TQP CHI V - DUOC HOC OURN SUSO 5-2014
NGHIEN CQU TAC DUNG LAM SANG CUA THUOC CYTOFLAVIN d BENH NHAN NHO! MAU TRONG HAI TUAN DAU
Nguyin Van Tuan*; Nguyin Minh Hifn*; Nguyin Th'i Huvmg**
T O M T A T
Nghien c u u dieu tn a6t quy n h i i mau nao (NMN) trong hai t u i n dau trfin 100 b$nh nhan (BN), gom 50 BN nhom chi>ng d i l u tri phac do NMN c a ban v^ 50 BN nh6m nghign ci>u si>
dung k i t hop them t h u l c cytoflavin. K i t qua BN > 50 tuoi c h i i m 94%, t;^ Ig nam/niJ = 1,8. Roi loan y thiic 26%, liet nCca ngu'oi 98%, liet day VII trung u'ang 79%, r l i loan cam gi^c 55% v^ roi loan ngon ngu' 4 1 % . 0 n h i i mau kich thu'ac 3 - 5 cm c h i i m 79,3%, vfjng bao trong 3 1 % va VLing nhan xam 3 6 % Cai thign lam sang chung theo thang diem NIHSS tCr mO'C trung binh d^n t i t a nhOm dung cytoflavin la 86%; cai thign mtjc dg Iigt theo thang diem MRC la 92%, kh^c bigt cd y nghia t h i n g ke (p < 0,05) Tac dyng khOng mong m u l n trSn iam sang g$p ty Ig thap (12%), tat ca o mO'C dg nhe, thoang qua va khdng de lai nguy hai gi. Chu'a c6 b i n g chi>ng ve tac dung khong mong m u l n tr6n chCpc nSng c h u y i n hoa gan, than, du-ang mSu va cgng thi>c mau.
Ket luan cytoflavin cai thign trgn lam sang c6 y nghTa t h i n g kg so vd'i nhom chiing trong hai tuan d i u d i l u tr; (p < 0,05). T h u l c an toan, It tac dyng phy va khgng ggy nguy hai.
" TO' khda. €)6t quy n h i i mau nao; Cytoflavin.
CLINICAL EFFECTS OF CYTOFLAVIN DRUGS ON PATIENTS WiTH ISCHEMIC STROKE IN THE FIRST TWO WEEKS
SUIVIMARY
A study on the treatment of cerebral ischemic stroke in the first two weeks in 100 patients, including 50 patients as a control group who were treated ischemic stroke for basic regimen and 50 patients whose regimen combined with cytoflavin. Results: over 50 years old accounted for 94%, the ratio of male/female = 1.8. Consciousness disorders' 26%, hemiplegio 98%, paralyzed central cord VII: 79%, sensory disorders: 55% and language disorders: 41%. Drive Infarct at the size of 3 - 5cm accounted for 79.3%, basal ganglionic: 36% and internal caspules was 31%.
For the group of Cytoflavin, 85% of patients were improved in general clinical based on NIHSS scale from medium to good: The rate of Improvement in the level of paralysis according to the MRC scale was 92%, statistically significant different with p < 0.05. Undesirable effects were low (12%), mild, transient without any harm. There Is no evidence of adverse effects on metabolic liver function, kidney, blood sugar and blood counts.
Conclusion: Cytoflavin drug on clinical improvement was statistically significant compared to placebo after two weeks of treatment (p < 0.05). Drugs are safe, few side-effects and does not cause harm.
* Key words Ischemic stroke, Cytoflavin ' Benh viin Quan y 103
" Benh viin Da khoa tinh Bic Giang
NgiPiriphan hoi (Corresponding): Nguyen Van Tuan ([email protected]) Ngiy nhan bii: 21/03/2014; Ngiy phin biin danh gia bii bio: 08/05/2014
Ngiy bai bio du-oc dang: 26/05/2014
116
TRP CHi V - DUOC Hpc QUfiN SU Sd' 5-2014 DAT VAN DE
Opt quy nao la nguyen nhan gSy ti>
vong dLPng thLr hai sau b$nh tim mgch va ung thu, la nguyen nhan hang d i u gay tan phi. Ucfc tfnh m l i nam Vi?t Nam co khoang 200.000 nguai bj dgt quy, 15 - 20% tan p h i hoan toan va 20 - 25% ty phyc vy [3, 6], Opt quy nao g i m hai the:
chay mau nao chiem khoang 15 - 20% va NIVIN (80 - 85%) [3].
Ngay nay cung vai sy phat trien cua khoa hgc cong ngh$, vl$c chin doan duac nhanh chong va chinh xac. Dieu tn kip thai dac hi0u bang thulc tieu sal huyit (actylase) da mang lai k i t qua phyc hii rit t i t vai t h i dpt quy NMN. Tuy nhien, do thai gian cua s l dilu trj ngan (3 - 4,5 gia dau) nen ty 10 nguai b$nh duac dilu trj tieu huyet khoi thip (< 7%) a My [3, 5]. Do vay, vi^c nghien cuu them c^c thulc bao v0 va dinh duang than kinh la cln thilt de lam phong phu them phac do dilu trj, gop phin nang cao hi$u qua dilu tri, cai thi§n chit luang song cho nguai bdnh.
Thuoc cytoflavin thupc nhom dilu chinh trao d i i chat, cua Hang Khoa hpc - Cong nghe Duac phim "POLYSAN"
Cpng hoa Lien bang Nga. Cytoflavin da dup'c su dung dilu trj dpt quy nao a Lien bang Nga va mpt s l nuac ch^u Au, nhung hien nay a Vi^t Nam chua c6 nhilu nghien cuu v l thuoc nay. Do vgy, chung toi tiln hanh nghien cuu nay nhim:
- Mo ta mot so d§c diem lam sang va hinh inh chijp cat l&p vi tinh a BN NI\^N trong 2 tuin dau.
- Danh gia tac dung ho tro tren lam sang cua thuoc cytoflavin a nhom BN nghien cO'u co dung phac do nin.
D 6 | T U - O N G V A PHU'aNG PHAP NGHIEN CU'U 1. Ddi tipgng nghien ciru.
100 BN dpt quy NMN tren llu tieu nao giai dogn cap, nam dilu trj npi tru tgi Khoa Dot quy nao, B$nh vien Quan y 103 tu 12 -2012 d i n 7 - 2013, tuoi dai ti> 30 - 80.
2. Tieu c h u i n l^a chon BN.
- Lam sang: can cu vao dinh nghTa dot quy nao cua T l chuc Y te T h i giai (1990): bpnh khai phat dot ngpt vai cac tri^u chung than kinh khu tru t i n tgi > 24 gia hoac t u vong truac 24 gia. Nhi>ng tripu Chung t h i n kinh khu tru phii hap vai viJng nao do dpng mach bi t i n thuang phan b l , khong do nguyen nhan chan thuang sp nao [3].
- Can lam sang: 100% BN duac chup cat lap vi tinh sp nao (CLVT).
* Tieu chuin lo^i tru':
- BN khong du tieu chuin chan doan - Mac cac benh ung thu, viem nao, bpnh nao do ky sinh trung.
- BN NMN chuyen the, NMN tai dien.
- Phu nij' CO thai, r l i logn nhip tim, huyet ap thap.
- Chong chi dinh dung cytoflavin - Hon me sau, nhii mau than nao va vung dual llu.
- BN khong hp'p tac nghien cuu.
• Chat lieu nghien cCru:
Cac thulc y hpc hien dgi dgng dung theo phgc d l n i n danh cho BN dpt quy NMN tgi Benh vipn Quan y 103 va cytoflavin:
- Cerebrolysin (Ao): tiem tTnh mach; ham luang moi ong 10 ml.
- Gliatilin (Y): tiem bap hoac tTnh mach;
ham luang m l i Ing 1 g/4 ml.
117
TAP CHl V • Dirge Hpc OUaNSy so 5-2014 - Cytoflavin (Nga): 6ng tietn 10 ml chu-a succinic axit 1 g, nicotinamide 100 mg, riboxin 200 mg, riboflavin sodium phosphate 20 mg; ta du'O'c gom meglumin 1,65 g, hydroxit natri 0,34 g, nu-ac cat vCfa ail 10 ml. Cyttoflavin la mot phCfc hp'p cSn bang tir hai chat chuyin hoa (axit succinic, riboxin) va 2 coenzym-vitamin.
+ Axit succinic - chat chuyen hoa npi sinh da nang noi tS bao, thu'c hien chuc nang xuc tac trong chu trinh Krebs, tang cudng vong tu§n hoan, tang khoi lugng nang luong can thiet de t6ng hop ATP va protein, co tac dung chdng giam oxy do tang nong do GABA trong mo nao.
+ Nicotinamid - chat bao ve th&n l<inh, CO tac dgng chong oxy hoa.
+ Riboxin - dan chit cua purin, la tien chat cua ATP.
+ Riboflavin - mononucleotid duoc tao thanh trong co the tu riboflavin, tham gia cac enzym di§u chfnh oxy hoa khu, tham gia vao qua trinh trao doi protein va chit beo.
Nhu vgy, cac hg-p chat c6 trong cytoflavin c6 t^c dung dieu chlnh qua trinh chuyen hoa nang luong, chong giam oxy va chong oxy hoa. d i n din binh thuong hoa qua trinh trao ddi chat trong co t h i .
2. Phycng phap nghien CLPU.
* Thiit ki nghien ciru: nghien cuu tien ciru, can thiep bang thuoc, co doi chCfng, k i t hop mo ta phan tich.
* Phuvng phap nghien ciru:
Chia ngau nhien 100 BN dgt quy NMN thanh 2 nhom theo each chon 1:1. Ca 2 nhom deu du'gc dieu tri theo phac 66 nen tuan theo nguyen tac dieu tn dot quy nao tai Benh vien Quan y 103:
+ Duy tri chuc nang song va dilu chinh cac hang $6 sinh ly tiJy theo miic dp benh.
+ Chong phu nao: khi co bilu hi$n phu nao.
+ Thuoc ching k i t tap t i i u c i u : aspirin 100 mg/ngay.
+ Thulc dinh du&ng va bao v$ t l bao nao: cerebrolysin 10 ml/6ng x 2 6ng/ngay, tiem tTnh mgch sang, chilu; gliatilin 1 g x 2 ong tiem b l p thit sang, chilu.
Nhom chung gom 50 BN du'gc dilu tri vdi phac d l n i n thudng dung cua vien.
Nhom nghien cuu gom 50 BN dugc dilu tri cytoflavin k i t hgp vdi phac do nen thudng dCing cua vign. cytoflavin 10 mi/lng X 2 ong/24 gid, pha vdi natri clorua 0,9%
truyin Hnh mach 40 giot/phut.
ChI tieu danh gia: BN dugc kham chuyen khoa lam sang than kinh, danh gia tinh trgng lam sang chung theo thang dilm NIHSS, danh gia y thuc theo thang dilm Glasgow, danh gia dp liet theo thang dilm Hpi d i n g Anh (MRC) [3, 6]
Theo doi tic dyng phy cOa thulc cytoflavin: d| ung, s i c phan ve, dau byng, b i n chon...; xet nghiam ure, creatinin, GOT, GPT, GGT danh gia thay d i i trugc va sau dilu trj.
Xu ly so ligu tren may tinh theo phu'ong phap thong kS bang phin nim SPSS 18.0 (My).
K t T QUA NGHIEN CIPU VA BAN LUAN 1. Oac d i l m BN phan b6 theo tuoi va giffi.
Bieu do 1: Phan b l BN theo nhom tuli.
118
TRP CHl V - Diroc HOC QUAN Stf Sd' 5-2014 Ty lg mac b$nh tang d i n theo tuli, dac
bigt nhom > 50 tuli. Nhom tuli > 70 chiim ty IS cao nhat (46%), khac bigt giCra 2 nhom khong cd y nghia thing ke (p > 0,05), phu hgp vdi nghidn ciJu cua Nguyin Van Bang: dot quy NMN > 65 tuli la 75%; Nguyen Van Chuong: NMN
> 50 tuli chiem 92,45% [1].
2. Trieu chijng lam sang.
Sang 1:
Ty le mac bgnh d nam 64% va nir 36%. Ty lg nam/nu' la 1,78. Su khac bigt ty le v l gidi tinh giCra 2 nhdm khdng co y nghia thing ke (p > 0,05). Kit qua nay phii hgp vdi nghien ciru cua Nguyin Van Chugng (1,7/1) va Nguyin Van Thdng (2010) (2,2/1) [4].
TRlfiU CHONG R6i logn y thCi'c Dau d i u N5n, buon non R6i lo?n CO- vong R6i logn ng^n ngu' Roi logn cam gidc nOa ng\r&]
Li^t nu'a ngu'di List day VII TW
NHOM NGHIEN Cilu n 14 9 6 9 21 28 48 39
28,0
%
18,0 12,0 18,0 22,0 56,0 96,0 78,0
NHOM CHCTNG n 12 8 3 10 20 27 50 40
24,0
%
16,0 6,0 40,0 40.0 54,0 100 80,0
TONG n 26 17 9 19 41 55 98 79
26,0
%
170 9,0 19,0 41,0 55,0 98,0 79,0
P
>0,05
Tri#u ehifng hay ggp nhit la Iigt nCra ngudi (98%), Iigt day VII trung ugng (79%). Cac trigu chiJng giua 2 nhom khong khac bigt (p > 0,05). K i t qua ciia chiing toi phu hgp vdi nghien ciru cua Nguyin Van T u i n (2010): Iigt niJa ngudi 98,6% [6]; theo Le Van Thinh; ty lg nay la 98,18% [5]. R l i logn y thifC chiim ty l§
cao (26%), chii y i u roi logn y thirc nhg va
vira, cao hgn nghien ciru cua Nguyin van Chugng va CS (20,8%) [1]; cua H i Hu'u Lugng va Phan Vigt Nga la 19%
va Nguyen Minh Hign, Nguyen Van Tuin (2010) la 22,25% d i i vdi BN bi dpt quy NMN [6].
* Danh gii mire do liet khi vao vi$n theo thang diim HQI ddng Nghien ciru Y hoc Anh (IVIRC):
m Nh6m NC • Nh6m chCrng
0$ 0 0$ 1 0$ 2 0$ 3 0$ 4 e$ 5 Bleu d6 2: Oanh gia muc dp lipt theo MRC.
Lipt dp 3 chiim ty Ip cao nhit (39%), khac bipt khong co y nghTa thing kd (p > 0,05)
TAP CHf V - DirplC HOC OUAN SIT s 6 5-2014
Sang 2: Danh gia mire dp lam sing theo thang dilm NIHSS.
NHOMBISM 4 2 - 3 5 34 -25 2 4 - 1 5
SU Tong
NHOM NGHIEN COU n
1 5 23 21 50
2,0
%
10,0 46.0 42.0 100,0
NHOM cnaNG n 1 1 27
• 21 50
2,0
%
2,0 54,0 42,0 100.0
T 3 N G n 2 6 50 42 100
2,0
%
6,0 50,0 42,0 100,0
P
>0,05
Nhom 1 5 - 2 4 dilm NIHSS chiim ty lg cao nhat (50%).
3. K i t qua hinh anh CLVT $p nao.
S^ng 3:
D A C B I ^ M T O N THUONG
Vitri
Kich thyoc
Nhan xam Bao trong Vung tran Viing cham Viing thiiy du'ai
Viing dinh
< 3 c m 3 - 5 c m
> 5 cm
N H 6 M NGHIEN CUU n
18 12 2 5 5 3 5 36 4
%
42,0 26,0 4,0 0 11,0
6,0 11,0 80,0 9.0
N H O M CHCTNG n 14 16 2 7 7 1 7 37 3
%
30,0 34,0 4,0 15,0 15,0 2,0 15,0 79,0 6,0
T 6 N G n 32 28 4 12 12 4 12 73 7
%
36,0 31,0 4,3 12,2 12,2 4,3 13,0 79,3 7,7 Hinh anh CLVT sp nao cho thiy t i n thugng ban cau trai 5 1 % , ban c i u phai 49%, 6 nho 13%, I Idn: 7,7%. Viing bao trong nhan xam chiim ty le cao nhat (67%), tuong dugng nghien cifu Nguyin Mmh Hign va Nguyin Van Bang (55,1%) [2]
4. Danh gia hieu qua cua t h u l c tren \im sang
* Cai thien mCrc do iam sang theo thang diim NIHSS:
iNhomNC ahlhomchij-ng
^ 2
T6t Kha Trung binh Kem Biiu do 3: Cai thign lam sang theo thang diilm NIHSS ciia 2 nhom nghien ciru.
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T^P CHi V - D i r o c H p c QUfiN S i ; s o 5-2014 Cytoflavin lam cai thign lam sang t i t va
kha danh gia theo thang dilm NIHSS la 30%, cao hon so vdi nhdm chirng 16%;
cai thi^n mire dp trung binh 56% so vdi 62% nhom chii'ng. Nhu vgy, nhom diing cytoflavin cai thi#n lam sang (86%), cao hon so vdi nhdm chirng (68%), khac bigt CO y nghia thong ke (p < 0,05). K i t qua nghien ciru cua chiing tdi phii hgp vdi
S.A. Rumyantseva [9], Shestakov [10].
Mire dp lam sang trudc dilu tri theo thang dilm NIHSS tif 15 - 24 chiem 46%, nhdm dilm NIHSS £ 14 c6 42%. Sau dilu tri k i t hgp cytoflavin, nhdm BN NIHSSS s 14 dilm tang len 88%, cdn nhdm NIHSS 1 4 - 2 4 giam xuong 8%
* Cai thien mire dg liet theo thang diim ciia H0i dong Nghien ciru Yhgc Anh (MRC):
100 -^ . . _ 50 / . , .
T6t KhS
• Nh6mNC
r^~
Trung binh
• Nhom Chiang
^^HJir..
Kem
Biiu do 4: Cai thign mire do Iigt theo thang diilm MRC
Cai thi^n Iigt chung g nhom diing cytoflavin la 92%, cao hgn dang k l so vdi nhdm chirng (66%), da so BN co cai thign mpt dp Iigt (60%), khac bigt cc y nghia thing kS (p
< 0,05). CM t h i , 10% nhdm cai thien t i t (+3 dilm), 22% cai thign kha (+2 dilm) va 60%
cai thien mire trung binh (+1 dilm) va 24% nhdm khdng cai thien.
5. Tac dung khong mong m u l n tren \im sang va can lam sang cua cytoflavin.
Bang 4: Tac dyng khdng mong muln tren lam sang.
TAC D U N G K H O N G MONG M U 6 N Kho hong N6ng birng mgt O^nh trong nguc Qu^ min Chay mau Tong
N H O M NGHlfeN CiAl n
2 3 1 0 0 6
%
4,0 6,0 2,0 0 0 12,0
N H O M CHifNG n 1 2 0 0 0 3
%
2,0 4,0 0 0 0 6,0
T6NG n 3 5 1 0 0 9
%
3,0 5,0 1,0 0 0 9,0
P
>0,05
Khong gap BN nao s i c phan vg hogc co phan irng qua man nguy hiim d i n tinh mgng, khong cd chay mgu nao chuyin t h i hoac ton thugng cac eg quan khac. Ty le tac dung khong mong muln: 12%, cao hgn nhdm chirng (6%), nhung khac bigt khdng
CO y nghia thing ke (p > 0,05). Nghien ciru cua Belolipetskaya V.G cd ty lg tac dung khdng mong muln d nhdm diJng cytoflavin cao hgn nhilu so vdi nghien ciru cua chiing tdi: khd hong 79,1%, ndng birng mgt 58,3% [7]. Nguyen nhgn cd t h i do nghien
121
Ti;p CHi V - Diroc npc OUAN sir sd' 5-2014
ciru cug Belolipetskaya V.G cho truyin hit, khdng cd trudng hgp nao phai dirng cytoflavin vdi t i c do nhanh, tuy nhien tac nghien ciru [7]. Theo Fedin A.I va CS [8], dung khong mong muln cht xuit hign trong tac dung khdng mong muln trSn lam sang qua trinh diing thulc va nhanh chdng t u ciia cytoflavin nhg, khdng keo dai.
Sang 5: Biln d i i cac chi tieu sinh hda va huyit hpc mau sau d i l u tri.
C H I TIEU SINH H O A Glucose tang Ure tang Creatinin tang Men gan tdng Chi tieu huy^t hpc Tang bach cau Giam hong ciu Giam tieu ciu
N H 6 M CHt/NG Truoc dieu fri
12 (24%) 4 (8%) 3 (6%) 9(18%)
7(14%) 4 (8%) 0 (0%)
Sau dieu tr|
4(8%) 3 (6%) 2 (4%) 7 (14%)
5 (10%) 4 (8%) 0 (0%)
NHOM NGHIEN CCtU Trud-c dieu tri
11 (22%) 7 (14%) 2 (4%) 13 (26%)
9 (18%) 4 (8%) 1 (2%)
Sau dilu tri 5 (10%)
2 (4%) 2 (4%) 13(26%)
8 (16%) 4 (8%) 1 (2%)
P
>0,05
>0,05
Nhdm diing cytoflavin sau dilu trj cd tang ure mau (4%), tang creatinin (4%); d nhdm chii'ng tang ure mau 6% va tang creatinin 4%. Nhu vgy, biln d i i cae chi s l sinh hog g hgi nhdm sau dilu trj tugng dugng nhau Do do, chua cd bang chirng v l tac dung khdng mong muln eua thuoc tren ehire nang thgn. Vdi tac dung iam ting glucose mau eho thgy ty lg tgng dudng mgu trudc dieu trj cug nhdm nghien ciru va nhdm chirng Iln lugt la 22% va 24%, sau dilu trj giam xuing 10% va 8%. Nhu vay, ca 2 nhdm khong khac nhau v l chirc nang tang dudng mau. Ty le tang men gan (GOT, GPT) g hai nhdm trudc dilu trj la 26% va sau dilu tri la 26%; nhdm ehOng so vdi nhdm nghien ciru khong cd su khac biet va khong anh hudng d i n chirc nang tang men gan. V l su thay d i i cua hing cau, bgch c i u va tieu egu t h i y khong khac bi$t giira hai nhdm trudc va sau dilu trj. Nhu vgy, k i t qua cho thiy cytoflavin khong
anh hugng tdi men gan, chirc nang thgn va cac thanh p h i n huu hinh ciia mau giing nhu nghien cii-u ciia Belolipetskaya V.G va Fedin A.I [7, 8],
KET LUAN
Qua k i t qua nghien ciru tren 100 BN dgt quy NMN tren l l u t i i u nao trong 2 tuan d i u , chiing toi rut ra k i t lugn sau:
Ty lg m l e benh tang nhanh khi > 50 tuoi, ty l# nam/nu = 1,8.
- R l i logn y thirc 26%, Ii6t nu'a ngudi 98%, Iigt day VII trung ugng 79%, r l i loan cam giac 55% va r l i logn ngdn ngu" 41%.
- 6 nhii mau kich thudc 3 - 5 cm chiim 79,3%; vung bao trong 3 1 % va viing nhan xam 36%
- Cai thien lam sang chung theo thang dilm NIHSS tir mire trung binh d i n t i t a nhdm nghien ciru la 86%. Cai thign mire dd Iigt theo thang diem MRC d nhdm nghien ciru la 92%. Khac bigt ed y nghia thing ke tren lam sang (p < 0,05)
122
TQp CHi V - Duac HOC QUAN sir sd' 5-2014
- T ^ c d u n g k h o n g m o n g m u l n tren lam sang g g p ty le t h i p ( 1 2 % ) , t i t ca d m u c dp nhp, t h o a n g q u a va k h d n g d l Igi n g u y hgi g i . C h u a c 6 b a n g c h u n g v l tac d y n g khong m o n g m u l n tren c h u c n a n g c h u y i n h o a g a n , t h g n , d u d ' n g m a u v a cQng thu'c m a u .
T A I L I E U T H A M K H A O 1. Nguyin VSn Chuung, Trdn Nguyen Hdn. Nghi&n cu'u 6^c d i l m lam sang cua dOt quy nSo do ch^y m^u n&o vS NMN. Tgp chi Y - DU'O'C hoc Quan sy. 2012, s l 2, tr-104-109
2- NguySn Minh Hien, NguySn VSn DSng.
D$c diem ISm sSng v^ hinh anh chgp c i t 16'p vi t(nh so nSo o BN dOt quy NMN- Tgp chi Y - DU'O'C hoc QuSn s u . 2007, so 1.
3. Nguyin Minh Hi$n, Nguyin VSn TuSn.
Dot quy NMN. DOt quy nSo- NhS X u i t ban Y hoc. 2013, tr.163-193.
4. Nguyin VSn Thdng. Nghign cu'u hi0u qua d i l u tri cua aggrenox tren BN NMN giai dogn d p , Tgp chf Y - Dup'c QuSn sy. 2010, s6 2, tr.52-58.
5- L§ VSn Thinh. D^t quy nSo, tai b i l n mgch mciu nSo. Tai b i l n mgch mau nSo, hiF^ng d i n c h i n do^n v^ XLP tri. NhS xuat ban YhpC-2008, tr.217-225.
6- Nguyin VSn Tuin Nghien ci>u m<it s l d$c diem ISm s^ng va hinh anh CT, MRl so nSo tren BN dgt quy NMN- Tgp chi Y d u p c hoc lam s^ng- Bgnh vien TW QuSn dgi 108.
2010, s l dgc bigt thang 10/2010, tr.162-169.
7- Belolipetskaya V.G. Bambysheva E.i, Beloiipetskiy N A et al Study of pharmacokinetics of cytoflavin solution for intravenous use in health volunteers.
Cardiovascular therapy for and preventing medicine 2005, No 4, pp 38-43.
8- Fedin A.I, Rumyantseva S.A, Piradov M.A. Multi-centered placebo-controled clinical trial of cytoflavin solution for intravenous use in patients with consequences of acute ischmic cerebrovascular accident in the early recovery period. Vrach. 2006, No 13, pp-52-58.
9. S.A. Rumyantseva, A.i.Fedin, S.BBolevlch et al. Effects of early correction of energy and free radical homeostasis on the clinical and morphological picture of cerebral infarction.
Neuroscience and Behavioral Physiology 2011,41 (8), pp.843-84a.
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