The document discusses various treatments for rheumatoid arthritis including Disease-modifying antirheumatic drugs (DMARDs) such as Methotrexate, Leflunomide, Sulfasalazine, and Hydroxychloroquine, as well as biological DMARDs like Tumor necrosis factor (TNF) inhibitors. It notes the importance of early and aggressive treatment to prevent further joint damage and disability. Guidelines recommend starting with conventional synthetic DMARDs alone or in combination, and adding biological DMARDs if the disease is not adequately controlled.

1. 275 .enitexom [PGRF [TG { esaeler wolS(.
-otA ;enilomeP ;enimatehpmaxeD ;llareddA ;atrecnoC ;etadinehp MBZCT [TG GJCNKG [N 02 P"D [P[L VTGNQ M[[ TE
-lyhteM ;nilatiR ;redrosiD ytivitcarepyH/ticifeD noitnettA :sdrow yeK NXGZL JKVGN )JCNKG [N 01 P"D NJKVGN YXZ-JGGI FRP[L
1
FY"Z { FVZT Y[C GZKMGH.
CPBPZ HF RPYE CJKVGN CZGVG [BKRG FZKJNKQ FPYGCN
FY"Z KMGNKO NKFRG PJKVGN CZGVG ~2|. FFGZKF NJKVGN NJKVGN CPKNVRKEBJ.
CNGYKO CF FGB IKRGMK, VSKMGNGDK GVBZPYGNGDK. ZGC FKNEKO TO 5( K[ NJVN CZGVG INGVKG CBGF BGMNGSKKF FPRDE
KSPGR HG VGDT C-%3=%9 PMNN FBGMNGSKKF ~1|, GFJKVGN MB[Z VSKMGSJKPGNRJKO BKRO KTKNKO.
FPBGVKKR CBKPVGNSKCKG, CFVZTF CZKMGH GCVTKNG-KZ. 4( REZ[G ZGVG CTNG PRDRGQ VTGNF [GRF [FKKRF KTKNG
F DHDA ± redrosiD ytivitcarepyH, FKB KSPGR RKEBJ, BL NNB F[VTG-FNGGBK FBGVKKRKG NZGVF.
VZT Y[C GZKMGH )FY"Z( { ticifeD noitnettA 3( REZ[KO VSKMGSJKPGNRJKO RGSVKO TO KTKNG HFF NPKNV-
JGGI CTNG JGGIK VTGNF [GRKO.
FYEPF 2( PKNVRKEBJ KTKN NJGGI YXZ, GREZ[G ZGVG BZGMG-
1( PKNVRKEBJ KTKN C-%07=%08 PFIGNKO CNCE ~11|.
BG [NYG CF[VTG-NGGBK PFJKVGN. SKCG:
PSVYG PTRF NBGO VNIK BGMNGSKKF [BKRO PDKCKO NZKJNKQ FXGZL CJKVGN CZGVG RGSVG NPKNVRKEBJ RGCT PMPF
FRDEG [TKYZF PMGGQ NZKJNKQ TXPG. CRGSU, ZGVG BNF
PVKDG INY PQ FFRDEG FCSKSK NJKVGN CZGVG CFY"Z, RPGL PFREZ[ FQ CBZF"C ~9| GFQ CK[ZBN ~01|.
KTKNG GCJGIG MPG ZKJNKQ, BNB [PTXO FKGQ "NB ZKJNKQ" PHG, NPZG TNKKF PPE CPSVZ FPJGVNKO CZGVF HG, FJKVGN
MINGVF JKVGNK NZKJNKQ. FZGVG FIE[G NB HG CNCE [FQ FZDKN GFQ CBNF FNGPEKO CPKSDZ FIKRGL FPKGIE ~9|. KZF
GREGGI CYXZF TN ZGVG RGSVG [FGTNG NBGZL F[RKO NBGZL F[RKO, FQ CBGMNGSKG FKNEKO FNGPEKO CPKSDZ FIKRGL
RPRK TO FVSKMGSJKPGNRJKO { BJGPGYSJKQ )SJZJZF(, CVSKMGSJKPGNRJKO [GRKO GCTKYZ CPKNVRKEBJ, TGNF CFPEF
R FF[VTF FJKVGNK. MQ REGQ CZGVF IE[F RGSV, [BKRF Y K G P F [ N YC G X P RD E K O N J KV G N H F , [ MK I G F J KV G N
PCIKR F[VTG-FNGGBK FY[G [RDZPG PRJKNG GFQ PCIK- P[RKO B ET FPRDEKO NJKVGN CPKNVRKEBJ. BL NPZG
PGNRJ [FKF TE MF BI FINGVG FTKYZKG, BGNO CTKKK FQ CJKIGG GFRKSKGQ [RXCZ CJKVGN CZGVF PHF 07 [RF, BKRO
GISZGRGKFQ. RHMKZ B FVPGNKQ )SKKNZJ, RKBQ(, VSKMGSJK- GXBG PIYZKO RGSVKO ZCKO FPTKEG TN KTKNG FJKVGN,
FPKET FPIYZK FTEMRK NDCK FZGVG FIE[G, KZGRGKFQ DO CYCGXF HG, FGB PK[NC [N JKVGN ZGVK GVSKMGNGDK ~8|.
[N RDHZG BPVJPKRKO, GEYSEZKQ )EYSBPVJPKQ(. RXKD B JKVGN VSKMGNGDK KTKN CPKEF [GGF. BGNO FJKVGN FKTKN CKGZ,
[FKB PKNVRKEBJ BZGL-JGGI CPKGIE, BEZN, [FKB TZGC PKNVRKEBJ. CBO YKKP INGBF RNGGK, MDGQ FVZT IZEF,
FGGKYG KGZ. REGQ CVSKMGSJKPGNRJKO FIE[KO YGRXZJF, CSPKRK FBKPVGNSKCKG GVTKNG FKZ CFY"Z FGB CZGVF
R S YZ G F ZG VG F IE [G F TK Y ZKG G I N Y PF ZG VG FPSYRG PPIYZ ZC-F[VTF HF FQ, MK FJKVGN FKTKN CKGZ
ZGVG IE[G FPFGG INGVF FGNP NZKJNKQ. CPBPZ HF
PTRF PSVY NCTKG [VGZJG. NBIZGRF, FGIN C[KGGYQ [N CZGVG CFVZTF FRFDGK HG.
FHPKRG NB RKPRG TO YG FJKVGN FZB[GQ CFVZTF, GNB RRG NTGP JKVGNKO VSKMGNGDKKO, NRGMI FFRDEG FR[RK NJKVGN
NXGZL CPXKB INGVG NZKJNKQ. TE NBIZGRF FINGVG HIN. FPIYZ RGTE NCEGY PF KTKNG FJKVGN CPKNVRKEBJ
FZKJNKQ FRVGXG FQ YXZG-JGGI KISK. SKCG BNF FCKBG CG 975 KNEKO TO FY"Z, C[KGU PZMHK JKVGN [GRKO GCPKPGQ F-
RHYYKO NJKVGN CZGVG NP[L [TG ZCG, CTGE [ZGVG C[RKO FBIZGRG RTZL PIYZ I[GC, VZGSVYJKCK, [RMNNG
CFVZTG-NGGBK FDGZPG NFVSY FJKVGN, GINY PFPJGVNKO MKVKGQ ~6|, GMQ CKNEKO TO [KGY PGIKQ GFY"Z ~7|.
P DK C K O N J K V G N C P K N V R K E B J , I N Y P F P J GV N K O N G Y K O CKNEKO TO FY"Z GPINF MKVKGRK FPBGHR CJKVGN ZGVK RGDE-
FRZTKO PRJKN ZGVF HG. CRGSU, INY PFKNEKO BKRO CPCDZKO GCPCGDZKO TO FY"Z ~4|, CKNEKO TO VKDGZ GFY"Z ~5|,
CYZC FXKCGZ FZIC GFQ CYZC FPJVNKO PFIGPKO F[GRKO, KTKN CKNEKO CDKN FDQ ~3|, CKNEKO CCK-FSVZ FKSGEK, BL DO
T[ZG [RKO MZGVF KTKNF GCJGIF. NPZG HB, ZCKO, FQ JKVGN CVSKMGSJKPGNRJKO, GCTKYZ CPKNVRKEBJ )ZKJNKQ(,
GZKMGH )FY"Z(.1 PKNVRKEBJ FGMI CPIYZKO ZCKO NBGZL CCK GCCK-FSVZ FQ CIGO FNKPGEK GFQ CIGO FICZK ~1|.
ZKJNKQ, FGB FZGVF FTKYZK FRKR MJKVGN CFVZT Y[C P[VIK BG PINF FPIYF FY"Z. FSPKRKO VGDTKO CKVYGE
PKNVRKEBJ, FVSKMGSJKPGNRJ FPGMZ C[PG FPSIZK FRVGW NPTNF PIXK [RF GBKRO RGCTKO PSKCF PGDEZ BIZ, MDGQ P[CZ
YXKZ CZGVG FKB NKNEKO TO SKPRKO GSPKRKO [N FY"Z FPPKEKO
FKI' NRKZGNGDKF [N FKNE, PZMH ZVGBK [TZK-XEY, KZG[NKO
EGZK [PGBNK, GZEF DZGS-XGZ
PKNVRKEBJ YXZ-JGGI )ZKJNKQ(
FVZT Y[C GZKMGH { JKVGN CZGVG [BKRQ
SYKZG
FZVGBF MZL 441, IGC' I' )BGDGSJ 5002(

2. PBPZKO ZCKO ~91|, GNMQ NB REGQ CG FVTO, BNB CINGVGKG. 6=21 [RF N[NG[ YCGXG [JGVNG CBI P[NG[ BV[ZGKG: 375
FVMG B FVSKMGSJKPGNRJKO NJKVGN RVGW CFY"Z. NZKJNKQ KGIEG CPIYZ EGPF [N hciarloW GIC' ~12|, SGGDG 282 KNEKO CRK
C[KNGC TO PKTGJ F[VTG-FNGGBK GFRGIG FKISK CJKVGN, NJKVGN CP[L MN [TG FKGO CEGPF N[NG[ PRG ZKJNKQ.
FFRFDGK [NF )BKPVGNSKCKG GFKVZBYJKCKG( ~31|. MGRF HG, ZKJNKQ. PSYR FIGYZKO FKKF, MK YGRXZJF KTKNF GCJGIF
RKJKCK [N FY"Z )Y[C GZKMGH( CRGSU NF[VTF TN FPZMKC FTEKVG CPGCFY JKVGN CYGRXZJF TN-VRK PQ [NG[ PRG
NVSKMGSJKPGNRJKO KTKNG PKGIE C[KVGZ FPZMKC FYGD- CGEE [N YGRXZJF FKKF KTKNF MPG [NG[ PRG ZKJNKQ. FGZKO
FPYGCNKO CFY"Z ~81|. P[PTGK CKQ FZGVG TXPQ GCF[VTG-FNGGBK [RDZPG. PRF
~71|. F[KRGKKO FYZEKGGBSYGNZKKO CKNEKO FO PKHTZKKO CPKRGRKO BKRCG. F[KVGZ FKF FQ FRFDGK GFQ NKPGEK. NB FKF FCEN
C[N FVTKNG FSKPVJK [N FZGVG, NKYGVRKF GVSKMGHF TNF, CBGVQ [BKRG PVKT, MK NJKVGN CZGVG KZGQ TN-VRK
CFKZEPG GBK-[YJ, GFREKZG KGZ FQ TNKKF CNIW-FEO GCEGVY N[NG[ PRG ZKJNKQ YXZ-JGGI GNZGV BKRCG. PGXBG FPIYZ
FN G G BK F [MK I G F Q K ZK EF C K BC G Q, M B CK - Z B[ , Y [ KK O mahleP GIC' ~22| FK[GG PQ PRF CGEE [N YGRXZJF
YCGTF GDGZPKO NF[VTG-NGGBK PGTJG KISK ~61|. F[VTG- CFKZEPG, MBCK-CJQ, JKYKO GK[RGRKG ~42|.
ZGC FVSKMGSJKPGNRJKO RGIKO NJKVGN, BKRO PIKKCKO RJKNF [FZK FIGPZ FVTKN HFF: KZKEF CKBCGQ, MBCK-ZB[, Y[KKO
GRGZBEZRNKQ ~31|. F[VTG-FNGGBK FTKYZKG [TNKFQ PEGGI EGPG NZKJNKQ,
CZKMGH FYJMGNBPKRKO CPKZGGI FSKRBVJK ~3| CTKYZ EGVBPKQ PKNVRKEBJ NPKRKFQ ~6|.
BKRG CZGZ EKG. TO HB, KEGT MK VSKMGSJKPGNRJKO DGZPKO NTNKKF CVKZMGSKO GNFVSKYO IKNF, GBH RKQ NJVN CZGVG
GTKYZK CFY"Z. PRDRGQ FVTGNF FPEGKY [N FVSKMGSJKPGNRJKO NSPKO BG NBNMGFGN. CIGNK MKVKGQ )yspelipE( K[ NJVN
VSKMGSJKPGNRJKO PFGGKO YG JKVGN ZB[GQ MQ, K[ NFKHFZ CPQ FZGVF CIGNKO TO BRBPRHF [N FPMZG
ZKSKG )msidioryhtrepyH(. MPG-
VSKMGSJKPGNRJKO NDZGO P[CZ NIW-EO DCGF GKZ-
ìèéôåì áä÷¢ø® IGSPK PGRGBPKRKEBHF { TNGNKO
FPGNKMKO FTXCKKO CPKZGGI FSKRVJK ~31|.
3 øéèìéï äåà òãééï äúøåôä äòé÷øéú KZ NZKJNKQ, JKVGN CZGVG PSGD
MJKVGN CFY"Z PKGTEG NFTNG B ZKMGH áäôøòú ÷ùá åøéëåæ ©ä÷¢ø¨® [FZGVF KMGNF NFIPKZO, ZDK[G-
CPKZGGI FSKRVJK. ZGC FZGVG FRKRG ùáäí éù äåøéúÐðâã ìèéôåì áøéèìéï IZEF BG PI YKXGRKKO { MKGGQ
KISK CZP FEGVBPKQ GFRGZBVKRVZKQ ìúä¬ åéëåìéí ìúú îòðä áîöáéí [KYGN-ET NVRK JKVGN CZGVF FO
FFVZTF RDZP MMN FRZBF PKZKEF ùì÷å áäùôòåúÐìååàé áò÷áåú ðèéÐ FZGVF FPXCKO CFO K[ NFVTKN
FCSKS GFPGIGQ ~51|. CZPF FBK ìàåúí éìãéí ùìà äâéáå ìøéèìéï àå P B K P F N M N P J G VN . N V K T N G Q
FJZGO-YEPKKO )latnorf-erP(, DZTKRK 3 äçìåôåú äçãùåú éëåìåú ìäúàéí YGRXZJF, MMN ZGVF, BKRF
GZKMGH GFBIZBKKO NFVZTF FO FBHGZKO ìèéôåì áîéãä ùååä® BZGMG.
BHGZK FPGI FY[GZKO NKVYGEK Y[C äååúé÷åú éåúø¬ äï éòéìåú åáèåçåú PPG[L C[N [TG NKPGEKO-TCGEF
SCKCKKO, GZ[KKO GCKGNGDKKO ~41|. ìôðéãàè ©øéèìé館 ùáðéâåã ìçìåôåú PCDZKO GPCGDZKO FHYGYKO NMKSGK
M K F Y "Z R D ZP PP K [ N C [ N D G ZP K O 3 ÷ééîåú äéåí çìåôåú çãùåú ìîúéÐ FX G F ZK K O G FT Z C F P G Y E P G , B G
RKZGVSKMKBJZKG BIZG, FF[TZF FKB CCKO GTO P[VIO C[TG BIZ-
FVGVKHKGNGDKF [N FY"Z PGZMC, GCEGPF NFVZTG FIGGKO Y[KKO MGXBF PFY"Z DO
YGRXZJF KMGNF NFKG PTRF NPXCKO BNF { NEGDPF, CKNEKO
~21| BG FY"Z TO FVZTF EKMBGRK )RGDEK-EKMBGQ( ~31|. PRG KGPKG GZO NKZKEF CFKTRG NJKVGN GNMK[NGRG ~81,32|.
MDGQ FY"Z TO FVZT JKYKO BG CTKG FRFDG Y[G )YNGRKEKQ( KISK. NTKKO REZ[ F[VTF BZGM-JGGI [N FZGVF. ZKCGK
FBIZGRG [FGHMZG RKRG CEZL-MNN MJKVGN CFVZTF P[GNC, ZGVG PKNVRKEBJ FRVGXG CK[ZBN FQ YXZG-VTGNF
BIZKO, MPG GRNVYSKQ )roxefE ,enixafalneV( GTGE. FZGVG RKQ NINY, N[CGZ, NNTGS BG NFPKS B FYGVSK.
XKYNKKO )stnanesserpeditnA cilycirT ± ACT(, RGDEK-EKMBGQ MKSGK JKVGNK NMN [TG FKPPF ~22|. C[N FPKCRF FPKGIE NB
NEGDPF, YNGRKEKQ )enidinolC ,tirinnolC(, RGDEK-EKMBGQ N- FF[VTF FGB 21 [TG ~12|, ML [EK CPRF BI CCGYZ NXGZL
FRKRG NTKKO MJKVGN CFY"Z GBKRQ YG FJKVGN FZB[GQ, KZ FYGVSK BKRF PSKSF GPGVZ[ CXGBF. SL HPQ
arettartS(. PVB YGXZ FKZKTF NB REGQ CZGVG RGSVG FZGVF ~02|.
PRDRGRK VTGNF BIZKO, MDGQ BJGPGYSKJKQ ),enitixomotA
)natiN ,trelyC ,enilomeP(, GZGVG RGSVG FVGTNG CBPXTG
metsys(. ZP F[KB PYCN [[ TE [PGRF [TG NBIZ RJKN
GINY [RK IEKZ NPIXF TO [KIZGZ FRP[L T[Z [TG )SORO
)llareddA(, EYSJZGBPVJPKQ )EYSEZKQ ~nirdexeD|( GVPGNKQ
INYKO: INY BIE FPBV[Z [KIZGZ PKKEK [N %22 PFIGPZ,
VSKMGSJKPGNRJKO BIZKO [FJKVGN CFO [MKI, MDGQ BEZN
FKKIGEK [N FZGVF FGB YGVSK )eluspaC( FPGZMC P[RK
GKTKNGO FG[GGF NKTKNG PKNVRKEBJ. BNF MGNNKO
F[KIZGZ FPPG[L [NG FPCGSS TN JMRGNGDKK SORO. FPKCRF
BKRG PKNVRKEBJ, [FGMIG CPIYZKO MKTKNKO NJKVGN CFY"Z
ZGVF HG PMKNF, CEGPF NZKJNKQ, PKNVRKEBJ, GKKIGEF CPRDRGQ
JGGI { YGRXZJF )atrecnoC(, GMQ ZGVG [FIGPZ FVTKN CFQ
CSYKZF HG REGRF ZGVF PSGD PKNVRKEBJ IE[F GBZGM- YGRXZJF
FZVGBF MZL 441, IGC' I' )BGDGSJ 5002( SYKZG%

3. 475 FIGNKO PJVGNKO DO CGMRK FRFDGK ~23|. MJKVGN CFY"Z ~43|.
BEZN KTKNF MPG [K PRG PKNVRKEBJ, CTKYZ M[CPYCKN CBZXG-FCZK, EYSBPVJPKQ FKB BI FZGVG FRVGXG
CPIYZ BIZ [N BGF YCGXF RPXB, MK PR CGYZ CGEE [N FJKVGN GNPT[F VIG I FJKVGN C[K FZGVG ~53|.
CFY"Z NVIG MPG PKNVRKEBJ, GCPKRGRKO RPGMKO KISK ~13|. MPG MBCK-CJQ GMBCK-ZB[, EGGIG CPIYZ HF TGE NVRK IKN
KGZ I F[VT FPKRGQ FDCGF. BEZN RPXBF KTKNF CJKVGN NGRG ZCG FRI[CG MF[VTG-NGGBK [N VSKMGSJKPGNRJKO,
CKBCGQ, MBCK-CJQ, MBCK-ZB[ GY[KK FKZEPG. MBCK-ZB[ CNJG FKZEPG CNJG KGZ I EYSBPVJPKQ NTGP PKNVRKEBJ ~53|.
BIE PFO NVIG. F[VTG-FNGGBK FKG PTJG GMNNG KZKEF FVSKMGSJKPGNRJKO { KZKEF CKBCGQ GY[KKO CFKZEPG. Y[KK
FGZF GPGZF, GCYZC %98 F[VZG PEEKO BNF NVK EKGGI [N F[VTG-FNGGBK FTKYZKG [N EYSBPVJPKQ FKG M[N [BZ
CYZC %95 PFKNEKO F[VZG PEEK FY[C GFZKMGH NVK EKGGI F[VTG-FNGGBK.
PRF G-3.0 P"D/Y"D/PRF. [RK FPKRGRKO RPXBG KTKNKO PBGE. CBGVQ EGPF N[K FZGVG FQ PCIKR KTKNGO GFQ PCIKR
[NF. RCEYG [RK PKRGRKO [GRKO CF[GGBF NBKRCG: 51.0 P"D/Y"D/ CEYSBPVJPKQ NPKNVRKEBJ, GPXBG [BGO 521 KNEKO FDKCG
ZB[GQ CKNEKO [BGCIRG MNGYKO CFY"Z GB F[VTG-FNGGBK N[BZ FVSKMGSJKPGNRJKO ~33|. norfE GIC' ~43| F[GG CKQ JKVGN
nnamahA GIC' ~92| CEYG B KTKNGF [N BEZN MJKVGN EYSBPVJPKQ FKB RDHZ [N BPVJPKQ GCTN VTKNG EGPF
FRZ[PG CKGZ ~13|. NBIZGRF FGIN C[KGGYF CK[ZBN. EYSBPVJPKQ { enimatehpmaxeD )enirdexeD(
P[GGY CBZF"C P[R 4991, GFKB BI PPBKKO FZGVG
MBCK-ZB[, KZKEF CKBCGQ GY[KK FKZEPG ~82,92|. BEZN
NFRKI MK FJKVGN CZGVF HG KVI GKNL.
[N BEZN EGPG NBNF [N VSKMGSJKPGNRJKO BIZKO GMGNNG
PGPNW, GMKGO, TO FIEZ ZGVG IE[G N[GY FZGVG, SCKZ
RDHZG FBPVJPKQ: 4=01 [TG ~31|. F[VTG-FNGGBK FTKYZKG
PMN FSKCG [XGKRG NTKN, FJKVGN CVPGNKQ MYG ZB[GQ BKRG
NB CZGZF, NTZGC HG F[VTF BZGM-JGGI KGZ PB[Z N[BZ
GIGCF NKJGN BGF CYCKTG GNTCGZ PTYC BIZ KVYGEK MCE.
PK[NC HF KGXZ KIS 1:3 [N EYSJZG NNCGBPVJPKQ ~82|. PSKCF
PYCN ZY [NG[F TE BZCTF [CGTG NBIZ IKN FJKVGN,
etarahccas enimatehpma-d, { etaflus enimatehpma-l ,d ~72|. VTKNGF RP[M TE T[Z [TG { BL FF[VTF FJKVGNK
BZCTF INYKO [GGKO [N enimatehpma-d, enimatehpma-l, d,
CTN F[VTF BZGM-JGGI KISK NVSKMGSJKPGNRJKO BIZKO {
BEZN FKB TZGC [N BZCT RDHZG BPVJPKRKO. MN JCNK PMKNF
{ GVTF REKZF BL FTNGNF NDZGO NPGG. HGFK BGPRO ZGVF
BEZN )llareddA( ZB[GQ NJKVGN CFY"Z, P[GO [FGB TNGN NDZGO NBK-SVKY MCE
PTZM FTXCKO FPZMHK NZKJNKQ ~33|. FGB BKRG PFGGF YG
C[NPGF. PKCRF FMPGSF [N YGRXZJF BKRG PBV[Z VTGNF HG. VPGNKQ FGB VSKMGSJKPGNRJ FEGPF CPKCRFG GCF[VTG TN
PHGQ ZL, MEK NFYN TN KNEKO [BKRO PXNKIKO NCNGT BGF VPGNKQ { enilomeP )natiN ,trelyC(
FBV[ZG NVGI B MPGS FZKJNKQ AL GNVHZ B GMRF TN
CCK-FSVZ, DEGNF KGZ ~52,62|. FCEN RGSU CKQ FZGVG FGB
KGZ CF[GGBF NYGRXZJF, GKTKNGF C[TG BNF [CFQ FPJGVN
vog.adf.www(.
)FPKET RNYI PGL BZ PKRFN FPHGQ GFZGVG FBPZKYBK
FKGO. ZP FZGVF CEO CCGYZ NBIZ PQ ZKJNKQ AL DCGFF
YXZ-JGGI, BKQ EKGGIKO TN [MKIG PGDCZ [N PGG VBGPK
F[KIZGZ F[GRG PYCN [GRK CKTKNG FZGVG FNNG NBGZL
CPJGVNKO TO PGO CNC. NDCK FZGVF FP[GGY CK[ZBN, BEZN
P[IZZ PKKEK GF[BZ BZCT [TG NBIZ-PMQ ~52|. C[N XGZG
NDCK ZGVG BEZN BHFZF CECZ SKMGQ PGDCZ NPGG VBGPK
C[GRF PYGRXZJF, NZKJNKQ AL [KIZGZ EG-[NCK: %05 PFIGPZ
FRIKGKG NDCK BEZN RX. BRG PHMKZKO, MK PBGDGSJ 4002 YKKP
KGPK CGEE [NF F[VTF BZGM-JGGI NP[L ZGC [TG FKGO.
FGEKT PKRFN FPHGQ GFZGVG FBPZKYBK, MK BKRG P[RF B
FRG[B BU FKB B F[O ZKJNKQ GRKR, CEGPF NYGRXZJF, CPRF
BKQ Y[Z SKCK CKQ RJKN BEZN NCKQ PGF. NRGMI RGRKO BNF
NBIZGRF FGIN CK[ZBN C[KGGY ZGV PKNVRKEBJ RGSV,
FVBGPK PCTKF ZVGBK BIZ, [BKRF Y[GZF NBEZN. RZBF MK
ZKJNKQ BZGL-JGGI )gnitcA gnoL( AL nilatiR ZPG ZTKNG [N BEZN CEO, GC[BZ FKNEKO RDZO FPGG
CNC, PXC FPTNF B FSKMGQ NPGG VBGPK. CKNE BIE RPXBG
FJKVGN CYGRXZJF C[N F[VTG-NGGBK. FZGVG GFPHGQ FBPZKYBK FGEKT [NIPK[F PFO FKF PGO PKCRK
VIGF TN Y[KKO CFKZEPG GFGVT JKYKO. ZY %7.6 FVSKYG B BKZGTK PGG VBGPK [N 21 KNEKO [RJNG B FZGVF. PKRFN
NF[VTG-NGGBK EGPG NZKJNKQ, BGNO NYGRXZJF FKKF F[VTF RX, C[GY FYREK. FVTGNF FCSSF TN EKGGIKO PBZF"C, NDCK
CPEEK FY"Z CYCGX FPJGVNKO NTGP BKRCG. YGRXZJF DZPF ZGVG B [KGGYF [N FZGVF BZGM-FJGGI [N BEZN, BEZN
FTKEG TN ML [NBGZL MN [R FPTYC FPKE F[KVGZ FPGCFY CIKN [R 5002 FK[TF FSGMRG FYREK NVKYGI TN
CYGRXZJF CP[L [RF ~42|. FPTYC RTZL PEK IGE[, GGXBGKG FJGCF CKGZ TCGZG.
BGF YCGX PIYZ FPKEF CPTYC BIZ FPJGVNKO [N ZGVG [GRG MEK [RKQ KFKF NFBKO NMN KNE B FZGVF
CZKJNKQ BG CYGRXZJF. [GGF N[K FZGVG ~33|. PKPXB HF PIHY B FXGZL CHPKRGQ
TN-VRK BKRCG C[KVGZ PEEK FY"Z, NNB FCEN P[PTGK CKQ JKVGN PFKNEKO FDKCG JGC KGZ NJKVGN CBEZN, G-%83 FDKCG CXGZF
CP[L IGE[ GFGXBG FKG EGPG { KZGQ NJKVGN CZGVG %52 PFKNEKO FDKCG JGC KGZ NJKVGN CPKNVRKEBJ, %73
PRF CGEE [N YGRXZJF, BKRCG G[NG[ PRG ZKJNKQ. RTZL PTYC NB MN FKNEKO FDKCG CBGVQ [GGF NPKNVRKEBJ GNBEZN:
SYKZG
FZVGBF MZL 441, IGC' I' )BGDGSJ 5002(

4. CEGPF NZKJNKQ, GMK FQ ZBGKG NFKG INY PZGVG FYG FZB[GQ .37-06 :22 ;1002 ,rtaideP vaheB 575
[RPXBG CPIYZKO F[GGBKKO, MK FQ KTKNG GCJGIG NJKVGN veD J .sredivorp erac yramirp rof snoitacilppa dna snoitacilpmi
C[RKO FBIZGRG FGIN C[KGGYQ [N PSVZ ZGVG IE[G : )A T M ( D H DA fo y d u tS t ne m t a e r T l a d om i t l u M H M I N
NP[KPF [BKRF V[GJF.
eht morf sgnidniF ,la & MJ nosnawS ,PS wahsniH ,SP nesneJ .8
MGRG BNF FVMG B FJKVGN CKNEKO [ZKJNKQ NB FBKO NFO
.668
-368 :71 ;2002 ,lorueN dlihC J .)DHDA( redrosid ytivitcarepyh
NMGNO F[VTG-NGGBK ZCG KISK GBU PSMRG-IKKO )VPGNKQ(. ticifed noitnetta dna yslap larberec htiw nerdlihc ni etadin
)YNGRKEKQ(, GHPQ PPG[L TGCZ TE NYCN F[VTF JKVGNK. CRGSU, -ehplyhtem fo ycaciffE ,la & N ihidaB ,SR velehS ,V ruzT-ssorG .7
CFY"Z. ZGVG BNG PIKKCG RJKNF YCGTF, NTKKO MKGN BKJK .44-04 :031 ;6991 ,scirtaideP J ?evitceffe dna
N-XKYNKKO GYNGRKEKQ, MGNO BKRO PFGGKO YG JKVGN ZB[GQ efas ti si :yspelipe dna redrosid ytivitcarepyh ticifed noitnetta ni
NBIZGRF INKVK FZKJNKQ FRVGXKO FKG VPGNKQ, RGDEK-EKMBGQ etadinehplyhteM ,la & J reeM red naV ,O ronaM ,V ruzT-ssorG .6
ZCKO. BGNO ZKJNKQ, MMN ZGVF, BKRG PBKO NMN BIE. TE .612-902 :24 ;3002 ,yrtaihcysP
CKGZ NFY"Z, GFKB DO FZGVF FPBKPF CKGZ TCGZ KNEKO cslodA dlihC dacA mA J .DHDA dna noitadrater latnem
PPKNVRKEBJ { FKB TEKKQ FZGVF FKTKNF, FHPKRF GFHGNF htiw nerdlihc ni tnemtsujda laroivaheb no etadinehplyhtem
fo stceffe tnemtaerT ,la & DJ ehcaoR ,WC sotnaS ,AD nosraeP .5
NSKMGO, ZKJNKQ { FZGVF FRVGXF CKGZ FPGZMC
.866-856 :151 ;4991 ,yrtaihcysP J mA .ypareht tnalumits cinorhc
F[VTGKF BZGMG-FJGGI. retfa ytivitcarepyh ticifed noitnetta htiw stluda ni msilobatem
HG P[GGY PHF [RKO SVGZG CNCE, GNB RXCZ TEKKQ PKET NDCK esoculg larbereC ,la & CA gniK ,LL reuanebeiL ,AL kihcotaM .4
CZGVF, GNB EGGI TN IGNKO [RVJZG PRJKNF. TO HB, ZGVF .222-191
EGGI TN BKZGTKO Y[KO BG PSMRK-IKKO [RKQ NY[ZO NJKVGN
:51 ;2991 ,mA N nilC cirtaihcysP .ygolocamrahpohcysP cirtaideP
.)dE( ,D reffhS :nI .stnalumits ehT ,J namredeiB & ET sneliW .3
FTNKKF CP[YN FKKXC. PBH FGIN FJKVGN CBJGPGYSJKQ NB .0991 ,kroY weN ,sserP drofliuG .tnemtaerT dna sisongaiD
KZKEF PTJF CKBCGQ GCP[YN, BL GVTF HG INVF CFP[L GYXC rof koobdnah A .redrosid ytivitcarepyh ticifed noitnettA .)dE(
GBK-KXKCG ZD[K ~63|. CIKN FJKVGN CBJGPGYSJKQ RKXVF ,AR yelkraB :nI .ypareht noitacideM ,AR yelkraB & JG luaPuD .2
YNF, NNB P[PTG ZVGBK, CNIW-FEO FEKBSJGNK GCYXC FNC, .4991 ,CD notgnihsaW
PRJKN BJGPGYSJKQ FQ MBCK-ZB[, MBCK-CJQ, CIKNG, TNKKF ,noitaicossA cirtaihcysP naciremA .)noitide htrof( launaM
MJKVGN CFY"Z { YNGRKEKQ ~73|. F[VTG-FNGGBK FTKYZKG lacitsitatS dna citsongaiD ,noitaicossA cirtaihcysP naciremA .1
GRSCN JGC KGZ PB[Z ZGVF BEZRZDK BIZ FRKR BU FKB CKCNKGDZVKF
BJGPGYSJKQ CZKZRK PBGE CVTGNG, GNMQ FGB KTKN KGZ
GCJKIG JKVGNK MPG NPKNVRKEBJ. FGTN PFJKVGN CFQ.
FSKYG [NBJGPGYSJKQ, NVIG CPIYZ ZB[GRK HF, KTKNG NFXKT JKVGN CZGVG NKNEKO FHYGYKO NG G[RPRTF PFO CTCZ
F[VTG-FNGGBK BG CXGZL CFVSY FJKVGN CDKRQ. FIGYZKO PVKDF INY PFFRDEG FCSKSK [N FFGZKO NJKVGN, GPBV[Z
F T ZM F F G Z K O G F I G Y ZK O , NN B F CE N P [ P T G K C [ K T G Z FTGCEF FV[GJF [[PQ [N FZGVG FIE[G BKRG "ZKJNKQ",
YSJKQ(. C[K FYCGXG IN [KVGZ P[PTGK CPEEK FY"Z NVK M[FSKCF NEIKK FJKVGN CZGVG FKB FZKTF PZKJNKQ.
[JGVNF CPKNVRKEBJ NTGP 481 CYCGXF [JGVNF CBJGPG- FZGVG FIE[G PYNG TN FJKVGN CKNEKO TO FY"Z
MVGN-SPKG BJGPGYSJKQ BG PKNVRKEBJ )FKG 44 KNEKO CYCGXF CNCE, GBKQ TEKKQ PKET TN F[VTGKG BZGMG-FJGGI.
KNEKO TO FY"Z [SGGDG BYZBK N[K YCGXG GYKCNG CBGVQ [N FVSKMGSJKPGNRJKO. BJGPGYSKJKQ RKQ MJKVGN [RKO SVGZG
CBIE FPIYZKO RTZL PTYC CP[L T[ZF [CGTG BIZ 822 { ZGVF CTN PRDRGQ [GRF, BL TO ZP CJKIG FEGPF NHG
CPSVZ PIYZKO ~83=04|, GFKB [GG-TZL NKTKNGG [N FZKJNKQ. NJKVGN CVSKMGSJKPGNRJKO RKQ NFXKT MKGO JKVGN CBJGPGYSJKQ
NRJKO. KTKNGF [N FZGVF CF[GGBF NBKRCG FGMIF TE TF JGC KGZ NNB SKCF CZGZF ~23|. NBGO KNEKO [BKRO PDKCKO
PRDRGQ FVTGNF [N BJGPGYSJKQ [GRF P[N FVSKMGSJKPG- FINV FJKVGN ~23|. CRGSU, K[ KNEKO [KDKCG NBI FZGVG
CPCGDZKO. ZKJNKQ, F[VTG-FNGGBK VIGG GNTKKO NB GVTRF MNN NBIZ
[BG[ZF NXGZL JKVGN CFY"Z GFZB[GRF [BG[ZF NXGZL JKVGN NGGBK, BL FPIYZ GFRKSKGQ PTKEKO TN ML [KISK NZGVF
CKNEKO TO FY"Z. HGFK FZGVF FZB[GRF [BKRF VSKMGSJKPGNRJ FBIZKO K[ BGPRO PRDRGQ VTGNF EGPF GBGG PKDGGQ F[VTG-
CRGCPCZ 2002 BG[Z BJGPGYSJKQ TN-KEK F-ADF NJKVGN NF[VTG-NGGBK, RKQ NFXKT MKGO INGVG. NVSKMGSJKPGNRJKO
srezialobatem(. MKGO CZGZ [BKQ NMGRF HG P[PTG JKVGNK ~73|. GBJGPGYSJKQ. CKNEKO [ZKJNKQ BKRF KTKNF TCGZO BG DGZP
PFKZKO )srezilobatem evisnetxE( GNPVZYKO BKJKKO )rooP BZGMG-JGGI RGSVG, MDGQ BEZN, EYSBPVJPKQ )EYSEZKQ(
)6D2PYC(. RKQ NSGGD B FBGMNGSKKF NVK FDRGJKV, NPVZYKO ZKJNKQ BZGMG-FJGGI, MPG YGRXZJF GZKJNKQ AL, GMQ PZGVG
BJGPGYSJKQ TGCZ IKNGU-IGPZKO TN-KEK XKJGMZGO 6D2054P NMKSGK ZGVK CP[L [TG BZGMG KMGNKO NKFRG PZGVG
[N FPTCKZ FJZGO-SKRVJK [N RGZBEZRNKQ )Mn5.4iK(. CGMRK FJKVGN K[ N[YGN B XGZMK FKNE. KNEKO FHYGYKO
rotibihni ekatpuer enilanerdaron evitceleS ~63| TN-KEK TKMGC NFPNKW TN FTZCG ZGVK.
BJGPGYSJKQ FGB PTMC CZKZRK [N YNKJF R[RK [N RGZBEZRNKQ {
JKVGNKG, BL FQ PDEKNG B PZIC FVTGNF [N FPJVN CCGBG
BJGPGYSJKQ { )arettartS( enitexomotA CFY"Z. DO NZGVG FIE[G K[ F[VTG-NGGBK GPKDCNG
FZVGBF MZL 441, IGC' I' )BGDGSJ 5002( SYKZG

5. 675 EGB"N: moc.liamtoh@66ileumhstirod .104-393 :24
JNVGQ: 3112346=20, RKKE: 035506=250. ;3002 ,tenikocamraF nilC .stluda yhtlaeh ni noitalumrof esaeler
PICZ PMGC: EGZK [PGBNK, ZIGC DNCZ 4, KZG[NKO. ± deifidom owt fo noitartsinimda laro retfa etadinehplyhtem fo
scitenikocamrahP ,la & SK kcirtaP ,BA nhguartS ,SJ ztiwokraM .52
.334-424
.57e :011 ;2002 ,scirtaideP .redrosid ytivitcarepyh ticifed :24 ;3002 ,yrtaihcysP cselodA dlihC mA J .yduts lebal mret gnol
noitnetta htiw slrig ega-loohcs ni obecalp susrev enitexomota a morf stluser htnom 21 miretni :etadinehplyhtem SORO yliad
fo ycaciffE ,la & ED seiraF ,HJ nietsnegnilieH ,J namredeiB .04 -ecno htiw tnemtaert DHDA ,la & M nietS ,W mahleP ,T sneliW .42
.1091-6981 :951 ;2002 ,yrtaihc .732-622 :68 ;0991 ,scirtaideP .enilomep dna enimatehpmaortxed
-ysP J mA .yduts dellortnoc-obecalp ,dezimodnar a :redrosid esaeler-deniatsus ,etadinehplyhtem esaeler-deniatsus ,etadinehp
y t i v i t c a r ep y h t i c i f e d no i t n e tt a h t i w n e r d l ih c ro f tn em t a e r t -lyhtem dradnats fo nosirapmoc a :redrosid ytivitcarepyh ticifed
enitexomota yliad-ecnO ,la & J rensurB ,JA nellA ,D noslehciM .93 noitnetta htiw nerdlihc no stnalumits gnitca-gnol fo ycaciffe
.7411-0411 :36 ;2002 ,yrtaihcysP evitaleR ,la & M notlimaH-eddoV ,FK edalsneerG ,EW mahleP .32
nilC J .redrosid ytivitcarepyh ticifed noitnetta htiw nerdlihc .501E
ni enitexomota fo seiduts dellortnoc-obecalp ,tpecnoc-fo-foorp :701 1002 ,scirtaideP .sgnittes larutan dna yrotarobal ni etadin
2 morf stluseR ,la & J namredeiB ,HJ nietsnegnilieH ,J recnepS .83 -ehplyhtem yliad-semit-eerht susrev etadinehplyhtem atrecnoC
.94-24 yad-a -ecnO ,la & L naelcaM-sworruB ,ME yganG ,EW mahleP .22
:)7 lppus( 95 ;8991 ,yrtaihcysP nilC J .stnecseloda dna nerdlihc .298-388 :801
:DHDA fo ygolocamrahpohcysP ,WJ nigoD & LR gnildniF .73 ;1002 ,scirtaideP .redrosid ytivitcarepyh ticifed noitnetta htiw
.22-61 :)21 lppus( 36 ;2002 ,yrtaihcysP nerdlihc ni yad a ecno etadinehplyhtem SORO fo liart dellortnoc
nilC J .nerdlihc ni redrosid ytivitcarepyh ticifed noitnetta ,dezimodnaR ,la & L mahleP ,W llihneerG ,LM hciarloW .12
rof tnemtaert levoN ,la & ET sneliW ,J namredeiB ,SJ recnepS .63 .503-592 :66 ;9991 ,rehT locamrahP nilC .nerdlihc ni redrosid yti
.666-266 :001 -vitcarepyh ticifed noitnetta fo tnemtaert eht ni etadinehplyhtem
;7991 ,scirtaideP .lairt revossorc ,dnilb-elbuod a :redrosid ytivitca ot ecnarelot etucA ,la & D atniuG ,S atpuG ,J nosnawS .02
-repyh ticifed noitnetta htiw nerdlihc ni enimatehpmaxed dna .)werbeH nI( 47-17
etadinehplyhtem fo stceffe ediS ,M rekraB & F namraJ ,D norfE .53 :231 ;7991 ,hauferaH .emordnys ytivitcarepyh ticifed noitnetta
.6e :001 ;7991 ,scirtaideP .lairt revossorc ,dnilb-elbuod a :redrosid rof tnemtaert etadinehplyhteM ,V rusT-ssorG & SR velahS .91
ytivitcarepyh ticifed noitnetta htiw nerdlihc ni enimatehpmaxed .674-374 :54 ;4891 ,yrtaihcysP nilC J .gninoitcnuf ralucsavoidrac
susrev etadinehplyhteM ,M rekraB & F namraJ ,D norfE .43 dna laroivaheb ,noitnetta no etadinehplyhtem fo tceffe eht dna
.1002 ,kroY weN ,noisiviD gnihsilbuP lacideM lliH-warGcM redrosid ticifed noitnettA ,WL remmilS & EM ennyW ,TR nworB .81
. no i t i de h t 0 1 , sc i t ue p a r eh T fo s i s a B l a c i g o lo c am r ah P eh T .861-321
,s'amreliG dna namdooG :nI .)sdE( ,EL dribmiL ,GJ namdraH .33 :4 ;5991 ,mA htroN nilC cirtaihcysP cselodA dlihC .stnalumits
.1131-0031 :401 ;9991 eht : r e d r o s id y t i v it c a r e p y h t i c i f e d n o i t n e t t A , L L l l i h n e e r G .71
,scirtaideP .redrosid ytivitcarepyh ticifed noitnetta htiw nerdlihc .234-904 :53 ;6991 ,yrtaihcysP cselodA dlihC dacA
ni etadinehplyhtem yliad-semit eerht dna ,yliad-eciwt ,ylno mA J .elcyc efil ssorca redrosiD ytivitcarepyH ticifeD noitnettA
-gninrom ot llareddA noonretfa etal/gninrom dna ylno-gninrom fo yparehtocamrahP ,la & T sneliW ,J namredeiB ,T recnepS .61
fo nosirapmoc A ,la & MA sinorhC ,ME yganG ,EW mahleP .23 .18
.34e -36 :611 ;03 ;2002 ,seR yrtaihcysP .emordnys etteruoT ro redrosid
:301 ;9991 ,scirtaideP .redrosid ytivitcarepyh ticifed noitnetta ytivitcarepyh ticifed noitnetta htiw syob ni ebol latnorf eht fo
htiw nerdlihc ni esruoc-emit dna ycaciffe :llareddA dna nilatiR noitallecrap IRM ,la & HS yksfotsoM ,M eskirederF ,RW setaK .51
fo nosirapmoc A ,la & KJ maldiM ,RH ffonorA ,EW mahleP .13 .9-3 :)21 lppuS( 36 ;2002 ,yrtaihcysP
nilC J .redrosid ytivitcarepyh ticifed noitnetta fo ygoloiboruen
.9991 ,scimonocE dna weivrevO ,la & ET sneliW ,J namredeiB ,SJ recnepS .41
lacideM .sgurd noitpircserp eman dnarb 002 poT ,JN elavtnoM .03 .92-41 :)41 lppuS(
.01e :701 ;1002 ,scirtaideP 85 ;7991 ,yrtaihcysP nilC J .redrosiD ytivitcarepyH ticifeD
.stceffe edis dna etar ycaciffe :)llareddA( stlas enimatehpma dna noitnettA fo tnemtaert eht ni stnasserpeditnA ,WC reppoP .31
stlas enimatehpmaortxed ± erutxim enimatehpma fo noitaulave .498-688 :24 ;3002
dellortnoc-obecalP ,la & R greB ,WF eyehT ,AP nnamhA .92 ,yrtaihcysP cslodA dlihC dacA mA J .nerdlihc evissergga dna
.8901-5801 :54 ;8991 ,mA htroN nilC rtaideP evitcarepyh rof noitacidem tnalumitsohcysp ot dedda enidinolc
.tneitap cirtaidep eht ni stnalumitsohcysp fo esu ehT ,RS aksilP .82 fo lairt dellortnoc dezimodnar A ,EJ trautS & LP llezaH .21
.4003-3003 .7011-0011 :972 ;8991 ,AMAJ .stnecseloda
;9991 ,scimonocE deM .ecnerefeR kseD 'snaicisyhP .)etaflus dna nerdlihc ni redrosid ytivitcarepyh ticifed noitnetta fo
enimatehpma ,etaflus enimatehpmaortxed ,etatrapsa enimat tnemtaert dna sisongaiD ,la & JR namzeB ,M leneG ,SL namdloG .11
-ehpma ,etarahccas enimatehpmaortxed( llareddA ,JN elavtnoM .72 .729-529 :3 ;1002 ,J cossA deM rsI
.555-545 :5 ;3002 .eussi laisrevortnoc a ± learsI nrehtron ni redrosid ytivitcarepyh
,sgurD rtaidaeP .yad loohcs eht ssorca redrosid ytivitcarepyh ticifed noitnetta rof esu etadinehplyhteM ,E nahaK & Y namlegoF .01
t ic i fe d n o i tn et ta h t i w n e rd l i hc n i o be c a lp dna ) at r ec no C .7701-1701 :061 ;3002 ,yrtaihcysP
dna AL nilatiR( snoitalumrof etadinehplyhtem yliad ecno J mA .redrosid ytivitcarepyh ticifed noitnetta fo tnemtaert
owt fo ycaciffe evitarapmoC ,la & L hciertseP ,R avliS ,F zepoL .62 eht ni sdnert lanoitaN ,la & CS sucraM ,JM fforemaG ,M nosflO .9
SYKZG
FZVGBF MZL 441, IGC' I' )BGDGSJ 5002(