Tgp chl Tai MOI Hpng Vi$t Nam - Volume (57-10). N°4 - July, 2012
DANH GIA HIEU HTC CUA DI NGUYEN MAT B p NHA NU6l CAY D. PTERONYSSINUS QUA KET QUA DIEU TRI G I A M MAN CAM
D A C H l f U B E N H V I E M Mtfl DI ITNG DO B y i NHA Va Minh Thuc'' Phgm Van Thuc", Nguyin Quang Hung"
T6M TAT
Di nguyen do chung toi tack chiit lit mgt btfi nha nudi cdy D. Pteronyssinus da dugc sir dmg dedieu tri GMC BHcho 40 b$nh nhdn viSm mui di ting do bui nha. Kit qua diiu Iri bu&c dau dd mang Igi hi$u qua tick cue, dufc thi Men qua cac chi sS: Cic Irifu chiing Idm sang thuyen giam rd ret: ty 14 duang tinh vai cdc test invivo gidm mgnh, ddc bi^l la test h'ch thich mui (P<0.01); ham lugng IgE loan phdn gidm tit 1128,1 ± 457,6 lU/ml xuSng con 863,2 ± 147,5 lU/ml; ham luang IgG torn phdn tang tic 16,34 ± 4,81 mg/ml lin 27,47 ± 5,20 mg/ml; sau diiu Irj ty 1$ b^nh nhdn dot mite tSt vd khd Id 47,2%.
RESUME
Nous avons obtenu des antigenes d'origine de D. Pteronyssinus en culture, utilises dans la desesibilisation specefique ppour 40 malades de rhinite allergique, a cdue de la PM. Des les premiers pd, nous avons obtenu de bon resultats, representes cliniques sont ameliorees, taux des test in vivo positifest diminue nettement, en particulier le test in vivo de rhino - provocation (P< 0.01), la concentration d' IgE serique totale dimunue de 1128,1 ± 457,6 lU/ml a 863,2 ± 147,5 lU/ml; la concentration d' IgG serique totale augment 16,34 ± 4,81 mg/ml a 27,47 ± 5,20 mg/ml:
Apres le traitement, le pourcentage des patients dont le reultat du traitement est bon et assez bon est de 47,2%.
Keys Words: Rhinite allergique l . M d D A U
Mat byi nha la nguyen nhan chinh cua c^c benh di ling duong ho hap tren nhu Hen ph6 quan, viem mui di ung. Vifc sii dving di nguySn dac hi$u de chan d o ^ va dieu tri b#nh Hen phS quan va viem mili di ling hien nay dang la mpt bien ph4p chu ySu duoc nhiSu nude trSn th8 gioi dp dyng.
d nuac ta, nhieu tac gia da diSu che, t i t o chuin hoa dj nguy&i bui nha to4n phSn va
• B$nh vien TMH l U
**Daihoc YHMPhdng
NhSn Mi 25/6/2012. Duvet in 10/7/2012
ap dung chung trong di^u tri trong cac l)^nh di ling. Trong nhOng c6ng trinh tru6c, chiing toi da ngtiien ciiu tach cliiet, xac dinh mot s6 d ^ tinh Hoa sinh, Mien dich ciaa di nguySn D. Pteronyssinus nu6i cdy.
Di nguyen da dieu che buac d i u dugc ling dyng trong dieu tri viem miii di ling do bui nM, thoi gian dieu tri 6 thang. Trong bai nay chiing toi neu mpt s6 ket q u i diiu tri (GMC DH) b$nh viem miii di ling do bui n h ^ qua do danh gia lii|u luc cua di nguyen da diSu che.
Tap chl Tai MQi Hpng Vi^t Nam - Volume (57-10). N°4 • July, 2012
2. D 6 I TirONG VA PHlTONG P H A P NGHlfeN C<ru
2.1. Doi tirgrng
+ Nh6m b^nh nhta: 40 b^nh nhin v i t o mui dj ling Augc c h ^ dodn theo cdc ti§u chu4n nhu; C6 tiln sii di ling rd, c6 bieu hi^n Idm sang ciia b^nh dj ling: ngtia mQi, hdt hoi, chdy mui, ng^t mui....; test l^y da duong tinh v6i dj nguy€n D. Pteronyssinus, hdm lu<piig IgE trong huylt thanh cao, ddp ling du<;rc cdc tieu c h u ^ vh chi dinh vd chong chi djnh.
+ Nh6m chiing: 30 nguiri kh6e m ^ , khong mdc cdc b^nh di ling ciing nhu cdc b$nh khdc, c6 test l4y da dm tinh v6i dj nguyen D. Pteronyssinus.
2.2. Phinnig phdp nghi€n ciru
ZZL KbiiD cbgn b^ib nbaa vi abdtn cbung:
Khdm lam sang (bao g6m diiu tra tiln sii theo mlu 25B cua t6 chiic Y tS the gioi).
2.2.2. Test lay da (Pricktest) (7):
Lam sach m|t da vimg truoc cdng tay bang con 70" de khd len roi Ian lugt nho len mat da vai cho each nhau 3-4cm, moi chS 1 gipt cdc dung djch chiing (NaCI 0.9%;
Histamin 0.01%) va thii (thung djch DN nengdOlOOOPhaJ/ml).
Dvmg kim xuyen qua dung djch cdm nh? vao myrt da qua lop thu<;mg hi (khdng chdy mdu) t ^ mgt goc 45° rdi lAy nh? len (moi gipt dung m§t kim lay da rieng), dpi 3-5 phut sau dCmg bong tham 6 ria gipt dung dich cho khd hit. Dpc kit qud sau 15- 20 phiit theo cdc miic d^: dm tinh (-), nghi ngt" (=•=). duong tinh nh? (-f), duong tinh vtia (++), duong tinh n^nh (+++), ducmg tinh rdt manh (++++).
2.2.3. Test kick Ihlch mBill2J:
D$t b$nh nhdn ndm tu thI thda mdi, nghi ngcri 10-15 phiit. Libi lupt tiln hdnh cdc budc:
I) Kilm tra h6c mOi trudc khi 1dm test xem c6 d tr^ng thdi binh thudng hay khdng.
II) Nhd vdo mSi bdn mGi 3 gipt dung mdi DN (chiing) dl xem c6 phdn ling khdng, d ^ hi$u khdng.
III) Sau 30 phiit nlu blnh thtremg, bdt dAu nhd 3 gipt dung djch DN thii nSng d$
1000 PNU/ml vdo m5i bdn mm (lO.OOOPNU/ml nlu Ian dau khdng ddp ung). Ddnh gid kit qud sau 30 phiit, 1 gid, 2 gi6, 3 gid, 4 gid. Thdi gian vd s\r xuAt hi^n cdc tri$u chiing nhu chdy nude miii, hdt hoi, ndng rdt mui, ngat mui dupe b ^ nhan trd Idi. Kit qud dupe xdc dinh bimg ddp ling d lieu thip nhdt, b^nh nhdn dupe coi Id cd ddp ling duong tinh khi cd it nhdt 2 trong 4 tri^u chiing tren. Ddp ling dupe coi Id nghi ngd khi chi xu^t hi^n mpt trong cdc tri^u chiing tren. Ddp ling dupe coi Id dm tinh khi khdng cd bilu hi^n gl cd.
2.2.4. Binh lufng IgE toin phin:
Dupe tien hdnh theo kj thu^ ELISA, dita tren nguydn ly bdnh kpp (Sandwich).
Khi x6t nghi$m IgE ciia hdng General Biological corporation Ltd., Taiwan. Mdy dpc ELISA cua hdng organon, Nerthelaod vdi birdc sdng 450mm. Tinh todn n6ng dp IgEcuar cdc mlu xdt nghi^m bdng p h ^ mim TCWIN2. Kit qud dupe bieu diln theo don vj qu6c tl (lU/ml).
2.2. J. Binh lufTttg IgG toon phin:
Dupe Unrc hi?n trSn mdy phin tfch tvr dpng Autolab - BM, Hitachi 704, diing kit ciia hdng Roche. Djnh lupng cdc khdng thI trong 6ng nghifm tien hdnh theo phirong
Tap chl Tai MQi Hpng Vijt Nam - Volume (57-10). N°4 - July, 2012 phdp do do dvc mien djch. Kit qtid dupe
bilu dien theo don vj mg/ml.
2.2.6. Phmmgphip GMCBH:
GMC DH Id phuong phdp dua dj nguyen vdo CO thI ngudi b^nh vdi lilu lupng nhd, thdng dan vd kdo ddi theo duong tiem dudng da nhdm kich thich co thI sinh ra khdng thI bao vdy, Idm thay dli cdch ddp ling cua h? thing mien djch, khdng cho khdng thI dj ling tilp xilc vdi di nguyen gdy b$nh dan din khdng xudt hi$n cdc tri^u chiing di ling.
GMC DH thudng dupe bit diu lilu lupng 0.1 ml di nguyen ndng dd 10 PNU/ml. Vdi VMDU, dyra vdo su nh?iy cam cau ca the, lieu bat ddu cd the cao hon khodng 0.1ml di nguyen lOOPNU/ml. Tifim dudi da theo phuong phdp Ado (bang 1).
Bang 1. Quy trlnh GMC DH theo phu-ong phdp Ado [6]
Thdi gian Thdng ttiii nhat (2 mOi/
tuSn)
Thdng thii 2 (1 mCi/tu^n)
Thdng thii 3 (ImOi/tu^n)
Tuan 1 Tudn2 Tudn3 Tudn4 Tudnl Tudn2 Tudn3 Tudn4 Tudnl Tudn2 Tulin3 Tuan 4 Thdng thii 4 Thdng thii 5-6 (1 mai/2 tudn)
Li^u lupng (ml)
0.1 0.2 03 0.4 0.1 0.2 0.3 0.4 0.1 0.2 0.3 0.4 Nhutrdn Nhutr§n
Ndng dO PNU/ml
10 10 10 10 100 100 100 100 1000 1000 1000 1000 10.000 10.000
Trong nghi6n cuu v6i b|nh nhM VMDU qua phSn tfch thii nghi^m c6 the dp dyng ngay tir d^u mui tigm 0.1 ml n6ng dg 100 PNU/ml. Dinh gid k^t qud diiu trj dyra vdo cdc tieu chuan sau (bdng 2).
Bdng 2: TiSu chuSn ddnh gid Wh qua di^u trj GMC DH.
Miicdd Tidu chudn Tri$u chiing Idm sdng Sii dung thudc Test lay da Test kfch thich Ndng dd IgE
Ndng dO IgG Tdt
Giam
Tdng Khd
Rdt It Rdt It
Giam
Tang Trung
blnh Thinh thodng
±
+ Blnh thudng
Blnh thudng
Kdm
Khdng thay ddi
Khdng thay ddi Khdng thay del
Khdng thay ddi
Ift l
Khdna tiiay doi 3.KET QUA VA BAN L U ^ 3.1. Danh gid sy tiln triln vl \km sdng 3.1.1. Tiitt triin c&a cdc tri$u chung cff ndng
Sau dgt dieu tri bdng phuong phdp GMC DH v6i di nguyfin D. Pteronyssinus todn p h ^ , if cac b|nh nhan da ca nhOng thay doi tich cue ve bilu hi^n Idm sdng.
Tiln triln v8 lam sang dugrc chung toi theo d6i va ddnh gid sau 6 thdng, doi chieu v6i kit qud tnrdc GMC DH. Kit qud thu duoc nhu sau (bdng 3)
Tap chl Tai MQi Hpng Vidt Nam - Volume (57-10). N°4 - July, 2012
Bdng 3. Tidn triin cOa cdc tridu chiing co ndng sau GMC BH
Tri0u chiing
Trifdc di^u trj (n = 40) Sau iJi^u tri (n
= 36) P
Ngiia mGi (thu-dng
xuv6n) 37/40 (92.26%)
24/36 (66,7%)
<0.001
Hit hcl (thudng xuvdn) 36/40 (90.00%)
20/36 (55.6%)
<0.001
Chdy mOi trong tiing can
37/4 (92.25%)
20/36 (65.6%)
<0.001
Ndng rdt trong mDI 24/40 (60.00%)
13/36 (36.1%)
<0.01
21/40 (52.5%)
17/36 (47.2%)
>0.05
Ho, ngiia hpng (thirdng
xuvdn) 26/40 (70.0%)
16/36 (44.4%)
<0.001
Kit qud cho th4y c6 sv thay d6i r5 r$t vl tri^u chilmg ca ndng tru6c vd sau dieu trj. Cdc tri$u chiing ngiia miii, hat hoi, chdy mui va bi€u hi^n n6ng rdt mili, ho ngura hong da gidm r5 rdt cd vl t^ 1§ (P<0.001) va cuong dp ciia tri?u chung. Rieng bieu hi?n ngeit mui da giam nhung chua a muc CO y nghia (p>0.05), co the do qud phdt cuon duoi lau ngay, miic dfi phuc h6i khong dang ke. Da so cdc benh nhan deu trd liri co tien trien tot len ro rft sau dieu tri, khong phai dung thuoc di ling thudng xuyen nhu truac.
3.1J. Tiin triin cua cdc tri$a chung tb^ thi Cac trieu chung thirc the sauy d i i u trj dugc ttid hiSn a bdng 4
Bang 4. Tiln triln cua h1nh dnh khdm thi/c th4 mOi sau di^u trj.
Tri#u chdng Tru-dc di^utrj (n = 40) Sau di^u
tn(n = 36)
P Nigm mac nhiTt nhat 36/40 (90.0%)
19/36 (52.8%)
<0.001 Bong d|ch
nhdy 26/40 (65.0%)
17/36 (47.2%)
<0.01 Phi dai cudn dudi
22/40 (55.0%)
14/36 (38.9%)
<0.p6., Polyp, thodihda nl6m mac cudn 6/40 (16%)
5/36 (13.9%)
• .>0.05,!,
v l khdm th\rc thI sau diiu trj, c6 nhilu b^nh nhdn da c6 thay dbi vl hlnh thdi, mdu sdc niem m^c mui. S^ phii nl, IJT dpng dich nh4y da gidm m^nh. Rigng nhihig tniong hgrp trur6c ddy c6 thodi hoa niem m^c ho$c dang t6n thucmg man tinh nhu PoUp, pM dai cu6n mui du6i thi mu:c gidm khdng nhilu, s\i thay doi chua c6 y nghia th6ng ke (p>0.05). Tren 59% s6 b^nh nhdn din^c hoi khdng c6n phdi ddng thu6c chong di ijtng, VA so b$nh nhan cdn I^i thdy b^nh chua thuyen gidm.
3.2. Tien triln cda test \ky da Bdng 5. Kit qud test 1 ^ da \jvirc vd sau diiu trj-
Ddi tu^ng
Nhdm chdng (n=30) Tru'dc di4u
In (n = 40) Sau diSu tii (n = 36)
P
Ty 1$ duong tinh
0 (0.0%)
27/40 (67.5%)
20/36 (55.6%)
<0.01
Ty 1$ am tinh
30 (100%)
13/40 (32.5%)
16/36 (44.4%)
Dtfdng kinh bansdn
(mm)
5.11 ±1.77
4.35 ±1.38
>0:06 ,-
Tap chl Tai MOi Hpng Vidt Nam - Volume (57-10). N°4 - July, 2012
Ket qud cho th^y ty I? phdn ling ducmg tinh ciia test lay da trudc vd sau di^u trj gidm 11.9%, dudmg kinh ban s4n trung bmh gidm 0.76mm.
Sau diiu hi bdng li$u phdp miln djch, ty 16 test duong tinh gidm di cdn ty 1$ test am tuih tdng Idn cd y nghia th6ng ke (p<0.01). Dudng kinh frun bhih cua ban sin gidm 0.76% (p>0.05).
3.3 Tien trien cAa test kich thfch mfii.
Bdng 6: Kdt qud test kich thich mOi tivdc vd sau didu tn
Odi tupng
Nhdm Chung (n=30) Tnfdc didu
t n ( n = 4 0 )
Sau didu tri (n = 36)
P
Ty Id duong tinh
1/30 (3.3%)
28/40 (70 %)
17/36 (47.2%)
Tf Id am tinh
29/30 (96.7%)
12/40 (30.0%)
19/36 (52.8%)
<0.01
Kdt qud diiu trj bdng lipu phdp miln djch cho thay d cdc b^nh nhdn VMDU ty le test kich thich miii duong tinh gidm cd </
nghia thong ke ( p<0.01).
Qua 2 test in vivo test lay da vd test kich tMch,cd nhjn xet ring chl pham di nguyen D. Pteronyssinus do chiing tdi tdch chilt budc d4u dd cho kit qua diiu tri tich cvtc.
3.4. Thay doi hdm luimg IgE todn ph^n sau diiu tri GMC DH
Chung tdi tiln hdnh dinh lupng IgE todn phin cho 30 ngudi binh thudng vd 40 b^nh nhan VMDU (trudc vd sau khi diiu trj GMC DH). Kit qud thu duoc d bdng 7.
Bdng 7. Kdt qud djnh luong IgE todn phdn trudc vd sau didu trj GMC OH.
Bdl tuong
NhOm chi>ng (n=30) Tnfdc dieu til (n
= 40) Sau di4u
tii(n = 36)
Ham lu^ng thdp
nhdt (lU/ml)
4 6 7
308.4
287.8 Ham luong cao
nhdt (lU/ml)
239.5
1926.3
1441.6 Ham llfOng tnjng binh (lU/ml) 147.8 ± 76.4
1128.1 ± 457.6
863.2 ± 147.5
Qua ket qud a bdng 7 chung toi c6 nhan xet: Ham lupng IgE toan phim ciia nhom b|nh nhdn (truac va sau di6u tri) cao hon so vai nhom chijmg ve gid tri trung binh cjjng nhu gid tri cao nhdt, thIp nhdt. So sanh kit qud dinh lupng IgE todn phdn truoc va sau diiu tri, chung toi nh$n thdy ham luong IgE todn ph4n trung buih trudc diiu trj la 1128.1 ± 457.6 lU/ml, sau diiu tri gidm con 863.2 ± 147.5IU/ml. Sv khdc bi$t ndy c6 -^ nghia th6ng kS (P<0.01). Kit qud nay phii hpp vai s\r thuyen gidm miic dp phdn ling duong tinh cua cdc test invivo.
Tap chl Tai MOi Hpng Vidt Nam - Volume (57-10). N°4 - July, 2012
Mot so tdc gid trong nude nhu Phjm Vdn Thilc, Trjnh M?nh HClng, Vii Vdn Sdn cOng thu dugc nhihig kit qud tuong t\r khi dCmg dj nguydn diiu frj HMC DH cho b$nh nhta di ling [3] [4] [5].
3.5. Thay dli hdm lirrng IgG todn phin sau diiu tri GMC DH.
Song song vdi vi$c djnh Iui?ng IgG todn phin cho cdc b$nh nhta trdn dl tim hilu su thay dli ning dd cua Immunoglobulin ndy trdn cung ngudi b^nh VMDU trudc vd sau diiu tri GMC DH. Ngodi ra, chiing tdi cdn dinh lugmg IgG tota phin cho 30 ngudi binh thudng (nhdm chumg) kit qud duij/c trinh bdy d btag 8.
Bdng 8. Kdt qua djnh iuQ'ng IgG todn phdn tnidc vd sau didu trj GMC QH.
Ooi tuong
Nhdm chdng (n=30) Tnpdcdidu
trl(n=40) Sau didu trj (n = 36)
Hdm luong thdp nhdt
(mg/ml) 8.54
8.92 21.66
Hdm lucmg cao
nhdt (mg/ml)
19.78
22.67 36.53
Hdm luong tmng blnh (mg/ml)
16.69 ±3.17
16.34 ±4.81 27.47 ± 5.20 Qua kit qud d btag 8 chdng tdi cd n h ^ xdt: Ham ludng IgG trung blnh cua b^nh nhta trudc dieu tri vd cau nhihig ngudi binh thudng tuong duong. Hdm lu^ng IgG trung binh cua bfnh nhta sau diiu tri (27.47 ± 5.20mg/ml) cao horn so vdi trudc diiu tri (16.34 ± 4.81mg/ml) vd nhdm
chiing (16.69 ± 3.17 mg/ml) svt ttag cd y nghia thing kd (p<0.01). Kit qud cdu chiing tdi phi hflip vdi nghidn ciiu cua cdc tdc gid khdc [9] [10].
Khtag thI IgG dudc coi Id khtag thI bdo V? thay thI cho khdng thI di ung IgE sau khi diiu tri litag li^u phdp miln dich [11]. Hdm luong IgG, djc bift Id IgGi djc hi^u Id m^t tidu chuin ddnh gid hi$u qud cCia li^u phdp miln dich. Sv ttag kich sinh cdc khtag thI thu^c Idp IgG ndy cd tdc dyng bdo v$ co thI ngta chta khdng cho IgE gta vdo cdc tl bdo Mast vd basophi, do dd khdng gdy ra hi^n tuQng thodt hat cua cdc tl bdo ndy.
Brostoff vd cpng s\r (1993) [10] nhan xdt ring theo thdi gian GMC DH cdc tri|u chung gidm dan,lugng IgG d$c hi|u khdng thI ttag len va lupng IgE d^c hi$u khdng thI gidm di.
Kit qud cua chiing tdi ciing phii hpp vdi nhta xdt cdu cdc tdc gid tren.
Nhu v$y, cdng vdi svr thuydn gidm cdc trifu chiing, s\i gidm miic ddp umg duong tinh cdu cdc test invivo vd S\T biln dli ham lupng IgE vd IgG Id m$t chiing cii khdch quan dl khdng dinh tdc dymg t6t cua phuong phdp GMC DH, qua ddcdtbl ddnh gid h i ^ Iftc cao cua chl phim di nguyen D.
Pteronyssinus do chiing tdi tdch chilt 3.6. Ddnh gid chung kit qui diiu trj GMC DH it bf nh nhdn VMDU.
D\ra vdo btag S miic tieu chuin ddnh gid (theo chrpm 1994) kit hpp giOa tiln triln cdc tri^u chiing lam sdng, cac test
Tap chl Tai MOi Hpng Vidt Nam - Volume (57-10). N°4 - July, 2012
invivo vd invitro, chiing toi cd kit qud sau khi tiln hdnh diiu t4 GMC DH d 36 b?nh nhta viem miii di ling (btag 9).
Bdng 9. Odnh gid mdc dd tidn triln cOa bdnh VMDU sau didu trj GMC SH
Sd bdnh nhdn
%
Miic kdt qud Tdt
6 13.9
Khd
12 33.3
Tmng blnh
14 38.9
Kdm
5 13.9
Tdng cdng
36 100 Kit qud ndy dupe tinh cho 36 ngudi cd dli cdc sd li|u ve lam stag va xdt nghiem.
NIU tinh gpp kit qud tit va khd thi ty 1? dat duptc cua chtag tdi trong diiu hi bdng phuong phdp GMC DH sau 6 thtag la 47.2%, tuong duong vdi ket qua cua cac tdc gid trong va ngodi nuoc [1] [2] [3] [4]
[8] khi dung cdc di nguyen khdc nhau de diiu hi GMC DH VMDU.
4. K 4 T LU.iN
Mdc du mdi tiln hdnh diiu tri 6 thtag nhung phuong phdp ditag di nguyen tdch chilt tir mat byii nhd nudi cay D.
Pteronyssinus dl diiu tri GMC DH cho cdc hdnh nhta VMDU budc diu dd mang lai hieu qud tich cue. Chdng tdi cd mpt s6 ket It^n nhu sau:
+ Cac hi?u chiing lam stag (chu quan vd khdch quan) dIu thuydn gidm rd ret. Su khdc bi^ vl 1dm stag mrdc vd sau didu tri cd i nghia th6ng kd (p<0.01).
+ Ty li ducmg thih vd miic dO duong
tinh cda cd test invivo gidm m^nh. Ddc bif t Id test kich thich mui (p<0.01).
+ Hdm lupng IgE tota phin trung binh gidm tir 1128.1 ± 457.6 lU/ml xuing cdn 863.2 ±147.5IU/ml.
+ Hdm lupng IgG tota phin trung binh ttag td 16.34 ± 4.81mg/ml Idn 27.47 ± 5.20mg/ml.
+ Sau diiu tri, ty id b$nh nhta dgt miic tit vd khd tot la 47.2%.
T A I LIfU THAM KHAO 1. Phan Quang Dota (1995), "ling dyng di
nguydn bui nha trong chta dota vd didu tri ddc hi|u Hen phe quta", Ndi khoa, s6 3, Tr. 22-26.
2. Dota Thi Thanh Ha (2002), "nghien cdu chin dota vd diiu tri mien dich vidm miii di ling do di nguyen bui nha", Luta ta Tiln si Y hpc, Trudng Dai hpc Y Ha Ndi.
3. Trinh M?nh Hung (2000), "Kit qua budc diu trong chta dota vd diiu tri ddc hi^u di ling dudng ho hap do bui nhd, Luta ta Tiln sT Y hpc, Trudng Dai hpcYHaNpi.
4. Vu Vta Sfa (2002),, " nghidn cihi mpt sd ddc dilm cdu bpnh viem mui di ling nghi ngidp do b\ii bdng - len t^ Hdi Phdng", Luta ta Tiln si Yhocj, Hoc vi^n Quta Y.
5. Phgm Vta Thiic, Vti Vta Sdn, Truong Thi An (1999), "Nhihig kit qud budc diu cdu phuong phdp gidm mta cam ddc hipu trong VMDU do b\ii nhd va
Tap chl Tai MQi Hpng VIdt Nam - Volume (57-10). N°4 - July, 2012
biii long vu", bdo cdo Khoa hpc, HOi nghi gitag dgy vd ngidn ciiu miln dich hpc hing nam lin IX, thtag 3/1999.
6. Ado AD (1986), "di ling hpc dji cucmg", ngudi dich: TSKH Nguyin Ntag An, TS Truong Dinh Ki^t, NXB Mir, Moscow, tr. 74-85.
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