin, G. V. Aydinov // M.: Rostov state scientific research institute of hygiene, of the industry and ecologically unfavorable situation, lack of ecology and certification, 2001. – P. 308. specialized ENT-offices, shortage of otolaryngologists and necessary 4. Kosarev V. V. Vocational illnesses: the tutorial. / Kosarev V. V., Babanov S. A. // – M.: equipment for diagnostics and treatment of patients. INFRA-M, 2011. – P. 252. 5. Potapov A.I. Population’s health and problems of hygienic safety. / Potapov A.I., Vinokur REFERENCES I.L., Gildenskiold R. S. // M.: INFRA-M. 2013. P. 35-36. 1. Routine observations records of the state network of monitoring FSBI, the Yakutsk 6. Babiyak V. I. Vocational illnesses of upper airways and ear: The management for doctors Hydrometeorology and Environmental Monitoring Management for 2014-2015. / Edited by V. I. Babiyak, YA.A. Nakatis. // SPb.: Hippocrates, 2009. – P. 696.

ADDRESS FOR CORRESPONDENCE: Lebedeva N.A. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street 89142221555 [email protected],

568 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Ex peri m e n t a l i n v estig a ti o n

Protopopova A.I., Tobokhov A.V., Gogolev N.M. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT The search for the most perfect way of hollow organ obturation has been done through the history of gastro-intestinal tract surgery. Till present time such aspects of the problem asmorphological changes peculiarities in the process of intestine wound repair in the zone of anastomosis and biological impermeabilty of intestine fistula, possibilities of entero entero anastomosis different types formation are not researched enough and remain actual.

Key words: anastomosis, surgery, compressional, gastro-intestinal tract.

Wiad Lek 2015, 68 (4), 569-577

Physical and technical parameters of titanium – nickeled alloy well as based on the provisions of the Helsinki Declaration of were studied in tendometric device at Tomsk Research Institute of the World Medical Association of 1964 supplemented in 1975, materials and alloys with the effect of the return form under the 1983 and 1989 . leadership of RATS Gunter V.E. [1]. Taking into account the diameter All experimental animals were in the same vivarium conditions of the large and small intestines the size of the compression device and feeding regime. One day before the experimental operations ranged from 12-20 mm x 25-30 mm. Considering the consistency the animals were fasted , given „Fortrans” 1/3 or ¼ dissolved of chyme the structure had a circular shape . The diameter of the sachet in 1 liter of water, depending on the weight of the dog. drive section is 1.9-2.3 mm, which creates compression between The operation was carried out in compliance with aseptic and the turns of 600-800 g/mm [2] . antiseptic requirements, combined anesthesia was provided with Features of a titanium-nickelide alloy – it is manifested shape the use of hypnotics and local anesthesia. After the sedation. memory effect, super elasticity, high corrosion resistance and 1% solution of “Rometar” was intrapleurally administered. biological inertness [4]. The memory effect is that the product Additionally with a view to more effective anesthesia 20 ml of chilled below a certain temperature, can be easily deformed. This 0.25% solution of novocaine was administered into the mesentery. deformation is eliminated by heating the product at a temperature Postoperatively, during the first days animals received analgesics range ofa shape recovery start and end. At a temperature higher and antibiotics. Subsequently reintroduction of solutions was than that at the end of the shape recovery material exhibits performed according to the state of the animal for 2-3 days. superelastic properties: non-linear product deformation by In a day the dog was allowed to drink . Feeding began on the 8-10%, occurs when load is completely eliminated by external second day, at first liquid food was given, then on the 5-6-th effect removal [5]. day the dogs had a regular feeding schedule . An important feature of the titanium-nickelide alloy implant is that if preventing restoration of the original shape by heating them the reactive stresses arise. Therefore, titanium-nickelide alloy implants can make the programmed mechanical action on the body structure [3]. Presence of 3 turns provides more equal compression between the turns of the titanium-nickelide alloy implant (Fig. 1). We have conducted a comprehensive study of intestinal anastomosis using a superimposed compression-titanium- nickelide implant and ligature performed for 44 mongrel dogs of both sexes weighing 7-10 kg. The studies were performed in compliance with the rules of the humane treatment of animals, which are regulated by the „Rules of work with experimental animals , approved by Order of the Ministry of Health of the USSR № 755 of 12.08.1977, as Fig. 1. Titanium nickelide implant with a shape memory.

569 Protopopova A.I., et al.

Table I. Research Volume and Methods of Experimental animals depending on the type of anastomosis (n (%). Methods of Research Type of anastomosis Number R-research Colonoscopy Manometry Infection Histology 24 10 5 7 7 10 Compressive (54,5) (41,7) (20,8) (29,1) (29,1) (41,7) 20 4 7 7 11 Ligature - (45,5) (20,0) (35,0) (35,0) (55,0) 44 10 9 14 14 21 Total (100,0) (22,7) (20,4) (31,8) (31,8) (47,7)

Table II. Mechanical strength of intestinal anastomosis in mmHg. including the terms of the postoperative period in days Type of anastomosis 1 3 5 7 10 14 21 30 45 Ligature 130 80 50 70 90 120 160 300 300 Compressive 130 110 130 170 210 240 280 300 300

A B C Fig. 2. Plan R- graphy of abdominal cavity.

Operated animals were taken out of the experiment by the Implant rejection and migration were observed on the 3-5 standard technique at different times after surgery, depending on days after surgery (Fig. 2): in 2 (20,0±12,6%) observations – on the purpose of the study. According to the type of anastomosis the 3day, in 5 (50,0±15,8%) on the 4-thday, and in 3 –on the 5 methods animals were divided into 2 groups: with the use of the day (30,0±14,5%). The average elimination time was equal to titanium – nickelide alloy and ligature intestinal anastomosis 8,0 ± 0,42 days . (Table. I). The mechanical strength of the anastomosis was checked Research Volume and Methods of Experimental animals by manometric studies on isolated preparations in 14 (31.8 %) depending on the type of anastomosis (n%). operated animals out of which 7 (50.0%) – with a titanium –

570 Experimental i n v e s t i g a t i o n nickel alloy implant, in 7 (50.0%) – with a ligature anastomosis. implant with a shape memory. Formed tissue roll did not break The measurement was performed on the 1 , 3 , 5, 7, 10, 14, 21, the passage of intestinal contents (Fig. 3B) . 30 and 45 days after surgery . 14 days after surgery ,the anastomoses formed by ligature As shown in Table 2 the mechanical strength of compressive (Fig. 4A) were deformed by massive adhesive process or were anastomosis on the 3-rd day 3 was 110 mmHg Art., ligature narrowed due to the formation of coarse wide scar on the anastomosis 80 mmHg Art. On the 7-th day, – compressive suture line. Because of this there was a marked compensatory anastomosis – 170 mmHg Art., ligature anastomosis-70 mmHg. hypertrophy adductorof an intestine. Intestinal fistula formed Art. On the 14-th day: compressiive anastomosis – 240 mmHg. by nikelid – titanium compression devices healed by the type of Art., ligature anastomosis – 140 mmHg. Art.On the 30-th day primary intention with formation of a thin delicate scar (Fig. 4B) compressive anastomosis – 300 mmHg. Art., ligature anastomosis without causing a narrowing of the intestinal lumen – 300 mmHg. Art. On the 21-st day , i.e., by the end of the observation period Thus, a difference of mechanical strength ranged from 30 the fistula formed with the use of a titanium nickelide alloy to 120 mmHg Art. The maximum mechanical strength was implant with a shape memory visually washardly detectable achieved by applying a compressive anastomosis on the 21-st day (Fig. 5). after surgery , when ligature suture was applied the maximum mechanical strength was achieved only on the 30-th day . The study of the mechanical strength of the anastomosis revealed that Histological studies results even in the most critical period (3 days) compressive anastomosis We studied the comparative histology of intestinal anastomoses with stood intracavitary pressure of 1.4 times higher than the when applied both suture ligature and compression anastomosis ligature anastomosis . titanium nickelide alloy. In our work we adhere histogenesis of Colonoscopy with taking of a biopsy material was performed intestinal anastomosis consisting of 4 periods [91]: in 9 (20.4%) of the experimental animals. Studies were made The 1-st period – the development of an acute inflammatory on the days 7, 14 and 21-st days . Anastomosis with titanium- response (Fig. 6), compression and adaptation of tissues; nikelide implant –was made in 5 (55.6%) dogs, in 4 (44.4%) – When applying ligature anastomosis an inflammatory ligature method of anastomosis was used. Macroscopic picture reaction was most pronounced when compared with compression of the anastomosis on the 7-th day (Fig. 3) after surgery in the anastomosis, as evidenced by neutrophils that prevailed in the formation of ligature method of anastomosis (Fig. 3A) was as composition of the inflammatory infiltrate. Leukocytes level follows: there was observed expressed entero paresis phenomena was the highest inligature anastomosis. By the end of this stage with inflammatory changes. Tissue roll considerably protruded in a compressive anastomosis, the reduction in the number of into lumen overlaid with the sutures, causing partial intestinal neutrophils and increased number of fibroblasts was marked; obstruction, indirectly indicated by hypertrophy of the mucosa The 2-nd period – epithelialization of the mucous membranes and a resulting expansion of the loop which we observed when and the formation of the primary connective tissue scar (Fig. 7); collecting material. All these phenomena were not observed in The start of restorative changes was characterized by animals after anastomosis formation using titanium-nikelide epithelialization of the mucous membranes and the formation

A B Fig. 3. Macroscopic colonic anastomoses picture on the 7th day (A – ligature anastomosis B – compressive anastomosis).

571 Protopopova A.I., et al.

A B Fig. 4. Macroscopic colonic anastomoses picture on the 14-th day (A – ligature anastomosis B – compression anastomosis).

number of goblet cells in the newly-for medglandular crypts were detected. Due to the recovery of alymphoplasmacytic layer which was formed faster in a compressive anastomosis a primary connective tissue scar formation with an excessive amount of collagen fibers and a decrease in the width of the scar was completed. Formation of the primary connective tissue scar in the compressive anastomosis took place with the formation of a true intestinal epithelium. Conducting the thread through the mucosa when applied ligature anastomosis was quitea severe injury capable to cause rapid development of reactive inflammatory changes that lead to necrosis and rejection of its layers. This affected the level of the inflammatory response, the nature and time of anastomosis regeneration. As a result, there were secondary necrotic ulcerative defects. In a compression seam as there was Fig. 5. The macroscopic picture of a compression anastomosis on the 21-st day. no passage of the suture through the mucosal layer the ulcerative defects did not occur or were not expressed. The 4-th period - the restoration of the mucous membrane (Fig. 10). The muscular layer proliferation of smooth muscle cells lead of the primary connective tissue scar. Healing in ligature to its thickening in the edges of the anastomosis and ingrowth anastomosis was slower: only on the 21-st day after surgery, of cells into the scar. It was most clearly seen in the compressive and in the compressive anastomosis – on the 14-th day. This is anastomosis (Fig. 10B) . When applying a ligature anastomoses an due to prolonged retention of inflammatory changes because of excessive proliferation of connective tissue with the formation of the suture presence and the infection of the anastomosis deep rough scar was detected (Figure 10) . Pronounced sclerosis in the layers, as well as the repeated partial mucosal necrosis. With formation of scar anastomosis led to atrophy and deformation of compressive anastomosis the scar was originally formed in the the lips anastomosis with manual anastomosis and the complete submucosa, with ligature anastomosis the scar was formed in absence of it in the compressive anastomosis . serosa, due to inflammatory changes hampering the development Therefore, in all periods a histogenesis of a compressive anastomosis of granulation tissue . was faster than in manual method. So in the second period the The 3-rd period –a recovery of lymphohistiocytic layer and epithelialization time of the mucous membranes and the formation muscle plate of mucosa, formation of the secondary ulcero- of connective tissue scar in the compressive anastomosis was 14 necrotic defects of mucosa (Fig. 9) ; days, and in the manual 21. Comparative analysis of histogenesis The mucous membrane epithelium thickness was increased of manual and compressive anastomoses methods showed that , the recovery ratio of the parenchyma and stroma, an increased the application of compressive intestinal a nastomoses one third

572 Experimental i n v e s t i g a t i o n

A B Figure 6 .The development of an acute inflammatory response. The 1-st day after surgery. H & E stain . Increased 7x4. (A – ligature anastomosis B – compression anastomosis).

A B Fig. 7. Epithelialization of mucous membranes.H & E stain . Increased 7x8 . (A – ligature anastomosis 21 days , B -compressive anastomosis the 14-th days).

accelerated the regenerative processes, histogenesis proceeded The table shows that there is a downward trend in the total much faster and more efficiently by 7 days. number of main microbes consisting of obligate parasites, We studied the anastomosis condition of colon microflora in it is more pronounced when applying conventional ligature 14 dogs, including the imposition of a titanium – nickelide alloy anastomosis. However, there is rapid growth of the accompanying compressive anastomosis in 7 dogs (29.1%) and a superimposed microflora – conditionally pathogenic microbes or their ligature anastomosis in 7 dogs (35.0%). Quantitative and qualitative associations . composition of the gut microflora, depending on the method The type and incidence of microbes in dogs is shown in of anastomosis is presented in Table III . Table IV.

573 Protopopova A.I., et al.

A B Fig. 8. Formation of the primary connective tissue scar . 14 days after surgery . H & E stain . Increased 7x20. (A – ligature anastomosis B – compressive anastomosis).

A B Fig. 9. Recovery oflymphohistiocytic layer and muscularis plate of mucosa. Secondary ulcerative necrotic defects. A – ligature anastomosis , H & E stain . Increased 7x8. B – compressive anastomosis , H & E stain . Increased 7x8 .

As shown in the table, Escherichia coli was detected in 38 Proteus, Staphylococcus, Streptococcus, Bacteroides, Cryptococcus, (90.5%) dogs at different postoperative time in any type of and Clostridium which in all periods of the experiment were anastomosis. Lacto-negative pathogenic enterobacteria and significantly lower than in the ligature method. When applying Staphylococcus were detected only in 1 dog (14.3%) when applying ligature anastomosis infection was 82.8% on the 1-st day,in compressive anastomosis, while ligature they were detected during compressive anastomosis – 42.8 %. On the 3rd-5-th day with all stages of the experiment. From the compressive anastomotic ligature method 88.6 % and in compressive anastomosis – 31.4%, zone there were sown such microorganisms as Enterobacter, on the 10-th day infection up to 64.3% in the ligature method and

574 Experimental i n v e s t i g a t i o n

A B Fig. 10. The proliferation of smooth muscle cells. H & E stain . Increase 7x20. (A – manual anastomosis , B – compressive anastomosis).

Table III. Characteristics of microflora , depending on the method of anastomosis. anastomosis type characterized sign theoretical norm compressive ligature Number of species : 5,5 5,1 4,3 -microbes -anaerobes 2,7 3,0 2,1 -aerobes 2,8 2,1 2,2 Number of anaerobes in e / m : 27,0 10,0 9,6 - asporogenous - spore 4,0 2,6 2,9 Number of aerobic in n / mm 15,0 14,0 10,2 The frequency of opportunistic microbes in % до 15,0 36,0 46,5 The frequency of association of conditionally pathogenic microbes in % no - 13,4 The frequency of detection of Proteus in % Up to 15,0 18,0 20,5 The number of opportunistic pathogens Not more than 3,0 3,6 4,6

22.8% in compressive anastomosis . Infection of the anastomosis The titanium – nickelide alloy peculiarity is a shape memory in ligature suture was determined on the 21-st day. effect, super elasticity, high corrosion resistance and biological Infection of compressive anastomosis was significantly lower inertness. NiTi cooled below a certain temperature is easilily 1.9 times on the 1-st day, 2.8 times on the 3-5-th day, and 2.8 deformed. This deformation is removed by heating the metal. times on the 7-10 days, in average infection was 2.5 times lower An important feature of the implant of titanium – nickelide than anastomoses performed by ligature . alloy is that if preventing restoration of the original shape by In the experimental group of animals deaths related to the heating them the reactive stresses arise. process of anastomosis was not detected. In the early postoperative All experimental animals were in the same vivarium period there was 1 complication – postoperative wound festering conditions and feeding regime. Operated animals were taken when ligature anastomosis was applied. out of the experiment by the standard technique at different

575 Protopopova A.I., et al.

Table IV. Type of anastomosis zoneflora and frequency of its detection. Compressive anastomosis Manual anastomosis n=7 n = 7 Type of flora including postoperative period day 1 3-5 7-10 1 3-5 7-10 6 6 6 7 6 Colibacillus 7 (100,0) (85,7) (85,7) (85,7) (100,0) (85,7) 2 2 6 5 4 Lactose-negative enterobacteria(normally 10%) - (28,6) (28,6) (85,7) (71,4) (57,1) 1 5 7 5 Hemolytic E. coli (normally not available) - - (14,3) (71,4) (100,0) (71,4) 1 5 7 5 Pathogenic staphylococcus - - (14,3) (71,4) (100,0) (71,4) 3 2 2 6 6 5 Bacteroides (42,8) (28,6) (28,6) (85,7) (85,7) (71,4) 4 3 2 6 6 4 Enterococci (57,1) (42,8) (28,6) (85,7) (85,7) (57,1) 4 3 2 6 6 5 Cryptococcus (57,1) (42,8) (28,6) (85,7) (85,7) (71,4) 3 2 1 6 6 3 Hemolytic streptococcus (42,8) (28,6) (14,3) (85,7) (85,7) (42,8) 3 2 2 6 6 3 Proteus (42,8) (28,6) (28,6) (85,7) (85,7) (42,8) 3 2 1 6 6 5 Clostridia (normally 60 %) (42,8) (28,6) (14,3) (85,7) (85,7) (71,4) Total flora 30 22 16 58 62 45 Total infection 42,8 % 31,4% 22,8% 82,8 % 88,6% 64,3%

times after surgery, depending on the purpose of the study. membranes and the formation of connective tissue scar in the Depending on type of anastomosis animals were divided into compressive anastomosis was 14 days, and in the manual – 21 two groups: titanium-nickelide alloy and ligature intestinal days. When applying compressive intestinal anastomoses the anastomosis. We conducted: R- study, colonoscopy, manometry, regenerative processes were accelerated 1/3 times, histogenesis and histological studies and investigated infection of anastomosis. was considerably faster and more efficient by 7 days. When comparing the time of anastomosis formation it was Infection of compressive anastomosis was significantly below significantly found that the compressive anastomosis was formed 1.9 times on the first day, 2.8 times on the 3-5-th day and 2.8 5-6 times faster than conventional anastomosis performed by times on the 7-10-th day, in average, 2.5 times lower infection traditional ligature nodal seam. The average elimination time of anastomoses performed by ligature suture. is equal to 8,0±0,42 days . Thus, the use of titanium – nickelide alloy implant for The difference of mechanical strength ranged from 30 to applying intestinal anastomoses has sufficient mechanical 120 mmHg. Art. The maximum mechanical strength when strength, and after rejection of compressing constructions the applying compressive anastomosis was achieved on the 21-st foreign bodies helping to maintain long-term inflammatory day after surgery, in application of ligature suture the maximum reactions do not remain. It provides reliable tightness offormed mechanical strength was achieved only on the 30-th day. The anastomosis from penetration of microflora of hollow organs study of the mechanical strength of the anastomosis revealed into the abdominal cavity, which reduces the infection in the that even in the most critical period (3 days) the compressive area of an anastomosis. anastomosis with stood intracavitary pressure 1.4 times higher than the ligature anastomosis . REFERENCES Histogenesis of a compressive anastomosis was faster than 1. Dambaev G. TS. Methods of diagnosis of functional disorders of the gastrointestinal the ligature method. Epithelialization time of the mucous tract / S.V. Gunter, V.K. Zhukov, V.F.Votyakov . // Recourse book.- Tomsk, 2005.- 40 p.

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2. V.G. Dmitriev The use of titanium-nickelid alloy constructions in abdominal surgery / 4. Wingate D.L. Motility of the small intestine / Wingate D.L. // Gastroenterology.- V.2, S.V.Lohanskiy.// – Karaganda, 2008.- P. 1-3 2009.- P. 130-154 . 3. A.V.Tobokhov Diagnosis of motor-evacuation function of the colon / V.N.Nikolaev, 5. SchotA.V. Changes in the quality of intestinal sutures in peritonitis / S.A. Alekseev, P.A.Neustroev [et al].//- Scientific and Practical Conference. National project of high-tech A.A.Zaporozhets.//- Health of Belarussia, 1995, №5.- P. 17-19 . medical aid availability increase to the population of the Republic of Sakha (Yakutia) .- Yakutsk, 2007.- 226 p.

ADDRESS FOR CORRESPONDENCE: Protopopova A.I. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street Ph. 89143000131 [email protected]

577 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Su rger y o f c o n ge n it a l m a l f o r m a ti o n s in n e w b o r n s

Savvina V.A1,2, Varfolomeyev A.R.1, Nikolayev V.N.1,2, Tarasov A.Yu2, Vasilyev Ye.P.2, Grigoryev V.A.2, Sleptsov A.A.2, Grigoryeva L.A.1, Kolmogorov V.V.1, Sofronova M.S.1, Koryakina A.D.1 1f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a 2r e p u b l i c a n h o s p i t a l n o . 1, n a t i o n a l c e n t e r o f medicine, y a k u t s k , r u s s i a

aBSTRACT The development of neonatal surgery is an important task of health care system, because birth defects have been the 2nd most prevalent cause of infant mortality for many years. In order to improve the quality of care for neonates with surgical diseases we studied the main causes of neonatal deaths during the period from 1995 to 2014, on the basis of data from the Children’s Surgery Department of Yakutsk. In 77% of cases, the causes of lethal outcomes in neonates with surgical pathology were conditionally preventable. We singled out the basic organizational problems, the solution of which led to a 3.5 times reduction in mortality of infants with surgical pathology during the second period of the study (2005-2014). The main organizational aspects of the regional model of improving medical care of infants with surgical pathology are: antenatal diagnosis of malformations and prenatal consultation with children’s surgeon, competent and timely transportation of newborns from district hospitals, the centralization of aid at level 3 hospitals, the introduction of modern diagnostic and treatment algorithms, methods of minimally invasive endosurgery.

Key words: newborns, organization of surgical care, congenital malformations.

Wiad Lek 2015, 68 (4), 578-581

INTRODUCTION hernia, etc.). The groups are comparable in basic characteristics Surgical neonatology, especially over the past decade, has (Table I). greatly improved, but the results of surgical treatment of infants We conducted an analysis of the incidence of congenital have been different​​depending on the region [1, 2]. The special malformations in the Republic of Sakha (Yakutia), on the basis of characters of our region which affect the organization of providing data by the National Information and Analytical Center. We studied medical care to infants with surgical pathology is the vast territory the efficiency of antenatal diagnosis of malformations in the region, with a low population density, most district hospitals being 1 level identified the percentage of newborns indicated for transportation. hospitals, which means that it is impossible to organize newborn A comparative analysis was carried out between the groups of care in the postoperative period in these hospitals, given the newborns transferred antenatally and those evacuated postnatally poor quality of antenatal diagnosis of congenital malformations to a 3-level hospital surgery. We evaluated the clinical results by in the areas. Therefore, to improve the quality of medical care groups of nosology, and the frequency of deaths by period. provided to infants with surgical pathology in our region it is necessary to create a system that includes organizational and RESULTS AND DISCUSSION medical aspects of interaction between perinatal and pediatric The frequency of congenital malformations in the republic has services, republican health facilities and district hospitals that been steadily rising over the analyzed period and has more than provide care for newborn children. doubled – from 14 per 1000 child population in 1995 to 29 per Research objective: to improve the results of treatment 1000 child population in 2014. The frequency of malformations of newborns with surgical diseases in the Republic of Sakha especially increased in the Promyshlennaya group of districts – 2.5 (Yakutia). times, there is also an increase in the frequency of malformations in the Arctic and Zarechnaya groups of districts (Table II). MATERIALS AND METHODS Congenital malformations steadily occupied 2nd place in the In retrospect, we reviewed medical records of newborns structure of infant mortality, in recent years there has been a admitted to the Children’s Surgery Department over the past 20 reduction in perinatal causes, while mortality due to defects has years. In total, over the given period 452 newborns were admitted increased since 1995 by 24%. The leading cause of mortality in to the department. 82% of surgical pathology of newborns are the neonatal period is the congenital heart disease, followed by accounted for by congenital malformations, 7% – neoplasms, multiple anomalies, and then – defects of the central nervous 6.8% – peritonitis (necrotizing enterocolitis, spontaneous gastric system and respiratory system. Half of infant deaths occur during perforation), 4.2% – other pathology (ovarian cysts, strangulated the first week of newborns’ lives.

578 Su r g e r y o f c o n g e n i t a l malformations in n e w b o r n s

Table I. Newborn characteristics by periods. 1995 – 2004 2005 – 2014 Sign p n=163 n=289 Average body weight 2.065 + 0.980 2.235 + 0.850 0.054* Gestational age 36 + 2.5 35 + 3.1 0.001* Apgar score at 1st minute 6 + 2 7 + 1 <0.001 Apgar score at 5th minute 7+2 7+2 1.0 Age at admission (days) 3 + 0.5 2 + 0.6 <0.001* Multiple defects 45 (28%) 72 (25%) 0.530** Somatic pathology 57 (35%) 84 (29%) 0.193** Complicated obstetric history 106 (65%) 165 (57%) 0.098** р* — current level of statistical significance of differences using the Student t-test; р** — using Pearson χ2.

Table II. Frequency of congenital malformations per 1000 child population by groups of districts (data provided by the Yakut Republican Medical Information and Analytical Center). Group 1995 2000 2003 2006 2009 2014 Arctic 12.5 9.6 16.5 19.9 20.2 25.3 Vilyi 14.6 18.6 19.6 21.3 21.5 19.0 Zarechny 13.4 11.1 17.1 22.7 24.2 26.7 Promyshlenny 10.7 12.5 19.4 24.9 23.9 26.9 Central 11.3 11.7 12.4 14.6 21.2 21.2 Republic of Sakha (Yakutia) 14.0 14.9 22.0 24.8 26.5 29.0

Screening of antenatal diagnostics of malformations has The main positive factor in improving the results of surgical been carried out in the Republic since 2000. The effectiveness treatment of the newborn for the second period (2005 to 2014) is of antenatal diagnostics of malformations was 45%, 75% cases the organization of the neonatal intensive care unit at the Perinatal were detected before the 22nd week of gestation. Antenatal Center in 1998. Since 2000, there has been a change in medical diagnostics of nosologies is as follows: malignancy of the fetus and organizational, tactical and therapeutic algorithms for all was identified in 100%, gastroschisis – 90%, lung defects – 80%, major groups of surgical pathology in newborns. During this congenital diaphragmatic hernia – 68% and omphalocele – 61%. period, the mortality rate has decreased by 3.5 times: mortality For other fetal malformations prenatal diagnostics is as follows: for cases of esophageal atresia decreased from 93% to 19%, congenital bowel obstruction – 27%, esophageal atresia – 19%, congenital diaphragmatic hernia from 43% to 10%, gastroschisis anal atresia – 12%. There is a large percentage of abortions due from 66% to 44%, omphalocele 50% to about 10%, high bowel to detected defects – 45% over multiple malformations and obstruction from 53% to 35%, low obstruction from 60% to associated chromosomal aberrations, in other cases, due to 17%, anorectal malformations from 29% to 4.8%, necrotizing isolated anomalies at the request of the families. But since 2008, enterocolitis from 66% to 28%, spontaneous gastric perforations while medical and genetic prenatal consultations have been held from 80% to 25%. with the participation of pediatric surgeon, the percentage of While studying the causes of deaths of infants with surgical prolongation of pregnancy has been increasing, and antenatal pathology, it was found that 77% of these causes can be termed transfers over the past 5 years have amounted to 45%. According as conditionally preventable or so-called manageable causes to annual reports by district hospitals the percentage of pregnant of death. For example, only in 8.6% of newborns in the first women undergoing screening is 80-92%. period of study death was uncontrollable (Fig. 1). In the rest During the first study period (1995 to 2004), the results of of the cases, the unfavorable outcome was mainly due to late treatment of infants with surgical pathology were unsatisfactory. diagnosis, inadequate preoperative preparation, improper

579 Savvina V.A., et al.

Fig. 1. Comparative structure of the causes of deaths by periods.

treatment tactics, iatrogenic causes and septic complications. So, the tactics for centralization of surgical care for newborns The iatrogenic causes of mortality include deaths due to errors is justified in our region. In solving this problem, an invaluable of operational machinery (4 for the first period), internal organ role is played by timely antenatal diagnostics of malformations, injuries and tumors of childbirth (4 of 5 during the first period), but there remains a large percentage of newborns in need of complications due to infusion therapy (3 out of 6 during the emergency evacuation – in most cases these are infants with first period). Errors during transportation, which were the main prenatal developmental disabilities which are difficult to detect. The cause of the unfavorable outcome for newborns, were registered task of neonatal transportation is complicated in our conditions in 1.2% only. Thus, the objectives were identified that needed to by the vast territories, so the main transport is represented by air be resolved to eliminate controllable causes of mortality. ambulance. The percentage of transportation of newborns with In order to provide counselling to the newborn during the congenital malformations by period remains unchanged, there critical situation in the republic, the Resuscitation and Consultation is an established transport safety algorithm, mortality in this Center for Newborns was established in 2005. In the context of group for the second period reduced by 5 times and amounted our region, where it is not possible to have district hospitals of to 8% (Table III). No deaths occurred during transportation. sufficient capacity in both personnel and technical equipment Based on the foregoing, we may note the following: due to low population density, an invaluable role is played by - Without timely evacuation of newborns with surgical the resource-saving telemedicine technologies. Currently, all pathology in our region favourable outcome is difficult to district hospitals of the republic are equipped with telemedicine achieve; stations. Each year over 200 infants from all over the republic - Competently conducted transportation does not worsen are remotely monitored and get on average 3 to 4 consultations the prognosis of the newborn in the postoperative period. (more than 900 consultations per year), mortality among the The main task at the level 3 hospital is the implementation monitored children being 6% – 12%. The main pathology leading of new treatment algorithms for infants with surgical pathology, to death in monitoring is immaturity respiratory distress syndrome applying high-tech methods of surgical treatment. Thus, over accounting for 56% of deaths, severe asphyxia, intrauterine the last 5 years, the department introduced minimally invasive infections, congenital heart defects 30%, the share of other surgery for endosurgical diaphragmatic hernia, congenital pyloric congenital malformations amounts to 6%. stenosis, lung defects, high anorectal atresia, coloesophagoplasty,

580 Su r g e r y o f c o n g e n i t a l malformations in n e w b o r n s

Table III. Mortality in infants with congenital malformations transported from the Central Republican Hospital, by periods. 1995 – 2004 2005 – 2014 Without transportation Transported Without transportation Transported 55 (54%) 47 (46%) 97 (58%) 71 (42%) 32 mortalities 20 mortalities 23 mortalities 6 mortalities 58% 42% 23.7% 8% р=0.094 р=0.01 Р – is the current level of statistical significance of differences in mortality depending on transportation in different periods using the Pearson χ2.

endorectal colon pull-through for Hirschsprung’s disease, CONCLUSIONS levatorosphincteroplasty methods, etc. In addition to the 40.4% of malformations are within the pediatric surgeon’s introduction of new technologies, improvement of surgical competence and can be corrected in infancy. methods for correction of congenital malformations, adoption Eliminating controllable causes of mortality of infants with of new diagnostic and therapeutic algorithms in our region, in surgical pathology, introduction of new algorithms and standards order to improve the quality of care provided to newborns with of treatment reduced the mortality rate by 3.5 times. surgical pathology it is necessary to create a whole system that The main link of the regional models of organizing surgical includes the interrelation between the perinatal and pediatric care for newborns is the centralization of health care, with major services. medical and organizational methods being remote monitoring So, the modern model of organizing surgical care to newborns and competently performed transportation of newborns. with congenital malformations in the conditions of our region Specialized surgical care for the newborn is only possible in includes: quality antenatal diagnostics of malformations, prenatal the level 3 hospital, which unites perinatal and pediatric centers, consultation with the pediatric surgeon which determines the ensuring continuity in the treatment of neonates. tactics of pregnancy and childbirth for each child. But some malformations are difficult to diagnose prenatally, i.e. a number REFERENCES of the newborn – 42% are indicated for transportation to the 1. J.G. Mokrushina // Medical care from newborns with surgical diseases. – Abstract of level 3 hospital [3]. Specialized surgical care is provided in a large dissertation paper. – Moscow: 2013 – 52 p. children’s hospital, which has a sufficient reserve of diagnostic 2. E.N. Baybarina Improvement of early surgical care for children with congenital and operational capabilities, preparation in the preoperative and malformations. / E.N. Baybarina, D.N. Degtyarev, Yu.I. Kucherov [et al.]// – Russian early postoperative period should be carried out in a specialized newsletter of Perinatology and Pediatrics, 2011, №2, р.12-19. neonatal intensive care unit. 3. E.M. Hamathanova Transportation of newborns with malformations under different models of healhcare. / E.M. Hamathanova, Yu.I. Kucherov, O.G. Frolova [et al.]//- Obstetrics and Gynecology, 2010, №6, р.109-113

ADDRESS FOR CORRESPONDENCE: Savina V.A. Russia, Republic of Sakha (Yakutia), 677018, Yakutsk city, Sergelyakhskoye shosse 4 Ph. 8-914-225-30-94. Fax – 32-17-76. [email protected]

581 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Immunomodula ti o n a n d tre a t m e n t o f a c u te d estr u cti v e p a n cre a titis in a multidisciplinar y s u rgic a l h o spit a l

Vinokurov M.M., Saveliev V.V., Gogolev N.M. Yalynskya T.V.

f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT This work is based on the analysis of complex treatment of 497 patients with pancreatic necrosis treated at the surgical department of the Republican Hospital №2 - Center for Emergency the Republic of Sakha (Yakutia) in the period from 2010 to 2015. The study was able to adapt and improve the two-tier immunocorretion in pancreatic necrosis in a multidisciplinary surgical hospital that along with the other constituents of intensive therapy has allowed a whole to reduce the amount of intra-abdominal and extraabdominal complications - sterile pancreatic necrosis phase - from 23.6% to 14.6 and 31 6% to 15.0% respectively, total lethality - from 17.6% to 7.2% lethality in patients with non-operated group - from 15.6% to 2.2% lethality in the group of patients operated - 18, 4% to 10.9%. In the phase of infectious complications of pancreatic necrosis lethality rate decreased from 45.8% to 37.7%.

Key words: Pancreatic necrosis,immunocorretion therapy.

Wiad Lek 2015, 68 (4), 582-586

INTRODUCTION All patients included in the study cohort were separated into The last decade marked a qualitatively new stage of two groups and three subgroups in each group, depending on comprehensive research in this area of concern abdominal surgery the fact of infection and embodiments pathomorphogenesis as urgent pancreatology, the structure of which, acute destructive pancreatic necrosis. The first group of observations - the group pancreatitis ranks first [1, 2, 10]. The range of the main directions «A», consisted of patients with sterile clinical and pathologic of scientific and practical research includes not only the study of forms of pancreatic necrosis. The second group of observations various aspects of pathogenesis and tanatogenesis disease and - the group «B», consisted of patients infected with clinical and its complications, and improved methods of diagnosis, intensive pathologic forms of pancreatic necrosis. Group «A» is divided care choices and tactics of surgical procedures [3, 9, 13, 14]. into three subgroups: the subgroup «a» - those with enzymatic Target: A significant part of the researchers involved in the ascites-peritonitis; subgroup «b» - patients with the formation problem of the treatment of acute destructive pancreatitis found parapancreatic infiltration, morphological basis which was „aseptic” that the risk of complications, including purulent destructive abscess of various departments of the retroperitoneal fat; subgroup processes directly related to developing this category of patients «c» - patients with pseudocyst formation postnecrotic alternatively with secondary immunodeficiency [1, 3, 4, 5, 7, 9, 11, 12, 13, the evolution of necrosis occurring in abacterial conditions (time 14]. It is for this reason that one of the main problems facing of formation of a false cyst usually accounted for more than 4 the surgeon is timely, reasonable and adequate immunotherapy. weeks from the onset of the disease, provided these posts with Consequently, the question of choice of tactics of treatment of large formations of pancreatic duct). In turn, the group «B» is patients with different clinical and pathologic forms of complications divided into three groups depending on the different options sterile and infected pancreatic necrosis and the inclusion of a for transforming the sterile clinical and pathological forms in comprehensive treatment program immunotherapy require infected necrotizing pancreatitis: a subgroup «d» - patients with further research and development, which was the basis for the abscess formation pancreatogenic; subgroup «e» - patients with implementation of this work. infected pancreatic necrosis formation; subgroup «f» - patients with infected pancreatic necrosis formation in conjunction with MATERIALS AND METODS pancreatogenic abscess. This work is based on a comprehensive analysis of the results The diagnosis of pancreatic necrosis and the development of of conservative and surgical treatment of 497 patients with its complications was verified based on a comprehensive survey pancreatic necrosis treated at the surgical department of the include: clinical findings, laboratory tests (including an assessment Republican Hospital №2 - Center for Emergency Medical Aid of the level of endogenous intoxication (EI) on the content of low of the Republic of Sakha (Yakutia) in the period from 2010 to and medium molecular weight (SL & AMW) by the method MY 2015. Malakhov [6] and oligopeptide (ARS) at the Lowry [8] in plasma,

582 Immunomodulation a n d t r e a t m e n t o f a c u t e destructive pancreatitis in a multidisciplinary s u r g i c a l h o s p i t a l erythrocytes and urine with the release of five phases of EI, as (σ); confidence factor differences (p) was determined by the well as control and accounting of important biochemical markers Mann-Whitney test. of pancreatic tissue necrosis and retroperitoneal tissue, systemic inflammatory response (SVR), and infection of pancreatic necrosis RESULTS AND DISCUSSION (LDH , C-reactive protein, procalcitonin). Instrumental methods According to several authors [1, 3, 5, 10, 14], in 24-68% of of diagnosis include ultrasound and radiopaque computer scan patients with necrotizing pancreatitis develop immune system of the abdominal cavity, retroperitoneal fat, videolaparoscopy, disorders and functional impairment of the liver, which greatly transdermal therapeutic and diagnostic puncture liquid formations exacerbates the severity of the disease due to the development of the pancreas, abdominal and retroperitoneal tissue under of secondary immunodeficiency and eventually worsens its ultrasound followed by microbiological and cytological analysis prognosis. of the resulting material. Assessment of the severity of the general The causes immunodeficiency in necrotizing pancreatitis are: condition and the severity of multiple organ failure in patients significant loss of proteins with exudate, pus; insufficient intake with pancreatic necrosis was performed using integrated systems of complete proteins from food (forced starvation, malnutrition); scales, APACHE II [4] and TFS [10]. toxic inhibition of liver function, including protein-synthesizing; Immune status was evaluated by the number of lymphocytes and immunosuppression drug due to prolonged administration of their subpopulations (T lymphocytes and B lymphocytes). antibiotics and others. [11, 12, 14]. To study the T-system of immunity were determined by The object of our study was to evaluate the immune status of plaque subpopulation of T cells: T helper (Th), T-suppressor 188 (37.8%) patients with a sterile and in 57 (82.6%) patients with (TS), and calculates the immunoregulatory index (IRI), equal positive clinical and pathologic forms of pancreatic necrosis. Cellular to the ratio Tx to Tc (Th / Ts) [7]. (T-lymphocytes and their subpopulations immunoregulatory index ANALYSIS-immune system include its quantitative (SDI)), and humoral immunity (B-lymphocytes, immunoglobulins characteristics - determination of B-lymphocytes in the blood (the A, M and G) were evaluated during the first day after admission percentage and absolute content) [7] and functional characteristics and then every 3-5 days. - determination of serum immunoglobulin classes A, M, G by Studies on the first day, showed a violation of the immune radial immunodiffusion C. Manchini [7]. status in all representations of groups and subgroups of patients Statistical analysis of clinical material produced using the (Table I). software package Stat Plus 2007 for Windows XP. In assessing Presented in Table 1 data show that major shifts in sterile the totality of the average value (μ) and standard deviation pancreatic necrosis characteristic of cellular immunity and appear

Table I. Immune status of patients sterile (group A) pancreatic necrosis in the first days of intensive care. Subgroup«c» Indicator Control Subgroup «a» (n=75) Subgroup «b» (n=102) (n=11) Leukocytes(·109/л) 6,7±1,3 12,6±1,4** 15,1±1,8*** 8,2±1,3* Lymphocytes (%) 20,1±2,1 15,3±2,3** 12,1±3,5** 17,4±1,5* (·109/л) 1,4±0,1 0,7±0,4* 0,6±0,3* 1,1±0,6* T-lymphocytes (%) 44,9±2,3 22,3±1,5** 19,3±1,2** 36,6±2,4* (·109/л) 1,1±0,9 0,7±0,4* 0,5±0,2* 0,9±0,7* T-helpercells (%) 39,6±3,3 28,1±3,3** 26,1±3,4** 31,4±2,3* (·109/л) 0,8±0,8 0,4±0,3* 0,3±0,4* 0,6±0,8* T-suppressors (%) 25,5±2,8 19,5±2,7** 18,1±3,1** 22,3±4,1* (·109/л) 0,7±0,4 0,4±0,2* 0,3±0,4* 0,5±0,5* IRI (у.е.) 1,6±0,1 1,4±0,3* 1,4±1,6* 1,4±0,4* B-lymphocytes (%) 27,3±2,6 17,4±7,1** 15,3±4,1*** 24,6±1,6* (·109/л) 0,7±0,3 0,4±0,9* 0,3±0,5* 0,6±0,1* IgA (г/л) 2,4±0,1 3,7±1,1** 4,1±0,3*** 3,2±1,5** IgM (г/л) 1,48±0,7 1,0±0,1* 0,9±0,2** 1,1±0,4* IgG (г/л) 14,2±2,6 17,6±4,1** 19,8±1,5*** 16,5±2,4** * - index significantly different from control (р<0,05), ** - index significantly different from control (р<0,01), *** - index significantly different from control (р<0,001)

583 VinokurovM.M., et al. absolute and relative decline in the number of lymphocytes, relative amount of T-lymphocyte populations and Tx and Tg predominantly T-lymphocytes and their subpopulations. Absolute significantly below as reference numbers and indexes of patients content of T lymphocyte Th and Tc, in patients, especially in the subgroup «d». The most pronounced decrease in Tj and Tc, the subgroups «a» and «b» is reduced as compared with the control absolute content in the blood was 0,3±0,5 (• 109/l), 0,4±2,4 value of 1.5; 1.6 and 1.4; 1.3 times, respectively. It may be noted (• 109/l) and 0,2±1,2 ( • 109/l), 0,3±0,9 (• 109/L), respectively, that among the subpopulations of T-lymphocytes, Tx quantity lower than the values of the subgroup of patients with «d» is change, compared with T is somewhat more pronounced. Presented almost 1.5 times and check digits 2 times. Analyzing changes in changes have led to a decrease in Iran, which has made these Iran, it may be noted that its value amounted to USD 1,4±0,5 and values 1,4±0,4 subgroups and 1,4±0,3 USD respectively, which 1,5±1,1 respectively, which is also lower than in the subgroup could indicate a moderate immunodeficiency. In the subgroup of patients with «d» and the reference values provided in the «c» change of cellular immunity were much less pronounced study groups. in comparison with the subgroups «a» and «b» and generally The total number of B-lymphocytes in infected pancreatic approached the check digit. necrosis forms (Table. II), especially in the subgroups «e», and Changes in the immune system in the presented study groups «f» were significantly lower than those in the subgroup «d», and were less pronounced and expressed decrease in absolute and compared with values in a group of patients with clinical sterile relative content of B-lymphocytes. The indicator of its functional pathomorphological forms an average of 2.5-3. Quantitative characteristics - blood levels of immunoglobulins, usually remained values of immunoglobulins, especially IgA and IgG, quite clearly within normal limits, except for IgA and IgG, the absolute values correlated with the severity of sepsis and pancreatogenic above the are exceeded in 1,6-2,5 times or more check digits. This fact, in reference value and the subgroup «d» in 3-4 times. However, from spite of dissimmunoglobulinemia, according to the literature, is Table. 2 shows that in patients with sepsis is noted pancreatogenic characterized as increased activity of humoral immunity [11]. It greater variation of the standard deviation of the mean, which should be noted, since the voltage of the immune system of the can be explained by the different severity of sepsis. human body is realized in the North, mainly due to the activation For patients with severe sepsis pancreatogenic except pronounced of B-cell level [7], therefore, we can expect its early failure. decrease T-cell immunity, there is significant compared with the More significant changes were observed in the immune status of control and with the patients with uncomplicated, reduction in patients subgroups «e» and «f» in the phase of infected pancreatic the absolute and relative number of B-lymphocytes. Thus, the necrosis. Against the backdrop of severe general condition of content of B lymphocytes in the blood of an average amounts patients and the manifestation of clinical signs of systemic at 0,2±0,1 (• 109/L), significantly lower than control values inflammatory response of the body, these changes correspond and the subgroups «d». Reduction of IgM and in some cases, to a pronounced degree of secondary immunodeficiency (SID). especially in severe sepsis pancreatogenic IgA and IgG require Thus, in patients subgroups «e», and «f» content absolute and uniform application of tactics immunomodulation.

Table II. Immune status of patients infected (group B) pancreatic necrosis in the first days of intensive care. Subgroup «f» Indicator Control Subgroup «d» (n=9) Subgroup «e» (n=28) (n=20) Leukocytes(·109/л) 6,7±1,3 7,6±1,1* 19,3±2,8*** 16,1±1,1** Lymphocytes (%) 20,1±2,1 15,5±1,8* 11,1±3,3** 11,9±3,3** (·109/л) 1,4±0,1 1,0±1,6* 0,4±2,4* 0,5±1,6* T-lymphocytes (%) 44,9±2,3 34,1±2,2* 19,2±3,5** 18,1±2,2** (·109/л) 1,1±0,9 0,8±0,3* 0,5±0,3* 0,6±1,7* T-helpercells (%) 39,6±3,3 29,4±1,3* 24,2±1,3** 25,4±1,4** (·109/л) 0,8±0,8 0,5±3,1* 0,3±0,5* 0,4±2,4* T-suppressors (%) 25,5±2,8 20,1±2,1* 16,8±2,1** 17,5±3,3** (·109/л) 0,7±0,4 0,4±1,5* 0,2±1,2* 0,3±0,9* IRI (у.е.) 1,6±0,1 1,4±0,6* 1,4±0,5* 1,5±1,1* B-lymphocytes (%) 27,3±2,6 22,5±1,3* 15,7±3,5** 16,1±2,1** (·109/л) 0,7±0,3 0,5±3,1* 0,3±0,1* 0,4±0,2* IgA (г/л) 2,4±0,1 4,6±3,5** 6,3±4,1*** 5,5±1,6** IgM (г/л) 1,48±0,7 1,0±0,2* 0,8±0,9* 0,9±1,2* IgG (г/л) 14,2±2,6 18,1±1,4** 21,8±1,1*** 20,3±2,5**

584 Immunomodulation a n d t r e a t m e n t o f a c u t e destructive pancreatitis in a multidisciplinary s u r g i c a l h o s p i t a l

Table III. Immunotherapy of patients with pancreatic necrosis. Thenumberofpatients Methodsforimmunotherapy absolute % Immunotherapyfirstlevel Passivereplacementtherapy Freshfrozenplasma 57 100 Immunoglobulins 44 77,2 Immunostimulatorytherapy Taktivin 15 26,3 Immunotherapysecondlevel Immunocorrectorscomplexaction Polyoxidonium 54 94,7

Thus, the analysis of the immune status of patients with CONCLUSION necrotizing pancreatitis shows the development of VID, due Summarizing the results of the study it can be concluded mainly deficient T cell immunity. At the same time observed that that the main changes of the immune status in necrotizing immune deficiency is more pronounced in the transformation pancreatitis characterized by T-cell immunity and managers of a sterile clinical and pathological forms in infected pancreatic are most pronounced in patients with common clinical and necrosis, the development of pancreatogenic sepsis, and in general, pathologic forms of pancreatic necrosis as sterile, and the it depends on the nature of the clinical course of the disease. phase of infection in which there is a decrease in more than The ongoing evaluation of the immune status in the course of twice the absolute and relative number of T lymphocytes and the treatment process and identify the nature VIEW allowed T helper cells in 1.5 immunoregulatory index. These violations to draw up a program for immunotherapy of patients with demonstrate the need for immunotherapy, the choice of which is necrotizing pancreatitis. determined individually and depends on the nature and extent Immunotherapy patients with sterile pancreatic necrosis, of the identified changes. often had a preventive focus and includes therapeutic doses of thymus peptides (Taktivin) during the period of the patients in REFERENCES the ICU and Share after their transfer to relevant department (for 1. Barykov V.N. Peculiarities of severe necrotizing pancreatitis complicated abdominal 7-10 days). On the contrary, an immunomodulating treatment sepsis blood / V.N. Barykov, A.V. Potemkin, I.L. Ryshkov, A.V. Ekimov // Proceedings XI in patients with infected pancreatic necrosis and generalization Congress of Russian surgeons. - Volgograd, 2011. - P. 501-502. of infection is a more complicated task, requiring individual 2. Filimonov M.I. Surgery pancreatic necrosis / MI Filimonov, SZ Burnevich // 80 lectures approach and includes two levels (Table III). on surgery / Edited by V.S. Saveliev. - Moscow: Publishing House „Litterra”, 2008. - P. At the initial stage (1-3 days), expressed in terms of the 447-455. inflammatory syndrome, correction VIEW conducted with 3. Garipov R.M. Immune disorders and their role in the prognosis of acute destructive a focus on passive, replacement therapy. Correction of deep pancreatitis / R.M. Garipov, A.Z. Gilmanov, Z.R. Garipova // Proceedings of the XIX disorders of immunity in patients was carried out by introducing International Congress of surgeons-hepatologists of Russia and CIS countries „Urgent subgroups «e» and «f» of fresh frozen plasma, intravenous problems of surgical hepatology”. - Irkutsk, 2012. - P. 117. immunoglobulin. 4. Knaus W.A. APACHE II-acute physiology and chronic health evaluation: physiologically It should be noted that only after the improvement of the general based classification system / W.A. Knaus, J.E. Zimmerman, D.P. Wagner, E.A. Draper // condition, normalization of central and peripheral hemodynamics, J. Crit. Care Med. - 1981. - Vol. 9. - P. 591-597. reduce signs of inflammatory syndrome and a stabilization of the 5. Lobanov S.L. Modern approaches to the treatment of acute pancreatitis / S.L. Lobanov, immunity indices prescribed immunotherapy second level. As A.V. Stepanov, L.S. Lobanov.// - Chita: Publisher of IC „Business Baikal”, 2008. - 160 p. a rule, it happened not earlier than 7-10 days after the operation 6. malakhova M.Y. Determination of SL & AMW / MJ Malakhov // Medical laboratory and the beginning of immune therapy. So, against first- level technologies. - 1999. - V.2. - P. 618-647. immunotherapy, further, to activate cellular immune defense 7. Potapov A.F. Comprehensive assessment of the intensive care surgical abdominal mechanisms in 54 (94.7%) patients were given Polioksidony. infections in a specialized center for emergency medical care of the Sakha Republic Thus, the usefulness of the scheme provided immunotherapy (Yakutia): Diss. ... Dr. med. Science / A.F. Potapov//. - Moscow, 2004. - 237 p. was confirmed by the stabilization of the immune status at all 8. RogozhinV.V. Methods of biochemical research / V.V. Rogozhin.// - Yakutsk: Publishing stages of treatment (Table I, II). „YSU”, 1998. - 93 p.

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9. Runzi M. Severe acute pancreatitis: nonsurgical management of infected necrosis / M. 13. Winnick Y.S. Prevention immune deficiency at acute destructive pancreatitis / Y.S. Winnick, Runzi, W. Niebel, H. Goebel [et al] // J. Pancreas. - 2005. - Vol. 30. - №3. - P. 195-199. N.M. Markelov, S.V. Miller, E.S. Cherepanov // Proceedings of the XIX International 10. Savelyev V.S. Pancreatonecrosis / V.S. Savelyev, M.I. Filimonov, S.Z. Burnevich.// - Moscow: Congress of surgeons-hepatologists of Russia and CIS countries „Urgent problems of Publishing „MIA”, 2008. - 264 p. surgical hepatology”. - Irkutsk, 2012. - P. 112. 11. Sotnichenko B.A. The use of recombinant interleukin-2 in acute destructive pancreatitis 14. Yermolov A.S. Immunological assessment of the severity and prognosis of acute pancreatitis / B.A. Sotnichenko, E.V. Markelov, S.V. Salienko // Surgery. - 2005. - №5. - P. 20-22. / A.S. Yermolov, N.V. Borovkov, P.A. Ivanov, A.V. Grishin, D.A. Blagovestnov, V.B. Grips // 12. Tenner S. Acute pancreatitis. Nonsurgical management / S. Tenner, R.A. Banks // World Herald surgery. - 2005. - №6. - P. 22-28. J. Surg. - 1997. - Vol. 21. - №2. - P. 143-148.

ADDRESS FOR CORRESPONDENCE: Vinokurov M.M. Russia, Republic of Sakha (Yakutia), 677000, Yakutsk city, Street Dzerzhinsky 26 square meters. 41. [email protected]

586 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Ex perie n ce o f tre a t m e n t o f c o n ge n it a l d i a p h r a g m a tic h er n i a a m o n g b a b ies

Savvina V.A.¹,², Tarasov A.Yu.², Varfolomeyev A.R.¹, Nikolaev V.N.¹,², Petrova N.E.², Emeliynova Z.E.¹, Grigoriev V.A.², Sleptsov A.A.² ¹f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a ²r e p u b l i c a n h o s p i t a l n o . 1 n a t i o n a l c e n t e r o f medicine, y a k u t s k , r u s s i a

ABSTRACT The article presents our experience of treatment of congenital diaphrogmatic hernia at newborns and hernia of an esophageal opening of a diaphragm among children of early age. Since 2010 surgical tactics has been changed: the prolonged preoperative preparation with use of the device of high-frequency ventilation of lungs, correction of symptoms of pulmonary hypertensia is carried out, operation is carried out according to plan after stabilization of the patient in parameters of oxygenation and an acid-base state, operative treatment is executed by method of low-invasive endosurgery. Over the last 5 years 25 children with good functional and cosmetic results have been operated. The lethality in the case of congenital diaphragmatic hernia at newborns decreased to 12%, it was noted generally among patients with the expressed hypoplasia of lungs which died during preoperative preparation. In recent years we place emphasis on antenatal diagnosis of pathology and prenatal diagnostics of degree of a hypoplasia of a lung on indicators of a pulmonary and head index at a fetus. It wasn’t noted a postoperative lethality.

Key words: congenital diaphragmatic hernia, hernia of an esophageal opening of a diaphragm, surgical treatment

Wiad Lek 2015, 68 (4), 587-590

INTRODUCTION MATERIAL AND METHODS Surgical treatment of children with the case of congenital In the period from 2010 to 2014 in surgical department of the anomaly of diaphragm , especially at newborns and babies, Pediatric center 25 children with congenital diaphragmatic hernia remains one of actual and complex challenges for children’s were on treatment. The first thoracotomy plasticity of defect of a surgeons and anesthesiologists so far. The lethality at congenital diaphragm was executed in March, 2010. Since this period to all diaphragmatic hernia and an elevation of a diaphragm, even children with diapharagmatic hernia of various localization who at the optimum organization of the perinatal help, remains came to clinic planned endosurgical intervention. Preoperative high that is connected with a pulmonary hypoplasia and the inspection included: survey, survey X-ray analysis of a thorax, combined persistent pulmonary hypertension [1, 2]. Considerable roentgenoscopy of a gullet and stomach, irrigoscopy, abdominal improvement of a situation is connected in recent years with echocardiography, neurosonography and echocardiography, application of new technologies, such as permissive ventilation computer tomography of organs of a thorax and abdominal cavity. with a hypercapnia, by high-frequency ventilation, extracorporal Preoperative preparation at newborns with false diaphragmatic membrane oxygenation and the delayed surgery in group at the hernia was carried out on average within 3 days by means of heaviest patients [3, 4, 5]. high-frequency ventilation of lungs and was directed on fight The choice of surgical access for correction of congenital against pulmonary hypertensia and the developed persistent anomaly of a diaphragm is extremely important and depends fetal blood-circulation. In cases of true hernia and hernia of an on its type. Traditional accesses in surgical treatment are esophageal opening operations were performed in a planned laparotomy – and a thorocotomy. Development laparoscopic and order after relief of anemia and treatment of exacerbations the thorocoscopic interventions essentially changed approach to of bronchus-pulmonary pathology. Surgery was carried out treatment of defects of a diaphragm. Indications to carrying out under a standard endotracheal anesthesia with application of endoscopic operations at the diaphragmatic hernia intensively endovideocomplex and the “Karl Storz” tool set. extend in many respects due to the best visualization of organs of Technology of operation at false diaphragmatic hernia. In a chest cavity during surgical intervention, good functional and cases of operations for false diaphragmatic hernia used 3 troacar cosmetic results, more favorable course of the early postoperative with a diameter of 3,5 mm for the telescope and manipulators. period and fast rehabilitation of patients after surgeries [6, 7, Troacars were established in the fourth intercostal space on 8, 9, 10, 11]. the posterior axillary line and in the sixth intercoastal space

587 Savvina V.A., et al.

Fig. 1. In the left pleural cavity intestines loops are visualized. Fig. 2. Defect of a diaphragm, possibility of plastic are estimated by means of local tissue.

Fig. 3. Defect is taken in by nodal seams. Fig. 4. Termination of thoracoscopic plastic.

on anterior axillary and scapular lines. For prevention of a loops of intestines and parenchymatous organs were immersed hypercapnia and the minimum haemo dynamic violations during in an abdominal cavity. The defect of a dome of a diaphragm, toracoscopic operation, the low pressure of CO2 in a pleural its sizes, existence of the “parietal” muscular embankment were cavity of 5 mm Hg with a speed of stream of 1 l/min were used. estimated. Defect was taken in separate nodal (in most cases) Primary entry into the left pleural cavity was carried out by a or continuous seams (Ethibond 2/0 Ethicon, Mersilen 2/0) with thoracocentesis of 3,5 mm. troacar in the fourth intercoastal intracorporal formation of node, drained a pleural cavity through space on posterior axillary line. An operational interference an opening of a troacar. Skin wounds were adapted by means was continued in the case of absence of deterioration of key of “Dermabond’ glue. parameters of monitoring. A pleural cavity was examined after Technology of operation in a case of a true diaphragmatic an insufflation of carbon dioxide and a collapse of a lung. Then hernia. The Thoracoscopic phrenoplication was carried out in troacars for manipulators were administered. Under the influence position of the patient on the left side with the roller under a of the positive pressure of CO2 and by means of manipulators, thorax. In the right hemithorax 3 troacars with a diameter of

588 Ex p e r i e n c e o f t r e a t m e n t o f c o n g e n i t a l d i a p h r a g m a t i c h e r n i a a m o n g b a b i e s

Fig. 5. Hiatoplastic by sewing together of crura of a diaphragm behind a gullet. Fig. 6. Hiatoplastic by sewing together of crura of a diaphragm in front of a gullet.

3.5 mm for the telescope and manipulators were established. In all cases defect was left-side and posterolateral. Average sizes Places of introduction of troacars corresponded to the above were 3.5x2.0 cm. Contents of the left pleural cavity of all newborns described intervention, only on the right. Thanks to a carboxythorax had loops of a small and large intestine, in 4 cases the spleen and the stretched dome of a diaphragm is flattened that facilitates the left kidney were also found. The average time of operation further manipulations. Goffering of a diaphragm was carried out made 50+10 minutes. Blood loss and intraoperative complications imposing of 3 “goffering” continuous seams parallel to pericardiac were not noted. There weren’t cases of conversion. Owing to diaphragmatic sine with extracorporal formation of nodes. the revealed aplaziya of a dome of a diaphragm two patients Technology of operation of a laparoscopic hiatoplastika and were applied the artificial plastic material Permacol. Average Tal’s fundoplication at hernia of an esophageal opening of a terms of artificial ventilation of lungs after operation made 5,6 diaphragm. Position of the patient is on a back with the roller days, pleural drainage of 4,7 days. Enteral loading began on under lumbar part of a backbone. In the course of surgery 2-3 days. Anesthesia wasn’t appointed. The average duration of changed a tilt angle of the operating table from horizontal level postoperative hospitalization made 15,4 patient-days. Children to the provision of anti-Trendelenburg with a small inclination were examined in 3-4 months, all patients develop according to to the right. At laparoscopic correction of hernia used 5 troacars age and a functional condition of a diaphragm is satisfactory. with a diameter of 3.5 mm. The stomach was reduced in an Cases of recurrence of false diaphragmatic hernia among our abdominal cavity after crossing of proximal part of a gastrohepatic patients were not noted. Good functional and cosmetic results ligament and a peritoneum on edge of an esophageal opening were received among all patients. of a diaphragm, esophageal diaphragmatic and gastrophrenic The Thoracoscopic phrenoplication was executed to 5 patients. ligament. The expanded esophageal opening of a diaphragm Duration of operation made 65 minutes. The laparoscopic was taken in behind and in front of a gullet by imposing of hiatoplastic with a fundoplication was executed to 6 patients. nodal seams on crura of diaphragm by non absorable material Time of operation made 80 minutes. Blood losses during (Ethibond 2/0 Ethicon) with intracorporal formation of nods. operations were not noted. There were no cases of intraoperative The acute angle of Gis is recreated by a front gastroscopy of complications. Average terms of ALV after operations made Tal by suturing between a stomach, a gullet and an esophageal 2,5 days. Terms of drainage of a pleural cavity in average were opening of a diaphragm. 5,4 days. Enteral loading, as a rule, began on the 2nd day after Children were in the next postoperative period on the operation. Children received the full volume of enteral load by the prolonged artificial ventilation of lungs in the conditions of 5th 6th day. Need for purpose of the anesthetizing preparations resuscitation department. They received a sedation and relaxant. wasn’t. Wounds from punctures on a thorax epithelized under Terms of the transfer to independent breath and the beginning a glue film. Cases of a wound infection weren’t registered. All of enteral load depended on stabilization of respiratory function children are written out in a satisfactory condition. Average and restoration of a gastrointestinal transit and, as a rule, didn’t patient-day after operation made 12,5. Children were examined exceed 5 days after operation. in 3-6 months, control roentgen examination was executed. One recurrence after a thoracoscopic frenoplication was revealed, the RESULTS AND DISCUSSION patient was operated repeatedly with a good remote result. Thoracoscopic plastic was executed to 14 patients with Traditional access for correction of false diafragmal hernia is false congenital diaphragmatic hernia. All children were of the the laparotomy at which there are certain difficulties of bringing neonatality period. Middle age at the time of operation made 3 down of loops of intestines and parenchymatous bodies from days. The average body weight of newborn children was 3.200 g. a pleural cavity. Sometimes even the wide laparotomy isn’t

589 Savvina V.A., et al. capable to provide the demanded quality of quick access that CONCLUSIONS can lead to a trauma of hollow bodies and bleeding from the 1. Thoracoscopic plastic of defect of a diaphragm in case of parenchymatous. The additional section of a diaphragm in the false congenital diaphragmatic hernia – rather safe procedure field of defect can be one of solutions of this problem. Suture at newborns. on a diaphragm because of the loops of intestines, stomach and 2. Fine visualization of all stages of intervention, lack of technical spleen prelying to a wound is also rather complicated. With difficulties at bringing down of bodies and actually plasticity of development of endosurgery correction of false diaphragmatic a diaphragm, fast restoration in the next postoperative period hernia became safe procedure among babies and newborns. are undoubted advantages of endosurgical intervention. According to combined statistics the frequency of conversion 3. Unlike an open laparotomy or a toracotomiya, at the is rather small now. Thoracoscopy allows visualize the bodies endovideosurgical low-invasive interventions due to the lack of which moved to a pleural cavity and atraumatically to set them a considerable operational trauma there is no need of purpose in an abdominal cavity. In one case we didn’t meet technical of analgetics, there is possible an early enteral loading, patient- difficulties when moving bodies, bringing down of bodies is day is considerably reduced, dressing is saved. promoted by an insuffliation of carbon dioxide in a pleural 4. The outcome of similar interventions depends on experience cavity. Pressure in a pleural cavity of 5 mm Hg allows to collapse of the doctors participating in treatment of this extremely difficult a lung in absolute majority of cases and to create optimum category of patients, and also developments of neonatal anesthetic- conditions for manipulations on a diaphragm. Also such pressure resuscitation service in each certain medical institution. is determined as safe for newborns which doesn’t cause haemo dynamic violations. As easy access to a diaphragm is possible, REFERENCES the sealing of defect doesn’t represent technical difficulties. 1. Ashcraft K.U., Holder T.M. //Children’s surgery. — SPb. Hardford, 1996.-384 p. We don’t note a basic difference in imposing of nodal seams 2. Downard C.D. Analysis of an improved survival rate for congenital diaphragmatic hernia or a continuous seam. Thoracoscopic access is preferable due / Downard C.D., Jaksic Т., Garza J.J. [et al.] // J. Pediatr. Surg. — 2003. —Vol. 38.- P. to the lack of a section of the big massif of muscles that can 729-732. break function of breath in the postoperative period. Lack of 3. Krasovskaya T.V. Optimization of diagnostic and medical programs in surgery of newborns damage of a peritoneum doesn’t lead to postoperative paresis of a at the present stage /Krasovskaya T.V., Kucherov YU.I., Golodenko N. V., [et al] // Surgery. digestive tract and development of an adhesive illness. The small 2003. – No. 7. – P. 29-31. term of the prolonged artificial ventilation of lungs is caused by 4. Stepanov E.A. Optimum terms of surgery at the diaphramatic hernia / Stepanov E.A., Krasovskaya absence of an operational injury of thorax, a postoperative pain T.V., Kucherov YU.I., Belyaev I.D., [et al.]//Children’s surgery. 2002. – No. 2. – P. 28-30. syndrome and violation of biomechanics of breath. 5. Bagolan P. Impact of a current treatment protocol on outcome of high-risk congenital The greatest distribution was gained by a fundoplication diaphragmatic hernia / Bagolan P., Casaccia G., Crescenzi F [et al.] // J. Pediatr, Surg. on Nissen in case of endosurgical treatment of hernia of an — 2004. – Vol. 39. – P. 313-318. esophageal opening of a diaphragm at children. But this intervention 6. Area M.J. Early experience with minimally invasive repair of congenital diaphragmatic completely eliminates a physiological gastro-esophageal reflux, hernias: results and lessons learned / Area M.J., Barnhart D.C., Lelli Jr.J.L. [et al.] // J. excludes possibility of an eructation and the act of vomiting that Pediatr. Surg. — 2003. — Vol. 38. – P. 1563-1568. can lead to “sharp expansion of a stomach”. Also in connection 7. Becmeur F. Thoracoscopic repair of congenital diaphragmatic hernia in children / Becmeur F., with hypostasis of a cuff patients are in certain cases compelled Reinberg O., Dimitriu C. // Semin. Pediatr. Surg. — 2007. — Vol. 16.- № 4. — P. 238-244. to receive about 1 – 1,5 months the liquid and wiped food. 8. Liem N.T. Thoracoscopic surgery for congenital diaphragmatic hernia: a report of nine Recurrence of GER owing to insolvency of a cuff and formation of cases / Liem N.T. // Asian J. Surg. 2003. – Vol. 26, №4. – P. 210-212. postoperative hiatal hermia, and also the compelled splenectomy 9. Nguyen Т. Thoracoscopic repair of congenital diaphragmatic hernia:­ lessons from 45 at intraoperative wound of a spleen is frequent during mobilization cases / Nguyen Т., Le A. // J. Pediatr. Surg.— 2006.— Vol. 41.— P. 1713-1715. of a bottom of a stomach. We applied an alternative method 10. Taskin M. Laparoscopic repair of congenital diaphragmatic hernias / Taskin M., Zengin of a fundoplication – a front gastropexy of Tal which allows K., Unal E. [et al.] // Surg. Endosc. — 2002. — Vol. 16. — № 5. — P. 869. to recreate a normal angle of Gis, and is deprived of all above- 11. Yang E.Y. Neonatal thoracoscopic repair of congenital diaphragmatic hernia: selection mentioned shortcomings of a full cuff of Nissen. criteria for successful outcome / Yang E.Y., Allmendinger N., Johnson S.M. // J. Pediatr. Surg. — 2005. — Vol. 40. – P. 1369-1375.

ADDRESS FOR CORRESPONDENCE: Savina V.A. Russia, Republic of Sakha (Yakutia), 677018, Yakutsk city, Sergelyakhskoye shosse 4 Ph. 8-914-225-30-94. Fax – 32-17-76. [email protected]

590 © Aluna Wiadomości Lekarskie 2015, tom LXVIII, nr 4

Clinical c a se o f c o n d u cti n g preg n a n c y a n d c h i l d b irt h a t t h e w o m a n w it h c h r o n ic v ir a l h ep a titis b in t h e rep l ic a ti v e f o r m

Sleptsova S.S.1, Duglas N.I.1, Shek L.A.2 1f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a 2s t a t e establishment o f t h e r e p u b l i c o f s a k h a (y a k u t i a ), m a n a g e m e n t o f h e a l t h c a r e o f t h e r e p u b l i c o f s a k h a (y a k u t i a ), y a k u t s k , r u s s i a

ABSTRACT Introduction: because of a wide circulation of the hepatitis B (HB) among persons of young age, so-called vertical transmission of a virus from mother to the child is of particular importance. Relevance of this problem of HB increases in connection with a set of ways of infection, failures are more often observed at infection by natural ways: sexual and from mother to a fetus that demands development of effective measures of prevention of transfer from mother to a fetus. Aim: to develop algorithm of maintaining pregnant women with the chronic hepatitis B (HBV) for prevention of perinatal transfer of a HBV infection in the Republic of Sakha (Yakutia) (RS (Y)). Materials and methods: materials of official statistics of Territorial administration of Rospotrebnadzor of RS (Y) are studied, incidence of chronic viral hepatitises B, C and D in RS (Y) from 2003-2013 was analyzed. Clinical, laboratory and tool, serological, molecular and biological methods of research were carried out. Results: the high incidence of CHV, considerable frequency of delectability of markers of a HB infection at pregnant women, feasibility of a vertical way of a transmission of infection cause interest of doctors of different specialties in this problem. In this scientific publication we analyzed an example of maintaining the pregnant woman, woman in childbirth period with chronic viral hepatitis B, with long «experience» of an illness, with existence of replication of HBV-DNA. Conclusions. To decrease the risk of perinatal transfer of a HBV infection it is recommended a quantitative PCR-research among pregnant women with HBsAg which will provide decrease in transmission frequency of HB by carrying out in need of antiviral therapy to the woman and the individualized schedule of vaccinal prevention with introduction of specific immunoglobulin to the newborn.

Key words: viral hepatitis B, pregnancy, perinatal transfer.

Wiad Lek 2015, 68 (4), 591-595

INTRODUCTION of cliniko-epidemiological data of patients with chronic viral Hepatitis B is a serious medical-social problem of health care hepatitis B to develop algorithm of maintaining pregnant women owing to prevalence of this infection, high risk of synchronization with existence of HBsAg for prevention of perinatal transfer of with development of cirrhosis and primary cancer of a liver. a HBV infection in the Republic of Sakha (Yakutia). The Republic of Sakha (Yakutia) (RS (Ya)) is the unsuccessful region on incidence of the viral hepatitis B [1,2]. According to MATERIALS AND METHODS the population register «Сhronic Viral Hepatitises in RS (Y)» for In work materials of official statistics of Territorial administration January 1, 2013 on the account 6188 patients with the chronic of Rospotrebnadzor of RS (Ya) have been used, incidence of hepatitis B (CHB) and 4356 carriers of a virus of hepatitis B chronic viral hepatitises B, C and D in RS (Ya) from 2003-2013 consist, thus HBV share in the general structure of chronic have been analyzed. Extracts from clinical records and the out- hepatitises made 47,2%. patient card of the patient who was on treatment in department Because of a wide circulation of hepatitis B among persons for patients with viral hepatitises of State Budgetary Institution of young age, so-called vertical transmission of a virus from RS (Ya), and also the card of pregnancy and history of childbirth mother to the child is of particular importance. The perinatal (State Budgetary Institution RS (Y) «Republican hospital No. HBV transfer is of great importance in spread of a HBV infection: 1-NSH») have been studied. The full complex clinical, laboratory 25% of carriers are infected in the perinatal period [3]. Relevance and instrumental, the serological, molecular and biological of this problem increases in connection with a set of ways methods of research have been carried out. of infection, failures are more often observed in infection by natural ways: sexual and from mother to a fetus that demands RESULTS AND DISCUSSION development of effective measures of prevention of transfer from Incidence for the first time of the established forms of chronic mother to a fetus. Research objective: on the basis of the analysis viral hepatitises V (HBV) and C (HСV) in RS (Ya) remains

591 Sleptsova S.S., et al.

Fig. 1. Incidence of HBV in comparison with the general indicator of incidence of CH in RS (Y) during 2000-2013.

Fig. 2. Detectability of HBsAg among pregnant women and a carriage of HBsAg among children till 14 years in RS (Y) taking into account vaccination against HBV.

592 Clinical c a s e o f c o n d u c t i n g p r e g n a n c y a n d childbirth a t t h e w o m a n w i t h c h r o n i c v i r a l h e p a t i t i s b in t h e replicative f o r m at rather high level, following the results of 2013 701 cases of out a noninvasive method of diagnosis of fibrosis of a liver – a the chronic hepatitis (CH) that made 73,2 on 100 thousand of fibroelastometriya is recommended. population have been registered (fig. 1). All pregnant women with a chronic HBV infection have to be The important characteristic of epidemic process at infectious brought in the republican register on chronic viral hepatitises, and diseases is the width of distribution of markers of these infections in the subsequent, dynamic supervision has to be obligatory, with among indicator groups. Frequency of pregnant women with HBs- carrying out a necessary complex of diagnostic actions and in the antigenemiya in the territory of RS (Y) for 2005-2011 fluctuated presence of indications antiviral therapy is recommended. ranging from 3,1% to 3,9%, all 234140 tests of serums were The risk of infection of the newborn increases in direct ratio surveyed, from them in 7646 HBsAg (3,27%) is revealed. Despite with the level of virus load of mother before childbirth therefore it, in absolute values the number the seropositive persons at a development of the actions promoting decrease in a viremiya at the HBV infection from 2005 to 2011 grew by 1,9 times (fig. 2). woman in the period of childbirth [4] is important. In the absence However against the carried-out specific immunization in of prevention, the risk of infection reaches 80%. Depending on the the region HBsAg carriage level among children till 14 years, level of virus loading of HBV tactics of maintaining the pregnant which reduced from 86,3 on 100 thousand of population in woman is chosen [5, 6]. At quantity of DNA-HBV 107 ME/ml 2000 reduced to 0,49 by 2011 and I showed efficiency of the from 32nd week of pregnancy antiviral therapy is carried out. From held activities for vaccination against HB that is confirmed by the nucleoside anologues can be used lamivudine,telbuvidine, very high return correlation communication (coefficient of tenofovir. Telbivudine and tenofovir are referred to category B ranging correlation Spirmena) (rsp =-0,96, p<0,001) between (when studying in experiment it isn’t revealed teratogenic influence indicators of a carriage of HBsAg and coverage by vaccination on a fetus). Lamivudine and entecavir are referred to category C, the population of the republic. that is perhaps teratogenic impact on a fetus. Failure predictors Identification of HBsAg during 2005-2011 among newborns for the pregnant woman and a fetus is the high level of virus from women with a manifest HBV infection, and also patients loading, HBe-positive hepatitis and fibrosis 2-4, at such patients with asymptomatic forms of an infection made 2,3% on the the advantage of antiviral therapy is higher, than without it. republic and fluctuated in different years from 0 to 5,2%. Selective It is known that for the newborn whose mother has positive inspection of 1832 newborns from groups of risk on existence of HBsAg and HBeAg, for lack of immunoprevention the risk of HBsAg during the previous period, from 2000 to 2003, allowed development of chronic HBV of an infection makes 70-90%. to reveal a superficial anti-gene of hepatitis B among 120 children For the children born from mothers with positive HBsAg, but that made 6,5%. Decrease of this indicator shows efficiency of negative HBeAg, risk of vertical transfer much less: from 10% the carried-out work on specific prevention of HB; frequency to 40% in the absence of immunoprevention [7]. of identification of anti-HCV among newborns didn’t tend to At all newborns from women with existence of a superficial decrease. anti-gene of hepatitis B vaccination is carried out according to Results of inspection of newborns on a HBV infection should the individual scheme, offered by Poland G.A., Jacobson R.M., be compared with dynamics of incidence of this infection among 2004 [8] and that received display in our algorithm of actions children of the first year of life as these data demand further in fig. 3. A basis of prevention of perinatal infection – active supervision. In RS (Y) among group of children till 1 year during (vaccination) and passive (introduction of specific immunoglobulin 2003-2010 cases of an acute hepatitis weren’t observed, but against HBV) immunization which will provide protection of HBsAg carriage fact was elicited by us, and in 2011 and 2012 was the newborn against infection in 90-95% of cases [9]. recorded in 1 case of an acute hepatitis B among the children till In the subsequent supervision over this group of women one year born from mothers with an active HBV infection. This is obligatory, it is necessary to watch dynamically them, in fact confirms need of profound inspection of the children born the presence of indications (increase of the HBV ALT, ACT, from HBsAg-positive mothers, the individualized approach to DNA level, progressing of fibrosis of a liver) antiviral therapy immune prevention and the subsequent dynamic observation is recommended. over children till 1 year. We will give a clinical example where to the pregnant woman Studying the course of pregnancy at a HB-infection provides with a HBV infection all complex of preventive actions (passive not only risk of perinatal transfer and its prevention, but also and active prevention) concerning perinatal infection with a influence of hepatitis B on a current and an outcome of pregnancy hepatitis virus was carried out. and possibility of therapy of pregnant women with chronic Patient N., 1989, is observed at infectiologists since 1994 hepatitis B. Pregnancy with HBV can cause an exacerbation concerning chronic viral hepatitis B in a replicative form, received owing to a physiological immunosuppressive among patients, in in the childhood an interferonotherapy course within 6 months such situations activity of enzymes – ALT and AST replication with a positive effect. From the epidemiological anamnesis it is of a virus [3] increases. known that often she was ill in the childhood and she received Now at the first visit of the pregnant woman to the gynecologist, repeatedly hospitalization, including with surgery. along with all-clinical methods of inspection, doctors define Since 2008 HCV exacerbation with increase of virus loading existence of markers of viral hepatitises B and C, including to 100 million ME/ml is noted, the genotype A HBV, in EIA HBsAg in blood serum by the immunofermental analysis. At – HBsAg positiva is defined., HBeAg positive, treatment of detection of a superficial anti-gene of hepatitis B, establishment entecavir 0,5 mg is begun, from 12th week in PCR DNA-HBV in PCR not only existence of DNA of HBV, but also definition of it wasn’t found, antiviral therapy was completed in 2,5 years, its quantity, in EIA – HB-antigen has to be obligatory carrying the steady virologic answer was observed.

593 Sleptsova S.S., et al.

Fig. 3. Algorithm of maintaining pregnant women with HBsAg.

In 2014 the patient became pregnant, pregnancy desired, of pregnancy treatment of anemia was carried out by iron against pregnancy in PCR DNA-HBV in number of 21 000 ME/ml, preparations. Considering existence of a viremiya of a HB virus, biochemical analyses in norm, the general blood test without from 32 weeks antiviral therapy telbivudine in a dose of 600 deviations, according to F-1-0 elastometry is found. In the first mg is recommended, by 38th week of pregnancy virus loading half pregnancy proceeded with toxicosis of easy severity to against specific therapy decreased to 5000 ME/ml. 12 weeks, anemia, pregnancy interruption threat concerning In the term of pregnancy of 39 weeks the woman came to with which hospitalization in gynecologic dapartment of the maternity department , the diagnosis at receipt – the period Yakut city clinical hospital was carried out. In the second half of childbirth in time, head prelying. the complicated obstetric

594 Clinical c a s e o f c o n d u c t i n g p r e g n a n c y a n d childbirth a t t h e w o m a n w i t h c h r o n i c v i r a l h e p a t i t i s b in t h e replicative f o r m anamnesis. Chronic viral hepatitis B without Delta agent in a is a tendency to decrease in indicators of incidence, however replication stage, with small virus loading (5000 ME/ml), F-1-0 in comparison with all-Russian indicators their excess by 2-3 complicating pregnancy, childbirth and the postnatal period. times is observed. Carriage of a cytomegalovirus infection. Diffuse goisture of For the purpose of prevention of perinatal infection with a the Ist degree. Euthyrodism. Angioneurosis on the mixed type. virus of hepatitis B introduction in algorithm of maintaining Vascular parpura in the anamnesis. pregnant women with HBV definition of virus loading of DNA- Conservative conducting childbirth in natural patrimonial HBV in PCR-research that will allow to develop a complex of ways is chosen as a council of physians. In childbirth prevention preventive actions with application of antiviral therapy by analogs of bleeding was carried out. 31.03 there was childbirth by the of nucleosides and the individualized scheme of vaccination live full-term fetus without asphyxia and visible uglinesses. The with use of specific immunoglobulin is necessary. The major assessment on a scale Apgar 8/8, weight is 3440 grams, growth – moment is observance of continuity in work of the following 52 cm. Blood on the immunofermental analysis is taken from the experts: infectiologist, obstetrician-gynecologist, neonatologist, child, HBsAg in blood wasn’t defined. During the first hours of life pediatrician, infectiologist-pediatrician. to the newborn were given at the same time specific hepatitis B Such questions as determination of risk factors of perinatal immunoglobulin (1 dose – 100 ME) and the first dose of a vaccine infection with a hepatitis B virus, ways of a giving birth of against hepatitis B, into different parts of a body. women with a HB infection, opportunity and expediency of The woman with the child in a satisfactory condition are breastfeeding of newborns demand further studying. written out home. Supervision and treatment at the infectiologist of mother and the child, with control of analyses on hepatitis B REFERENCES in EIA and PCR is recommended further, refusal of breastfeeding 1. Alexeeva M.N. Viral hepatitises in the Republic of Sakha (Yakutia): dissertation doctor is desirable. of med sciences: 14.00.10 / Alexeeva Marpha Nickolaevna // – SPb, 2002. – 285 p. Thus, considering “experience” of an illness of mother and 2. Sleptsova S.S. Viral hepatitises in the Republic of Sakha (Yakutia) and their role in existence of activity of the HB-infection, complex prevention development of primary cancer of liver. dissertation abstract doctor of med sciences: of infection is carried out: decrease in a viremia at mother and 14.01.09., 14.02.03. / Sleptsova Snezhana Spiridonovna // – SPb., 2013. – 44 p. passive and active prevention of hepatitis B at the newborn. 3. Rakhmanova, A.G. Chronic viral hepatitises and HBV infection / A.G. Rakhmanova, A.A. For the purpose of secondary prevention and detection of Yakovlev. // – SPb.: “VVM”, 2011. – 164 p. an illness at early asymptomatic stages inspection of the child at 4. Wong, S. Hepatitis В carrier and perinatal outcome in singleton pregnancy/S. Wong, the birth is recommended, in 3, 6, 9 and 12 months and further L.Y. Chan, V.Yu et al. // Am. J. Perinatol. – 1999. – №16. – P. 485-488. till 3 years two times a year. Inspection includes carrying out the 5. Wiseman, E. Perinatal transmission of hepatitis B virus: an Australian experience/ immunofermental analysis on hepatitis B markers, identification Wiseman E., Holden S. et. al. // Med J. Aust. – 2009, 4, 190 (9). – P. 489-492. of DNA-HBV in blood by PCR method, definition of biochemical 6. Yogeswaran, K. Chronic hepatitis B in pregnancy: unique challenges and opportunities indicators, carrying out ultrasonography of abdominal organs. / Yogeswaran K., Scott K. //Korean J. Hepatol. 2011 Mar; 17(1): 1-8. At statement of the diagnosis of viral hepatitis B children 7. Stevens, CE. Perinatal hepatitis B virus transmission in the United States: prevention by should be hospitalize in an infectious hospital where the issue passive–active immunization / Stevens CE, Troy PT, Tong MJ [et al.] // JAMA. – 1985.- of opportunity carrying out antiviral therapy and dispensary 253. – P. 1740–1745. supervision is resolved. 8. Poland, G.A. Evaluating existing recommendations for hepatitis A and B vaccination / Poland G.A., Jacobson R.M. // Am J Med 2005;118 Suppl. 10A:16S-20S. CONCLUSION 9. Abdurakhmanov, D. T. Chronical hepatitis delta: cliniko-morphological characteristic, The Republic of Sakha (Yakutia) is the unsuccessful territory current, outcomes / D. T. Abdurakhmanov, T.N. Lopatkina, P.E. Crelle, A.V. Odintsov // on incidence of chronic forms of viral hepatitis B. Thanks to the Russian journal of gastroenterologies, hepatology and coloproctology. – 2004. – No. carried-out work on immunization against a HBV infection, there 2. – P. 42-47.

ADDRESS FOR CORRESPONDENCE: Sleptsova S.S. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street Ph. 8-914-2718770 [email protected]

595 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

He a l t h st a t u s o f preg n a n t w o m e n

Filippova R.D., Stepanova N.R., Nikiforova V.N. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a p e r i n a t a l c e n t e r o f r e p u b l i c a n h o s p i t a l n o . 1, y a k u t s k

ABSTRACT The article covers the study into the structure of extragenital pathology in pregnant women based on the data obtained at the antenatal clinic of the perinatal center of the State Organization of the Ministry of Health of the Sakha Republic (Yakutia) National Center of Medicine – Republican Hospital No. 1 in 2013. The presence of extragenital pathology in pregnant women is a major factor in the high risk of maternal mortality. The majority of women (90%) have two or more extragenital pathologies simultaneously. In the structure of extragenital pathology in pregnant women the first most prevalent diseases are urinary system diseases, 2nd most prevalent – diseases of the cardiovascular system, 3rd most prevalent – diseases of the hematopoietic system. Diseases of the circulatory system are the leading indications for termination of pregnancy. It is necessary to increase the efficiency of cooperation between gynecologists, internists and specialists to identify women at high risk of perinatal pathology, to form prognosis in terms of carrying of pregnancy and timely decision on its prolongation and perinatal care.

Key words: pregnancy, extragenital pathology, pathology of internal organs.

Wiad Lek 2015, 68 (4), 596-597

INTRODUCTION RESULTS AND DISCUSSION One of the important components of modern obstetrics aimed In total, 1150 pregnant women were examined in 2013, at reducing maternal and perinatal mortality is to identify pregnant of which 931 were from rural areas (81%). The patients were women at high risk of perinatal pathology. One of the major divided into the following age groups: women from 21 to 30 high-risk factors is the presence of extragenital pathology. years of age (58.3%) are the ones who visit the antenatal clinic According to some epidemiological studies from 50 to 82% of with extragenital pathology of pregnancy most often, the second pregnant women have chronic diseases of internal organs, 60% most frequent group – women of 31 to 40 years (29.4%), the during pregnancy (at the height of the capacity of adaptation third most frequent group – women of senior reproductive age mechanisms) suffer acute diseases of internal organs. (over 41 years old – 3.1%). The development of high-tech medical care has contributed During 2013, 18 young primigravidas under 18 years of age to the formation of groups of women with severe pathology of were examined (2012 – 16 women). internal organs. Over the period of two consecutive years (2012 – 2013) cases The introduction of state support for families under the of extragenital pathology in pregnant women have increased “Mother’s capital” program increased the age criterion of pregnant by 15.2%. The majority of women (90%) have two or more women [1-6]. Research objective – to study the structure of extragenital pathologies simultaneously. extragenital pathology in pregnant women. Most frequently extragenital pathology in pregnant women in 2012-2013 is represented by urinary system diseases which MATERIALS AND METHODS account for 18.6%, with 753 pregnant women suffering from The research into the structure of extragenital pathology chronic and gestational pyelonephritis. Of all the diseases of in pregnant women was carried out on the basis of the data the urinary tract, 1.3% are cases of glomerulonephritis [3, 4, 6], obtained at the antenatal clinic of the perinatal center of the State which gravely worsens the prognosis of pregnancy. During the Organization of the Ministry of Health of the Sakha Republic reporting year, there were 2 cases of chronic renal insufficiency in (Yakutia) National Center of Medicine – Republican Hospital pregnant women, which is the absolute indication for termination No. 1 in 2013. of pregnancy [3, 4, 6]. Pregnant women are examined by a physician during their The second most frequent extragenital pathology is diseases first visit to the antenatal clinic to identify and assess extragenital of the cardiovascular system – 16.1%, the largest percentage of pathology, and to decide on the possible prolongation of pregnancy which falls on the vegetative-vascular dystonia – 47.7%. The use and perinatal care tactics. of echocardiography in the examination of pregnant women

596 He a l t h s t a t u s o f p r e g n a n t w o m e n helps to identify small-scale anomalies of the heart up to 22.5%, to the age of the pregnant woman; 90% of pregnant women have and congenital heart disease – 3.8%. 2 or more extragenital pathologies simultaneously; Hypertensive disease aggravates pregnancy in women and - In the structure of extragenital pathology in pregnant women accounts for 9.3% of all heart disease cases [2, 4, 5, 6]. In 2013 the first most prevalent diseases are urinary system diseases, there was an increase in pregnant women with hypertension 2nd most prevalent – diseases of the cardiovascular system, 3rd stage 3 from 1.2% (2011) to 3.5%. most prevalent – diseases of the hematopoietic system. During the year, 29 women were examined who had undergone - Pregnancy in women of late reproductive age is 3.1%, which heart operation for congenital heart defects. Congenital heart is the result of the implementation of the National project and defects increase the percentage of cardiovascular complications and the use of maternity capital, as well as other social benefits to are ranked among the most frequent indications for termination improve the material situation and living conditions; of pregnancy for medical reasons [4, 5, 6]. - Decompensated diseases of the cardiovascular system are Blood diseases are the third most frequent pathology (12.9%). the leading indications for early pregnancy termination (in Of all blood diseases 97% cases are accounted for by anemia of 2013 – 10 women were offered termination of pregnancy for pregnancy. In 2013, 6 pregnant women were diagnosed with medical reasons); severe anemia. - The medical and social aspects of teenage pregnancy Every year there are isolated cases of pregnancy in women with prevention still pose a problem: ignorance about the physiology hemostasic disorders: in 2013 – pregnancy with thrombophilia due of the human reproductive system, negative attitude toward to deficiency of antithrombin III, state after occlusive thrombosis family and childbirth, accidental pregnancy; of the right axillary vein of August 02, 2012, at Rh negative blood, - More work needs to be done about family planning offices; to which is the absolute indication for termination of pregnancy improve the efficiency of joint therapeutic and obstetric-gynecologic for medical reasons [4, 6]. But due to the woman’s categorical examination of women with extragenital pathology and the refusal to terminate her pregnancy, she is under strict dynamic formation of high-risk groups of women of childbearing age; supervision by obstetrician-gynecologists and hematologists. the prognosis in terms of gestation pregnancy and timely decision Endocrine system diseases account for 11,5% of the cases. In on its prolongation of reference and perinatal care tactics. 2013, the largest number of women with diabetes were registered – 22 (in 2012 – 16 pregnant women); detection rate of gestational REFERENCES diabetes remains at the same level each year – 4 cases (in 2012 – 1. Evsyukova, I. I. Diabetes: pregnant women and newborns / I. I. Evsyukova, N. G. Kosheleva. 3 cases). There is also a marked growth in the number of obese – M .: Miklosh, 2009. – 272 p. women (in 2012 – 47, in 2013 – 94 women). 2. okorokov, A. N. Diagnosis of diseases of the internal organs in 9 volumes / A. N. Okorokov. There is a high percentage of digestive system diseases (12.7%); – M .: Med. lit., 2004. chronic viral hepatitis accounts for 10.4% of all diseases of the 3. ordzhonikidze, N. V. Pregnancy and childbirth in diseases of the urinary organs, edited digestive system in pregnant women. by Academician G. T. Sukhikh / N. V. Ordzhonikidze, A. I. Emelyanova, V. O. Panov, M. I. The share of respiratory diseases is 12.4%. In the reporting Kesova, S. Y. Potapova. – M., 2009. – 432 p. year, there was an increase in the level of ARI: from 14.5% to 4. Sokolova M. Y. Extragenital pathology in pregnant women / M. Y. Sokolova. // – M .: 18.4% of all respiratory diseases in pregnant women. Miklosh, 2010. – 200 p. 5. Stryuk, R. I. Diseases of the cardiovascular system and pregnancy / R. I. Stryuk. M .: CONCLUSIONS GEOTAR Media, 2010. – 280 p. - Every year more and more cases of extragenital pathology have 6. Shekhtman, M. M. Guide for extragenital pathology in pregnant women / M. M. been detected in pregnant women, which is directly proportional Shekhtman.- M .: “Triada – X”, 2008. – 816 p.

ADDRESS FOR CORRESPONDENCE: Filippova R.D. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street Ph. 8-924-662-49-14 [email protected],

597 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Su rgic a l tre a t m e n t o f n ec k a n d retr o ster n a l g o iter , clinical c a se

Tobohov A., Nikolaev V. f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a

ABSTRACT Here is a clinical case of neck and retrosternal goiter. We describe the clinical course characteristics and diagnosis of cervical-retrosternal goiter, when intrathoracic goiter was not locatedby palpation.

Key words: retrosternal goiter, thyroscintigraphy, surgical treatment.

Wiad Lek 2015, 68 (4), 598-599

INTRODUCTION goiter is very difficult. It is usually detected incidentally underthe A goiter is referred to as the retrosternal one, much of which chest radiography and diagnosed as a tumor. X-rays and falls below the jugular notch of the sternum. The degree of ptosis computer and magnetic resonance imaging, contrast studies can be different, but the upper pole of the crop is generally available of the esophagus andthyroscintigraphy are of great importancein to palpation. The retrosternal goiter is the result ofthyroptosis, the diagnosis. the gradual lowering of the thyroid gland in the chest[1]. The main source of retrosternal goiter is low thyroid gland MATERIALS AND METHODS location. Nodesemerging in the lower pole of this gland may Patient M. born in 1944, villager,visited the endocrinologist gradually sink behind the breastbone and collarboneduring clinical advisory department at the Republic’s Hospital N1 –the the growth. The resistance of the powerful anterior muscles National Center for Medicine ofthe Republic of Sakha (Yakutia) of the neck (especially in people with a short neck) inhibits Health Ministry with complaints of feeling short of breath on the anteversion of the crop, and the ganglion movement when exertion, and change in body position, discomfort sense in the swallowing and its own weight contribute to the growth toward neck and sweating. The anamnesis said that she was suffering the least resistance, towards the mediastinalwith extremely pliable multinodular goiter for 5 years, the last year the thyroid body tissues [2]. increased. Two years ago,she was diagnosed themultinodular Retrosternal goiter does not come under the rare diseases. goiter with subclinical hyperthyroidism atan endocrinology Frequency of chest goiters among goiters with usual localization clinic. She took thyrozolby a scheme, since then, she had not varies widely – from 0.2% to 50%, forming 3-6% on average. requested medical assistance. The patient was not hereditary This diversity of statistics is above all explained by the lack tainted for the thyroid disease. of a “retrosternal goiter” clear definition, because there is no The patient got the thyroscintigraphyat the clinical advisory unanimous opinion, what degree of lowering the thyroid gland department. Thyroscintigrams showed enlargement of the thyroid should be referred to the retrosternal localization [3]. gland more on the right. The size of the right lobe made up 7.3 x According to B. Petrovsky, approximately 12-20% of all 4.9 cm, the left lobe came to 4.1 x 2.2 cm. Location of the thyroid goiters in varying degrees fall behind the breastbone. gland was at the normal level. Contours of both lobes were rough According to our data, 12.4% of patients surgically operated and fuzzy. The both lobeshad areas with increased accumulation for thyroid cancer have the neck and retrosternal goiter, with of the radiopharmaceutical by type of the “warm” sites. the 1:11.5male to female ratio (8% and 92% respectively). The Patient was routinely hospitalized to the 2ndsurgical department neck goiter is prevalent at the age of 50, while more than a half of the Republic’s Hospital Clinical Center N1. Under the study of patients with the neck and retrosternal goiter were older than at the clinical advisory department and hospital admission 50 years, which coincides with the majority of domestic and atthe surgical department N2,the enlarged thyroid gland foreign publications. The neck and retrosternal goiter is most was estimated as of the 2 degree one by O.Nikolaev. In a few common in women of brachymorphic build over 50 years, with days after admission, the patient had subtotal resection of the a relatively short neck and a wide upper thoracic aperture, living thyroid gland performed under endotracheal anesthesia.The in regions of Yakutiabeing goiter endemic. transcript of the operation was as follows: the patient M.got The clinical presentation depends on the crop size and its the typical Kocher incision on the neck withthe neck rectus relation to the surrounding organs. Diagnosis of the intrathoracic musclespartedand the thyroid gland separated.The checkup

598 Su r g i c a l t r e a t m e n t o f n e c k a n d retrosternal g o i t e r, clinical c a s e

and squeezed to the left, the right lobe extendedretrotracheally. The lower pole passedto retrosternal space (Fig. 1). Both lobes snugged against the trachea. The left lobe with dimensions of 4.0 x 3.5 x 1.0 cm contained calcification of 0.7 cm. Rapid biopsy was carried out during the operation. Cytology detected the colloidal goiterin the left lobe and mixed adenomas on the background of cystic-colloid goiter in the right lobe. The urgent histological test of the left lobe revealed the macrofollicularcolloid goiter with focal cystic fibrosis, the right lobe had macrofollicularcolloid goiter with focal adenomatosis, fibrosis with marked lymphoid infiltration. The final morphological diagnosis stated: macrofollicularcolloid goiter with cystic degeneration, focal fibrosis.

RESULTS The presented case is interesting because during the preoperative neck examination, the palpation determined not only the upper pole of the right lobe, but also the “lower” pole of the right lobe above the jugular notch, as a narrow portion of thyroid gland tissue connected itsretrosternal part with its cervicalone. This area was so narrow that only the operating surgeon’slong-term experience allowed not leavingthe part of the right lobe off the Fig. 1. Macropreparations right lobe of the thyroid gland isthmus and retrosternal part. sternum. Under the thyroscintigraphy,the retrosternal site did not accumulate radioactive iodine due to pronounced degenerative changes that did not give a full picture of the crop size. Therefore, the radiological diagnostic methods have the special value, allowing objectively evaluate the degree of magnification and location of the thyroid gland, as well as the degree of narrowing showed that the right lobe sharply increased to 8.0 x 4.0 x 3.0 of the trachea lumen. cm, and included the tumor formation by diameter of 4.5 cm in a whitish capsule of adenomatous and colloid nature; having REFERENCES isthmus sizing 4.0 x 4.5 x 1.5 cm. In the deeper part of the cut 1. BreidoI.S. // Surgical treatment of thyroid diseases. — SPb., 1998.336 p. there was the whitish portion measuring 1.5 x 0.7 cm.Because 2. ValdinaE.A.// Thyroid Disease Guide. 3rd ed. —SPb.: Peter, 2006.368 p. of the right lobe’sformation volume,the trachea was compressed 3. Romanchishen A.F. // Thyroid and parathyroid surgery. “Vesti” St.Petersburg, 2009.648 p.

ADDRESS FOR CORRESPONDENCE: Nikolaev V.N. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street [email protected]

599 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Descripti o n o f g a str o es o p h a ge a l re f l u x d ise a se in d i f f ere n t et h n ic gr o u ps , living in t h e n o rt h

Chibyeva L.G.1, Balanova O.P.2, Vasilev N.N.2 1f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a 2y a k u t s k c i t y clinical h o s p i t a l ,y a k u t s k , r u s s i a

ABSTRACT Introductiod: over the past 15 years, the relative frequency of detection of erosive form of GERD has increased from 3,1 to 16%. Manifestations of GERD in different ethnic populations of Yakutia are not well understood. Aim: studying kliniko-endoscopic and the morfofunktsionalnykh of features of GERD in various ethnic groups living in conditions of Yakutia. Materials and methods: the study included 168 patients with GERD of different ethnic origins. Yakuts, Evens and Evenks, were considered as indigenous people and newcomers were all persons of other nationalities, who arrived at different times from other regions of Russia. The average age was 41,75±24,73 years. Results: clinical manifestations of GERD in different ethnic groups living in Yakutia. Leukoplakia of the esophagus was detected in the indigenous population are four times more likely than newcomers. With GERD associated with thyroid disorders prevalent low level of contamination of Helicobacter pylori. Helicobacter pylori infection in patients with GERD in Yakutia was higher among immigrants than among the indigenous, with a high degree of contamination of Helicobacter pylori was detected more frequently in immigrants than among the indigenous. Pathological gastroesophageal reflux during the daily pH-metry of the esophagus was detected more frequently in patients visiting than among the indigenous. Conclusions: the found features of a current of GERD can be further the basis for the individualized and differentiated approaches to treatment of this disease.

Key words: gastroesophageal reflux disease, gastroesophageal reflux, Helicobacter pylori, thyroid dysfunction, newcomers, indigenous populations.

Wiad Lek 2015, 68 (4), 600-603

INTRODUCTION of departments of a gullet of the reflux nature even without Relevance of the research related to the frequency of temporary clinical manifestations [1, 4]. disability and the presence of serious complications – erosions, The study included 168 patients with GERD of different peptic ulcers, bleeding, strictures of Barrett’s esophagus, that is a ethnic origins. Yakuts, Evens and Evenks, were considered as precancerous condition, and adenocarcinoma of the esophagus indigenous people and newcomers were all persons of other [1]. Over the past 15 years, the relative frequency of detection nationalities, who arrived at different times from other regions of erosive form of GERD has increased from 3,1 to 16% [2]. of Russia. The average age was 41,75±24,73 years. Manifestations of GERD in different ethnic populations of There were 31 patients with concomitant diseases of the Yakutia are not well understood. thyroid gland, among them 18 people were with hypofunction The combination of GERD with thyroid disease, given that and 13 – with hyperfunction. The control group consisted of Yakutia is one of the areas with high levels of iodine deficiency 15 people. diseases, is interesting [3]. However, the abdominal symptoms Patients underwent the following investigations: of thyroid disease are the least understood.The study of clinical, fibrogastroduodenoscopy, X-ray examination of the esophagus endoscopic, morphological and functional characteristics of and stomach (if indicated), intraesophageal pH-metry, GERD in the various ethnic groups, living in Yakutia. histomorphological study of esophageal mucosa and identification of Helicobacter pylori in the biopsy using histomorphological MATERIALS AND METHODS method (51 patients), the definition of Helicobacter pylori using The study was conducted on materials of the gastroenterology rapid urease test (38 patients) and enzyme immunoassay (all department of Yakutsk City Hospital. patients). The diagnosis of GERD was made on the basis of characteristic The classification of the severity of endoscopic signs of GERD complaints of the patient – heartburn at least 2-3 times a was made according to Savary-Miller. The study was associated week, the eructation, nausea and other esophageal symptoms with mucosal biopsy of the lower third of the esophagus, to influencing quality of life of the patient, damage the distalnykh diagnose Helicobacter pylori – from the antrum. Antibodies to

600 De s c r i p t i o n o f g astroesopha g e a l re f l u x d i s e a s e in d i f f e r e n t e t h n i c g r o u p s , living in t h e n o r t h

Helicobacter pylori were determined using enzyme immunoassay Reducing the time a combination of GERD is associated diagnostic system “HelikoBest antibodies” (CJSC “Vector-Best”, with chronic gastritis, perhaps, so that long-term contamination Novosibirsk). of the mucous membrane of the stomach Helicobacter pylori To confirm the eradication of Helicobacter pylori rapid results in the development of atrophic process and reduce acid urease was used test with sets of URE-HP test Pliva-Lachema production in the stomach [5]. (Brno, Czech Republic). Daily monitoring of esophageal pH was In the study of concomitant disease of the gastrointestinal carried out by an autonomous acidogastrometr “Gastroskan-24” tract and other organs was revealed that the failure of the lower (“Istok-System”, Fryazino, Russia). esophageal sphincter was found 1.6 times more often among newcomers (39,4±5,8%), than among the indigenous (25,8±4, 4%) RESULTS AND DISCUSSION (p<0,05), and hiatal hernia – five times more often (15,5±4,3%), The study showed that patients with GERD mostly complained than among the indigenous (3,1±1,8%) (p<0,05). According of heartburn (81,3±4,4% of indigenous and 92,9±3,4% of visitors), to published sources, 20-33% of patients with a diaphragmatic epigastric pain (77,5±4,7 and 84,2±10,6%), eructation (50±5,6 hernia have GERD, and 25-50% of patients with GERD have a and 71,9±5,9%, respectively), while the newcomers had reflux concomitant hiatal hernia [6]. symptoms such as heartburn and regurgitation more often than Daily monitoring of esophageal pH showed abnormal the indigenous people (p<0,05) (tab. I). gastroesophageal reflux in third of the patients of the indigenous Nausea occurred in a quarter of patients (28,8±5,1% of population – the main indicators of pathological reflux, such as indigenous and 26,3±5,8% of visitors of patients). Dysphagia the total time with pH <4.0, were found in 38,1±4,9%, the number and odynophagia had only indigenous patients, and esophageal of reflux more than 5 minutes – in 38 , 1±4,9%, symptom index pain and the feeling of a lump behind the breastbone were was increased from 26,8±4,5% of patients (tab. II). recorded infrequently,as confirmed by other researchers. Such In the group of newcomers pathological gastroesophageal clinical Caucasians’ GERD results do not contradict the work reflux was observed in half of the patients – total time with of other authors [1]. pH<4.0 was found in 53,5±5,9%, the number of reflux more than Indigenous patients had GERD combined with chronic 5 minutes – at 45,1±5,9%, higher symptom index DeMeester – gastritis more often (77±4,3%), than newcomers (43,7±5,9%), from 46,5±5,9%, that is, the number and duration of pathological p<0,05. Newcomers had duodenal ulcer 2, 8 times more often gastroesophageal reflux in patients with GERD in different ethnic (43,7±5,9%), than the indigenous (16,7 ± 3,8%), p <0,05. Gastric groups had a significant and reliable distinction – pathological ulcer accompanied GERD in the indigenous people was half as reflux detected in newcomers to 1,5 times more frequently likely (6,3±2,5%), than newcomers (12,6±3,9%), p>0,05. and significantly more obvious than among the indigenous Almost half of the indigenous patients (47,1±5,1%) the population (p<0,05). duration of the combination of chronic gastritis with GERD In our study, a significant proportion of all patients with ranged from 1 to 3 years, and after three years, the number of GERD (without thyroid disease) had reflux esophagitis I patients decreased (15,5±3,7%). The number of newcomers, degree (58,7±5,5% of indigenous and 52,6±6,6% of visitors, who had GERD from 1 to 3 years in conjunction with chronic p>0,05). A third of patients had endoscopy-negative (0-I) level gastritis was 21,1±4,8%, and also decreased after 3 years to (30±5,1% of indigenous and 29,8±6,1% of newcomers, p>0,05). 11,3±3,8% – Significant differences were found between the groups More severe damage of the lower third of the esophagus (II in duration of GERD with a combination of chronic gastritis and III degree) were more common among immigrants – from 1 to 3 years (p<0,05). GERD to 1 year in combination 8,8±3,8 and 7±3,4% respectively (the indigenous to 5,0±2,4%). with duodenal ulcer was noted in 5,2±2,3% of indigenous and Barrett’s esophagus (IV degree) was detected in one patient in quarter of newcomers (26,8±5,3%) (p<0,05). in each group.

Table I. Clinical manifestations of GERD in patients without pathology of a thyroid gland Radical, n=80 Visitors, n=57 Symptom Р n (M±m%) n (M±m %) Heartburn 65 (81,3±4,4) 53 (92,9±3,4) <0,05 Feeling of bitterness in an oral cavity 5 (6,3±2,7) 9 (15,8±4,8) <0,05 Eructation 40 (50,0±5,6) 41 (71,9±5,9) <0,05 Dysphagia 2 (2,5±1,7) - - Odynophagia 7 (8,8±3,2) - - Epigastric pain 62 (77,5±4,7) 48 (84,2±10,6) >0,05 Esophageal pain (behind a breast) 11 (13,8±3,9) 4 (7,1±3,4) >0,05 Nausea 23 (28,8±5,1) 15 (26,3±5,8) >0,05 Vomiting 8 (10,0±3,4) 5 (8,8±3,8) >0,05 Feeling of a lump behind a breastbone 4 (5,0±2,4) 1 -

601 Chibyeva L.G., et al.

Table II. Identification of the pathological gastroesophageal refluxes during daily monitoring рН of a gullet in patients with GERD. It is carried out рН-metriya Indicator pathological Radical, Visitors, Everything, n=168 Р gastroesophageal reflux n =97 n=71 n (M±m%) n (M±m%) n (M±m%) General time рН<4,0, % 75 (44,6±3,8) 37 (38,1±4,9) 38 (53,5±5,9) <0,05 The same, vertically, % 59 (35,1±3,7) 23 (23,7±4,3) 36 (50,7±5,9) <0,05 The same, horizontally, % 60 (35,7±3,7) 28 (28,9±4,6) 32 (45,1±5,9) <0,05 Total number of refluxes 64 (38,1±3,8) 28 (28,9±4,6) 36 (50,7±5,9) <0,05 Number of refluxes&>5´ 69 (41,1±3,8) 37 (38,1±4,9) 32 (45,1±5,9) >0,05 The most long reflux, min 61 (36,3±3,7) 31 (31,9±4,7) 30 (42,3±5,8) >0,05 Index DeMeester 59 (35,1±3,7) 26 (26,8±4,5) 33 (46,5±5,9) <0,05

According to different authors, during the endoscopic and in patients with hyperthyroidism in both ethnic groups heartburn histological examination of the esophagus the normal esophageal (100%) and epigastric pain (76,9±11,7%) were found more often mucosa is found in more than 50% cases of patients with symptoms than in hypothyroidism (38,9±11,4 and 50±11,8%, respectively) of GERD [1, 7]. (p<0,05). Nausea (22,2±9,8%) and the feeling of lump in the chest When assessing morphological changes in the mucous (27,8±10,6%) were found only in hypothyroidism. Endoscopic membranes of the lower third of the esophagus in patients examination showed that the majority of patients in both ethnic with GERD in the study was found a high prevalence of groups had 0-th degree – from 71,4 to 100%. hypertrophic esophagitis various manifestations of dyskeratosis When assessing morphological changes in the mucous (the indigenous 52,6±11,5%, and the newcomers 53,3±12,9%), membranes of the lower third of the esophagus in GERD which corresponds to the main histologic features of pathological patients with thyroid disorders more often occurred prevalent gastroesophageal reflux. Leukoplakia of the esophagus was proliferation of the surface epithelium (50% and 100% of indigenous detected in the indigenous population four times more often immigrants with hypothyroidism, and 100 and 50%, respectively, (52,6±11,5%), than in newcomers (13,3±8,8%), p<0,05. Small for hyperthyroidism). Hypertrophic esophagitis occurred only bowel metaplasia stratified squamous epithelium was observed during hypothyroidism (in 33,3% of native). in one patient in each group. The prevalence of Helicobacter pylori by histomorphological The prevalence of Helicobacter pylori in the gastric method with GERD in conjunction with hyperthyroidism was antrum of patients from indigenous groups with GERD using more likely (71,4%) than with hypothyroidism (50%), and a high histomorphological method was lower (73,7±10,1%), than visitors degree of contamination of Helicobacter pylori is not detected. (86,7±8,8%). The degree of colonization of Helicobacter pylori Helicobacter pylori infection of the indigenous groups of patients antrum high (+++) from newcomers (40±12,6%) exceeded that was lower in both cases. of the native (10,6±7,1%) four times (p<0.05). In the control Recent studies show that digestive disorders in hypothyroidism group, Helicobacter pylori was detected by histomorphological can dominate or preceded by an explicit manifestation of method in 36,4±4,5%. hypothyroidism. By the rapid urease test Helicobacter pylori was detected in For the treatment of GERD in our study used antisecretory patients with GERD 71,4±9,9% in indigenous and 88,2±7,8% drugs – the first week, all patients in both groups received as in newcomer groups. monotherapy only proton pump inhibitors. Detection of Helicobacter pylori by enzyme immunoassay During treatment with omeprazole and rabeprazole in the in patients with GERD showed a positive result in 91,1±2,2% two groups there was a significant reduction in the severity and in both ethnic groups. In the control group, Helicobacter pylori the disappearance of heartburn, epigastric pain (p<0,05). detection by this method showed a positive result of varying Endoscopic control efficacy of omeprazole and rabeprazole severity in half of the patients (53,3%). found that scarring of erosive and ulcerative lesions of the esophagus At 0-degrees and I GERD Helicobacter pylori is revealed occurred in the period from 1 to 4 weeks. using histomorphological and urease methods in more than Daily intraesophageal pH-meter before starting treatment half of the cases (55 and 60% respectively), with II degree of with proton pump inhibitors, and on the 7th – 10th day after reflux oesophagitis – in 80%, III and IV – half of the patients treatment showed a reduction in all parameters pH-meters. (50%). Because of the decrease acid contact time with the mucosa Our study examined the possible relationship of GERD of the esophagus symptoms rapidly decrease in intensity and symptoms and diseases of the thyroid gland. The clinical picture disappear in most cases within the first week [2, 7].

602 De s c r i p t i o n o f g astroesopha g e a l re f l u x d i s e a s e in d i f f e r e n t e t h n i c g r o u p s , living in t h e n o r t h

CONCLUSION during the daily pH-metryof the esophagus was detected more Clinical manifestations of GERD in different ethnic groups frequently in patients visiting (from 42,3 to 53,5%) than among living in Yakutia, had the following characteristics: the newcomers the indigenous (from 23,7 to 38,1%), p<0,05. reflux symptoms such as heartburn (92,9%) and regurgitation (71,9%) occurred more frequently than in the indigenous (81,3 and REFERENCES 50,0%, respectively), p<0,05. In patients with GERD, regardless of 1. Zimmermann Y.S. Clinical Gastroenterology / Moscow. – 2012. – P.22-51. the ethnicity of the morphological study of the lower third of the 2. Assimakopoulos S.F. Changes in the prevalence of upper gastrointestinal tract diseases esophagus was observed prevalence of hypertrophic esophagitis in patients referred for endoskopy during the last fifteen years/ Assimakopoulos S.F., (53%). In 60% of patients and 54,4% of the indigenous newcomers Thonopoulos K.C., Louvros E., Theocharis G. // Gut. – 2007. – Vol. 56.№ 3. – P. 202. I revealed the extent of reflux esophagitis. Leukoplakia of the 3. Zefirova G.S. // Thyroid disease. – M.: 1999. – 215 p. esophagus was detected in the indigenous population (52,6%) 4. Hunt R.H. Whistler consensuns/ Hunt R.H., Tytgat G., Malfertheiner P. [et. al]// J. Clin. are four times more likely than newcomers (13.3%), p<0,05. Gastroenterol. – 2007. – Vol. 41, № 2. – P. 72-77. With GERD associated with thyroid disorders prevalent low 5. o’Morain C. Indications for Helicobacter pylori eradication revisited / O’Morain C. level of contamination of Helicobacter pylori. Helicobacter // Maastricht-3 Guidelines for Helicobacter pylori infection – 13 United European pylori infection in patients with GERD in Yakutia was higher Gastroenterology Week. – Copenhagen, 2005. among immigrants (86,7%) than among the indigenous (73,7%), 6. Sheptulin A.A. Gastroesophageal reflux disease: the controversial and unresolved issues with a high degree of contamination of Helicobacter pylori was (memory A.L.Grebneva) / Sheptulin A.A. // Clin. honey. – 2008. № 6. – P. 8-12. detected more frequently in immigrants (40%) than among the 7. Tytgat G.N.J. Gastroesophageal reflux disease: reflection ANO. 2006/ Tytgat G.N.J. // J. indigenous (10,6%), p<0,05. Pathological gastroesophageal reflux Clin. Gastoenterol. – 2007. – Vol. 41, № 2. – P. 222-225.

ADDRESS FOR CORRESPONDENCE: Chibyeva L.G. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street Ph. 8-924-173-44-45 [email protected]

Within scientifically research work of Public Educational Institution of Higher Professional Training Severo-Vostochny federal university to them M. K. Ammosova “Physiological and medical aspects of health protection of various age groups of the population of the Republic of Sakha (Yakutia)”.

603 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Co n tri b u ti o n o f cere b r a l v a sc u l a r a n o m a l ies in h e m o rr h a gic str o k e str u ct u re in d i f f ere n t r a ci a l gr o u ps o f y a k u ti a

Chugunova S.A.1, 2, Nikolaeva T.Y.1, Semenov A.1 1f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a 2 y a k u t scientific c e n t r e o f c o m p l e x m e d i c a l p r o b l e m s , siberian b r a n c h o f t h e r u s s i a n a c a d e m y o f m e d i c a l s c i e n c e , y a k u t s k , r u s s i a

ABSTRACT Introduction: hemorrhagic stroke (HS) has higher incidence in Asian population compared to Caucasian. The reason for this phenomenon is not clearly understood. Aim: to investigate the contribution of cerebral vascular anomalies in hemorrhagic stroke structurein different racial groups of Yakutia. Materials and methods: the study group included 1078 consecutively hospitalized patients with acute HS. A comparative analysis of demographic data and frequency of CVA, which were identified as a cause of HS, was carried out between the group of indigenous patients of Asian race and the group of Caucasian patients. Results: the proportion of hemorrhage due to rupture of cerebralarterial aneurysms (CAA) in the hospital HS structure was higher in Asians, compared to Caucasians(p=0.001; OR=1.7; 95% CI: 1.2-2.4). No difference in the arteriovenous malformations’ (AVM) frequency was found between groups (p=0.345), as well as in age and gender distribution (p=0.052 and p=0.759, respectively). The CAA frequency was higher amongfemalepatients compared to male in both racial groups (p<0.0001; OR=1.71; CI 95% 1.3-2.3). Conclusions: in Yakutia, the proportion of hemorrhage due to rupture of cerebral arterial aneurysmsin hemorrhagic stroke structure is higher among indigenous ethnic group of Asian race, compared toCaucasians. No difference in thearteriovenous malformations’frequency was found between racial groups, as well as in age and gender distribution. The cerebral aneurisms’frequency was higher among female patients compared to male in both racial groups.Further studies of cerebral vascular anomalies and stroke risk factors using a population-based data in different racial groups are needed.

Key words: hemorrhagic stroke, cerebral vascular anomalies, cerebral aneurysms

Wiad Lek 2015, 68 (4), 604-607

INTRODUCTION Yakutsk,in 2011-2014. All Yakutsk city citizens with suspected Hemorrhagic stroke (HS) is a significant medical and social acute cerebrovascular disease are admitted to RVC. This also problem due to the high levels of mortality and disability [1, 2, applies to stroke patientsfrom other parts ofYakutia who need 3]. The most common cause of HS is hypertension [1]. Cerebral in high-techinterventions. Inclusion criteria in study group: vascular anomalies (CVAs), including cerebral arterial aneurysms hemorrhagic stroke (nontraumatic intracranial hemorrhage, (CAAs) and arteriovenous malformations (AVMs) are the including intracerebral hematoma, subarachnoid hemorrhage, second common cause of cerebral hemorrhage [1]. Several intraventricular hemorrhage, and combinations thereof (codes studies revealed the differences in the incidence of spontaneous I60 to I61.9, International Statistical Classification of Diseases subarachnoid hemorrhage (sSAH) due to CAA, depending on and Related Health Problems, 10th revision (ICD-10)). Exclusion gender [4, 5] and ethnicity [4, 6, 7, 8, 9]. In the previous study, criteria: ischemic stroke with hemorrhagic transformation; we found that there are ethnic features in stroke in Yakutia. hemorrhage in cerebral tumor; traumatic intracranial hemorrhage; HS is higher among the indigenous population of the Asian unruptured vascular anomalies. race compared to the Caucasians[10]. To clarify the causes of Study group included 1,078 patients. The diagnosis of HS this phenomenon, we conducted a study of cerebral vascular was established by experienced neurologist using neurological anomalies (CVA) in HS structure in different racial groups in examination, neuroimaging (computed tomography (CT)) and/ Yakutia. Aim of the study. To investigate the contribution of or magnetic resonance imaging (MRI) (1.5T) (n=1078; 100%). cerebral vascular anomalies in hemorrhagic stroke structure in Neuroimaging data was studied and described by a radiologist different racial groups of Yakutia. (n=1078; 100%). All patients were consulted by neurosurgeon. If CVA rupture was suspected, a subtraction cerebral angiography MATERIALS AND METHODS (SCAG) was performed (n=385, 35.7%). SCAG was repeated in We conducted the retrospective study of patients with acute period of 3 to14 days if the initial study was negative. Selected HS, consecutively hospitalized in Regional Vascular Centre (RVC), patients were consulted by endovascular surgeon (n=293; 27.2%).

604 Contribution o f c e r e b r a l v a s c u l a r a n o m a l i e s in h e m o r r h a g i c s t r o k e s t r u c t u r e in d i f f e r e n t r a c i a l g r o u p s o f y a k u t i a

All patients were also seen by cardiologist and underwent cardiac analysis of the characteristicswas held between the two largest ultrasound and electrocardiogram, Doppler and duplex ultrasound groups (first and second group) (n=1043). scan of brain vessels. According to the results of clinical examination, 743 cases Patients were included in the study as “indigenous ethnic of intracerebral hemorrhage (ICH) (68.9% of total HS), 204 group of Asian race” if their ethnicity was listed as Sakha, Even, cases of subarachnoid hemorrhagic (SAH) (18.9%), 129 cases Evenki, Chukchi, Yukagir, Dolgan (the first group); as “Caucasian” of subarachnoid-parenchymal hemorrhage(11.9 %), 2 isolated if their ethnicity was listed as Russian, Ukrainian, Belarusian, intraventricular hemorrhage (IVH) cases (0.2%) were identified. Polish (second group). Patients of other ethnic groups, including Hypertension was diagnosed in 966 patients (89.6%), coagulopathy not indigenous Asians, such as Buryats, Koreans, Chinese, etc., due to the liver disease – 16 (1.5%), coagulopathy due to antiplatelet were included in the study as “other ethnicity” (third group). therapy – 15 (1.4%), coagulopathy due to the blood diseases – 2 Statistical analysis was performed using STATISTICA 6 (0.2%), septicemia – 2 (0.2%). Clinical examination revealed 293 software. The critical level of significance was assumed to be CVAs, which were identified as a cause of acute hemorrhage, 0.05. In case, when the significance level exceeded this value, accounting for 27.2% of the HS cases. Among CVAs,there are 270 null hypothesis was accepted.Kolmogorov-Smirnov test was used cerebral arterial aneurysms (CAA)(25% of HS cases), 21 AVM to validate the normality of quantitative data. For comparison cases (1.9%), 2 cases of cavernous angioma (CA) (0.2%). of the central group settings without normal distribution, non- HS cause’s frequencies in the studied groups, depending on parametric Mann-Whitney U-testwas used. For quantitative data the race and gender, are presented in Table 1. In the first group with normal distribution Student’s t-test for unpaired samples (n=738) there were 223CVA cases (30.2% of the HS indigenous was used. For all quantitative data in two groups we calculated patients). In the second group (n=305) CVAswereidentified in average and standard deviation. These descriptive statistics are 64 cases (20.9%of the HS Caucasians). There was a significant presented as “M±σ”. Study of the interrelationship between the difference in CVA frequencies between first and second groups pairs of discrete qualitative characteristics was performed using (p=0.002; OR=1.63; 95% CI: 1.2-2.3). Also, there was a significant paired analysis of conjugation tables. In addition to the Fisher’s difference in CAA frequency between first and second group exact test and the achieved level of statistical significance we (28.2% (n=208) vs.18.4% (n=56), respectively) (p=0.001; OR=1.7; assessed strength of associations in the values of the relative 95% CI: (1.2-2.4)). No difference in the AVMfrequency between risk (OR) with 95% confidence intervals (CI). studied groups were found (p=0.345) (Table 1). CAAs in both groups (n = 264) were diagnosed more RESULTS frequently in femalepatients (n=158, 26%) compared to male Our study included 1,078 patients. The distribution by ethnicity (n=106, 11.6%) (p<0.0001; OR=1.71; CI 95% 1.3-2.3). 85 men was as follows: first group –738 (68.5%), the second group –305 (40.9%) and 123 women (59.1%)from the first group (n=208), (28.3%), third group– 35 (3.2%). Subsequently, a comparative and 21 men (37.5%) and 35 women (62.5%) from second group

Table I. Causes of hemorrhagic stroke depending on race and gender 1st group 2nd group p-value 3rd group Causes of HS/gender Total (n, %) (n, %) OR (95% CI)* (n, %) 1. General group, n (%) 738 (100) 305 (100) 35 (100) 1078 (100) - male, n (%) 374 (50.7) 149 (48.9) 0.634 23 (65.7) 546 (50.6) 0.002 2. CVA, n (%) 223 (30.2) 64 (21) 6 (17.1) 293 (27.2) 1.63 (1.2-2.3) - male, n 94 27 1.00 4 125 0.001 2.1 CAA, n (%) 208 (28.2) 56 (18.4) 6 (17.1) 270 (25) 1.7 (1.2 – 2.4) - male, n 85 21 0.759 4 110 2.2 AVM, n (%) 13 (1.8) 8 (2.6) 0.345 - 21 (1.9) - male, n 9 6 1.00 - 15 2.3 CA, n (%) 2 (0.3) - - - 2 (0.2) - male, n - - - - - 0.002 3 HS without CVA, n (%) 515 (69.8) 241(79) 29 (82.9) 785 (72.8) 0.61(0.4-0.8) - male, n 280 122 0.349 19 (65.5) 421(53.6) p – Fisher’s exact test HS – hemorrhagic stroke, CVA –cerebral vascular anomalies, CAA – cerebral arterial aneurysm, AVM – arteriovenous malformation, CA –cavernous angioma

605 Chugunova S.A., et al.

(n=56) were revealed to have CAA. No difference was established SAH, are probably caused by genetic factors, which induce the when the gender frequency was compared between the studied difference in the wall’s structure of the cerebral arteries. groups (p=0.759). We did not establish any significant difference in age between Other CVAs have made a small proportion of the HS causes the two racial groups. The mean age of patients of both groups (2.1%). There were 13 AVM cases in the first group (1.6%) and didn’t have any significant differences, including patients with 8 AVM cases in the second group (2.6%) (p=0.345). 2 patients HS due to rupture of CVA, and for patients with HS without from first group had CA (0.3%) (Table 1). ruptured CVA. In both groups, frequency of HS due to rupture The mean age of general groupwas 56.2±13.1 years. This figure of CAA is more common in women (p<0.0001; OR=1.71; CI was lower among male patients compared to female (54.04 ± 95% 1.3-2.3). These findings are consistent with other studies, 12.6 vs. 58.4 ± 13.2, respectively) (p<0.0000001, t-test). The mean which found the prevalence of aneurysmal SAH in women age of patients of first group was lower compared to the second compared to men [4, 5].According to our study, HS develops group, but the difference did not reach statistical significance in men at a younger age than in women. This is true for the HS (55.7±13.1 vs. 57.5±13.1, respectively) (p=0.052, t-test). There due to rupture of CVA, including CAA, in indigenous patients, were no significant differences between first and second groups but not for Caucasians patients. when compared the CVA patients’ mean age (p=0.967, Mann- The results of this study characterize the features of the Whitney U-test), as well as CAA patients’mean age (p=0.549, development of severe acute cerebrovascular disease in different U-test Mann-Whitney) and HS patients’ without CVA (p=0.055, racial groups living in identical climatic and social conditions. U-test Mann-Whitney). The advantage of this study is that the diagnosis of all stroke In the first group, the mean age of men was lower compared to cases was confirmed by neuroimaging data. Furthermore, the women, either among patients with CVA (47.2±12.4 vs. 52.1±12.1, number of patients included in our study was relatively large respectively) (p=0.01, U-test Mann-Whitney), patients with (n=1,078). A limitation of our study is that it was conducted CAA (47.4±12.4 vs. 52.7±11.5, respectively) (p=0.007, U-test using data from hospital data. To determine the contribution of Mann-Whitney), or HS patients without CVA (56.2 ± 12.1 vs. modifiable and non-modifiable factors in the development of 60.2 ± 13.1, respectively) (p=0.002, U-test Mann-Whitney). hemorrhagic stroke in different racial groups, further study must Similarly, in the second group, the mean age of men was lower be conducted using data from territorial population registers. compared to women amongHS patients without CVA (55.6±11.9 vs. 63.2±11.2, respectively) (p<0.00001, U-test Mann-Whitney). CONCLUSION But there were no significant differences in age by gender among In Yakutia, the proportion of hemorrhage due to rupture of CVA patients in second group, including CAA patients (p=0.09 cerebral arterial aneurysms in hemorrhagic stroke structure is and p=0.232, respectively, U-test Mann-Whitney). higher among indigenous ethnic group of Asian race, compared to Caucasians. No difference in the arteriovenous malformations’ DISCUSSION frequency was found between racial groups, as well as in age Our study identified the features of CVA’s contribution to and in gender distribution. The cerebral aneurisms’frequency HS structure depending on the ethnicity. We found, that the was higher among female patients compared to male in both proportion of hemorrhage due to rupture of cerebral arterial racial groups.Further studies of cerebral vascular anomalies and aneurysms (CAAs) in the hospital HS structure was higher in stroke risk factors using a population-based data in different Asians, compared to Caucasians (p=0.001; OR=1.7; 95% CI: 1.2- racial groups are needed. 2.4). No difference in the AVM frequency was found between groups (p=0.345), as well as in age and gender distribution REFERENCES (p=0.052 and p=0.759, respectively). The CAA frequency was 1. SkvortsovaV.I. Gemorragicheskij insult [Hemorrhagicstroke]: Pract. Guide/ ed. higher among female patients compared to male in both racial V.I.Skvortsova,V.V.Krylov.// Moscow:”GEOTAR-Media”,2005 (in Russian) groups (p<0.0001; OR=1.71; CI 95% 1.3-2.3). 2. Nieuwkamp D.J. Changes in case fatality of aneurysmal subarachnoid haemorrhage Differences in the spontaneous SAH incidence, depending over time, according to age, sex, and region: a meta-analysis / Nieuwkamp D.J., Setz on ethnicity and race, are described in several studies [4, 6, L.E., Algra A. [et al.]// Lancet Neurol. – 2009. – №8. – P.635-642. 7, 8, 9]. In general, Asian race have higher incidence of HS 3. ConnollyE.S. Guidelines for the management of aneurysmal subarachnoid hemorrhage: compared to Caucasian race [11]. In Yakutia, the proportion of a guideline for healthcare professionals from the American Heart Association/American HS in stroke structure is higher compared to average incidence Stroke Association / E.S. Connolly, A.A. Rabinstein, J.R. Carhuapoma [et al.] // Stroke. rate in Russia. Thus, the ratio of ischemic stroke to HS is 2.2:1in – 2012. – V.43(6). – P.1711-1737. Yakutia[12]. We have previously found that the proportion 4. Rooij N. K.Incidence of subarachnoid haemorrhage: a systematic review with emphasis of HS among indigenous ethnic group is higher than among on region, age, gender and time trends Rooij N. K., Linn F. H. [et al.]// J NeurolNeurosurg Caucasians in Yakutia[10]. The reasons for this phenomenon Psychiatry. – 2007. – V.78 (12). – P.1365–1372. doi: 10.1136/ jnnp.2007.117655. are currently unclear. PMCID: PMC2095631 The thinning of the structural elements of the vascular wall, 5. Ziemba-Davis M. Incidence, epidemiology, and treatment of aneurysmal subarachnoid such as the internal elastic membrane and extracellular matrix hemorrhage in 12 midwest communities / .Ziemba-Davis M., Bohnstedt B.N. [et [13], as well as collagen remodeling [14], are cause of the cerebral al.] // J Stroke Cerebrovasc Dis. – 2014. – V. 23(5). – P.1073-1082. doi: 10.1016/j. arterial aneurism. Recent studies point to the involvement of jstrokecerebrovasdis.2013.09.010. . certain genetic factors in the development of CAA [15]. Racial 6. Eden S.V. Gender and ethnic differences in subarachnoid hemorrhage/ Eden S.V.,M eurer differences in morbidity of HS, and in particular, spontaneous W.J., Sanchez B.N. [et al.]. // Neurology. – 2008. – V.71. – P.731-735.

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7. Kissela B. Stroke in a biracial population: the excess burden of stroke among blacks/ 11. Tsai С.-F Epidemiology of stroke and its subtypes in Chinese vs white populations. A Kissela B., Schneider A., Kleindorfer D. [et al.]. // Stroke. – 2004. – V. 35(2) – P.426- systematic review / Tsai С.-F., Thomas B., Sudlow C. // Neurology. – 2013. – V. 81(3). – P. 431. 264–272. doi: 10.1212/WNL.0b013e31829bfde3; PMCID: PMC3770160 8. Labovitz D.L. Subarachnoid hemorrhage incidence among Whites, Blacks and Caribbean 12. Nikolaeva T. Ya. // MD dissertation (Nervous Diseases). Russian State Medical University, Hispanics: the Northern Manhattan Study/ Labovitz D.L., Halim A.X., Brent B. [et al.]// Moscow, 2006 (in Russian) Neuroepidemiology. – 2006. – V.26. – P.147-150. 13. Alberts M. D. // Stroke (Russian Edition), 2004,№ 4,P. 5-7 (in Russian) 9. Broderick J.P. The risk of subarachnoid and intracerebral hemorrhages in blacks as 14. Etminan R. N. Age of collagen in intracranial saccular aneurysms / Etminan R. N., compared with whites / Broderick J.P., Brott T., Tomsick T. [et al.]. // N Engl J Med. – Dreier, B.A. Buchholz [et al.]// Stroke. – 2014. – 45(6). – P.1757-1763. doi: 10.1161/ 1992. – V.(11) 326. – P.733-736. STROKEAHA.114.005461. Epub 2014 Apr 29. 10. Chugunova S.A. The ethnic differences of stroke in Yakutia/ Chugunova S.A., Nikolaeva 15. Alg V.S. Genetic risk factors for intracranial aneurysms. A meta-analysis in more than T. Ya. // International Journal of Circumpolar Health. – 2013. – Vol. 72, supplement 116,000 individuals /Alg V.S., Sofat R., Houlden H., Werring D.J. // Neurology. – 2013. 1. – P. 321-324. – Jun 4; 80(23). – P.2154–2165. doi: 10.1212/WNL.0b013e318295d751 PMCID: PMC3716358]

ADDRESS FOR CORRESPONDENCE: ChugunovaS.A. Russia, Republic of Sakha (Yakutia), 677013, Yakutsk city, 27, Oyunsky street [email protected]

607 Wiadomości Lekarskie 2015, tom LXVIII, nr 4 © Aluna

Regi o n a l pec u l i a rities in se m e n q u a l it y a n d ser u m h o r m o n a l c o n ce n tr a ti o n s o f citi z e n s f r o m y a k u ti a

Troev I.P.1, Petrova P.G.1 Osadchuk A.V.2, Osadchuk L.V.2, Kleshchev M.A.2, Gutorova N.V.2 1f s a e i h p e «n o r t h e a s t f e d e r a l u n i v e r s i t y o f m.k. a m m o s o v », y a k u t s k , r u s s i a . 2i n s t i t u t e o f c y t o l o g y a n d g e n e t i c s , t h e siberian b r a n c h o f t h e r u s s i a n a c a d e m y o f s c i e n c e s , novosibirsk , r u s s i a

ABSTRACT The objective of the present study was to evaluate sperm quality and reproductive hormonal level in an unselected population of men who were permanent residents of the Yakutsk city and compare the semen and hormonal parameters with the World Health Organization (WHO, 2001) recommended normal values and the results from other countries. A total of 145 men (mean age 24 years) agreed to be included in the study. All the volunteers completed a questionnaire, received a general and reproductive health examination by an andrologist, gave semen and blood samples. There are no differences between Yakut and Slavs in anthropometric, hormonal or sperm measures, but height and ejaculate volume were higher in Slavs than Yakut men. The data obtained indicated high frequency of suboptimal quality of sperm in males of both nations from this Siberian region in comparison with other Russian regions or European countries.

Key words: semen quality, sperm concentration and motility, reproductive hormones, anthropometry, human

Wiad Lek 2015, 68 (4), 608-611

It is established that the specific morphological and functional and its adaptation to the environment and have a negative impact characteristics and features vital activity of the organism, on fertility and reproductive health. These facts highlight the including the physiological mechanisms at different levels of global problem of the study and saving of the male reproductive the organization, directly or indirectly determined by the usual potential of human communities, including – conducting large- conditions of the human environment, the natural environment scale studies of male fertility and its hormonal regulation in the and the overall environment. The ideal choice harmonization Russian Federation. It should be noted that the assessment of the of conditions and mechanisms of endogenous and exogenous real state of reproductive health of the male population and the factors of environment is to identify for each person of the forecast of its changes in the future is not only a scientific problem, region to live and work [1]. but it is essential for monitoring of reproductive health, as well This work is done under the multi-year project “Human as for the creation of new medical programs for conservation adaptation to the north” and focus the coverage laws of the and improvement. mechanisms of influence of exogenous factors on the reproductive The authors of many studies of male fertility in different health of men of the Sakha Republic (Yakutia). The work aimed countries concludes that the region of residence is an important at identifying regional characteristics of functional quality of determinant of the quality of sperm. It is expected that as natural, male fertility, hormonal profile, spermatogenesis, a study of lipid for example, climate, and cultural factors, such as lifestyle, level metabolism and other physiological and pathophysiological of social stress or pollution can determine the regional variability aspects. of reproductive parameters [3-8]. In many regions of the world in recent decades, decreased The new performance about etiology of the majority of fertility of the male population. In particular, the spermatogenesis reproductive disorders does not exclude the relationship and of men in reproductive age fell by half, the number of andrology the direct influence of the degree of obesity. Proved a direct diseases, morphological disorders of the male reproductive system negative impact of increased body mass index (BMI) on the and increased the number of couples with infertility caused by hormonal status and quality of sperm, especially in men who are “male factor” [2]. Also, over the past decades have seen a rise overweight. The native inhabitants of the northern regions of the in the prevalence of obesity in the male population, regardless noted tendency to increased lipid and protein metabolism, which of their place of residence and ethnicity [17]. are formed as a result of the traditional lifestyle is characterized In some regions of Russia, including Eastern Siberia, technogenic mainly by protein type of feeding [18-19]. pollution, urbanizationin conjunction with increased social The goal of this study – to evaluate sperm quality and the pressure, widespread heavy migration of people to the area of level of reproductive hormones in men the East Siberian region climate discomfort can disrupt the homeostasis of the organism of Russia on the example of the Yakutsk city and identify ethnic

608 Re g i o n a l peculiarities in s e m e n q u a l i t y a n d s e r u m h o r m o n a l concentrations o f c i t i z e n s f r o m y a k u t i a characteristics of the male reproductive function by comparing figures for normal sperm [9], but the proportion of motile sperm the Yakut men and Slavic ethnicity, as well as assess the impact of was lower than the standard values. Azoospermia was found in overweight and obesity on a visceral on the level of metabolites 4.3%, oligozoospermia – at 27.0% and asthenozoospermia – at of lipid metabolism in young males. 68.1% of men. As such the semen, sperm concentration and Conditions for the inclusion of volunteers in a group of subjects percentage of motile sperm only 68.8% and 31.9% of subjects, were: they were permanently resident in Yakutsk, at the time respectively, meet WHO standards, and 31.2% of men ejaculate of the study were clinically healthy, did not complain, did not in both parameters (concentration and mobility) met WHO pass medical treatment. Before the start of the survey every man standards for normal sperm [9]. Determination of the main was familiar with the methods and aims of the study, and then reproductive hormones in the blood serum of men of Yakutsk gave his written consent for the examination. In a preliminary did not reveal a significant deviation of the mean of LH, FSH conversation with the test indicating a need to abstain from and testosterone from the reference values (Table. I). sex and alcohol for 2-3 days prior to the survey. According to Comparison of semen residents of Yakutsk and other regions the results of an anonymous survey assessed demographic and of Russia and other countries has shown that the volume of the ethnic composition fertility (number of children) male study ejaculate of men from the city of Yakutsk did not differ from group. The Yakuts were 49.0% (taking into account national to that of the inhabitants of France, Denmark, Scotland, Finland, a depth of 3 generations), Yakuts with different levels of cross- the USA, Japan [3, 5, 6, 8] but it was higher than that of Chinese breeding – 35.2%, the Slavs (Russian, Ukrainian) – 11.0%, other or Singaporean men [3, 9]. The average concentration of sperm nationalities – 2.0%, mestizo Slavs and other nationalities – 2.8%. in the ejaculate of men of Yakutsk was lower than the values ​​ Unmarried 39.3% of the men, had children – 13.8%, smoking – published in foreign papers [4, 5, 6, 8, 10]. The proportion of 42.8% drank alcohol – 58.6%. Collecting blood and samples of motile sperm in the sample Yakut men was the lowest compared ejaculate and physical examination by andrologist performed to the French, Japanese, Danish or residents of Singapore [3, 8, in the morning. 23.4% of men said in their questionnaires that 5, 10], but it was close to the quantities released for the Chinese in the past have suffered and been treated for an STI (sexually people. [4] A survey of men, not previously on the population transmitted infections by – gonorrhea, chlamydia, ureaplasmosis of selected and potential fertility, we conducted in Novosibirsk, etc.). According to the physical examination 55.2% of men had at Kemerovo and Arkhangelsk same methods give comparable the time of the survey signs of disease of the reproductive system, results in terms of volume of ejaculate and sperm motility with including prostatitis, varicocele, testicular cysts, hypospadias, residents of Yakutsk, but the concentration of spermatozoa in and others. yakutians significantly lower than kemerovchan or Arkhangelsk Anthropometric, spermatogenic and hormonal characteristics [11-13]. A comparison of the quality of sperm in men of Yakutsk of the studied groups of men are presented in Table I. The mean and other geographical regions shows that male East Siberian values of BMI and bitestikulyarnogo volume is within normal region of Russia are characterized by a relatively high level of limits, but 27.3% of the subjects were characterized by male BMI suboptimal sperm quality. It is assumed that the ecological and ≥ 25.0, ie, overweight, and 10.0% had BTO ≤ 30 ml, ie below geographical environment, and ethno-cultural characteristics WHO standards [9]. Attention is drawn to the fact that the may be important factors affecting the functioning of the male average ejaculate volume and pH, as well as the concentration reproductive system and defining the heterogeneity of male and the total number of sperm in the ejaculate conform to WHO fertility.

Table I. Anthropometric, spermatogenic and hormonal characteristics of the studied groups of men of Yakutsk. Mean ± Osh. The median average (5-95%) Reference values Age, fullyears 24.1±0.5 22.0 (18.0-34.0) Bodyweight, kg 71.8±1.2 69.0 (55.0-95.0) Height 174.6±0.6 175.0 (163.0-187.0) BMI, kg / m2 23.48±0.33 23.20 (17.70-31.24) ≤25.0 BTO, Jr. 40.7±1.0 40.0 (28.0-60.0) ≤30.0 The volume of ejaculate, Jr. 3.3±0.1 3.2 (1.5-5.6) ≥2.0 pHofejaculate 7.72±0.02 7.69 (7.38-8.16) 7.2-8.0 The concentration of sperm in the ejaculate, million / ml 34.69±2.32 30.25 (0.62-95.11) ≥20.0 The total number of sperm in the ejaculate, million / ejaculate 111.47±8.13 88.15 (1.87-298.00) ≥40.0 The proportion of motile sperm categories A + B,% 39.6±2.2 37.4 (4.1-90.1) ≥50.0 The concentration of LH mIU / ml 4.07±0.18 3.61 (1.48-7.42) 0.8-7.6 The concentration of FSH mIU / ml 5.61±0.42 4.61 (2.45-9.89) 0.7-11.1 The concentration of testosterone nmol / L 19.08±0.56 17.61 (10.12-32.14) 8.5-55.5 Note: The number of subjects in the group was 145, the reference values for semen parameters taken from [8], and hormones - site www.labdiagnostic.ru.

609 Troev I.P., et al.

In the present study established a positive relationship between According to the results of our study, men with overweight bitestikulyarnym volume and sperm fertility indicators such as the was an increase in blood levels of TC, TG, LDL-cold and cold- total number, concentration and proportion of motile sperm (r = reduction of HDL relative to the control group. In general, it is 0.32, r = 0.29, r = 0.29, respectively, p <0.05 in all cases). Indeed, confirmed the literature data that obesity dyslipidemia expressed these figures are functionally interrelated, since the mass of the hypertriglyceridemia, increased formation nonesterified LCD, testes is mainly dependent on the number of Sertoli cells, which VLDL, HDL reduction of formation, which in turn, is a major remained relatively constant for each species, determines the risk of cardiovascular disease [21, 22]. potential in relation testis sperm production [14]. Consequently, Another aspect of the present work was to find ethnic the value bitestikulyarnogo volume is a prognostic criteria and differences in anthropometric, hormonal and spermatogenic can be used as an Andrology at the indirect estimation of fertility rates of male reproductive function among residents of Yakutsk. of sperm. In the study group of men between the concentration The data presented in Table 3 suggest that the Yakut men and and the proportion of motile sperm was a significant positive Slavic ethnicity do not differ on a range of reproductive options. correlation (r = 0.79, p <0.05). Thus, sperm concentration and An exception is the volume of ejaculate, which is higher in the motility are closely interrelated, and the factors which cause Slavic ethnic group compared to Yakutia (Table. III). In addition, deterioration of the one usually will have a negative effect on no significant differences in growth – Slavs higher than the other parameters. It is interesting to note the presence of weak but Yakuts. Lack of ethnic differences in reproductive parameters statistically significant negative correlation between the levels of established in the present study suggests that the reason we FSH and BTO, total amount and concentration of spermatozoa in have found other authors of regional differences in the level of the ejaculate (r = -0.19, r = -0.18, r = -0.21, respectively, p <0.05 fertility of sperm and reproductive hormones may be due to in all cases) reflecting the nature of the regulatory action of FSH environmental factors rather than genetic differences. Of course, in the hypothalamus – pituitary – testes [15]. this aspect of the problem should receive more attention from Since the population of men living in the city of Yakutsk, was physiologists and physicians involved in the study of reproductive characterized by a high level of oligozoospermia (27.0%), it was physiology and medicine. of interest to identify her anthropometric, spermatogenic and Thus, the present study demonstrates for the first time in hormonal correlates (Table. II). The comparison showed that men the East Siberian region of the Russian Federation (on the oligozoospermia is characterized by a significant decrease (p example of Yakutsk) reduced sperm quality, as well as the absence <0.05) bitestikulyarnogo volume, the total number and motility, of significant differences between Yakutsk and Slavic ethnic group as well as an increase in the concentration of luteinizing hormone in the spermatogenic and hormonal parameters of reproductive and follicle-stimulating hormone in the blood. Although the function. Identified patterns demonstrate the relationship of causes of oligozoospermia can be very diverse [16], including the basic blood lipids and fatty acids with a body mass index, with effect of environmental and genetic factors, our data suggest that the nature and extent of changes in lipid profile due to ethnicity. the decline in the functional activity of Sertoli cells of the testes In men, overweight different ethnicity observed changes in can make a contribution to the formation of the reproductive lipid metabolism compared with men of normal weight. Men syndrome male East Siberian region of Russia. Indeed, with Yakut ethnic group was an increase in glucose, triglycerides, a reduced activity or insufficient amount of Sertoli cells sperm significant increase in atherogenic index with increasing BMI. production decreases and levels of pituitary gonadotropins Traced a clear connection overweight men both ethnic groups increased [14-16], which is observed in this study. with a share of palmitoleic acid in blood plasma.

Table II. Anthropometric, spermatogenic and hormonal correlates of oligospermia in men of Yakutsk. Standard (n=95) Oligospermatism (n=44) The concentration of sperm million / ml 46.68±2.54 9.59±0.80 Age, fullyears 24.0±0.6 23.7±0.7 Bodyweight, kg 71.1±1.4 72.7±2.3 Height 174.5±0.6 174.5±1.1 BMI, kg / m2 23.3±0.4 23.8±0.6 BTO, Jr. 43.2±1.2 34.7±1.5* The volume of ejaculate, Jr. 3.3±0.1 3.3±0.2 pHofejaculate 7.67±0.02 7.85±0.03* The total number of sperm in the ejaculate, million / ejaculate 148.95±9.52 28.85±3.59* Percentage of motile sperm (A + B),% 49.7±2.3 13.9±1.8* The concentration of LH mIU / ml 3.71±0.17 4.92±0.45* The concentration of FSH mIU / ml 4.64±0.17 7.81±1.28* The concentration of testosterone nmol / L 19.36±0.70 18.70±0.99 Note: * - significance of differences between groups (p <0.05), given in parentheses the number of subjects in the group.

610 Re g i o n a l peculiarities in s e m e n q u a l i t y a n d s e r u m h o r m o n a l concentrations o f c i t i z e n s f r o m y a k u t i a

Table III. Anthropometric, spermatogenic and hormonal characteristics of men of different ethnicity of Yakutsk. with varying degrees Yakuts Yakuts (n = 71) TheSlavs (n=16) cross-breeding (n = 51) Age, fullyears 23.9±0.8 23.3±0.6 26.9±1.2 Bodyweight, kg 69.8±1.7 72.2±1.9 74.1±2.9 Height 173.4±1.7* 174.3±1.0* 179.6±1.4 BMI, kg / m2 23.2±0.5 23.7±0.5 22.9±0.8 BTO, Jr. 39.4±1.2 42.1±2.1 43.9±2.0 The volume of ejaculate, Jr. 3.2±0.2* 3.1±0.2* 3.9±0.4 The concentration of sperm million / ml 34.08±3.31 40.25±4.16 27.55±5.59 Percentage of motile sperm (A + B),% 37.1±2.9 43.2±3.9 35.7±6.2 The concentration of LH mIU / ml 3.97±0.19 4.02±0.30 4.46±1.00 The concentration of FSH mIU / ml 5.29±0.30 5.50±0.76 6.62±2.64 The concentration of testosterone nmol / L 19.42±0.79 19.03±1.02 18.87±1.45 Note: * - significant differences between the Slavs and the Yakuts, or between Slavs and Yakuts with varying degrees of cross-breeding (p <0.05), is given in brackets the number of subjects in the group.

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