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M. Mamdani Iiioeyoeiiiia, 66 eao e noa?oa Eiio?ieu (n=100 000) – 1,0 • Oaaee?aiea ?enea EI ia
et al. [55] «neo?ae–eiio?ieu»/ Oaeaeienea (n=15 271) – 0.9 oiia ea?aiey IIAI e
ino?ue EI ?ioaeienea (n=12 156) – 1,0 eieneaaie ionoonoaoao
Iai?ienai (n=5669) – 1,0 • Iai?ienai ia iaeaaaao
IIAI (n=33 868) – 1,2 «ea?aeii?ioaeoeaiui»
aaenoaeai
D. Solomon Iiioeyoeiiiia, 65 eao e noa?oa ?ioaeienea vs oaeaeienea = 1,24 (p = 0,011) • Ea?aiea ?ioaeieneaii (<
et al. [51] «neo?ae–eiio?ieu»/ n=54 475 ?ioaeienea v aac IIAI = 1,14 (? = 0,054) 90 aiae) annioee?oaony n
ino?ue EI Oaeaeienea vs aac IIAI = 0,93 ?eneii EI ii n?aaiaie?
?ioaeienea vs iai?ienai = 1,17 n oaeaeieneaii eee io?
Oaeaeienea vs iai?ienai = 0,95 noonoaeai i?eaia IIAI
?ioaeienea >25 ia/noo. vs oaeaeienea = 1,7
?ioaeienea < 25 ia/noo. vs oaeaeienea = 1,21
?ioaeienea 1–30 aiae=1,43 (? = 0,005)
?ioaeienea 31–90 aiae=1,46 (? = 0,003)
?ioaeienea > 90 aiae=1,04 (? = 0,8) • I?eai ?ioaeieneaa a
W. Ray Iiioeyoeiiiia, 50–84 aiaa Eaoi?ioai = 1,01 aunieeo aicao annioee?
et al. [52] ?ao?iniaeoeaiia/ Iai?ienai = 0,92 ?oaony n oaaee?aieai ?e?
oy?aeua ea?aeiaa? Oaeaeienea = 0,88 nea ea?aeiaaneoey?iuo
neoey?iua inei?ia? ?ioaeienea(? 25 ia/noo.) = 1,02 inei?iaiee
iey ?ioaeienea (> 25 ia/noo.) = 1,93 • I?eai ?ioaeieneaa anni?
D. Graham Iiioeyoeiiiia, 18–84 aiaa N?aaiaiea n ia i?eieia?ueie IIAI oee?oaony n oaaee?aiei
et al. [54 ] «neo?ae–eiio?ieu»/ n=1 394 764 • Oaeaeienea = 0,84 ?enea oy?aeuo ea?aeiaa?
ino?ue EI, «aia? • Eaoi?ioai = 1,06 neoey?iuo inei?iaiee
caiiay» nia?ou • Iai?ienai = 1,14 (ii n?aaiaie? n oaeaeie?
• ?ioaeienea (iacaaeneii io aicu) = 1,39 neaii)
(?= 0,066) • Iai?ienai ia iaeaaaao
< 25 ia/noo. = 1,23 ea?aeii?ioaeoeaiui yo?
> 25 ia/noo. = 3,00 (? = 0,03) oaeoii
• A?oaea IIAI = 1,13 (? = 0,03)
N?aaiaiea n oaeaeieneaii
• Eaoi?ioai = 1,26
• Iai?ienai = 1,36 (? = 0,016)
• ?ioaeienea (iacaaeneii io aicu) = 1,32 (?
= 0,015)
< 25 ia/noo. = 1,47 (? = 0,016)
> 25 ia/noo. = 3,58 (? = 0,016)
• A?oaea IIAI = 1,35 (? = 0,015) • I?eai ?ioaeieneaa anni?
S. Kimmel «Neo?ae–eiio?ieu»/ 40–75 eao Any a?oiia oe?oaony n oaaee?aieai
et al. [57] oy?aeua ea?aeiaa? n=1718 n ia?aui • Ia i?eieia?uea IIAI = 1,0 ?enea oy?aeuo ea?aeiaa?
neoey?iua inei?ia? EI • IIAI = 0,55 neoey?iuo inei?iaiee
iey n=6800 aac EI • ?ioaeienea = 1,16
• Oaeaeienea = 0,43
Ia i?eieia?uea aoaoeenaeeoeeiao? eeneioo
• Ia i?eieia?uea IIAI = 1,0
• IIAI = 0,68
• ?ioaeienea = 1,19
• Oaeaeienea = 0,35
I?eieia?uea aoaoeenaeeoeeiao? eeneioo
• Ia i?eieia?uea IIAI = 1,0
• IIAI = 0,77
• ?ioaeienea = 1,14
• Oaeaeienea = 0,67
?ioaeienea vs oaeaeienea = 2,72 (? = 0,01)
?ioaeienea vs iai?ienai = 3,39


386 13, 7, 2005
oOaeCOa a aOaAeeiCe
?oi iiiaea iaoeaiou, eia?uea ea?aeiaaneoey?iue ?ene, iaiia?aiaiii ?acaeoeai ea?aeiaaneoey?iuo eaoano?io ia i?inea?eaaeinu [7,75,76]
n IIAI i?eieia?o ieceea aicu aoaoeenaeeoeeiaie eeneiou. Ii aaiiui eee aa?a ioia?aeinu nie?aiea eo ?anoiou [77,78]. Iaeiiao, eia?ony
yenia?eiaioaeuiuo enneaaiaaiee (in vitro e ex vivo), iaeioi?ua IIAI aaiiua i nouanoaaiiii oaaee?aiee ?enea ino?iai EI a oa?aiea 1–30
(eaoi?ioai, eiaiiaoaoei) iiaoo eiieo?e?iaaou n aoaoeenaeeoeeiaie aiae o iaoeaioia, i?ae?aoeaoeo i?eai IIAI iinea aeeoaeuiiai eo i?e-
eeneioie ca naycuaaiea n aeoeaiui oaio?ii OIA–1 [65,66] e ioiaiyou iaiaiey (I?=2,60), a oi a?aiy eae o iaoeaioia, i?eieiaaoeo IIAI a
aai «aioeaa?aaaioiue» yooaeo [67]. Iaiaei acaeiiaaenoaey a?oaeo i?ioeii (I?=1,05) eee i?iaie?a?ueo i?eai IIAI oaaee?aiey ?enea
IIAI – eaoii?ioaia [68], aeeeioaiaea [67], ?ioaeieneaa [67,69,70] e ino?iai EI ia iaae?aaeinu (I?=1,07) [79]. I?eia?aoaeuii, ?oi iniaai-
oaeaeieneaa [71] n aoaoeenaeeoeeiaie eeneioie ia ioia?aii. Iaoa?eaeu ii nouanoaaiiia oaaee?aiea ?enea EI eiaei ianoi o iaoeaioia n ?A e
yieaaieieiae?aneeo enneaaiaaiee, eana?ueany ?enea ea?aeiaaneoey?- nenoaiiie e?aniie aie?aieie (eia?o aunieee aacaeuiue ea?aeiaaneo-
iuo eaoano?io o iaoeaioia, iaiia?aiaiii i?eieia?ueo IIAI e ey?iue ?ene, naycaiiue n onei?aiiui ?acaeoeai aoa?ineea?ioe?aneiai
aoaoeenaeeoeeiao? eeneioo, ia iiiai?eneaiiu e i?ioeai?a?eau [72]. Ia- ii?a?aiey ninoaia) [80–82], i?ae?aoeaoeo i?eieiaou IIAI (I?=3,68).
i?eia?, ii aaiiui iaieo aaoi?ia, i?eai eaoi?ioaia [73] eee e?auo I?aaeaii, ?oi i?iaeaia eaea?noaaiiuo acaeiiaaenoaee IIAI e
I–IIAI (aieaa 60 aiae) [74] annioee?oaony n oaaee?aieai ?enea EI. aoaoeenaeeoeeiaie eeneiou i?aanoaaeyaony iniaaiii aeooaeuiie aey
Ia?ao oai a a?oaeo enneaaiaaieyo nayce ia?ao ni?aoaiiui i?eaiii iaoeaioia, no?aaa?ueo ?aaiaoe?aneeie caaieaaaieyie. Iiyoiio aieu-
aoaoeenaeeoeeiaie eeneiou e I–IIAI [58,59] (aee??ay eaoi?ioai) e oeinoao ec ieo iioaioeaeuii iieacaii iacia?aiea ieceeo aic
aoaoeenaeeoeeiaie eeneiou. I?aaeaii, ?oi eiaiii o yoie eaoaai?ee ia-
oeaioia iiei?eoaeuiua e io?eoaoaeuiua «ea?aeiaaneoey?iua» yooae-
Yiaioaeeaeuiua
O?iiaioeou
ou IIAI e eaea?noaaiiua acaeiiaaenoaey IIAI e aoaoeenaeeoeeiaie
eeaoee
eeneiou iiaoo auou iniaaiii eeeie?anee cia?eiuie e o?aao?o niaoe-
Ia naeaeoeaiua

OIA–1 OIA–1 aeuiiai eco?aiey.
IIAI
A i?ioeaiiiei?iinou i?aanoaaeaiiui auoa iaoa?eaeai i iioai-
OIA–2
Eiaeaeoi?u OIA–2 oeaeuii iaaeaaii?eyoiuo iineaanoaeyo ia?ooaiey aaeaina PGI2/TXA2
iia aeeyieai eiaeaeoi?ia OIA–2 ia na?aa?ii–ninoaenoo? nenoaio, ia-
O?iiaienai (OoA2) I?inoaoeeeei (PGI2)
no?aaaony aii?in ia «aioeaoa?iaaiiii» aaenoaee yoeo i?aia?aoia. Yoi,
No?aao ninoau ?anoe?yao ninoau eae iieaaa?o, ii?ao auou naycaii n iiaaaeaieai OIA–2–caaeneiiai
Niinianoaoao aa?aaaoee Iiaaaeyao aa?aaaoe?
eiiiiiaioa ainiaeeoaeuiiai i?ioanna, ea?a?uaai aa?io? ?ieu a ?ac-
o?iiaioeoia o?iiaioeoia
aeoee e i?ia?anne?iaaiee aoa?ineea?ioe?aneiai ii?a?aiey ninoaia e
aanoaaeeecaoee aoa?ineea?ioe?aneie aeyoee [83–85]. Iaiiiiei, ?oi
Aaiinoac O?iiaic
iaiei ec iaeaieaa ?oanoaeoaeuiuo e niaoeoe?iuo «ainiaeeoaeuiuo»
ia?ea?ia ea?aeiaaneoey?iiai ?enea yaeyaony N–?aaeoeaiue aaeie
?en. 2. Aaenoaea IIAI e OIA–2 eiaeaeoi?ia
ia neioacaOoA2 e PGI2 (N?A), a oae?a eioa?eaeeei (EE)–6 [86]. Eia?ony aaiiua, ?oi o iaoeai-
oia n oy?aeie eoaie?aneie aieaciu? na?aoa (EAN) (a n?aaiai noaiice-

Oaaeeoa 3. I?eiaiaiea IIAI e ea?aeiaaneoey?iue ?ene (I?iaie?aiea)
/

L.E. Levesque Iiioeyoeiiiia, Cai?iaua ii?e? Ia i?eieia?uea aoaoeenaeeoeeiao? eeneioo: • I?eai IIAI, oaeaeieneaa
et al. [110] «neo?ae–eiio?ieu»/ eua e?ae aac EI • IIAI = 1,04 e iaeieneeaia ia anni?
ia?aue EI a aiaiiaca • Iai?ienai = 1,59 oee?oaony n ?eneii EI
n = 113 927 • Oaeaeienea = 1,07 • I?eai ?ioaeieneaa anni?
• ?ioaeienea = 1,37 oee?oaony n oaaee?aieai
< 25 ia/noo. = 1,38 ?enea EI
> 25 ia/noo. = 1,23 • I?eai aoaoeenaeeoeeiaie
• Iaeieneeai = 0,59 eeneiou nie?aao ?ene EI
I?eieia?uea aoaoeenaeeoeeiao? eeneioo ia oiia ea?aiey iecee?
IIAI = 0,94y ie, ii ia aunieeie aica?
• Iai?ienai = 0,60 ie ?ioaeieneaa
• Oaeaeienea = 0,88
• ?ioaeienea = 1,07
< 25 ia/noo. = 1,0
> 25 ia/noo. = 2,36
Iaeieneeai = 1,59
F.T. Shaya Iiioeyoeiiiia Iiioeyoey n au? Oaeaeienea = 1,19 • I?eai eieneaia ia anni?
et al. [111] eiai?oiia/EI nieei ea?aeiaa? ?ioaeienea=1,09 oee?oaony n ?eneii EI
neoey?iui ?eneii

Oaaeeoa 4. O?iiaiyiaiee?aneea inei?iaiey ia oiia ea?aiey iaeieneeaiii,
?ioaeieneaii e oaeaeieneaii [61,62]
(n=19 087) (n=15 268) (n=17 458)
Ea?aeiaaneoey?iua 0,10% 0,14% 0,16%
o?iiaiyiaiee?aneea inei?iaiey I? = 1,38 (0,71–2,67) I? = 1,72 (0,87–3,40)
Oa?aa?iaaneoey?iua 0,27% 0,48% 0,39%
o?iiaiyiaiee?aneea inei?iaiey I? = 1,68 (1,15–2,46) I? = 1,66 (1,10–2,51)


387

13, 7, 2005
oOaeCOa a aOaAeeiCe
?iaaiea >2,6 ei?iia?iuo a?oa?ee) iacia?aiea oaeaeieneaa i?eaiaeo e Aaiiua, naeaaoaeunoao?uea i aieaa aeaaii?eyoiii aeeyiee oaea-
nouanoaaiiiio oeo?oaie? yiaioaeee–caaeneiie aaciaeeaoaoee eieneaa ia na?aa?ii–ninoaenoo? nenoaio (ii n?aaiaie? n ?ioaeiene-
(?=0,026), ?oi ei??aee?oao ni nie?aieai eiioaio?aoee N?A (?=0,019) e aii) iieo?aiu e a eeeie?aneeo enneaaiaaieyo [105–108,113,114]. Aua a
a?oaiai ia?ea?a ea?aeiaaneoey?iiai ?enea – ieeneaiiiai eeiii?ioaeia i?ioanna aiaeeca aaiiuo enneaaiaaiey VIGOR auei onoaiiaeaii, ?oi o
ieceie ieioiinoe (?=0,028) ii n?aaiaie? n iaoeaioaie, iieo?aaoeie iaoeaioia, i?eieiaaoeo ?ioaeienea, nenoiee?aneia AA ia 3,6 ii ?o. no.
ieaoaai [87]. ?oi eanaaony ?ioaeieneaa, oi, ii aaiiui iaieo aaoi?ia, auoa, ?ai o iaoeaioia, i?eieiaaoeo iai?ienai, a ?anoioa ?acaeoey AA
yoio i?aia?ao iaeaaaao «iaeo?aeuiui» yooaeoii a ioiioaiee yiaioa- a n?aaieaaaiuo a?oiiao ninoaaeea niioaaonoaaiii 9,7% e 5,5% [115].
eee–caaeneiie aaciaeeaoaoee o cai?iauo aia?iaieuoaa [88] e o aieu- ?anoioa ?acaeoey AA a enneaaiaaiee CLASS ia oiia ea?aiey oaeaeie-
iuo n EAN [89], e ia aeeyao ia eiioaio?aoe? ainiaeeoaeuiuo ia?ea?ia neaii ninoaaeea 2,7% e ia ioee?aeanu io ieaoaai (3,4%) [7]. Oaeaeienea
– N?A e ?aoaioi?ia EE–6 [89]. A oi ?a a?aiy, ii aaiiui a?oaiai ieaoa- a iaiuoae noaiaie aanoaaeeece?oao AA e aucuaaao caaa??eo ?eaeinoe,
ai–eiio?iee?oaiiai enneaaiaaiey, o iaoeaioia n ino?ui ei?iia?iui ?ai ?ioaeienea [105], aey eioi?iai oa?aeoa?ai aicicaaeneiue aeia?-
neia?iiii ea?aiea ?ioaeieneaii (25 ia/noo.) a oa?aiea 6 ian. annioe- oaiceaiue yooaeo, ia aeeyao ia aeiioaiceaiue yooaeo eiaeaeoi?a AIO
e?oaony n ainoiaa?iui nie?aieai eiioaio?aoee N?A e EE–6 a ionoono- – eeceiii?eea [106]. I?e i?yiii n?aaiaiee aeia?oaiceaiiai yooaeoa
aea iaaaoeaiiai aeeyiey ia yiaioaeee–caaeneio? aaciaeeaoaoe? [90]. yoeo i?aia?aoia o iaoeaioia n inoaia?o?icii (n=1000) ni noaaeeuiie AA
Ianiiiaiiue eioa?an i?aanoaaey?o aaiiua F. Cippolone e niaao. [91], onoaiiaeaii, ?oi oaaee?aiea nenoiee?aneiai AA (ii e?aeiae ia?a, ia 2
eioi?ua i?iaaee i?iniaeoeaiia enneaaiaaiea neo?ae–eiio?ieu ?anoiou ii ?o.no.) ioia?aii a 14,9% neo?aaa o iaoeaioia, iieo?aaoeo ?ioaeie-
ano?a?aaiinoe aeeaeae OIA o 864 iaoeaioia, ia?aianoeo ia?aue ino- nea (25 ia/noo.) e oieuei a 6,9% neo?aaa – oaeaeienea (200 ia/noo.)
?ue EI eee eoaie?aneee einoeuo e o 864 iaoeaioia aac yoeo inei?ia- (p<0,001). Ii aaiiui F. Wolfe e niaao. [96], o iaoeaioia n ?A e inoaia?o-
iee. Ieacaeinu, ?oi ?anoioa –765GC aaoa?iceaio e –765NN aiiiceaio no- ?icii ?anoioa ?acaeoey ioaeia e AA auea ainoiaa?ii ie?a o iaoeaioia,
uanoaaiii auoa a eiio?ieuiie (43,3% e 6,4%), ?ai a iniiaiie a?oiia i?eieiaaoeo oaeaeienea e I–IIAI, ?ai ?ioaeienea. M. Mamdani e ni-
(17,9% e 1,1%) (p<0,001 e p<0,04, niioaaonoaaiii.). N?aae iineoaeae aao. [53] ia iniiaaiee iiioeyoeiiiiai ?ao?iniaeoeaiai enneaaiaaiey
–765GC e –765CC aaiioeiia ?ani?ino?aiaiiinou EI e einoeuoa auea (aieaa 1 400 000 iaoeaioia ii?eeiai aic?anoa) iaia?o?eee, ?oi ?ene
nouanoaaiii ie?a (I?=0,48 e 0,33, niioaaonoaaiii). I?eia?aoaeuii, ?oi ia?aie (a oae?a iiaoi?iuo) ainieoaeecaoee ii iiaiao na?aa?iie iaai-
iieeii?oeci OIA–2 ia aeeyao ia neioac IAI2 eeaoeaie ninoaenoiai yi- noaoi?iinoe nouanoaaiii ia?anoae o iaoeaioia, aia?aua ia?aaoeo i?e-
aioaeey e yiaioaeee–caaeneio? aaciaeeaoaoe?. Yoe aaiiua iiaoaa?- ieiaou I–IIAI (I?=1,8) e ?ioaeienea (I?=1,5), ii ia oaeaeienea
?aa?o aa?io? ?ieu OIA–2 a ?acaeoee aoa?io?iiaica. Ia enee??aii, (I?=1,0). A a?oaeo n?aaieoaeuiuo enneaaiaaieyo oae?a auei iieacaii,
?oi iaoeaiou n ?acee?iuie aaiioeiaie OIA–2 iiaoo ii–?aciiio «ioaa- ?oi o iaoeaioia n inoaia?o?icii, no?aaa?ueo AA eee naoa?iui aeaaa-
?aou» ia I–IIAI e eiaeaeoi?u OIA–2, iaiaei yoio aniaeo i?eiaiaiey oii, i?eai oaeaeieneaa e ?ioaeieneaa annioee?oaony n oaaee?aieai
oeacaiiuo i?aia?aoia ia enneaaiaaeny. nenoiee?aneiai e aeanoiee?aneiai AA, ii yoio yooaeo nouanoaaiii ai-
Aanoaaeeecaoey AA e aaeiiiainaoey na?aa?iie iaainoaoi?iinoe – eaa au?a?ai ia oiia ea?aiey ?ioaeieneaii [107,108]. Iaaaaii auee
oi?ioi ecaanoiua inei?iaiey i?eaia IIAI [92–99]. A oi ?a a?aiy ni- iioaeeeiaaiu ?acoeuoaou iaoa–aiaeeca eiio?iee?oaiuo enneaaiaaiee,
a?aiaiiay oa?aiaaoe?aneay no?aoaaey ea?aiey a?oa?eaeuiie aeia?oai- eana?ueany aeeyiey eieneaia ia AA. [113] Ieacaeinu, ?oi ?ene AA ia
cee (AA) iai?aaeaia ia oieuei ia ii?iaeecaoe? AA, ii e ia ei??aeoe? oiia ea?aiey eieneaaie auoa, ?ai ieaoaai (I?=1,81) e I–IIAI
yiaioaeeaeuiie aenooieoee [100], ia?ooaiea eioi?ie ii nia?aiaiiui (I?=1,29). I?e yoii ea?aiea ?ioaeieneaii annioee?iaaeinu n aieaa
aunieei ?eneii AA (I?=2,63 vs ieaoaai e I?=1,78 vs I–IIAI), ?ai oa-
i?aanoaaeaieyi ea?aao aa?io? ?ieu a iaoiaaiaca e eeeie?aneii oa?a-
iee AA e naycaiiuo n iae na?aa?ii–ninoaenouo inei?iaiee [101]. Ii eaeieneaii (I?=1,53 e I?=0,82 niioaaonoaaiii) e yoi?eeieneaii
aaiiui M.E. Wildansky e niaao. [102], o iaoeaioia n AA ia oiia i?eaia (I?=1,25 e I?=1,47 niioaaonoaaiii). Ii aaiiui yieaaieieiae?aneiai
oaeaeieneaa ioia?aaony ainoiaa?iia oneeaiea yiaioaeee–caaeneiie enneaaiaaiey («neo?ae–eiio?ieu») ?ene ?acaeoey AA ia oiia i?eaia
aaciaeeaoaoee ?a?ac 3 ?ana (iinea i?eaia ia?aie aicu) e ?a?ac iaaae? ?ioaeieneaa ainoiaa?ii auoa, ?ai oaeaeieneaia (I?=1,6) e I–IIAI
iinoiyiiiai i?eaia. Yoi yooaeo eiae ianoi, ianiio?y ia ainoiaa?iia (I?=1,4), e ii n?aaiaie? n eeoaie, ia i?eieia?ueie IIAI (I?=1,6)
nie?aiea eiioaio?aoee PGI2 a ii?a e ionoonoaea aeiaieee eiioaio?a- [114]. Oioy e?aoeia?aiaiiui iiauoaieai AA a?ya ee ii?ii iauynieou
oee F1–ecii?inoaia eee TxA2. Ii aaiiui a?oaeo aaoi?ia, oaeaeinea (ii oaaee?aiea ?enea ino?iai EI ia oiia ?ioaeieneaa, yoio yooaeo, iani-
ia ?ioaeienea e aeeeioaiae) nouanoaaiii oeo?oaao ooieoe? ninoae- iiaiii, ii?ao eiaou cia?aiea a iaino?aiee EAN e ia?ooaiee iicaiai-
noiai yiaioaeey e iiaaaeyao ?acaeoea ieeneeoaeuiiai no?anna ia iiaa- ai e?iaiia?auaiey.
ee yenia?eiaioaeuiie aeia?oaicee o iao?ee–?oanoaeoaeuiie eeiee e?un A caee??aiea neaaoao iia?a?eioou, ?oi i?aanoaaeaiiua auoa ia-
Dahl [103]. I?eia?aoaeuii, ?oi oeo?oaiea ooieoee yiaioaeey annioee- oa?eaeu, oioy, ia ia?aue acaeya, iiaoaa??aa?o oi?eo c?aiey i oii, ?oi
?iaaeinu n oaaee?aieai yeni?annee neioaoacu ieneaa acioa a noaiea ea?aeiaaneoey?iua inei?iaiey – «eeann–niaoeoe?aneee» yooaeo eie-
ai?ou, a oae?a ii?iaeecaoeae aaci?aeaenaoeee a ioaao ia noia?ienea neaia (ii e?aeiae ia?a, a aicao auoa ?aeiiaiaoaiuo), iinyo i?aaaa?e-
aeniooaco, nie?aieai o?iaiy 8–ecii?inoaia e «i?iainiaeeoaeuiiai» oaeuiue oa?aeoa? e iiiaea ec ieo inoa?ony iaainooiiuie aey aaoaeuii-
oeoieeia – EE–1. A a?oaii enneaaiaaiee, auiieiaiiii yoie ?a a?oiiie ai iacaaeneiiai aiaeeca. Ia aiaa?e?iaaiiua yenia?ou ia?aua?o aie-
aaoi?ia, auei iieacaii, ?oi o e?un Dahl n iao?ee–caaeneiie AA aaaaa- iaiea ia oi, ?oi aa?a iaoa?eaeu enneaaiaaiey APPROVe, eioi?ua, eae
iea oaeaeieneaa (ii ia ?ioaeieneaa) i?eaiaeo e iiei?eoaeuiie aeia- o?a ioia?aeinu, iineo?eee oi?iaeuiui iniiaaieai aey i?ae?auaiey
ieea ii?oieiae?aneeo ia?ooaiee a ii?eao, nie?aie? yeni?annee e?IE auionea ?ioaeieneaa, ia iiaaa?ony iaiicia?iie o?aeoiaea. I?e aieaa
N?A a ii?a?iie oeaie e i?ioaeio?ee [119]. aaoaeuiii aiaeeca ia?auaao ia naay aieiaiea ia?aaienaeuiia nie?a-
A oi ?a a?aiy, ii aaiiui D. Bulut e niaao. [104], o iaoeaioia n AA ia iea ?anoiou ea?aeiaaneoey?iuo inei?iaiee a a?oiia iaoeaioia, iieo-
oiia aaaaaiey ia?aeieneaa ioia?aeinu ainoiaa?iia nie?aiea yiaioa- ?aaoeo ieaoaai, a oa?aiea iineaaieo ianyoaa yoiai eniuoaiey, ii n?aa-
eee–caaeneiie aaciaeeyaoaoee, oiaaa eae I–IIAI (aoaoeenaeeoeeao), iaie? n eiinoaioiui o?iaiai yoeo inei?iaiee o iaoeaioia, iieo?aaoeo
iai?ioea, oeo?oaee ooieoe? yiaioaeey. Aaeuaaeienea i?iyaeyao ?ioaeienea [121]. I?e nio?aiaiee noiaiie i?eaaaiie aeiaieee yoeo in-
aicicaaeneiue aeia?oaiceaiue yooaeo i?e oaaee?aiee aicu i?aia?a- ei?iaiee a iniiaiie e eiio?ieuiie a?oiia (i?aaeaii, ?oi ieaoaai a?ya
oa a aeaiaciia io 20 ia/noo. ai 80 ia/noo. ee ii?ao iaeaaaou «aioeo?iiaioe?aneei» yooaeoii), ?acee?ey a ?anoi-




388 13, 7, 2005
oOaeCOa a aOaAeeiCe
oa ea?aeiaaneoey?iuo inei?iaiee aie?iu auee au auou eeeie?anee ia ea?aeiaaneoey?iuie iiai?iuie yooaeoaie [122]. Oai ia iaiaa ai ioa-
cia?eiuie. Iano?aaiey iioaioeaeuiuo iaainoaoeia eiio?iee?oaiuo eeeaoee aiiieieoaeuiuo aaiiuo ia eo ea?aeiaaneoey?iie aaciianiinoe
enneaaiaaiee, naycaiiuo n aaoa?iaaiiinou? iaoeaioia, a oao neo?ayo, iaiaoiaeii i?eieiaou ai aieiaiea neaao?uea iniiaiua iiei?aiey e
eiaaa aa?iyoiia inei?iaiea ii?ao iaae?aaouny i?aiu ?aaei, auoiaeo ca i?eaa??eaaouny neaao?ueo ?aeiiaiaaoee [123]:
?aiee caaa? yoie ioaeeeaoee e caneo?eaaao niaoeaeuiie aeneonnee nia- • aaoaeuii eioi?ie?iaaou iaoeaioia i iioaioeaeuiuo ea?aeiaa-
oeaeenoia a iaeanoe iaaeoeineie noaoenoeee. N aua aieuoae inoi?i?- neoey?iuo iiai?iuo yooaeoao anao i?aia?aoia, iaeaaa?ueo oa?aeoa-
iinou? neaaoao ioiineouny e ?acoeuoaoai ?ao?iniaeoeaiuo yieaaieiei- ?enoeeaie eiaeaeoi?ia OIA–2;
ae?aneeo enneaaiaaiee, iniiaaiiuo ia aiaeeca aaieieno?aoeaiuo aac • iacia?aou IIAI n iniaie inoi?i?iinou? (eee ecaaaaou?), o iaoe-
aaiiuo [51–54], eioi?ua eia?o ?ya iaainoaoeia e ia?aie?aiee [109] e ii- aioia, eia?ueo ?ene ea?aeiaaneoey?iuo inei?iaiee;
yoiio iiaoo nouanoaaiii ?anoiaeouny n aaiiuie, iieo?aiiuie a i?ioan- • i?iaiaeou ouaoaeuiia «iiieoi?e?iaaiea» ea?aeiaaneoey?iuo
na eeeie?aneeo enneaaiaaiee [57]. A?ya ee ii?ii niaeaneouny n iiaieai inei?iaiee (iniaaiii AA) ia i?ioy?aiee anaai a?aiaie i?eaia;
iaeioi?uo yenia?oia i oii, ?oi i?eiaiaiea ?ioaeieneaa neaaiaaei ia- • ia i?aauoaou ?aeiiaiaoaiua aicu, iineieueo iaeucy enee??eou,
?aie?eou (eee aiiaua cai?aoeou) ianeieueeie aiaaie ?aiuoa [29,50], a ?oi ea?aeiaaneoey?iue ?ene iiauoaaony i?e aeeoaeuiii i?eaia i?a-
oai aieaa naycuaaou oieuei n aai i?eaiii oaaee?aiea ea?aeiaaneoey?- ia?aoia a aunieeo aicao;
iie eaoaeuiinoe a NOA [54]. A iueo ao?iie, ia anaaaa ei??aeoiie iiea- • i?e iaiaoiaeiinoe iacia?aou ieceea aicu aoaoeenaeeoeeiaie
ieee i iaainoaoeao eiaeaeoi?ia OIA iacaneo?aiii ioioee ia aoi?ie eeneiou, oioy yooaeoeaiinou yoie oa?aiee aey i?aaioa?auaiey ea?ae-
ieai eo ainoieinoaa, naycaiiua n aieaa aunieie aano?iyioa?ieiae?aneie iaaneoey?iuo inei?iaiee o iaoeaioia, i?eieia?ueo IIAI, ia aieaca-
aaciianiinou?. E ni?aeaie?, oi?iaeuiua ia?aaiau ca?oaa?iuo ioaee- ia.
eaoee, aac eo ei??aeoiiai aiaeeca ia?aee iiyaeyouny ia no?aieoao ioa- • I?e auai?a i?aia?aoia eiaou a aeao, ?oi iaeioi?ua IIAI (ia-
?anoaaiiuo ?o?iaeia [124]. N iaoae oi?ee c?aiey, oaeea iaoa?eaeu ii- i?ienai – 500 ia/2 ?aca a noo e oaeaeienea 200 ia/noo.) i?iyaey?o aieaa
aoo i?eianoe aieuoa a?aaa, ?ai iieucu, a ieaia ?aaeuiiai iiauoaiey aunieo? ea?aeiaaneoey?io? aaciianiinou, ?ai a?oaea IIAI (?ioaeie-
aaciianiinoe oa?aiee IIAI. nea, aaeuaaeienea, aeeeioaiae, eaoi?ioai).
Iaeucy enee??eou, ?oi ia?anoaiea ?enea ea?aeiaaneoey?iuo in-
ei?iaiee ia oiia i?eaia ?ioaeieneaa (oieuei a aunieeo aicao?) nay- aEUA?UU?
1. Brune K, Hinz B. The discovery and development of antiinflammatory drugs. Arthritis
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2. cOOIO‚ O.a. e?EIAIAIEA IAOUA?OEI?? O?OUE‚O‚OOOIEUAI?I?? O?AO?UO‚ ‚
ia?, anee oaeaeienea (e aaeuaaeienea) i?aanoaaey?o niaie i?iecaia-
IAE?EIA ‚ I?IA 21 ‚AI. eaU, 2003; 11 (7), 375–378
iua noeuoiiaieaa, oi ?ioaeienea (e yoi?eeienea) – i?iecaiaiua noeu- 3. FitzGerald GA, Patrono C. The Coxibs, selective inhibitors of cyclooxygenase–2. New Engl
oiia. Ia?eia iieo?ecie ?ioaeieneaa ninoaaeyao 18 ?ania, ii n?aaia- J Med 2001; 345: 433–442
4. Simon DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin
ie? n 11 ?anaie o oaeaeieneaa e 8 ?anaie o aaeuaaeieneaa. ?ioaeienea
synthesis and inhibition. Pharmacol Rev 2004; 56: 387–437
iaoaaieece?oao aeaaiui ia?acii ca n?ao aeoeaiinoe oeoicieuiuo oa?-
5. Warner TD, Mitchel JA. Cycloxygenase; new isoforms, new inhibitors, and new lessons
iaioia (a ia ?450, eae oaeaeienea), a ?acoeuoaoa ?aai ia?acoaony ia ia-
from clinic. FASEB J 2004; 18: 790–804.
iaa 5 iaoaaieeoia, eioi?iaoey i naienoaao eioi?uo e?aeia neoaiay. 6. Bombardier C, Lane L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of
Eia?ony aaiiua i oii, ?oi ?ioaeienea (a ioee?ea io oaeaeieneaa e ia- rofecoxib and naproxen in patients with rheumatoid arthritis. New Engl J Med 2000; 343:
1520–1528
eieneeaia) eioaineaii iaeaieeaaaony a ii?eao, ?oi a ii?aaaeaiiie noa-
7. Silverstein FE, Faich G, Goldstein JL et al. Gastrointestinal toxicity with celecoxib ver-
iaie iicaieyao iauynieou, ii?aio yoio i?aia?ao a aieuoae noaiaie au-
sus nonsteroidal anti–inflammatory drugs for osteoarthritis and rheumatoid arthritis: the
cuaaao caaa??eo ?eaeinoe e, aa?iyoii, aanoaaeeecaoe? AA, ?ai a?oaea
CLASS study: a randomized controlled trial. Celecoxid long–term arthritis saferty study.
IIAI. ?aiaa naycu ia?ao oeie?aneie no?oeoo?ie e iiai?iuie yooae- JAMA 2000; 284:1247–1255
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aa i?aia?aoia, oioy eo aiaeiae n oniaoii i?iaie?a?o i?eiaiyouny a
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iaaeoeia. A ea?anoaa i?eia?ia ii?ii i?eaanoe IIAI – aaiienai?ioai
sus nonsteroidal anti–inflammatory drugs for osteoarthritis and rheumatoid arthritis: the
(aaiaoioiene?iinou), noaoei – oa?eaanoaoei (?aaaiieieec) e aioeaeaaa-
CLASS study: a randomized controlled trial. Celecoxid long–term arthritis saferty study.
oe?aneee i?aia?ao oaioi?iei (eaeoiaoeaic). JAMA 2000; 284:1247–1255
Oai ia iaiaa iaiaoiaeiinou niaoeaeuiuo eiio?iee?oaiuo aee- 10. Goldstein H, Silverstein FE, Agarwal NM et al. Reduced risk of upper gastrointestinal
ulcers with celexocib: a novel COX–2 inhibitors. Am J Gastroenterol. 2000; 95:
oaeuiuo eniuoaiee, iai?aaeaiiuo ia ioaieo ea?aeiaaneoey?iuo yooa-
1681–1690

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