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(1)

Y HOC VI^T NAM THANG 4 - SO 2/2012 TAI UEU T H A M KHAO

1. Cao Minh Thanh (2009), "Mpt so dSc diem ve benh ly tai trong 5 n3m tai Khoa Tai Ben vien Tai Mui Hpng Trung u'dng", Tap chf Tai MIJI Hong(A), Hpi Tai Mui Hong Viet Nam, Tr 83-89.

i.. Committee on hearing and Equilibrium (1995), "Committee on Hearing and Equilibrium guidelines for evaluation of results of treatment of conductive hearing loss", Oto'aryngology - Head and Neck Surgery, 113 (3), Pubished by Mosby New Orleans, pp. 186-190.

3 Franklin MR (2004), "Stapeidectomy", Middle Ear and mastoid Surgery, Edit 4"' Thieme Medical Publishers Inc, pp.108-273.

4. Tang RA, et.al (2004), "Gold and Titanium in Oval Window: A Comparision of Two Metal Stapes

Prostheses", Otology & Neurotology, vol 25, Otology & Neurotology Inc, pp.102-105.

Vincent R (2002), "Stapedotomy for Tympanosclerosis Stapes Fixation; Is It and Efficient? A Review of 68 Cases", Otology &

Neurotology, vol 23, Otology & Neurotology Inc, pp.866-872.

Yung M (2006), " Matenals for Osicular chain reconstruction", Middle Ear Surgery, Springer, pp.55-62

Zuur CL et.al (2001), "Retrospective Analysis of Eariy Postoperative Hearing Results Obtained After Stapedotomy With Implatation of a New Titanium Stapes Prosthesis", Otology &

Neurotology, voi 34, Otology & Neurotology Inc, pp.863-867.

SUTDUNG KY THUAT PCR VIRUS TRONG DIEU TRj VA THEO DOI DENH NHAN GHEP THAN D! N H I I M EPSTEIN DARR VIRUS VA POLYOMA DK VIRUS

Nguyen Thj Quy'nh Hu'dng*, Nguyen Thj Y e n *

T 6 M TAT

sy dyng qua lieu cac thuoc yc che mien djch trong dieu tri benh nhi ghep than co the gay hien tuWng nhiem cac virus dSc biet la EBV(Epstein Ban- virus) va BKV(Polyoma BK virus), vims khong co thuoc dieu trj d^c hieu. Oe tai nay dUpc thUc hien nham nghien cutJ sy dyng ky thuat PCR EBV va BKV de dieu chinh thuoc dc die mien dich tren 96 benh nhan ghep than t y 1/1/1998 den 31/12/2005 tai benh vien tre em Touiouse-Phap. Ket qua nghien CLI\J cho thay thdi gian tmng binh nhiem BKV (7 thang) ngan hdn EBV (37 thang). Khi benh nhan bj nhiem EBV, giam hoac dimg anticalcineurine da cho kgt qua PCR EBV(-), chye nang than van on djnh ma khong dy thai ghep cap. Khi benh nhan bi nhiem BKV, giam hoSc dUng anticalcineurine da cho ket qua PCR BKV{-), chye nSng than van on dinh ma khong co thai ghep cap. Tom lai, theo dSi sU xuat hien ciia virus bang PCR la rat can thiet trong ghep thSn 6 tre em. PCR virus cho pheg phat hien sdni vims va giam lieu thudc dc che mien djch co the phong va/ho|c dieu trj khoi benh nhiem virus EBV va BKV ma khong co thai ghep cap.

Tu'k/ioa: Epstein-Barr virus, polyoma BK Virus, ghep than. Polymerase Chain Reaction

SUMMARY

EBV and BK virus PCR monitoring in kidney

* Trudng 0^1 hgc r Ha Aid/

Phan bifn khoa hgc: PGS.TS. Nguyen Phu Oat

transplantation as a guide line of immunosuppressive therapy.

Overuse of immunosuppressive drugs in the treatment of renal transplant patients can cause the phenomenon of viral infection, especially EBV (Epstein Barr virus) and BKV (polyoma BK virus), virus have no specific drug to treat. This research was done to study the EBV and BK virus PCR as guidline to reduce immunosuppressive drugs in 96 children with renal transplantation in Children hospital in Toulouse, France from 01/01/1998 to 31/12/2005. Results showed that the average time of BKV infection (7 months) was shorter than EBV (37 months). When patients with symptomatic or asymptomatic EBV infection, EBV PCR (-) respond very well with stop or reducing of anticalcineurine and have no stable renal ftjnction without acute rejection. When patients with symptomatic BKV infection, BKV PCR (-) respond very well with stop or reducing of anticalcineurine and have no stable renal function without acute rejection.

In conclusion, monitoring of virus PCR is necessary in children renal transplantation. Virus PCR allows early viral detection and allows reducing doses of immunosuppressive dmgs. Immunosuppressive drugs reducing can prevent and/or cure EBV and BKV virus infection without acute rejection.

Keyvmrds: Epstein-Barr vims, polyoma BK Virus, Renal transplantation. Polymerase Cham Reaction.

(2)

Y HQC VIET NAM THANG 4 - S6 2/2012

I,

OAT VAN OE

Benh nhan ghep than khi bj n h l l m Epstein- Barr virus (EBV) hoSc BK Virus (BKV). EBV c6n goi la herpesvirus 4 fl ngu'di, no cfl t h i gay nhiem triing bach cau dfln nhan, gay ung t h y aac biet la U lympho Hodgltln co the gay de doa cuoc song benh nhan [ 1 ] . Khoang du^fll 5% trfl dyflc ghep than bj nhiem EBV [ I J . BK virus (BKV) thupc gia dinh polyomavlrus, nfl it gay b?nh vei 80% dan so cfl virus nay fl dang khong hoat dpng[4]. Khi benh nhan ghflp than bl nhiem BKV c6 the gay viem than do BKV va cfl nguy cd rat cao gay mat qua than ghep. Khi tre bi ghep than tre phai dung thuoc u'c che mien d|ch nen EBV va BKV se nhan cd hoi nay trfl thanh dang hoat dong va gay benh n5ng tham chi cfl the gay mat qua than ghep' [ 1 , 2, 4 ] . iilen tai dieu tri chong thai ghep van cfln la dieu tri theo kinh nghiem, sir diing qua nhieu thuoc thai ghep se gay hien tu'dng tang sinh virus nay tren ngu'di benh. Tir nam 1998, tai benh vien tre em fl Touiouse-Phap da dua PCR EBV va s i w vao xet nghiem thu'dng quy. PCR cho phep phat hien sflm cac virus nay.

Chinh vi vay de tai nay du'dc tien hanh nhSm:

Nghien cuh s&dung PCR EBV va BK vims dedlSu chinh thuoc (tc che mien djch d tre em ghep than bi nhiem EBV va/hoac BK virus.

II. 0 6 l TU«?NG VA PHLfONG P H A P NGHIEN COU 1. Ooi tu'dng nghien cihj:

Gom 12 trong 96 benh nhi ghep than tir 1/1/1998 den 31/12/2005 tai benh vien tre em Touiouse-Phap.

Tieu chuan chon benh nhan: Tat ca cac benh nhi ghep than co PCR EBV du'dng tinh v^/hoac PCR BKV du'dng tinh.

2. Phifdngphip nghien cvfu:

Phu'dng phap nghien cu'u mo ta hoi CIJTJ vfli c9 mau thuan ldi.

Cac chi so nghien ciTu:

Tuo'l, gidi, ngu'di cho than (chet, song).

Cac thuoc ire che mien djch sir dung ban dau ngay truflc ghep than.

- Thdi gian bat dau bl nhiem virus, this gian PCR virus am tinh

- PCR mau tim nhiem EBV. PCR mau va nu'dc tieu de tim BK virus

PCR EBV va BKV chung toi dung phu'dng phap LightCycler Polymerase Chain Reaction (PCR). DNA cua virus dUflc tach ra bdi MagNA Pure automated instrument (Roche Applied Science) tir mau toan phan. Khuyech dai diroc phat hien bSng huynh quang (fluorescence resonance energy transfer). Ket qua du'dng b'nii khi > 250 copies/ml.

- Creatinin mau iam theo phu'dng phap Jaffeklnetic (khong khCr tap) dUdc do tren may Olympus AU 400.

- Liieu thuoc u'c che mien djch du'dc t'nh theo mg/kg/ngay

- EBV lymphoma duWc chan doan khi; gan, lach hach to, tach rau mau tang cao, lympho tang.

Ttiai ghep cap: sot, dau qua than g l i ^ , than ghep to, doi khi benh nhan khong cfl trieu chirng iam sang nhuTig creatinin mau tang cao 25%

so vdi mire creatinin mau binh thudng so vdi tuoi.

Viem than do BK virus: protein nieu du'dng tinh > 0,5 g / l , hong cau (tren +), creatinin mau tang cao, PCR BK du'dng tinh.

Viem bang quang: cfl dau hieu rui loan tieu tien, hong cau nieu ( + ) , bach cau nieu (+), decoy cell ( + ) trong nu'dc tieu, PCR BK virus trong nu'dc tieu (-»•).

3. Xifly sSlliu va phin tich so lieu - Sir dung phan mem thong ke y hpc SPSS vdi tinh cac gia trj trung binh, tinh cac ti le %, so sanh cac ti le giita cac nhom bSng test Rsher exact k i l m dinh 2 phia p < 0.05 du'dc xem la c6 y nghTa thong ke.

III. KET Q u A NGHIEN CCU

Trong 96 benh nhi ghep than tir 1/1/1998 den 31/12/2005 tai benh vien tre em Touiouse-Phap chiing toi gSp 12 benh nhan (BN j bi nhiem EBV va BKV. Trong so 12 BN nay cfl 9 BN bj nhiem EBV va 5 BN b| nhiem BKV, trong dfl cfl 2 BN vira bj nhiem EBV va BKV.

Benh nhan ( n = 1 2 ) Tuoi trung binh Gidi Ngu'di cho

Dieu tri thudc mien dich ban dau

*Khanq the (12)

Ckc thonq sff nqhiin citu

13,2 + 9,6 tuoi (tuoi nho nhat; 3 tuoi; I6n nhat: 23 tuoi).

Nam/nu" =3 (Nam 9 benh nhan; nCr" 3 benh nhan) 11 nqu'di dio c h ^ , 1 nqu'di cho sonq OKTS: 2 benh nhan ; antithymocyte : 10 benh nhan

(3)

Y HQC VigT NAM THANG 4 - SO 2/2012

*Anticalcineurlne (12)

•Sterolde (12)

*Antimetabolite (12)

Thcfigian phat hi^ nhiem vims (thing):

•EBV

•BKV

EBV tru'dc ghep(n=9) igG (+) igG (-) BKV trwdc ghep(n~5)

IgG (+) IgG (-)

Prograf: 6 benh nhan ; cyciosponn A : 6 benh nhan Steroids: 12 b?nh nhan

AZA: 10 benh nhanj MMF: 2 benh nhan 1-132 thang {30,8 + 7thang) 1-132 thang (37 ± 8 thang) 4-11 thanq {7 + 7 thanq)

2 benh nhan vira nhiem EBV VLft nhiem BKV 3 benh nhan

6 benh nhan 2 benh nhan 3 benh nhan

WAan Afet Tuoi trung binh cua benh nhan ghep than bi nhiem EBV va BKV thu'dng Idn: 13,2 + 9,6 tuoi, tuo'l gap nhfl nhat la 3 tu6"i. Cac thuoc mien djch ban dau tre diing deu co steroide, anbcalcineurine va antimetabolite. Thdi gian trung binh nhllm BKV (7 thang) ngan hdn EBV (37 thang).

Bang 2 : Cac thonq so tren benh nhan nhiem EBV T r i | u chulig lam

sang ( n = 9 ) U lympho B do EBV (2BN) Thai ghep cap (IBN) Mononucleosis (IBN) Khong trieu chiihg (5BN)

Lfeu thuoc I S * thich h^(p

Duhg CsA, MMF

Rituximab + t3ng steroid + zelitrex Dimg FK va AZA,

Si^dung MMF+Steroid Dimg FK va AZA, SLT dunq MMF+ t§nq Steroid Giam FK va (AZA hoSc MMF), gii?

nguyen steroid

PCR VR sau IS

(-) sau do (+) thoang qua ( - ) s a u d 6 ( + ) thoang qua (-) sau do (-F) thoanq qua 2BN (+) lau dai;

3BN (-) sau do 2BN (-I-) thoang qua,lBN (-).

Great, p m o l / l

on dinh (120, 147) on dinh (82) on djnh (81) on dinh (tir 69 den 130)

Theo doi 5 n3m va 8nam 6 n3m 7 nSm 5 thang den 5,5 nam

* IS: Thuoc CTC che mien dich.

(**) th6i gian theo do! trung binh la 4,2 ± 4,7 nam.

Nh$nxet:Mii\ thdi gian theo doi trung binh 4 nam, chung toi thay:

Khi BN bj nhiem EBV co trieu chiihg, PCR EBV (-) dap iJng rat tot vdi duTng anticalcineurine va giup chu'c nang than on dinh kem theo khong co thai ghep cap.

Khi BN bi nhiem EBV khong co trieu chuhg thi giam lieu anticalcineurine cung giup cho chu'c nang than on djnh va khong gay thai ghep cap.

Bang 3: Cac thonq so tren benh nhan nhiem BKV Tri^u chu'ng lam

sang (n=5) Viem bang quang (IBN) Viem than (3 BN)

Khong trieu chuhg (IBN) (PCR mau va nudc tieu(+), decoy cellsU.

Lieu thuoc I S thich h0p

Giam FK va MMF, giu- nguyen steroid 2BN: giam FK va/hoac MMF, IBM diihg FK, MMF va diing Leflunomide Giam CsA/FK va MMF, giff nguyen steroid

PCR VR sau IS

(-)

1 BN ( + ) iau dai, 2 BN (-)

(-)

Creat. ^ m o l / l on dmh (196) 1 BN bl benh thai ghep man (300),

2 BN khac on djnh (139,116) BN bl benh thai ghep man nhuhg creatinin on dinh (161)

Theo doi 5 thang 8 thang den 4,5 nam 4 nam

Nhan x4t: Khi BN bj nhiem BKV co trieu chiihg, PCR EBV (-) dap utig rat tot vdi giam lieu anticalcineurine va giup chCrc nang than on djnh kem theo khong cd thai ghep cap.

(4)

Y H 9 C V I $ T N A M T H A N G 4 - S 6 2/2012

Bang 4 : Lieu thuoc ire che mien dich dieu chinh khi PCR EBV va/hoac BKV(+) Thuoc

Steroid Anticalclneurin (FK) Anticalcineurin (CsA) Lieu MI^F

Lieu ichi bSt d^u nhi^m virus (mq/kq/nq4v) 0,29 + 0,M 0,10 + 0,03 2,6 + 0,06 26 + 6,4

Lieu khi PCR virus (-) (mg/kq/nqay) 0,17 + 0,08 0,03 + 0,03 0,09 + 0,02 M,2 + 6,56

f^han xet: Hau nhu' c^c thufic deu phai glcim khoang gan mpt nira lieu so vdi lieu khi bSt dau phat hien virus, D5c biet thudc nhdm anticalclneurin phai giam tdl lieu chi con khoang 1/3 lieu khi bat dau phat hl?n virus.

IV. BAN LUAN

Tuoi trung binh ciia tre ghep thSn bl nhiem EBV va BKV la 13,2 ± 9,6 tuoi, Idn hdn nghiSn cu'u cua Sato T, Fujieda M [7] la 7,8 tuoi cd le do nghien cihj cua chung toi gop chung ca nhiem EBV va BKV trong khi nghien culi cua Sato T. chi tinh rieng cho tre bi nhiem EBV [ 7 ] . Tuoi nhd nhat d day chung toi g3p la 3 tuoi cho thay tien bp trong ghep than d tre em da cd the vu'dn tdi nhuhg tre con kha nho.

Thdi gian nhiem BKV (7 thang) ngan hdn hSn EBV (37 thang). Tuy nhien cd nhiJng benh nhan cua chung tdl xuat hien nhiem EBV ngay tu" thang thd 1 sau ghep. Nghien culi cua chung toi cung phu hdp vdi nghien culi cua Ishihara M, Tanaka E [3]. Thdi gian nhiem BKV sdm nhat chiing toi phat hien duHc la 4 thang sau ghep than.

Vdi thdi gian theo doi trung binh 4 nam, chiing toi thay khi 2 benh nhan bj nhiem EBV bj phat thanh U lympho B do EBV, mot benh nguy hiem cd the gay anh hu'dng tdi cugc song ciia benh nhan, thi ca 2 benh nhan nay da cd PCR EBV (-) dap iirng rat tot vdi viec dCfng thuoc u'c che mien djch anticalcineurine va cac benh nhan nay da cd ehii'c nang than dn djnh kem theo khong cd thai ghep cap. Khi benh nhan ghep than bj nhiem EBV khong cd trieu chii'ng thi giam lieu anticalcineurine cung giiip cho chu'c n3ng than on djnh va khdng gay thai ghep cap.Dleu nay cung 6a du'dc nhdm chuyen gia ghep than chau Au khuyen cao trong Nephrol Dial Transplant ve viec phong va dieu trj U lympho B do EBV sau ghep than [ 1 ] . D3c biet chung toi gap 1 benh nhan bj thai ghep cap do EBV, chiing tdl lap tdc difng anticalcineurine va Azathioprin, chi duy tri moi thuoc Steroid ket qua la benh nhan het thai ghep cap sau theo doi 6 nam benh nhan van cd ehii'c nang than on djnh va khong he bj thai ghep man tmh.

Khi benh nhan bi nhiem BKV co trieu chii'ng, PCR EBV (-) dap d'ng rat tot vdi giam lieu 34

anticalcineurine va giiip ehii'c n§ng than on dinh kem theo khdng cd thai ghep cap. Chiing tdi gap 3 benh nhan bj viem than do BKV, mot tien lu'dng rat xau cho qua than ghep, tham chi cd the gay mat quci than ghep nhu'ng chiing toi da giam lieu va dirng prograf va MMF, ket qua cho thay 2 benh nhan cua chung tdi da cd ehii'c nang than on djnh vdl creatinin mau la 139 Mmol/l va 116 Mmol/l, con mot benh nhan do ton thu'dng than qua nSng nen da b| thai ghep man tuy nhien hien nay nong dp creatinin mau van on djnh d miic 300 Mmol/l sau 8 thang theo doi. Dac biet mot benh nhan khong thay cd trieu chiihg tren lam sang nhuhg PCR BKV trong mau va nu'dc beu du'dng ttnh, trong nu'dc tieu cd Decoy Cell, benh nhan nay da du'dc giam liieu anticalcineurin va MMF, 010" nguyen liieu steroid nhu'ng benh nhan nay van bj thai ghep man vdi c h i i t nang than hien van on djnh vdi creatinin mau 161 Mmol/l sau 4 nam theo doi.

Khi benh nhan bj nhiem EBV va/ hoac BKV hau nhu" cac thuoc ifc che mien dich dang dieu trj deu phai giam khoang gan mot nda lieu so vdi lieu khi bSt dau phat hien virus. Oac biet thuoc nhdm anticalcineurin phai giam tdi lieu chi con khoang 1/3 lieu khi b k dau phat hien vinjs mdi cd the dat du'dc ket qua tot. Dieu nay cung phiJ hdp vdi cac nghien ciili khac [5,6].

V. KET LUJSiN

Theo doi su* xuat hien ciia virus b§ng PCR la rat can thiet trong ghep than d tre em.

PCR virus cho phep phat hien sdm virus va cho phep giam lieu thudc u'c che mien djch do si/

nhan Ien cua EBV va BKV cd the la bang chiing ciia sd thda thudc u'c che m i l n djch.

Giam lieu thuoc u'c che mien djch cd the phdng va/hoac dieu tri khdi benh nhiem virus EBV va BKV ma khong cd thai ghep cap.

(5)

Y HQC VIET NAM THANG 4 - SO 2/2012 TAI UEU T H A M KHAO

1. EBPG Expert Group on Renal Transplantation (2002). "European best practice guidelines for renal transplantation.

Section IV: Long-term management of the transplant recipient. IV.6.1. Cancer risk after renal

transplantation. Post-transplant lymphoproliferative disease (PTLD): prevention

and treatment". Nephrol Dial Transplant. Vol 17 SuppI 4:31-3, 35-36.

2. Gupta G, Shapiro R, Thai N, Randhavi/a PS, Vats A.(2006) "Transplantation". Vol 15;82(3):382-388.

3 Ishihara M, Tanaka E, Sato T et al. (2011}

"Epstein-Ban- vinjs load ibr early detection of lymphopnaiiferative disorder in pediatrK renal transplant recipients". Oin Nephrol. Vol 76(1):4CM8.

Koleilat I , Kushnir L, Gallichio M, Conti DJ.(2011) "Initiation of a screening protocol for polyoma virus results in a decreased rate of opportunistic non-BK viral disease after renal transplantation". Transpl Infect Dis. Vol 13(l):l-8.

Maeda E, Akahane M, Kiryu S, et al. (2009).

"Spectrum of Epstein-Barr virus-related diseases:

a pictorial review". Jpn J Radiol Vol 27 (1): 4-19.

Quinlan SC, Pfeiffer RM, Morton LM, Engels EA. (2011) "Risk factors for early-onset and late- onset post-transplant lymphoproliferative disorder in kidney recipients in the United States". Am J Hematol. Vol 86(2):206-209.

Sato T, Fujieda M, Tanaka E et al.(2008)

"Monitoring of Epstein-Sarr virus load and antibody in pediatric renal transplant patients"

Pediatr Int. Vol 50(4):454-458.

TANG COftNG KHA NANG CHONG XOAY CHO CHUM DINH NOI TUY CO DjNH GAY THAN XlTONG CANG TAY

N g u y i n D a c NghTa*, N g u y i n DiJc B i n h * T 6 M TAT

Cfng dung ky thuat ghim chCim dinh kin noi tCiy trong d i l u tii gay than xUdng cJing tay, cac tac gia da cai tiSn each ghim chan dinh vao dau di/di xiTong quay v^ dau tren xUOng tru de tang cu'dng kha nSng chong xoay. 39 trudng hop gay than xUdng quay, xuong tnj hoac ca hai xUong da duac nghien cifu dl^u trj trong mgt thi!f nghiem 13m sang dat ket qua nan chinh giai p h i u rat tot 37,-tot 1, trung binh 1, 22 trudng hdp theo doi xa (3 thang - 1 2 thang) deu lien xuong dung thdi han. dat ket qua phuc hoi chifc nSng tot va rat tot 100%. 8 trudng hpp da rut dmh, theo doi chUa thay c6 bien chiJfng gay lai.

SUMMARY

Strengthening rotational instability control of multiple flexible intramedullary nails in fixation

of ulna and radius shaft fractures When applying multiple flexible intramedullary nailing technic for treatment of ulna and radius shaft fractures, the authors have improved on the fixation of the end of nails by stapling it into the distal radius and proximal ulna In order to strengthen the rotational instability control. 39 cases of radius or ulna or both bones fractures were treated in a clinical trial and the excellent anatomic reduction

* Benh viin Xanh Pon

was obtained in 37 cases, good in 1 case and medium in 1 case. 22 cases have been followed up longer (3 months -12 months) showed bone healing in time; excellent and good fonctional outcome obtained in 100%. 8 cases undergone nail removal without iterative fracture.

I.

OAT VA'N

o f

Van de khd nhat trong cd dinh gay than XLfdng ciing tay la chdng di Idch xoay. Chifc nang sap - ngCfa cling tay se bj han che nhieu n^u true XLfdng bi lech dii chi chiit it so vdi giai phau sinh ly. Vi vay, cho d^n hien nay, k^t xu'dng nep vit vin di/dc coi Id ky thuat chuan;

mac du chiing ta biet cd khdng it bien chi^g

do mo md '''^' .Dl phat huy cac dilm manh cOa

k j thuat ket xu'dng it xam hai (Minimally

Invasive Internal Fixation) ma van bao dam

chdng xoay dUdc - dinh ndi tCiy cd chdt

Foresight da dUdc Crenshaw va Staton thii

nghidm ISm sdng cho 37 tordng hdp vdi k^t

qua lien xUdng 100%. Tuy nhien cac tac gia

cho biet nhieu loi ky thuat d l xay ra: dng tiiy

khdng ddng deu nen chi ddng difdc dinh qua

ngin, khdng chdt du'dc, doa dng tCiy r^t khd, de

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