Chapter 16

1. 16 !:

2. * J. Segura and M. Zorzoli

3. EPO ! ( ) *

4. + , ,-.[2-5] !%

5. $ [1] ! # (+ 4 563 23 $ . /

6. !01 ,- 23 = 1) =

7. (rhEPO) 1 EPO 7 89 !3 /

8. .[6] ) ) =+ + EF 1988 ! =

9. + ?@A1.

10. = 23 =

12. J%H @K . # WADA F 1@ ! G , 3H , 3 + 4,M@,- N.[7]

13. = )) 0

14. L, 23 EPO

15. ,6+ /

16. ?,. = 3 43 $! ?, =

17. 3 ! ?FO ! 3 ) = 3 6+ ?,. = (( TH , UG 1 V)) PQRS 3 $ + (+ . 4 - + W* ,G 3 6 1,G +

18. + [, !FW3 $

19. = 13 $ ) ((4,M@3 YZ

20. )) XQRS =, ?, ] (

21. F ! ) 4,M@ Q ) @+ ,

22. F =* $3 8# `8- ?,.[8]

23. ^F+ _L `1 =F H ?W [, $ (+ rhEPO =

25. J%H$ UG 1 V

26. F (+ 3 51 F . a # $ % ' ()* * ! ` , $ 3 ?W 3 !

27. J@ F UG 1 V 6+ ! J%H 6* 3 $ d, 6@ X c $ F3 bG9 [,.[9-10]

29. , + F ,

30. 1X$ [, 3 =

32. = a -,

33. 64F4 ,$ FK 6+ ?,. 25e R !4 ?W ` $ [11] 6@ 3 K ). F 1 f, 4F +@ + W 4,M@ ?@+. 3 (quantitative) PCR =

34. 3 $ ?A+ 3 5RNA `4H ! ` ULX H%3 : Hct) , ?W ` d, 6@ `4H ! ` ULX H%3 : retHct)

35. @4 , (

36. + , ULX 3

37. + , S : %macro)

39. + , S + (

40. @4 9 = ) + ([EPO]) EPO 6 hV ?F. + ! ` $ (120 fl )3 @

41. : OFF + EPO i 8 ?X ?W : ON), 3 +.3 _

42. ([sTfr])?, 1 : [12-13]3 , YS 3 (

43. = R# EPO i 8 4F, W3 ?W

44. ON = 3.721 Hct + 30.45 retHct + 0.1871 In [EPO] + 0.1267 In [sTfr] + 0.115 In [%macro + 0.1] OFF = 6.149 Hct – 92.87 retHct - 0.1463 In [EPO] 3 = J%H Q5# $retHct L3 5# @W - 43 _ 3 [ hF 3 retHct ,* . K

46. 3 . a$ = L,

47. + , @ j F8 `4 3 - ?W

49. 3 $ ! @

50. ULX

52. @4 G = J%H K 3 @

53. ULX T 13+ 3 $ ?,

54. 3 X . ) # N 9 .

55. 5 $ ,k N G , + = l =G@3 R3 $ 3 + =H

56. $ ) = ?, 3

57. GGX ?, $ T, L H3 Y# 3 6@ + `1 ?, 3F3. ) = ] +@ 3 6F F .[14] L, =

58. 3 + + ?, 1 9 = ) + EPO$([Hb]) ?3) 6 hV ,* @W ` G 3 1,G

59. @4 S : ret S)

60. @4 S ?F.

61. +.

62. = =

63. ( F53 4

64. @4 G 3 [15] ;

65. + , s + r,e,h i+ X 3 -d R3 6 .

66. = 6FH OFF U + ON U 3 @W $ [EPO] $ [Hb] 3 7 3 ) - 43 /

67. 3 = k) H : , YS 3 $ ( [sTfr] + ret S ON-he = Hb + 9.74 In [EPO]; ON-hes = Hb + 6.62 In [EPO] + 19.4 In [sTfR] OFF -hr = Hb − 60 (%ret)1/2 ; OFF-hre = Hb −50 (%ret)1/2 −−−− 7 In [EPO] W [, L, $ OFF-hre * OFF–hr + ON-hes * ON-he ! 3 43 #+.

68. J%H , * + _L F, $ )

69. F 3

71. 3# ?3 ON 6@ 63 8%H , OFF 6@ $ _L % , 6H, U , T,

72. 3 =G@3 R3 OFF + ON

73. * 7@*$ !H `5# $ F - ,- $ F EPO , !+ @ $ =FF f) 01 3

74. $(1-16 +*) !01 U + H- U m , ? - ) # . =

75. !4+

76. p+F H- U , b, c $ 4 5e R f,

77. 3 OFF + ON : 1-16 +* =+ ) [, 3

78. b3R ?T.3 4 Y + + 5 + +

79. H- U m 3 6* - H3 Ya* 3.=+ ) = ?, )

80. 4+ H (H- U m)3 L =+ ) [, + ( F)* .F53 [16] $ - @c

81. 3 Y83 (follow-up) J%H s - 3 / $ T,

82. , L . W* 5F 3 +9 ,G 3 1,G 3 =FF + 13 1,G ! c ] - [, =

83. 3 $ = _

84. `1 89 [, i 8

85. ?4 $ FK i 9 [, 4F, X + F . [17-19] F ?% L, TF+ U (NO),1 [, @ ) !+ =

86. F ,* 6+ $ =0,+ R3. ) # * $ rhEPO i 8 UG 1 V =G@3 68 !FW3 ! # 6@

88. !*)X .[20] = W@R 3 ?@ +

89. + ?M `

90. + , @W- ) = 3 $ F

91. c 3

92. ?4 U rhEPO i 8 s H $U E ?

93. - @W- ,-.+ 43 $ 1 YZ

94. $ rhEPO $

95. @4 ) t3 Wd+ RF . [21]3 rhEPO i 8 . [22]

96. 3 CD71 ?, 1 = ) [,

97. ( ) ?W b, c V ( TH ) J !F 3 $ -,

98. ! ?W U 4 M 6+ N FK $ UhF

99. F (+ ,

100. 4

101. =

102. 3 $ F , UG 1 $ rhEPO =

103. I

104. ! !H ! J%H Y# 3 ! 563 6 W#+ 3 Q5#(quantitative) rtPCR + = _L , 3 [,. !, !FW3 Q13 ? + U, + [5

105. = L ? , - $ a+ , i 6M mRNA . [23]

106. = = $ =G@3 TH u % ) + ( 6* $ rhEPO J%H UG 1 V (+ , !, 3 + 2001 !, 3F3.?+ + vd+ T -, W

107. F [,$

108. G + 3H - W darbepoetin alpha (AMGEN)?T$ h rhEPO 89 bX L

109. b, c

110. = @ 5 (Dynepo) ZF, L %3 .(NESP or ARANESP) .1

111. + 5- @

112. [, $ !+ !M

113. W- =, 3 +3 , = =, $z4HIHF 3 3 $ T, 7 Yy89 13 (SEP) WFS 1 ?A+ !FW3 ([ F

114. ) WFS 3H Q5# =+QW3. [24] F .

115. = , [26] (CERA)1 = ) =FF W- + [25] 2/ ( #!)'

116. 1 2#

117. +, -.

118. /0 * $ F U 3 f, $

119. 3 @c Y83 W@R #+ $ ` 3

120. ! =G@3 $ 4F +

121. F F, 6+ l EF F F5 4 . [27-28] 6H, !

122. ^F !G- + 3 )

123. F + ?3) 6, ) = 5 $ = y3 G 1 V 6@ 3 1* 3 9 = ) 3 + EPO 3

124. F F, 6H, ?F. +

125. @4 .

126. _

127. ?, 1 ?3 EF 3 LF ) # N 9 4 M + R9 `

128. 3 ?3) ,G (intraindividual) - !+ EF 4@X $ )3 [29] (interindividual) -

129. Q ULX =0,3 $ 3 T 13 W - 3 ! ?,.F ?, + E $ !3 @X $(hydration) T3 F , )

130. 3 eX 6+ + F !4+ hXQ `3# R3 [Hb] K 1

131. [Hb] ) = $ 9 h RG . [30-31] F 1 5# `3# $ S 10 .

132. z !(analytical)9 Y+ +

133. = `@ 3 $ !%

134. Y J%H

135. @4 ) = $ `3G . 9 EF 3 R3 =0,3

136. /1X $

137. GW $ ^F+ `@3 $ !H )3 9 ,k

138. @4 $ ?3) 3 /# #+ [15] =FF @ + M@F4 *+ + =FF = 5@ !G- 43 )) M@F4 #+ $ U6 6+ 3 6 F

139. = * , X+ M@F4 [, )43 b, c $ 9 ,k 3 ?, 3F3.+

140. @4 =+QW3. [28] *+ !)) U 1

141. `SX f, v98 b, c ^F+ 3 {5 ? 3 !+3 $ ) # N 9 * `

142. 3 X `X

143. k@ .@ + ) ?3 ! , !% F . * + , 1,3 $ !H ?, $ 9 + 9 = H F EPO 3 F, 3, ! ?,FK$

144. !+ ) = 3 * 3 6@ =

145. 3 = = EPO @ 3 =0,+ R3 W@R [,. [13,32-36]

146. H- ! 1,G . [37]

147. = _L = P LF, G 1 V y3 d, 6@ W

148. 6* Q5# $ ELISA ! 3 (chemiluminescence) , = ) ,

149. F 3 ! , W LF, 3H R3. = =

150. = ) [ 3 3 ELISA ! = $ 6 ?, 3 $ *+ ?, 1 9 + (turbidimetry)LF

151. y

152. 3 ) = + (polyclonal)) FK+ (monoclonal) _L 1,G bG9 FK U 3.

153. (nephelometry) 9 = hV LF

154. = ) `SX f, 1,G ! ,3 7

155. F @W . [13,38-46]

156. - ) . [47] = 3 43

157. =

158. 3 u % 64F4 $ 9 ?, 1 1,G hF 3 6+ ?, b# LF

159. 5

160. ?, $ F ?, YW@R *+ + ! + TH, ?3 $ TH, !+ `

161. U6 13 ! . 2*: * ; : 2*: 8),,9 )) 56/*

162. 7 #! * h-9 $ ^F+ =5 i 4, $ * 3# , ! U - 3 =+Q 3

163. TF+ 6+ + 5* Y N `3G 4+ Q

164. = P ?, p 13 rhEPO 5* Y N.( G, NX F) 23 $

165. (thromboembolic) 1 $ S T + $ [48]= j G

166. 6 3# ]8%3 $ ) `61 p !

167. `@3 ?F. . `9 rhEPO 4M) N c%3 $ ,k N ?, H3 ,6. ! ) ?, 3 + *+ rhEPO !4+ =

168. W, 1990 G 3 H,- $ =H F `4 3 ?, _L 53 $ # R | W N `@3 6 .( @

169. 3 _ ) 2 + S 60 y3) L, ! Hct , Hb y3 13 _L 3 b,H$ [49] VO2max ,- i 3 rhEPO 9d+ (,)4M) @ ?3

170. 3 1988

171. K ) $ W#+ ?, c%3 + ?FK ?, 3F3 $ 5 * ! J%H 3 TF+ d , } @+ $3 = EF [Z@ 4K 9F, 3.5 $ _

172. TF+ F 3 ! - ) ! T !4+ )

173. 3 4,M@,- ~

174. [, L, 23 rhEPO i 8 , Hct 3 _

175. ?# F - ) U8 + YG k@ $

176. ) = `3# 4,M@ + 3 ?, 3 W* =+9 [, L, #+ $ =, . F 6FH Hb $+

177. 3 G31 X = * , b# R3 G31 `5# !4+ !F 3 . 3 ?, $ = ?W `5#

178. $ 6 ,G S + E+ 1997 € (UCI)

179. K+ @ ?3 ,9

180. Q

181. 6H, _Q `4 3 3# _L 3 X `5# v5S $ G31 `9 $ _L * ! s

182. [, | f, + = @

183. 3 6. + * $ =H

184. - ) # /

185. 3 , , ) U8 ?, * !4+ + $ ! + +9 b, c 4+ Q

186. ‚X y+ !# ?, i . L V , L ! G31 3 5 Q

187. =FF,6 R ?

188. ?, 3F3 + rhEPO 4

189. X ! ! b, c 3# * + @ , + + 3 ! 4

190. 6 @X .rhEPO =

191. 3 * 3 * =3 0

192. -d - _ [,$ [50] , ) _L `3# 2001

193. rhEPO J%H , #+ d F hF 3 T@3 V 6H, !FW3 ! 3 f, ?, 3, 3 ^F+ (+ 23 U 1 E3 . [51] =

194. H3 TF+ + ! rhEPO + + 4 =

195. ) !4+ 3 =

196. 9 Wd+ ?, 3 1,3 3 ?, 3F3.( b, L =

197. X$ 3#

198. Q , $ OFF –hr $ %ret ) -d ,* (k@) + , T b5RF $ = .(Hb !+3 )) ?, $ f, @ b, c $ (FIS) 4

199. @ ?3 !

200. - 4F, 7@* + 3 3 T@ $ ?, ) = 3 #+ . a ^F+ =

201. F `3# )

202. 3 ( [19] 9S 4

203. + {16.1 `4}

204. K+) .(OFF –hr + Hb ,- $ ret S )3 OFF –hr `@3 $ = _Q L V !4+ W ,- ?F. ?, Y# $ OFF = E3

205. ?, =F H ?, .

206. = s4WF Hct , Hb y3

207. ?4

208. = -d L V + Y6 3 !4+ ?W 3 H3 J%H = L, (,+9) pKK ! 3 ? -, + F3 = _L ^F+ .Hb , Hct 3

210. ) !

211. K+ ( ) %ret + ( ) [Hb] ?T.

212. @4 + ?3) Y -16.1 `4 …K

213. y 9 . = a `8- ?T /

214. 3 =. 2007 1997 (=* !

215. K+ .

216. `8- =F H x 9 .%ret =F H

217. y 9 + [Hb] =F H

218. 2=? @*: , % 56/*

219. 7 #! * ! F) ^F+ J%H UG 1 V 68 + L * ,- + W

220. 3 ( ! 3 5 , !+ V , ^F+ 3 5

221. F $ 4,M@3 68 #+. FK (+ + - @c j :

222. = LF , h [, ?, L $ F !H 4+ ?3 EF ?, 4+ !+ EF [, ! 343 * 3 ,3 $= - ,+9 $

223. 3 5 Ed (Malcovati)+4@ 2003 Q5#. [52,53] - ) h $ 3 !14, 5 = 3 89F * =X + 4a*$ a [31] 4,M@3 (k)) YZ

224. , h !FW3 $ V + 4,M@,- EF ?3 J%H 6FH J% ?, _ 4F, `@3 T, i c . = 3 43 ^F+ , 3 hF3 + F !H F+ ^F+ 3 51 + `4 3 ( TH)68 .3 = 6FH FK 7 $!, +(#)

225. 1X ,- 3 $ ! , 3 ) !

226. - )F, + !FH WADA $ 2007 + 2006 d ?# ? b-. + U ) 4+ YZ

227. LF

228. !4

229. 3 hF ) # * $ G31 ‡ + ` 3 5 3 1,3 $ ^F+ =* $ [54,55](Bayesian) ?,,3 3 [, )43 3 ,3 !4+ f, + hF 3 b- sZ

230. .

231. 3 $ j !3 V X 5

232. 9

233. 1,3 $ 9 + 9 ` `@3 $ ( ,k ) EF !4 ?

234. * ,3 TK F !H F

235. ?,. ) _L `+

236. [, s

237. 2 6F$ : F5 S 3. @ + `G F $ + 3 G $ - ) [, 6F $ [56] + *(G31 , ?, )3 (Q ) ! s

238. 36 Y ,3 @$ [57] 3 U - ,3 LF YS [, ,3 6F $ = W#+ ?, 3 e R3 $U6 T, . [58]3, bG9 LF

239. 3 13+ ,k ?

240. hF 3 $ ) = M@F4 3 ,3 W + 3 F [, $ =

241. [15]

242. @4 $ 63H (+ ,3 =TH, _ 4F, + 3 /

243. = a =TH, .F, =

244. $ FF @ + = 5@ =T

245. #+ ( WADA)^F+ d 6* sM + (UCI)

246. K+ @ ?3 ,9 $ 2008 4+ 800 3 ` $ b-

247. K+ H, =M+ [, = LF (+ ?, . , G31 ‡ + ` + $

248. c 5 ?,FK 3 [59] ( V - _

249. W3 8% `,-+ L, 3 =

250. - `G 1 !

251. F 3 + ( ?,,3 T + `1 , p1X =

252. 3) $ WADA + UCI 3 $ ^F + # H *+ YS + 3, s .

253. - W $ W5c V `,-+ !4+

254. ! 3 3 `X V hF 3 $ ^F+ `@3 4+ + 9 L $ WADA 2009 `W@

255. #+ . ,3 $ =F, 6@

256. .F S $ W5c V , (`,-+ ) j /

257. 3 3 $ d+ + - W ^F+ d 3 N 5* =5 [, i 3 ,* 68 , [17,60] a+

258. j : ^F+ UG 1 V 3 * . [61,62] ! =

259. I

260. UG 1 V :

261. @A * = _L (+ EPO =

262. I

263. J%H 3 ! [, hF 3 % X ?, 3 $ = k) , G 1 S /

264. 3 {6+}6 13 4@X .

265. , 6+. =

266. (4 ) H `4H3 H3 8%H - O hF 3 F 6 + (erythropoiesis) 1 W V ,k /

267. 3 $UG 1 V 68 =FF ,6 Y R 3 =+QW3 $ = k) ,$ T, ,3 i 8 3 ! z4H $ y3 13 68 3 4+ $ 3# c Q

268. , _L hF 3 z4H - p% !4 3 $ , ) L G , 3H $ EPO $ UG 1 V 6+ b, c - p% . F U - H3 UG 1 $ H3 3 3G i 3 UG 1 6+ ! F $ = = # * H3 E3 3 .rhEPO WFS G + 3H + + !X c !+-+ ,+ 6 - H ˆG U - ^F+ d !yA1 3 T, S - $ WADA ,* 2009 `W@

269. ?T =

270. 3 V j b, c ^F+ d ?# =G@3 .FF J%H (4+ YZ

271. ) @c - (follow-up) T

Chapter 16

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Chapter 16