KHO ST INTERLEUKINE-6, INTERLEUKINE-8, V TNF- TRONG TIấN ON SM NNG VIấM TY CP BS.CKII Ngụ Dng Cng, ThS.BS Cao Tn Phc, BS V Th Minh Phng TểM TT Viờm tu cp (VTC) nng cú t l t vong cao so vi VTC nh Song song vi tỡm nguyờn nhõn, chn oỏn sm VTC nng l quan trng cú chin lc iu tr sm, tớch cc giỳp ci thin t l t vong Giỏ tr ca nhng cytokines (Interleukin [IL]-6, IL-8, v TNF-alpha) cú nhiu hn v ó c nghiờn cu Nghiờn cu tin cu 47 bnh nhõn VTC vi phỏt au bng trc 48 gi thi im nhp vin Tiờu chun ca Atlanta 1992 c s dng phõn bit VTC nng v nh Nhúm chng gm 47 ngi tỡnh nguyn o nng IL-6, IL-8, TNF-alpha, v CRP thi im nhp vin S dng ng cong ROC v din tớch di ng cong (AUC) c tớnh toỏn cho mi cht CRP, IL-6, IL-8 v TNF-alpha phõn bit gia hai nhúm VTC nng v nh S dng phn mm Stata 8.0 s lý thng kờ, v p < 0,05 xỏc nh ý ngha Cú s khỏc bit cú ý ngha ca IL-6, IL-8 v TNF-alpha gia nhúm chng v nhúm VTC (p < 0,001), cng nh ca IL-6, IL-8, v TNF-alpha gia hai nhúm VTC nng v nh (p = 0,0026, p = 0,0017, p = 0,001) (theo th t) Khụng cú s khỏc bit ý ngha ca CRP gia hai nhúm VTC nng v nh (p = 0,381, p >0,05) Giaự tr ca AUC ca IL-6 cao nht (AUC= 0,961), v gim dn theo th t: IL-8 (AUC=0,767), TNF-alpha (AUC = 0,49) IL-6, IL-8, v TNF-alpha cú th c s dng c lp phõn bit sm VTC nng v nh T VN - Viờm tu cp (VTC) l quỏ trỡnh viờm cp tớnh ca tuyn tu c chn oỏn ch yu bng au bng cp v s gia tng ng thi Amylase v Lipase huyt (tng gp ln gii hn trờn) [3], [12], [37], [45], [46], [66] Nguyờn nhõn thng gp l si ng mt v ru [23], [37], [45] - VTC nng (xut huyt, hoi t) vi nhng bin chng ti ch (hoi t, nang gi tu, ỏp xe) v nhng bin chng h thng (hi chng nguy ngp hụ hp cp, sc, ụng mỏu ni mch lan to ) vi t l t vong 15-25% [3], [23], [41], [62], [67] - Vn tiờn oỏn nng ca bnh l rt quan trng giỳp hng dn iu tr v d phũng ri lon chc nng a c quan v bin chng ti ch Thang im Ranson, Glasgow, v APACHE ó c s dng [15], [23], [45] Tuy nhiờn, cỏc h thng ny cú nhiu thụng s v cn 48 gi sau nhp vin mi ỏnh giỏ mt cỏch y [11] CT scan ca Balthazar cú giỏ tr cao v cú th thc hin bt c thi im no nhng cú hn ch l khụng ỏnh giỏ c cỏc bin chng h thng v cú tỏc dng ph d ng ca cht cn quang cng nh khỏ t [15], [30], [51], [62] - Giỏ tr ca nhng cytokines (Interleukin [IL]-6, IL-8, v TNF-alpha) cú nhiu hn v ó c nghiờn cu - Vit Nam, hin ti cha cú h thng tiờn lng VTC nng ti phũng cp cu, ú chỳng tụi mun tin hnh kho sỏt nng TNF-, IL-6 v IL-8 huyt bnh nhõn VTC vi mong mun l tiờn oỏn sm nng ca VTC Trang 21 Mc tiờu tng quỏt: Kho sỏt mi liờn quan gia nng TNF-, IL-6 v IL-8 vi nng ca VTC Mc tiờu chuyờn bit: - Kho sỏt mi liờn quan gia nng TNF-, IL-6 v IL-8 vi VTC nng vũng 48 gi u t khi phỏt au bng, thi im nhp vin - So sỏnh giỏ tr ca TNF-, IL-6, IL-8 vi CRP I TNG V PHNG PHP NGHIấN CU: 1.1 i tng nghiờn cu: 47 bnh nhõn au bng cp trc 48 gi n khỏm v nhp vin ti khoa Cp cu tng hp BVCC Trng Vng t thỏng nm 2007 n thỏng nm 2008 c chn oỏn VTC * Tiờu chun chn oỏn viờm tu cp: - au bng cp, kốm ma - Kốm amylase mỏu tng gp ln gii hn trờn bỡnh thng (bỡnh thng 23-125 U/L) hoc cú dch bng, dch mng phi - ng thi Lipase mỏu tng gp ln gii hn trờn (bỡnh thng < 190 U/L) - Hoc hỡnh nh VTC trờn siờu õm bng, CT scan hoc qua phu thut (i th v vi th) * Tiờu chun loi tr: - Nhim trựng phi, nhim trựng tiu Nhi mỏu c tim Suy thn mn tớnh Viờm gan siờu vi 1.2 Phng phỏp nghiờn cu: 1.2.1 Loi hỡnh nghiờn cu: Mụ t ct ngang 1.2.2 Phng phỏp tin hnh: * Bc 1: - Tt c i tng nghiờn cu u c khỏm lõm sng v khai thỏc k tin s nht l bnh lý v gan, thn, tu mn tớnh, nghin ru - Tin hnh xột nghim: Huyt , amylase mỏu v niu, amylase dch mng phi, dch mng bng (nu cú), lipase mỏu, ion mỏu, urờ, creatinine mỏu, ng huyt, LDH, SGOT, SGPT, bilirubine mỏu, khớ mỏu ng mch, ECG, X quang ngc, xột nghim ụng mỏu: TP, TCA, fibrinogen v D-dimer, tng phõn tớch nc tiu, HBsAg, HCV - Xột nghim IL-6, IL-8, TNF-, CRP lỳc nhp vin ti khoa cp cu tng hp Mu mỏu 2mL mỏu ụng (xột nghim IL-6, IL-8, TNF-) c d tr nhit 200 C, c phõn tớch bng phng phỏp dn tri vi mch sinh hc phỏt hoỏ quang t ng (fully automated chemiluminescent biochip array) CRP thc hin bng mỏy HITACHI 717 vi nhy 0,07 mg/L IL-6, IL-8, TNF- thc hin bng phng phỏp Biochip array vi mỏy phõn tớch vi mch sinh hc phỏt hoỏ quang t Trang 22 ng (fully automated chemiluminescent biochip analyzer), mỏy Evidenceđ, hóng RANDOX ca nc Anh; mu mỏu ụng (2mL) vi nhy 0,2pg/ mL i vi IL6 v 0- 1,5 pg/ mL i vi IL-8; nhy l 0,6 pg/ mL i vi TNF- - Siờu õm bng giỳp tỡm nguyờn nhõn ca viờm tu cp l si ng mt CT scan bng (khụng cn quang hoc cú cn quang) nghi ng chn oỏn viờm tu qua siờu õm v tỡm bin chng ti ch ca viờm tu cp * Bc 2: Phõn loi cỏc i tng nghiờn cu lm nhúm: VTC nng v VTC nh da vo tiờu chun phõn loi Atlanta 1992 Nhúm chng thu thp t nghiờn cu ca Phan Th Danh vi 47 ngi tỡnh nguyn khe mnh [1] * Bc 3: So sỏnh mi tng quan v nng ca IL-6, IL-8, TNF- v CRP gia hai nhúm VTC nng v nh cng nh vi nhúm chng qua phõn tớch s liu bng Mann-Whitney U test vi phn mm thng kờ Stata 8.0 1.2.3 Mt s tiờu chun s dng nghiờn cu: Thang im RANSON: Lỳc nhp vin - Tui > 55 - Bch cu > 16.000/mm - LDH > 350 UI/ L - Glucose mỏu > 200mg% - AST > 250 UI/ L Trong vũng 48 gi - Hct gim > 10% - Urờ mỏu tng > 5mg/ dL - Canci mỏu < 8mg/ dL ( 4mEq/l - S t dch > lớt Tiờu chun Atlanta v VTC nng: 01 nhng tiờu chun sau[69]: (1) Suy c quan: cú mt nhng biu hin sau: - Huyt ỏp tõm thu < 90mmHg - p sut phn oxy mỏu ng mch: PaO2 60mmHg - Creatinine mỏu > 2mg% (176,8àM/L) sau bự dch - Xut huyt tiờu hoỏ > 500ml 24 gi (2) Bin chng ti ch: - Hoi t - p xe - Nang gi tu (3) Tiờu chun Ranson 1.2.3 X lý v phõn tớch s liu: S dng phn mm Stata 8.0 x lý v phõn tớch s liu * S dng phng phỏp phõn tớch Mann-Whitney U test so sỏnh nng ca mi IL-6, IL-8, v TNF- gia nhúm VTC nng v nhúm VTC nh, gia nhúm VTC v nhúm chng So sỏnh nng ca CRP gia hai nhúm VTC nng v nh * S dng ng cong ROC (Receiver Operating characteristic curves) v din tớch di ng cong (AUC: Area under the curves) ca CRP, IL-6, IL-8, Trang 23 TNF- so sỏnh giỏ tr chn oỏn phõn bit gia hai nhúm VTC nng v nh Tớnh nhy, c hiu v chớnh xỏc cho mi cht CRP, IL-6, IL-8, TNF- KT QU: 47 BN (34 nam v 13 n; tui trung bỡnh l 47 18,1; tui nh nht l 24, tui cao nht l 85) S bnh nhõn VTC nh 30/47 (chim 63,8%) s ú 13 VTC ru, VTC si, v 10 VTC cha rừ nguyờn nhõn S bnh nhõn VTC nng 17/47 (chim 36,2%) s ú VTC ru, VTC si, VTC tng triglyceride (nng 2553mg/L), v 5VTC cha rừ nguyờn nhõn Bng 2.1 Nng huyt ca Cytokines nhúm chng, VTC nh, VTC nng Nhúm Viờm tu cp nng (N= 17) p: so vi nhúm viờm tu cp nh Viờm tu cp nh (N= 30) **Nhúm chng (N=47) p: so vi nhúm viờm tu cp v nhúm chng TNF- (pg/mL) 13,7 (7,6-19,5) 0,0026 IL-8 (pg/mL) 676,74 (182,52-2249,52)* 0,0017 IL-6 (pg/mL) 380 (316,84-700) < 0,001 5,35 (2,39-9,61) 4,85 3,05 122,15 (61,63-355,42) 49,60 54,90 30,48 (7,86-63,69) 0,29 0,47 < 0,001 < 0,001 < 0,001 * Kt qu ca nng IL-6, IL-8, v TNF- c trỡnh by l trung v (medians) v khong t phõn v (interquartile ranges) **Nhúm chng: Thu thp s liu t nghiờn cu ca Phan Th Danh thc hin trờn ngi tỡnh nguyn kho mnh [1] Bng 2.2 Nng CRP huyt theo nhúm viờm tu Nhúm Nng (mg/L) Viờm tu cp nng (N = 17) Viờm tu cp nh (N = 30) 53 (11,6 - 110)* 25,5 (6,57 - 88,37) p 0,381 * Kt qu ca nng CRP c trỡnh by l trung v v khong t phõn v Trang 24 ng cong ROC (AUC=0,49) 0.4 O 0.0 0.2 sensitivity nhy 0.6 0.8 1.0 Duong cong ROC (AUC=0.49) 0.0 0.2 0.4 0.6 0.8 1.0 1-specificity 1- c hiu Din tớch di ng cong (AUC) = 0,49 Biu 2.1 ng cong ROC phõn bit VTC nng v nh theo CRP ng cong ROC (AUC=0,961) 1.0 Duong cong ROC (AUC=0.961) 0.6 0.4 0.0 0.2 nhy sensitivity 0.8 O 0.0 0.2 0.4 0.6 0.8 1.0 1-specificity 1- c hiu Din tớch di ng cong (AUC) = 0,961 Biu 2.2 ng cong ROC phõn bit VTC nng v nh theo IL-6 Trang 25 sensitivity 0.6 0.8 1.0 ng cong ROC (AUC=0,767) Duong cong ROC (AUC=0.767) 0.4 nhy 0.0 0.2 O 0.0 0.2 0.4 0.6 0.8 1.0 1- c hiu 1-specificity Din tớch di ng cong (AUC) = 0,767 Biu 2.3 ng cong ROC phõn bit VTC nng v nh theo IL-8 ng cong ROC (AUC=0.725) 0.8 1.0 Duong cong ROC (AUC=0.725) 0.4 0.6 O 0.0 0.2 sensitivity nhy 0.0 0.2 0.4 0.6 0.8 1.0 1- c hiu 1-specificity Din tớch di ng cong (AUC) = 0,725 Biu 2.4 ng cong ROC phõn bit VTC nng v nh theo TNF- Trang 26 @ Nhn xột: AUC ca IL-6, IL-8, TNF-alpha, v CRP gim dn theo th t: 0,961 ; 0,767 ; 0,725 ; 0,49 Bng 2.3 nhy, c hiu, v chớnh xỏc ca IL-6, IL-8, TNFalpha, v CRP tiờn oỏn nng ca VTC Ngng giỏ tr (pg/mL) CRP 165,12 IL-6 202,47 IL-8 989,02 TNF- 20,04 nhy (%) c hiu (%) chớnh xỏc (%) PPV (%) NPV (%) 52,94 66,66 61,7 47,36 71,42 100 96,66 97,87 94,44 100 35,29 96,66 74,46 85,71 72,50 64,70 73,33 70,21 57,89 78,57 * PPV (Positive predictive value): Giỏ tr tiờn oỏn dng tớnh NPV (Negative predictive value): Giỏ tr tiờn oỏn õm tớnh BN LUN: 3.1 Nhn nh chung: Nghiờn cu ca chỳng tụi bao gm 47 bnh nhõn (30 VTC nh, 17 VTC nng) ó chng t: S tng cao cú ý ngha ca IL-6, IL-8, TNF- nhúm bnh nhõn VTC nng so sỏnh vi nhúm bnh nhõn VTC nh: IL-6 (p < 0,001), IL-8 (p = 0,0017), TNF- (p = 0,0026) (bng 2.1) Khụng cú s khỏc bit ca CRP gia hai nhúm VTC nng v VTC nh (p = 0,381) (bng 2.2) ng thi cho thy IL-6, IL-8, v TNF- cú giỏ tr tiờn oỏn nng hn CRP thi im nhp vin vũng 48 gi sau khi phỏt triu chng ú IL-6 l cú giỏ tr nht (vi nhy l 100%, c hiu l 96,66%, ngng giỏ tr l 202,47 pg/mL; cng nh AUC ca IL-6, IL-8, TNF- v CRP ln lt l 0,961, 0,767, 0,725 v 0,49) (Biu 2.1, 2.2, 2.3, 2.4) Tng t vi PPV, NPV cng gin dn theo th t i vi IL-6, IL-8, TNF-alpha, v CRP (bng 2.3) Nghiờn cu ca chỳng tụi mt ln na xỏc nh kt qu ca nhng nghiờn cu trc õy l nhng cytokines ny (IL-6, IL-8 v TNF- cú th c s dng phõn bit VTC nng vi VTC nh [8], [24], [41], [56]. 3.2 í ngha ca cỏc Cytokines tiờn oỏn nng ca bnh: 3.2.1 IL-6: Nghiờn cu ca chỳng tụi (30 VTC nh v 17 VTC nng), cú s gia tng cú ý ngha nng huyt ca IL-6 VTC nng so vi VTC nh (p < 0,001) (bng 2.1) Kt qu ny phự hp vi nhng nghiờn cu trc õy [8], [20], [21], [24], [27], [41], [53], [54], [56], [59] Ngoi vi ngng giỏ tr 202,47pg/mL thỡ nhy l 100% (17/17) v c hiu l 96,66% (29/30) T ú cú th kt lun: IL-6 l du n sinh hc cho nng ca VTC giai on sm Trang 27 Bng 3.4 Bng so sỏnh cỏc kt qu nghiờn cu i vi IL-6 Nghiờn cu Heath Pezzilli Gurleyik Jiang Chỳng tụi S BN nng/ Tng s 10/24 15/38 06/30 14/33 17/47 Thi im Nhp vin Nhp vin 24gi 24 gi Nhp vin Ngng giỏ tr 130U/L 2,7pg/mL 50pg/mL 50pg/mL 202,47pg/mL nhy (%) 100 100 100 100 100 c hiu (%) 71 81 88 89,4 96,66 3.2.2 IL-8: Nghiờn cu ca chỳng tụi, cú s gia tng cú ý ngha nng ca IL-8 VTC nng so vi VTC nh (p=0,0017) (bng 2.1), phự hp vi nhng nghiờn cu ca Pezzilli R, 1995; Berney v cs, 1999 v Nakechand Pooran, 2003 [8], [41], [53] Bng 3.5 Bng so sỏnh cỏc kt qu nghiờn cu i vi IL-8 Nghiờn cu Stoelben Pezzilli Chỳng tụi S BN nng/ Tng s 11/23 15/38 17/47 Thi im Nhp vin 24 gi Nhp vin Ngng giỏ tr 200pg/L 30pg/mL 989,02pg/mL nhy (%) 82 81 35,29 c hiu (%) 75 77 96,66 3.2.3 TNF-: Nghiờn cu ca chỳng tụi chng t nng TNF- tng cú ý ngha VTC nng (p = 0,0026) (bng 2.1), phự hp vi nghiờn cu trc õy [24], [41] Bng 3.6 Bng so sỏnh cỏc kt qu nghiờn cu i vi TNF- Nghiờn cu Jiang Chỳng tụi S BN nng/ Tng s 14/33 17/47 Thi im 24 gi Nhp vin Ngng giỏ tr 2pg/mL 20,04pg/mL nhy (%) 63,2 64,7 c hiu (%) 72,7 73,33 3.2.4 CRP: Nghiờn cu ca chỳng tụi chng t khụng cú s khỏc bit cú ý ngha v nng huyt ca CRP gia hai nhúm VTC nng v VTC nh vũng 48 gi sau khi phỏt triu chng au bng, thi im nhp vin (p = 0,381 > 0,05) (Bng 2.2) 3.2.5 So sỏnh IL-6, IL-8, v TNF- vi CRP Mt s nghiờn cu trc õy ó so sỏnh giỏ tr ca IL-6, IL-8, v TNF- vi CRP: * Nghiờn cu ca chỳng tụi, vi ngng giỏ tr ca IL-6 phõn bit VTC nng v nh l: 202,47pg/mL thỡ nhy l 100% (17/17), c hiu l 96,66% (29/30) v chớnh xỏc (97,87%) cao hn CRP (bng 2.3, 3.4, 3.7) Ngoi giỏ tr ca AUC ca IL-6 cao hn CRP (0,961 > 0,49) (biu 2.1 v 2.2) Trang 28 Bng.3.7 Bng cỏc kt qu nghiờn cu so sỏnh IL-6 vi CRP Nghiờn cu Pezzilli *IL-6 *CRP Pezzilli *IL-6 *CRP Jiang *IL-6 *CRP Chỳng tụi *IL-6 *CRP S BN nng/ Tng s 15/38 Thi im Ngng giỏ tr nhy (%) c hiu (%) Nhp vin 2,7pg/mL 11mg/dL 100 86 95 Nhp vin 3,7àg/L 6-7mg/L 100 87 83 46 24 gi 50pg/mL 16mg/dL 100 42,9 89,7 89,5 Nhp vin 202,47pg/L 165,12mg/L 100 52,9 96,66 66,66 15/40 14/33 17/47 -IL-8: ớt nghiờn cu so sỏnh IL-8 v CRP tiờn oỏn nng ca VTC 24gi u nhp vin * Trong nghiờn cu ca chỳng tụi: vi ngng giỏ tr (cut-off) ca IL-8 phõn bit VTC nng v nh l 989,02pg/mL thỡ nhy l 35,29% (6/17) v c hiu l 96,66% (29/30) So vi CRP nhy thp hn (35,29% so vi 52,9%), nhng c hiu cao hn (96,66% so vi 66,66%) (bng 2.3, 3.8); ngoi ra, AUC ca IL-8 ln hn CRP (0,767 sovi 0,49) (biu 2.1 v 2.3) Bng.3.8 Bng cỏc kt qu nghiờn cu so sỏnh IL-8 vi CRP Nghiờn cu Pezzilli *IL-8 *CRP Chỳng tụi *IL-8 *CRP - TNF-: S BN nng/ Tng s 15/38 Thi im Ngng giỏ tr nhy (%) c hiu (%) Nhp vin 30pg/mL 11mg/dL 100 81 95 Nhp vin 989,02pg/mL 165,12mg/L 35,29 52,9 96,66 66,6 17/47 * Nghiờn cu ca chỳng tụi: vi ngng giỏ tr ca TNF- phõn bit viờm tu cp nng v nh l 20,04pg/mL thỡ nhy l 64,7% (11/17) v c hiu l 73,33% (22/30) vi chớnh xỏc 70,21% cao hn CRP (bng 2.3) AUC ca TNF cng ln hn CRP (0,725 so vi 0,49) (biu 2.1 v 2.4) Trang 29 Bng 3.9 Bng cỏc kt qu nghiờn cu so sỏnh TNF- vi CRP Nghiờn cu Jiang *TNF- *CRP Chỳng tụi *TNF- *CRP S BN nng/ Tng s 15/38 Thi im Ngng giỏ tr nhy (%) c hiu (%) Nhp vin 2pg/mL 16mg/dL 62,3 42,9 78,9 89,5 Nhp vin 20,04pg/mL 165,12mg/L 64,7 52,9 73,33 66,6 17/47 3.3 Nhng khú khn, tn ti nghiờn cu: - Vn tm soỏt nguyờn nhõn ca VTC cha y , nht l nguyờn nhõn di truyn, nờn khụng th ỏnh giỏ s thay i ca IL-6, IL-8, v TNF- theo tng nhúm nguyờn nhõn - Mu nghiờn cu cha nhiu (47 bnh nhõn), thi im ly mu khụng th thc hin trc 24 gi - Cha kho sỏt c ng hc ca tng Cytokines nờn cha ỏnh giỏ mt cỏch ton din giỏ tr ca nhng Cytokines tng thi im KT LUN: - Nghiờn cu ca chỳng tụi (47 bnh nhõn VTC) mt ln na chng t IL-6, IL8, TNF- l nhng cytokines cú th c s dng tiờn oỏn sm nng ca VTC vũng 48gi t khi phỏt au bng ú IL-6 cú giỏ tr tt nht vi nhy 100% v c hiu 96,66% (ngng giỏ tr l 202,47pg/mL) - õy l nghiờn cu bc u ca nc ta v nhng cytokins, hy vng gúp phn vo tiờn oỏn sm nng ca VTC - Vn cũn tn ti hin l phng phỏp tm soỏt nhng cytokins cha tr thnh thng quy, nhiờn, chỳng tụi hy vng rng vi s phỏt trin ca dch hc trờn th gii v ti Vit Nam, cỏc trang thit b tm soỏt nhng Cytokines s c trang b y nhm gúp phn vo nghiờn cu, chn oỏn v iu tr nhng bnh lý ỏp ng viờm ú cú VTC ngh: Qua nghiờn cu ny, kt hp vi nhng y th gii, chỳng tụi ngh s dng nhng du n sinh hc huyt tiờn oỏn nng ca VTC: IL-6, IL-8, TNF- thi im nhp vin (trong ú IL-6 l du n sinh hc cú giỏ tr nht) v CRP lỳc 48 gi cú th lm gim t l t vong VTC nng Trang 30 TI LIU THAM KHO Ti liu ting Vit Phan Th Danh (2006), S dng k thut Biochip xột nghim v ng dng lõm sng cytokines,Y hc thnh ph H Chớ Minh, 10, (1), tr 385-389 Phm Hong Phit (2004), Cytokin, Min dch- Sinh lý bnh, Nh xut bn Y hc thnh ph H Chớ Minh, Ch 7, tr.82-93 Ti liu ting nc ngoi Ahmed Z, Al-Bahrani, Basil J Ammori (2005), Review clinical laboratory assessment of acute pancreatitis Elsevier B.V Antonio Carnovale, Pier Giorgio Rabitti (2005), Mortality in Acute Pancreatitis: Is It an Early or a Late Event?, JOP J Pancreas (Online); 6(5):pp 438-444 Andrew Kingsnorth and Derek O'Reilly (2006), Acute pancreatitis, BMJ;332;pp.1072-1076 Avery B Nathens, MD, PhD (2004), Management of the critically ill patient with severe acute pancreatitis, Crit Care Med Vol 32, No 12 Bei Sun, Ha-Li Li (2003), Factors predisposing to severe acute pancreatitis: evaluation and prevention, World J Gastroenterol ;9(5), pp.1102-1105 Berney T (1999), Serum profiles of interleukin-6, interleukin-8, and interleukin-10 in patients with severe and mild acute pancreatitis, Pancreas ;18(4), pp.371-377 Bertsch T, Aufenanger J (1997), Interleukin-6 and Phospholipase A2 isoenzymes during acute pancreatitis, Pancreas.;14(1), pp.1-8 10 Catherin M Pastor, MD, PhD (2003), Pancreatitis- associated acute lung injury, Chest, 124, pp 2341- 2351 11 Chun-Chia Chen (2004), Serum Markers in the Early Assessment of Severity of Acute Pancreatitis: Which is the Most Useful?, J Chin Med Assoc,67, pp.439-441 12 David C Whitcomb, M.D., Ph.D (2006), Acute Pancreatitis, N Engl J Med; 354, pp.2142-2150 13 Derek A O'Reilly and Andrew N Kingsnorth (2004), Management of acute pancreatitis, BMJ;328, pp.968-969 14 Elena Citkowitz (2005), Hypertriglyceridemia, eMedicine World Medical Library 15 Emil J Balthazar, MD (2002), Acute pancreatitis: Assessment of severity with clinical and CT evaluation, Radiology; 223, pp 603-613 16 Florence C Richộ MD, Bernard P (2003), Inflammatory cytokines, C reactive protein, and procalcitonin as early predictors of necrosis infection in acute necrotizing pancreatitis, Surgery, Volume 133, Issue 3, pp 257262 17 Gurlich R, Maruna P, Spicak J (2006), Prediction and monitoring of severe acute pancreatitis, Cas Lek Cesk.;145(6), pp.437-441 18 Giedrius Barauskas (2004), C-reactive protein in early prediction of pancreatic necrosis, MEDICINA Vol 40, No - http://medicina.kmu.lt Trang 31 19 Gross V (1992), Interleukin-8 and neutrophil activation in acute pancreatitis, Eur J Clin Invest.;22(3), pp.200-203 20 Heath DI, Cruickshank A, Gudgeon M, Jehanli A, Shenkin A, Imrie CW (1993), Role of interleukin-6 in mediating the acute phase protein response and potential as an early means of severity assessment in acute pancreatitis, Gut.;34(1), pp.41-45 21 Inagaki T(1998), Interleukin-6 is a useful marker for early prediction of the severity of acute pancreatitis, Pancreas.;16(4),pp.557-558 22 Jean Louis Frossard (2001), Trypsin activation peptide (TAP) in acute pancreatitis: From pathophysiology to clinical usefulness JOP, J pancreas (online); (2),pp 69-77 23 Jean louis Frossard (2001), New serum markers for the detection of severe acute pancreatitis in human, American Journal of respiratory and critical care medecin, vol 164, pp.162- 170 24 Jiang CF, Shiau YC, Ng KW, Tan SW (2004), Serum interleukin-6, tumor necrosis factor alpha and C-reactive protein in early prediction of severity of acute pancreatitis, J Chin Med Assoc.;67(9), pp.439-441 25 J Mayer, B Rau, F GanSauge, HG Beger (2000), Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications, Gut; 47, pp 546-552 26 J Toouli, M Brooke- Smith (2002), Guilines for the management of acute pancreatitis, Journal of Gastroenterology and Hepatology 17 (Suppl), pp S15- S39 27 Kaw M, Singh S (2001), Serum lipase, C-reactive protein, and interleukin-6 levels in ERCP-induced pancreatitis, Gastrointest Endosc.;54(4), pp.435-440 28 Kazunori Takeda, Tadahiro Takada (2006), JPN Guidelines for the management of acute pancreatitis: medical management of acute pancreatitis, J Hepatobiliary Pancreat Surg;13,pp.4247 29 Kimmo Halonen (2004), Outcome prediction and quality of life in severe acute pancreatitis, Helsinki University Central Hospital 30 Lawrence K Gatees Jr (1999), Severity scoring for acute pancreatitis:Where we stand in 1999?, Current Science,Inc.ISSN,1:134-138 Copyright by Current Science,Inc 31 Leser HG (1991), Elevation of serum interleukin-6 concentration precedes acute-phase response and reflects severity in acute pancreatitis Gastroenterology.;101(3), pp.782-785 32 Louis R Lambiase (2006), Pancreatic Pseudocysts, eMedicine World Medical Library 33 Manes G, Spada OA, Rabitti PG, Pacelli L, Iannaccone L, Uomo G 1997), Serum interleukin-6 in acute pancreatitis due to common bile duct stones A reliable marker of necrosis Recenti Prog Med.;88(2), pp.6972 34 Marja-Leena Kylnp-Bck(2001), Acute pancreatitis: Diagnosis and assessment of severity with markers of inflammation Helsinski Trang 32 35 Miho Sekimoto, Tadahiro Takada (2006), JPN Guidelines for the management of acute pancreatitis: epidemiology, etiology, natural history, and outcome predictors in acute pancreatitis, J Hepatobiliary Pancreat Surg ; 13, pp.1024 36 Marko Lempinen (2004), Trypsin- related markers in the severity assessment of acute pancreatitis Helsinski Website:http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/lempinen/trypsinr pdf 37 Mark Topazian and Fred S Gorelick (2003), Acute pancreatitis, Textbook of Gastroenterology - chapt 94 38 Masahiko Hirota, Masaki Ohmuraya, Hideo Baba (2006), Genetic background of pancreatitis, Postgrad Med J;82, pp.775778 39 M M Lerch and W Halangk (2006), Human pancreatitis and the role of cathepsin B, Gut;55, pp.1228-1230 40 Motoo Y, Xie MJ, Mouri H, Sawabu N (2004),Expression of interleukin-8 in human obstructive pancreatitis,JOP.;5(3),pp.138-144 41 Nakechand Pooran,MD (2003), Cytokines (IL-6, IL-8, TNF),Early and reliable predictors of severe acute pancreatitis, J Clin Gastroenterol; 37 (3), pp.263-266 42 Nikou GC (2004), Effect of octreotide administration on serum interleukin-6 (IL-6) levels of patients with acute edematous pancreatitis Hepatogastroenterology.;51(56), pp.599-602 43 Oezcueruemez-Porsch M (1998), Diagnostic relevance of interleukin pattern, acute-phase proteins, and procalcitonin in early phase of post-ERCP pancreatitis,Dig Dis Sci.;43(8), pp.1763-1769 44 Padmam Puneet, Shabbir Moochhala, and Madhav Bhatia (2005), Chemokines in acute respiratory distress syndrome, Am J Physiol Lung Cell Mol Physiol,288: L3L15 45 Pamela A Lipsett (2005), Acute pancreatitis- Textbook of critical care, fifth Edition, Elsevier Saunders;Chapt 112, pp 1020-1031 46 Pancreatic disease group, chinese society of gastroenterology and chinese medical association (2005), Consensus on the diagnosis and treatment of acute pancreatitis, Chinese Journal of digestive disease; 6, pp 47-57 47 Papachristou GI, Whitcomb DC.(2005),Inflammatory markers of disease severity in acute pancreatitis,Clin Lab Med.;25(1),pp.17-37 48 Papachristou GI, Whitcomb DC (2004), Predictors of severity and necrosis in acute pancreatitis, Gastroenterol Clin North Am.;33(4), pp.871-90 49 Paredes Cotore JP, Bustamante Montalvo M (1995), Prognosis of acute pancreatitis: Ranson or APACHE ?, Rev Esp Enferm Dig, 87 (2), pp 121-126 50 Peter A Banks, M.D (2006), Practice Guidelines in Acute Pancreatitis, Am J Gastroenterol;101, pp.23792400 51 Patrick W Vriens, Pieter van de Linde (2005), Computed tomography severiry index is an early prognostic tool for acute pancreatitis- Am Coll Surg;201,pp 497-502 Copyright by the American College Surgeons Trang 33 52 Pedersen N, Larsen S, Seidelin JB, Nielsen OH (2004), Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein1 in chronic pancreatitis J Gastroenterol.;39(3), pp.277-282 53 Pezzilli R, Billi P, Miniero R, Fiocchi M, Cappelletti O, Morselli-Labate AM, Barakat B, Sprovieri G, Miglioli M (1995), Serum interleukin-6, interleukin-8, and beta 2-microglobulin in early assessment of severity of acute pancreatitis Comparison with serum C-reactive protein, Dig Dis Sci.;40(11), pp.2341-2348 54 Pezzilli R, Miniero R, Cappelletti O, Barakat B (1998), Serum interleukin in the prognosis of acute biliary pancreatitis, Ital J Gastroenterol Hepatol.;30(3), pp.295-296 55 Pietro Renzulli, Stephan M Jakob (2005), Severe Acute Pancreatitis: CaseOriented Discussion of Interdisciplinary Management, Pancreatology;5,pp.145156 56 Raffaele Pezzilli (1999), Simultaneous serum assays of lipase and Interleukin6 for early diagnosis and prognosis of acute pancreatitis, Clinical chemistry,pp 1762-1767 57 Rau B, Steinbach G, Gansauge F, Mayer JM, Grunert A, Beger HG (1997), The potential role of procalcitonin and interleukin in the prediction of infected necrosis in acute pancreatitis, Gut.;41(6), pp.832-840 58 R M S Mitchell, M F Byrne, J Baillie (2003), Pancreatitis, Lancet; 361,pp.14471455 59 Satoshi Ikei, Michio Ogawa and Yasuo Yamaguchi (1998), Blood concentration of polymorphonuclear leucocyte elastase and interleukine6 are for the occurrence of multiple organ failure at the early stage of acute pancreatitis, Journal of Gastroenterology and Hepatology ; 13, pp.1274-1283 60 S Rickes, C Uhle, S Kahl (2006), Echo enhanced ultrasound: a new valid initial imaging approach for severe acute pancreatitis, Gut; 55, pp.74 78 61 Stimac D, Fisic E, Milic S (2006), Prognostic value of IL-6, IL-8, and IL-10 in acute pancreatitis, J Clin Gastroenterol.;40(3), pp.209-212 62 Stuart L Triester and Kris V Kowdley (2002), Prognostic factors in acute pancreatitis- J Clin Gastroenterol;34(2), pp.167-176 63 Timothy B Gardner (2006), Acute pancreatitis, eMedicine World Medical Library 64 Tran DD (1993), Interleukin-6 in the early assessment of acute pancreatitis, Gut.;34(1), pp.41-45 65 Ueda T, Takeyama Y, Hori Y, Nishikawa J, Yamamoto M, Saitoh Y (1997), Hepatocyte growth factor in assessment of acute pancreatitis: comparison with C-reactive protein and interleukin-6, J Gastroenterol.;32(1), pp.63-70 66 UK Working Party on Acute Pancreatitis (2005),UK guidelines for the management of acute pancreatitis, Gut;54, pp.1-9 Trang 34 67 Vallath Balakrishnan (1998), Cytokines as predictors of severity in acute pancreatitis, Journal of Gastroenterology and Hepatology ; 13, pp.11771179 68 Viedma JA, Perez-Mateo M, Dominguez JE, Carballo F (1992), Role of interleukin-6 in acute pancreatitis Comparison with C-reactive protein and phospholipase A2, Gut.;33(9), pp.1264-1267 69 Vege Santhi Swaroop, MD (2004), Severe Acute Pancreatitis, JAMA, ;Vol 291, (23),pp,2865-2868 70 Wereszczynska-Siemiatkowska U (2003), Serum profiles of E-selectin, interleukin-10, and interleukin-6 and oxidative stress parameters in patients with acute pancreatitis and nonpancreatic acute abdominal pain, Pancreas.;26(2), pp.144-152 71 W R Matull, S P Pereira and J W ODonohue (2006), Biochemical markers of acute pancreatitis, J.Clin.Pathol.;59, pp.340-344 72 Waldemar Uhl, Andrew Warshaw, Clement Imrie (2002), IAP Guidelines for the surgical management of acute pancreatitis, Pancreatology;2, pp.565573 73 Zilvinas Dambrauskas (2006), Predicting development of infected necrosis in acute necrotizing pancreatitis, Medicina; 42(6),pp.441-449 Trang 35 [...]...TÀI LIỆU THAM KHẢO Tài liệu tiếng Việt 1 Phan Thị Danh (2006), “ Sử dụng kỹ thuật Biochip trong xét nghiệm và ứng dụng lâm sàng cytokines”,Y học thành phố Hồ Chí Minh, tập 10, (1), tr 385-389 2 Phạm Hoàng Phiệt (2004),“ Cytokin”, Miễn dịch- Sinh lý bệnh, Nhà xuất